Risk of Age-Related Macular Degeneration 3 Years After Cataract Surgery: Paired Eye Comparisons

Risk of Age-related Macular Degeneration 3 Years after Cataract Surgery: Paired Eye Comparisons

Jie Jin Wang, MMed, PhD,1,2 Calvin Sze-un Fong, MBBS,1 Elena Rochtchina, MApplStat,1 Sudha Cugati, MBBS, PhD,1 Tania de Loryn, MA, DipClinPsych,1 Shweta Kaushik, BMed (Hons), PhD,1 Jennifer S. L. Tan, MBBS, PhD,1 Jennifer Arnold, MBBS, FRANZCO,3 Wayne Smith, MBBS, PhD,4 Paul Mitchell, MD, PhD, FRANZCO1

Objective: To clarify possible associations between cataract surgery and progression of age-related macular degeneration (AMD). Design: Clinic-based cohort. Participants: We followed cataract surgical patients aged 65ϩ years in the Australian Cataract Surgery and Age-related Macular Degeneration (CSAMD) study. Patients who remained unilaterally phakic for at least 24 months after recruitment were included. Methods: We performed annual examinations with retinal photography. We assessed AMD using side-by- side grading of images from all visits. Paired comparisons between operated and nonoperated fellow eyes (defined as nonoperated or operated Ͻ12 months previously) were made using generalized estimating equation models. Main Outcome Measures: Incident early AMD was defined as the new appearance of soft indistinct/ reticular drusen or coexisting retinal pigmentary abnormality and soft distinct drusen in eyes at risk of early AMD. Incident late AMD was defined as the new appearance of neovascular AMD or geographic atrophy (GA) in eyes at risk of late AMD. Results: Among 2029 recruited, eligible participants, 1851 had cataract surgery performed at Westmead Hospital, Sydney, and 1244 (70.7%) had 36-month postoperative visits. Of these participants, 1178 had gradable photographs at baseline and at least 1 follow-up visit. Of 308 unilaterally operated participants at risk of late AMD, this developed in 4 (1.3%) operated and 7 (2.3%) nonoperated fellow eyes (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.23–2.36) after adjusting for the presence of early AMD at baseline. Of 217 unilaterally operated participants at risk of early AMD, this developed in 23 (10.6%) operated and 21 (9.7%) nonoperated fellow eyes (OR, 1.07; 95% CI, 0.74–1.65). Incident retinal pigment abnormalities were more frequent in operated than nonoperated fellow eyes (15.3% vs. 9.9%; OR, 1.64; 95% CI, 1.07–2.52). There was no difference in the 3-year incidence of large soft indistinct or reticular drusen between the 2 eyes (8.8% vs. 7.9%; OR, 1.12; 95% CI, 0.79–1.60). Conclusions: Prospective follow-up data and paired eye comparisons of this older surgical cohort showed no increased risk of developing late AMD, early AMD, or soft/reticular drusen over 3 years. There was a 60% increased detection of retinal pigmentary changes in surgical eyes. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;119:2298–2303 © 2012 by the American Academy of Ophthalmology.

Age-related cataract is a major cause of visual impairment We hypothesize that the discrepancy in ﬁndings of a in elderly Americans and Australians.1–4 Cataract surgery is cataract surgery–AMD link between population- and clinic- currently the most frequently performed ocular surgical pro- based studies is likely due to different distributions of AMD cedure. However, a potential for cataract surgery to increase risk factors between the 2 types of samples.19 Population- the risk of progression to late-stage age-related macular degen- based studies generally have used healthy older persons as eration (AMD) has led to concern.5,6 Discrepancy in the cur- controls, whereas clinic-based patient samples have used rently available evidence for this risk seems divided by the cataract surgical patients who did not develop late AMD as nature of the study samples: Population-based studies have controls. Further, cataract surgery or the postsurgical ocular mostly supported an association between postcataract surgical state may not in itself lead to a higher risk of AMD pro- status and late AMD over the longer term,6–12 whereas clinic- gression but could do so if other contributory factors are based studies have mostly reported a negative ﬁnding of the present. Compared with generally healthy, community-living association,13–17 although inconsistently.18 older persons, clinic patients may be more likely to have

