Diabetic

Retinopathy
Prepared by the American As a service to its members and the public, the American Academy of
Academy of Ophthalmology Ophthalmology has developed a series of guidelines called Preferred
Retina Panel Practice Patterns™ that identify characteristics and components of
quality eye care.
Retina Panel Members
Emily Y. Chew, MD, Chair The Preferred Practice Patterns are based on the best available
William E. Benson, MD
H. Culver Boldt, MD
scientific data as interpreted by panels of knowledgeable health
Tom S. Chang, MD professionals. In some instances, such as when results of carefully
Louis A. Lobes, Jr., MD conducted clinical trials are available, the data are particularly
Joan W. Miller, MD persuasive and provide clear guidance. In other instances, the panels
Timothy G. Murray, MD have to rely on their collective judgment and evaluation of available
Marco A. Zarbin, MD, PhD evidence.
Leslie Hyman, PhD, Methodologist
Preferred Practice Patterns provide guidance for the pattern of
Preferred Practice Patterns Committee
practice, not for the care of a particular individual. While they
Members
Joseph Caprioli, MD, Chair should generally meet the needs of most patients, they cannot possibly
J. Bronwyn Bateman, MD best meet the needs of all patients. Adherence to these Preferred
Emily Y. Chew, MD Practice Patterns will not ensure a successful outcome in every
Douglas E. Gaasterland, MD situation. These practice patterns should not be deemed inclusive of
Sid Mandelbaum, MD all proper methods of care or exclusive of other methods of care
Samuel Masket, MD reasonably directed at obtaining the best results. It may be necessary
Alice Y. Matoba, MD to approach different patients’ needs in different ways. The physician
Donald S. Fong, MD, MPH must make the ultimate judgment about the propriety of the care of a
particular patient in light of all of the circumstances presented by that
Academy Staff
Nancy Collins, RN, MPH patient. The American Academy of Ophthalmology is available to
Flora C. Lum, MD assist members in resolving ethical dilemmas that arise in the course
Mario Reynoso of ophthalmic practice.
Medical Editor: Jeff Van Bueren
Design: Socorro Soberano Preferred Practice Patterns are not medical standards to be
Reviewed by: Council adhered to in all individual situations. The Academy specifically
Approved by: Board of Trustees disclaims any and all liability for injury or other damages of any kind,
September 2003 from negligence or otherwise, for any and all claims that may arise
out of the use of any recommendations or other information contained
Copyright © 2003
American Academy of Ophthalmology ® herein.
All rights reserved
Innovation in medicine is essential to assure the future health of the
American public, and the Academy encourages the development of
new diagnostic and therapeutic methods that will improve eye care. It
is essential to recognize that true medical excellence is achieved only
when the patients’ needs are the foremost consideration.

All Preferred Practice Patterns are reviewed by their parent panel

annually or earlier if developments warrant and updated accordingly.
To ensure that all Preferred Practice Patterns are current, each is valid
for 5 years from the “approved by” date unless superseded by a
revision.

Financial Disclosures:
No proprietary interests were disclosed by members of the Preferred Practice Patterns Retina Panel for the past 3 years up to and including
June 2003 for product, investment, or consulting services regarding the equipment, process, or products presented or competing equipment,
process, or products presented.
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TABLE OF CONTENTS

INTRODUCTION ...........................................................................................................2
ORIENTATION..............................................................................................................3
Entity .............................................................................................................................3
Disease Definition..........................................................................................................3
Patient Population .........................................................................................................3
Activity ...........................................................................................................................3
Purpose .........................................................................................................................3
Goals .............................................................................................................................3
BACKGROUND ............................................................................................................4
Epidemiology .................................................................................................................4
Risk Factors ..................................................................................................................4
Natural History...............................................................................................................4
PREVENTION AND EARLY DETECTION....................................................................6
CARE PROCESS..........................................................................................................8
Patient Outcome Criteria ...............................................................................................8
Diagnosis.......................................................................................................................8
History ...................................................................................................................9
Examination...........................................................................................................9
Examination Schedule...........................................................................................9
Type 1 (Diabetes Onset Usually between Ages 0 and 29 Years) ...................9
Type 2 (Diabetes Onset Usually at Age 30 Years or Older) ...........................9
Diabetes Associated with Pregnancy ...........................................................10
Ancillary Tests .....................................................................................................10
Color Fundus Photography...........................................................................10
Fluorescein Angiography ..............................................................................10
Ultrasonography (Echography).....................................................................11
Optical Coherence Tomography...................................................................11
Treatment ....................................................................................................................11
Normal or Minimal NPDR ....................................................................................12
Mild to Moderate NPDR without Macular Edema ................................................13
Mild to Moderate NPDR with Clinically Significant Macular Edema.....................13
Severe and Very Severe NPDR and Non-High-Risk PDR...................................14
High-Risk PDR ....................................................................................................15
High-Risk PDR Not Amenable to Photocoagulation ............................................15
Other Treatments ................................................................................................16
Side Effects and Complications of Treatment..............................................................16
Focal Photocoagulation for Diabetic Macular Edema ..........................................16
Scatter Photocoagulation for Severe NPDR or PDR ...........................................16
Vitrectomy ...........................................................................................................16
Follow-up.....................................................................................................................16
History .................................................................................................................16
Provider .......................................................................................................................17
Counseling/Referral.....................................................................................................17
APPENDIX 1. SUMMARY OF MAJOR RECOMMENDATIONS FOR CARE .............18
APPENDIX 2. TREATMENT TRIAL RESULTS..........................................................20
APPENDIX 3. GLYCEMIC CONTROL........................................................................22
APPENDIX 4. COST-BENEFIT ANALYSES ..............................................................23
GLOSSARY ................................................................................................................24
RELATED ACADEMY MATERIALS...........................................................................27
REFERENCES ............................................................................................................28

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INTRODUCTION
The Preferred Practice Patterns (PPP) series of guidelines has been written on the basis of three
principles.
! Each Preferred Practice Pattern should be clinically relevant and specific enough to provide useful
information to practitioners.
! Each recommendation that is made should be given an explicit rating that shows its importance to
the care process.
! Each recommendation should also be given an explicit rating that shows the strength of evidence
that supports the recommendation and reflects the best evidence available.
In the process of revising this document, a detailed literature search of articles in the English
language was conducted on the subject of diabetic retinopathy for the years 1997 to 2002. The
results were reviewed by the Retina Panel and used to prepare the recommendations, which they
rated in two ways. The panel first rated each recommendation according to its importance to the
care process. This “importance to the care process” rating represents care that the panel thought
would improve the quality of the patient’s care in a meaningful way. The ratings of importance are
divided into three levels.
! Level A, defined as most important
! Level B, defined as moderately important
! Level C, defined as relevant but not critical
The panel also rated each recommendation on the strength of evidence in the available literature to
support the recommendation made. The “ratings of strength of evidence” also are divided into
three levels.
! Level I includes evidence obtained from at least one properly conducted, well-designed,
randomized controlled trial. It could include meta-analyses of randomized controlled trials.
! Level II includes evidence obtained from the following:
! Well-designed controlled trials without randomization
! Well-designed cohort or case-control analytic studies, preferably from more than one center
! Multiple-time series with or without the intervention
! Level III includes evidence obtained from one of the following:
! Descriptive studies
! Case reports
! Reports of expert committees/organization
! Expert opinion (e.g., PPP panel consensus)
The evidence cited is that which supports the value of the recommendation as something that
should be performed to improve the quality of care. The panel believes that it is important to make
available the strength of the evidence underlying the recommendation. In this way, readers can
appreciate the degree of importance the committee attached to each recommendation and they can
understand what type of evidence supports the recommendation.
The ratings of importance and the ratings of strength of evidence are given in bracketed
superscripts after each recommendation. For instance, “[A:II]” indicates a recommendation with
high importance to clinical care [A], supported by sufficiently rigorous published evidence,
though not by a randomized controlled trial [II].
The sections entitled Orientation and Background do not include recommendations; rather they are
designed to educate and provide summary background information and rationale for the
recommendations that are presented in the Care Process section. A summary of the major
recommendations for care is included in Appendix 1.

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ORIENTATION
ENTITY
Diabetic retinopathy (ICD-9 #362.01 and 362.02)

DISEASE DEFINITION
Diabetic retinopathy is a disorder of the retinal vasculature that eventually develops to some
degree in nearly all patients with long-standing diabetes mellitus. The earliest visible clinical
manifestations of retinopathy include microaneurysms and hemorrhages. Vascular alterations can
progress to retinal capillary nonperfusion, resulting in a clinical picture characterized by increased
numbers of hemorrhages, cotton-wool spots, and intraretinal microvascular abnormalities (IRMA).
Finally, increasing nonperfusion can lead to closure of retinal vessels and pathologic proliferation
of retinal vessels, characterized by neovascularization on the disc or elsewhere. Increased
vasopermeability results in retinal thickening (edema) during the course of diabetic retinopathy.
Visual loss results mainly from macular edema, macular capillary nonperfusion, vitreous
hemorrhage, and distortion or traction detachment of the retina.
A description of the fundus findings in various stages of diabetic retinopathy is located in the
Natural History section. Important terms are defined in the Glossary.

PATIENT POPULATION
The patient population includes all patients with diabetes mellitus.

ACTIVITY
Evaluation and management of diabetes-related retinal disease.

PURPOSE
The primary purpose of evaluating and managing diabetic retinopathy is to prevent, retard, or
reverse visual loss, thereby maintaining or improving vision-related quality of life.

