Glistenings in a large series of hydrophobic acrylic intraocular lenses

ARTICLE

Glistenings in a large series of hydrophobic acrylic intraocular lenses Joseph Colin, MD, Isabelle Orignac, MD, David Touboul, MD

PURPOSE: To evaluate the incidence and severity of glistenings in hydrophobic acrylic intraocular lenses (IOLs) and assess the potential correlation between glistenings and clinical and demographic factors. SETTING: Service d’Ophtalmologie, Centre Hospitalier et Universitaire Bordeaux, Bordeaux, France. METHODS: Eligible patients received an AcrySof IOL between September 2000 and December 2007 and had a routine ophthalmic visit between January 2007 and March 2008. The incidence and severity of glistenings were graded subjectively and analyzed in relation to patient age and sex, length of follow-up, IOL model, IOL power, neodymium:YAG laser capsulotomy, corrected distance visual acuity (CDVA), spherical equivalent (SE), and selected ocular and systemic diseases and medications. RESULTS: Glistenings occurred in 157 (60.4%) of the 260 eyes; they were absent in 103 eyes (39.6%). Glistenings were of grade 1 severity in 87 eyes (33.5%) and of grade 2 severity in 70 eyes (26.9%). CONCLUSIONS: The results suggest a potential association between the incidence of glistenings and IOL power and glaucoma, but not between glistenings and age, sex, IOL model, length of follow-up, CDVA, SE, or most ocular and systemic diseases and medications. J Cataract Refract Surg 2009; 35:2121–2126 Q 2009 ASCRS and ESCRS

Glistenings are small (1 mm to 5 mm) refractile microvacuoles that are thought to result from the condensation of tiny accumulations of water within the matrix of intraocular lenses (IOLs).1–5 Extensive studies1,6–9 indicate that intralenticular glistenings do not affect visual acuity. Glistenings have been observed in most IOL

Submitted: February 12, 2009. Final revision submitted: June 12, 2009. Accepted: June 16, 2009. From Service d’Ophtalmologie, Hoˆpital Pellegrin, Centre Hospitalier et Universitaire de Bordeaux (Colin, Orignac), and Centre de Re´fe´rence Nationale du Keratcˆone citu de Bordeaux (Touboul), Bordeaux, France. Neither author has a financial or proprietary interest in any material or method mentioned. Presented in part at the XXVI Congress of the European Society of Cataract & Refractive Surgeons, Berlin, Germany, September 2008. Supported by Alcon, Inc., Fort Worth, Texas, USA. Corresponding author: Joseph Colin, MD, Service d’Ophtalmologie, Hoˆpital Pellegrin, CHU de Bordeaux, Place Ame´lie Raba Le´on, 33 000 Bordeaux, France. E-mail: [email protected]. Q 2009 ASCRS and ESCRS Published by Elsevier Inc.

materials, including poly(methyl methacrylate) (PMMA), silicone, and hydrophilic and hydrophobic acrylic.8,10,11 The AcrySof IOL (Alcon, Inc.) was approved by the U.S. Food and Drug Administration in 1994 and has become the most frequently implanted acrylic IOL. Constructed from a hydrophobic acrylic copolymer of 2-phenylethyl acrylate and 2-phenylethyl methacrylate, the IOL’s high refractive index and slow, controlled unfolding offer advantages over other foldable IOLs.12 Although glistenings in the material of this IOL were first described in 1996,1 their significance has not been fully elucidated. The current study was performed to evaluate the relationship between glistenings in AcrySof IOLs and several clinical and demographic factors to facilitate the development of future studies. PATIENTS AND METHODS This retrospective study comprised eligible patients who had implantation of an AcrySof IOL (model SN60AT, SN60WF, SA60AT, or MA) between September 2000 and December 2007 and had a routine ophthalmic visit between January 2007 and March 2008. The same surgeon (J.C.) performed all surgeries using the same technique 0886-3350/09/$dsee front matter doi:10.1016/j.jcrs.2009.06.029

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Figure 1. Examples of glistening grading. A: Grade 0 (absent). B: Grade 1. C: Grade 2.

