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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 65⫹ 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-byside grading of images from all visits. Paired comparisons between operated and nonoperated fellow eyes (defined as nonoperated or operated ⬍12 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 in elderly Americans and Australians.1– 4 Cataract surgery is currently the most frequently performed ocular surgical procedure. However, a potential for cataract surgery to increase the risk of progression to late-stage age-related macular degeneration (AMD) has led to concern.5,6 Discrepancy in the currently available evidence for this risk seems divided by the nature of the study samples: Population-based studies have mostly supported an association between postcataract surgical status and late AMD over the longer term,6 –12 whereas clinicbased studies have mostly reported a negative finding of the association,13–17 although inconsistently.18
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© 2012 by the American Academy of Ophthalmology Published by Elsevier Inc.
We hypothesize that the discrepancy in findings of a cataract surgery–AMD link between population- and clinicbased studies is likely due to different distributions of AMD risk factors between the 2 types of samples.19 Populationbased studies generally have used healthy older persons as controls, whereas clinic-based patient samples have used cataract surgical patients who did not develop late AMD as controls. Further, cataract surgery or the postsurgical ocular state may not in itself lead to a higher risk of AMD progression but could do so if other contributory factors are present. Compared with generally healthy, community-living older persons, clinic patients may be more likely to have ISSN 0161-6420/12/$–see front matter http://dx.doi.org/10.1016/j.ophtha.2012.07.003
Wang et al 䡠 AMD 3 Years after Cataract Surgery coexisting systemic and ocular pathologies, which may jointly with cataract surgery or postsurgical factors contribute to the greater observed risk of progression to late AMD. For these reasons, an ideal study design to address the question about the role of cataract surgery in AMD progression is to take advantage of the 2 eyes per patient and conduct a paired comparison between surgical and nonsurgical eyes of the same patients.19 The current report aimed to assess whether a link exists between postcataract surgical status and AMD progression in a clinic-based older cohort of cataract surgical patients, the Australian Cataract Surgery and Age-related Macular Degeneration (CSAMD) study,20 using paired eye comparisons among patients who retained a unilateral operated state for 24 to 36 months after their first eye had cataract surgery.
Materials and Methods The CSAMD study is a longitudinal follow-up of patients aged 65 years of age or older who underwent cataract surgery at Westmead Hospital or private ophthalmic facilities in the Western Sydney region. Participants were noninstitutionalized residents of the Western Sydney region, Australia. The study was approved by the University of Sydney and Western Sydney Area Health Service Human Research Ethics Committees and was conducted adhering to the tenets of the Declaration of Helsinki. Study methods and procedures have been described.20 In brief, 2029 patients aged 65 years of age or older were 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 consultants. All eligible cataract surgical patients (aged 65 years of age or older, without late AMD in the surgical eye) were invited to participate. Consenting participants were interviewed and examined in a standardized manner at the time of recruitment (baseline), either before cataract surgery (76.8%) or within the first month after surgery (23.2%). Demographic data were obtained during face-to-face interviews, and systemic and ocular conditions were recorded. Questions asked about medical history included history of diabetes, hypertension, angina, hypercholesterolemia, myocardial infarct, stroke, transient ischemic attack, arthritis, and surgical procedures. Medical history and medications used were validated against patient records. At examinations, height and weight were recorded, and body mass index (BMI) was calculated as weight (kilograms)/height (meters squared), with overweight defined as BMI ⱖ25 kg/m2 and obesity defined as BMI ⱖ30 kg/m2. Visual acuity of each eye was assessed at each visit following the study protocol.20 Baseline retinal photographs taken before surgery or within the first postoperative month were graded for AMD lesions, closely following the Wisconsin Age-Related Maculopathy Grading System,21 modified for use in the Blue Mountains Eye Study (BMES).22,23 Late AMD was defined as neovascular AMD or geographic atrophy (GA) of at least 175 m diameter present within the macular area, as described by the International AgeRelated Maculopathy classification.24 Early AMD was defined as the presence of indistinct large (ⱖ125 m diameter) soft or reticular drusen, or coexisting large soft distinct drusen and retinal pigmentary abnormalities.
The incidence of late and early AMD was assessed in both operated (the study eye) and nonoperated or only recently operated (⬍12 months) eyes (the control eye) of participants using side-byside grading of the retinal photographs taken at baseline and at each of the annual follow-up visits, up to 36 months after surgery. Incident late AMD was defined as the presence of neovascular AMD or GA in follow-up visits of eyes having no late AMD lesions at baseline. Incident early AMD was similarly defined as the presence of large soft indistinct or reticular drusen, or the co-presence of both large soft distinct drusen and retinal pigmentary abnormalities in follow-up visits of eyes having no late or early AMD signs at baseline. Eyes with only large soft distinct drusen or retinal pigmentary abnormalities at baseline, but not both lesions, that developed complementary lesions, together comprising a diagnosis of early AMD, were included as incident early AMD.23 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 unilaterally phakic for at least 24 months, using generalized estimating equation models and adjusting for the presence of preexisting early AMD lesions. We also analyzed data from participants who were followed for at least 36 months since cataract surgery in their study eyes to assess AMD incidence in eyes with a pseudophakic state for ⱖ24 months compared with nonoperated or only recently operated (⬍12 months) eyes (nonpaired eye comparison). Supplementary analyses were performed comparing all operated eyes (regardless of the duration of operations in the eyes) with nonoperated eyes at the 36-month visits. Odds ratios (ORs) and 95% confidence intervals (CIs) are presented.