GOALS
! Identify patients at risk for developing diabetic retinopathy.
! Encourage involvement of the patient and primary care physician in the management of the
patient’s systemic disorder, with specific attention to control of blood sugar (hemoglobin A1c),
serum lipids, and blood pressure.
! Encourage and provide lifelong evaluation of retinopathy progression.
! Treat patients at risk for visual loss from diabetic retinopathy.
! Minimize the side effects of treatment that might adversely affect the patient’s vision and/or
vision-related quality of life.
! Provide visual rehabilitation for patients with visual loss from the disease or refer for visual
rehabilitation.

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BACKGROUND
EPIDEMIOLOGY
Diabetic retinopathy is the leading cause of new cases of legal blindness among working-age
Americans. An estimated 29 million Americans age 20 years or older have either diagnosed
diabetes mellitus, undiagnosed diabetes, or impaired fasting blood glucose levels; about one third
are not aware that they have the disease.1
For the purposes of this PPP, two forms of diabetes mellitus are recognized. Type 1, previously
called juvenile-onset or insulin-dependent diabetes, is characterized by beta-cell destruction and
usually leads to absolute insulin deficiency. Type 2, previously called adult-onset or noninsulin-
dependent diabetes, is characterized by insulin resistance with an insulin secretory defect that
leads to relative insulin deficiency.2 Many patients with type 2 diabetes take insulin. Between 90%
and 95% of patients with diabetes have type 2 diabetes. Because of the disproportionately large
number of patients with type 2 diabetes, this group comprises a substantial proportion of patients
with visual impairment secondary to diabetic retinopathy, even though type 1 diabetes is
associated with more frequent and more severe ocular complications.3 The increased frequency of
childhood obesity may result in an increased frequency of type 2 diabetes in the pediatric age
group.4

RISK FACTORS
Duration of diabetes is a major risk factor associated with the development of diabetic retinopathy.
After 5 years, approximately 25% of type 1 patients have retinopathy. After 10 years, almost 60%
have retinopathy, and after 15 years, 80% have retinopathy. Proliferative diabetic retinopathy, the
most vision-threatening form of the disease, is present in approximately 25% of type 1 patients
with 15 years’ duration of the disease.5
Of type 2 patients who have a known duration of diabetes of less than 5 years, 40% of those
patients taking insulin and 24% of those not taking insulin have retinopathy. These rates increase
to 84% and 53%, respectively, when the duration of diabetes has been documented for up to 19
years. Proliferative retinopathy develops in 2% of type 2 patients who have diabetes for less than 5
years and in 25% of patients who have diabetes for 25 years or more.6
The severity of hyperglycemia is the key alterable risk factor associated with the development of
diabetic retinopathy. Support for this association is found in results of both clinical trials and
epidemiologic studies.7-9 There is general agreement that duration of diabetes and severity of
hyperglycemia are the major risk factors for developing retinopathy. After retinopathy is present,
duration of diabetes appears to be a less important factor than hyperglycemia for progression from earlier
to later stages of retinopathy.9 Intensive management of hypertension has been demonstrated to slow
retinopathy progression.10, 11 There is less agreement between studies concerning the importance of other
factors such as age, type of diabetes, clotting factors, renal disease, and use of angiotensin-converting
enzyme inhibitors.9, 12-14 Many of these factors are associated with the significant cardiovascular
morbidity and mortality and other complications associated with diabetes. Thus, it is reasonable to
encourage patients with diabetes to be as compliant as possible with therapy of all medical aspects of
their disease.

NATURAL HISTORY
Diabetic retinopathy progresses in an orderly fashion from minimal changes to more severe stages
if there is no intervention. It is important to recognize the stages in which treatment may be
beneficial. Several decades of clinical research have provided excellent data on the natural course
of the disease and on treatment strategies that are 90% effective in preventing the occurrence of
severe vision loss. These studies include five major clinical trials: the Diabetes Control and
Complications Trial (DCCT),8, 15, 16 the Diabetic Retinopathy Study (DRS),17-19 the Early
Treatment Diabetic Retinopathy Study (ETDRS),20-31 the Diabetic Retinopathy Vitrectomy Study
(DRVS),32-35 and the United Kingdom Prospective Diabetes Study (UKPDS).10, 36, 37 The outcomes

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of these trials are solid foundations underlying the Preferred Practice Pattern for treating diabetic
retinopathy. The results of these studies are presented in Appendices 2 and 3.
Diabetic retinopathy in its earliest stages is called nonproliferative diabetic retinopathy (NPDR)
and is characterized by retinal vascular abnormalities including microaneurysms, intraretinal
hemorrhages, and cotton-wool spots. Increased retinal vascular permeability that occurs at this or
later stages of retinopathy may result in retinal thickening (edema) and lipid deposits (hard
exudates). Clinically significant macular edema (CSME) is a term commonly used for retinal
thickening and/or adjacent hard exudates that either involve the center of the macula or threaten to
spread into it. Patients with CSME should be considered for focal laser photocoagulation,
particularly if the center of the macula is already involved or if retinal thickening/adjacent hard
exudates are very close to it (see Care Process).
As diabetic retinopathy progresses, there is a gradual closure of retinal vessels, which results in
impaired perfusion and retinal ischemia. Signs of increasing ischemia include venous
abnormalities (beading, loops, etc.), IRMA, and more severe and extensive vascular leakage
characterized by increasing retinal hemorrhages and exudation. When these signs progress beyond
certain defined thresholds, severe nonproliferative diabetic retinopathy (severe NPDR) is
diagnosed (see Glossary for definition). Patients with this degree of retinopathy should be
considered for possible treatment with scatter laser photocoagulation (see Care Process).
The more advanced stage, proliferative diabetic retinopathy (PDR), is characterized by the onset
of neovascularization on the inner surface of the retina induced by the retinal ischemia. New
vessels at the optic disc (NVD) and new vessels elsewhere in the retina (NVE) are prone to bleed,
resulting in vitreous hemorrhage. These new vessels may undergo fibrosis and contraction; this
and other fibrous proliferation may result in epiretinal membrane formation, vitreoretinal traction
bands, retinal tears, and traction or rhegmatogenous retinal detachments. When new vessels are
accompanied by vitreous hemorrhage, or when new vessels at the optic disc occupy greater than or
equal to about 1/4 to 1/3 disc area, even in the absence of vitreous hemorrhage, PDR is said to be
in the high-risk stage (high-risk PDR; see Glossary for definition). Neovascular glaucoma can
result from new vessels growing on the iris and anterior chamber angle structures. Patients with
neovascular glaucoma or high-risk PDR should receive prompt scatter photocoagulation (see Care
Process).
In an attempt to improve communication worldwide between ophthalmologists and primary care
physicians caring for patients with diabetes, an international clinical disease severity scale was
recently developed for diabetic retinopathy and macular edema (Tables 1 and 2).38 This scale is
based on the ETDRS classification of diabetic retinopathy and on the data collected in clinical
trials and epidemiologic studies of diabetic retinopathy. However, the scheme remains to be
validated.

TABLE 1 International Clinical Diabetic Retinopathy Disease Severity Scale

Proposed Disease Severity Level Findings Observable upon Dilated Ophthalmoscopy

No apparent retinopathy No abnormalities

Mild nonproliferative diabetic retinopathy Microaneurysms only
Moderate nonproliferative diabetic retinopathy More than just microaneurysms but less than severe NPDR
Severe nonproliferative diabetic retinopathy Any of the following:
♦ More than 20 intraretinal hemorrhages in each of four quadrants
♦ Definite venous beading in two or more quadrants
♦ Prominent IRMA in one or more quadrants
And no signs of proliferative retinopathy
Proliferative diabetic retinopathy One or both of the following:
♦ Neovascularization
♦ Vitreous/preretinal hemorrhage

IRMA = intraretinal microvascular abnormalities; NPDR = nonproliferative diabetic retinopathy

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TABLE 2 International Clinical Diabetic Macular Edema Disease Severity Scale

Proposed Disease Severity Level Findings Observable upon Dilated Ophthalmoscopy

Diabetic macular edema apparently absent No apparent retinal thickening or hard exudates in posterior pole
Diabetic macular edema apparently present Some apparent retinal thickening or hard exudates in posterior pole

If diabetic macular edema is present, it can be categorized as follows:

Proposed Disease Severity Level Findings Observable upon Dilated Ophthalmoscopy*

Diabetic macular edema present ♦ Mild diabetic macular edema: Some retinal thickening or hard exudates in posterior pole but
distant from the center of the macula
♦ Moderate diabetic macular edema: Retinal thickening or hard exudates approaching the center of
the macula but not involving the center
♦ Severe diabetic macular edema: Retinal thickening or hard exudates involving the center of the
macula

* Hard exudates are a sign of current or previous macular edema. Diabetic macular edema is defined as retinal thickening; this requires a three-
dimensional assessment that is best performed by dilated examination using slit-lamp biomicroscopy and/or stereo fundus photography.

