The Glaucoma Handbook PDF

PART 2 OF 2
SEPTEMBER 2009
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CHAPTERS
1 | Introduction 5 | Risk Assessment as an Evolving Tool 9 | Adherence in Glaucoma Therapy
Murray Fingeret, OD for Glaucoma Care Steven R. Hahn, MD
Robert D. Fechtner, MD, Albert S. Khouri, MD,
2 | The Diagnosis of Glaucoma and Murray Fingeret, OD 10 | Communication in the Management
John G. Flanagan, PhD, MCOptom of Glaucoma
6 | Understanding IOP Lowering Steven R. Hahn, MD
3 New Thoughts on Tonometry and
| Medications
Intraocular Pressure Murray Fingeret, OD 11 | Secondary Glaucomas
David Pye, MOptom John J. McSoley, OD
7 | The Management of Glaucoma
4 | New Technologies in the Diagnosis Murray Fingeret, OD 12 | Primary Angle Closure Glaucoma
and Management of Glaucoma David S. Friedman, MD, MPH, PhD
John G. Flanagan, PhD, MCOptom 8 | When Medical Therapy Fails: Surgi-
cal Options for Glaucoma
Kathy Yang-Williams, OD
1 | Introduction
I would like to welcome you to the fifth edition of Perimeter (HEP) shortly which continues in the quest
the Glaucoma Handbook, a publication developed un- for early perimetric detection of glaucomatous damage.
der the auspices of the Optometric Glaucoma Society Whether the HEP perimeter is a step forward will not
(OGS). This handbook is meant to serve as a guide to be known for several years. Another new functional
the diagnosis and management of glaucoma and is not test under development is pupil perimetry, which is an
an exhaustive review. The material includes a review objective method to assess central vision and reduces
of basics in regards to glaucoma diagnosis and therapy patient involvement. Similar to the HEP, it will take
while providing new insights into the condition. Our several years before we know if this will be a viable test.
goal with each new edition is to keep the material In regards to therapeutics, we are anxiously waiting for
fresh and up-to-date. In certain sections, there is new the next class of drugs. It has been several years since
information while all chapters have been updated. Glau- a new glaucoma drug was made available with combina-
coma diagnosis and management is in an evolutionary tion drugs being the most recent addition to glaucoma
phase with small improvements occurring. In regards medical therapy. Glaucoma surgery is evolving, however
diagnosis, spectral domain OCTs have been available for slowly, with the quest for procedures that reduce IOP
18 months with several companies now building these with fewer complications.
devices. When first launched, OCT analysis schemes used I would like to thank the members of the OGS for
older methods to assess the data such as TSNIT curves their support and help in developing these materials.
and optic disc cross-sectional cuts. The 3-D cube of data I would like to recommend the OGS electronic journal,
was not utilized except visually but this is now chang- which is available free of charge. It comes out quarterly
ing with new schemes being developed to evaluate this and covers many different aspects of glaucoma. One may
huge amount of data. On the cover are images taken sign up for this at www.optometricglaucomasociety.org.
with the Carl Zeiss Meditec, inc. Cirrus Spectral OCT that On behalf of the OGS, I would like to thank our team of
provide examples of where imaging is going. Imaging of authors who contributed to this effort. I would also like
both the anterior and posterior segment are available, to thank Karen Fixler, Ravi Pherwani, Tom Wright and
with resolution not previously possible in commercial Jill Burdge from Pfizer for their continuing support of
instruments. In these examples, the angle and optic disc the OGS, and specifically for the unrestricted grant that
from a healthy individual are seen along with an image allowed us to continue with this publication. We hope
of optic disc drusen. The spectral OCTs are evolving as that you find this handbook useful.
both the Cirrus and RTVue can also image the anterior
segment, and software for glaucoma progression is avail- Murray Fingeret, OD
able on several instruments. Executive Vice-President, Optometric Glaucoma Society
We should see the release of the Heidelberg Edge Editor, The Glaucoma Handbook
2 REVIEW OF OPTOMETRY/OPTOMETRIC GLAUCOMA SOCIETY

2 | The Diagnosis of Glaucoma
John G. Flanagan, PhD, MCOptom
Most glaucomas are asymptomatic until the late stages of the

disease, and therefore a careful, comprehensive eye examination, in-
cluding history, is essential to the early diagnosis. The majority of in-
formation important in the patient’s history relates to our knowledge
of the disease’s epidemiology and risk factor analyses. Age and race
have clear clinical implications for the risk of developing glaucoma,
with peoples of African descent showing a four to five times greater
prevalence, a higher risk of blindness and a tendency to be diagnosed Figure 1. Anterior segment imaging using the Cirrus HD-OCT, showing multiple scans of a
at a younger age. More recently it has been shown that while younger narrow angle. (Images courtesy of Carl Zeiss Meditec, Inc.)
Hispanic-Americans develop primary open-angle glaucoma (POAG) at
a rate similar to Caucasian-Americans, the ratio increases dramatically tor continuous, 24 hour IOP, in order to evaluate sleep IOP profiles
in older age, eventually exceeding even African-American rates after and potentially to combine such data with measures of diurnal blood
the age of 75. Pigmentary glaucoma is more common in Caucasians, pressure. Such technology is not yet available but promises to be a
as is exfoliative glaucoma—the latter appearing to cluster in certain significant advance of great clinical potential. See Chapter 3 for a
regions; for example, the Scandinavian countries. Age and ethnicity discussion of IOP, its clinical importance and relationship to corneal
are also important in regards to the angle closure glaucomas, which thickness and corneal biomechanics.
will be discussed in Chapter 12. Risk factors for the development
of this condition include older age as well as individuals of Asian GONIOSCOPY
heritage. The careful examination of the anterior chamber angle is essential
Family history is well established as a risk factor for glaucoma. in evaluating glaucoma suspects and diagnosing glaucoma. Gonios-
Having a sibling with glaucoma increases a person’s chance of devel- copy enables the visualization of the anterior angle and its assess-
oping POAG 3.7-fold, according to some evidence. The prevalence of ment permits the exclusion of angle closure, angle recession, plateau
POAG in people having a first-degree relative with POAG is estimated iris or secondary angle block as the cause of raised IOP. Gonioscopy
to be between 4% and 16%. Up to 25% of patients with glaucoma are is most commonly performed indirectly by using a contact lens with
reported to have a positive family history. The overall proportion of a mirror system that overcomes the inherent total internal reflection
POAG attributable to genetics is thought to be around 16%. of the angle anatomy. The angle is graded to relate information of its
Ocular history is very important, as well. An essential aspect of visible anatomical features (see gonioscopy.org for review, including
any initial glaucoma diagnosis is a careful review of previous ocular excellent video clips). Several non-contact OCT devices can be used to
findings. Ocular hypertension is strongly associated with an increased evaluate the angle; these include the stand alone Visante (Carl Zeiss
risk of POAG, as are specific aspects of the optic nerve and nerve fiber Meditec) and Slit Lamp (SL)-OCT (Heidelberg Engineering), and the
layer appearance. Indeed, risk assessment tools have been developed analysis modules available on some of the new generation spectral
following the Ocular Hypertension Treatment Study (OHTS) and the domain (SD) OCTs including the RTVue (Optovue Inc.), Cirrus HD-OCT
European Glaucoma Prevention Trial (EGPS) and their application is (Carl Zeiss Meditec) and Spectralis (Heidelberg Engineering) (Figure
discussed in Chapter 5. There has been a renewed interest in the risk 1). Although considerably more expensive than a classic contact go-
related to ocular perfusion pressure (OPP), the difference between niolens, they have the advantage of being objective and quantitative.
blood pressure (particularly diastolic) and IOP. Low OPP at the optic In addition, these devices can accurately measure and map corneal
nerve may lead to ischemic insult and ultimately initiate glaucoma- thickness. They can also image bleb quality following trabeculectomy
tous optic neuropathy. The Barbados Eye Studies confirmed their and the integrity of peripheral iridotomies. However, due to the na-
earlier finding that there was an approximately three-times increased ture of OCT its is often not possible to see the complete angle due to
risk of developing OAG in those with low OPP at baseline. They also the signal being blocked and therefore assumptions need to be made
found an increased risk of progression. This has also been reported for the positioning of the sclera spur when measuring the angle.
by the Early Manifest Glaucoma Trial (EMGT) in an 11 year follow up
that reported patients with low OPP to be at 1.5-times increased risk STRUCTURE
of progressive disease. Of less diagnostic importance, but still worth Evaluation of the optic nerve head and nerve fiber layer (NFL) is
documenting, are myopia and a history of systemic disease such as important in identifying early structural damage. Such structural
diabetes mellitus, systemic hypertension, vasospastic disease, auto- changes frequently occur prior to the presence of repeatable visual
immune disease and severe hypotension. function deficits. Clinical evaluation should be performed at the slit
lamp using a magnified, stereoscopic view through a dilated pupil.
TONOMETRY The lens should be handheld. Perform careful, systematic documen-
Intraocular pressure (IOP) remains the single most important risk tation of the neuroretinal rim, including evaluation based on the
factor for the development of glaucomatous optic neuropathy, and ISN’T mnemonic device. That is, healthy rim tissue should always
its measurement is vital in the initial diagnosis and management be thicker in the inferior (I) region, followed in decreasing thick-
of the glaucomas. It is also the only major risk factor that can be ness by the superior (S), nasal (N) and temporal (T) regions. It has
treated. There has been much recent interest in the ability to moni- been suggested that this clinical schema performs better if the nasal
OPTOMETRIC GLAUCOMA SOCIETY/REVIEW OF OPTOMETRY 3

quadrant is ignored owing to the obscuration of the nasal rim tissue
by the nerve head vasculature, resulting in the IST device (this is
particularly true when considering the quantitative data provided by
imaging devices such as the HRT). Other observations that require
documentation include: focal thinning of the rim tissue, vertical
elongation of the cup, concentric enlargement of the cup, increased
cup depth, saucerization, disc asymmetry, beta-zone parapapillary
atrophy and vascular signs such as disc hemorrhage, focal narrowing,
baring of circumlinear vessels, bayoneting and nasalization of the
vascular tree. The size of the optic disc needs to be evaluated because
the cup size correlates directly with the optic disc size. In a healthy
individual, the larger the optic disc, the larger the optic cup. The disc
size may be qualitatively measured with the small spot of a direct
ophthalmoscope, with a fundus lens at the slit lamp or with an optic
nerve imaging instrument. Practitioners should use a red-free filter to Figure 2. New glaucoma progression analysis printout for the HFA, incorporating
evaluate the nerve fiber layer (NFL) within two disc diameters of the the Visual Field Index, which quantifies the rate of progression and illustrates the
optic nerve. However it should be noted that modern digital fundus projected loss. The left printout shows a relatively stable patient with a slow rate of
progression, whereas the right printout shows a rapid rate of progression in a patient
cameras give unprecedented images of the nerve fiber layer and are who underwent a change in therapy before the rate of progression reduced as seen in
highly recommended. Several grading systems have been suggested, the last 6 fields plotted in the VFI.
with the aim of evaluating the level of diffuse NFL atrophy and the
identification of localized wedge or slit defects. with a -2dB/year change, leading to profound loss within seven to
eight years, it is necessary to have multiple fields to confidently
FUNCTION interpret the measurement within the noise. This was inspired by
Visual function is generally evaluated by measuring the visual the important findings of studies such as the EMGT, within which
field via standard automated perimetry. In glaucoma, the central a small but significant percentage of patients exhibited dramatic
vision is not affected until late in the disease process. Consequently and rapid progression even at the earliest manifestation of their
there is little diagnostic value in evaluating only central visual glaucoma. This is also the thinking behind the excellent new Visual
function by way of visual acuity. Clinical evaluation of automated Field Index available for interpretation of rate of progression on
perimetry charts remains a standard for the detection of glaucoma. the Humphrey Field Analyzer (HFA) (figure 2). There are several
Typical glaucomatous visual field defects were first described by von standard analyses for glaucomatous progression, the most common
Graefe in 1869 and result from apoptotic death of the retinal gangli- being the Humphrey Field Analyzer’s Glaucoma Progression Analy-
on cells. The field defects reflect damage to the NFL bundles as they sis (GPA). The analysis empirically compares serial fields to results
track from the optic nerve, although the primary site of damage is collected in a group of patients with stable glaucoma. The original
thought to be at the level of the lamina cribrosa within the optic application used age-matched normal data to perform the analysis
nerve. Classic defects include early isolated paracentral, arcuate, (Total Deviation), but the EMGT found results to be more accurate
nasal step and occasional temporal wedge defects. It is likely that when based on the Pattern Deviation analysis, by reducing the
a generalized defect due to diffuse loss of axons is present in many influence of diffuse loss.
glaucomatous visual fields, but such defects have limited diagnostic The relationship between Structure and Function has gained
value as they are difficult to distinguish from the effects of media much recent attention and is clearly not as simple as many would
opacity and pupil size. hope. However, it is inevitable that we will soon be considering the
The standard clinical application of static threshold automated complexities of this relationship when attempting to diagnose and
perimetry entails the assessment of the central 30 degrees. A manage our patients with glaucoma. Indeed the first available com-
variety of threshold estimation algorithms are available, with the bined analysis of Structure and Function will soon be available from
faster strategies based on Baysian methods—for example the SITA Heidelberg Instruments and combines results from the Heidelberg
strategy found on the Humphrey Field Analyzer (HFA). It is impor- Retina Tomograph (HRT3) and the Heidelberg Edge Perimeter (HEP)
tant to re-test abnormal looking visual fields to ensure repeatabil- (see chapter 4).
ity, particularly in the naïve patient, as there is a clearly defined The diagnosis of glaucoma requires the clinician to perform a
learning curve that can mimic early defects. Interpretation can be series of tests, including a risk factor analysis, measurement of
aided by statistical packages that analyze the data relative to age- IOP, assessment of corneal thickness and evaluation of the anterior
matched normal values (Total Deviation), and scan for focal defects chamber angle, optic nerve, retinal nerve fiber layer and visual field.
by removing the influence of diffuse loss (Pattern Deviation). There The skilled clinician will integrate these results in an attempt to
are also analyses that judge subjects’ intra-test reliability and the diagnose glaucoma at its earliest manifestation. There is an increas-
symmetry between the upper and lower field, such as the glaucoma ing awareness of the importance and necessity to carefully monitor
hemifield test. It is essential to establish good quality baseline rate of progression, both functional and structural, in patients with
data for both the early diagnosis and the management of manifest newly diagnosed disease.
disease. Indeed, recent recommendations have stated the need for
six fields in the first two years in order to appropriately manage Dr. Flanagan is a Professor at both the School of Optometry, University of
patients with glaucoma. To successfully identify those patients Waterloo, and the Department of Ophthalmology and Vision Sciences, Univer-

sity of Toronto. He is Director of the Glaucoma Research Unit, Toronto Western better determine the IOP, and the second is to develop a method of
Research Institute and a Senior Scientist at the Toronto Western Hospital. He tonometry which directly measures the IOP by overcoming the bio-
is also the President of the Optometric Glaucoma Society. mechanical influences of the cornea.
The Reichert Ocular Response Analyzer (ORA) is a non-contact
Suggested Readings tonometer which measures the time delay between the initial ap-
1. Epstein DL, Allingham RR, Shuman JS, eds. Chandler and Grant’s Glaucoma. 4th ed.Baltimore: Lippincott
Williams and Wilkins, 1996. planation measurement as a result of the puff of air and the second
2. Ritch R, Shields MB, Krupin T, eds. The Glaucomas. 2nd ed. St. Louis: CV Mosby Co, 1995. applanation which occurs as the cornea begins to regain its shape as
3. Fingeret M, Lewis TL, eds. Primary Care of the Glaucomas. 2nd ed. New York: McGraw Hill. 2001.
4. Litwak AB, ed. Glaucoma Handbook. Boston: Butterworth-Heinemann. 2001. a result of the topographical change produced by the initial stimulus.
5. Preferred Practice Patterns: Primary Open Angle Glaucoma. American Academy of Ophthalmology. 2003.
6. Anderson DR, Patella VM. Automated Static Perimetry. 2nd ed. St. Louis: CV Mosby Co, 1999.
The instrument provides a measure of the corneal behavior, a Gold-
7. Medeiros FA, Sample PA, Zangwill LM, Bowd C, Aihara M, Weinreb RN. Corneal thickness as a risk factor mann equivalent IOP (IOPg) and a “corrected” IOP (IOPcc) measure-
for visual field loss in patients with preperimetric glaucomatous optic neuropathy. Am J Ophthalmol. 2003
Nov;136(5):805-13. ment as a result.
8. Hawerth RS, Quigley HA. Visual field defects and retinal ganglion cell losses in patients with glaucoma. Measurements of corneal behavior taken with the ORA are called
Arch Ophthalmol. 2006;124:853-859
9. Giangiacomo A, Garway-Heath D, Caprioli J. Diagnosing glaucoma progression: Current practice and prom- corneal hysteresis (CH) and corneal resistance factor (CRF). A number
ising technologies. Current Opinions in Ophthalmology. 2006. 17: 153-162.
10. Alward WLM. www.gonioscopy.org/
of papers have been published during the year attempting to relate
11. Leske, MC, Heijl A, Hyman, L et al. Predictors of long-term progression in the Early Manifest Glaucoma corneal hysteresis (CH), in particular, to corneal disease and varying
Trial. Ophthalmology. 2007 Nov;114(11):1965-72.
12. Leske, MC, Wu SY, Hennis A et al. Risk Factors for Incident Open-Angle Glaucoma. Ophthalmology. 2008 forms of glaucoma. Some of these studies suggest that CH may be
Jan;115(1):85-93. useful in differentiating between patients with and without primary
13. Chauhan BC, Garway-Heath DF, Goñi FJ, Rossetti L, Bengtsson B, Viswanathan AC, Heijl A. Practical
recommendations for measuring Rates of visual field change in glaucoma. British Journal of Ophthalmology, open-angle glaucoma. It is anticipated that a new version of the ORA
2008;92:569-573.
software will be released soon which will improve the ease of use, a
greater analysis of the waveform obtained and provide a quality index.
The Pascal tonometer (Dynamic Contour Tonometry or DCT) has
3 | New Thoughts on Tonometry and a tip with a surface contour which resembles the corneal contour
Intraocular Pressure when the pressure on both sides of the probe tip is equal (Figure 1).
David Pye, MOptom When this occurs, the biomechanical effects of the cornea on IOP are
significantly reduced, if not eliminated, and the small pressure sen-
Intraocular pressure (IOP) is a risk factor for the development of sor located in the probe tip provides an accurate measure of the IOP.
glaucoma though the condition may develop at any IOP pressure There is a considerable amount of literature which suggests that the
level. IOP is the only modifiable risk factor and is determined by the Pascal is less affected by corneal properties than GAT, although Kote-
amount of aqueous humor produced along with trabecular outflow, cha et al reported that DCT IOP changes during the day were related
uveoscleral outflow and episcleral venous pressure. IOP shows greater to changes in CCT, but there was inter-subject variability.
variability in individuals with glaucoma, with IOP variation correlated Boehm et al reported on a prospective trial involving 75 eyes of
with higher mean pressures, but there is independent risk factor. IOP 75 patients who were examined prior to undergoing phacoemulsifica-
is higher in individuals in the supine position, and often peaks just tion. Prior to phacoemulsification, the anterior chamber was cannu-
before awakening. lated and a closed system was utilized to set the IOP within the eye to
Prior to the 2007 ARVO meeting, the 4th Global World Glaucoma 15, 20 or 35 mmHg. IOP measurements were then taken with a hand
Association consensus meeting on IOP was conducted. The emphasis held Pascal device and compared to the intracameral measurements.
was placed on evidence based research, and the topic areas included The authors claimed that the results with the Pascal tonometer dem-
the basic science of IOP, measurement of IOP as a risk factor for glau- onstrated good concordance with intracameral IOP measurements.
coma development and progression, epidemiology of IOP, clinical tri- New tonometers such as the ICare seem to perform similarly to
als and IOP, and target IOP in clinical practice. The highlights of the GAT, and other forms of tonometry using acoustic or infra-red tech-
meeting are available from the World Glaucoma Association website: nologies may appear in the future.
www.e-igr.com/MR/index.php?issue=91&MRid=188. Anyone who is In 2004, Leonardi et al pub-
seriously interested in the topic of the current status of IOP and its lished a paper which discussed
measurement, the book containing the discussion and consensus the development of a contact
statements published by Kugler Publications is recommended. lens device which could be worn
During the year more papers, both theoretical and clinical in na- to continuously measure IOP.
ture, have appeared which discuss the potential influence of central Devices which monitor blood
corneal thickness (CCT) and the biomechanical behavior of the cornea pressure and heart rate, and
on IOP measurement. However, there is still no specific algorithm more recently blood sugar lev-
which would correct Goldmann applanation tonometry (GAT) read- els, over a 24 hour period are
ings for these aspects of the cornea and, as a result, some authors are now available. There is some
recommending that pachymetry findings be used to classify corneas suggestion that a contact lens
as thin, normal or thick rather than using a specific CCT correction device based on the Leonardi et
nomogram for GAT. This then leads to two approaches to attempting al principle may be available in
to measure the true IOP, and a considerable number of papers have the near future. This presents
been published investigating both techniques. the interesting concept of be-
Figure 1. The Pascal Dynamic Contour Tonome-
One technique is to try to measure the biomechanical behavior of ter is seen with a measurement being taken. ing able to monitor the IOP of
the cornea and make an allowance for these material properties to The IOP is displayed in the digital display. patients at frequent intervals