Results Approximately 80% of age-eligible patients undergoing cataract surgery at the Eye Clinic, Westmead Hospital, agreed to participate in the CSAMD study. Of the 2029 participants recruited, 69.6% were Caucasian, 11.0% were Asian, 11.0% were Middle Eastern, and 8.4% were of other ethnicities or mixed race. The mean age of this sample was 75.2⫾6.1 years, and there were more women (57.6%) than men (42.4%, P ⬍ 0.0001). Past smokers and current smokers comprised 37.1% and 14.2% of the sample, respectively, whereas overweight and obese participants comprised 35.4% and 25.5% of the sample, respectively. Systemic comorbidities were present in 81.4% of the sample. Hypertension was the most frequent systemic comorbidity (61%), followed by hypercholesterolemia (45.2%) and diabetes (29.3%) (Table 1). Of the 2029 participants, retinal photographs were gradable for 1499 at the preoperative visit and for 1688 at the 1-month postoperative visit (most patients had photographs at both visits). Ocular conditions detected from photographs taken at either or both of these 2 baseline visits were considered to represent preexisting lesions before surgery (baseline). Overall, 1954 participants (96.3%) had retinal photographs taken and 1760 participants (86.7%) had gradable photographs from at least 1 of these 2 baseline visits. Late AMD was present in 2.0% (0.9% neovascular AMD and 1.1% GA) of the study eyes. The proportion of study eyes with early AMD lesions at baseline was 15.3% (Table 1). Preoperatively, the average mean number of letters read correctly in the study eyes was 25.2 (standard deviation, 17.5) letters for presenting visual acuity and 32.3 (standard deviation, 19.2) letters for pinhole visual acuity.
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Ophthalmology Volume 119, Number 11, November 2012 Table 1. Prevalence of Systemic and Ocular Comorbidities in the Cataract Surgery and Age-related Macular Degeneration Study Sample (65 Years of Age or Older) at Baseline % with Comorbidity (Nⴝ1760 surgical eyes)
Systemic Comorbidity Hypertension Hypercholesterolemia Diabetes Angina Myocardial infarction Stroke Any systemic comorbidities
60.6 45.2 29.3 14.2 14.6 12.9 81.4
95% CI, 0.23–2.36) after adjusting for the presence of early AMD at baseline. Of 217 unilateral cataract surgical patients at risk of early 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 retinal pigment abnormalities was more frequent in operated than in nonoperated fellow eyes (15.3% vs. 9.9%; OR, 1.64; 95% CI, 1.07– 2.52). There was no difference in the incidence of large soft indistinct or reticular drusen between the 2 eyes over the 3-year period (8.8% vs. 7.9%; OR, 1.12; 95% CI, 0.79 –1.60) (Table 2).
Nonpaired Comparison of All Operated versus Nonoperated Eyes
AMD lesions
% with lesions (Nⴝ1760 surgical eyes)
Any AMD Late AMD Early AMD Retinal pigmentary abnormalities Soft indistinct drusen Soft distinct drusen
17.3 2.0 15.3 18.9 12.6 9.9
AMD ⫽ age-related macular degeneration.