PREVENTION AND EARLY DETECTION

Although a healthy lifestyle with exercise and weight control may decrease the risk of developing
diabetes in some patients,39, 40 in many cases diabetes cannot be prevented. In contrast, in many
cases the blinding complications of diabetes mellitus can be prevented or moderated. Treatment
can yield significant cost savings compared with the direct costs for those disabled by vision loss
(see Appendix 4). Analyses from two clinical trials show that the treatment for diabetic
retinopathy may be 90% effective in preventing severe vision loss (visual acuity less than 5/200)
with current treatment strategies.41 Although effective treatment is available, the number of
patients with diabetes referred by their primary care physicians for ophthalmic care is far below
the guidelines of the American Diabetes Association and the American Academy of
Ophthalmology.42 In a community-based intervention trial, at enrollment 35% of participants did
not follow the vision care guidelines; two thirds of this group reported no eye examination in the
year prior to enrollment and one third had an undilated examination.43
In one epidemiologic study of over 2000 diabetes patients, 11% of type 1 patients and 7% of type
2 patients with high-risk PDR had not been seen by an ophthalmologist within 2 years.44 In this
study, 46% of eyes with high-risk PDR had not received photocoagulation surgery.44 According to
the National Committee for Quality Assurance’s Health Plan Employers Data Information Set 3.0
System, the average rate of annual eye examinations for patients with diabetes was 45% across
participating health plans in 2000. Among prepaid health plan enrollees, 77% of patients with
diabetes received an eye examination over a 3-year study period.45 A longitudinal analysis of
Medicare claims data for beneficiaries age 65 years or older found that 50% to 60% had annual
eye examinations in a 15-month period.46 Ophthalmologists, physicians who care for patients with
diabetes, and patients themselves need to be educated about indications for referral.
Recommended intervals for eye examinations for patients with diabetes are given in Table 3.

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TABLE 3 Recommended Eye Examination Schedule for Patients with Diabetes Mellitus
Diabetes Type Recommended Time of Recommended Follow-up*
First Examination

Type 1 5 years after onset5 [A:II] Yearly5 [A:II]

Type 2 At time of diagnosis6 [A:II] Yearly6 [A:II]
Prior to pregnancy Prior to conception or early in the first No retinopathy to mild or moderate NPDR: every 3–12 months47-49 [A:I]
(type 1 or type 2) trimester47-49 [A:I] Severe NPDR or worse: every 1–3 months47-49 [A:I]

* Abnormal findings may dictate more frequent follow-up examinations.

NPDR = nonproliferative diabetic retinopathy

The primary prevention and screening process for diabetic retinopathy varies according to the age
of onset of the disease. Several forms of retinal screening with standard fundus photography or
digital imaging, with and without dilation, are being investigated as a means of detecting
retinopathy early, and they warrant further evaluation.50 Some studies have shown that screening
to identify sight-threatening retinopathy with photography is more sensitive than clinical
examination with ophthalmoscopy.51-54 It is not clear whether the new digital photography
techniques (e.g., single-field, 45-degree photo) are as sensitive and specific as traditional standard
seven-field stereoscopic 30-degree fundus photographs for determining the level of diabetic
retinopathy.55 Most digital nonmydriatic cameras lack stereoscopic capability, which is useful for
identifying subtle neovascularization and macular edema.42 However, digital nonmydriatic
cameras that operate stereoscopically have been validated against fundus photography and may
eventually prove to be useful tools in future studies. At this time it is not clear that photographic
screening programs achieve a greater reduction in vision loss compared with routine community
care in areas where access to ophthalmologists is straightforward.42 Of course, such screening
programs have great value in circumstances in which access to ophthalmic care is limited.53, 55 At
this time, these technologies are not considered a replacement for a comprehensive eye evaluation
by an ophthalmologist experienced in managing diabetic retinopathy.
Ophthalmologists can play an important role in diabetic care apart from treating eye disease.
Patients can be counseled about the importance of blood glucose and blood pressure control, for
example, at the time of the eye examination.
The results of the DCCT showed that the development and progression of diabetic retinopathy in
patients with type 1 diabetes can be delayed if glucose concentrations are maintained in the near-
normal range (see Appendix 3).15 After 3 years of intensive treatment to reduce glucose levels, the
DCCT showed that among patients without retinopathy, the development of any retinopathy was
reduced by 75% but not prevented completely over the 9-year course of the study. The benefit of
strict glucose control also was evident in patients with existing retinopathy (50% reduction in the
rate of progression of retinopathy compared with controls). At the 6- and 12-month visits, a small
adverse effect of intensive treatment on retinopathy progression was seen, similar to that described
in other trials of intensive glucose control. This small adverse effect was a transient early
worsening of the retinopathy in the intensive treatment group within the first 2 years of treatment,
with no effect on visual acuity. Beyond 3.5 years of follow-up, the risk of progression was five
times lower with intensive insulin treatment than with conventional treatment.
Evidence about the effects of controlling hyperglycemia in type 2 patients comes from
observational data as well as randomized clinical trials. Definitive results were seen in the
UKPDS,37, 56 a randomized, controlled clinical trial of blood glucose control in 3867 patients with
newly diagnosed type 2 diabetes. Intensive blood glucose control by either the sulfonylureas or
insulin decreased the risk of microvascular complications but not the risk of macrovascular
disease. There were no adverse effects of the individual drugs on the cardiovascular outcome. In
this study, there was a 29% reduction in the need for retinal photocoagulation surgery in the group
with intensive glucose therapy compared with those with conventional treatment (relative risk,
0.71; 95% confidence interval, 0.53–0.96; P=0.003).

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Also in the UKPDS, 1148 patients with both diabetes and hypertension were randomly assigned to
antihypertensive treatment.10 Additional analyses from this nested trial of antihypertensive
medications (captopril, an angiotensin-converting enzyme inhibitor, or atenolol, a beta blocker)
showed that tight blood pressure control achieved a clinically important reduction in the risk of
deaths related to diabetes and in the risk of progression of diabetic retinopathy. There was a 34%
reduction in the risk of progression of retinopathy from baseline by two or more steps by a median
of 7.5 years (P=0.004) and a 47% reduced risk of decreased vision by three lines on the ETDRS
chart (P=0.004). There was no difference in the progression of retinopathy or the final visual
acuity in those patients treated with an angiotensin-converting enzyme inhibitor compared with
those treated with a beta blocker.
It is important to educate all patients with diabetes about the disease and to stress the value of
maintaining blood glucose (as monitored by hemoglobin A1c) as near normal as is safely possible.
The results of the DCCT showed that lowering blood glucose reduces other end-organ
complications as well, including nephropathy and neuropathy (see Appendix 3). The results of the
UKPDS demonstrate the value of controlling blood glucose and blood pressure in all patients with
type 2 diabetes.
Medical treatment such as aspirin therapy has been evaluated for the prevention and retardation of
diabetic retinopathy. The ETDRS found no evidence that aspirin therapy retards or accelerates the
progression of diabetic retinopathy22 or that it causes more severe or more long-lasting vitreous
hemorrhages in patients with PDR.57

CARE PROCESS
The care process for diabetic retinopathy includes a medical history, an ophthalmic examination,
and vigilant follow-up. Early detection of retinopathy depends on educating patients with diabetes
as well as their families, friends, and eye care providers about the importance of regular eye
examination even though the patient may be asymptomatic. Patients with diabetes mellitus without
diabetic retinopathy should be encouraged to have annual dilated eye examinations to detect the
onset of diabetic retinopathy.[A:III] Patients should also be informed that effective treatment for
diabetic retinopathy depends on timely intervention, despite good vision and no ocular
symptoms.[A:III] (The recommended timing of the first ophthalmic exam and subsequent follow-up
exams for patients with diabetes is given in the section Examination Schedule and in Table 3.)
Patient education about the importance of maintaining near-normal glucose levels and near-normal
blood pressure and lowering serum lipid levels is an important aspect of the care process.[A:III]
Many patients are still not aware of the importance of maintaining good glucose control and
monitoring serum glycosylated hemoglobin levels. Aspirin may be used without concern for
worsening diabetic retinopathy by patients with diabetes who require aspirin for other medical
indications and have no contraindications.22, 57 [A:I]

PATIENT OUTCOME CRITERIA

Patient outcome criteria include the following:
! Improvement or stabilization of visual function
! Improvement or stabilization of vision-related quality of life
! Coordination of care management to achieve optimal glycemic control

DIAGNOSIS
The initial examination for a patient with diabetes mellitus includes all features of the
comprehensive adult medical eye evaluation,58 with particular attention to those aspects relevant to
diabetic retinopathy.

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History
An initial history should consider the following elements:
! Duration of diabetes5, 7, 9 [A:I]
! Past glycemic control (hemoglobin A1c)7, 9, 16 [A:I]
! Medications[A:III]
! Medical history (e.g., onset of puberty,[A:III] obesity,[A:III] renal disease,5, 6 [A:II] systemic
hypertension,5, 6 [A:I] serum lipid levels,59 [A:II] pregnancy47, 48 [A:I])

Examination
The initial examination should include the following elements:
! Best-corrected visual acuity9 [A:I]
! Intraocular pressure[A:III]
! Gonioscopy when indicated[A:III]
! Slit-lamp biomicroscopy[A:III]
! Dilated funduscopy including stereoscopic examination of the posterior pole28 [A:I]
! Examination of the peripheral retina and vitreous[A:III]
Iris neovascularization may be recognized best prior to dilation. If neovascularization of the iris is
present or suspected, or if the intraocular pressure is elevated, gonioscopy can be used to detect
neovascularization of the anterior chamber angle. A dilated pupil is necessary to ensure optimal
examination of the retina, because only 50% of eyes are correctly classified for presence and
severity of retinopathy through undilated pupils.60 [A:I] Slit-lamp biomicroscopy with accessory
lenses is the recommended method to evaluate retinopathy in the posterior pole and midperipheral
retina.28 [A:III] The examination of the peripheral retina is best performed with indirect
ophthalmoscopy or with slit-lamp biomicroscopy, combined with a contact lens.[A:III]
Since treatment is effective in reducing the risk of visual loss, detailed examination is indicated to
assess for the following features that often lead to visual impairment:
! Presence of macular edema
! Optic nerve head neovascularization and/or neovascularization elsewhere
! Signs of severe NPDR (extensive retinal hemorrhages/microaneurysms, venous beading, and
IRMA)
! Vitreous or preretinal hemorrhage
It is also strongly recommended that a patient with these ocular findings be referred to an
ophthalmologist who has expertise and experience in caring for such patients.[A:III]