throughout the day and night which should help with patient diag- +3.6mmHg measurement error.
nosis and management. These results would suggest that GAT instrument calibration
It is still difficult to compare studies which have investigated the should be conducted as the manufacturer suggests on a monthly
relative performance of different tonometers. Often the protocols basis, to try to ensure comparable measurements of IOP over time.
vary, the statistical analyses are different and differing populations
are used for the studies. Mr David C Pye, MOptom, is Senior Lecturer and Clinic Director at the School
Another approach has been used to investigate the effects of of Optometry and Vision Science, University of New South Wales, Australia.
changes in the biomechanical behavior of the cornea on GAT. Hamil-
ton et al reported on the effects on GAT of corneal swelling produced Suggested Readings
1. Weinreb RN, Brandt JD, Garway-Heath DF, Meideros FA eds. Intraocular Pressure. Kugler Publications. The
by two hours of eye closure and thick soft contact lens wear. The re- Hague. The Netherlands. 2007.
sults suggest that at low levels of corneal edema, the cornea becomes 2. Kwon TH, Ghaboussi J, Pecknold DA, Hashash YM. Effect of cornea material stiffness on measured intra-
ocular pressure. J Biomech. 2008;41:1707-13.
stiffer and that the GAT results may overestimate the true IOP. The 3. Hamilton KE, Pye DC. Young’s modulus in normal corneas and the effect on applanation tonometry. Optom
Vis Sci 2008;85:445-50.
clinical implications are twofold. One is that if patients wear contact 4. Brandt JD. Central corneal thickness, tonometry, and glaucoma risk – a guide for the perplexed. Can J
lenses, an estimation of their IOP with GAT will be less affected by Ophthalmol. 2007;42:1-5.
5. Luce D. Determining in vivo biomechanical properties of the cornea with an ocular response analyzer. J
corneal material properties if the patient does not wear their contact Cataract Refract Surg. 2005;31:156-162.
lenses on the day of measurement. If this is not possible, trying to 6. Sullivan-Mee M, Billingsley SC, Patel AD, Halverson KD, Alldredge BR, Qualls C. Ocular response analyzer in
subjects with and without glaucoma. Optom Vis Sci. 2008;85:463-70.
measure the IOP of the patient after the same period of contact lens 7. Kangiesser HE, Kniestedt YC, Robert YC. Dynamic Contour Tonometry: Presentation of a New Tonometer. J
Glaucoma. 2005;14:344-350.
wear at each visit may be appropriate. The second implication relates 8. Kaufmann C, Bachmann LM, Thiel MA. Comparison of dynamic contour tonometry with goldmann applana-
to the diurnal variation of IOP. On eye opening, the average CCT is tion tonometry. Invest Ophthalmol Vis Sci. 2004;45:3118-3121.
9. Boehm AG, Weber A, Pillunat LE, Koch R, Spoerl E. Dynamic contour tonometry in coparison to intracam-
thicker than it will be for the rest of the daytime, and the measured eral IOP measurements. Invest Ophthalmol Vis Sci 2008;49:2472-2477.
IOP with GAT is highest. 10. Kotecha A, Crabb DP, Spratt A, Garway-Heath DF. The relationship between diurnal variations in intra-
ocular pressure measurement and central corneal thickness and corneal hysteresis. Invest Ophthalmol Vis Sci
Interestingly, the CCT and IOP measured in this fashion reduce at Apr 30. [Epub ahead of print].
11. Pepose J, Feigenbaum SK, Qazi MA, Sanderson JP, Roberts CJ. Changes in corneal biomechanics and
a similar rate over the first two hours after eye opening, suggesting intraocular pressure following LASIK using static, dynamic, and noncontact tonometry. Am J Ophthalmol.
a link between the two results. The increase in CCT alone does not 2007;143:39-47.
12. Brusini P, Salvetat ML, Zeppieri M, Tosoni C, Parisi L. Comparison of Icare tonometer with Goldmann ap-
explain the increased GAT result, and the soft contact lens swelling planation tonometer in glaucoma patients. J Glaucoma. 2006;15:213-217.
suggest that some of the increased IOP measurement is due to stiff- 13. Leonardi M, Leuenberger P, Bertrand D, Bertsch A, Renaud P. First steps toward noninvasive intraocular
pressure monitoring with a sensing contact lens. Invest Ophthalmol Vis Sci 2004;45:3113-3117.
ening of the corneal tissue. Half of the increased GAT measurement 14. Pitchon EM, Leonardi M, Renaud P, Mermoud A, Zografos L,. First in vivo human measure of the in-
traocular pressure fluctuation and ocular pulsation by a wireless soft contact lens sensor. IOVS, 49: ARVO
of IOP on eye opening may be a result of increased CCT and Young’s E-Abstract, #687,2008.
modulus of the cornea. To reduce the corneal effects on IOP mea- 15. Tonnu PA, Ho T, Sharma K, White E, Bunce C, Garway-Heath D. A comparison of four methods of tonom-
etry: method agreement and interobserver variablility. Br J Ophthalmol. 2005;89:847-850.
surements obtained with GAT, it would be advisable to ensure that 16. Hamilton KE, Pye DC, Hali A, Lin C, Kam P, Nguyen T. The effect of contact lens induced edema on Gold-
the measurements are taken after the patient has been awake with mann applanation tonometry measurements. J Glaucoma. 2007;16:153-158.
17. Hamilton KE, Pye DC, Kao L, Pham N, Tran A-Q N. The effect of corneal edema on dynamic contour and
eyes open for at least two hours. The biomechanical behavior of the Goldmann tonometry. Optom Vis Sci. 2008; 85:451-56.
18.Hamilton KE, Pye DC, Aggarwala S, Evian S, Khosla J, Perera R. Diurnal variation of central corneal thick-
cornea has also been reported to be affected by age. Elsheikh et al ness and Goldmann applanation estimates of intraocular pressure. J Glaucoma. 2007;16:29-35.
have reported in vitro studies of human corneas which were subjected 19.Elsheikh A, Wang D, Brown M, Rama P, Campanelli M, Pye D. Assessment of corneal biomechanical proper-
ties and their variation with age. Curr Eye Res. 2007;32:11-19.
to relatively slow and rapid rates of corneal inflation in an attempt 20. Romppainen T, Bachmann LM, Kaufmann C, Kniestedt C, Mrochen M, Thiel MA. Effect of Riboflavin-
to imitate GAT and non-contact tonometry respectively. The results UVA-induced collagen cross-linking on intraocular pressure measurement. Invest Ophthalmol Vis Sci.
2007;48:5494-5498.
demonstrated that corneas became stiffer with age, and this stiffen- 21. Choudhari NS, George R, Baskaran M, Vijaya L, Dudeja N. Measurement of Goldmann Applanation Tonom-
eter Caibration Error. Ophthalmology 2009; 116:3-8.
ing could significantly affect GAT results, and may be a significant 22. Sandhu SS, Chattopadhyay S, Amariotakis GA, Skarmoutsos F, Birch MK, Ray-Chaudhuri N. The accuracy
factor to consider when measuring the IOP of patients who have had of continued clinical use of Goldman Applanation Tonometers with known calibration errors. Ophthalmology
2009;116: 9-13.
UVA and riboflavin treatment, although Romppainen et al found the
effects of this treatment to be relatively small in an in vitro model.
It is difficult to know what a single IOP measurement means, and 4 | New Technologies in the Diagnosis and
how it should be interpreted, as there seems to be more we need
to know and understand before a meaningful determination of IOP Management of Glaucoma
can be made. Whilst research into the measurement of the true IOP John G. Flanagan, PhD, MCOptom
continues, IOP is still an important measurement in clinical practice.
However, recent papers by Choudhari et al and Sandhu et al remind The last decade has seen an explosion of new technologies that
us of the need to frequently calibrate our GAT instruments and how have begun to challenge our understanding of the structural and
these errors in calibration may affect our IOP measurements. Choud- functional relationships in early glaucoma, while at the same time
hari et al performed calibration testing on 132 slit-lamp mounted introducing potentially new standards of care. In this chapter, I will
GAT instruments and found only 1% to be within the manufacturer’s review several of the latest technologies and developments.
recommended calibration error tolerance at all levels of testing. Even Methods for the non-invasive, objective, quantitative, structural
if one applied a greater tolerance of ± 2mmHg, 30% of the instru- assessment include scanning laser tomography and optical coherence
ments were faulty. tomography for the optic nerve (ON) and retinal nerve fiber layer
Even if one knows the calibration error, Sandhu et al demonstrated (RNFL); and scanning laser polarimetry for exclusive RNFL analysis.
that the error is not linear, so that a 1mmHg calibration error gave All three technologies are reported to have excellent diagnostic per-
a change in GAT of +1mmHg, a 3mmHg calibration error gave a formance in the detection of early glaucoma. These instruments are
+1.6mmHg measurement error and a 4mmHg calibration error gave a not meant for stand-alone use but rather support the clinical evalua-

A B it operates using a 670nm diode laser light source and a field of
view of 15x15 degrees, with a two-dimensional resolution for each
image plane of 384 x 384 pixels. The scan depth is automatically
selected from a range of 1.0 to 4.0 mm, and 16 scans are obtained
per millimeter of scan depth. A 2-mm scan depth with 32 image
scans has a one-second acquisition time (24msec per scan). The
HRT3 offers several important developments over its predeces-
sors. A sophisticated image acquisition quality control system has
been incorporated. This reduces the learning curve for new users,
and helps to ensure adequate image quality for future progression
analysis. There is a new alignment algorithm that has reduced the
intra-test variability, which in turn, enables more sensitive analysis
of structural progression. The database for analysis of the stereo-
metric parameters and Moorfields Regression Analysis (MRA) has
C been expanded to include 700 of Caucasian descent, 200 of African
descent and 200 from Southeast Asia. This database is also used for
the new, contour independent Glaucoma Probability Score (GPS),
which is based upon automated analysis of the shape of both the
optic nerve head and the parapapillary retina in both normal and
glaucomatous eyes. The printout reflects these new measures and
emphasizes the analysis of cup, rim, retinal nerve fiber layer and
ocular asymmetry. There are additional improvements in the Topo-
graphic Change Analysis (TCA) that can now display graded levels
of significance and Trend Analysis overview plots of cluster volume
and area. The HRT was, until recently, the only imaging technology
specifically designed to analyze progression, and has the added ad-
vantage of being backwardly compatible to its very first model. This
means that some centers now have 17 years of consecutive data.
The HRT has the ability to both align and analyze serial images.
This is of particular importance as the greatest potential of the new
Figure 1a (top left), b (top right), c (bottom). HRT (a), GDx (b) and OCT (c) images of a patient imaging technologies lies in their detection of subtle structural
with primary open-angle glaucoma. The loss is in the left eye only. All three technologies reveal changes early in the disease, rather than cross sectional classifica-
the damage to be in the superior portion of the left optic nerve and retinal nerve fiber layer. This is tion and staging of the disease. Data from the ancillary study of
seen as areas in the left eye that are flagged in the superior region. The GDx also shows loss in the
inferior portion of the left eye, which does not correspond to the other tests or visual fields. the Ocular Hypertension Treatment Trial has indicated that baseline
HRT measures were highly predictive for the development of POAG
tion of the ON/RNFL. They may provide corroboration of a working di- during the course of the study (MRA for the temporal inferior sector
agnosis or require the clinician to re-evaluate his or her assessment of had a hazard ratio approaching 9.0).
the ON/RNFL. They may also be used to follow for change over time. Scanning laser polarimetry combines scanning laser ophthalmos-
Scanning laser tomographers (SLT) were first introduced in the copy with polarimetry to measure the retardation of polarized laser
late 1980’s and are amongst the most common of the imaging light caused by the birefringent properties of the retinal nerve fiber
systems for use in glaucoma. The technology is based on the opti- layer (Figure 1b). The commercially available instrument is called
cal principals of confocal
microscopy. A series of im-
ages are recorded along the
axial axis of the eye, thus
enabling three-dimensional
reconstruction of the sur-
face of the retina and/or
the optic nerve head. The
Heidelberg Retina Tomo-
graph (Heidelberg Engineer-
ing) is the most common of
the SLTs (Figure 1a). The
current, third-generation
model, the HRT3, was in-
troduced toward the end of
2005. The HRT3 is similar to Figure 2: Glaucoma printouts for three of the new SD-OCTs. Left: The RTVue (Optovue Inc.) Center: Cirrus (Carl Zeiss Meditec) Right: Spectralis
the previous model in that (Heidelberg Engineering). Note the common TSNIT plots.

analysis of serial data. This is an important new feature, long miss-
ing in the GDx, permitting both trend and event-based analysis of
disease progression.
Optical coherence tomography is the one technology that has
changed exponentially with the introduction of high resolution,
fourier or spectral domain (SD) OCT. Presently, the most commonly
used of the OCTs is the Stratus OCT (Carl Zeiss Meditec) which is
a third generation, time domain OCT that employs low-coherence
interferometry to enable high-resolution, cross-sectional imaging
of the retina and optic nerve. A superluminescent 830nm diode
provides a near infrared, low-coherence source, which is divided
and beamed to a reference device in the eye. Each light path goes
back to a detector where the reference beam is compared to the
measurement beam. The Stratus can be used in the diagnosis and
Figure 3a,b. These FDT Matrix 24-2 Full Threshold fields are from the patient seen in Figure 1. management of glaucoma by measuring retinal nerve fiber layer
The right visual field is within normal limits, and the loss in the left correlates with the images (RNFL) thickness around the optic nerve head. Radial tomograms
in Figure 1 and SITA SWAP field in Figure 4. are then used to assess the cross-sectional profile of the optic
nerve (Figure 1c). The OCT’s RNFL assessment correlates well with
the clinical assessment of focal defects and visual fields in patients
with glaucoma, and demonstrates a significant difference between
normal and glaucomatous subjects. Results are compared to an
age-matched normative database. A recent addition to the Stratus
OCT is a GPA utility that illustrates potential change by overlaying
serial thickness plots and performs linear regression on the average
thickness data. The nature of time domain OCT means that it does
not lend itself well to progression analysis, as serial alignment is
uncertain. However it is both desirable and important to have even
this rudimentary progression analysis.
SD-OCT was recently launched by nine different companies, includ-
ing Optovue (RTVue), Heidelberg Engineering (Spectralis), Carl Zeiss
Meditec (Cirrus) and Topcon (Figure 2). SD-OCT uses a stationary
Figure 4. These are SITA SWAP fields for the patient seen in Figure 1 and 3. The loss is in the reference mirror, as opposed to the moving reference mirror found in
left eye, with the inferior points being flagged. The field in the right eye is consistent with a
trial lens artifact. time domain OCT. The interference between the sample and reference
reflections are split into a spectrum and all wavelengths are simulta-
the GDx VCC (Carl Zeiss Meditec), although the new GDxPRO will neously analyzed using a spectrometer. The resulting spectral inter-
be available shortly. Like its predecessor, the PRO uses an 820nm ferogram is Fourier transformed to provide an axial scan at a fraction
diode laser source in which the state of polarization is modulated. of the time previously required. This has resulted in up to a 100 times
Image acquisition takes 0.7 seconds and the scan field is 20 degrees. increase in the number of A-scans per second (Spectralis at 40,000
Results are compared to an age-matched normative database, and scans per second compared to the Stratus at 400 scans per second).
a machine classifier is used to define the likelihood that a map is In several of the new machines the OCT scans are paired with com-
normal or glaucomatous. Unlike the GDxVCC, the PRO uses Enhanced plimentary imaging modes, for example SLT, to enable registration of
Corneal Compensation (ECC) algorithms with the idea of further all A-scans. This allows image alignment of serial images, essential
reducing image noise and the effect of
atypical scans. ECC is a sixth-generation
approach, which like VCC employs in-
dividual specific compensation of the
ocular birefringence but was developed
to reduce the atypical “tie dye” appear-
ance found in some lightly pigmented
and myopic patients.Other new features
of the GDxPRO include the evaluation of
retinal nerve fibre layer integrity (RNFL-
I). The idea being that unhealthy gan-
glion cells will cause disruption of the 5a (above). The Heidelberg Edge Perimeter
integrity of the RNFL and reduce the (Heidelberg Engineering)
quality of the retardation image. There 5b (center) OU printout of a HEP examination
showing superior arcuate defects.
is also Glaucoma Progression Analysis 5c (right) OU Structure Function Map
(GPA) that enables the alignment and showing a matching borderline defect OD and an inferior defect of the ONH with an accompanying superior defect in the HEP field OS.