Paired Comparison of Operated versus Nonoperated Eyes Of the 1760 participants with gradable photographs at baseline who were followed annually, 1244 (70.7%) had 36-month postoperative visits. Of these subjects, 1178 had gradable photographs from at least 1 follow-up visit. There were 308 participants at risk of late AMD and 217 participants at risk of early AMD who remained unilaterally phakic for at least 24 months. Of the 308 unilateral surgical patients at risk of late AMD, this developed in 4 (1.3%) operated and 7 (2.3%) nonoperated fellow eyes (OR, 0.74;
By the time the 36-month visits were scheduled, 336 subjects had undergone unilateral cataract surgery and 842 subjects (71.5%) had undergone bilateral cataract surgery. Of the 842 subjects undergoing bilateral operations, 282 already had surgery on 1 eye before being recruited into the study and 560 had no cataract surgery in either eye at the time of study recruitment. Of these 560 subjects (1120 eyes), 491 (982 eyes) had undergone operation ⬎12 months previously, and all these eyes were included in this comparison as operated eyes. The remaining 69 subjects had 1 eye operated ⬎12 months previously and the second eye operated ⬍12 months previously by the time the 3-year follow-up visit was conducted. There were thus 1951 (336⫹282⫻2⫹982⫹69) operated eyes and 405 (336⫹69) eyes that had not yet had surgery or had surgery ⬍12 months previously. After excluding eyes that did not have gradable retinal photographs at both the baseline and at least 1 follow-up visit, or that had late AMD present at baseline (i.e., not at risk of late AMD), there were 1711 operated eyes that had surgery ⬎12 months previously and 348 eyes that had not yet had surgery or had surgery ⬍12 months previously for the nonpaired eye comparison. After adjusting for age, sex, smoking, and preexisting early AMD lesions before surgery, cataract surgery was not significantly associated with the incidence of early AMD (OR, 0.99; 95% CI, 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 (⬎12 Months Previously) with Nonoperated or Recently Operated Eyes (⬍12 Months Previously),* the Cataract Surgery and Age-related Macular Degeneration Study No. at Risk Incidence Paired eye comparison Late-stage AMD Early-stage AMD Soft indistinct/reticular drusen Retinal pigmentary abnormalities Nonpaired eye comparison Late-stage AMD Early-stage AMD Soft indistinct/reticular drusen Retinal pigmentary abnormalities
OR
Subjects, n
Incidence in Operated Eyes, %
Incidence in Nonoperated Eyes, %
(95% CIs)
308 217 227 223
1.3 10.6 8.8 15.3
2.3 9.7 7.9 9.9
0.74 (0.23–2.36)† 1.07 (0.74–1.65) 1.12 (0.79–1.60) 1.64 (1.07–2.52)
Operated/nonoperated eyes,* n 1711/348 1366/282 1408/288 1400/283
1.7 10.1 7.4 15.1
2.6 10.6 8.3 11.3
0.66 (0.29–1.50)‡ 0.99 (0.66–1.49)‡ 0.94 (0.65–1.35)§ 1.46 (1.00–2.14)§
AMD ⫽ age-related macular degeneration; CI ⫽ confidence interval; OR ⫽ odds ratio. *Operated eyes are defined as those that had surgery ⬎12 months previously, and nonoperated eyes are defined as those that had not yet had surgery or had surgery ⬍12 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.
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Wang et al 䡠 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 Incidence Paired eye comparison Late-stage AMD Early-stage AMD Soft indistinct/reticular drusen Retinal pigmentary abnormalities Nonpaired eye comparison Late-stage AMD Early-stage AMD Soft indistinct/reticular drusen Retinal pigmentary abnormalities
OR
Subjects, n
Incidence in Operated Eyes, %
Incidence in Nonoperated Eyes, %
(95% CIs)
252 175 183 183
0.8 9.7 7.7 13.1
2.4 8.0 6.6 9.3
0.33 (0.08–1.33)† 1.24 (0.75–2.04) 1.18 (0.75–1.87) 1.47 (0.88–2.48)
Operated/nonoperated eyes,* n 1769/284 1411/234 1453/240 1448/230
1.7 10.2 7.9 14.9
2.5 10.3 7.5 11.7
0.73 (0.29–1.83)‡ 1.07 (0.68–1.68)‡ 0.98 (0.65–1.47)§ 1.30 (0.86–2.14)§
AMD ⫽ age-related macular degeneration; CI ⫽ confidence interval; OR ⫽ 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 retinal pigmentary abnormalities (OR, 3.90; 95% CI, 2.42– 6.27) or soft distinct drusen (OR, 3.31; 95% CI, 2.30 – 4.75) were predictors of incident early AMD in eyes that had surgery. Cataract surgery also was not significantly associated with incident late AMD (OR, 0.66; 95% CI, 0.29 –1.50), after adjusting for age, sex, smoking, and preexisting (baseline) early AMD lesions (Table 2). Supplementary analyses comparing all operated eyes with nonoperated eyes only at the time of 36-month visits showed the findings unaltered in both the paired eye and nonpaired eye comparisons (Table 3).