EXAMINATION SCHEDULE

Type 1 (Diabetes Onset Usually between Ages 0 and 29 Years)

Many studies of patients with type 1 diabetes have reported a direct relationship between the
prevalence and severity of retinopathy and the duration of diabetes.6, 61-63 The development of
vision-threatening retinopathy is rare in children prior to puberty.61, 64 Among patients with type 1
diabetes, significant retinopathy may become apparent as early as 6 to 7 years after onset of
disease.5 Ophthalmic examinations should be performed beginning 5 years after the diagnosis of
type 1 diabetes and will discover the vast majority of type 1 patients who require therapy at that
time.5 [A:II]

Type 2 (Diabetes Onset Usually at Age 30 Years or Older)

The time of onset of type 2 diabetes is often difficult to determine and may precede the diagnosis
by a number of years.65 Up to 3% of patients whose diabetes is first diagnosed at age 30 or later
will have CSME or high-risk characteristics at the time of the initial diagnosis of diabetes.5
Approximately 30% of patients will have some manifestation of diabetic retinopathy at diagnosis.
Therefore, the patient should be referred for ophthalmologic examination at the time of
diagnosis.6 [A:II]

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Diabetes Associated with Pregnancy
Diabetic retinopathy can worsen during pregnancy because of the pregnancy itself or the changes
in metabolic control.47-49 Patients with diabetes who are planning to become pregnant should be
encouraged to have their eyes examined prior to conception, should be counseled on the risk of
development and/or progression of diabetic retinopathy, and should be told to make every attempt
to lower their blood glucose levels to as near normal as possible for their own health and the
health of the fetus.47-49 [A:I] During the first trimester, another eye examination should be
performed; subsequent follow-up will depend on the level of retinopathy found (see Table 3).
Women who develop gestational diabetes do not require an eye examination during pregnancy
because such individuals are not at increased risk for diabetic retinopathy during pregnancy.
After the examination is completed, the ophthalmologist should discuss the results and their
implications with the patient.[A:III] Both eyes should be classified according to the categories of
diabetic retinopathy and macular edema discussed in the Treatment section.[A:III] Each category has
an inherent risk for progression. The diagnostic category determines the timing for both the
intervention and for follow-up exams.

ANCILLARY TESTS
If used appropriately, a number of tests ancillary to the clinical examination may enhance patient
care. The most common tests include the following:
! Color fundus photography
! Fluorescein angiography
! Ultrasonography
! Optical coherence tomography

Color Fundus Photography

Fundus photography is a more reproducible technique than a clinical examination for detecting
diabetic retinopathy in clinical research studies. However, clinical examination is often superior
for detecting retinal thickening associated with macular edema and may be better at identifying
fine-caliber NVD or NVE. Good-quality fundus photographs require a photographer skilled in
obtaining rigorously defined and technically challenging photographic fields of appropriate quality
(according to established ETDRS protocols23). Stereoscopic photographs offer an advantage over
nonstereoscopic photographs, and the traditional “seven stereo fields” provide the most complete
coverage.23 Large-field (60-degree) photographs may be more efficient at documenting the disease
status than multiple 30-degree photographs, but the former usually provide less detail and less
effective stereopsis.
Fundus photography is seldom of value in cases of minimal diabetic retinopathy or when diabetic
retinopathy is unchanged from the previous photographic appearance.[A:III] Fundus photography
may be useful for documenting significant progression of disease and response to treatment.[B:III]

Fluorescein Angiography
Fluorescein angiography is a clinically valuable test for selected patients with diabetic retinopathy
and is commonly used in the following ways (see Table 4):
! As a guide for treating CSME.28 [A:I]
! As a means of evaluating the cause(s) of unexplained decreased visual acuity.[A:III] Angiography
can identify macular capillary nonperfusion31 [A:II] or macular edema (or both) as possible
explanations for visual loss.
Fluorescein angiography is not routinely indicated as a part of the examination of patients with
diabetes.[A:III] It is not needed to diagnose CSME or PDR, both of which are diagnosed by means
of the clinical examination. However, because the test is useful in various situations, facilities for
fluorescein angiography should be available to physicians who diagnose and treat patients with
diabetic retinopathy.

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TABLE 4 Use of Fluorescein Angiography for Diabetic Retinopathy
Situation Usually Occasionally No

To guide treatment of CSME !

To evaluate unexplained visual loss !

To identify suspected but clinically obscure retinal neovascularization !

To screen a patient with no or minimal diabetic retinopathy !

CSME = clinically significant macular edema

The ophthalmologist who orders fluorescein angiography must be aware of the potential risks
associated with the procedure; severe medical complications may occur, including death (about
1/200,000 patients).66 Each angiography facility should have in place a care plan or emergency
plan and a clear protocol to minimize the risks and manage any complications.[A:III] Although
detrimental effects of fluorescein dye on the fetus have not been documented, fluorescein dye does
cross the placenta into the fetal circulation.67

Ultrasonography (Echography)
Ultrasonography is a valuable test for diabetic eyes with opaque media (most commonly due to
cataract or vitreous hemorrhage). This test should be considered when media opacities preclude
exclusion of retinal detachment by indirect ophthalmoscopy.

Optical Coherence Tomography

Optical coherence tomography provides high-resolution (10 micron) imaging of the vitreoretinal
interface, retina, and subretinal space. Optical coherence tomography can be useful for quantifying
retinal thickness, monitoring partial resolution of macular edema, and identifying vitreomacular
traction in selected patients with diabetic macular edema caused by a taut posterior hyaloid
face.68-70 This test might be considered in patients unresponsive to laser treatment for macular
edema for whom the ophthalmologist is considering vitrectomy with removal of the posterior
hyaloid face.

TREATMENT
Laser photocoagulation surgery is the standard, most widely used technique for treating diabetic
retinopathy. In general, it is advised for patients with high-risk PDR and for patients with CSME
and neovascularization of the anterior chamber angle (Table 5).71 [A:I] Individuals who are treated
according to methods used in the DRS and ETDRS have better visual outcomes than those who
are not treated. In a randomized, controlled clinical trial of scatter laser photocoagulation with
either argon or krypton, there was no statistically significant difference in the clinical effect of
these two wavelengths in the rates of regression of high-risk PDR.72 Although there is theoretical
and histologic evidence to suggest that other laser wavelengths also would be effective, clinical
studies evaluating the different wavelengths are limited. Regardless of the wavelength used, it is
important to avoid excessively intense burns, especially for focal laser photocoagulation.
Vitrectomy is also an important part of the treatment strategies for advanced diabetic retinopathy.
Laser photocoagulation techniques can be classified as scatter, focal, or grid (see also Glossary).
Scatter photocoagulation, also referred to as panretinal photocoagulation,30 is used for the
treatment of proliferative diabetic retinopathy and indirectly treats neovascularization on the optic
nerve, retinal surfaces, or in the anterior chamber angle by placing laser burns throughout the
peripheral fundus. Focal and grid photocoagulation are used for the treatment of diabetic macular
edema. Focal photocoagulation applies light, small-sized burns to leaking microaneurysms in the
posterior fundus. Grid photocoagulation applies a grid or pattern of burns (mimicking scatter
photocoagulation) to the areas of edema arising from diffuse capillary leakage or nonperfusion
shown on fluorescein angiography.31

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Management recommendations for patients with diabetes are summarized in Table 5 and are
described more fully in the following pages. The table provides guidance for a preferred practice
pattern for the general population of patients with diabetes; specific needs may vary on a case-by-
case basis.

TABLE 5 Management Recommendations for Patients with Diabetes

Severity of Retinopathy Presence of Follow-up Scatter Fluorescein Focal Laser†
CSME* (Months) (Panretinal) Angiography
Laser

1. Normal or minimal NPDR No 12 No No No

2. Mild to moderate NPDR No 6-12 No No No

Yes 2-4 No Usually Usually*‡

3. Severe or very severe NPDR No 2-4 Sometimes§ Rarely No

Yes 2-4 Sometimes§ Usually Usually║

4. Non-high-risk PDR No 2-4 Sometimes§ Rarely No

Yes 2-4 Sometimes§ Usually Usually‡

5. High-risk PDR No 3-4 Usually Rarely No

Yes 3-4 Usually Usually Usually║

6. High-risk PDR not amenable to -- 1-6 Not Possible¶ Occasionally Not Possible¶
photocoagulation (e.g., media
opacities)

* Exceptions include: hypertension or fluid retention associated with heart failure, renal failure, pregnancy, or any other causes that may
aggravate macular edema. Deferral of photocoagulation for a brief period of medical treatment may be considered in these cases.73 Also,
deferral of CSME treatment is an option when the center of the macula is not involved, visual acuity is excellent, close follow-up is
possible, and the patient understands the risks.
† Focal photocoagulation refers to direct focal laser to leaking microaneurysms or a grid photocoagulation pattern to areas of diffuse leakage
or nonperfusion seen on fluorescein angiography.
‡ Deferring focal photocoagulation for CSME is an option when the center of the macula is not involved, visual acuity is excellent, close follow-
up is possible, and the patient understands the risks. However, initiation of treatment with focal photocoagulation should also be
considered because although treatment with focal photocoagulation is less likely to improve the vision, it is more likely to stabilize the
current visual acuity.
§ Scatter (panretinal) photocoagulation surgery may be considered as patients approach high-risk PDR. The benefit of early scatter
photocoagulation at the severe nonproliferative or worse stage of retinopathy is greater in patients with type 2 diabetes than in those with
type 1.74 Treatment should be considered for patients with severe NPDR and type 2 diabetes. Other factors, such as poor compliance
with follow-up, impending cataract extraction or pregnancy, and status of the fellow eye will help in determining the timing of the scatter
photocoagulation.
║ Some experts feel that it is preferable to perform focal photocoagulation first, prior to scatter photocoagulation, to minimize scatter laser–
induced exacerbation of the macular edema.
¶ Vitrectomy is indicated in selected cases.
CSME = clinically significant macular edema; NPDR = nonproliferative diabetic retinopathy; PDR = proliferative diabetic retinopathy