for the analysis of progression and overcoming the most significant predictive of early
problems associated with time domain OCT. The key to successful glaucomatous SAP
progression analysis is likely to be whether or not such images are visual field defect,
acquired simultaneously with the OCT scans. If not, eye movements in some cases by up
may remain a significant artifact. Glaucoma specific analyses are now to five years. SWAP
available. The Cirrus, Spectralis and RT-Vue display RNFL maps and is tested, analyzed
TSNIT plots of RNFL (Figure 2). In addition the RT-Vue segments the and displayed in a
Ganglion Cell Complex (GCC), which comprises the RNFL, ganglion cell way intuitively sim-
layer and inner plexiform layer, and currently displays the GCC in the ilar to SAP. SWAP is
macular region. The idea being that early glaucomatous damage is de- limited by the rela-
tectable in the macula. There are currently no published studies with tively greater influ-
respect to the diagnostic performance of the new glaucoma utilities. ence of cataracts
To date none of the manufacturers permit automated segmentation and other media
and analysis of three dimensional scans, undoubtedly the ultimate opacities, a com-
clinical tool. pressed dynamic
New technologies for visual function have concentrated on se- range, poor test-re-
lectively testing specific anatomical and/or perceptual pathways, test characteristics
so called Visual Function Specific Perimetry. The goal of such an and increased test
approach is to detect loss of retinal ganglion cells (RGCs) earlier and time. The latter Figure 6: Glaucoma Progression Analysis summary printout
with improved repeatability. has improved since showing a patient with slowly progressive glaucoma. The two
Frequency Doubling Technology perimetry (FDT) is based on the the introduction fields at the top of the printout are the selected baseline fields;
the center graph is the trend analysis for the Visual Field
frequency-doubling illusion, whereby a low-spatial frequency grating of SITA-SWAP. Index (87%) showing a slow rate of progression; the bottom
(<1 cycle/degree) is flickered in counterphase at a high temporal However, SWAP field shows the most recent result. There is clear progression
frequency (>15Hz). When this occurs the spatial frequency of the will probably not particularly in the inferior temporal region.
grating appears to double. The technique has been applied clinically replace SAP and
using a grating of 0.25 cycles/degree and temporal frequency of should be considered a complementary test to be used in selected
25Hz. It was initially proposed that the illusion was due to selec- situations, such as high-risk glaucoma suspects with normal SAP
tive processing of the My cells, a subset of magnocellular projecting results.
RGCs. However, this is now thought unlikely, as there is no evidence Heidelberg Engineering is planning to launch a new visual func-
for such cells in primates—although the illusion does preferentially tion test called the Heidelberg Edge Perimeter (Figure 5). This is
stimulate the magnocellular system. It is likely that the stimulus, as based upon an illusionary stimulus called flicker defined form, in
used clinically, is a flicker contrast threshold task. which a 5° stimulus region within a background of random dots is
The original FDT tested up to 19 large, 10 degrees x 10 degrees flickered in counterphase at a high temporal frequency (15Hz). The
targets in either a threshold mode or a rapid (<1 minute) screening pahse difference between the background dots and the stimulus
test. During testing, the stimulus flicker and spatial frequency are dots gives rise to an illusionary edge or border that is perceived as a
held constant while the contrast is modified in a stepwise process circle or patch, against the mean luminance background. The stimu-
similar to the bracketing method used in conventional perimetry. In lus targets the magnocellular projecting retinal ganglion cells and is
response to concerns over the ability of such large targets to detect proposed for the early detection of glaucomatous damage. HEP has
subtle, early defects, a second-generation machine was developed, been reported to have good test-retest repeatability and be capable
the FDT Matrix, which uses smaller 5-degree targets and measures of detecting early, pre-SAP glaucoma (figure 5c). Defects tend to
with a standard 24-2 pattern (Figure 3). A video camera is incorpo- be larger and deeper than those found using SAP. The HEP also
rated for fixation monitoring, and it is possible to view serial fields. features full range SAP, advised for use in neurological cases and
A ZEST-like strategy is used to estimate the sensitivity and ensure a advanced disease. Of particular note is the availability of the first
standardized test time, regardless of defect. ever combined Structure-Function Map, in which the HRT’s MRA
FDT has been reported to have high sensitivity and specificity for analysis is combined with the visual field analysis of the equivalent
the detection of glaucoma. Even when used in the screening mode, it ON sectors (figure 5).
may detect some defects earlier than standard automated perimetry Current methods for the analysis of visual field progression include
(SAP). FDT is relatively resistant to optical blur, small pupils and the inspection of the Overview printout and the Glaucoma Progression
influence of ambient illumination—all of which make it ideal in a Analysis (GPA), an updated version of the original Glaucoma Change
screening environment. Recent reports on the Matrix suggest that it Probability (GCP) analysis. Both are empirically based and compare a
is capable of diagnosing early disease before SAP and often prior to patient’s pattern of change to “typical” change experienced by oth-
SWAP. As disease progresses there is little difference with SAP results. ers with glaucoma. GCP was based on the total deviation plots, and
Short-wavelength automated perimetry (SWAP), or blue-yellow was criticized for being prone to error in the presence of developing
perimetry, uses a large Goldmann size V blue stimulus (centered on cataract and changing pupil size. The GPA was developed for the
440nm) against a bright yellow background (100 cd/m2) (Figure 4). Early Manifest Glaucoma Treatment Trial (EMGT) and uses the pat-
The rationale is to selectively test the blue cones and their projection tern deviation plots, allowing an analysis that is less sensitive to the
through the koniocellular pathway, thus taking advantage of their effects of cataract and reduced pupil size. GPA is available on the
reduced redundancy. Several longitudinal studies found SWAP to be Humphrey Field Analyzer (HFA). The analysis uses estimates of the

inherent variability of glaucomatous visual fields. This is combined the principles of detecting damage, then lowering intraocular pres-
with the EMGT criterion of three significantly deteriorating points sure to a level at which we believe the pressure-related component
repeated over three examinations. A minimum of two baseline and of damage will be reduced or eliminated. Then we follow the patient
one follow-up examination are required. Each exam is compared to to monitor for progression. This model has obvious limitations. Early
baseline and to the two prior visual fields. Points outside the 95th glaucoma is asymptomatic and difficult to detect. Only as the disease
percentile for stability are highlighted, as are points that progress progresses are detectable structural and functional changes observed.
on two or three consecutive examinations. Two additional qualifying Also, changes are irreversible and even a small achromatic visual field
statements alert the clinician to the likelihood of “probable progres- defect usually represents significant damage to the optic nerve.
sion” (3x2 consecutive) and “likely progression” (3x3 consecutive). We treat patients with ocular hypertension and glaucoma by
The Visual Field Index has recently been introduced and provides a reducing intraocular pressure (IOP). However, it is important to
method for the monitoring of rate of progression (see Chapter 2). The remember that the goal of glaucoma care is not to reduce IOP, not
most recent version of GPA uses a single printout to illustrate the to preserve optic nerve and not to preserve visual field, but rather
baseline fields, the VFI and its regression, and the most recent field to preserve sufficient vision for acceptable quality of life. It is the
with its GPA results (Figure 6). loss of vision from glaucoma that impacts upon the quality of life
New technologies have been developed and are gaining clinical ac- for our patients. If our tools allow us only to base our treatment
ceptance. These new tests complement the examination and allow a decisions on the degree of loss already present or on the detection
better understanding of the visual field, optic nerve or retinal nerve of additional loss, we are missing an opportunity to identify and
fiber layer. The new technologies supplement tests we have been treat appropriately patients at greatest risk for losing vision before
using for many years. As we gain better understanding of their use additional damage occurs.
and strengths, they will only improve our ability to diagnose and Risk assessment is a well-accepted tool in other fields of medicine.
manage glaucoma. Perhaps the best known example is cardiovascular medicine. Most
adults are at least aware that elevated blood pressure and abnormal
Suggested Readings blood lipid profile increase the risk of coronary heart disease (CHD).
1. Fingeret M., Flanagan J., Lieberman J. (eds). The Heidelberg Retina Tomograph II Primer. Jocoto, San
Ra1. Fingeret M., Flanagan J., Lieberman J. (eds). The Heidelberg Retina Tomograph II Primer. Jocoto, San Many have had blood pressure measured and a lipid profile tested.
Ramon. 2005 Risk assessment and modification is the fundamental tool for pre-
2. Weinreb RN, Greve EL, eds. Glaucoma Diagnosis Structure and Function. The Hague, Kugler Publications.
2004. venting coronary heart disease. No one wishes to learn of their risk
3. Chauhan BC, McCormick TA, Nicolela MT, LeBlanc RP. Optic disc and visual field changes in a prospective
longitudinal study of patients with glaucoma: comparison of scanning laser tomography with conventional
by having the first heart attack! True, the consequence of gradual
perimetry and optic disc photography. Arch Ophthalmol. 2001;119(10):1492-9. atherosclerosis is a cardiovascular event—quite dramatic compared
4. Zangwill LM, Weinreb RN, Berry CC, Smith AR, Dirkes KA, Liebmann JM, Brandt JD, Trick G, Cioffi GA, Cole-
man AL, Piltz-Seymour JR, Gordon MO, Kass MA; OHTS CSLO Ancillary Study Group. The confocal scanning with the chronic optic neuropathy and gradual loss of vision of glau-
laser ophthalmoscopy ancillary study to the ocular hypertension treatment study: study design and baseline coma—but there are some parallels in the underlying principles of
factors. Am J Ophthalmol. 2004;37(2):219-27.
5. Zangwill LM et al. The CSLO ancillary study to OHTS: Baseline measurements associated with development risk assessment. We can use the example of cholesterol.
of POAG. Arch. Ophthalmol. 2005;123:1188–97.
6. Medeiros FA, Zangwill LM, Bowd C, Weinreb RN. Comparison of the GDx VCC scanning laser polarimeter,
The understanding of “cholesterol” as a risk factor has dramatically
HRT II confocal scanning laser ophthalmoscope, and stratus OCT optical coherence tomograph for the detec- evolved over time. Early in the evolution of risk assessment for CHD,
tion of glaucoma. Arch Ophthalmol. 2004;122(6):827-37.
7. Reus NJ, Zhou Q, Lemij HG. Enhanced Imaging Algorithm for Scanning Laser Polarimetry with Variable cholesterol was identified as a risk factor. Initially, normal cholesterol
Corneal Compensation. Invest Ophthalmol Vis Sci. 2006;47:3870-3877. levels were defined as being within two standard deviations (SDs) of
8. Paunescu LA, Schuman JS, Price LL, et al. Reproducibility of nerve fiber thickness, macular thickness, and
optic nerve head measurements using Stratus OCT. Invest Ophthalmol Vis Sci. 2004;45:1716-1724. the mean (200 mg/dL to 310 mg/dL). Later, it was appreciated that
9. Johnson CA, Adams AJ, Casson EJ, Brandt JD. Blue-on-yellow perimetry can predict the development of
glaucomatous field loss, Arch Ophthalmol. 111;645-650, May 1993.
there was a continuous effect, even within normal ranges. It soon
11. Heijl A, Leske MC, Bengtsson B, Bengtsson B, Hussein M, and the Early Manifest Glaucoma Trial Group. became evident that subjects with the “normal range” of cholesterol
Measuring visual field progression in the Early Manifest Glaucoma Trial. Acta Ophthalmol Scand. 2003;81:286-
293. levels included an excessively high incidence of CHD. In fact, the cor-
12. Haymes SA, Hutchison DM, McCormick TA, Varma DK, Nicolela MT, LeBlanc RP, Chauhan BC. Glaucoma-
tous visual field progression with frequency-doubling technology and standard automated perimetry in a
relation between cholesterol levels and CHD occurred in a continuous,
longitudinal prospective study. Invest Ophthalmol Vis Sci. 2005;46(2):547-54. graded fashion, and normal cholesterol levels were still associated
13. Fingeret M, Lewis TL, eds. Primary Care of the Glaucomas. 2nd ed. New York: McGraw Hill. 2001.
16. Anderson DR, Patella VM. Automated Static Perimetry. 2nd ed. St. Louis: CV Mosby Co, 1999.
with increased risk of CHD.
17. Goren D. and Flanagan JG. Is flicker-defined form (FDF) dependent on the contour? J Vis. 2008. The understanding of elevated IOP as a risk factor is analogous.
22;8(4):15.1-11.
18. Quaid PT and Flanagan JG. Defining limits of flicker defined form: Effect of stimulus size, eccentricity Originally, abnormal IOP was described as two standard deviations
and number of random dots. Vis Res 45(8): 1075-1084, 2005.
19. See JL. Imaging of the anterior segment in glaucoma. Clin Experiment Ophthalmol. 2009 ;37(5):506-13.
from the mean (21 mmHg). We have subsequently learned that IOP is
20. Sakata LM, Deleon-Ortega J, Sakata V, Girkin CA. Optical coherence tomography of the retina and optic a continuous risk factor, even at statistically normal levels. Further,
nerve - a review. Clin Experiment Ophthalmol. 2009;37(1):90-9.
it is clear that one can have high IOP without glaucoma and one can
have glaucoma with statistically normal IOP.
With the emerging evidence from large, prospective glaucoma
5 | Risk Assessment as an Evolving Tool trials, we are beginning to amass the data to allow us to be able to
for Glaucoma Care identify risk factors for both the development and the progression of
Robert D. Fechtner, MD, Albert S. Khouri, MD, and Murray Fingeret, OD glaucoma. Models allow the creation of risk calculators, tools to esti-
mate individual rather than population risk. We can then determine
Whom should we treat? When? And how aggressively? The clini- who is at greatest risk. This can lead to better decisions regarding
cian treating patients with glaucoma or glaucoma suspects is faced earlier or more aggressive intervention.
with these challenging questions. Not all patients with glaucoma will The results of recent large-scale trials have encouraged a reas-
lose vision to the extent that quality of life will be compromised. sessment of the way clinicians evaluate and manage patients with
Our current model of diagnosing and treating glaucoma is based on ocular hypertension (OHT) or glaucoma. The potential benefits of IOP

developing POAG in ocular hypertensive subjects.
An unanticipated observation from OHTS was that subjects with
thinner corneas were at higher risk for glaucoma. While we know
that the thickness of the cornea affects IOP measurements, this alone
did not account for the increased risk. Thinner central corneal thick-
ness was an independent risk factor. This has prompted clinicians to
measure corneal thickness in patients with ocular hypertension and
glaucoma on a routine basis.
The EMGT study identified factors for the progression of glaucoma
in newly diagnosed patients. Risk factors present at the baseline visit
that predicted who would progress included higher IOP, eligibility in
Figure 1. The Discoveries in Sight risk calculator, available on the Internet at www. both eyes (glaucoma in both eyes), presence of exfoliation material,
discoveriesinsight.org. worse visual field (mean defect) and older age. Once the patients
returned for follow-up, additional factors that predicted progression
reduction have been clearly demonstrated. The Ocular Hypertension included initial response to treatment (better initial response was
Treatment Study (OHTS) investigated the effect of lowering IOP on protective), IOP at first visit and mean IOP at all follow-up visits, as
progression to open-angle glaucoma (OAG) in over 1600 subjects with well as percentage of visits at which a disc hemorrhage was detected.
OHT but no evidence of glaucomatous damage. Treatment with topi- In subsequent analysis of the Early Manifest Glaucoma Trial with a
cal ocular-hypotensive medication reduced the risk of progression to median follow-up of eight years the results confirmed earlier findings
glaucoma by approximately half, from 9.5% in untreated patients to that elevated IOP is a strong factor for glaucoma progression, with a
4.4% in patients receiving treatment. A similar study, the European hazard ratio increasing by 11% for every 1 mmHg of higher IOP (95%
Glaucoma Prevention Study (EGPS), found no benefit from treatment confidence interval 1.06–1.17; P<0.0001). Longer follow up (seven-11
of ocular hypertension with dorzolamide compared with placebo years) from EMGT have refined our understanding of some of the risk
(vehicle of dorzolamide). However, the IOP reduction in the placebo factors. While level of IOP was an important risk factor, fluctuation
group in EGPS was nearly the same as that in the dorzolamide treated of IOP was not an independent risk factor. A thinner central corneal
group, a curious finding that has not been fully explained. thickness was a risk factor in those subjects with higher baseline IOP.
In the Early Manifest Glaucoma Trial (EMGT), subjects with newly Recently, ocular perfusion pressure has been identified as a risk
diagnosed early glaucoma were randomized to either treatment or factor in both the EMGT study and the Barbados Eye Study. Perfusion
observation. This study demonstrated a benefit from treatment. IOP pressure is defined as the blood pressure minus the IOP. It is not clear
reduction slowed the rate of progression from 62% in controls to 45% what cut-off indicates perfusion may be compromised. Still, the dia-
in the treated population (median follow-up of six years). stolic blood pressure may become an important factor in addition to
For most clinicians, it is not surprising to get confirmation that the intraocular pressure as we evaluate risk in our glaucoma patients.
lowering IOP prevents or delays the progression from OHT to glau- This is a topic of considerable current interest. We will need to bet-
coma or from glaucoma to further visual field loss. Despite these en- ter understand the implications of these observations before we can
couraging findings, individualizing therapy based on the results from integrate them into clinical practice. Blood pressure measurements
large-scale clinical trials is difficult. Although IOP reduction may de- may become part of glaucoma assessment in the future.
crease risk of glaucoma and vision loss, treatment costs and potential The OHTS publication included two 3x3 tables that included central
side effects also need to be considered. It would be helpful to know corneal thickness and either IOP or C/D ratios. We could consider
who is at greatest risk and most likely to benefit from treatment. these as the first risk calculators. It was possible to combine two risk
Perhaps more important than the clear demonstration of the ben- factors to derive an individual risk for the development of glaucoma.
efits of IOP lowering in these studies was the identification of risk Steven Mansberger, MD, MPH, at Devers Eye Institute posted an
factors for the development or progression of glaucomatous damage. interactive risk calculator based on the OHTS data on the internet
Several risk factors were identified at baseline in OHTS for the group at www.discoveriesinsight.org/GlaucomaRisk.htm (Figure 1). It has
who developed glaucoma. Older age was associated with increased undergone modification since it was originally introduced. A version
risk of developing the disease over the course of the 5-year study. is available for download.
Despite this correlation, it is important to remember that glaucoma The first validated risk calculation model was published in 2005.
takes many years to progress to visual loss. Although increasing age This was also based on the OHTS risk model. The calculator was tested
is a risk factor, younger patients should have frequent eye exams on an independent population of ocular hypertensive subjects fol-
since they have a greater remaining life span over which to develop lowed at the University of California, San Diego. A cardboard “slide
vision loss. Higher untreated IOP in OHTS was also associated with a rule” and then a digital handheld risk calculator were produced. To
greater frequency of developing glaucoma. This is not surprising since be used precisely as designed, these calculators require input of data
IOP is a consistent risk factor in many studies. Patients with a greater just as it was collected in the OHTS study. This data includes the age,
cup-to-disc diameter (a measure of optic nerve damage) were more intraocular pressure, central corneal thickness, vertical cup-to-disc
likely to develop glaucoma. It is not clear if some of the subjects with ratio, pattern standard deviation (PSD) from a HFA II threshold visual
the larger cup-to-disc diameters already had early glaucoma without field and diabetes status. However, in clinical practice a less stringent
demonstrable visual field defects when they entered the study. In use should still provide reasonable estimates of risk.
another analysis of OHTS data, optic disc hemorrhages were associ- More recently a risk calculator was developed by the OHTS study
ated with a six-fold increase (95% CI 3.6-10.1; p<0.001) in risk of center (Figure 2). A prediction model was developed from the obser-