Discussion We followed a large clinic cohort of older cataract surgical patients and documented no significantly increased risk of developing late or early AMD in operated compared with nonoperated eyes of the same patients 3 years after surgery. However, there seems to be a modest increased risk of detecting or developing retinal pigmentary abnormalities in surgical eyes. The latter finding may have been the result of detection bias due to difficulty in detecting subtle retinal pigmentary abnormalities in cataractous eyes relative to that in aphakic or pseudophakic eyes. Surgical intervention is a highly effective therapy for cataract, and uncorrected visual acuity (⬎20/30) can usually be restored by intraocular lens implantation. Although cataract surgery is arguably the most cost-effective surgical procedure worldwide, whether it could lead to an increased risk of progression of late AMD has been a long-standing but unresolved question.5 A greater risk of developing late AMD after cataract surgery has been documented in some clinic25,26 and in most population-based, crosssectional7,8 and longitudinal studies.9 –12 However, this link has not been consistently observed in clinic-based
patient samples,5,13–15,17,18 including the Age-Related Eye Disease Study sample.16 Population-based longitudinal studies to document this association were able to exclude the possibility that subtle, unrecognized, choroidal neovascularization was present before surgery, because the observed higher risk of late AMD was a longerterm risk over ⱖ5 years.6 –12 In this surgical cohort, we observed that more than 80% of 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 studies, including a retrospective review conducted in the same hospital27 and several other studies of cataract surgical patients,28 –32 all of which documented that coexisting medical conditions are frequent among patients undergoing cataract surgery. The Auckland Cataract Study reported that 80% of 480 cataract surgical patients had coexisting systemic medical conditions,28 an identical proportion to that found in our sample despite some age differences between the 2 studies. Whether these systemic conditions partly explain discrepancies in evidence supporting a link between cataract surgery and subsequent progression of AMD between population-based and clinic-based studies is unclear and depends on the associations of these systemic conditions with late AMD, for which evidence has been inconsistent.33–36 Of note, the proportion of cataract surgical patients with early AMD (15.3%) was slightly higher than that reported in the BMES population (⬃11.6% among subjects aged 65⫹ years22). The presence of early AMD lesions is the strongest risk factor for progression to late AMD.23,37 The higher prevalence of early AMD could partly explain the previously reported association between prior cataract surgery and subsequent risk of progression to late AMD in population-based studies because, in these studies,
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Ophthalmology Volume 119, Number 11, November 2012 cataract surgical patients were compared with generally healthy older individuals. Previous reports from pooled 5-year incidence data of BMES and Beaver Dam Eye Study (BDES) samples,10 and from the 10-year BMES follow-up11 and the 10-year Rotterdam Study followup,12 all adjusted for preexisting early AMD lesions or its stage of AMD in their statistical models. We took advantage of the 2 eyes per patient19 to conduct paired comparison between surgical and nonsurgical eyes of the same patients, where all other covariables such as age, smoking, and AMD-risk genes are exactly matched. Because of the relatively high rate of bilateral surgery among the surgical cohort, we were limited to a small number of unilateral surgery patients who were eligible for paired eye comparison. Given that the previously documented positive association between cataract surgery and AMD was over a period of ⱖ5 years, to maximize sample size we included patients who had the second eye operated less than 1 year previously in paired 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. 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 early AMD lesions, other ocular pathologies associated with cataract surgery could also increase the risk of progression to late AMD. In the BDES, the presence of cataract at baseline predicted a slight increase in the 10-year incidence of early AMD.9 In pooled BMES and BDES data, we reported that baseline cortical cataract predicted a 2.8-fold (95% CI, 1.3– 6.1) greater 5-year risk of GA.10 In the Copenhagen City Eye Study, baseline cataract also predicted 14-year incident early or late AMD (OR, 2.8; 95% CI, 1.2– 6.2).38 Of particular interest, the Rotterdam Study documented that only carriers of the CFH-Y402H risk allele had a significantly increased risk of developing GA after cataract surgery or in association with the pseudophakic state.12 Although longer-term follow-up (at least 5 years) is needed to further clarify this important question, our findings seem to indirectly support the speculation that the risk of AMD is higher among surgical patients than among generally healthy older persons (who were the controls in population-based studies), regardless of cataract surgery status. In a patient-to-patient comparison (which is the case in clinic-based studies), a difference may not be detected. However, a difference may be evident when patients are compared with generally healthy older persons living in the community (which is the case in population-based studies). There may be differences between patient samples and population-based controls but not between surgical and nonsurgical states. The different distributions of comorbidities between clinic-based and population-based samples highlight the importance of study sample and control group selection to the research question under investigation and to the appropriate interpretation of study findings.19 The strengths of this study, in addition to the paired eye comparison of the same patients enabling the exact match for systemic AMD risk profile between the 2 comparison groups (operated and nonoperated eyes), include photographic documentation of the macula before or shortly after surgery and
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annually after surgery for up to 3 years. A limitation of the study is the self-reported nature of most of the ocular and systemic conditions, even though validation was undertaken from clinic notes. In conclusion, paired eye comparison of this older surgical cohort showed a 50% higher risk of detecting or developing retinal pigment changes in surgical eyes over 3 years, but no increased risk of developing late or early AMD or soft/reticular drusen. We also documented that the distribution of early AMD lesions was more frequent among patients undergoing cataract surgery than among their age peers in the older population. Our study findings may provide a partial explanation for the inconsistent observations on the potential links between cataract surgery and AMD from population- and clinic-based studies. Future studies are needed to assess whether cataract surgery or postsurgical ocular status jointly with other AMD risk factors contributes to a greater risk of late AMD in cataract surgical patients.