Normal or Minimal NPDR

The patient with a normal retinal exam or minimal NPDR (i.e., with rare microaneurysms) should
be reexamined annually5 [A:II] because within 1 year, 5% to 10% of patients who are initially
normal will develop diabetic retinopathy. Existing retinopathy will worsen by a similar
percentage.8, 12, 13 Laser surgery, color fundus photography, and fluorescein angiography are not
indicated. [A:III]

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Mild to Moderate NPDR without Macular Edema
Patients with retinal microaneurysms and occasional blot hemorrhages or hard exudates should
have a repeat examination within 6 to 12 months, because disease progression is common.12 [A:III]
In one study of type 1 patients, 16% of patients with mild retinopathy (hard exudates and
microaneurysms only) progressed to proliferative stages within 4 years.12
Laser surgery and fluorescein angiography are not indicated for this group of patients. Color
fundus photography may occasionally be helpful as a baseline for future comparison (see
Ancillary Tests section).
For patients with mild NPDR, the 4-year incidence of either CSME or macular edema that is not
clinically significant is 12%. For moderate NPDR, the risk increases to 23% for patients with
types 1 and 2 diabetes.20 Patients with macular edema that is not clinically significant should be
reexamined within 3 to 4 months because they are at risk of developing CSME.28 [A:I]

Mild to Moderate NPDR with Clinically Significant Macular Edema

Clinically significant macular edema is defined by the ETDRS to include any of the following
features:
! Thickening of the retina at or within 500 microns of the center of the macula.
! Hard exudates at or within 500 microns of the center of the macula, if associated with thickening
of the adjacent retina (not residual hard exudates remaining after the disappearance of retinal
thickening).
! A zone or zones of retinal thickening 1 disc area or larger, any part of which is within 1 disc
diameter of the center of the macula.
It is convenient to subdivide CSME according to involvement at the center of the macula, because
the risk of visual loss and the need for focal photocoagulation is greater when the center is
involved. The diagnosis of diabetic macular edema can be difficult. Macular edema is best
evaluated by dilated examination using slit-lamp biomicroscopy and/or stereo fundus
photography. An ophthalmologist who treats patients for this condition should be familiar with
relevant studies and techniques as described in the ETDRS.28, 31 [A:I] Fluorescein angiography prior
to laser surgery for CSME is often helpful for identifying treatable lesions (although it is less
important when there are circinate lipid exudates in which leaking lesions are often obvious within
the lipid ring) and for identifying pathologic enlargement of the foveal avascular zone, which may
be useful in planning treatment.28 [A:I] Color fundus photography is often helpful to document the
status of the retina even if surgery is not performed (see Ancillary Tests section). Ocular
coherence tomography may be helpful to detect subtle edema and to follow the course of edema
after treatment.
Patients with CSME should be considered for laser surgery.28, 31 [A:I] The risk of moderate visual
loss (i.e., doubling of the visual angle; for example, a visual acuity decrease from 20/40 to 20/80)
is reduced by more than 50% for patients who undergo appropriate laser photocoagulation surgery,
compared with those who are not treated (see Appendix 2). Vision improves for a minority of
patients; for the majority of cases, the goal of treatment with laser photocoagulation is to stabilize
the visual acuity. Patients with CSME and excellent visual function should be considered for
treatment before visual loss occurs, because substantial recovery of reduced visual acuity is
relatively unusual after treatment.28, 31, 75 [A:I] Most patients require more than one treatment session
(three to four on average), 2 to 4 months apart, for macular edema to resolve.31 When treatment is
deferred, as may be desirable when the center of the macula is not involved or imminently
threatened, the patient should be observed closely (at least every 3 to 4 months) for
progression.[A:III]
Effective surgical treatment and retreatment protocols have been detailed in the DRS and the
ETDRS.17, 29, 30 Preoperatively, the ophthalmologist should discuss with the patient the side effects
and risks of treatment.28, 31 [A:I] A follow-up examination for individuals with CSME should be
scheduled within 2 to 4 months of surgery22 [A:II] (see Table 5).

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Severe and Very Severe NPDR and Non-High-Risk PDR
These categories are combined for discussion because the ETDRS data showed their similar
clinical course, and subsequent recommendations for treatment are similar. In eyes with severe
NPDR, the risk of progression to proliferative disease is high. Half of patients with severe NPDR
will develop PDR within 1 year, and 15% will be high-risk PDR.20 For patients with very severe
NPDR, the risk of developing PDR within 1 year is 75%, and 45% will be high-risk PDR.
Therefore, these patients should be reexamined within 2 to 4 months.20, 74 [A:I]
The value of laser surgery for this group of patients was studied by the ETDRS. The ETDRS
compared early panretinal photocoagulation with deferral of photocoagulation, defined as careful
follow-up (at 4-month intervals) and prompt panretinal photocoagulation if progression to high-
risk PDR occurred (see Appendix 2). Although the study did not provide definitive guidelines, the
ETDRS suggested that panretinal photocoagulation should not be recommended for eyes with mild
or moderate NPDR, provided that follow-up could be maintained. When retinopathy is more
severe, panretinal photocoagulation should be considered and usually should not be delayed if the
eye has reached the high-risk proliferative stage (see Appendix 2).20 [A:I] Careful follow-up at 3 to 4
months is important: if the patient will not or cannot be followed closely or if there are associated
medical conditions such as impending cataract surgery or pregnancy, then early laser
photocoagulation may be indicated.20, 74 [A:I] Laser photocoagulation may be indicated particularly
when access to health care is difficult. If laser surgery is elected, full panretinal photocoagulation is
a proven surgical technique, while partial panretinal photocoagulation is not recommended.17 [A:I]
Additional analyses of visual outcome in ETDRS patients with severe NPDR to non-high-risk
PDR suggest that the recommendation to consider scatter photocoagulation prior to the
development of high-risk PDR is particularly appropriate for patients with type 2 diabetes. The
risk of severe vision loss or vitrectomy was reduced by 50% in those who were treated early
compared with deferral until high-risk PDR developed. For patients with type 1 diabetes, the
timing of the scatter photocoagulation will depend on the compliance with follow-up and the
status and response to treatment of the fellow eye. For both type 1 and type 2 diabetics, impending
or recent cataract surgery or pregnancy may increase the risk of progression and may influence the
decision to perform panretinal photocoagulation.
The goal of laser surgery is to reduce the risk of visual loss. Preoperatively, the ophthalmologist
should assess macular edema, discuss side effects of treatment and risks of visual loss with the
patient, and obtain informed consent.29, 30 [A:I] If retrobulbar or peribulbar injections are used prior
to photocoagulation, plans should be made to manage anticipated complications.[A:III] Serious
complications are rare, but they do occur.76 The ETDRS protocol provides detailed guidelines for
treatment.29, 30 [A:I] The patient should be seen at follow-up visits every 1 to 4 weeks until
completion of panretinal photocoagulation, and then every 2 to 4 months thereafter (see Table
5).[A:III]
When scatter photocoagulation for severe NPDR or non-high-risk PDR is to be carried out in eyes
with macular edema, many experts feel that it is preferable to perform focal photocoagulation
before scatter photocoagulation. Based on clinical trials, there is evidence that scatter
photocoagulation as used in the DRS and ETDRS may exacerbate macular edema and may cause
increased rates of moderate visual loss (i.e., doubling of the visual angle) compared with untreated
control eyes.20 Scatter laser surgery should not be delayed, however, if PDR is well into the high-
risk stage (i.e., if NVD is extensive or vitreous/preretinal hemorrhage has occurred recently). In
such cases, focal and scatter photocoagulation may be performed concomitantly.
Fluorescein angiography may be used to determine the presence or absence of areas of
nonperfusion and/or clinically undetected areas of retinal neovascularization and to establish the
cause of a documented loss of visual acuity.

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High-Risk PDR
DRS high-risk characteristics for severe visual loss with high-risk PDR include:
! New vessels within 1 disc diameter of the optic nerve head that are larger than 1/3 disc area.
! Vitreous or preretinal hemorrhage associated with less extensive NVD or with NVE 1/2 disc area
or more in size.
The risk of severe visual loss among patients with high-risk PDR can be reduced substantially by
means of scatter photocoagulation as described in the DRS and ETDRS. Most patients with high-
risk PDR should receive laser scatter photocoagulation treatment expeditiously.17, 19 [A:I] Scatter
photocoagulation causes regression of neovascularization. This technique has been fully
described17, 30 and the results are summarized in Appendix 2. Additional scatter photocoagulation
may be required for the following indications:
! Failure of the neovascularization to regress
! Increasing neovascularization of the retina or iris
! New vitreous hemorrhage
! New areas of neovascularization
Because scatter (panretinal) photocoagulation can exacerbate macular edema, the scatter treatment
is often divided into two or more treatment sessions. For patients who have CSME in addition to
high-risk PDR, combined focal and panretinal photocoagulation at the first treatment session
should be considered. Fluorescein angiography does not usually need to be performed in order to
apply the panretinal photocoagulation effectively. If CSME is present, however, a fluorescein
angiogram may be used to guide application of focal photocoagulation. In some cases, vitreous
hemorrhage may recur in patients who have had extensive panretinal photocoagulation. These
hemorrhages often clear spontaneously and do not necessarily require additional laser surgery.
In the setting of previously untreated PDR, some patients who have vitreous opacities and active
proliferation of neovascularization (e.g., rubeosis iridis) should have early vitrectomy.32-35 [A:II]
Vitrectomy also may be helpful for selected patients who have extensive active neovascular or
fibrovascular proliferation. The value of early vitrectomy tends to increase with the increasing
severity of neovascularization (see Appendix 2).

