Glistening Formation in A New Hydrophobic Acrylic Intraocular Lens
Glistening Formation in A New Hydrophobic Acrylic Intraocular Lens
Glistening Formation in A New Hydrophobic Acrylic Intraocular Lens
Abstract
Background: The formation of fluid-filled microvacuoles, termed glistenings, is a common complication of
intraocular lenses (IOLs) made from hydrophobic acrylate. Using our well-established in-vitro laboratory method, we
evaluated a new IOL material’s resistance to glistening formation.
Methods: An in-vitro stress test for glistening induction was performed on 20 samples of hydrophobic acrylic IOLs:
ten of the new Eyecryl ASHFY600 (Biotech Vision Care, Ahmedabad, India) compared with ten samples of AcrySof
IQ SN60WF (Alcon, Fort Worth, USA). The number of microvacuoles per square millimetre (MV/mm2) was evaluated
in five sections of each IOL. The results for each model were compared and rated on a modified Miyata Scale for
grading glistening severity.
Results: In all cases, glistening number was higher in the central section of the IOL optic than in the periphery.
Mean number of MV/mm2 was highest in the central part of the AcrySof IQ SN60WF, with 41.84 (±27.67) MVs/mm2.
The lowest number of glistenings was found in the five sections of the Eyecryl ASHFY600 with 0.52 (±0.24) MVs/
mm2. Mean value of the Eyecryl ASHFY600 IOL, using the Miyata Scale, was Zero.
Conclusion: In this in-vitro laboratory study, the new hydrophobic acrylic IOL showed a high resistance to
microvacuole formation. Results from this in-vitro study suggest that glistening numbers will be low in clinical use
in the Eyecryl ASHFY600.
Keywords: Glistenings, Hydrophobic acrylic, IOL material quality, IOL pathology, IOL material change, AcrySof,
Eyecryl, IOL aging
have been developed to intentionally generate ex-vivo behind the IOL that separates the lens optic into five stan-
glistenings [1]. Then, in accordance with the clinical dardized rectangular sections, an overview image in 14-fold
grading system, IOLs can be divided into different glis- magnification was obtained of the whole optic as a qualita-
tening categories depending on the number of microva- tive overview image (Fig. 2). Using 90-fold magnification,
cuoles per square millimetre that are produced after the an image was made for each section: the central section
aging procedure. Using such methods, the impact of glis- and four peripheral sections: to evaluate the number of glis-
tenings on the optical performance has been studied and tenings in each section.
is now well understood. Glistenings have a rather small Image analysis was performed using the ImageJ soft-
effect on the central image quality; their impact on light ware 1.49v. [11] Prior to image analysis parameters for
scattering, on the other hand, is greater [8, 9]. the median filter and automated thresholding have been
We evaluated, using an established in vitro laboratory predefined using test images with low to high glistening
method, the formation of glistenings of a new hydrophobic numbers. Investigators were blinded for the IOLs under
IOL, one which the manufacturer claims is more resistant test. Irregular optical fluctuations have been removed by
to glistening formation: the Eyecryl Plus ASHFY600, and a smoothing procedure using a nonlinear median filter.
compared it to the well-established and accepted AcrySof Contrast and brightness were optimized using the same
IQ SN60WF. settings for each IOL (Fig. 3a). An automated threshold
technique was used with the predefined threshold value
Methods to separate image information in a binary image - to dis-
Intraocular lenses tinguish glistenings from the background. The software
Ten monofocal Eyecryl Plus ASHFY600 IOLs (Biotech automatically counted the number of glistenings (Fig. 3b).