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26. Pollack A, Marcovich A, Bukelman A, et al. Development of exudative age-related macular degeneration after cataract surgery. Eye (Lond) 1997;11:523–30. 27. Pham TQ, Wang JJ, Rochtchina E, et al. Systemic and ocular comorbidity of cataract surgical patients in a western Sydney public hospital. Clin Experiment Ophthalmol 2004;32:383–7. 28. Riley AF, Malik TY, Grupcheva CN, et al. The Auckland cataract study: co-morbidity, surgical techniques, and clinical outcomes in a public hospital service. Br J Ophthalmol 2002;86:185–90. 29. Reeves SW, Tielsch JM, Katz J, et al. A self-administered health questionnaire for the preoperative risk stratification of patients undergoing cataract surgery. Am J Ophthalmol 2003; 135:599 – 606. 30. Desai P, Minassian DC, Reidy A. National cataract surgery survey 1997-8: a report of the results of the clinical outcomes. Br J Ophthalmol 1999;83:1336 – 40. 31. McKibbin M. The pre-operative assessment and investigation of ophthalmic patients. Eye (Lond) 1996;10:138 – 40. 32. Gilvarry A, Eustace P. The medical profile of cataract patients. Trans Ophthalmol Soc U K 1982;102:502– 4. 33. Klein R, Deng Y, Klein BE, et al. Cardiovascular disease, its risk factors and treatment, and age-related macular degeneration: Women’s Health Initiative Sight Exam ancillary study. Am J Ophthalmol 2007;143:473– 83. 34. Wong TY, Tikellis G, Sun C, et al. Age-related macular degeneration and risk of coronary heart disease: the Atherosclerosis Risk in Communities Study. Ophthalmology 2007; 114:86 –91. 35. Tan JS, Mitchell P, Smith W, Wang JJ. Cardiovascular risk factors and the long-term incidence of age-related macular degeneration: the Blue Mountains Eye Study. Ophthalmology 2007;114:1143–50. 36. Fraser-Bell S, Wu J, Klein R, et al, Los Angeles Latino Eye Study Group. Cardiovascular risk factors and age-related macular degeneration: the Los Angeles Latino Eye Study. Am J Ophthalmol 2008;145:308 –16. 37. Wang JJ, Rochtchina E, Lee AJ, et al. Ten-year incidence and progression of age-related maculopathy: the Blue Mountains Eye Study. Ophthalmology 2007;114:92– 8. 38. Buch H. Fourteen-year incidence of age-related maculopathy and cause-specific prevalence of visual impairment and blindness in a Caucasian population: the Copenhagen City Eye Study. Acta Ophthalmol Scand 2005;83:400 –1.
Footnotes and Financial Disclosures Originally received: March 20, 2012. Final revision: June 14, 2012. Accepted: July 5, 2012. Available online: September 5, 2012.
Manuscript no. 2012-403.
1
Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Sydney, Australia.
2
Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia.
3 4
The study was supported by the Australian National Health & Medical Research Council, Canberra Australia (Grant ID 302010, 2004 –2006) and Retina Australia (2005). JJW is funded by a National Health & Medical Research Council Senior Research Fellowship (Grant IDs 358702, 2005– 2009, and 632909, 2010 –2014). J.J.W. and E.R. had full access to all the data in this study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Marsden Eye Specialists, Parramatta, New South Wales, Australia.
Centre for Clinical Epidemiology & Biostatistics, University of Newcastle, Newcastle, Australia. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Correspondence: Jie Jin Wang, MMed, PhD, Centre for Vision Research, Department of Ophthalmology, Westmead Millennium Institute, University of Sydney, Westmead Hospital, Hawkesbury Rd, Westmead, NSW Australia, 2145. E-mail: [email protected].
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Age-related cataract is a major cause of visual impairment in elderly Americans and Australians.1– 4 Cataract surgery is currently the most frequently performed ocular surgical procedure. However, a potential for cataract surgery to increase the risk of progression to late-stage age-related macular degeneration (AMD) has led to concern.5,6 Discrepancy in the currently available evidence for this risk seems divided by the nature of the study samples: Population-based studies have mostly supported an association between postcataract surgical status and late AMD over the longer term,6 –12 whereas clinicbased studies have mostly reported a negative finding of the association,13–17 although inconsistently.18
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© 2012 by the American Academy of Ophthalmology Published by Elsevier Inc.
We hypothesize that the discrepancy in findings of a cataract surgery–AMD link between population- and clinicbased studies is likely due to different distributions of AMD risk factors between the 2 types of samples.19 Populationbased studies generally have used healthy older persons as controls, whereas clinic-based patient samples have used cataract surgical patients who did not develop late AMD as controls. Further, cataract surgery or the postsurgical ocular state may not in itself lead to a higher risk of AMD progression but could do so if other contributory factors are present. Compared with generally healthy, community-living older persons, clinic patients may be more likely to have ISSN 0161-6420/12/$–see front matter http://dx.doi.org/10.1016/j.ophtha.2012.07.003
Wang et al 䡠 AMD 3 Years after Cataract Surgery coexisting systemic and ocular pathologies, which may jointly with cataract surgery or postsurgical factors contribute to the greater observed risk of progression to late AMD. For these reasons, an ideal study design to address the question about the role of cataract surgery in AMD progression is to take advantage of the 2 eyes per patient and conduct a paired comparison between surgical and nonsurgical eyes of the same patients.19 The current report aimed to assess whether a link exists between postcataract surgical status and AMD progression in a clinic-based older cohort of cataract surgical patients, the Australian Cataract Surgery and Age-related Macular Degeneration (CSAMD) study,20 using paired eye comparisons among patients who retained a unilateral operated state for 24 to 36 months after their first eye had cataract surgery.