and ultimately developing a visual disability? OHTS identified risk
factors for the progression from OHT to open-angle glaucoma (OAG).
Risk calculators are now available to help the clinician estimate
individual risk of progression. The EMGT and other studies identi-
fied some of the risk factors for progression of OAG. As we refine
models of risk, we will better be able to determine which patients
are at highest risk and may need aggressive treatment. Conversely,
we should identify patients at low risk who can be followed closely
without treatment. This requires a fundamental change in our view of
glaucoma treatment. Rather than think of it simply as IOP-lowering
treatment, we might start to consider it as risk reduction. Of course,
we must consider patient preferences and views about risk in making
these determinations.
Well-designed clinical trials in glaucoma will continue to advance
our understanding of the spectrum of this disease. It is not only reas-
Figure 2. The Ocular Hypertension Study and The European Glaucoma Prevention Study
Glaucoma 5-year risk estimator is available at http://ohts.wustl.edu/risk/calculator.html. In suring that many of our cherished traditions are now supported by
this figure is the continuous method calculator. A point-system calculator is also available. evidence, but also intriguing to explore new concepts about glaucoma
based on large, well-designed studies. At first, we will make qualita-
vation group of the OHTS that was then tested on the placebo group tive determinations by identifying risk factors in our patients and
of the European Glaucoma Prevention Study (EGPS). A calculator to altering our treatment decisions. Eventually, we can expect to have
estimate the five-year risk of developing POAG, based on the pooled risk calculators as tools to help decide whom to treat, when to treat
OHTS-EGPS predictive model, was found to have high precision in and to what extent.
assisting clinicians deciding on the frequency of tests and examina- Dr. Fechtner is professor at the Institute of Ophthalmology and Visual
tions during follow-up and the advisability of initiating preventive Science, University of Medicine and Dentistry of New Jersey, New Jersey Medi-
treatment. The OHTS- EGPS calculator can be found online at http:// cal School and director of the Glaucoma Division, UMDNJ-New Jersey Medical
ohts.wustl.edu/risk/calculator.html. School.
One question when the OHTS risk calculator was initially developed Dr. Khouri is at the Institute of Ophthalmology and Visual Science, University
was whether to input diabetes status. OHTS found having diabetes of Medicine and Dentistry of New Jersey, New Jersey Medical School.
to be protective of developing glaucoma but only diabetics without Dr. Fingeret is chief of the Optometry Section, Dept Veterans Affairs New
retinopathy were allowed into the study. Diabetes was not found to York Harbor Health Care System, Brooklyn Campus and Clinical Professor, SUNY
be a risk factor in the analysis of pooled OHTS-European Glaucoma College of Optometry. Dr. Fingeret sits on the board of directors of the Glaucoma
Prevention Study dataset. Thus the influence of diabetes on the de- Foundation and is executive vice-president of the Optometric Glaucoma Society.
velopment of POAG remains questionable. A recent publication from
OHTS, when the data were reevaluated after assessing the medical Supported in part by Research to Prevent Blindness
history, further found that diabetes was neither protective or a risk and the Glaucoma Research and Education Foundation, Inc.
for glaucoma development.
How can a risk calculator add to the quality of clinical care? At Suggested Readings
1. Brandt JD, Beiser JA, Kass MA, Gordon MO, and the Ocular Hypertension Treatment Study (OHTS)
the very least, we should better be able to determine whom to treat Group. Central corneal thickness in the Ocular Hypertension Treatment Study (OHTS). Ophthalmology.
and whom to follow without treatment. It can be educational for 2001;108:1779-1788.
2. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive
the patient to demonstrate their risk status to explain treatment summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detec-
tion, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA.
options and recommendations. One consensus group published sug- 2001;285:2486-2497.
gestions that we should observe low-risk patients, consider treat- 3. Girkin CA, Kannel WB, Friedman DS, Weinreb RN. Glaucoma risk factor assessment and prevention: Les-
sons from coronary heart disease, American Journal of Ophthalmology, Volume 138, Issue 3, Supplement 1,
ment for moderate risk patients, and treat those at highest risk. The September 2004, Pages 11-18.
exact treatment threshold have not been clearly determined but this 4. Gordon MO, Beiser JA, Brandt JD, et al, for the Ocular Hypertension Treatment Study Group. The Ocular
Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch
group selected ranges of <5% for low risk, 5-15% for moderate risk, Ophthalmol. 2002;120:714-720.
5. Grundy SM, Pasternak R, Greenland P, Smith S Jr, Fuster V. Assessment of cardiovascular risk
and >15% for high risk. The rationale is that a glaucoma patient at by use of multiple-risk-factor assessment equations: a statement for healthcare professionals f
highest risk to progress from OHT to glaucoma is also probably at rom the American Heart Association and the American College of Cardiology. J Am Coll Cardiol.
1999;34:1348-1359.
relatively high risk for developing a glaucomatous visual disability 6. Hattenhauer MG, Johnson DH, Ing HH, et al. The probability of blindness from open-angle glaucoma. Oph-
in his of her lifetime. Other factors will also influence the decisions thalmology. 1998;105:2099-2104.
7. Kannel WB. Contributions of the Framingham Study to the conquest of coronary artery disease. Am J
regarding treatment. Cardiol. 1988;62:1109-1112.
8. Medeiros FA, Sample PA, Weinreb RN. Corneal thickness measurements and visual function abnormalities
Risk calculators have not yet been developed for progression once in ocular hypertensive patients. Am J Ophthalmol. 2003;135:131-137.
a patient has glaucoma. But knowing the relevant risk factors can 9. National Cholesterol Education Program (NCEP) Expert Panel. Detection, Evaluation, and Treatment of High
Blood Cholesterol in Adults (Adult Treatment Panel III). Final Report. NIH (National Institute of Health);
help us identify patients who might be at higher risk even if we 2002. Publication no. 02-5215.
cannot get a quantitative estimate of that risk. For now, we should 10. Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M, for the Early Manifest Glaucoma Trial
Group. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma
evaluate our patients for known or suspected risk factors and either Trial. Arch Ophthalmol. 2002;120:1268-1279.
11. Kass MA, Heuer DK, Higginbotham EJ, et al, for the Ocular Hypertension Treatment Study Group. The
test for progression more frequently or treat more aggressively those ocular hypertension treatment study: a randomized trial determines that topical ocular hypotensive medica-
we consider at higher risk. tion delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:701-713.
12. Weinreb RN, Friedman DS, Fechtner RD, et al. Risk assessment in the management of patients with ocu-
Can we predict which glaucoma patient is at risk for progressing lar hypertension, American Journal of Ophthalmology, Volume 138, Issue 3, September 2004, Pages 458-467.

13. Coleman AL, Singh K, Wilson R, et al. Applying an evidence-based approach to the management of
patients with ocular hypertension: Evaluating and synthesizing published evidence, American Journal of
were within reach using a single agent. In addition, compliance im-
Ophthalmology, Volume 138, Issue 3, Supplement 1, September 2004, Pages 3-10. proved and diurnal IOP variation was reduced.
14. Friedman DS, Wilson MR, Liebmann JM, et al. An evidence-based assessment of risk factors for the pro-
gression of ocular hypertension and glaucoma, American Journal of Ophthalmology, Volume 138, Issue 3, Beta-adrenergic antagonists were introduced in 1978 with timolol
Supplement 1, September 2004, Pages 19-31.
15. Weinreb RN, Ocular hypertension: Defining risks and clinical options, American Journal of Ophthalmol-
maleate. Since then, additional beta-adrenergic antagonists include
ogy, Volume 138, Issue 3, Supplement 1, September 2004, Pages 1-2. levobunolol, betaxolol, metipranolol and carteolol. Betaxolol is
16. Results of the European Glaucoma Prevention Study. Ophthalmology. 2005 Mar;112(3):366-75.
17. Medeiros FA, Weinreb RN, Sample PA, Gomi CF, Bowd C, Crowston JG, Zangwill LM. Validation of a predic- different from other medications in this class in that it is a cardio-
tive model to estimate the risk of conversion from ocular hypertension to glaucoma. Arch Ophthalmol. 2005 selective agent that primarily blocks beta1 adrenergic receptors.
Oct;123(10):1351-60
18. Ocular Hypertension Treatment Study Group, European Glaucoma Prevention Study Group. Validated pre- Carteolol is also unique in that in addition to being a nonselective
diction model for the development of primary open-angle glaucoma in individuals with ocular hypertension. beta-adrenergic antagonist has intrinsic sympathomimetic activity
Ophthalmology. 2007;114:10-19.
19. Bengtsson B, Leske MC, Hyman L, Heijl A. Fluctuation of intraocular pressure and glaucoma progression (ISA). Nonselective adrenergic antagonists are available in both so-
in the early manifest glaucoma trial. Ophthalmology. 2007;114:205-9.
20. Budenz DL, Anderson DR, Feuer WJ, et al. Detection and prognostic significance of optic disc hemor- lution and gel formulations. A gel formulation increases the drug’s
rhages during the Ocular Hypertension Treatment Study. Ophthalmology. 2006;113:2137-2143. contact time, enhances efficacy and reduces systemic absorption but
21. Leske MC, Heijl A, Hyman L, Bengtsson B, Dong L, Yang Z; EMGT Group. Predictors of long-term progres-
sion in the early manifest glaucoma trial. Ophthalmology. 2007 Nov;114(11):1965-72. is usually uncomfortable. Istalol is a specific formulation of timolol
22. Leske MC, Wu SY, Hennis A, Honkanen R, Nemesure B; BESs Study Group. Risk factors for incident open-
angle glaucoma: the Barbados Eye Studies. Ophthalmology. 2008 Jan;115(1):85-93.
maleate that increases the drug’s penetration into the eye, allowing
23. Kass MA, Gordon MO. Ocular Hypertension Treatment Study Group. Diabetes and glaucoma. Arch Ophthal- it to be used once per day. The beta-adrenergic antagonists reduce
mol. 2008 May;126(5):746- 747.
24. The Ocular Hypertension Treatment Study Group and the European Glaucoma Prevention Study Group. IOP between 22 -28% by inhibiting the production of aqueous hu-
The accuracy and clinical application of predictive models for primary open angle glaucoma in ocular hyper- mor. The nonresponder rate is approximately 20%. While the dosage
tensive individuals. 2008; Ophthalmology.
25. Boland MV, Quigley HA, Lehman HP. The impact of risk calculation on treatment recommendations made for solutions is listed as bid, the nighttime dosage has little impact
by glaucoma specialists in cases of ocular hypertension. J Glaucoma. 2008; 17:631-638.
on IOP reduction. The morning instillation is the more important
for the patient to perform. Topically, the drugs are well-tolerated.
The larger concern with the use of topical adrenergic antagonists
6 | Understanding IOP Lowering Medications is their systemic absorption and potential side effects. Side effects
Murray Fingeret, OD include confusion, lethargy, fatigue, bronchospasm and bradycardia.
While beta-adrenergic blockers appear to be safe as long as patients
Medical therapy is the most common method used for the re- with known contraindications (such as pulmonary conditions) avoid
duction of the intraocular pressure (IOP) associated with ocular them, their use nonetheless has declined over the past decade with
hypertension (OHT) and open-angle glaucoma (OAG). Several classes the introduction of PGs. PGs have less systemic side effects than
of drugs (prostaglandin derivatives, beta-adrenergic antagonists, beta blockers and a better dosing schedule. Also, oral adrenergic
carbonic anhydrase inhibitors, adrenergic agonists and cholinergic antagonists are used by internists and cardiologists to treat many
agonists) may be used to reduce the IOP. Medications may be clas- cardiovascular conditions. When given systemically, they often re-
sified in several ways: their mechanism of action, efficacy, safety, duce the IOP, minimizing the impact if a topical beta blocker is also
tolerability and patient acceptance. Mechanism refers to what recep- utilized. In most situations when patients requiring IOP reduction are
tor is stimulated or blocked as the drug achieves its effect. Efficacy on oral beta-adrenergic antagonists, PGs become the drug of choice.
refers to how well the medication reduces IOP, both in the short-and Still, one advantage of this drug class is that drugs such as timolol or
long-term. What is the drug’s response rate? For example, how many levobunolol are available as generics, which are less expensive than
individuals will have their IOP reduced from the baseline level by branded medications.
15%, 20%, 25%, 30% or more? How often will the IOP creep back Apraclonidine (Iopidine) was the first drug in a class known as ad-
towards pre-treatment levels months to years later? Tolerability re- renergic agonists. Brimonidine (Alphagan, Alphagan P) is the other
fers to how well the drug is tolerated and accepted. How often does member of this category and the most commonly used drug in this
the patient or doctor feel that side effects preclude continuing the class. Adrenergic agonists inhibit the production of aqueous humor
medication? In the perfect world, the clinician would like to select an and enhance outflow mechanisms, which leads to an IOP reduction
agent that shows excellent efficacy and persistency, as well as being of 22% to 28%. Several side effects occur with apraclonidine includ-
safe and well-tolerated. ing the development of an allergic follicular conjunctivitis and loss
Cholinergic agents, such as pilocarpine, were the most commonly of effect over time (tachyphylaxis). Brimonidine is affected to some
used agent to treat open angle glaucoma until the introduction of extent by these same side effects but has replaced apraclonidine as
timolol. In 1978, beta-adrenergic antagonists were introduced and the adrenergic agonist of choice. One important difference between
soon thereafter became the drug of choice. Their popularity stemmed adrenergic agonists and beta-adrenergic antagonists is the dura-
from improved efficacy, a reduced dosing schedule and favorable side tion of action. The short duration of action of adrenergic agonists
effect profile. Over the next two decades, other drug classes (topi- requires that they be used on a tid dosage when they are the only
cal carbonic anhydrase inhibitors, adrenergic agonists, cholinergic medication utilized. This peak-and-trough effect associated with
agents) became available to complement beta-adrenergic blockers. adrenergic agonists is one reason why they are commonly used in a
During this period, several adrenergic agonists (epinephrine, dipiv- secondary role. When used in conjunction with other agents, they
efrin) became obsolete as newer drugs with significant advantages can be used on a bid basis. Brimonidine is available in a branded
came to market. In 1996, a further evolution occurred with the intro- product (Alphagan P, 0.10%, 0.15%) and a generic formulation
duction of prostaglandins (PGs). The first PG introduced, latanoprost (0.2%). Adrenergic agonists are relatively safe medications, though
(Xalatan), soon replaced beta-adrenergic blockers such as timolol, as they should not be used in children due to concerns regarding leth-
the primary agent to lower IOP in ocular hypertension and glaucoma. argy. Other side effects include dry mouth, fatigue and drowsiness.
With the use of PGs, IOPs once obtainable with multiple medications Brimonidine 0.2% along with Timolol 0.5% makes up the fixed-

combination product Combigan, and is a bid agent. The indication side effect and is seen least commonly with latanoprost, followed
for this medication is when additional IOP reduction is needed. It is by travoprost, with bimatoprost causing hyperemia most often.
not typically used as a first line agent but rather run in after one Other side effects include iris darkening, which is most commonly
of the drugs components is tried found to be safe and effective but seen in individuals with mixed-colored iris, periorbital skin darken-
additional IOP lowering is desired. ing, eyelash growth, anterior uveitis, cystoid macula edema (CME)
Topical carbonic anhydrase inhibitors (CAI) inhibit the production and irritation. Travatan Z is a newer formulation of travoprost,
of aqueous humor and reduce the IOP by 16% to 22%. They work by with Sofzia being used as the preservative instead of benzalkonium
inhibiting the enzyme carbonic anhydrase in the ciliary processes of chloride (BAK). The intent with the introduction of a non-BAK
the eye. Originally, CAIs were available only in an oral form (acet- preserved solution is to reduce symptoms that may be associated
azolamide, methazolamide) and were known to induce systemic side with chronic BAK use. CME and anterior uveitis are rare and, when
effects, such as paresthesias, depression, diarrhea, metallic taste, present, almost always occur in eyes with a risk factor such as prior
kidney stones and aplastic anemia. Because CAIs reduce IOP so ef- intraocular surgery or a history of iritis. Eyelash growth is reason-
fectively, a topical formulation was developed. With topical prepara- ably common, but fortunately is only a cosmetic concern. The iris
tions, the inhibition of the carbonic anhydrase enzyme is limited to color change is caused by an increase in the size and number of
the eye, dramatically reducing systemic side effects. Dorzolamide melanin granules within the iris stromal melanocytes. The pigment
2% (Trusopt) solution was the original drug in this class, followed is contained within the iris, and no signs of increased pigmentation
by brinzolamide 1% (Azopt) suspension. These topical formulations are seen anywhere else in the eye. Periorbital skin darkening is
have been shown to be safe, with the most common side effects be- another commonly encountered side effect that typically disappears
ing local irritation such as burning and stinging (more pronounced upon discontinuation of the agent.
with dorzolamide). However, one concern is that the drugs are from There has been controversy as to which of the PGs most effectively
the sulfa family and are therefore contraindicated in individuals with reduces IOP. Well-conducted studies provide conflicting results. For
sulfa allergies. CAIs are rarely a primary medication and are almost example, the XLT study evaluated the three PGs and showed that
always used with other agents. Topical CAIs are quite effective when they were comparable in efficacy, while hyperemia was most com-
employed in combination with other agents. When combined with mon with bimatoprost. A meta-analysis published by van der Valk
timolol to produce Cosopt (timolol-dorzolamide), which is used twice et al also showed PGs to be similar in efficacy. In a study performed
per day. CoSopt has recently become available generically. Topical by Noecker, Bimatoprost showed slightly greater efficacy along with
CAIs are an excellent secondary agent, used when the individual’s increased side effects. Another area of question is whether switching
primary drug is effective and tolerated but further IOP reduction is PGs within the class is an effective strategy. There are several rea-
needed. sons why a PG may not be effective in a particular patient. Different
Cholinergic agents reduce the IOP by causing the ciliary muscle studies have shown that approximately 9% of individuals will show
to contract, leading to improved flow through the trabecular mesh- <15% IOP reduction when any of the PGs are utilized. Will switching
work. Pilocarpine is the most common of the agents making up this from one PG to another lead to a greater IOP drop? Possibly, but the
class and is available in concentrations ranging form 0.5% to 12%. studies used to evaluate this question are confusing. Switch studies
The most frequently used strengths are 1%, 2% and 4%. Pilocarpine have shown that no matter what the first or second drug is, IOPs will
is used infrequently due to its qid dosing schedule and commonly be lower on the second drug. Reasons why the IOP may be reduced
induced local side effects including browache, dim vision, blurred include improved compliance or a phenomenon called regression to
vision and headache. It is a safe drug systemically and can reduce the mean. Regression to the mean describes the situation in which it
IOP up to 25%. takes several IOP readings (data points) to know what the true IOP
The introduction of timolol led to a quiet revolution in the way range is throughout the day (diurnal variation). Whether a switch
glaucoma was managed. Therapy went from an irritating, difficult- within class lowers IOP over the long term is still open to question.
to-tolerate agent (pilocarpine) to one that was well-tolerated and It may reasonable to switch within class to obtain lower IOPs but
effective (timolol). A further revolution occurred in 1996 with the the clinician should understand that short term IOP reduction may
introduction of latanoprost (Xalatan). Dosage was reduced to once not be achieved in the long term. Still, if a person is experiencing
per day, IOP reduction enhanced (26% to 34%) and systemic and lo- side effects with one PG, switching to another is an advisable step in
cal side effects reduced. The increase in uveoscleral outflow is caused reducing these symptoms.
by the elevated presence of metalloproteinases, which break down Fixed combination (FC) products include timolol 0.5%-dorzolamide
the collagen matrix within the uveoscleral region that surrounds 2% (CoSopt) and timolol 0.5%-brimonidine .2% (Combigan). Combi-
the ciliary muscle bundles. New channels for aqueous outflow are gan is the first combination product approved by the FDA in 10 years.
created, boosting uveoscleral outflow to greater than 50% of total There are other fixed-combination products available throughout the
flow from the eye. Since the introduction of latanoprost, additional world but the FDA has stringent requirements in regards to both
PGs have become available including bimatoprost (Lumigan) and IOP reduction and safety and only recently approved Combigan. FC
travoprost (Travatan). Both latanoprost and bimatoprost are listed products are typically used as adjunctive agents when further IOP
on the drug’s package insert as capable of being a primary agent. reduction is required. These agents reduce the IOP additionally by ap-
PGs have a long duration of action, allowing them to be used once proximately 20-25%. Both drugs mirror the side effect profile of their
per day while maintaining a flattened diurnal curve throughout a individual components. Surprisingly, the side effect profile for Com-
24-hour period. If needed, other glaucoma agents may be added to bigan appears to be better than expected. One issue with brimondine
PGs. Tachyphlaxis and systemic side effects are rare with local side 0.2% was the development of allergic conjunctivitis which is lower
effects while irritating, not serious. Hyperemia is the most common with Combigan as compared to use of brimonidine alone.