High-Risk PDR Not Amenable to Photocoagulation

In some patients with severe vitreous or preretinal hemorrhage, it may be impossible to perform
laser photocoagulation surgery. In other cases, advanced active PDR may persist despite extensive
panretinal photocoagulation surgery. In some of these cases, vitreous surgery may be indicated.
Vitreous surgery is frequently indicated in patients with traction macular detachment (particularly
of recent onset), combined traction–rhegmatogenous retinal detachment, and vitreous hemorrhage
precluding scatter photocoagulation. Patients with vitreous hemorrhage and rubeosis iridis also
should be considered for prompt vitrectomy and intraoperative panretinal photocoagulation
surgery.
The DRVS demonstrated that in selected cases, early vitrectomy is effective in the management of
(1) nonclearing vitreous hemorrhage and (2) severe fibrovascular proliferation before traction
detachment involves the macula (see Appendix 2). The DRVS was conducted before the advent of
some modern surgical technology (e.g., endolaser, modern bimanual instrumentation, and
perfluorocarbon), so the DRVS result probably should be viewed as only general guidelines for
the current surgical management of diabetic retinopathy.[A:III] Multiple case series have indicated
that pars plana vitrectomy to manage selected patients with diffuse CSME that is unresponsive to
previous macular laser photocoagulation may improve visual acuity when significant
vitreomacular traction is present.77-79 However, the value of vitrectomy in CSME has not been
studied in a randomized clinical trial.

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Other Treatments
A number of studies are under way to evaluate treatments for diabetic retinopathy. These include
intravitreal administration of short- and long-acting corticosteroids for the treatment of diabetic
macular edema. Other drugs with antiangiogenic activity that are currently being investigated are
inhibitors of the vascular endothelial growth factor, protein kinase C inhibitors, and growth
hormone antagonists. Routes of delivery such as oral, direct intravitreal injection, or implantation
with slow release of the pharmacologic agent are also being assessed. There is insufficient
evidence to guide treatment recommendations for these therapies at this time.

SIDE EFFECTS AND COMPLICATIONS OF TREATMENT

Focal Laser Photocoagulation for Diabetic Macular Edema

Focal laser photocoagulation for diabetic macular edema may result in an initial decrease in
central vision. Patients undergoing this treatment should be informed of this possibility.[A:III]
Rarely, this treatment may induce subretinal fibrosis with CNV, which may be associated with
permanent central vision loss.80, 81 The most important factors associated with subretinal fibrosis
include the most severe degree of subretinal hard exudates in the macula and elevated serum lipids
prior to laser photocoagulation.82 Only 8% of cases of subretinal fibrosis were directly related to
focal laser photocoagulation. Laser photocoagulation causes disruption of the retina with
destruction of the photoreceptors. In cases where laser burns have been placed close to the fovea,
especially burns that are confluent, the patient may be aware of paracentral scotomas.83 In
addition, inadvertent foveal burns may produce a permanent central scotoma. It is important to
avoid placing laser burns in or close to the center of the fovea.

Scatter Photocoagulation for Severe NPDR or PDR

Scatter treatment was shown in the DRS to result in some central vision loss. Peripheral visual
field constrictions with poor dark adaptation are side effects of extensive scatter photocoagulation
treatment. In the presence of neovascularization, the patient should be warned that vitreous
hemorrhage may occur during the course of scatter laser photocoagulation.[A:III]

Vitrectomy
Vitreous surgery has the potential for serious complications, including recurrent vitreous
hemorrhage, retinal detachment, and rubeosis iridis, and these complications may result in severe
visual loss and eye pain.84-87

FOLLOW-UP
The follow-up evaluation includes a history and examination.

History
A follow-up history should include changes in the following:
! Symptoms[A:III]
! Systemic status (pregnancy, blood pressure, renal status)[A:III]
! Glycemic status (hemoglobin A1c)7, 9, 16 [A:I]

Examination
A follow-up examination should include the following elements:
! Visual acuity9 [A:I]
! Intraocular pressure[A:III]
! Slit-lamp biomicroscopy with iris examination88 [A:II]
! Gonioscopy (if iris neovascularization is suspected or present or if intraocular pressure is
increased)88 [A:II]

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! Stereo examination of the posterior pole with dilation of the pupils28 [A:I]
! Peripheral retina and vitreous examination, when indicated25, 89 [A:II]
Recommended intervals for follow-up are given in Table 5.

PROVIDER
Although the ophthalmologist will perform most of the examination and all surgery, certain
aspects of data collection may be conducted by another trained individual under the
ophthalmologist’s supervision and review. Because of the complexities of the diagnosis and
surgery for PDR, the ophthalmologist caring for patients with this condition should be familiar
with the specific recommendations of the DRS, ETDRS, UKPDS, and DCCT.[A:III] The
ophthalmologist should also have training in and experience with the management of this
particular condition.[A:III]

COUNSELING/REFERRAL
While it is clearly the responsibility of the ophthalmologist to manage eye disease, it is also the
ophthalmologist’s responsibility to ensure that patients with diabetes are referred for appropriate
management of their systemic condition. It is the realm of the patient’s family physician, internist,
or endocrinologist to manage the systemic diabetes. The ophthalmologist should communicate
with the attending physician.[A:III]
Some patients with diabetic retinopathy will lose substantial vision despite being treated according
to the recommendations in this document.74 Those whose conditions fail to respond to surgery and
those for whom further treatment is unavailable should be provided with proper professional
support and offered referral for counseling, rehabilitative, or social services as appropriate.[A:III]
Referral to a provider experienced in vision rehabilitation care who can equip the patient with
appropriate low-vision aids can also be useful.90 It is important for the ophthalmologist to be
sensitive to and assist in addressing the implications of visual impairment in patients with
diabetes.90

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APPENDIX 1. SUMMARY OF MAJOR

RECOMMENDATIONS FOR CARE
DIAGNOSIS
The initial examination for a patient with diabetes mellitus includes all features of the
comprehensive adult medical eye evaluation, with particular attention to those aspects relevant to
diabetic retinopathy.

History
An initial history should consider the following elements:
! Duration of diabetes[A:I]
! Past glycemic control (hemoglobin A1c)[A:I]
! Medications[A:III]
! Medical history (e.g., onset of puberty,[A:III] obesity,[A:III] renal disease,[A:II] systemic
hypertension,[A:I] serum lipid levels,[A:II] pregnancy[A:I])

Examination
The initial examination should include the following elements:
! Best-corrected visual acuity[A:I]
! Intraocular pressure[A:III]
! Gonioscopy when indicated[A:III]
! Slit-lamp biomicroscopy[A:III]
! Dilated funduscopy including stereoscopic examination of the posterior pole[A:I]
! Examination of the peripheral retina and vitreous[A:III]
Slit-lamp biomicroscopy with accessory lenses is the recommended method to evaluate
retinopathy in the posterior pole and midperipheral retina.[A:III] The examination of the peripheral
retina is best performed with indirect ophthalmoscopy or with slit-lamp biomicroscopy, combined
with a contact lens.[A:III]

EXAMINATION SCHEDULE

TABLE A-1 Recommended Eye Examination Schedule for Patients with Diabetes Mellitus
Diabetes Type Recommended Time of First Recommended Follow-up*
Examination

Type 1 5 years after onset[A:II] Yearly[A:II]

Type 2 At time of diagnosis[A:II] Yearly[A:II]
Prior to pregnancy Prior to conception or early in the first No retinopathy to mild or moderate NPDR: every 3–12 months[A:I]
(type 1 or type 2) trimester[A:I] Severe NPDR or worse: every 1–3 months[A:I]

* Abnormal findings may dictate more frequent follow-up examinations.

NPDR = nonproliferative diabetic retinopathy

TREATMENT
Management recommendations for patients with diabetic retinopathy are summarized in Table 5 in
the main body of the text.

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FOLLOW-UP
The follow-up evaluation includes a history and examination.

History
A follow-up history should include changes in the following:
! Symptoms[A:III]
! Systemic status (pregnancy, blood pressure, renal status)[A:III]
! Glycemic status (hemoglobin A1c)[A:I]

Examination
A follow-up examination should include the following elements:
! Visual acuity[A:I]
! Intraocular pressure[A:III]
! Slit-lamp biomicroscopy with iris examination[A:II]
! Gonioscopy (if iris neovascularization is suspected or present or if intraocular pressure is
increased)[A:II]
! Stereo examination of the posterior pole with dilation of the pupils[A:I]
! Peripheral retina and vitreous examination, when indicated[A:II]
Recommended intervals for follow-up are given in Table 5 in the main body of the text.