Materials and Methods The CSAMD study is a longitudinal follow-up of patients aged 65 years of age or older who underwent cataract surgery at Westmead Hospital or private ophthalmic facilities in the Western Sydney region. Participants were noninstitutionalized residents of the Western Sydney region, Australia. The study was approved by the University of Sydney and Western Sydney Area Health Service Human Research Ethics Committees and was conducted adhering to the tenets of the Declaration of Helsinki. Study methods and procedures have been described.20 In brief, 2029 patients aged 65 years of age or older were 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 consultants. All eligible cataract surgical patients (aged 65 years of age or older, without late AMD in the surgical eye) were invited to participate. Consenting participants were interviewed and examined in a standardized manner at the time of recruitment (baseline), either before cataract surgery (76.8%) or within the first month after surgery (23.2%). Demographic data were obtained during face-to-face interviews, and systemic and ocular conditions were recorded. Questions asked about medical history included history of diabetes, hypertension, angina, hypercholesterolemia, myocardial infarct, stroke, transient ischemic attack, arthritis, and surgical procedures. Medical history and medications used were validated against patient records. At examinations, height and weight were recorded, and body mass index (BMI) was calculated as weight (kilograms)/height (meters squared), with overweight defined as BMI ⱖ25 kg/m2 and obesity defined as BMI ⱖ30 kg/m2. Visual acuity of each eye was assessed at each visit following the study protocol.20 Baseline retinal photographs taken before surgery or within the first postoperative month were graded for AMD lesions, closely following the Wisconsin Age-Related Maculopathy Grading System,21 modified for use in the Blue Mountains Eye Study (BMES).22,23 Late AMD was defined as neovascular AMD or geographic atrophy (GA) of at least 175 m diameter present within the macular area, as described by the International AgeRelated Maculopathy classification.24 Early AMD was defined as the presence of indistinct large (ⱖ125 m diameter) soft or reticular drusen, or coexisting large soft distinct drusen and retinal pigmentary abnormalities.
The incidence of late and early AMD was assessed in both operated (the study eye) and nonoperated or only recently operated (⬍12 months) eyes (the control eye) of participants using side-byside grading of the retinal photographs taken at baseline and at each of the annual follow-up visits, up to 36 months after surgery. Incident late AMD was defined as the presence of neovascular AMD or GA in follow-up visits of eyes having no late AMD lesions at baseline. Incident early AMD was similarly defined as the presence of large soft indistinct or reticular drusen, or the co-presence of both large soft distinct drusen and retinal pigmentary abnormalities in follow-up visits of eyes having no late or early AMD signs at baseline. Eyes with only large soft distinct drusen or retinal pigmentary abnormalities at baseline, but not both lesions, that developed complementary lesions, together comprising a diagnosis of early AMD, were included as incident early AMD.23 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 unilaterally phakic for at least 24 months, using generalized estimating equation models and adjusting for the presence of preexisting early AMD lesions. We also analyzed data from participants who were followed for at least 36 months since cataract surgery in their study eyes to assess AMD incidence in eyes with a pseudophakic state for ⱖ24 months compared with nonoperated or only recently operated (⬍12 months) eyes (nonpaired eye comparison). Supplementary analyses were performed comparing all operated eyes (regardless of the duration of operations in the eyes) with nonoperated eyes at the 36-month visits. Odds ratios (ORs) and 95% confidence intervals (CIs) are presented.
Results Approximately 80% of age-eligible patients undergoing cataract surgery at the Eye Clinic, Westmead Hospital, agreed to participate in the CSAMD study. Of the 2029 participants recruited, 69.6% were Caucasian, 11.0% were Asian, 11.0% were Middle Eastern, and 8.4% were of other ethnicities or mixed race. The mean age of this sample was 75.2⫾6.1 years, and there were more women (57.6%) than men (42.4%, P ⬍ 0.0001). Past smokers and current smokers comprised 37.1% and 14.2% of the sample, respectively, whereas overweight and obese participants comprised 35.4% and 25.5% of the sample, respectively. Systemic comorbidities were present in 81.4% of the sample. Hypertension was the most frequent systemic comorbidity (61%), followed by hypercholesterolemia (45.2%) and diabetes (29.3%) (Table 1). Of the 2029 participants, retinal photographs were gradable for 1499 at the preoperative visit and for 1688 at the 1-month postoperative visit (most patients had photographs at both visits). Ocular conditions detected from photographs taken at either or both of these 2 baseline visits were considered to represent preexisting lesions before surgery (baseline). Overall, 1954 participants (96.3%) had retinal photographs taken and 1760 participants (86.7%) had gradable photographs from at least 1 of these 2 baseline visits. Late AMD was present in 2.0% (0.9% neovascular AMD and 1.1% GA) of the study eyes. The proportion of study eyes with early AMD lesions at baseline was 15.3% (Table 1). Preoperatively, the average mean number of letters read correctly in the study eyes was 25.2 (standard deviation, 17.5) letters for presenting visual acuity and 32.3 (standard deviation, 19.2) letters for pinhole visual acuity.