that included a 5.0 to 6.0 mm continuous tear capsulorhexis followed by phacoemulsification and IOL implantation in the capsular bag using a Monarch II IOL delivery system (Alcon, Inc.). The surgeon evaluated the incidence and severity of glistenings by examining patients with a slitlamp beam set at 10.0 mm  2.0 mm with an angle of 30 degrees. The pupil was dilated to allow evaluation of the complete IOL optic. Glistenings seen in the slitlamp beam were subjectively graded as 0 (absent), 1, or 2. Figure 1 shows examples of slitlamp grading of glistenings. The frequency and severity of glistenings were evaluated in relation to the following parameters: patient age and sex, length of follow-up, IOL model and power, need for neodymium:YAG (Nd:YAG) laser capsulotomy, corrected distance visual acuity (CDVA), spherical equivalent (SE), selected ocular and systemic medications, and selected ocular and systemic diseases. Because the duration of postoperative follow-up was different for each IOL model, eyes were divided into those that had fewer than 24 months of follow-up and those with 24 months or more of follow-up. The severity of glistenings in each model was compared and stratified by follow-up duration and IOL power. In addition, to determine whether the presence of a yellow chromophore for blue-light filtering in the IOL material had an effect on the occurrence of glistenings, a direct comparison of the incidence and severity of glistenings between the SA60AT and SN60AT models was performed. Both are 1-piece IOLs of almost identical size and construction with the exception of a blue light–filtering chromophore in the SN60AT model. Statistical analysis was performed using SAS software (version 9.1.3, SAS Institute, Inc.). The correlation between

the frequency of glistenings and qualitative variables was assessed by the chi-square test. For quantitative variables (eg, age, IOL power, SE), analysis of covariance was used for normal data and the Kruskal-Wallis test for nonnormal data. The Cochran-Mantel Haenszel test was used for analysis of multiple variables. A P value less than 0.05 was considered statistically significant.

RESULTS Patient Characteristics The study population comprised 260 eyes of 166 patients (65.1% women), 94 of whom had bilateral IOL implantation. Of the remaining 72 patients, 34 had IOL implantation in the right eye only. Table 1 shows the patients’ characteristics. An AcrySof model SN60AT IOL was implanted in 110 eyes (42.3%), a model SN60WF in 88 eyes (33.8%), a model SA60AT in 37 eyes (14.2%), and a model MA in 25 eyes (9.6%). The most frequently observed ocular disorders were retinal disease and glaucoma, which were observed in 70 eyes (27.0%) and 57 eyes (21.9%), respectively (Table 2). All other ocular diseases evaluated in the study were observed in fewer than 10% of eyes. Forty-three patients (25.9%) were taking ocular medication. The most frequently observed systemic diseases were hypertension and hypercholesterolemia, which were observed in 75 patients (28.8%) and 29

Table 1. Patient characteristics. Parameter

Mean G SD

Median

Min

Max

Age (y) Follow-up (mo) IOL power (D) CDVA (logMAR) SE (D)

70.53 G 9.99 32.74 G 17.20 18.30 G 6.98 0.29 G 0.51 0.36 G 0.99

71.00 32.50 20.00 0.18 0.12

32.00 0.00 5.00 0.00 6.75

87.00 86.00 C31.00 3.00 C2.00

CDVA Z corrected distance visual acuity; IOL Z intraocular lens; Max Z maximum; Min Z minimum; SE Z spherical equivalent

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the SA60AT and SN60WF models than in the other 2 models. No statistically significant differences were observed in the incidence and severity of glistenings and the following parameters: age (P Z .5774), sex (P Z .4408), length of follow-up (P!.0728), Nd:YAG laser treatment (P Z .4327), CDVA (P Z .7623), or SE (P Z .8754). In addition, there was no statistical association between intraoperative medication use and the incidence and severity of glistenings.

