Change in light scattering caused by glistenings in hydrophobic acrylic intraocular lenses from 10 to 15 years after surgery

ARTICLE

Change in light scattering caused by glistenings in hydrophobic acrylic intraocular lenses from 10 to 15 years after surgery Eva M€ onestam, MD, PhD, Anders Behndig, MD, PhD

PURPOSE: To analyze the long-term change in light scattering caused by glistenings in hydrophobic acrylic intraocular lenses (IOLs) and the clinical implications on high-contrast and low-contrast visual acuity. SETTING: Department of Clinical Sciences/Ophthalmology, Umea˚ University Hospital, Umea˚, Sweden. DESIGN: Prospective longitudinal case series. METHODS: The study comprised patients who had an Acrysof MA60BM IOL implanted between 1997 and 1998. Light scattering from the IOLs was assessed with digital analysis using Scheimpflug photography (Pentacam HR) from both the 10- year and 15-year follow-up. Associations were made between corrected distance visual acuity, low-contrast visual acuity (LCVA) 10.0%, LCVA 2.5%, and the degree of light scattering from the IOL. RESULTS: At the 15-year follow-up, the majority of the 90 patients had an increased amount of light scattering in all parts measured in the IOL than the patients at the 10-year follow-up. A subgroup of 71 patients without coexisting ocular pathology was selected for the visual function analyses. There was no correlation between light scattering and dioptric power. No clinically relevant reduction in visual function was detected in eyes with more pronounced light scattering. Patients with a larger increase in total light scattering of the IOL at the 15-year follow-up had significantly worse LCVA 2.5% than at the 10-year follow-up (P Z .042). CONCLUSIONS: Glistenings continued to increase in hydrophobic acrylic IOLs from 10 to 15 years after surgery. At 15 years, most patients had severe glistenings with a high level of light scattering from the IOL. No clinically significant effect on everyday visual function was found. Financial Disclosure: Neither author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2016; 42:864–869 Q 2016 ASCRS and ESCRS

Refractive microvacuoles or glistenings are found in all intraocular lens (IOL) materials; however, hydrophobic acrylic IOLs, especially the Acrysof MA series (Alcon Laboratories, Inc.) implanted from 1997 to 1999, have been reported to have significant glistenings.1–3 There are 2 types of refractive microvaculoles. One type is subsurface nanoglistenings, which are vacuoles often smaller than 200 mm situated at 120 mm or less from the IOL surface. The other type is glistenings located throughout the thickness of the IOL optic 864

Q 2016 ASCRS and ESCRS Published by Elsevier Inc.

that are bigger microvaculoles (0.5 to 200 mm).3–6 The microvacuoles are visible on slitlamp examination because of the difference in the refractive indices. Several studies7–9 report a continuously increasing incidence and intensity of subsurface nanoglistenings and deeper glistenings after IOL implantation. The glistenings show no tendency to stabilize for at least 10 years after surgery. Because of the progressive nature of the glistenings, follow-up is important to assess patient-perceived http://dx.doi.org/10.1016/j.jcrs.2016.02.047 0886-3350

LIGHT SCATTERING IN HYDROPHOBIC ACRYLIC IOLS

problems with visual function. An IOL could remain in the eye for 40 years or longer, making an extended follow-up essential. If the glistenings are bothersome to the patient, there is no known remedy other than IOL exchange. This study evaluated the change in glistenings in Acrysof hydrophobic acrylic IOLs from 10 to 15 years after surgery and the effect on visual function. Associations were made with corrected distance visual acuity (CDVA) and low-contrast visual acuity (LCVA) 10.0% and LCVA 2.5% and the degree of light scattering from the IOL as measured with digital analysis of Scheimpflug photography. PATIENTS AND METHODS Inclusion and Exclusion Criteria In 1997 and 1998, all patients had standard 3.2 mm incision phacoemulsification surgery with in-the-bag forceps implantation of a foldable IOL (Acrysof MA60BM) at the Eye Clinic, Umeå University Hospital, Sweden. The type of packaging for all IOLs was Wagon Wheel. Informed consent was obtained from all patients. The study followed the tenets of the Declaration of Helsinki and was approved by the local ethics committee. A subgroup of patients was selected for visual function analyses. These patients had a postoperative CDVA of 20/28 or better 15 years after surgery. None had previous ocular surgery or comorbidity that could affect contrast sensitivity, such as age-related maculopathy, glaucoma, diabetic retinopathy, ocular surface pathology, posterior capsule opacity, or optic nerve pathology.