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Ophthalmology Volume 119, Number 11, November 2012 Table 1. Prevalence of Systemic and Ocular Comorbidities in the Cataract Surgery and Age-related Macular Degeneration Study Sample (65 Years of Age or Older) at Baseline % with Comorbidity (Nⴝ1760 surgical eyes)
Systemic Comorbidity Hypertension Hypercholesterolemia Diabetes Angina Myocardial infarction Stroke Any systemic comorbidities
60.6 45.2 29.3 14.2 14.6 12.9 81.4
95% CI, 0.23–2.36) after adjusting for the presence of early AMD at baseline. Of 217 unilateral cataract surgical patients at risk of early 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 retinal pigment abnormalities was more frequent in operated than in nonoperated fellow eyes (15.3% vs. 9.9%; OR, 1.64; 95% CI, 1.07– 2.52). There was no difference in the incidence of large soft indistinct or reticular drusen between the 2 eyes over the 3-year period (8.8% vs. 7.9%; OR, 1.12; 95% CI, 0.79 –1.60) (Table 2).
Nonpaired Comparison of All Operated versus Nonoperated Eyes
AMD lesions
% with lesions (Nⴝ1760 surgical eyes)
Any AMD Late AMD Early AMD Retinal pigmentary abnormalities Soft indistinct drusen Soft distinct drusen
17.3 2.0 15.3 18.9 12.6 9.9
AMD ⫽ age-related macular degeneration.
Paired Comparison of Operated versus Nonoperated Eyes Of the 1760 participants with gradable photographs at baseline who were followed annually, 1244 (70.7%) had 36-month postoperative visits. Of these subjects, 1178 had gradable photographs from at least 1 follow-up visit. There were 308 participants at risk of late AMD and 217 participants at risk of early AMD who remained unilaterally phakic for at least 24 months. Of the 308 unilateral surgical patients at risk of late AMD, this developed in 4 (1.3%) operated and 7 (2.3%) nonoperated fellow eyes (OR, 0.74;
By the time the 36-month visits were scheduled, 336 subjects had undergone unilateral cataract surgery and 842 subjects (71.5%) had undergone bilateral cataract surgery. Of the 842 subjects undergoing bilateral operations, 282 already had surgery on 1 eye before being recruited into the study and 560 had no cataract surgery in either eye at the time of study recruitment. Of these 560 subjects (1120 eyes), 491 (982 eyes) had undergone operation ⬎12 months previously, and all these eyes were included in this comparison as operated eyes. The remaining 69 subjects had 1 eye operated ⬎12 months previously and the second eye operated ⬍12 months previously by the time the 3-year follow-up visit was conducted. There were thus 1951 (336⫹282⫻2⫹982⫹69) operated eyes and 405 (336⫹69) eyes that had not yet had surgery or had surgery ⬍12 months previously. After excluding eyes that did not have gradable retinal photographs at both the baseline and at least 1 follow-up visit, or that had late AMD present at baseline (i.e., not at risk of late AMD), there were 1711 operated eyes that had surgery ⬎12 months previously and 348 eyes that had not yet had surgery or had surgery ⬍12 months previously for the nonpaired eye comparison. After adjusting for age, sex, smoking, and preexisting early AMD lesions before surgery, cataract surgery was not significantly associated with the incidence of early AMD (OR, 0.99; 95% CI, 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 (⬎12 Months Previously) with Nonoperated or Recently Operated Eyes (⬍12 Months Previously),* the Cataract Surgery and Age-related Macular Degeneration Study No. at Risk Incidence Paired eye comparison Late-stage AMD Early-stage AMD Soft indistinct/reticular drusen Retinal pigmentary abnormalities Nonpaired eye comparison Late-stage AMD Early-stage AMD Soft indistinct/reticular drusen Retinal pigmentary abnormalities
OR
Subjects, n
Incidence in Operated Eyes, %
Incidence in Nonoperated Eyes, %
(95% CIs)
308 217 227 223
1.3 10.6 8.8 15.3
2.3 9.7 7.9 9.9
0.74 (0.23–2.36)† 1.07 (0.74–1.65) 1.12 (0.79–1.60) 1.64 (1.07–2.52)
Operated/nonoperated eyes,* n 1711/348 1366/282 1408/288 1400/283
1.7 10.1 7.4 15.1
2.6 10.6 8.3 11.3
0.66 (0.29–1.50)‡ 0.99 (0.66–1.49)‡ 0.94 (0.65–1.35)§ 1.46 (1.00–2.14)§
AMD ⫽ age-related macular degeneration; CI ⫽ confidence interval; OR ⫽ odds ratio. *Operated eyes are defined as those that had surgery ⬎12 months previously, and nonoperated eyes are defined as those that had not yet had surgery or had surgery ⬍12 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.