PROVIDER
Because of the complexities of the diagnosis and surgery for PDR, the ophthalmologist caring for
patients with this condition should be familiar with the specific recommendations of the DRS,
ETDRS, UKPDS, and DCCT.[A:III] The ophthalmologist should also have training in and
experience with the management of this particular condition.[A:III]

COUNSELING/REFERRAL
Patient education about the importance of maintaining near-normal glucose levels and near-normal
blood pressure and lowering serum lipid levels is an important aspect of the care process.[A:III]
Patients with diabetes mellitus without diabetic retinopathy should be encouraged to have annual
dilated eye examinations to detect the onset of diabetic retinopathy.[A:III] Patients should also be
informed that effective treatment for diabetic retinopathy depends on timely intervention, despite
good vision and no ocular symptoms.[A:III]
Those patients whose conditions fail to respond to surgery and those for whom further treatment is
unavailable should be provided with proper professional support and offered referral for
counseling, vision rehabilitation, or social services as appropriate.[A:III]

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APPENDIX 2. TREATMENT TRIAL

RESULTS
DIABETIC RETINOPATHY STUDY (1979)
The Diabetic Retinopathy Study (DRS) was designed to investigate the value of xenon arc and
argon photocoagulation surgery among patients with severe NPDR and PDR.17 The results are
shown in Table A-1.

TABLE A-1 Visual Outcome for Xenon Arc and Argon Laser Photocoagulation from the Diabetic Retinopathy Study
Baseline Severity of Retinopathy Duration of Follow-up Control Patients Treated Patients
(Years) (% with Severe Visual Loss) (% with Severe Visual Loss)

Severe nonproliferative 2 3 3
4 1 4
Mild proliferative 2 7 3
4 21 7
High-risk proliferative 2 26 11
4 44 20

NOTE: Severe visual loss was defined as worse than 5/200 visual acuity at two or more consecutive completed visits (scheduled at
4-month intervals).

EARLY TREATMENT DIABETIC RETINOPATHY STUDY (1985 TO 1990)

The Early Treatment Diabetic Retinopathy Study (ETDRS) investigated the value of
photocoagulation surgery for patients with NPDR or PDR without high-risk characteristics.28 The
results for eyes with macular edema are shown in Table A-2. Visual loss was defined as at least
doubling of the visual angle (e.g., 20/20 to 20/40, or 20/50 to 20/100).

TABLE A-2 Visual Outcome for Laser Photocoagulation Treatment from the Early Treatment Diabetic Retinopathy Study
Extent of Duration of Follow-up Control Patients Treated Patients
Macular Edema (Years) (% with Visual Loss) (% with Visual Loss)

CSME 1 8 1
(center of macula not involved) 2 16 6
3 22 13
CSME 1 13 8
(center of macula involved) 2 24 9
3 33 14

NOTE: Visual loss was defined as at least doubling of the visual angle.
CSME = clinically significant macular edema.

In eyes with NPDR or non-high-risk PDR, early scatter photocoagulation was compared with
deferral of photocoagulation, and although there was a beneficial treatment effect, the outlook for
maintaining vision was good in both groups. The 5-year rates of severe visual loss or vitrectomy
ranged from 2% to 6% in eyes assigned to early photocoagulation and from 4% to 10% in eyes
assigned to deferral. Early scatter photocoagulation was attended by side effects (small decreases
in visual acuity and visual field) in some eyes, and the ETDRS concluded that deferral of
photocoagulation was preferable at least until retinopathy was approaching the high-risk stage.
Eyes approaching that stage had a 50% risk of reaching it within 12 to 18 months. Eyes in this

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category had very severe NPDR or non-high-risk PDR characterized by NVD less than 1/4 to 1/3
disc area and/or NVE, without vitreous or preretinal hemorrhage.
Recent additional analyses of visual outcome in ETDRS patients with severe NPDR to non-high-
risk PDR suggest that the recommendation to consider scatter photocoagulation prior to the
development of high-risk PDR is particularly appropriate for patients with type 2 diabetes.74 The
risk of severe vision loss or vitrectomy was reduced by 50% in those who were treated early
compared with those who deferred treatment until high-risk PDR developed.
For patients with type 1 diabetes, the timing of the scatter photocoagulation will depend on the
compliance with follow-up, status and response to treatment of the fellow eye, impending cataract
surgery, and/or pregnancy status.

DIABETIC RETINOPATHY VITRECTOMY STUDY (1988)

The Diabetic Retinopathy Vitrectomy Study (DRVS) investigated the role of vitrectomy in
managing eyes with very severe PDR. The benefit of early vitrectomy for severe vitreous
hemorrhage (defined as hemorrhage obscuring the macula or major retinal vessels for 3 disc
diameters from the macular center) was seen in type 1 patients, but no such advantage was found
in type 2 patients, who did not benefit from earlier surgery. Among patients with visual acuity of
5/200 or worse and severe vitreous hemorrhage with reduced vision for at least 1 month and
without previous treatment or complications such as retinal detachment or neovascularization at
the iris, early vitrectomy was beneficial. Overall, at 2 years after surgery, 25% of the early
vitrectomy group and 15% of the deferral group had visual acuity of 20/40 or better. The
advantage was most pronounced in patients with type 1 diabetes (36% vs. 12% for early
vitrectomy vs. deferral of vitrectomy, respectively) and was not statistically significant for patients
with type 2 diabetes.
The DRVS showed that early vitrectomy was beneficial for patients with visual acuity of 20/400
or better plus one of the following: (1) severe neovascularization and fibrous proliferation; (2)
fibrous proliferation and moderate vitreous hemorrhage; or (3) moderate neovascularization,
severe fibrous proliferation, and moderate vitreous hemorrhage. Among such patients, 44% with
early vitrectomy and 28% in the observation group had visual acuity of 20/40 or better at 4 years
of follow-up.
The results of the DRVS should be interpreted in light of subsequent advances in vitreoretinal
surgery such as the introduction of endoscopic and indirect ophthalmoscopic laser
photocoagulation. The use of long-acting intraocular gases such as sulfur hexafluoride and
perfluoropropane, the use of viscodissection, and the use of heavier-than-water liquids such as
perfluoro-octane are advances in vitreoretinal surgery that developed after the DRVS. Thus, the
results may actually be better than those reported in the DRVS.91 Early vitrectomy should be
considered for selected patients with type 2 diabetes, particularly those in whom severe vitreous
hemorrhage prohibits laser therapy photocoagulation of active neovascularization.

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APPENDIX 3. GLYCEMIC CONTROL

The Diabetes Control and Complications Trial (DCCT) was a multicenter, randomized controlled
trial designed to study the connection between glycemic control and retinal, renal, and neurologic
complications of type 1 diabetes mellitus. Published results from this trial demonstrated that
improved blood sugar control can delay the onset and slow the progression of diabetic retinopathy,
nephropathy, and neuropathy in type 1 patients.8 The DCCT showed a strong exponential
relationship between the risk of diabetic retinopathy and the mean hemoglobin A1c level. For each
10% decrease in the hemoglobin A1c (e.g., from 9.0% to 8.1%), there was a 39% decrease in the
risk of progression of retinopathy over the range of hemoglobin A1c values. There was no
glycemic threshold at which the risk of retinopathy was eliminated above the nondiabetic range of
hemoglobin A1c (4.0% to 6.05%).
After 6.5 years of follow-up, the DCCT ended, and all patients were encouraged to pursue strict
control of blood sugar. Most of these patients are being followed in the Epidemiology of Diabetes
Interventions and Complications (EDIC) trial, which includes 95% of the DCCT subjects, half
from each treatment group. A total of 1294 to 1335 patients have been examined annually in the
EDIC study. Further progression of diabetic retinopathy during the first 4 years of the EDIC study
was 66% to 77% less in the former intensive treatment group than in the former conventional
treatment group. The benefit persists even at 7 years. This benefit includes an effect on severe
diabetic retinopathy, including severe NPDR, PDR, CSME, and the need for focal/grid or scatter
laser photocoagulation. The decrease in hemoglobin A1c from 9% to approximately 8% did not
drastically reduce the progression of diabetic retinopathy in the former conventional treatment
group, nor did the increase in hemoglobin A1c from approximately 7% to approximately 8%
drastically accelerate diabetic retinopathy in the former intensive treatment group. Thus, it takes
time for improvements in control to negate the long-lasting effects of prior prolonged
hyperglycemia, and once the biological effects of prolonged improved control are manifest, the
benefits are long-lasting. Furthermore, the total glycemic exposure of the patient (i.e., degree and
duration) determines the degree of retinopathy observed at any one time.
A positive relationship between the 4-year incidence and progression of retinopathy and
glycosylated hemoglobin remains after controlling for other risk factors, such as duration of
diabetes and severity of retinopathy at a baseline examination.7, 12, 13 Extrapolation of pathologic
and clinical experience strongly suggests that poor levels of control contribute to microangiopathy,
including retinopathy.96, 97 The development of PDR parallels an increased risk of nephropathy,
myocardial infarction, and/or cerebral vascular accidents.
Although good glycemic control is advised, there is some evidence that rapid improvement of
long-standing poor control may increase the risk of retinopathy progression over the first year in
some type 1 diabetic patients.98 Specifically, there may be a transient increase in the number of
cotton-wool spots seen on retinal examination. Frequent ophthalmologic monitoring is important
when patients are being brought under better control.98
In the DCCT, among patients using intensive treatment regimens, there was a threefold increase in
severe hypoglycemic events and excess weight gain. Increased risk of hypoglycemia is a
consequence of strict blood glucose control. Irregular food intake, failure to check blood glucose
before planned or unplanned vigorous exercise or before operating a motor vehicle, and excess
alcohol are risk factors for hypoglycemia. Diabetes mellitus education and regular reinforcement
should be provided by diabetes nurse and dietitian educators and may help minimize the risk of
hypoglycemia.
The United Kingdom Prospective Diabetes Study (UKPDS),37, 56 a randomized controlled clinical
trial of blood glucose control, enrolled 3867 patients with newly diagnosed type 2 diabetes.
Intensive blood glucose control by either the sulfonylureas or insulin decreased the risk of
microvascular complications but not the risk of macrovascular disease. There were no adverse

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effects of the individual drugs on the cardiovascular outcome. In this study, there was a 29%
reduction in the need for retinal photocoagulation in the group that had intensive glucose therapy
compared with those that had conventional treatment (relative risk, 0.71; 95% confidence interval,
0.53–0.96; P=0.003).