Table 2. Glistening severity by ocular and systemic disease. Glistening Severity (%) Grade Grade Grade P 0 1 2 Value*

Disease Ocular Retinal disease (n Z 70) Glaucoma (n Z 57) Additional surgery (n Z 19) Corneal disease (n Z 18) Uveitis (n Z 5) Systemic Hypertension (n Z 75) Depression (n Z 11) Hypercholesterolemia (n Z 29) Thyroid (n Z 28) Cardiopathy (n Z 25) Diabetes (n Z 24) Vasculopathy (n Z 14) Rheumatism (n Z 12) Inflammatory disease (n Z 10) Hyperuricemia (n Z 7)

37.1 19.3 21.1 38.9 40.0

31.4 31.6 36.8 38.9 2.0

31.4 49.1 42.1 22.2 4.0

.5698 .0001 .1647 .8364 .741

44.0 9.09 31.0 39.3 32.0 29.2 57.1 25.0 20.0 28.6

32.0 27.3 37.9 42.9 32.0 37.5 21.4 5.0 5.0 71.4

24.0 63.64 31.0 17.9 36.0 33.3 21.4 25.0 3.0 .0

.6334 .0137 .6046 .4093 .5302 .5323 .3765 .4223 .3874 .0722

Follow-up Duration Table 3 shows the incidence and severity of glistenings by follow-up duration; the follow-up was fewer than 24 months in 99 eyes and more than 24 months in 161 eyes. Comparison of the severity of glistenings stratified by duration of follow-up showed no statistically significant difference between IOL models (P Z .1098, Cochran-Mantel Haenszel test). Effect of Blue-Light Filtering

*Correlation between glistenings and ocular and systemic diseases (chi-square test); P!.05 statistically significant

patients (11.2%), respectively. One hundred thirty-five patients (81.3%) were taking systemic medication. No correlation between glistenings and any systemic medication was found. Glistenings Incidence by Patient Characteristics There were no glistenings in 103 IOLs (39.6%). Glistening severity was grade 1 in 87 eyes (33.5%) and grade 2 in 70 eyes (26.9%). Glistenings were observed in all IOL models evaluated. The number (frequency) of glistenings was 19 (51.4%) in the SA60AT model, 45 (55.7%) in the SN60WF model, 16 (64.0%) in the MA model, and 73 (66.4%) in the SN60AT model. There was a statistically significant relationship between the severity of glistenings and the IOL model (P!.0148), with fewer glistenings in

Of the 37 IOLs with no yellow chromophore, 18 (48.6%) had no glistenings and 10 (27.0%) had grade 2 glistenings. Of the 110 blue light–filtering IOLs, 37 (33.6%) had no glistenings and 41 (37.3%) had grade 2 glistenings. There was no statistically significant difference in the frequency of glistenings between the 2 IOL models (P Z .25); thus, the blue light–filtering chromophore did not seem to affect the incidence or severity of glistenings. Intraocular Lens Power Table 4 shows the incidence and severity of glistenings by IOL power; the power was less than C20.0 diopters (D) in 118 eyes and C20.0 D or more in 142 eyes. In the low power group, 57 IOLs (48.3%) had no glistenings, 38 (32.2%) had grade 1 glistenings, and 23 (19.5%) had grade 2 glistenings. In the higher power group, 46 IOLs (32.4%) had no glistenings, 49 (34.5%) had grade 1 glistenings, and 47 (33.1%) had grade 2

Table 3. Glistenings by duration of follow-up. Eyes, n (%) Follow-up %24 Months

Follow-up O24 Months

IOL Model

Grade 0

Grade 1

Grade 2

Grade 0

Grade 1

Grade 2

MA SN60AT SN60WF SA60AT

1 (14.3) 5 (35.7) 34 (43.6) d

5 (71.4) 3 (21.4) 32 (41.0) d

1 (14.3) 6 (42.9) 12 (15.4) d

8 (44.4) 32 (33.3) 5 (50.0) 18 (48.6)

8 (44.4) 29 (30.2) 1 (10.0) 9 (24.3)

2 (11.1) 35 (36.5) 4 (40.0) 10 (27.0)

IOL Z intraocular lens

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Table 4. Glistening grade by IOL power. Eyes, n (%) IOL Power !20.0 D

IOL Power R20.0 D

IOL Model

Grade 0

Grade 1

Grade 2

Grade 0

Grade 1

Grade 2

MA SN60AT SN60WF SA60AT

4 (21.0) 22 (45.8) 23 (56.1) 8 (80.0)