The advantages of FC products are convenience (one drop instead commences, a strategy is developed based upon the stage of disease,
of two), improved compliance, reduced exposure to preservatives and the person’s age, IOP level, as well as other factors. A target intra-
less chance of the second drop washing out the first. Approximately ocular pressure (IOP) range is determined and a medication selected.
40% of individuals on a PG require a second agent to achieve the If therapy is not indicated, the patient is often classified as a glau-
target pressure. A drug such as brimonidine or dorzolamide may be coma suspect and followed once to twice per year, depending upon
then added to the PG to further reduce the IOP. If this agent is ef- the individual’s characteristics. The category of glaucoma suspect
fective and tolerated but further IOP reduction is needed, the second includes individuals with ocular hypertension as well as suspicious
agent is then discontinued and replaced with the fixed combination optic nerves or visual fields.
product. This allows two bottles to be used with three agents going When medical therapy is initiated, the selection for the initial
into the eye to reduce IOP. While some clinicians may go directly to agent usually comes from one of two classes of drugs: prostaglandins
a fixed combination agent, this is not recommended since if either of (PGs) or topical beta-blockers. Over the last decade, PGs have replaced
the agents in the FC product is not effective or side effects occur, it beta-adrenergic antagonists as the most commonly used agent for
may not be clear which agent is the culprit. initial therapy. This is due to their ability to reduce IOP efficiently
Glaucoma medications have evolved over time. We are now at a on a once-per-dosage schedule, without inducing serious side effects,
point where PGs have become the primary agent for therapy, and as well as their dampening IOP fluctuations that may occur over a
timolol is used less often in a primary role. Other agents, including 24-hour period (diurnal curve).
FC products may be used to complement PGs, always with the aim The initial medication selected is based upon its ability to reduce
of reducing the IOP to the needed target levels while keeping side IOP, its safety profile, tolerability and patient acceptance. The drug
effects to a minimum. needs to be matched to the patient. For example, a patient with a
history of anterior uveitis or macula edema would not be a good
Suggested Readings candidate for PG therapy. Likewise, a patient with pulmonary disease
1. Lama PJ. Systemic adverse effects of beta-adrenergic blockers: an evidence-based assessment. Am J Oph-
thalmol. 2002 Nov;134(5):749-60. would not be a candidate for beta-adrenergic antagonist therapy.
2. Camras CB, Hedman K; US Latanoprost Study Group. Rate of response to latanoprost or timolol in patients Target IOPs must also be considered as a therapeutic agent is selected.
with ocular hypertension or glaucoma. J Glaucoma. 2003 Dec;12(6):466-9.
3. Latanoprost treatment for glaucoma: effects of treating for 1 year and of switching from timolol. United Target pressures refer to the range of IOP that we hope will prevent
States Latanoprost Study Group. Latanoprost treatment for glaucoma: effects of treating for 1 year and of
switching from timolol. United States Latanoprost Study Group. Am J Ophthalmol. 1998 Sep;126(3):390-9.
further deterioration. A patient’s target IOP may change over time,
4. Additive intraocular pressure lowering effect of various medications with latanoprost. Additive intraocular either as new knowledge becomes available indicating lower IOPs will
pressure lowering effect of various medications with latanoprost. Am J Ophthalmol. 2002 Jun;133(6):836-7.
5. Netland PA, Landry T, Sullivan EK, Andrew R, Silver L, Weiner A, Mallick S, Dickerson J, Bergamini MV, be advantageous or if progression is confirmed. Target IOPs are a best
Robertson SM, Davis AA; Travoprost Study Group. Travoprost compared with latanoprost and timolol in pa- guess of what IOP will control the condition. The best indicator to
tients with open-angle glaucoma or ocular hypertension. Am J Ophthalmol. 2001 Oct;132(4):472-84.
6. Schumer RA, Camras CB, Mandahl AK. Putative side effects of prostaglandin analogs. Surv Ophthalmol. show that target IOP has been achieved is when periodic optic nerve
2002 Aug;47 Suppl 1:S219.
7. Noecker RS, Dirks MS, Choplin N; Bimatoprost/Latanoprost Study Group. Comparison of latanoprost,
and visual field evaluations reveal no change. If change is noted, ad-
bimatoprost, and travoprost in patients with elevated intraocular pressure: a 12-week, randomized, masked- ditional reduction is necessary.
evaluator multicenter study. Am J Ophthalmol. 2004 Jan;137(1):210-1.
8. Parrish RK, Palmberg P, Sheu WP; XLT Study Group. A comparison of latanoprost, bimatoprost, and travo- Target IOPs are based on the amount of damage present and the
prost in patients with elevated intraocular pressure: a 12-week, randomized, masked-evaluator multicenter highest IOP reading, with greater reduction required as damage wors-
study. Am J Ophthalmol. 2003 May;135(5):688-703.
9. Zimmerman TJ, Review of clinical studies of beta-blocking agents.Surv Ophthalmol. 1989 Apr;33 Sup- ens. Recent clinical trials have provided evidence that lower target
pl:461-2.
10. Van der Valk R, Webers CA, Schouten JS, Zeegers MP, Hendrikse F, Prins MH. Intraocular pressure-lower-
IOPs are important, though no study has shown exactly what IOPs
ing effects of all commonly used glaucoma drugs a meta-analysis of randomized clinical trials. Ophthalmol- are optimal. The Ocular Hypertension Treatment Study (OHTS), which
ogy. 2005 July, 112 (7): 1-7.
11. Toris CB, Koepsell SA, Yablonski ME, Camras CB. Aqueous Humor Dynamics in Ocular Hypertensive Pa- had a target IOP reduction of 20%, found that 4.4% of individuals
tients. J Glaucoma. 2002 November; (1)53-258.
12. Toris CB, Yablonski ME, Wang YL, Camras CB. Aqueous Humor Dynamics in the Aging Human Eye. Am J
in the therapy group progressed. In a study of glaucoma patients,
Ophthalmol 1999. April; 127 (4): 407-412. the Early Manifest Glaucoma Trial (EMGT), in which the average IOP
13. Liu JH, Sit AJ, Weinreb RN. Variation of 24-hour intraocular pressure in healthy individuals: right eye
versus left eye. Ophthalmology. 2005 Oct;112(10):1670-5.
reduction was 25%, 45% of patients in the therapy group progressed
14. Mossaed S, Liu JH, Weinreb RN. Correlation between office and peak nocturnal intraocular pressures in over time. The Collaborative Initial Glaucoma Treatment Study
healthy subjects and glaucoma patients.
Am J Ophthalmol. 2005 Feb;139(2):320-4. (CIGTS) which also used a group of patients with glaucoma monitored
15. Liu JH, Zhang X, Kripke DF , Weinreb RN Twenty-four-hour intraocular pressure pattern associated with
early glaucomatous changes. Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1586-90
for progression. CIGTS found little change in the group whose IOP was
16. Sherwood MB, Craven ER, Chou C, DuBiner HB, et al. Tice-daily 0.2% brimonidine-0.5% timolol fixed com- reduced 38%. In the Advanced Glaucoma Intervention Study (AGIS),
bination therapy vs. monotherapy with timolol or brimonidine in patients with glaucoma or ocular hyperten-
sion: a 12-month randomized trial. groups were broken down based on the percentage of visits in which
the IOP was reduced below 18mmHg. One group with a mean IOP of
20.2mmHg showed significant deterioration while another group with
7 | The Management of Glaucoma a mean IOP of 12.3mmHg appeared to be stable over an eight-year
period. These studies, taken as a whole, do not provide evidence that
Murray Fingeret, OD IOPs need to be reduced to the low teens for all patients, but they
do illustrate the need to reduce IOPs to lower levels than previously
There are many situations that confront the optometrist as he thought.
or she decides whether to initiate therapy for ocular hypertension The EMGT found risk factors associated with glaucomatous
(OHT) or glaucoma. For ocular hypertension, the decision process, progression include higher IOP at the time of diagnosis, pseudoex-
which involves the concept of risk, is discussed in Chapter 5. In foliation, bilateral disease, disc hemorrhages, older age and worse
regard to glaucoma, when optic nerve and/or visual field damage as- visual field mean deviation. The AGIS found variation in IOP over a
sociated with glaucoma is recognized, therapy is in order. The signs 24-hour period as an additional risk factor. This is a separate risk
of glaucomatous damage are discussed in chapter 2. Before therapy that describes IOP fluctuation throughout the day, even when IOP

is low at certain time points. To recognize diurnal fluctuations, one the initial medication. In this case, the IOP response needs to be
should record the time of each visit and schedule exams at varying evaluated. For example, if the IOP was very high and/or the damage
times during the day. significant, leading to a target goal of 40% reduction, and the drug
Often it is helpful to begin therapy with a monocular or unilateral provides 25% of the target reduction, then the medication appears
trial in which medication is begun in one eye for a few weeks, with to be effective, but a second agent is needed. On the other hand, if
the contralateral eye serving as a control. The rationale is that IOP, the actual reduction is 15% or less, the patient may be considered
while often different between the two eyes, will rise and fall over the a non-responder. Inadequate responses do occur and are not often
day to a similar degree. Also, the response to a medication should be recognized, leading to unachieved target levels. We should ask if
similar in both eyes. Since non-responder rates vary from 8% to 25% progression may occur in 15 years at the present IOP level. It may
depending on the class of medication, a monocular trial is one way to be then easier to appreciate the urgency of attempting to achieve
ensure the medication is effective as well as determine if side effects target IOP levels.
are occurring. Anthony Realini has, in a series of studies, questioned There are different reasons why the IOP may not have been re-
the use of the monocular trial. His rationale is that IOP reduction duced with the initial agent, including lack of response or poor com-
in one eye does not predict performance of the drug in other eye. pliance with the clinician faced with a decision of how to proceed.
Moreover, monocular trials require at least one additional visit. Switching to a drug within the same class, such as going from one
Nevertheless, many experts continue to recommend the monocular PG to another (intra-class switches) is controversial since it is not
trial, recognizing its limitations but also using it as a way to control proven that such switches work. Switch studies with PGs have shown
initiation of a new drug. that the medication switched to always performs better. Also, most
At the outset of therapy, the patient needs to be educated in switch studies have been conducted over short periods, usually about
regard to the optimal time for drop instillation(s) and potential side 30 days which is not long enough to evaluate the response. The im-
effects. It is important to demonstrate proper eyedrop instillation proved efficacy may be due to the second drug’s greater response, but
technique and have the patient demonstrate that he/she can prop- other possible reasons for the reduction include improved compliance
erly instill the drops. If eyedrop instillation appears to be a problem, or fluctuations in IOP (regression to the mean).
there are devices to aid instillation. Also, a companion or family If the medication is effective but further reduction is needed,
member may aid in medication insertion. Finally, written dosing either because the IOP is above the target goal or progression is iden-
schedules should be provided as reminders. The first follow-up visit tified, the practitioner may choose an additional medication. If a PG
usually occurs two to four weeks after therapy commences. At each is the initial agent, the second agent may be a beta-blocker, alpha
visit, ask if any side effects have occurred and when the patient agonist or topical CAI. A beta-blocker offers the convenience of once-
last used the medication(s). Patient communication is discussed in per-day use; thus the patient would take it in the morning and take
Chapter 10. Even when written schedules are provided, some patients the PG at nighttime. Still, there is evidence that beta-blockers do not
misunderstand how to use the medication. Questions that should be offer much additional IOP reduction when added to a PG. When added
addressed at every visit include whether the patient is actually using to a PG, topical CAIs or alpha agonists may be more effective at lower-
the drug or if there are any problems or concerns. The IOP is mea- ing IOP than beta-blockers but they require twice-per-day dosage. If a
sured to assess whether the medication is effective and IOP is at tar- patient is on a PG along with a beta-blocker, alpha agonist or topical
get level. If the drug is well-tolerated and effective, then the patient CAI and further IOP reduction is needed, then these drugs may be
is followed over time, watching for medication side effects as well as discontinued and a fixed-combination agent containing timolol-
progression. Patients are seen every three to six months depending dorzolamide (Cosopt) or timolol-brimonidine (Combigan) begun. It
on severity and type of disease. Ocular hypertensives are monitored is important to stress to patients taking two medications that they
less often and individuals with significant loss more often. Dilated should wait five minutes before instilling the second agent to avoid
optic nerve evaluation, imaging and visual field testing should be washing the first from the eye. Also, remember to instruct patients
performed at least yearly. Testing more often is recommended if a taking beta-blockers to close their eyes or occlude their punctum for
greater degree of loss is present or a question of stability arises. three minutes. This will reduce systemic absorption, improve efficacy
Gonioscopy is usually performed every other year. and reduce side effects. Argon or Selective Laser Trabeculoplasty and
An important question that should be considered early in the filter surgery become options when the patient is progressing or the
course of follow-up is the rate of change. If a patient is progressing IOP is above the target level, and several medical options have been
rapidly, this needs to be recognized and therapy modified. One way tried (see Chapter 8).
to measure rate of change is to perform perimetry on a six-month ba- In some cases, even with patients who respond well to initial
sis for the first two years. This is best done with SITA visual fields and therapy, the IOP may slowly rise over time (long-term drift). Such
the Glaucoma Progression Analysis (GPA) software tool. If the fields increases could be due to the glaucoma worsening, problems with
are unchanged, the interval between field testing can be increased to compliance or the development of tachyphylaxis. The two questions
yearly. Approximately five fields are needed before a decision can be to ask are: is the drug effective, and is it being used? If the IOP is
rendered regarding stability. elevated, instill the medication and measure the IOP one-two hours
One challenge occurs when the IOP is not reduced adequately or later. Also, observe the patient’s drop instillation technique to de-
side effects develop with the initial medication. If side effects oc- termine if the drug is getting into the eye. And finally, the reverse
cur, what are they? Are they caused by the medication? May they monocular trial may be helpful to address whether tachyphlaxis has
be reduced if a switch occurs within the same class of drugs? An developed. In this trial, the drug is temporarily discontinued in one
intra-class switch may work if hyperemia develops with one PG. A eye and continued in the other. If tolerance has developed, there
more difficult question is if the target IOP level is not reached with will be little change in the untreated eye’s IOP over the next several

weeks. However, a rising IOP proves the drug is effective and should for repeat procedures has been proposed as a possible advantage to
be continued, but an additional agent is necessary. SLT with a recent retrospective case series demonstrating further IOP
The management of ocular hypertension and glaucoma is an art reduction with repeat 360° SLT as early as 6 months following loss of
that requires the clinician to make an ongoing series of decisions and efficacy from the initial SLT procedure. The IOP reduction from any
adjustments over the patient’s lifetime to ensure the IOP remains at form of laser trabeculoplasty is generally equivalent. The IOP decline
acceptable levels and the condition does not worsen. Periodic moni- is typically not permanent, with IOP often rising to pre-treatment
toring of the optic nerve, retinal nerve fiber layer and visual fields levels over a few years. New laser techniques include the 790 nm
are also necessary. The doctor needs to consider both the short and titanium: sapphire laser (TiSaLT by SOLX Inc., Waltham MA) which
long-term view to ensure stability occurs throughout the lifetime of has been shown to be comparable to ALT as well as micropulse laser
their patient. trabeculoplasty (MLT) which utilizes an 810 nm diode laser to pre-
vent cellular destruction as occurs in ALT (IQ 810, Iridex, Mountain
Suggested Readings View, CA).
1. Realini T, Fechtner RD, Atreides SP, Gollance S. The uniocular drug trial and second-eye response to glau-
coma medications. Ophthalmology. 2004 Mar;111(3):421-6. Glaucoma filtering surgery is intended to provide long-term con-
2. Realini T, Vickers WR. Symmetry of fellow-eye intraocular pressure responses to topical glaucoma medica- trol of IOP without medications and to maintain adequate diurnal
tions. Ophthalmology. 2005 Apr;112(4):599-602.
3. Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK 2nd, Wilson MR, control with minimal post-operative complications or subjective
Gordon MO. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular
hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol.
discomfort. The current gold standard for glaucoma filtering surgery
2002 Jun;120(6):701-13. is the trabeculectomy with adjunctive anti-fibrotic agents applied
4. Gordon MO, Beiser JA, Brandt JD, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish
RK 2nd, Wilson MR, Kass MA. Baseline visual field characteristics in the ocular hypertension treatment study. intraoperatively or injected postoperatively (e.g. mitomycin-C [MMC],
Ophthalmology. 2002 Mar;109(3):432-7. 5-fluorouracil [5-FU]). Trabeculectomy (guarded scleral fistulization),
5. Higginbotham EJ, Gordon MO, Beiser JA, Drake MV, Bennett GR, Wilson MR, Kass MA; Ocular Hypertension
Treatment Study Group. The Ocular Hypertension Treatment Study: topical medication delays or prevents pri- was first popularized by Cairns in 1968. Trabeculectomy remains as-
mary open-angle glaucoma in African American individuals. Arch Ophthalmol. 2004 Jun;122(6):813-20.
6. Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M; Early Manifest Glaucoma Trial Group.
sociated with a number of complications including bleb dysesthesia
Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. (symptomatic bleb), cataract, bleb failure, hyphema, wound leak,
Arch Ophthalmol. 2002 Oct;120(10):1268-79.
7. Heijl A, Leske MC, Bengtsson B, Bengtsson B, Hussein M; Early Manifest Glaucoma Trial Group. Measuring flat anterior chamber, ocular hypotony, hypotony maculopathy,
visual field progression in the Early Manifest Glaucoma Trial. Acta Ophthalmol Scand. 2003 Jun;81(3):286-93. choroidal detachment, suprachoroidal hemorrhage, bleb infection,
8. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular
pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol. 2000 Oct;130(4):429-40. and endophthalmitis. Surgical variations of this procedure have been
9. Feiner L, Piltz-Seymour JR; Collaborative Initial Glaucoma Treatment Study. Collaborative Initial Glaucoma
Treatment Study: a summary of results to date. Curr Opin Ophthalmol. 2003 Apr;14(2):106-11.
designed to reduce the frequency of these complications. The use
10. O’Connor DJ, Martone JF, Mead A. Additive intraocular pressure lowering effect of various medications of anti-fibrotics reduces the risk for bleb failure by repressing the
with latanoprost. Am J Ophthalmol. 2002 Jun;133(6):836-7.
11. Bengtsson B, Leske MC, Hyman L, Heijl A. Early Manifest Glaucoma Trial Group. Fluctuation of information of scar tissue at the surgical site but may lead to ischemic
traocular pressure and glaucoma progression in the early manifest glaucoma trial. Ophthalmology. 2007
Feb;114(2):205-9.
filtration blebs vulnerable to leak and late infection.
12. Sherwood MB, Craven ER, Chou C, DuBiner HB, et al. Tice-daily 0.2% brimonidine-0.5% timolol fixed com- Anti-metabolites are indicated for high-risk patients, such as
bination therapy vs. monotherapy with timolol or brimonidine in patients with glaucoma or ocular hyperten-
sion: a 12-month randomized trial. Arch Ophthalmol 2006; 124(9):1230-38.
younger patients, those with a history of failed filtration surgery,
13. Stone JL, Robin AL, Novack GD, et al. An objective evaluation of eyedrop instillation in patients with African-Americans and individuals with aphakic, uveitic, neovascular
glaucoma. Arch Ophthalmol 2009; 127 (6): 732-36.
or secondary angle closure glaucoma. One concern is that anti-me-
tabolites, particularly mitomycin, have been associated with a higher
8 | When Medical Therapy Fails: Surgical risk for late wound leak, blebitis and endophthalmitis. Patients may
present initially with an infected bleb, or “blebitis,” associated with a
Options for Glaucoma Management painful red eye, photophobia and discharge. If the infection extends
Kathy Yang-Williams, OD into the eye (bleb-associated endophthalmitis), significant anterior
chamber reaction or hypopyon can result. Even with aggressive anti-
Surgical intervention becomes an option in the management of biotic treatment, the prognosis for patients with bleb-associated en-
open-angle glaucoma when the intraocular pressure (IOP) cannot be dophthalmitis is poor. Trabeculectomy is a well-established technique
sufficiently reduced with medical or laser therapy to prevent progres- but poses significant risk for early and late post-operative complica-
sive optic nerve damage and/or visual field loss. Surgery should also tions. Frequent post-operative visits are necessary and additional
be considered when medical treatment is unavailable, the patient interventions may be required to ensure the success of the procedure.
cannot adhere to the treatment regimen or the cost of medical Even with adjunctive anti-fibrotics, up to 50% of trabeculectomies
therapy exceeds their means. Consideration for surgical interven- fail by five years.
tion should include disease severity, advanced optic nerve damage The FDA approved Ex-PRESS mini glaucoma shunt is a procedure
or visual field defects with threat to central vision, and the age and similar to trabeculectomy initially; however, no peripheral iridec-
systemic status of the patient. tomy is required (Optonol Inc, Kansas City, KS). Instead, a 3mm
Selective laser trabeculoplasty (SLT) is a newer procedure per- long, non-valved stainless-steel implant (usually with an internal
formed with a Q-switched 532nm Nd:YAG laser to reduce IOP (Lu- diameter of 50µ) is placed under a partial thickness flap [Figure 1].
menis Inc, Santa Clara CA). SLT may cause less collateral damage than Originally, the Ex-PRESS shunt was placed under the conjunctiva
argon (ALT) or Diode laser trabeculoplasty as it “selectively” targets alone but this was accompanied by a high incidence of extrusion,
the pigment-containing cells in the trabecular meshwork (TM) using hypotony and related complications. A revised technique places
a larger spot size, lower power setting and less total energy than ALT the device underneath a scleral flap and utilizes intraoperative
or diode. As compared to ALT, SLT creates less thermal damage to mitomycin. A retrospective study comparing the Ex-PRESS to stan-
the trabecular meshwork, less post-operative pain and inflammation, dard trabeculectomy reported the Ex-PRESS implant under a scleral
and is less dependent on pigmentation of the angle. The potential flap had similar IOP-lowering efficacy with a lower rate of early