2298 © 2012 by the American Academy of Ophthalmology ISSN 0161-6420/12/$–see front matter Published by Elsevier Inc. http://dx.doi.org/10.1016/j.ophtha.2012.07.003 Wang et al ⅐ AMD 3 Years after Cataract Surgery coexisting systemic and ocular pathologies, which may jointly The incidence of late and early AMD was assessed in both with cataract surgery or postsurgical factors contribute to the operated (the study eye) and nonoperated or only recently operated greater observed risk of progression to late AMD. For these (Ͻ12 months) eyes (the control eye) of participants using side-by- reasons, an ideal study design to address the question about the side grading of the retinal photographs taken at baseline and at role of cataract surgery in AMD progression is to take advan- each of the annual follow-up visits, up to 36 months after surgery. Incident late AMD was defined as the presence of neovascular tage of the 2 eyes per patient and conduct a paired comparison 19 AMD or GA in follow-up visits of eyes having no late AMD between surgical and nonsurgical eyes of the same patients. lesions at baseline. Incident early AMD was similarly defined as The current report aimed to assess whether a link exists the presence of large soft indistinct or reticular drusen, or the between postcataract surgical status and AMD progression co-presence of both large soft distinct drusen and retinal pigmen- in a clinic-based older cohort of cataract surgical patients, tary abnormalities in follow-up visits of eyes having no late or the Australian Cataract Surgery and Age-related Macular early AMD signs at baseline. Eyes with only large soft distinct Degeneration (CSAMD) study,20 using paired eye compar- drusen or retinal pigmentary abnormalities at baseline, but not both isons among patients who retained a unilateral operated lesions, that developed complementary lesions, together comprising a diagnosis of early AMD, were included as incident early state for 24 to 36 months after their first eye had cataract 23 surgery. AMD. SAS (v. 9.1, SAS Inc, Cary, NC) was used for data analyses, including descriptive and analytic analyses. The risk of developing early or late AMD in operated compared with nonoperated fellow eyes of the same patients was assessed in those who remained Materials and Methods unilaterally phakic for at least 24 months, using generalized estimating equation models and adjusting for the presence of preex- The CSAMD study is a longitudinal follow-up of patients aged 65 isting early AMD lesions. years of age or older who underwent cataract surgery at Westmead We also analyzed data from participants who were followed for Hospital or private ophthalmic facilities in the Western Sydney at least 36 months since cataract surgery in their study eyes to region. Participants were noninstitutionalized residents of the assess AMD incidence in eyes with a pseudophakic state for Ն24 Western Sydney region, Australia. The study was approved by the months compared with nonoperated or only recently operated University of Sydney and Western Sydney Area Health Service (Ͻ12 months) eyes (nonpaired eye comparison). Supplementary Human Research Ethics Committees and was conducted adhering analyses were performed comparing all operated eyes (regardless to the tenets of the Declaration of Helsinki. Study methods and of the duration of operations in the eyes) with nonoperated eyes at procedures have been described.20 the 36-month visits. Odds ratios (ORs) and 95% confidence inter- In brief, 2029 patients aged 65 years of age or older were vals (CIs) are presented. recruited from mid-2004 to early 2007. Patients were recruited during informed consent and scheduling for cataract surgery, after obtaining written, informed consent to participate in the CSAMD study. Westmead Hospital is the largest public hospital in Western Sydney, with a large ophthalmic department comprising 20 con- Results sultants. All eligible cataract surgical patients (aged 65 years of age or older, without late AMD in the surgical eye) were invited to Approximately 80% of age-eligible patients undergoing cataract participate. Consenting participants were interviewed and exam- surgery at the Eye Clinic, Westmead Hospital, agreed to partici- ined in a standardized manner at the time of recruitment (baseline), pate in the CSAMD study. Of the 2029 participants recruited, either before cataract surgery (76.8%) or within the first month 69.6% were Caucasian, 11.0% were Asian, 11.0% were Middle after surgery (23.2%). Eastern, and 8.4% were of other ethnicities or mixed race. The Demographic data were obtained during face-to-face inter- mean age of this sample was 75.2Ϯ6.1 years, and there were more views, and systemic and ocular conditions were recorded. Ques- women (57.6%) than men (42.4%, P Ͻ 0.0001). Past smokers and tions asked about medical history included history of diabetes, current smokers comprised 37.1% and 14.2% of the sample, re- hypertension, angina, hypercholesterolemia, myocardial infarct, spectively, whereas overweight and obese participants comprised stroke, transient ischemic attack, arthritis, and surgical procedures. 35.4% and 25.5% of the sample, respectively. Systemic comor- Medical history and medications used were validated against pa- bidities were present in 81.4% of the sample. Hypertension was the tient records. most frequent systemic comorbidity (61%), followed by hypercho- At examinations, height and weight were recorded, and body lesterolemia (45.2%) and diabetes (29.3%) (Table 1). mass index (BMI) was calculated as weight (kilograms)/height Of the 2029 participants, retinal photographs were gradable for (meters squared), with overweight defined as BMI Ն25 kg/m2 and 1499 at the preoperative visit and for 1688 at the 1-month post- obesity defined as BMI Ն30 kg/m2. Visual acuity of each eye was operative visit (most patients had photographs at both visits). assessed at each visit following the study protocol.20 Ocular conditions detected from photographs taken at either or Baseline retinal photographs taken before surgery or within the both of these 2 baseline visits were considered to represent pre- first postoperative month were graded for AMD lesions, closely existing lesions before surgery (baseline). Overall, 1954 partici- following the Wisconsin Age-Related Maculopathy Grading Sys- pants (96.3%) had retinal photographs taken and 1760 participants tem,21 modified for use in the Blue Mountains Eye Study (86.7%) had gradable photographs from at least 1 of these 2 (BMES).22,23 Late AMD was defined as neovascular AMD or baseline visits. Late AMD was present in 2.0% (0.9% neovascular geographic atrophy (GA) of at least 175 ␮m diameter present AMD and 1.1% GA) of the study eyes. The proportion of study within the macular area, as described by the International Age- eyes with early AMD lesions at baseline was 15.3% (Table 1). Related Maculopathy classification.24 Early AMD was defined as Preoperatively, the average mean number of letters read correctly the presence of indistinct large (Ն125 ␮m diameter) soft or retic- in the study eyes was 25.2 (standard deviation, 17.5) letters for ular drusen, or coexisting large soft distinct drusen and retinal presenting visual acuity and 32.3 (standard deviation, 19.2) letters pigmentary abnormalities. for pinhole visual acuity.