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tested using Sloan letter logarithmic translucent contrast charts (10.0% and 2.5%, Precision Vision) at 4 m with standardized lighting conditions. Participants who could not read the largest letters at 4 m were tested at 1 m and the logMAR value was corrected for the shorter distance. The CDVA, LCVA 10.0%, and LCVA 2.5% were scored as the total number of letters read correctly and transformed to logMAR units. All eyes had a dilated clinical eye examination at the slitlamp. Any past neodymium:YAG (Nd:YAG) laser capsulotomy was recorded. The glistenings were quantified using a method based on Scheimpflug photography (Pentacam HR, Oculus Surgical, Inc.) and subsequent digital image analysis, as previously described.7 The Scheimpflug camera system is a noninvasive device for measuring and characterizing the anterior segment based on Scheimpflug photography. Similar concepts to quantify IOL glistenings have also been suggested by others.10,11 Each eye had the same measurement procedure and was photographed under standardized mesopic light conditions with the Scheimpflug camera, as detailed.7,12 Scans not meeting acceptable criteria (blinks during scan or other artifacts) according to the Scheimpflug camera software were repeated. Data were extracted and analyzed. Briefly, 2 of the Scheimpflug images of the IOL taken at 0 degrees and 90 degrees were analyzed using the ImageJ image analysis program.A The degree of light scattering within the IOL was quantified from the Scheimpflug images at the visual axis and calibrated against the minute, backward light scattering recorded in the aqueous humor anterior to the IOL. The glistenings were analyzed as full thickness of the IOL and as deep glistenings with subtraction of the glistenings in the 73 mm (7 pixels) of the most anterior part of the IOL and the 73 mm of the most posterior part of the IOL.7,13 Figure 1 shows the locations of the measurements.

Examination The CDVA was tested using Early Treatment Diabetic Retinopathy Study (ETDRS) charts at 4 m. Lighting conditions were standardized using an ETDRS chart illuminator cabinet (number 2425, Precision Vision). The LCVA was

Submitted: November 10, 2015. Final revision submitted: February 16, 2016. Accepted: February 16, 2016. From the Department of Clinical Sciences/Ophthalmology, Umea˚ University Hospital, Umea˚, Sweden. Supported by grants from Capio, Medocular AB (2014-2658), and Crown Princess Margareta’s Committee for the Blind, Stockholm, V€asterbotten County Council Research Fund, Umea˚, and the Swedish Government (Agreement concerning Research and Education of Doctors ALF). The sponsor or funding organizations had no role in the design or conduct of this research. Presented in part at the XXXIII Congress of the European Society of Cataract and Refractive Surgeons, Barcelona, Spain, September 2015. Corresponding author: Eva M€onestam, MD, PhD, Department of Clinical Sciences/Ophthalmology, Umea˚ University, SE-901 85 Umea˚, Sweden. E-mail: [email protected].

Statistical Analysis To analyze specific effect on low-contrast acuity, the difference between LCVA 10.0% and CDVA (logMAR) was calculated for each eye. This was performed to control for the small differences in CDVA between the patients. The corresponding subtraction was made between LCVA 2.5% and CDVA. Independent-sample t tests and analysis of variance were used to compare age, sex, CDVA, and LCVA data for 2 and 3 groups (Tables 1 to 3), respectively. Paired-sample t tests were used to compare light scattering of the IOL at 10 years and 15 years. The 2  2 tables were analyzed using chi-square tests or the Fisher exact test. Pearson r correlation statistics were used to analyze the correlation between IOL power and the light scattering measured by the Scheimpflug camera. Statistical analyses were performed using the Statistical Package for the Social Sciences software (version 21.0, SPSS, Inc.). A P value less than 0.05 was considered statistically significant.

RESULTS Demographics Ninety eyes of 90 patients (31 men, 59 women) were included in the current study. Table 1 shows the demographic characteristics of all patients

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LIGHT SCATTERING IN HYDROPHOBIC ACRYLIC IOLS

P Z .94), or previous Nd:YAG capsulotomy (47% versus 34%; P Z .32). Table 2 shows the light scattering at different parts of the IOL measured by the Scheimpflug camera 10 years and 15 years after surgery (N Z 90). Light scattering increased from 10 to 15 years at all levels. Intraocular Lens Power Figure 1. Schematic figure of the areas measured. Deep glistenings were assessed by subtracting the light scattering of the superior 103 mm from each IOL surface (IOL Z intraocular lens).

included in the study. Also shown are the CDVA, LCVA 10.0%, and LCVA 2.5% in the subgroup of 71 patients (79%) without other ocular comorbidities who were selected for visual function analyses. Although the women were significantly older, there were no statistically significant sex-related differences in CDVA or LCVA. No patient had intraoperative or postoperative complications. Change in Light Scattering of the Intraocular Lenses Between 10 Years and 15 Years Seventy-three patients (81%) had increased total light scattering in the IOL at 15 years compared with at 10 years; however, in 17 (19%) of 90 patients, the measurement showed less light scattering (Figure 2). These 17 patients were analyzed separately and compared with those with increased light scattering. There were no significant differences in age (61.7 years versus 63.2 years; P Z .57), sex (35% versus 34% men;