hypotony compared with controlled infusion of balanced salt during surgery. Transient intra-
trabeculectomy. A recent operative hyphema due to blood reflux into Schlemm’s canal usually
prospective, randomized resolves within the first week. Initial results are promising, with IOP
trial found better success reduction in the 40% range at 36 months and limited data showing
with the Ex-PRESS shunt prolonged reduction (IOP reduction of 32%) at 60 months. Immedi-
compared to trabeculec- ate post-operative elevation of IOP may occur infrequently (5.8%)
tomy and similar rates of but there is no bleb formation or risk for flat anterior chamber and
post-operative complica- peri-limbal conjunctiva is preserved if further surgical intervention
tions and interventions. becomes necessary.
Figure 1. ExPRESS mini glaucoma shunt. (Courtesy of
Dr. Rouwen, Netherlands) An additional compara- Another innovation is the Glaukos iStent (Glaukos Corp., Laguna
tive case series of 345 Hills, CA). This trabecular micro-bypass stent is an L-shaped tita-
eyes (241 Ex-PRESS alone and 114 Ex-PRESS combined with cataract nium tube that is implanted ab interno into Schlemm’s canal with
surgery) with follow-up of 3 years reported 94.8% success for the an inserter via a small opening through TM. The iStent bypasses the
Ex-PRESS implant only group, and 95.6% for the combined group trabecular meshwork and restores aqueous flow from the anterior
(IOP≤21mmHg with or without medications). The most common chamber into Schlemm’s canal [Figure 4]. Again, no bleb is formed
device-related complication was obstruction of the tube in 6 eyes and the placement of the iStent preserves all future options for
(1.7%), which was treated successfully with Nd:YAG laser in all 6 glaucoma filtering surgery. A small case series with the latest version
eyes. Longer term complication rates related to the device or bleb of this device has demonstrated post-operative intraocular pressures
formation are yet unknown. of 14 mmHg-15 mmHg at 12 months. In tissue-culture autopsy eye
Non-penetrating glaucoma surgeries (such as viscocanalostomy studies, multiple implants were demonstrated to further reduce IOP
and deep sclerectomy with or without collagen implant) reduce the than one implant. Interim analysis of a study combining iStent
risk of flat anterior chamber in the immediate post-operative period implantation and cataract surgery showed a mean decrease in IOP
by creating an alternative outflow pathway without the anterior of 18.3%.
chamber being penetrated as occurs in trabeculectomy. Non-pene- The SOLX Gold Shunt (Solx Inc, Waltham, MA) is an implantable
trating glaucoma surgeries do not usually result in the formation of drainage device designed to reduce elevated intraocular pressure as-
a filtering bleb and if a bleb develops post-operatively, it tends to be sociated with glaucoma. The device is fabricated from biocompatible,
more shallow and diffuse than that observed following trabeculec- 99.95% pure gold and provides a pathway for the flow of aqueous
tomy. However, studies evaluating non-penetrating glaucoma surgery humor from the anterior chamber of the eye to the suprachoroidal
show that intraocular pressure reduction is generally not as great as space, utilizing a natural drainage pathway within the eye [Figure 5].
that achieved with trabeculectomy. If further IOP reduction becomes Ongoing clinical studies have demonstrated the safety and efficacy
necessary, laser goniopuncture can convert a non-penetrating glau- of the Gold Shunt. A pilot study has demonstrated a mean 36.2% or
coma surgery to a penetrating surgery. In a ten-year study of deep 9 mmHg decrease in IOP (27.6 mmHg to 18.2 mmHg) using the first
sclerectomy with collagen implant, approximately 60% of patients generation of this device. European data from open label studies of
required laser goniopuncture postoperatively to maintain function. the second generation Gold Shunt demonstrated pressure reductions
The newest approaches to glaucoma surgery include canaloplasty of 49% maintained to one year with fewer adjunctive glaucoma
(iScience Interventional, Menlo Park, CA), in which Schlemm’s canal medications. Serious complications following implantation of the
is circumferentially catheterized and dilated with Healon GV (sodium Gold Shunt are rare.
hyaluronate, Advanced Medical Optics, Santa Ana, CA) using an Several types of aqueous shunts (glaucoma drainage devices) are
iTrack 250 Canaloplasty Microcatheter™ 200 microns in diameter with now employed, usually in complicated cases when other surgical
a diode light at its tip, allowing the iTrack™ to be viewed through the approaches have failed. A glaucoma drainage device (GDD) consists
sclera providing physician guidance during the procedure [Figure 2]. of an equatorial endplate of varying surface area and design that is
Once the canal has undergone 360° catheterization, a 10-0 Prolene inserted via either a limbal or fornix based conjunctival flap under
suture (Ethicon Inc, Somerville, NJ) is attached to the microcatheter Tenon’s capsule. The end-plate is attached to a drainage tube inserted
and pulled around as the iTrack™ is withdrawn and viscodilation into the anterior chamber or the posterior chamber after vitrectomy
occurs. This suture, when tensioned, stretches the TM internally via the pars plana. GDDs direct fluid into an external equatorial fil-
and in initial studies, lowers IOP. Interim study results demonstrate tering bleb developed around the explant plate. Initially after instal-
significant reduction in IOP with mean IOP of 16.3 mmHg two years lation, non-valved shunts
after canaloplasty and 13.4 mmHg after combined canaloplasty and (Baerveldt, Molteno) offer
cataract surgery. Medication use decreased in both study groups and little or no resistance to
serious complications such as hypotony were infrequent. outflow, but may be tran-
The Trabectome (NeoMedix Inc, Tustin CA) provides direct access siently constricted with a
to the distal outflow channels by removing a strip of meshwork and surrounding ligature with
inner wall of Schlemm’s canal allowing direct communication be- a variety of techniques.
tween the anterior chamber and collector channels (Figure 3). This ab Two devices (Ahmed, Kru-
interno trabeculectomy was FDA approved in 2004. The Trabectome pin) include valves or flow
tip includes a foot-pedal controlled bi-polar cautery unit that ablates restrictors that decrease
Figure 2. Intraoperative photo of iTrack 250
tissue with simultaneous aspiration of debris via a 25 gauge tube. the rate of immediate hy- Canaloplasty Microcatheter.™ (Courtesy of iScience
The hand piece includes an 18 gauge infusion sleeve allowing gravity potony without the need Interventional, Menlo Park, CA)

for a surrounding ligature. development of new imaging techniques and materials. The ultimate
A recent randomized trial goal of surgical intervention is to achieve long term IOP control with
(Tube vs. Trabeculectomy lower risk for surgical complication.
Study) with one-year fol-
low-up found IOP results Acknowledgements: The author would like to acknowledge Don S. Minck-
equivalent comparing a ler, MD for his insights and contributions to this article.
GDD to trabeculectomy Dr. Yang-Williams is in group optometric practice in Seattle, WA and
with MMC. Drainage im- adjunct Clinical Faculty at PUCO.
plants can reduce IOP 50%
Figure 3. Schematic representation of Trabectome below pre-operative levels. Suggested Readings
procedure. (Courtesy of Neomedix Inc, Tustin, CA) 1. Bahler CK, Smedley GT, Zhou J, Johnson DH. Trabecular bypass stents decrease intraocular pressure in
However, they are also cultured human anterior segments. Am J Ophthalmol. 2004; 138: 988-994.
associated with complica- 2. Bissig A, Rivier D, Zaninetti M et al. Ten years follow-up after deep sclerectomy with collagen implant. J
Glaucoma. 2008; 17: 680-686.
tions including hypotony, 3. Busbee BG. Recchia FM, Kaiser R, et al. Bleb-associated endophthalmitis: Clinical characteristics and visual
outcomes. Ophthalmology. 2004; 111: 1495-1503.
corneal decompensation, 4. De Jong LA. The Ex-PRESS Glaucoma Shunt versus trabeculectomy in open-angle glaucoma: a prospective
encapsulation of end-plate, randomized study. Adv Ther. 2009; 26: 336-345.
5. Filippopoulos T, Rhee DJ. Novel surgical procedures in glaucoma: advances in penetrating glaucoma sur-
erosion of tube or plate, gery. Curr Opin Ophthalmol. 2008; 19: 149-154.
suprachoroidal hemorrhage 6. Francis BA, See RF, Rao NA et al. Ab interno trabeculectomy: Development of a novel device (Trabectome)
and surgery for open-angle glaucoma. J Glaucoma. 2006; 15: 68-73.
and diplopia. A newer de- 7. Gedde SJ, Schiffman JC, Feuer WJ et al. Treatment outcomes in the tube versus trabeculectomy study after
one year of follow-up. Am J Ophthalmol. 2007: 143; 9-22.
vice, the Oculieve (Aque- 8. Goldenfeld M, Melamed S, Simon G, Ben Simon GJ. Titanium: sapphire laser trabeculoplasty versus argon laser
ous Biomedical, Colorado trabeculoplasty in patients with open-angle glaucoma. Ophthalmic Surg Lasers Imaging. 2009; 40: 264-269.
Figure 4. Scanning electron microscopy of iStent Springs, CO) may reduce 9. Hong BK, Winer JC, Martone JF et al. Repeat selective trabeculoplasty. J Glaucoma. 2009; 18: 180-183.
10. Kanner EM, Netland PA, Sarkisian SR, Haiming D. Ex-PRESS miniature glaucoma device implanted under a
trabecular micro bypass stent. (Courtesy of Glaukos
Corp, Laguna Hills, CA) these complications by scleral flap alone or combined with phacoemulsification cataract surgery. J Glaucoma. 2009; Epub ahead of print.
11. Lewis RA, von Wolff K, Tetz M et al. Canaloplasty: circumferential viscodilation and tensioning of Sch-
creating a smaller volume, lemm canal using a flexible microcatheter for the treatment of open-angle glaucoma in adults: Two-year
interim clinical study results. J Cataract Refract Surg. 2009; 35: 814-824.
thinner walled capsule with maximized surface area to enhance filtra- 12. Lin SC. Endoscopic and transscleral cyclophotocoagulation for the treatment of refractory glaucoma. J
tion. Drainage implants, or tube shunts, have traditionally been re- Glaucoma. 2008; 17: 238-247.
13. Mansouri K, Orguel S, Mermoud A, et al. Quality of diurnal intraocular pressure control in primary open-
served for patients who have uncontrolled IOP and a history of failed angle patients treated with latanoprost compared with surgically treated glaucoma patients: a prospective
filtration procedures, scleral buckling surgery, extensive conjunctival trial. Br J Ophthalmol. 2008; 92: 332-6.
14. McIlraith I, Strasfeld M, Colev G, Hutnik CM. Selective laser trabeculoplasty as initial and adjunctive
scarring or exaggerated inflammatory response (neovascular or treatment for open-angle glaucoma. J Glaucoma. 2006; 15: 124-130.
15. Melamed S, Ben Simon GJ, Goldenfeld M, Simon G. Efficacy and safety of gold micro shunt implantation
uveitic glaucoma). Interestingly, implants are being done more com- to the supraciliary space in patients with glaucoma. Arch Ophthalmol. 2009; 127: 264-269.
monly and some glaucoma surgeons are using them as their primary 16. Mendrinos E, Mermoud A, Shaarawy T. Nonpenetrating glaucoma surgery. Surv Ophthalmol. 2008; 53: 592-630.
17. Minckler DS, Hill RA. Use of novel devices for control of intraocular pressure. Exp Eye Res. 2009; 88: 792-798.
filtration surgical modality. 18. Minckler DM, Mosaed S, Dustin L et al. Trabectome (Trabeculectomy-internal approach): Additional expe-
Cyclodestructive procedures are reserved for refractory glaucoma in rience and extended follow-up. Trans Am Ophthalmol Soc. 2008; 106: 149-160.
19. Minckler DS, Francis BA, Hodapp ES et al. Ophthalmology Technology Assessment: Aqueous shunts in
eyes with failed filtering or drainage implant procedures and poor visu- glaucoma. Ophthalmology. 2008: 115; 1089-1098.
20. Realini T. Selective laser trabeculoplasty: A review. J Glaucoma. 2008; 17: 497-502.
al prognosis. The ciliary epithelium is damaged using transscleral laser 21. Singh K, Lee BL, Wilson MR et al. A panel assessment of glaucoma management: modification of existing
or cryotherapy, which decreases aqueous production. Cyclocryotherapy RAND-like methodology for consensus in ophthalmology. Part II: results and interpretation. Am J Ophthal-
mol. 2008; 145: 575-581.
is a freezing technique that creates significant ocular tissue damage 22. Speigel D, Wolfgang W, Neuhann T et al. Coexistent primary open-angle glaucoma and cataract: interim anal-
and is non-selective for the ciliary epithelium. Pain, inflammation, hy- ysis of a trabecular micro-bypass stent and concurrent cataract surgery. Eur J Ophthalmol. 2009; 19: 393-399.
23. Spiegel D, Wetzel W, Haffner DS, Hill RA. Initial clinical experience with the trabecular micro-bypass
potony and phthisis are common side effects. Cyclophotocoagulation stent in patients with glaucoma. Adv Ther. 2007: 24:161-170.
24. Wilcox MJ, Barad JP, Wilcox CC et al. Performance of a new low-volume, high surface area aqueous shunt
can be performed externally (transcleral) or internally (endoscopic) in normal rabbit eyes. J Glaucoma 2000; 9: 74-82.
with laser energy that is selective for the melanin in the ciliary epithe-
lium to result in relatively localized damage. The transcleral approach
employs an Nd:YAG, diode or krypton laser and generally results in 9 | Adherence in Glaucoma Therapy
less inflammation and pain than cyclocryotherapy. Endoscopic cyclo-
photocoagulation (ECP) uses an 810 nm pulsed continuous-wave diode Steven R. Hahn, MD
laser combined with a high-resolution fiber optic camera to selectively
ablate the anterior ciliary body processes (Endo Optiks, Little Silver, Patients do not benefit from medicines they do not take and
NJ). An advantage of this procedure is the ability to directly visualize most clinicians are aware that patients commonly fail to take all the
the target tissue. ECP has been medication that they are prescribed. Yet nonadherence does not re-
advocated by some surgeons ceive attention proportionate to its recognized importance in clinical
as an alternative to filtering practice. Although some physicians may need to be reminded about
surgery in patients with re- the magnitude of the problem, it is not a fundamental ignorance of
fractory glaucoma, good visual nonadherence that explains the lack of attention it receives. One
potential and only moderately answer may be that clinicians intuitively know what research on
elevated IOP requiring com- adherence has demonstrated: Nonadherence is difficult to detect,
bined surgery for glaucoma its causes may be hard to identify, and the factors that determine
and cataract. adherence often seem to be beyond the clinician’s control or scope of
Figure 5. Schematic representation of SOLX Gold Glaucoma surgery will clinical expertise. These beliefs may create a sense of powerlessness
Shunt. (Courtesy of SOLX Inc, Waltham, MA) continue to evolve with the that is ultimately rationalized by the feeling that nonadherence is a