Vision Care, Ahmedabad, India) and ten monofocal Number of glistenings was evaluated for all five sections
AcrySof IQ SN60WF IOLs (Alcon, Fort Worth, USA) of the IOL optic. (Note, this approach is only suitable
were tested for their resistance to glistening formation. when the number of glistenings is moderate so that there
All IOLs had the same refractive power of + 21.0 diop- is no overlapping of glistenings.)
tres. The Eyecryl Plus ASHFY600 IOL and AcrySof IQ A 1200 × 1600 pixels area of the images in 90-fold
SN60WF are both single-piece IOLs, made from a magnification was selected to evaluate the number of
hydrophobic acrylic material (Table 1). glistenings. The central section was observed to corres-
pond to the region with the highest glistening density.
Accelerated aging An image of a micrometer in 90-fold magnification was
Microvacuoles (glistenings) were induced in-vitro by used to calibrate results with the dimensions of the lens
temperature changes using an established accelerated to determine the density of glistenings. As 1 mm corre-
aging protocol as previously described in our earlier sponds to 1086 Pixels and the original image size was
studies [8, 10]. In short, the lenses were hydrated in So- 1200 Pixels × 1600 Pixels, total image size was 1.63 mm2.
dium Chloride solution (0.9%) in glass flasks and stored Given number of glistenings was divided by 1.63 to ob-
in an oven at 45 °C for 24 h. After removal from the tain the number of microvacuoles per square millimetre
oven, the temperature was reduced to 37 °C by immers- (MVs/mm2).
ing the flasks in a water-bath. The lenses were kept at The number of glistenings of the central part of the
37 °C for 2.5 h. lenses was compared to a modification of the Miyata
scale [7]: Grade 0 (< 25 MVs/mm2), grade 1 (25–100
Evaluation of Glistenings MVs/mm2), grade 2 (100–200 MVs/mm2), grade 3 (>
All samples were examined under an EMZ-8TR Trinocular 200 MVs/mm2).
Zoom Stereo microscope (Meiji Techno, Saitama, Japan).
Microscopic images of all IOLs were taken immediately Data analysis
after aging process using an Infinity-2CB digital camera The number of MVs/mm2 in the central part and from all
(Lumenera, Nepean, Canada) (Fig. 1). After placing a grid five sections was averaged for ten IOLs from each group
Table 1 Characteristics of the studied IOL materials
IOL model Manufacturer Optic Copolymer Cross-Linker Equilibrium Water Blue-Light Manufacturing
Content Filter process
(in percent)
Eyecryl Plus Biotech Phenylethyl acrylate (PEA) and n.d. < 5% Yes Lathe-cut
ASHFY600 phenylethyl methacrylate (PEMA)
AcrySof IQ Alcon Phenylethyl acrylate (PEA) and butanediol diacrylate (BDDA) 0.1–0.5 Yes Cast-moulding
SN60WF phenylethyl methacrylate (PEMA)
IOL intraocular lens, n.d. not disclosed
Yildirim et al. BMC Ophthalmology (2020) 20:186 Page 3 of 7
Fig. 1 Setup for evaluation of glistenings. Left to right: Heated stage used to maintain and monitor the temperature during glistening evaluation;
Microscope over a Petri dish including an IOL under test on an illuminated, heated plate; Laptop with image analysis software
and given as mean (±standard deviation). Statistical analysis AcrySof IQ SN60WF IOL with 41.84 (±27.67) MVs/
was performed using Excel V.14.7.7 (Microsoft Corpor- mm2. The lowest amount of glistenings was obtained
ation, Redmond, USA) performing two-sided student’s t- averaging the five sections of the Eyecryl Plus ASHFY600,
tests. A P-value less than 0.05 was considered statistically with 0.52 (±0.24) MVs/mm2. For the AcrySof IOLs the
significant. glistening number in the central part was higher com-
pared to the value of all 5 sections (p < 0.05), for the
Results ASHFY600 both values were very similar, without a statis-
Material purity tically significant difference (p = 0.32) (Table 2).