There was no statistically significant correlation between the total light scattering of the IOL at 10 or 15 years and the IOL dioptric power (r Z 0.096, P Z .37 and r Z 0.029, P Z .78, respectively). There was also no significant correlation between the change in total light scattering between 10 years and 15 years and IOL dioptric power (r Z 0.03, P Z .75). Visual Function Relationship to Light Scattering There were no significant correlations between total sum light scattering of the IOL 15 years after surgery and CDVA, LCVA 10.0%, and LCVA 2.5% (P Z .89, P Z .71, and P Z .62, respectively). The associations between the change in light scattering between 10 years and 15 years and the change in CDVA, LCVA 10.0%, and LCVA 2.5% for each patient were also calculated. Patients with a larger increase in total light scattering of the IOL from 10 to 15 years had a significantly worse LCVA 2.5% at 15 years than at 10 years (P Z .042). The corresponding P values for CDVA and LCVA 10.0% were P Z .34 and P Z .33, respectively. To further show the possible effect of glistenings on visual function, the 71 patients without ocular comorbidity were divided into 3 groups depending on the

Table 1. Demographic characteristics of all patients and the subgroup selected for visual function analysis 15 years after cataract surgery. Number (%) Group All patients Age (y) 15 years postop Mean 95% CI Subgroup having visual function analysis Age (y) 15 years postop Mean 95% CI CDVA (logMAR) Mean G SD Snellen Mean LCVA 10.0% (logMAR) Mean LCVA 2.5% (logMAR)

Number

Men

Women

90

31 (34)

59 (66)

77.9 75.9, 79.9 71

74.2 70.4, 77.9 25 (35)

79.8 77.7, 82.0 46 (65)

.006

76.6 74.2, 79.0

73.1 68.6, 77.6

78.6 75.9, 81.2

.025

0.033 G 0.08 20/22 0.28 G 0.11 0.60 G 0.19

0.031 G 0.07 20/21 0.25 G 0.12 0.61 G 0.19

0.036 G 0.08 20/22 0.28 G 0.11 0.60 G 0.19

.77

CDVA Z corrected distance visual acuity; CI Z confidence interval; LCVA Z low-contrast visual acuity *Difference between men and women

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P Value*

.33 .89

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LIGHT SCATTERING IN HYDROPHOBIC ACRYLIC IOLS

Table 2. Mean light scattering at different parts of the IOL measured by the Scheimpflug camera system 10 years and 15 years after cataract surgery. Mean G SD Parameter Anterior deep† Total anterior Posterior deep† Total posterior Total deep† Total sum

10 Years Postop

15 Years Postop

P Value*

20.4 G 8.4 233 G 108 19.4 G 10.4 202 G 146 39.8 G 17.7 435 G 227

26.5 G 6.3 423 G 220 24.6 G 7.7 291 G 204 51.1 G 12.7 715 G 364

.000 .000 .000 .001 .000 .000

*Difference between 10 years and 15 years † Deep glistenings were defined as total glistenings subtracted by the glistenings in the 73 mm (7 pixels) of the most anterior part and most posterior part of the IOL.

degree of total sum light scattering of the IOL as measured by the Scheimpflug camera: group 1 Z 0 to 500 units; group 2 Z 501 to 800 units; and group 3 Z more than 800 units (Table 3). No statistically

significant effect on CDVA or in the difference between LCVA (10.0% and 2.5%) or CDVA was detected between the 3 groups. Also, there was no difference in age, sex, or previous Nd:YAG laser capsulotomy between those with less light scattering and those with more light scattering at 15 years.

DISCUSSION To our knowledge, this prospective case series presents the longest follow-up of postoperative light scattering in Acrysof hydrophobic acrylic IOLs, extending to 15 years for all patients. Light scattering caused by glistenings continues to increase in IOLs from 10 to 15 years after surgery. There was no stabilization at any level of the IOLs compared with the same IOLs 10 years postoperatively. This is in agreement with results in previous studies4,8,12,14 extending up to 10 years or longer. The Acrysof IOL was introduced in 1994 and has been used widely in cataract surgery. It provides good optical quality and was the first to use a foldable material.8 All Acrysof IOLs in the study had Wagon