revelation of the imperfection of human nature and might as well be record the opening of a pill bottle, or use of a medication dispenser
accepted. The goal of this chapter and the next one addressing doc- is one of the most reliable methods. In studies of adherence to glau-
tor patient communication is to reverse this pessimism and empower coma medications using MEMS devices almost half of patients (41%)
clinicians by providing necessary information on the prevalence and miss 10% of three times daily pilocarpine doses, i.e., one dose in
causes of nonadherence and, in the next chapter, communication every two days. In another study using the same technology, more
strategies to aid in detecting nonadherence and its causes, and in than a quarter of patients (27.3%) missed more than a quarter of
enhancing motivation and lowering barriers to adhere. timolol doses when used either alone or in combination with pilo-
Patient compliance was the term originally used to describe the carpine or another medication, and a small but significant number of
extent to which patients take medication and follow lifestyle and patients (8.2% and 15.2%) missed half or more of their medications.
behavioral recommendations prescribed by their clinicians. The term In a recent study, 44% patients using a travoprost electronic dosing
“adherence” has largely supplanted “compliance” because the latter aid that recorded and reported medication use took fewer than 75%
carries the connotation of a paternalistic clinician-directed relation- of doses. Medications that are taken more than once per day are also
ship in which patients “comply” with the directives of their doctor. vulnerable to problems with the timing of doses. Morning medica-
By contrast, adherence connotes a patient’s willingness to “stick to” a tions are taken more reliably than doses later in the day and noon
treatment that they have agreed upon with their clinician. A consen- doses are the most frequently omitted. Studies using MEMs recorders
sus panel convened by the World Health Organization chose to define are usually of short duration, and typically over sample more persis-
adherence as “the extent to which a person’s behaviour – taking tent patients and under sample those new to treatment. In theory,
medication, following a diet, and/or executing lifestyle changes, cor- analysis of pharmacy claims data presents an opportunity to study
responds with agreed recommendations from a health care provider.” patients who are new to treatment and follow adherence behaviors
Persistence is one aspect of adherence and refers to the extent to over a longer period of time. An early study using this approach
which patients sustain use of medication and lifestyle changes and suggested that one quarter of 2,440 patients who filled an initial
behavioral treatments over time. prescription for glaucoma medication never filled a second one and
The first, and probably most important problem presented by overall, patients were without medication for nearly a third (30%)
noncompliance is the difficulty of detecting it. Numerous studies of the 12 month period that was studied. Another study of 3,623
have demonstrated that patients consistently under report and, as patients with diagnosed glaucoma and 1,677 glaucoma suspects, all
discussed in the next chapter, actively conceal nonadherence from apparently newly treated, revealed that nearly half had discontinued
their clinicians. A meta analysis of 86 studies revealed that patients all glaucoma medication by the end of one year.
consistently overestimated adherence to treatment compared to The Glaucoma Adherence and Persistence Study (GAPS), based
non-self-report methods of measuring medication taking behavior. upon retrospective analysis of the pharmacy and medical claims data
Concordance between face to face interview-based self-report was of 13,956 subjects patients on glaucoma medication revealed signifi-
particularly low with electronic event monitors and somewhat bet- cant problems with nonadherence that are consistent with previous
ter with adherence questionnaires and diaries, pill counts, insur- studies. The principal measure of adherence used in GAPS was the
ance claims analyses, and plasma drug concentrations. Clinicians’ medication possession ratio or MPR, calculated by dividing the days
assessments of adherence are inaccurate and tend to over-estimate of supply of medication dispensed by the number of days between
adherence; in one recent study of 181 glaucoma patients, physicians prescription fulfillments. The MPR is therefore a ratio expressing the
thought that 71% of nonadherent patients were adherent and 28% proportion of days for which a patient possesses enough medication
of adherent patients were nonadherent. One reason for under detec- to use drops as directed. Although 89% of subjects claimed to take
tion in addition to relying on patients’ self-report may be reliance on their glaucoma medication “every day,” the average medication
measurement of rapidly responsive physiological parameters such as possession ratio (MPR) observed in GAPS was 0.64 (median 0.57),
intraocular pressure at the time of a doctor visit, because patients meaning that the average subject only had enough medication to
are often more adherent to medication just before their visits to the take 64% of prescribed doses. The most poorly adherent 25% of
doctor. This so-called “white coat adherence” has been observed in subjects possessed enough medication to take no more than 36% of
several therapeutic areas including glaucoma. Although self-report their prescribed doses, by contrast the most adherent 25% possessed
of nonadherence may be an insensitive measure of the problem, it is enough medication to take 88% of their doses. Over half (55%) of the
reasonably specific. A meta analysis of four studies comparing patient 10,260 subjects followed for at least one year stopped and restarted
self-report to pill count, showed that asking patients if they had medications within that 12-month period. Only 10% of subjects filled
missed any doses of any medication detected 55% of patients defined prescriptions continuously for 12 months.
as nonadherent by pill count (sensitivity), and had a specificity of Our understanding of the causes of nonadherence has evolved from
87%. Nonadherence to treatment is common across therapeutic areas. the original “Health Beliefs Model” which proposes that adherence
In a quantitative survey of 569 studies published between 1966 and to treatment is the result of a balance by the patient’s perception
1998 adherence ranged from 4.6% to 100% with a median of 76% and of their vulnerability to and the threat of the illness, the benefit
an overall average of 75.2%. Rates of adherence varied significantly of the treatment, the cost and burden of the treatment, and social
with the methods used to measure them from a low of 66.6% for and instrumental support for adherence. This model has evolved to
collateral report and 69% for MEMS caps to a high of 85% for pill focus on specific elements within these domains. For example, the
count. Rates of adherence to behavioral interventions such as diet “Information, Motivation, and Behavioral Skills” (IMB) model asserts
and exercise are often as low as 10%. that these are the three key independent determinants of adherence.
Although there is no gold standard for adherence measurement, This model makes the observation that patients can be motivated to
the use of surreptitious electronic devices (MEMS recorders) that adhere without being knowledgeable about the illness and vice versa,

but they must have the specific information that supports critical be- sustaining their motivation and in overcoming barriers to adherence.
havioral skills, such as those required for administration of drops, or The results of GAPS also point towards cost, taking medication while
for creating and integrating behavioral triggers to prompt medication traveling and away from home, and the physician’s practice commu-
taking into the daily routine. The closely related “Therapeutic Decision nication style as modifiable factors influencing adherence.
Model” calls attention to the fact that patients’ decisions about adher- Nonadherence to topical glaucoma medication is prevalent and
ence are dynamic and incorporate ongoing experience of side effects difficult to detect because nonadherence is a socially undesirable
and efficacy with their providers’ recommendations and other sources behavior which patients are reluctant to reveal. Current under-
of information. Most patients engage in an active testing process that standing of adherence behavior identifies the need for patients to
usually remains obscure to clinicians because they do not actively understand the progression of the disease over time in a way that
explore it with their patients. Finally, emerging research has demon- supports concern about future consequences. They also need to
strated the predictive power of the two-factor, “Beliefs in Medication” have the behavioral skills necessary to remember and administer
model which proposes that adherence is the net effect of belief that medication. Patients who are actively engaged in learning about
mediation is necessary balanced by concerns about taking medication. glaucoma and interested in participating in decision making are
These two factors are independent of one another, thus an ambivalent most likely to overcome barriers to adherence. Providers can screen
individual may believe that medication is necessary yet be equally or for active engagement in self-care and for the presence of a moti-
more concerned about the consequences of taking medication. vating concern about consequences by asking patients to describe
Factors influencing adherence have generally been classified into their understanding and concerns about what glaucoma might do in
four categories: patient characteristics, provider characteristics, the future. The epidemiology of barriers to adherence support the
characteristics of the medical regimen, and situational/logistical fac- value of screening for specific barriers to adherence such as cost
tors including cost. Tsai and colleagues identified 71 specific barriers of medication, taking medications while traveling and away from
that patients reported interfered with using glaucoma medication. home, and the mechanics of drop administration. Communication
Patients’ socio-demographic characteristics have been inconsistently strategies for addressing these factors are addressed in the chapter
associated: a review of early research in adherence to glaucoma medi- on communication.
cation found that age, and education were not associated with non-
adherence, that ethnicity and male gender probably were, but weakly Dr. Hahn is professor of clinical medicine and instructor in psychiatry at
and inconsistently. With regards to characteristics of the regimen, Albert Einstein College of Medicine in the Bronx, NY.
increase frequency of dosing but not number of medications, total
number of medicines for all conditions, and frequency of side effects Suggested Readings
1. Sabate, E. Adherence to long-term therapy:Evidence for action. 2003. World Health Organization.
have been related to nonadherence. Several studies have documented 2. Aaker E, Knudsen A, Wynn R, Lund A. General practitioners’ reactions to non-compliant patients. Scand J
better adherence for prostaglandins compared to other classes of Prim Health Care. 2001;19:103-106.
3. Patel UD, Davis MM. Physicians’ attitudes and practices regarding adherence to medical regimens by pa-
medication. Cost of medication and the need to integrate medication tients with chronic illness. Clin Pediatr (Phila). 2006;45:439-445.
4. Reif S, Smith SR, Golin CE. Medication adherence practices of HIV/AIDS case managers: a statewide survey
taking with the daily routine have been associated with adherence. in North Carolina. AIDS Patient Care STDS. 2003;17:471-481.
The result of GAPS identified eight independent factors associated 5. Roberts KJ. Physician beliefs about antiretroviral adherence communication. AIDS Patient Care STDS.
2000;14:477-484.
with nonadherence, five of which are amenable to clinical interven- 6. Sahm G, Bartsch A, Witt E. Reliability of patient reports on compliance. Eur J Orthod. 1990;12:438-446.
tion: (1) hearing all of what you know about glaucoma from your 7. Rand CS. Measuring adherence with therapy for chronic diseases: implications for the treatment of hetero-
zygous familial hypercholesterolemia. Am J Cardiol. 1993;72:68D-74D.
doctor (compared with some or nothing), i.e., “doctor-dependent 8. Garber MC, Nau DP, Erickson SR, Aikens JE, Lawrence JB. The concordance of self-report with other mea-
sures of medication adherence: a summary of the literature. Med Care. 2004;42:649-652.
learners”; (2) not believing that reduced vision is a risk of not tak- 9. Gilbert JR, Evans CE, Haynes RB, Tugwell P. Predicting compliance with a regimen of digoxin therapy in
ing medication as recommended, i.e., the “unconcerned”; (3) having family practice. Can Med Assoc J. 1980;123:119-122.
10. Mazze RS, Shamoon H, Pasmantier R et al. Reliability of blood glucose monitoring by patients with dia-
a problem paying for medications; (4) difficulty while traveling or betes mellitus. Am J Med. 1984;77:211-217.
away from home; and (5) not receiving a phone call visit reminder. 11. Miller LG, Liu H, Hays RD et al. How well do clinicians estimate patients’ adherence to combination anti-
retroviral therapy? J Gen Intern Med. 2002;17:1-11.
If perceived need for medication is adhering to treatment, then a ro- 12. Carroll CL, Feldman SR, Camacho FT, Manuel JC, Balkrishnan R. Adherence to topical therapy
decreases during the course of an 8-week psoriasis clinical trial: Commonly used methods of measuring
bust understanding of the consequences of glaucoma in the future is adherence to topical therapy overestimate actual use. Journal of the American Academy of Dermatology.
the foundation of critical “motivating concern.” GAPS revealed that, 2004;51:212-216.
13. Cramer JA, Scheyer RD, Mattson RH. Compliance declines between clinic visits. Arch Intern Med.
despite almost three years of therapy on average, 14% of patients 1990;150:1509-1510.
were not concerned that nonadherence could lead to vision loss. They 14. Kruse W. Patient compliance with drug treatment--new perspectives on an old problem. Clin Investig.
1992;70:163-166.
shared in common with the third of patients who were “doctor-de- 15. Schwed A, Fallab CL, Burnier M et al. Electronic monitoring of compliance to lipid-lowering therapy in
clinical practice. J Clin Pharmacol. 1999;39:402-409.
pendent learners” who learned everything they know about glaucoma 16. Simmons MS, Nides MA, Rand CS, Wise RA, Tashkin DP. Trends in compliance with bronchodilator inhaler
from their doctors, the experience of not having heard from their doc- use between follow-up visits in a clinical trial. Chest. 1996;109:963-968.
17. Kass MA, Meltzer DW, Gordon M, Cooper D, Goldberg J. Compliance with topical pilocarpine treatment.
tor what to expect in the future from glaucoma. Doctor-dependent Am J Ophthalmol. 1986;101:515-523.
learners reported other deficits in their understanding of glaucoma 18. Stephenson BJ, Rowe BH, Haynes RB, Macharia WM, Leon G. The rational clinical examination. Is this
patient taking the treatment as prescribed? JAMA. 1993;269:2779-2781.
and their communication with the physician; they were the least 19. Cramer JA, Mattson RH, Prevey ML, Scheyer RD, Ouellette VL. How often is medication taken as pre-
scribed? A novel assessment technique. JAMA. 1989;261:3273-3277.
confident in their knowledge about glaucoma, reported that doctors 20. Haynes RB, Taylor DW, Sackett DL, Gibson ES, Bernholz CD, Mukherjee J. Can simple clinical measure-
didn’t ask them if they had questions or understood, and got fewer ments detect patient noncompliance? Hypertension. 1980;2:757-764.
22. DiMatteo MR. Variations in patients’ adherence to medical recommendations: a quantitative review of 50
satisfactory answers to the questions they did ask. Patients who do years of research. Med Care. 2004;42:200-209.
not have a robust understanding of what glaucoma might do in the 23. Haynes RB. Improving patient adherence: State of the art, with special focus on medication taking for
cardiovascular disorders. Patient compliance in health care research: American Heart Association Monograph
future are less likely to adhere to treatment. Patients who passively Series. Futura Publishing Co; 2001:3-21.
24. Olthoff CM, Schouten JS, van de Borne BW, Webers CA. Noncompliance with ocular hypotensive
depend upon their providers and don’t actively engage in developing treatment in patients with glaucoma or ocular hypertension an evidence-based review. Ophthalmology.
their understanding of the disease are less likely to be successful in 2005;112:953-961.

25. Gurwitz JH, Glynn RJ, Monane M et al. Treatment for glaucoma: adherence by the elderly. Am J Public
Health. 1993;83:711-716.
There are significant barriers to the detection of nonadherence in
26. Nordstrom BL, Friedman DS, Mozaffari E, Quigley HA, Walker AM. Persistence and adherence with topical patients prescribed chronic medications. Research has demonstrated
glaucoma therapy. Am J Ophthalmol. 2005;140:598-606.
27. Amico KR, Toro-Alfonso J, Fisher JD. An empirical test of the information, motivation and behavioral that physicians have no better than a 50-50 chance of detecting
skills model of antiretroviral therapy adherence. AIDS Care. 2005;17:661-673.
28. Fisher JD, Fisher WA, Williams SS, Malloy TE. Empirical tests of an information-motivation-behavioral
nonadherence in their patients. In glaucoma in particular, a recent
skills model of AIDS-preventive behavior with gay men and heterosexual university students. Health Psychol. study demonstrated that physician thought that 71% of nonadherent
1994;13:238-250.
29. Carey MP, Braaten LS, Maisto SA et al. Using information, motivational enhancement, and skills training patients were adherent and misclassified 28% of adherent patients as
to reduce the risk of HIV infection for low-income urban women: a second randomized clinical trial. Health nonadherent. Three studies of occult nonadherence from studies of
Psychol. 2000;19:3-11.
30. Carey MP, Maisto SA, Kalichman SC, Forsyth AD, Wright EM, Johnson BT. Enhancing motivation to reduce the chronic diseases are illustrative:
risk of HIV infection for economically disadvantaged urban women. J Consult Clin Psychol. 1997;65:531-541.
31. Starace F, Massa A, Amico KR, Fisher JD. Adherence to antiretroviral therapy: an empirical test of the
Patients with “treatment resistant hypertension” who had told their
information-motivation-behavioral skills model. Health Psychol. 2006;25:153-162. physicians that they were taking their medications consistently were
32. Dowell J, Hudson H. A qualitative study of medication-taking behaviour in primary care. Fam Pract.
1997;14:369-375. told to continue their current treatment regimen using a pillbox that
33. Dowell J, Jones A, Snadden D. Exploring medication use to seek concordance with ‘non-adherent’ pa- they knew would record when they took their pills. Subjected to this
tients: a qualitative study. Br J Gen Pract. 2002;52:24-32.
34. Prochaska JO, Velicer WF, Redding C et al. Stage-based expert systems to guide a population of primary scrutiny, one-third of the patients were instantly “cured;” however,
care patients to quit smoking, eat healthier, prevent skin cancer, and receive regular mammograms. Prev
Med. 2005;41:406-416.
several had syncopal episodes when they complied with regimens that
35. Prochaska JO, Velicer WF. The transtheoretical model of health behavior change. Am J Health Promot. had previously been intensified in the mistaken belief that they been
1997;12:38-48.
36. Prochaska JO, DiClemente CC, Norcross JC. In search of how people change. Applications to addictive adherent. Another 20% of the subjects remained uncontrolled, but the
behaviors. Am Psychol. 1992;47:1102-1114. recording pill box demonstrated that the cause was nonadherence. In
37. Tsai JC. Medication adherence in glaucoma: approaches for optimizing patient compliance. Current Opin-
ion in Ophthalmology. 2006;17:190-195. another study, in this case using surreptitious micro recording devices,
38. Dasgupta S, Oates V, Bookhart BK, Vaziri B, Schwartz GF, Mozaffari E. Population-based persistency rates
for topical glaucoma medications measured with pharmacy claims data. Am J Manag Care. 2002;8:S255-S261.
Cramer et al demonstrated that adherence to antihypertensive treat-
39. Schwartz GF, Reardon G, Mozaffari E. Persistency with latanoprost or timolol in primary open-angle glau- ment was 88-86% during the week before and after a visit to the doc-
coma suspects. Am J Ophthalmol. 2004;137:S13-S16.
40. Shaya FT, Mullins CD, Wong W, Cho J. Discontinuation rates of topical glaucoma medications in a man- tor, but was only 67% six weeks earlier or later. Finally, home glucose
aged care population. Am J Manag Care. 2002;8:S271-S277.
41. Spooner JJ, Bullano MF, Ikeda LI et al. Rates of discontinuation and change of glaucoma therapy in a
diaries were compared to memory chip values in 19 Type I diabetics
managed care setting. Am J Manag Care. 2002;8:S262-S270. who were surreptitiously given the first generation of glucometers
42. Horne R, Weinman J. Patients’ beliefs about prescribed medicines and their role in adherence to treat-
ment in chronic physical illness. Journal of Psychosomatic Research. 1999;47:555-567.
with a recording memory. Over all, half the patients made up half the
43. Friedman DS, Hahn SR, Gelb L et al. Doctor-Patient Communication and Health-Related Beliefs: Results values, and physicians had a 50-50 chance of predicting which patients
from the Glaucoma Adherence and Persistence Study (GAPS). Ophthalmology 2008;115:1320-27.
44. Djafari F, Lesk MR, Harasymowycz PJ, Desjardins D, Lachaine J. Determinants of Adherence to Glaucoma and values were fabricated.
Medical Therapy in a Long-term Patient Population. Journal of Glaucoma. 2009;18:238-242.
45. Friedman DS, Okeke CO, Jampel HD et al. Risk Factors for Poor Adherence to Eyedrops in Electronically
Why should patients conceal nonadherence from their clinicians?
Monitored Patients with Glaucoma. Ophthalmology. 2009;116:1097-1105. Patients realize that providing misinformation may lead to poor deci-
46. Okeke CO, Quigley HA, Jampel HD et al. Adherence with Topical Glaucoma Medication Monitored Elec-
tronically The Travatan Dosing Aid Study. Ophthalmology. 2009;116:191-199.
sions about treatment, but their behavior is shaped by a more powerful
force: Nonadherence is a “socially undesirable” behavior and patients
want to be seen as “good patients.” This desire is often stronger than
10 | Communication in the Management their concern that concealing nonadherence might lead to bad deci-
of Glaucoma sions about treatment. This tendency is exacerbated by the fact that
patients expect their clinicians to be judgmental. Unless the clinician
Steven R. Hahn, MD does something to alter it, the default perception of the patient is that
the clinician will think they are a bad patient and be unsympathetic
A patient’s daily decision to use glaucoma medication is the result to any reason they have for not taking medication as directed. Under-
of a balance between their understanding of the potential risks of standing these key features of the psychology of patient self-report of
glaucoma, their belief in the benefit of medication and the burden nonadherence is the foundation for a four-step, semi-structured dialog
of taking their drops. For most patients, the risk of untreated glau- that reduces barriers to admitting to nonadherence by reversing the
coma is an idea about potential future loss of vision. On the other judgmental environment and redefining the “good patient” as one who
hand, the burden of treatment is not an idea; it is a tangible daily collaborates in solving treatment problems.
experience. Although not as burdensome as treatment for many other
conditions, glaucoma is vulnerable to all the barriers to adherence The four steps of the adherence detection interview are (table 1):
associated with any chronic medication and some unique ones as 1. Begin with a directive open-ended question: “Tell me how
well. In addition to inconvenience, cost, and integration into daily you’ve been taking your medications.” The patient’s response will
lifestyle, topical glaucoma medication is technically more complex reveal their level of understanding of their regimen. Follow up with a
to administer than a pill and often associated with unique nuisance question about how they organize their medication and remember to
side effects. take them. It is useful to have the patient describe the way they use
If adherence is the net balance of “perceived need for medicine,” all of their medications (both topical and systemic) even if the clinician
with the burdens and “concerns about taking medicine,” and clinicians asking is focused on the use of only some of them.
are the most important and sometimes only source of understanding 2. Change the patient’s expectation that you will be judg-
about glaucoma, then adherence is very much the story of the struggle mental: Tell the patient that you know that noncompliance is “uni-
between the effect of patients’ episodic communication with their versal,” everyone has difficulty adhering to a medication regime, and it
clinicians and the daily experience of taking drops. In short, clinician- is “normal” or understandable if a dose is missed because of problems
patient communication is the foundation of adherence, and adherence such as cost, side effects, inconvenience, etc.
is the key factor in treatment outcome, for patients do not benefit from 3. Explain how information about adherence will affect
medicines that they do not take. decisions about medication: For example, “Your pressure is higher