Images of the central part of the lens in 90-fold magnifi-
cation show only a few glistenings in the Eyecryl Plus
Miyata grading
ASHFY600 with low variability between all ten Eyecryl
All of the Eyecryl Plus ASHFY600 IOLs were classified
IOLs. A larger number of glistenings was observed in
as Miyata Grade 0. Three of ten AcrySof IQ SN60WF
the AcrySof IQ SN60WF IOLs (Fig. 4). Software image
IOLs reached Miyata grade 1 but none of them scored
analysis revealed that the number of microvacuoles per
Miyata grade 2 (Fig. 5).
square millimetre was highest in the central part of the
Discussion
The Eyecryl ASHFY600 IOL showed high resistance to
glistening formation using an established laboratory ac-
celerated aging model. Furthermore, compared to the
well-established AcrySof SN60WF, the ASHFY600 had a
lower mean glistening grade. In general, glistening num-
bers were higher in the central part of the lens compared
to the periphery in the AcrySof IOLs, corresponding to
the lens thickness, which is highest in centre of the IOL
optic. Due to the overall low number of glistenings in
the ASHFY600 IOLs, mean values for the central section
and the periphery did not differ significantly (0.7 and
0.5, respectively).
In general, hydrophobic acrylate has some advantages
over other IOL materials. Lenses made of hydrophobic
acrylate show a lower tendency to develop posterior cap-
sule opacification in comparison to those made of poly-
methyl methacrylate (PMMA) or hydrophilic acrylate
[12]. Complications associated with hydrophilic acrylate
lenses like IOL calcification have not been described in
Fig. 2 Intraocular lens optic sectioned by a standard grid. In all IOLs, hydrophobic IOL material [13]. Hydrophobic acrylate
5 sections of the lens optic were analysed (central, left, upper,
IOLs can be cost-effectively produced and offer good
right, lower)
handling during small incision cataract surgery [4].
Yildirim et al. BMC Ophthalmology (2020) 20:186 Page 4 of 7
Fig. 3 Binary transformed exemplary images. a Saturation and Brightness were adjusted and a color threhold technique was applied to separate
glistening particles (red) from the background (black). b Counting of the glistenings (here blue) was performed automatically by an image
analysis software (ImageJ, 1.49v) [11]
Despite these benefits, hydrophobic acrylic IOLs are from 0.580 in clear control lenses to 0.533 in lenses
prone to develop glistenings. This long-term change in with over 500 MV/mm2 at a special frequency of 100
the material can worsen the lens’ optical performance lp/mm and a 3-mm-aperture [8]. Thus, glistenings have
[8, 9]. In recent research, our group has examined the a rather small effect on the central image quality but
nature of this deterioration in vision that is attributable their main effect is in changing another optical per-
to glistenings. Our colleagues, Weindler et al. demon- formance parameter, as a recent study by our group has
strated that a large number of glistenings is needed to shown. Labuz et al. found that straylight increases pro-
affect the central image quality [8]. They induced vary- portionally to the number of microvacuoles per square
ing amounts of glistening in monofocal AcrySof IOLs millimetre. Glistenings were induced in six different
and evaluated glistenings’ impact on the image quality hydrophobic IOL models. IOLs with a mean central
by measuring the lenses’ modulation transfer function number of 3532 MV/mm2 showed elevated straylight
(MTF) and Strehl ratios. The MTF value was reduced levels of 19.3 deg2/sr, which would result in difficulties
Fig. 4 Microscopic images of the central part of all tested IOLs. Images were obtained under a microscope in a 90-fold magnification after
standardized accelerated glistening induction