2299 Ophthalmology Volume 119, Number 11, November 2012

Table 1. Prevalence of Systemic and Ocular Comorbidities in 95% CI, 0.23–2.36) after adjusting for the presence of early AMD at the Cataract Surgery and Age-related Macular Degeneration baseline. Of 217 unilateral cataract surgical patients at risk of early Study Sample (65 Years of Age or Older) at Baseline AMD, this developed in 23 (10.6%) surgical and 21 (9.7%) nonsurgical fellow eyes (OR, 1.07; 95% CI, 0.74–1.65). The incidence of % with Comorbidity retinal pigment abnormalities was more frequent in operated than in –surgical eyes) nonoperated fellow eyes (15.3% vs. 9.9%; OR, 1.64; 95% CI, 1.07 1760؍Systemic Comorbidity (N Hypertension 60.6 2.52). There was no difference in the incidence of large soft indistinct Hypercholesterolemia 45.2 or reticular drusen between the 2 eyes over the 3-year period (8.8% vs. Diabetes 29.3 7.9%; OR, 1.12; 95% CI, 0.79–1.60) (Table 2). Angina 14.2 Myocardial infarction 14.6 Stroke 12.9 Nonpaired Comparison of All Operated versus Any systemic comorbidities 81.4 Nonoperated Eyes % with lesions By the time the 36-month visits were scheduled, 336 subjects had (surgical eyes) undergone unilateral cataract surgery and 842 subjects (71.5% 1760؍AMD lesions (N Any AMD 17.3 had undergone bilateral cataract surgery. Of the 842 subjects Late AMD 2.0 undergoing bilateral operations, 282 already had surgery on 1 eye Early AMD 15.3 before being recruited into the study and 560 had no cataract Retinal pigmentary abnormalities 18.9 surgery in either eye at the time of study recruitment. Of these 560 Soft indistinct drusen 12.6 subjects (1120 eyes), 491 (982 eyes) had undergone operation Ͼ12 Soft distinct drusen 9.9 months previously, and all these eyes were included in this comparison as operated eyes. The remaining 69 subjects had 1 eye Ͼ Ͻ ϭ operated 12 months previously and the second eye operated 12 AMD age-related macular degeneration. months previously by the time the 3-year follow-up visit was conducted. There were thus 1951 (336ϩ282ϫ2ϩ982ϩ69) operated eyes and 405 (336ϩ69) eyes that had not yet had surgery or Paired Comparison of Operated versus had surgery Ͻ12 months previously. After excluding eyes that did Nonoperated Eyes not have gradable retinal photographs at both the baseline and at least 1 follow-up visit, or that had late AMD present at baseline Of the 1760 participants with gradable photographs at baseline (i.e., not at risk of late AMD), there were 1711 operated eyes that who were followed annually, 1244 (70.7%) had 36-month post- had surgery Ͼ12 months previously and 348 eyes that had not yet operative visits. Of these subjects, 1178 had gradable photographs had surgery or had surgery Ͻ12 months previously for the non- from at least 1 follow-up visit. There were 308 participants at risk paired eye comparison. of late AMD and 217 participants at risk of early AMD who After adjusting for age, sex, smoking, and preexisting early remained unilaterally phakic for at least 24 months. Of the 308 AMD lesions before surgery, cataract surgery was not signiﬁcantly unilateral surgical patients at risk of late AMD, this developed in 4 associated with the incidence of early AMD (OR, 0.99; 95% CI, (1.3%) operated and 7 (2.3%) nonoperated fellow eyes (OR, 0.74; 0.66–1.49) (Table 2). However, older age (per year increase; OR,