12 (63.2) 14 (29.2) 12 (29.3) 0

3 (15.8) 12 (25.0) 6 (14.6) 2 (20.0)

5 (83.3) 15 (24.2) 16 (34.0) 10 (37.0)

1 (16.7) 18 (29.0) 21 (44.7) 9 (33.3)

0 29 (46.8) 10 (21.3) 8 (29.6)

IOL Z intraocular lens

glistenings. Comparison of the severity of glistenings stratified by IOL power showed no statistically significant difference between IOL models (P Z .0474, Cochran-Mantel Haenszel test). Ocular and Systemic Diseases There was a statistically significant association between the incidence and severity of glistenings and glaucoma (P!.0001) (Table 2). Glistenings were observed in more than 80.0% of IOLs in the 57 eyes with glaucoma and were of grade 2 severity in 49.1% of those eyes. DISCUSSION Glistenings are the result of water absorption and subsequent phase separation within the IOL matrix and are clinically observed in almost all types of IOL material, including hydrophobic and hydrophilic acrylics, silicone, and PMMA.8,10,11 The results in this large retrospective study indicate that glistenings were present in approximately 60% of the hydrophobic acrylic IOLs examined. The glistenings, however, did not reduce visual acuity, a finding that agrees with those in previous studies.1,6–9 The ability to compare the glistening severity grades in our study with findings in similar studies is limited because grading scales vary. Studies include 3 to 5 categories for grading glistenings (eg, trace, C1, C2, C3, and C4).1,7–9 However, our findings were generally consistent with the results in a previous study10 in which the frequency of glistenings ranged from 40.0% to 67.5% in 7 types of hydrophilic and hydrophobic acrylic and silicone foldable IOLs, with the highest incidence in AcrySof IOLs. Glistenings are visible because of differences between the refractive index of water (1.33) and that of the IOL material. The larger the difference between the refractive indices, the more apparent the glistening. Glistenings may therefore be more noticeable in AcrySof IOLs because they have a higher refractive

index (1.55) than IOLs of other materials; the refractive index of silicone is 1.43 to 1.46; of PMMA, 1.49; and of hydrophobic acrylic material (ie, Sensar IOL, Abbot Medical Optics), 1.47. Statistical analysis in the current study found no relationship between the incidence and severity of glistenings in the hydrophobic acrylic IOLs and patient age and sex, length of follow-up, CDVA, selected ocular and systemic medications, and most ocular and systemic diseases. Furthermore, no relationship between SE and glistenings was established. Because patients do not observe glistenings and the glistenings do not interfere with IOL performance, glistenings could be considered largely cosmetic in nature. Intraocular lens explantation because of glistenings is rare. Although Werner et al.13 report 1 case of glistening-associated IOL explantation, they describe an unusual pattern of glistenings. Furthermore, although the patient’s CDVA was reduced, no improvement was observed after the IOL was explanted and replaced with a silicone IOL. Results in the current study do not suggest an increase in the incidence and severity of glistenings over time. Previous studies examined the incidence and severity of glistenings over time with varied results. In a prospective study, Miyata and Yaguchi5 evaluated 41 eyes with AcrySof IOL models MA60BM and MA30BA. Glistenings were apparent on average 6.6 months postoperatively and remained stable in 13 eyes followed for more than 6 months. Similarly, in an in vitro evaluation, Shiba et al.14 showed that glistenings appeared within the first month and remained stable during the 6 months of observation. A study by Christiansen et al.7 showed no significant increase in the rate and severity of glistenings over time in 42 AcrySof IOLs. Tognetto et al.10 prospectively evaluated glistenings in 273 patients with 1 of 7 types of silicone, hydrophobic, or hydrophilic acrylic IOLs. Although the frequency and severity of glistenings increased with time, postoperative follow-up was fewer than 2 years. Additional studies