Yildirim et al. BMC Ophthalmology (2020) 20:186 Page 5 of 7
Table 2 Density of glistenings. Comparison of the mean values of the two studied intraocular lens models
central part mean of 5 sections
IOL Eyecryl AcrySof p-value Eyecryl AcrySof p-value
Average MV/mm2 0.7 (±0.5) 41.8 (±27.7) < 0.05* 0.5 (±0.2) 19.9 (±10.6) < 0.05*
(± standard deviation)
IOL intraocular lens, MV/mm2 microvacuoles per square millimetre, *student’s t-test
for patients while driving [9, 14]. Fortunately, in the The Eyecryl lens is manufactured by lathe-cutting the
presented study, mean glistening numbers were lower polymer which is different to the way Acrysof IOL is
in both of the IOL models under test, suggesting im- made, which is cast-moulding manufactured. Possibly
provements in these hydrophobic materials. the Eyecryl lens retains a more homogenous copolymer
In 2013, Thomes and Callaghan reported on the con- distribution within the final IOL whereas the cast-
tinuous improvements (for which they unfortunately do moulding procedure of the Acrysof lens might be re-
not provide details) in manufacturing process of the arranging the polymer distribution. In cast-moulding,
Acrysof copolymer intended to reduce the incidence of care must be taken to avoid the development of inhomo-
glistening formation. They compared AcrySof lenses geneities that can re-distribute co-polymers, chances
manufactured in 2003 with those made in 2012 [1]. The which would make the lens susceptible to further mater-
2012 manufactured AcrySof demonstrated a significant ial changes such as microvacuole formation [15]. In a
reduction in glistening number (39.9 ± 35.0 MV/mm2) comparative clinical study, Nishihara et al. found that
compared to lenses produced in 2003 (315.7 ± 149.4 lathe-cut lenses show better long-term stability (regard-
MV/mm2). Our results showed similar values for Acry- ing surface light-scattering) compared to cast-moulded
sof produced in 2017, with a mean number of central lenses [15].
glistenings of 41.84 (±27.67) MVs/mm2 suggesting a After shaping the lens by lathe-cutting or cast-
maintenance of the improved process that leads to the moulding, a subsequent step in manufacturing usually
reduced glistening formation. includes a polishing process. This stage has been shown
The Eyecryl ASHFY600 IOL is made from a hydro- to be the potential cause of postoperative material
phobic acrylate polymer (Table 1). changes in hydrophilic acrylic lenses from a series of
Fig. 5 Number of glistenings in the central part of all tested IOLs after accelerated glistening induction. The secondary y-axis shows the
relationship to the Miyata grading system. MVs/mm2, microvacuoles per square millimetre
Yildirim et al. BMC Ophthalmology (2020) 20:186 Page 6 of 7
lenses affected by opacification, the residual polishing hydrophobic acrylic intraocular IOL materials: Vivinex
materials, like Aluminium Oxide, might have remained (Hoya, Singapore), Tecnis (Johnson&Johnson, New Jersey,
on the lens surface and provoking the postoperative USA) and RayOne (Rayner, Hove, UK). In our laboratory,
clouding of the lenses [16]. in-vitro accelerated aging studies have confirmed that
Thus, the IOL production process as well as the poly- lenses made of these materials and the Eyecryl ASHFY600
mer are crucial elements in providing a lens with a re- IOL are “glistening-free”. As this study was conducted in
sistance to material changes. Our results suggest that an in-vitro environment, results cannot be transitioned to
lathe-cutting a lens is superior to cast-moulding and we the clinic without restriction. Therefore, long-term clinical
consider the new technologies, such as laser-cutting the studies have to confirm the lower amount of glistenings in
lens, might further improve IOL manufacturing. IOLs made of advanced hydrophobic materials.