Table 2. Incidence of Early- and Late-Stage Age-related Macular Degeneration 3 Years after Cataract Surgery: Paired Eye and Nonpaired Eye Comparisons of Operated Eyes (Ͼ12 Months Previously) with Nonoperated or Recently Operated Eyes (Ͻ12 Months Previously),* the Cataract Surgery and Age-related Macular Degeneration Study

No. at Risk OR Incidence Subjects, n Incidence in Operated Eyes, % Incidence in Nonoperated Eyes, % (95% CIs) Paired eye comparison Late-stage AMD 308 1.3 2.3 0.74 (0.23–2.36)† Early-stage AMD 217 10.6 9.7 1.07 (0.74–1.65) Soft indistinct/reticular drusen 227 8.8 7.9 1.12 (0.79–1.60) Retinal pigmentary 223 15.3 9.9 1.64 (1.07–2.52) abnormalities Nonpaired eye comparison Operated/nonoperated eyes,* n Late-stage AMD 1711/348 1.7 2.6 0.66 (0.29–1.50)‡ Early-stage AMD 1366/282 10.1 10.6 0.99 (0.66–1.49)‡ Soft indistinct/reticular drusen 1408/288 7.4 8.3 0.94 (0.65–1.35)§ Retinal pigmentary 1400/283 15.1 11.3 1.46 (1.00–2.14)§ abnormalities

AMD ϭ age-related macular degeneration; CI ϭ confidence interval; OR ϭ odds ratio. *Operated eyes are defined as those that had surgery Ͼ12 months previously, and nonoperated eyes are defined as those that had not yet had surgery or had surgery Ͻ12 months previously by the time of the 36-month postoperative visits. †Adjusted for early AMD lesions at baseline because the stage of early AMD lesions can be different between the 2 eyes. ‡Adjusted for age, sex, smoking, and early AMD lesions at baseline. §Adjusted for age, sex, and smoking.

2300 Wang et al ⅐ AMD 3 Years after Cataract Surgery

Table 3. Incidence of Early- and Late-Stage Age-related Macular Degeneration 3 Years after Cataract Surgery: Paired Eye and Nonpaired Eye Comparisons of Operated and Nonoperated Eyes* by the Time of 36-Month Postoperative Visits, the Cataract Surgery and Age-related Macular Degeneration Study