APPENDIX 4. COST-BENEFIT ANALYSES

Computer-simulation models have been designed to predict the medical and economic effects of
applying accepted methods for controlling diabetic retinopathy among type 1 patients.92-94 In one
study, recommendations for screening were taken from the Public Health Committee of the
American Academy of Ophthalmology. Surgery recommendations and modeled treatment efficacy
were drawn from the reports of the Diabetic Retinopathy Study (DRS) and the Early Treatment
Diabetic Retinopathy Study (ETDRS). Costs of screening and surgery were drawn from published
Medicare reimbursement data.
The model predicted that over their lifetime, 72% of type 1 patients will eventually develop PDR
requiring panretinal photocoagulation and that 42% will develop macular edema.92 If treatments
are delivered as recommended in the clinical trials, the model predicted a cost of $966 per person-
year of vision saved from PDR and $1120 per person-year of central visual acuity saved from
macular edema. In addition, if all type 1 patients received eye care at federal expense, the
predicted savings exceed $167.0 million and 79,236 person-years of sight.94 These costs are less
than the cost of a year of Social Security disability payments for those disabled by vision loss.
Therefore, treatment yields a substantial savings compared with the direct cost to society of the
case of an untreated type 1 patient. The indirect costs, in lost productivity and human suffering,
are even greater.
A more recent analysis, using the same computer model, predicted the cost-effectiveness of
detecting and treating diabetic retinopathy from the insurers’ perspective.95 Screening and
treatment of eye disease in diabetic patients costs, on average, $3190 per quality-adjusted life-year
(QALY) saved. For patients with type 1 diabetes, it costs $1996 per QALY saved; for patients
with type 2 diabetes who use insulin, it costs $2933 per QALY saved; and for patients with type 2
diabetes who do not use insulin, it costs $3530 per QALY saved.

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GLOSSARY
Clinically significant macular edema (CSME): Retinal thickening at or within 500 microns of the
center of the macula; and/or hard exudates at or within 500 microns of the center of the macula, if
associated with thickening of the adjacent retina; and/or a zone or zones of retinal thickening 1
disc area in size, any part of which is within 1 disc diameter of the center of the macula.
DCCT: Diabetes Control and Complications Trial.
Diabetes mellitus: According to the American Diabetes Association expert committee, the criteria
for the diagnosis of diabetes mellitus are as follows.
Symptoms of diabetes plus casual plasma glucose concentration equal to or exceeding 200 mg/dL
(11.1 mmol/L). “Casual” is defined as any time of day without regard to time since last meal. The
classic symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss.
or
Fasting plasma glucose equal to or exceeding 126 mg/dL (7.0 mmol/L). Fasting is defined as no
caloric intake for at least 8 hours.
or

A plasma glucose measurement at 2 hours postload equal to or exceeding 200 mg/dL (11.1
mmol/L) during an oral glucose tolerance test. The test is be performed as described by the World
Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose
dissolved in water. However, the expert committee has recommended against oral glucose
tolerance testing for routine clinical use.

Diabetes type: Type 1, previously called juvenile-onset or insulin-dependent diabetes, is

characterized by beta-cell destruction and usually leads to absolute insulin deficiency. Type 2,
previously called adult-onset or noninsulin-dependent diabetes, is characterized by insulin
resistance with an insulin secretory defect that leads to relative insulin deficiency. (Source: Report
of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care
2003; 26[Suppl1]:S5-S20.)
DRS: Diabetic Retinopathy Study.

DRVS: Diabetic Retinopathy Vitrectomy Study.

Early proliferative diabetic retinopathy (i.e., proliferative retinopathy without DRS high-risk
characteristics): New vessels not meeting the criteria of high-risk proliferative retinopathy.
EDIC: Epidemiology of Diabetes Interventions and Complications study.
ETDRS: Early Treatment Diabetic Retinopathy Study.
Focal photocoagulation: A laser technique directed to abnormal blood vessels with specific areas
of focal leakage (i.e., microaneurysms) to reduce chronic fluid leakage in patients with macular
edema.
Grid photocoagulation: A laser technique in which a grid pattern of scatter burns is applied in
areas of diffuse macular edema and nonperfusion. Typically, fluorescein angiograms of these areas
show a diffuse pattern rather than focal leakage.
Hard exudate: Protein and lipid accumulation within the retina.

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High-risk proliferative diabetic retinopathy: New vessels on or within 1 disc diameter of the
optic disc equaling or exceeding standard photograph 10A (about 1/4 to 1/3 disc area), with or
without vitreous or preretinal hemorrhage; or vitreous and/or preretinal hemorrhage accompanied
by new vessels either on the optic disc less than standard photograph 10A or new vessels
elsewhere equaling or exceeding 1/2 disc area.
Intraretinal microvascular abnormalities (IRMA): Tortuous intraretinal vascular segments,
varying in caliber from barely visible to 31 microns in diameter (1/4 the width of a major vein at
the disc margin); they occasionally can be larger. IRMA may be difficult to distinguish from
neovascularization.
Macular edema: Thickening of the retina within 1 or 2 disc diameters of the center of the macula.
Mild nonproliferative diabetic retinopathy: At least one microaneurysm and less than moderate
nonproliferative diabetic retinopathy.
Moderate nonproliferative diabetic retinopathy: Hemorrhages and/or microaneurysms greater
than standard photograph 2A, and/or soft exudates, venous beading, or intraretinal microvascular
abnormalities present but less than severe nonproliferative retinopathy.
Moderate visual loss: The loss of 15 or more letters on the ETDRS visual acuity chart, or
doubling of the visual angle (e.g., 20/20 to 20/40, or 20/50 to 20/100).
Nonproliferative diabetic retinopathy (NPDR): The phases of diabetic retinopathy with no
evidence of retinal neovascularization.

NPDR: Nonproliferative diabetic retinopathy.

NVD: Neovascularization on or within 1 disc diameter of the optic disc.
NVE: Neovascularization elsewhere in the retina and greater than 1 disc diameter from the optic
disc margin.

PDR: Proliferative diabetic retinopathy.

Proliferative diabetic retinopathy (PDR): Advanced disease characterized by NVD and/or NVE.
Scatter (panretinal) photocoagulation: A type of laser surgery used for patients with proliferative
diabetic retinopathy. The surgery is delivered in a scatter pattern throughout the peripheral fundus
and is intended to lead to a regression of neovascularization.

Severe nonproliferative diabetic retinopathy: Using the 4-2-1 rule, the presence of at least one of
the following features: (1) severe intraretinal hemorrhages and microaneurysms, equaling or
exceeding standard photograph 2A, present in four quadrants; (2) venous beading in two or more
quadrants; or (3) moderate intraretinal microvascular abnormalities equaling or exceeding standard
photograph 8A in one or more quadrants.
Severe visual loss: Occurrence of visual acuity worse than 5/200 at any two consecutive visits,
scheduled at 4-month intervals.
UKPDS: United Kingdom Prospective Diabetes Study.

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Very severe nonproliferative diabetic retinopathy: Presence of two or more of the features
described in the definition of severe nonproliferative diabetic retinopathy.

Standard photograph 2A, the standard for

hemorrhages/microaneurysms. Eyes with severe NPDR
have this degree of severity of hemorrhages and
microaneurysms in all four midperipheral quadrants.
(Source: ETDRS.)

Standard photograph 8A, the standard for moderate

IRMA. Patients with severe NPDR have moderate IRMA
of at least this severity in at least one quadrant.
(Source: ETDRS.)

Standard photograph 10A defines the lower border of

moderate NVD. NVD covers approximately 1/3 the area
of the standard disc. This extent of NVD alone would
constitute PDR with high-risk characteristics.
(Source: ETDRS.)

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RELATED ACADEMY MATERIALS

Basic and Clinical Science Course
Retina and Vitreous (Section 12, 2003-2004).
Clinical Skills Videotape
Basic Techniques of Fluorescein Angiography (1998).
Evaluation and Treatment of Diabetic Retinopathy (1999).
Eye Fact Sheets
Fluorescein Angiography (2002).
Fluorescein and ICG Angiography (2001).
Focal Points
Practical Management of Diabetic Retinopathy (2003).
LEO Clinical Topic Update Online
Retina and Vitreous (2000). http://www.aao.org/education
LEO Clinical Update Course CD-ROM
Retina (2003).
Ophthalmic Technology Assessments
Indocyanine Green Angiography (1998).
Ophthalmology Monographs
Diabetes and Ocular Disease: Past, Present, and Future Therapies (Monograph 14, 2000).
Fluorescein and Indocyanine Green Angiography: Techniques and Interpretation (Monograph
5, 2000).
Laser Photocoagulation of the Retina and Choroid (Monograph 11, 2000).
Patient Education Booklet
Diabetic Retinopathy (2001).
Patient Education Brochure
Diabetic Retinopathy (1998).
Diabetic Retinopathy (Spanish: Retinopatia Diabetica) (1998).
Patient Education Videotape
Diabetic Retinopathy (1990).
Slide Scripts
Diabetes and Eyecare (2001).
Videotapes
Management of Diabetic Retinopathy for the Primary Care Physician (1999).

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