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may be required to fully reconcile these disparate results. In our series, there was a statistically significant relationship between the severity of glistenings and the IOL model, with fewer glistenings in the SA60AT and SN60WF models. However, this evaluation did not account for duration of postoperative follow-up, which varied by IOL model. Consistent with the nature of clinical practice over time, patients who had the longest duration of follow-up were those with 3-piece IOLs (model MA), followed by those with the SA60AT and SN60AT models. The SN60WF model, which was introduced into our practice in 2005, had the shortest mean follow-up time. Glistenings are not typically seen in AcrySof IOLs before 6 months postoperatively.10 When the severity of glistenings in each IOL model was stratified by the length of follow-up, no statistically significant difference was observed, indicating that there was no relationship between glistenings and IOL model. The results in our study suggest a potential association between the severity of glistenings and IOL power, with fewer glistenings in IOLs of C20.0 D or less. This result is consistent with findings in previous reports 9 and may be because IOLs with a high dioptric power are typically thicker than equivalent IOLs with a low dioptric power. Thus, glistenings may be more likely to accumulate in the thicker IOL matrix material in higher power IOLs. Our results also suggest a potential association between the frequency of glistenings and the incidence of glaucoma. The literature does not indicate a definitive association between glistenings and glaucoma. It has also been hypothesized that the active ingredients or preservatives in antiglaucoma medications may lead to rupture of the blood–aqueous barrier, thereby modifying the composition of the aqueous humor and increasing glistenings.15–21 It is also possible that the constituents of eyedrops have a direct effect on IOL material and induce glistenings. In our series, the reason for the higher frequency of glistenings in patients with glaucoma is unknown but could be associated with the pathology of glaucoma itself or with chronic topical medications used to lower intraocular pressure. In this study, 97% of patients with glaucoma used antiglaucoma medications. The association of glistening frequency and the incidence of glaucoma will be explored in a future study. In summary, this retrospective evaluation of a series of 260 AcrySof IOLs found glistenings in approximately 60% of the IOLs. Although an association between the incidence of glistenings and IOL power and glaucoma was suggested, the glistenings did not appear to reduce visual acuity or increase

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over time and were not associated with other clinical and demographic factors. Complete interpretation of the results in the current study is limited by its retrospective nature and the subjective method used to grade glistenings; however, these data have helped focus the objectives and design of a large ongoing prospective study of glistenings in hydrophobic acrylic IOLs.

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archopht.ama-assn.org/cgi/reprint/105/10/1360. Accessed August 19, 2009 16. Miyake K, Ota I, Maekubo K, Ichihashi S, Miyake S. Latanoprost accelerates disruption of the blood-aqueous barrier and the incidence of angiographic cystoid macular edema in early postoperative pseudophakias. Arch Ophthalmol 1999; 117:34–40. Available at: http://archopht.ama-assn.org/cgi/reprint/117/1/34. Accessed August 22, 2009 17. Miyake K, Ibaraki N. Prostaglandins and cystoid macular edema. Surv Ophthalmol 2002; 47(suppl 1):S203–S218 18. Miyake K, Ota I, Ibaraki N, Akura J, Ichihashi S, Shibuya Y, Maekubo K, Miyake S. Enhanced disruption of the blood-aqueous barrier and the incidence of angiographic cystoid macular edema by topical timolol and its preservative in early postoperative pseudophakia. Arch Ophthalmol 2001; 119:387–394.

Available at: http://archopht.ama-assn.org/cgi/reprint/119/3/ 387. Accessed August 22, 2009 19. Mabuchi F, Yoshimura K, Kashiwagi K, Shioe K, Yamagata Z, Kanba S, Iijima H, Tsukahara S. High prevalence of anxiety and depression in patients with primary open-angle glaucoma. J Glaucoma 2008; 17:552–557 20. Skalicky S, Goldberg I. Depression and quality of life in patients with glaucoma: a cross-sectional analysis using the Geriatric Depression Scale-15, assessment of function related to vision, and the Glaucoma Quality of Life-15. J Glaucoma 2008; 17:546–551 21. Patten SB, Williams JV, Lavorato DH, Modgill G, Jette´ N, Eliasziw M. Major depression as a risk factor for chronic disease incidence: longitudinal analyses in a general population cohort. Gen Hosp Psychiatry 2008; 30:407–413

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