than it should be. Before we change the prescription, let’s make sure mended medication.
that you’ve been able to use the medications you’re already on. Taking • Doesn’t understand why medication was started, specifically why
too much medicine or changing to a second-choice medication would his high intraocular pressure wasn’t a reason for starting medication
not be the best thing if the real problem has been with taking the before but is now.
medication you’ve already been prescribed.” This intervention is im- • Has the mistaken belief that he does not have glaucoma unless he
portant because it changes the definition of a “good patient” from the is experiencing noticeable vision loss.
unrealistic expectation that the patient will always be adherent, to an It is far better to learn what the patient already knows than it is
understanding that a “good patient” is one who discusses and solves to launch into a set patient-education speech for at least two reasons.
problems with adherence with the clinician. First, the clinician can avoid spending unnecessary time on informa-
4. Finally, ask about “forgetting” or “missing” medications: tion the patient already has. Second, asking first allows the clinician
The critical feature of the fourth step in the sequence is that it comes to overtly acknowledge the patient’s correct understanding thereby
last, after the stage has been set. If the patient claims to be adher- reinforcing his self-confidence, sense of self-efficacy, and praising him
ent before steps one through three, the task of getting the real story for his ability to collaborate in self-care and decision making.
becomes doubly difficult because the patient will have to admit to In our sample dialog, the clinician can tell the patient:
having not told the whole truth on top of now having to acknowledge “You’re right, your pressure is too high, and that does produce the
their nonadherence. problem of glaucoma if it is not corrected. It is time for medication in
When problems with adherence are detected, the clinician needs your case...”
to assess two things: the patient’s motivation to take the medicine The patient’s understanding of glaucoma and medication is like
and the presence of specific barriers to adherence. Even a patient a partially assembled jigsaw puzzle. Once the clinician understands
who experiences no burden or barrier to taking a medication will not which pieces have been connected and which are not yet aligned, it
take it without believing there is a good reason to do so. Therefore will become clear which piece of the puzzle needs to be put in place
the strategy is to determine that the patient is concerned about the next to allow the rest to fall into place. A set speech on glaucoma may
consequences of glaucoma and believes that taking it will be beneficial. include the critical information, but if it is presented along with too
The tactic for this assessment is to use “Open-Ended Questions” about much information or at the wrong time the patient will not be able to
concerns and perceived benefit in an “Ask-Tell-Ask” sequence. integrate it.
In our sample dialog, the clinician can tell the patient:
Consider the Following Dialog: “…But high pressure in the fluid in your eye is not the whole story
Optometrist: “Are you concerned about the consequences of glau- of glaucoma and when you need treatment. The pressure causes dam-
coma?” age to the nerve that goes from the eye to the brain, and we detected
Patient: “Yes.” the beginning of damage in that nerve at the last visit by testing
Compared With: your visual fields, the machine with the flashing lights. That’s why we
Optometrist: “Tell me what you understand about glaucoma, and knew that you need treatment.” Perhaps the most important benefit
what your concerns are?” of asking before telling is the opportunity to identify the patient’s
Patient: “Well, I’m not really sure because I haven’t noticed any misconceptions and mistaken beliefs. Erroneous beliefs dramatically
difference in my vision except for what the new glasses corrected. I interfere with patients’ motivation to adhere and self-care behaviors.
mean my vision is fine when I wear my glasses. I thought glaucoma An undiscovered error in understanding can render all of the correct
was where you had real problems seeing. I was told that my pressure information a clinician might provide useless. What is truly striking
is too high by the last doctor who saw me, the one who put me on the is how prevalent and unpredictable patients’ mistaken beliefs can be
drops, but my pressure was high before and I was told there was no across all chronic diseases. The only way to discover the patient’s mis-
need for treatment. So I don’t really know what to expect, or whether taken ideas is to ask.
I should worry or not.” In our sample dialog, the clinician can tell the patient:
The first question is “closed-ended”; one that calls for a yes or no “…A lot of people believe that they don’t have glaucoma unless they
answer. The second is an “open-ended question”; one that cannot be notice a problem with their vision in everyday life. We can detect the
answered yes or no, but rather calls for a broader response. This open- problem of glaucoma before you can yourself, and that’s a good thing
ended question is still focused. It is a “directed” open-ended question because it gives us a chance to prevent more serious damage.”
that points the patient’s response to a particular domain—concerns
about and understanding of glaucoma—but does not constrain the If the first ask reveals the patient’s initial knowledge, missing
way the patient answers. information, and misconceptions, the “second” ask reveals what has
The directed open-ended question, “Tell me what you understand happened to those dimensions of the patient’s understanding as a
about glaucoma, and what your concerns are” is the first “ask” in a result of the “tell”, and also takes the dialog on to the next step of
three step “ask-tell-ask” pattern that forms the basic building block explanation or instruction. The second ask should take the general
of all patient education interventions. The first ask of the sequence form, “What questions or concerns do you have now that you have
will tell you three things: What the patient already knows; what the heard what I just told you.” In our sample dialog, the patient’s re-
patient doesn’t know; and the patient’s misconceptions and mistaken sponse to this second question was: “So you mean I’ve already got
beliefs. damage to my eye? How bad is it? You said ‘prevent more serious
In the sample dialog above, the clinician learns that the damage,’ the medicine will do that? And what was that about the
patient: visual field test?”
• Knows his “pressure is too high” and that the last doctor recom- The second ask continues the dialog, and lets the clinician know

11 | Secondary Glaucomas
Learned from the first “ASK”
John J. McSoley, OD
1. What the patient already knows that is correct and important.
2. What the patient doesn’t know that they should. Secondary glaucomas are defined as the presence of elevated in-
3. The patient’s misconceptions and mistaken beliefs. traocular pressure (IOP) and/or glaucomatous damage as the result of
a specific causative etiology. Secondary glaucomas are often identi-
Focus of the “TELL” fied using a targeted history which would include specific questions
Reinforce what the patient understands correctly, without wasting time. regarding past injury or surgery as well as the current or past use of
Prioritize and present the next most important pieces of information.
corticosteroids. A deliberate anterior segment examination including
gonioscopy may reveal evidence of one or more causes of secondary
Correct misconceptions and mistakes. glaucoma. While there are numerous forms of secondary glaucomas
Learned from the second “ASK” the following discussion focuses on four of the more common types.
Assess improvement in confidence, self-efficacy and commitment. PSEUDOEXFOLIATION AND PSEUDOEXFOLIATIVE

Assess comprehension and impact of new information. GLAUCOMA
Assess comprehension and impact of corrected understanding and beliefs. Pseudoexfoliation is seen as a gray white material that accumulates
within the eye. This fibrillar substance has elastic properties and may
Table 1 be found in various structures throughout the body including skin,
heart, lung, kidney, liver and cerebral meninges. While definitive
which parts of the “tell” got through and which didn’t. Our patient’s support for systemic associations is lacking, it may be forthcoming as
response to the second ask makes it clear that the patient needs to more is understood about this condition. Deposition of this material
learn a little more about the stage and severity of his problem, is occurs predominantly on the structures of the anterior segment with
ready to hear a reassuring link between medication and preventing the earliest sign being a dull gray diminished luster of the anterior
vision loss, and didn’t quite get the role of visual fields in managing lens capsule. This thin grayish white sheet may become patchy and
glaucoma. discontinuous resulting in superficial gray flakes or scrolls of tissue.
Unfortunately, current clinical practice rarely employs these Movement of the pupil may cause the material to be pushed centrally
patient-centered communication strategies. A recent study of 50 pa- and peripherally resulting what has been described as a bull’s eye pat-
tient encounters with 23 ophthalmologists demonstrated that these tern. Contact between the iris and the lens may cause pigment to be
four steps, or their equivalent, are rarely employed in current clinical liberated from the posterior surface of the iris. Subtle, peripupillary
practice. Physicians were observed to ask an average of 5.6 questions transillumination defects may also be evident. Each of these findings
during the average 5.8 minutes they spent talking to their patients. may be more evident when the pupil is dilated. Pigment may be
They rarely (6% of questions) asked patient-centered open-ended deposited on the corneal endothelium and in the anterior chamber
questions that are likely to lead to substantial discussion of patients’ angle; dandruff-like flakes may be visible on the ciliary processes,
perceived need for medication or concerns about taking it. zonular fibers, lens, iris, and in the angle. IOP elevation is associated
Adherence is a result of the balance between a patient’s concern with the deposition of pseudoexfoliative material and pigment within
about the consequences of glaucoma, their belief in the benefit of the trabecular meshwork, and structural and functional alterations
treatment, and the burden of taking medication. Communication there, interfering with aqueous outflow.
between clinician and patient is the foundation of patients’ under- Pseudoexfoliation is found worldwide with varying prevalence
standing. Communication about adherence to medication is chal- rates reported. It has been reported to be the most common identifi-
lenging because patients would rather conceal nonadherence than able cause of open-angle glaucoma. This could be particularly useful
be perceived as bad patients. This barrier can be lowered by using to identify in patients with asymmetric glaucoma and when widely
a four-step semi-structured dialog that addresses the psychology of variable intraocular pressure measurements are found.
acknowledging socially undesirable behavior. Patient motivation and The presence of pseudoexfoliative material does not constitute
specific barriers can be discovered and addressed using open-ended a diagnosis of glaucoma. Conversion from pseudoexfoliation to the
questions in “ask-tell-ask” interviewing sequences that focus on development of glaucomatous damage (pseudoexfoliative glaucoma)
perceived need for medication, concerns about taking and integrating is variable depending on the population and length of follow up re-
medication use in daily life. ported, with conversion increasing with age to a level that may reach
40%. It is often unilateral or asymmetric especially early in the pre-
Suggested Readings sentation. Progression from unilateral to bilateral presentation is also
1. Burnier M, Schneider MP, Chiolero A, Fallab Stubi CL, Brunner HR. Electronic compliance monitoring in
resistant hypertension: the basis for rational therapeutic decisions. J Hypertens 2001;19:335-341.
variable, increases with age and is reported to range from 15-40%.
2. Cramer JA, Scheyer RD, Mattson RH. Compliance declines between visits. J. Hypertension. 1990;150:335-341. Grodum et al showed that patients with pseudoexfoliation and ocular
3. Mazze RS, Shamoon H, Pasmantier R, et al. Reliability of blood glucose monitoring by patients with diabe- hypertension were more likely to develop glaucomatous damage than
tes mellitus. Am J Med. 1984;77:211-217.
4. Horne R, Weinman J. Patients’ beliefs about prescribed medicines and their role in adherence to treatment age and intraocular pressure matched patients without pseudoexfo-
in chronic physical illness. Journal of Psychosomatic Research. 1999;47:555-567. liation (55.1% vs. 27.6% in over eight years of follow up). Pseudoex-
5. Friedman DS, Hahn SR, Gelb L et al. Doctor-Patient Communication and Health-Related Beliefs: Results
from the Glaucoma Adherence and Persistence Study (GAPS). Ophthalmology 2008;115:1320-27.
foliative glaucoma may be a more aggressive form of glaucoma than
6. Friedman DS, Hahn SR, Quigley HA et al. Doctor-Patient Communication in Glaucoma Care: Analysis of primary open-angle glaucoma. Intraocular pressure may be more
Videotaped Encounters in Community-Based Office Practice. Ophthalmology in press. 2009.
variable in eyes with pseudoexfoliation with wide swings and abrupt

changes in level of control of elevated pressure. With the expanding role of intravitreal steroids
intraocular pressure. Depending (injections and implantable devices) the clinician should be aware of
on the clinical circumstances, the possibility of secondary elevation of intraocular pressure which
including the extent of damage, may be severe or difficult to control. Appropriate follow up for an
this may prompt the clinician extended post injection period is indicated especially in those with a
to follow the patient at shorter family history of glaucoma or who have demonstrated susceptibility
intervals and attempt more ag- Figure 1. Slit-lamp photo reveals subtle gray to corticosteroids in the past.
concentric curvilinear deposition lines on the
gressive intraocular pressure anterior lens capsule with an intermediate The mechanism of the increased intraocular pressure is believed to
control. Therapy is similar to clear zone. be increased resistance in the conventional outflow pathway. This is
primary open angle glaucoma, very often reversible except in cases of long term elevated pressure.
with excellent response to laser trabeculoplasty. Recently, three com- It is important to take a thorough history when IOP elevation is
mon sequence variants in the lysyl oxidase-like 1 (LOXL1) gene were discovered to elicit whether steroids agents are being used and may
found to be associated with both pseudoexfoliation (PEX) and pseu- be the culprit. Another clinical circumstance that may present is the
doexfoliation glaucoma in individuals from Iceland. These genetic patient who appears to have normal tension glaucoma that in fact
variants in LOXL1 demonstrate a risk to developing PEX. has suffered prior damage during prolonged courses of corticosteroids
in the past. Alert those patients requiring treatment with corticoste-
PIGMENT DISPERSION AND PIGMENTARY GLAUCOMA roids to have their IOP measured periodically while under streatment.
Pigment dispersion results from pigment liberated from the poste- Clinicians may wish to obtain baseline stereodisc photographs of pa-
rior surface of the peripheral iris due to iridozonular contact. Clinical tients with the potential for steroid induced elevations of intraocular
manifestations of pigment dispersion include pigment accumulation pressure. Treatment of the elevated pressure is discontinuation or
on the corneal endothelium (often in a vertical arrangement, Kruck- substitution of the causative agent if possible and management of
enberg spindle), in the anterior chamber angle and on the zonular the intraocular pressure as appropriate for the clinical circumstances.
fibers, particularly at the interface of zonular fibers and lens capsule
(Scheie Stripe). There is often iris transillumination defects which GLAUCOMA ASSOCIATED WITH TRAUMA
are linear or slit-like in the equatorial or peripheral iris. The anterior Several signs and the past history may suggest prior ocular trauma.
chamber is deep and there may be an observable posterior bowing Iris sphincter tears, traumatic mydriasis, cataract, iridodialysis, cyclo-
of the iris. Occasionally excessive pigment may be liberated from a dialysis and recession of the anterior chamber angle are also sequelae
secondary cause such as iris chafing on an intraocular lens (second- to blunt trauma of the globe. Recession of the anterior chamber
ary pigment dispersion). angle appears as a deep anterior chamber evident on gonioscopy as a
The prevalence of pigment dispersion and incidence of related broadening of the ciliary body band (CBB) and a posterior or deeper
glaucoma is not well known. The mechanism of elevated intraocular insertion of the iris. The extent of angle recession may serve as a
pressure is related to impaired aqueous outflow through the trabecu- marker for the degree of injury. The mechanism of elevated intra-
lar meshwork. There may be a mechanical obstruction due to pig- ocular pressure is reduced aqueous outflow related to damage to the
ment granules in the trabecular meshwork. There are also increased trabecular meshwork; not the actual recession per se. The incidence
phagocytic and metabolic demands on the endothelial cells that lead of glaucoma is variable but is often reported around 10% of those
to degenerative changes in the trabecular meshwork anatomy. Pig- with angle recession.
ment dispersion refers to signs being present without the elevation Glaucoma associated with prior trauma follows similar management
of IOP. When elevated IOP is discovered, the patient is labeled as strategies as primary open angle glaucoma except for the use of laser
having pigmentary glaucoma. Management of IOP elevation is similar trabeculoplasty which should be avoided given a lower success rate.
to other open angle glaucomas with prostaglandins often the first There is also a possibility for an acute IOP elevation associated with
class of drugs considered. laser trabeculoplasty when performed on scarred and anatomically
abnormal trabecular meshwork.
CORTICOSTEROID INDUCED GLAUCOMA Secondary glaucomas are relatively common and need to be recog-
Exposure to corticosteroids may produce an elevated intraocular nized as being present since the management and prognosis may vary
pressure in susceptible individuals. The likelihood, extent and rapid- depending upon the form present.
ity of onset is related to the agent used, route of administration,
and individual susceptibility. A John J. McSoley, O.D. is a graduate of the New England College of Optometry.
steroid response is more likely After completing an optometric residency, he joined the staff at Bascom Palmer
in patients with a personal or Eye Institute. He is a founding member of the Optometric Glaucoma Society.
family history of open angle
glaucoma. While topical, intra- Suggested Readings
1. Fingeret M, Thimons JJ. Common Secondary Glaucomas. In Fingeret M, Lewis, TL. Primary Care of the
ocular and periocular administra- Glaucomas 2nd ed. McGraw- Hill 2001.
tion are most likely to produce 2. Naumann GOH, Schlotzer-Schrehardt U, Kuchle M, Pseudoexfoliation for the comprehensive ophthalmolo-
gist. Intraocular and systemic manifestations. Ophthalmol 1998; 105:951-968.
an increase in intraocular pres- 3. Ritch R, Schlotzer-Schrehardt U, Exfoliation syndrome. Surv Ophthalmol.2001; 45:265-315.
Schlotzer-Schrehardt U, Naumann GOH, Pseudoexfoliation Glaucoma. In 4. Grehn F, Stamper R, ed. Essentials
sure, systemically administered, in Ophthalmology: Glaucoma. Heidelberg 2004 Springer-Verlag.
including inhaled steroids as well 5. Grodum K, Heijl A, Bengston B. Risk of glaucoma in ocual hypertension with and without pseudoexfolia-
tion. Ophthalmology 2005;112:386-390.
as topical applications remote 6. Ritch R, Liebmann JM. ExfoliationSyndrome and Exfoliative Glaucoma. In Fingeret M, Lewis, TL. Primary
Figure 2. Scheie stripe. to the eye may contribute to Care of the Glaucomas 2nd ed. McGraw- Hill 2001.


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What are some of the new technologies discussed for glaucoma diagnosis?

What are some of the new technologies discussed for glaucoma diagnosis?

What are some new developments in glaucoma therapeutics mentioned?

What are some new developments in glaucoma therapeutics mentioned?

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Most glaucomas are asymptomatic until the late stages of the

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Assess improvement in confidence, self-efficacy and commitment. PSEUDOEXFOLIATION AND PSEUDOEXFOLIATIVE

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