No. at Risk OR Incidence Subjects, n Incidence in Operated Eyes, % Incidence in Nonoperated Eyes, % (95% CIs) Paired eye comparison Late-stage AMD 252 0.8 2.4 0.33 (0.08–1.33)† Early-stage AMD 175 9.7 8.0 1.24 (0.75–2.04) Soft indistinct/reticular drusen 183 7.7 6.6 1.18 (0.75–1.87) Retinal pigmentary 183 13.1 9.3 1.47 (0.88–2.48) abnormalities Nonpaired eye comparison Operated/nonoperated eyes,* n Late-stage AMD 1769/284 1.7 2.5 0.73 (0.29–1.83)‡ Early-stage AMD 1411/234 10.2 10.3 1.07 (0.68–1.68)‡ Soft indistinct/reticular drusen 1453/240 7.9 7.5 0.98 (0.65–1.47)§ Retinal pigmentary 1448/230 14.9 11.7 1.30 (0.86–2.14)§ abnormalities

AMD ϭ age-related macular degeneration; CI ϭ confidence interval; OR ϭ odds ratio. *Operated eyes are defined as those that had surgery, and nonoperated eyes are defined as those that had not had surgery by the time of the 36-month visits. †Unadjusted; unable to adjust for early AMD lesions at baseline because of small numbers. ‡Adjusted for age, sex, smoking, and early AMD lesions at baseline. §Adjusted for age, sex, and smoking.

1.08; 95% CI, 1.04–1.13) and the baseline presence of preexisting patient samples,5,13–15,17,18 including the Age-Related retinal pigmentary abnormalities (OR, 3.90; 95% CI, 2.42–6.27) Eye Disease Study sample.16 Population-based longitu- or soft distinct drusen (OR, 3.31; 95% CI, 2.30–4.75) were pre- dinal studies to document this association were able to dictors of incident early AMD in eyes that had surgery. Cataract exclude the possibility that subtle, unrecognized, choroi- surgery also was not significantly associated with incident late AMD (OR, 0.66; 95% CI, 0.29–1.50), after adjusting for age, sex, dal neovascularization was present before surgery, be- smoking, and preexisting (baseline) early AMD lesions (Table 2). cause the observed higher risk of late AMD was a longer- 6–12 Supplementary analyses comparing all operated eyes with nonoper- term risk over Ն5 years. ated eyes only at the time of 36-month visits showed the findings In this surgical cohort, we observed that more than 80% of unaltered in both the paired eye and nonpaired eye comparisons (Table 3). patients reported systemic comorbidities, which is substantially higher than for their age peers in the generally healthy older population. These findings are consistent with many previous Discussion studies, including a retrospective review conducted in the same hospital27 and several other studies of cataract surgical pa- 28–32 We followed a large clinic cohort of older cataract surgical tients, all of which documented that coexisting medical patients and documented no significantly increased risk of conditions are frequent among patients undergoing cataract developing late or early AMD in operated compared with surgery. The Auckland Cataract Study reported that 80% of nonoperated eyes of the same patients 3 years after surgery. 480 cataract surgical patients had coexisting systemic medical 28 However, there seems to be a modest increased risk of conditions, an identical proportion to that found in our sam- detecting or developing retinal pigmentary abnormalities in ple despite some age differences between the 2 studies. surgical eyes. The latter finding may have been the result of Whether these systemic conditions partly explain discrepancies detection bias due to difficulty in detecting subtle retinal in evidence supporting a link between cataract surgery and pigmentary abnormalities in cataractous eyes relative to that subsequent progression of AMD between population-based in aphakic or pseudophakic eyes. and clinic-based studies is unclear and depends on the associ- Surgical intervention is a highly effective therapy for cata- ations of these systemic conditions with late AMD, for which ract, and uncorrected visual acuity (Ͼ20/30) can usually be evidence has been inconsistent.33–36 restored by intraocular lens implantation. Although cataract Of note, the proportion of cataract surgical patients with surgery is arguably the most cost-effective surgical pro- early AMD (15.3%) was slightly higher than that reported in cedure worldwide, whether it could lead to an increased the BMES population (ϳ11.6% among subjects aged 65ϩ risk of progression of late AMD has been a long-standing years22). The presence of early AMD lesions is the stron- but unresolved question.5 A greater risk of developing gest risk factor for progression to late AMD.23,37 The late AMD after cataract surgery has been documented in higher prevalence of early AMD could partly explain the some clinic25,26 and in most population-based, cross- previously reported association between prior cataract sectional7,8 and longitudinal studies.9–12 However, this surgery and subsequent risk of progression to late AMD link has not been consistently observed in clinic-based in population-based studies because, in these studies,