Table 3. Visual function in relation to total sum light scattering in the IOL 15 years after surgery measured by the Scheimpflug camera system. Parameter Patients (n) Women, n (%) Age at surgery (y) Mean G SD Range Total sum light scattering (units) Mean 95% CI CDVA (logMAR) Mean 95% CI Snellen LCVA 10% (logMAR) Mean 95% CI LCVA 2.5% (logMAR) Mean 95% CI LCVA 10% CDVA (logMAR) Mean difference 95% CI LCVA 2.5% CDVA logMAR Mean difference 95% CI Past Nd:YAG laser capsulotomy, n (%)

Group 1 (0–500 Units)

Group 2 (501–800 Units)

Group 3 (O800 Units)

P Value*

21 15 (71)

28 18 (64)

22 13 (59)

.72

62.4 G 9.8 42, 79

62.2 G 9.7 41, 77

60.2 G 10.4 41, 66

352 301, 403

664 633, 695

1149 980, 1317

.030 0.003, 0.06 20/21

0.025 0.004, 0.05 20/21

0.051 0.01, 0.09 20/22

.50

0.25 0.2, 0.31

0.26 0.22, 0.31

0.31 0.26, 0.36

.23

0.61 0.52, 0.70

0.59 0.52, 0.67

0.62 0.53, 0.70

.87

0.31 0.24, 0.38

0.47 0.27, 0.68

0.27 0.19, 0.34

.11

0.58 0.51, 0.65 7 (33)

0.57 0.51, 0.63 11 (39)

0.57 0.50, 0.64 8 (36)

.97

CDVA Z corrected distance visual acuity; LCVA Z low-contrast visual acuity; Nd:YAG Z neodymium:YAG *Difference between the 3 groups using analysis of variance

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.71

.91

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LIGHT SCATTERING IN HYDROPHOBIC ACRYLIC IOLS

Figure 2. Change in total light scattering in the IOL for each eye from 10 years to 15 years after surgery (N Z 90).

Wheel packaging, which was believed to cause less glistenings than the Acrypac, the first type of packaging. All types of plastic material degrade with time, and progressive degradation of the IOL biomaterial is believed to be involved in the etiology of glistenings.12 In vitro studies have not shown glistenings to have a statistically significant influence on optical quality15,16 or IOL light transmission.17 Among several possible limitations of visual performance in vivo, the most important are light scattering, aberration, and diffraction in the visual system.18,19 Concerns have been raised regarding the effect of glistenings on visual function. Glistenings cause increased light scattering of the IOL, which in particular could affect contrast sensitivity. Many patients have coexisting pathology (eg, macular degeneration, posterior capsule opacification) that also lowers contrast senisitivity.20,21 In these cases, it is difficult to determine whether glistenings, the comorbidity, or both cause the reduced LCVA. In the present study, we selected a subgroup of patients without ocular comorbidity to prevent bias when analyzing CDVA and LCVA and the relative difference between these parameters. Although most patients in our study had pronounced glistenings and significantly increased light scattering 15 years after surgery, we found little

significant effect on visual function, assessed by measuring the CDVA, LCVA 10.0%, and LCVA 2.5%. Patients with a larger increase in total light scattering of the IOL had a significantly worse LCVA 2.5% 15 years postoperatively than 10 years postoperatively. Any effect on CDVA and LCVA 10.0% could not be detected. In absence of other significant differences (Table 3), we do not believe this borderline significance (P Z .042) to be clinically relevant. Our results are in agreement with those in most previous studies.2,13 We did not find a correlation between the amount of light scattering and the IOL dioptric power, which is in agreement with most previous studies.13,14 Limitations of the present study are that neither measurements of forward light scatter nor measurements using glare sources were performed. Glistenings adversely affect visual function by creating forward light scatter, which might cause patients to report phenomena such as hazy vision, loss of contrast, and loss of color. Light scattering had no correlation with CDVA, and the patient might be unhappy despite a CDVA of 20/20. These issues were evaluated in a recent study,22 which found decreased CDVA and contrast visual acuity with glare in patients with a large amount of glistenings. This subject merits further long-term longitudinal studies, perhaps also including the patients' experience. In conclusion, the present longitudinal study shows the progressive nature of the glistenings phenomenon up to at least 15 years. Although most patients in this case series had severe glistenings, the clinical everyday effect on visual function seemed to be low. WHAT WAS KNOWN  The prevalence and intensity of glistenings in hydrophobic acrylic IOLs increase over time up to at least 10 years postoperatively. The effect on visual function has been questioned. WHAT THIS PAPER ADDS  Prospective longitudinal data showed no stabilization at any level of the IOL compared with the same IOL 10 years postoperatively. No negative effect on visual function was detected, although many patients had pronounced glistenings.

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First author: Eva M€ onestam, MD, PhD Department of Clinical Sciences/ Ophthalmology, Umeå University, Umeå, Sweden