Another approach to reduce the tendency for glistening
formation is to improve the polymer by introducing hydro- Conclusion
phobic IOL polymer compositions that have increased The new Eyecryl ASHFY600 IOL has low tendency to-
hygroscopy. Hygroscopy describes a material’s ability to ab- wards glistening formation. With a mean value of 0.52
sorb and hold water inside the material. Water entering the (±0.24) MV/mm2 all over the IOL and 0.74 (±0.54) MV/
material connects with the hydrophilic groups, thus avoid- mm2 in its central part after accelerated aging, the corre-
ing water accumulation in vacuoles or pockets and forming sponding grade on the Miyata Scale was 0 for all tested
glistenings [4]. The more hygroscopic a material is, the lenses. Resistance against glistening formation was su-
higher its equilibrium water content (EWC) under certain perior to the well-established AcrySof IQ SN60WF IOL,
environmental conditions. Apart from the composition of which in comparison showed values of 19.89 (±10.57)
the material, the EWC depends on the concentration of MV/mm2 all over the IOL and 41.84 (±27.67) MV/mm2
salts in its surrounding solution and the environmental in the centre of the lens optic.
temperature. Early hydrophobic materials for IOLs had low
Abbreviations
hygroscopy: the AcrySof material introduced in the 1990s IOL: Intraocular lens; MV: microvacuoles; PMMA: polymethyl methacrylate;
has an EWC as low as 0.1–0.5% [17]. Some of the new MTF: modulation transfer function; EWC: equilibrium water content;
generation hydrophobic materials incorporate a certain HEMA: hydroxyethyl methacrylate; PHS: phenyl ether acrylate, hydroxyethyl
methacrylate, styrene
amount of acrylate with hydrophilic groups, thus leading to
equilibrium water contents around 4 to 5% [4]. Only a few Acknowledgements
companies disclose the exact copolymer composition used We would like to thank Mr. Donald J. Munro for his contribution to this
report. We acknowledge financial support by Deutsche
for their IOLs. One known composition is that of the
Forschungsgemeinschaft within the funding program Open Access
enVista IOL made by Bausch & Lomb (New York, USA). Publishing, by the Baden-Württemberg Ministry of Science, Research and the
Its copolymer consists of 3 different monomers: poly(ethyl- Arts and by Ruprecht-Karls-Universität Heidelberg.
ene glycol) phenyl ether acrylate (40%), 2-hydroxyethyl
Authors’ contributions
methacrylate (HEMA, 30%) and styrene (26%), cross-linked GUA, SKS and PRM were responsible for the conception and design of this
by ethylene glycol dimethacrylate (4%) - collectively called study. HF, QW and PRM acquired the data. TMY, GUA and SKS analysed and
PHS copolymer. Due to the hydrophilic groups of the interpreted the data. TMY drafted the manuscript. GUA, SKS and PRM revised
the manuscript critically for important intellectual content. All authors have
HEMA the material has a higher EWC of about 4% and read and approved the final manuscript and agree to be accountable for all
shows a low tendency towards formation of glistenings [4]. aspects of the work in ensuring that questions related to the accuracy or
Another new generation hydrophobic polymer formulation integrity of any part of the work are appropriately investigated and resolved.
support from Alcon, outside the submitted work. G. Auffarth reports grants, 18. Pagnoulle C, Bozukova D, Gobin L, Bertrand V, Gillet-De Pauw MC.
personal fees and non-financial support from Alcon, Johnson & Johnson Vi- Assessment of new-generation glistening-free hydrophobic acrylic
sion, Oculentis, Hoya, Kowa, Rayner, Sifi, Presbia, Oculus, Ursapharm, Glaukos intraocular lens material. J Cataract Refract Surg. 2012;38(7):1271–7.
and Carl Zeiss Meditec, grants and personal fees from Bausch+Lomb and
Biotech, grants and non-financial support from Santen and Alimera, grants
from Acufocus, Physiol, Anew and Contamac, outside the submitted work. H. Publisher’s Note
Fang, S. Schickhardt, Q. Wang and P. Merz have nothing to disclose. Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
Author details
1
The David J. Apple International Laboratory for Ocular Pathology,
Department of Ophthalmology, University of Heidelberg, Im Neuenheimer
Feld 400, 69120 Heidelberg, Germany. 2Department of Ophthalmology, The
Third Affiliated Hospital of Wenzhou Medical University, 108# Wansong Road,
Rui’an, Zhejiang 325200, China.
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