2301 Ophthalmology Volume 119, Number 11, November 2012 cataract surgical patients were compared with generally annually after surgery for up to 3 years. A limitation of the healthy older individuals. Previous reports from pooled study is the self-reported nature of most of the ocular and 5-year incidence data of BMES and Beaver Dam Eye systemic conditions, even though validation was undertaken Study (BDES) samples,10 and from the 10-year BMES from clinic notes. follow-up11 and the 10-year Rotterdam Study follow- In conclusion, paired eye comparison of this older surgical up,12 all adjusted for preexisting early AMD lesions or its cohort showed a 50% higher risk of detecting or developing stage of AMD in their statistical models. retinal pigment changes in surgical eyes over 3 years, but no We took advantage of the 2 eyes per patient19 to conduct increased risk of developing late or early AMD or soft/reticular paired comparison between surgical and nonsurgical eyes of drusen. We also documented that the distribution of early the same patients, where all other covariables such as age, AMD lesions was more frequent among patients undergoing smoking, and AMD-risk genes are exactly matched. Because cataract surgery than among their age peers in the older pop- of the relatively high rate of bilateral surgery among the ulation. Our study findings may provide a partial explanation surgical cohort, we were limited to a small number of unilateral for the inconsistent observations on the potential links between surgery patients who were eligible for paired eye comparison. cataract surgery and AMD from population- and clinic-based Given that the previously documented positive association studies. Future studies are needed to assess whether cataract between cataract surgery and AMD was over a period of Ն5 surgery or postsurgical ocular status jointly with other AMD years, to maximize sample size we included patients who had risk factors contributes to a greater risk of late AMD in cataract the second eye operated less than 1 year previously in paired surgical patients. comparison analysis. We found no significantly increased risk of the development of late or early AMD in operated versus nonoperated eyes of the same patients over 3 years. References In the nonpaired eye comparison analysis, we documented that only age and preexisting early AMD lesions were associated with incident late AMD in this surgical cohort. Apart from 1. Rahmani B, Tielsch JM, Katz J, et al. The cause-specific early AMD lesions, other ocular pathologies associated with prevalence of visual impairment in an urban population. The Baltimore Eye Survey. Ophthalmology 1996;103:1721–6. cataract surgery could also increase the risk of progression to 2. Klaver CC, Wolfs RC, Vingerling JR, et al. Age-specific late AMD. In the BDES, the presence of cataract at baseline prevalence and causes of blindness and visual impairment in predicted a slight increase in the 10-year incidence of early an older population: the Rotterdam Study. Arch Ophthalmol AMD.9 In pooled BMES and BDES data, we reported that 1998;116:653–8. baseline cortical cataract predicted a 2.8-fold (95% CI, 1.3– 3. Javitt JC, Wang F, West SK. Blindness due to cataract: epi- 6.1) greater 5-year risk of GA.10 In the Copenhagen City Eye demiology and prevention. Annu Rev Public Health 1996;17: Study, baseline cataract also predicted 14-year incident early or 159–77. late AMD (OR, 2.8; 95% CI, 1.2–6.2).38 Of particular interest, 4. Klein R, Wang Q, Klein BE, et al. The relationship of age- the Rotterdam Study documented that only carriers of the related maculopathy, cataract, and glaucoma to visual acuity. CFH-Y402H risk allele had a significantly increased risk of Invest Ophthalmol Vis Sci 1995;36:182–91. 5. Bockelbrink A, Roll S, Ruether K, et al. Cataract surgery and the developing GA after cataract surgery or in association with the 12 development or progression of age-related macular degeneration: pseudophakic state. a systematic review. Surv Ophthalmol 2008;53:359–67. Although longer-term follow-up (at least 5 years) is 6. Chakravarthy U, Wong TY, Fletcher A, et al. Clinical risk needed to further clarify this important question, our find- factors for age-related macular degeneration: a systematic ings seem to indirectly support the speculation that the risk review and meta-analysis. BMC Ophthalmol [serial online] of AMD is higher among surgical patients than among 2010;10:31. Available at: http://www.biomedcentral.com/ generally healthy older persons (who were the controls in 1471–2415/10/31. Accessed July 4, 2012. population-based studies), regardless of cataract surgery 7. Freeman EE, Munoz B, West SK, et al. Is there an association status. In a patient-to-patient comparison (which is the case between cataract surgery and age-related macular degenera- in clinic-based studies), a difference may not be detected. tion? Data from three population-based studies. Am J Oph- thalmol 2003;135:849–56. However, a difference may be evident when patients are 8. Krishnaiah S, Das T, Nirmalan PK, et al. Risk factors for compared with generally healthy older persons living in the age-related macular degeneration: findings from the Andhra community (which is the case in population-based studies). Pradesh Eye Disease Study in south India. Invest Ophthalmol There may be differences between patient samples and Vis Sci 2005;46:4442–9. population-based controls but not between surgical and 9. Klein R, Klein BE, Wong TY, et al. The association of nonsurgical states. The different distributions of comorbidi- cataract and cataract surgery with the long-term incidence of ties between clinic-based and population-based samples age-related maculopathy: the Beaver Dam Eye Study. Arch highlight the importance of study sample and control group Ophthalmol 2002;120:1551–8. selection to the research question under investigation and to 10. Wang JJ, Klein R, Smith W, et al. Cataract surgery and the the appropriate interpretation of study findings.19 5-year incidence of late-stage age-related maculopathy: pooled findings from the Beaver Dam and Blue Mountains The strengths of this study, in addition to the paired eye Eye Studies. Ophthalmology 2003;110:1960–7. comparison of the same patients enabling the exact match for 11. Cugati S, Mitchell P, Rochtchina E, et al. Cataract surgery systemic AMD risk profile between the 2 comparison groups and the 10-year incidence of age-related maculopathy: the (operated and nonoperated eyes), include photographic docu- Blue Mountains Eye Study. Ophthalmology 2006;113: mentation of the macula before or shortly after surgery and 2020–5.

2302 Wang et al ⅐ AMD 3 Years after Cataract Surgery

12. Ho L, Boekhoorn SS, Liana, et al. Cataract surgery and the 26. Pollack A, Marcovich A, Bukelman A, et al. Development of risk of aging macula disorder: the Rotterdam Study. Invest exudative age-related macular degeneration after cataract sur- Ophthalmol Vis Sci 2008;49:4795–800. gery. Eye (Lond) 1997;11:523–30. 13. Armbrecht AM, Findlay C, Aspinall PA, et al. Cataract sur- 27. Pham TQ, Wang JJ, Rochtchina E, et al. Systemic and ocular gery in patients with age-related macular degeneration: one- comorbidity of cataract surgical patients in a western Sydney year outcomes. J Cataract Refract Surg 2003;29:686–93. public hospital. Clin Experiment Ophthalmol 2004;32:383–7. 14. Sutter FK, Menghini M, Barthelmes D, et al. Is pseudophakia 28. Riley AF, Malik TY, Grupcheva CN, et al. The Auckland cataract a risk factor for neovascular age-related macular degenera- study: co-morbidity, surgical techniques, and clinical outcomes in a tion? Invest Ophthalmol Vis Sci 2007;48:1472–5. public hospital service. Br J Ophthalmol 2002;86:185–90. 15. Baatz H, Darawsha R, Ackermann H, et al. Phacoemulsifica- 29. Reeves SW, Tielsch JM, Katz J, et al. A self-administered tion does not induce neovascular age-related macular degen- health questionnaire for the preoperative risk stratification of eration. Invest Ophthalmol Vis Sci 2008;49:1079–83. patients undergoing cataract surgery. Am J Ophthalmol 2003; 16. Chew EY, Sperduto RD, Milton RC, et al. Risk of advanced age-related macular degeneration after cataract surgery in the 135:599–606. Age-Related Eye Disease Study: AREDS report 25. Ophthal- 30. Desai P, Minassian DC, Reidy A. National cataract surgery mology 2009;116:297–303. survey 1997-8: a report of the results of the clinical outcomes. 17. Dong LM, Stark WJ, Jefferys JL, et al. Progression of age- Br J Ophthalmol 1999;83:1336–40. related macular degeneration after cataract surgery. Arch Oph- 31. McKibbin M. The pre-operative assessment and investigation thalmol 2009;127:1412–9. of ophthalmic patients. Eye (Lond) 1996;10:138–40. 18. Kaiserman I, Kaiserman N, Elhayany A, Vinker S. Cataract 32. Gilvarry A, Eustace P. The medical profile of cataract patients. surgery is associated with a higher rate of photodynamic Trans Ophthalmol Soc U K 1982;102:502–4. therapy for age-related macular degeneration. Ophthalmology 33. Klein R, Deng Y, Klein BE, et al. Cardiovascular disease, its risk 2007;114:278–82. factors and treatment, and age-related macular degeneration: 19. Klein BE. Is the risk of incidence or progression of age-related Women’s Health Initiative Sight Exam ancillary study. Am J macular degeneration increased after cataract surgery? Arch Ophthalmol 2007;143:473–83. Ophthalmol 2009;127:1528–9. 34. Wong TY, Tikellis G, Sun C, et al. Age-related macular 20. Cugati S, de Loryn T, Pham T, et al. Australian prospective study degeneration and risk of coronary heart disease: the Athero- of cataract surgery and age-related macular degeneration: ratio- sclerosis Risk in Communities Study. Ophthalmology 2007; nale and methodology. Ophthalmic Epidemiol 2007;14:408–14. 114:86–91. 21. Klein R, Davis MD, Magli YL, et al. The Wisconsin Age- 35. Tan JS, Mitchell P, Smith W, Wang JJ. Cardiovascular risk Related Maculopathy Grading System. Ophthalmology 1991; factors and the long-term incidence of age-related macular 98:1128–34. degeneration: the Blue Mountains Eye Study. Ophthalmology 22. Mitchell P, Smith W, Attebo K, Wang JJ. Prevalence of 2007;114:1143–50. age-related maculopathy in Australia: the Blue Mountains Eye 36. Fraser-Bell S, Wu J, Klein R, et al, Los Angeles Latino Eye Study. Ophthalmology 1995;102:1450–60. 23. Mitchell P, Wang JJ, Foran S, Smith W. Five-year incidence Study Group. Cardiovascular risk factors and age-related mac- of age-related maculopathy lesions: the Blue Mountains Eye ular degeneration: the Los Angeles Latino Eye Study. Am J Study. Ophthalmology 2002;109:1092–7. Ophthalmol 2008;145:308–16. 24. International ARM Epidemiological Study Group, Bird AC, 37. Wang JJ, Rochtchina E, Lee AJ, et al. Ten-year incidence and Bressler NM, Bressler SB, et al. An international classification progression of age-related maculopathy: the Blue Mountains and grading system for age-related maculopathy and age-related Eye Study. Ophthalmology 2007;114:92–8. macular degeneration. Surv Ophthalmol 1995;39:367–74. 38. Buch H. Fourteen-year incidence of age-related maculopathy 25. Pollack A, Marcovich A, Bukelman A, Oliver M. Age-related mac- and cause-specific prevalence of visual impairment and blind- ular degeneration after extracapsular cataract extraction with intra- ness in a Caucasian population: the Copenhagen City Eye ocular lens implantation. Ophthalmology 1996;103:1546–54. Study. Acta Ophthalmol Scand 2005;83:400–1.

Footnotes and Financial Disclosures

Originally received: March 20, 2012. The study was supported by the Australian National Health & Medical Final revision: June 14, 2012. Research Council, Canberra Australia (Grant ID 302010, 2004–2006) and Accepted: July 5, 2012. Retina Australia (2005). JJW is funded by a National Health & Medical Available online: September 5, 2012. Manuscript no. 2012-403. Research Council Senior Research Fellowship (Grant IDs 358702, 2005– 1 Centre for Vision Research, Department of Ophthalmology and West- 2009, and 632909, 2010–2014). mead Millennium Institute, University of Sydney, Sydney, Australia. J.J.W. and E.R. had full access to all the data in this study and take 2 Centre for Eye Research Australia, University of Melbourne, Melbourne, responsibility for the integrity of the data and the accuracy of the data Australia. analysis. 3 Marsden Eye Specialists, Parramatta, New South Wales, Australia. 4 Centre for Clinical Epidemiology & Biostatistics, University of New- Correspondence: castle, Newcastle, Australia. Jie Jin Wang, MMed, PhD, Centre for Vision Research, Department of Financial Disclosure(s): Ophthalmology, Westmead Millennium Institute, University of Sydney, The author(s) have no proprietary or commercial interest in any materials Westmead Hospital, Hawkesbury Rd, Westmead, NSW Australia, 2145. discussed in this article. E-mail: [email protected].

2303