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Wang et al 䡠 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 Incidence Paired eye comparison Late-stage AMD Early-stage AMD Soft indistinct/reticular drusen Retinal pigmentary abnormalities Nonpaired eye comparison Late-stage AMD Early-stage AMD Soft indistinct/reticular drusen Retinal pigmentary abnormalities
OR
Subjects, n
Incidence in Operated Eyes, %
Incidence in Nonoperated Eyes, %
(95% CIs)
252 175 183 183
0.8 9.7 7.7 13.1
2.4 8.0 6.6 9.3
0.33 (0.08–1.33)† 1.24 (0.75–2.04) 1.18 (0.75–1.87) 1.47 (0.88–2.48)
Operated/nonoperated eyes,* n 1769/284 1411/234 1453/240 1448/230
1.7 10.2 7.9 14.9
2.5 10.3 7.5 11.7
0.73 (0.29–1.83)‡ 1.07 (0.68–1.68)‡ 0.98 (0.65–1.47)§ 1.30 (0.86–2.14)§
AMD ⫽ age-related macular degeneration; CI ⫽ confidence interval; OR ⫽ 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 retinal pigmentary abnormalities (OR, 3.90; 95% CI, 2.42– 6.27) or soft distinct drusen (OR, 3.31; 95% CI, 2.30 – 4.75) were predictors of incident early AMD in eyes that had surgery. Cataract surgery also was not significantly associated with incident late AMD (OR, 0.66; 95% CI, 0.29 –1.50), after adjusting for age, sex, smoking, and preexisting (baseline) early AMD lesions (Table 2). Supplementary analyses comparing all operated eyes with nonoperated eyes only at the time of 36-month visits showed the findings unaltered in both the paired eye and nonpaired eye comparisons (Table 3).
Discussion We followed a large clinic cohort of older cataract surgical patients and documented no significantly increased risk of developing late or early AMD in operated compared with nonoperated eyes of the same patients 3 years after surgery. However, there seems to be a modest increased risk of detecting or developing retinal pigmentary abnormalities in surgical eyes. The latter finding may have been the result of detection bias due to difficulty in detecting subtle retinal pigmentary abnormalities in cataractous eyes relative to that in aphakic or pseudophakic eyes. Surgical intervention is a highly effective therapy for cataract, and uncorrected visual acuity (⬎20/30) can usually be restored by intraocular lens implantation. Although cataract surgery is arguably the most cost-effective surgical procedure worldwide, whether it could lead to an increased risk of progression of late AMD has been a long-standing but unresolved question.5 A greater risk of developing late AMD after cataract surgery has been documented in some clinic25,26 and in most population-based, crosssectional7,8 and longitudinal studies.9 –12 However, this link has not been consistently observed in clinic-based
patient samples,5,13–15,17,18 including the Age-Related Eye Disease Study sample.16 Population-based longitudinal studies to document this association were able to exclude the possibility that subtle, unrecognized, choroidal neovascularization was present before surgery, because the observed higher risk of late AMD was a longerterm risk over ⱖ5 years.6 –12 In this surgical cohort, we observed that more than 80% of 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 studies, including a retrospective review conducted in the same hospital27 and several other studies of cataract surgical patients,28 –32 all of which documented that coexisting medical conditions are frequent among patients undergoing cataract surgery. The Auckland Cataract Study reported that 80% of 480 cataract surgical patients had coexisting systemic medical conditions,28 an identical proportion to that found in our sample despite some age differences between the 2 studies. Whether these systemic conditions partly explain discrepancies in evidence supporting a link between cataract surgery and subsequent progression of AMD between population-based and clinic-based studies is unclear and depends on the associations of these systemic conditions with late AMD, for which evidence has been inconsistent.33–36 Of note, the proportion of cataract surgical patients with early AMD (15.3%) was slightly higher than that reported in the BMES population (⬃11.6% among subjects aged 65⫹ years22). The presence of early AMD lesions is the strongest risk factor for progression to late AMD.23,37 The higher prevalence of early AMD could partly explain the previously reported association between prior cataract surgery and subsequent risk of progression to late AMD in population-based studies because, in these studies,
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Ophthalmology Volume 119, Number 11, November 2012 cataract surgical patients were compared with generally healthy older individuals. Previous reports from pooled 5-year incidence data of BMES and Beaver Dam Eye Study (BDES) samples,10 and from the 10-year BMES follow-up11 and the 10-year Rotterdam Study followup,12 all adjusted for preexisting early AMD lesions or its stage of AMD in their statistical models. We took advantage of the 2 eyes per patient19 to conduct paired comparison between surgical and nonsurgical eyes of the same patients, where all other covariables such as age, smoking, and AMD-risk genes are exactly matched. Because of the relatively high rate of bilateral surgery among the surgical cohort, we were limited to a small number of unilateral surgery patients who were eligible for paired eye comparison. Given that the previously documented positive association between cataract surgery and AMD was over a period of ⱖ5 years, to maximize sample size we included patients who had the second eye operated less than 1 year previously in paired 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. 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 early AMD lesions, other ocular pathologies associated with cataract surgery could also increase the risk of progression to late AMD. In the BDES, the presence of cataract at baseline predicted a slight increase in the 10-year incidence of early AMD.9 In pooled BMES and BDES data, we reported that baseline cortical cataract predicted a 2.8-fold (95% CI, 1.3– 6.1) greater 5-year risk of GA.10 In the Copenhagen City Eye Study, baseline cataract also predicted 14-year incident early or late AMD (OR, 2.8; 95% CI, 1.2– 6.2).38 Of particular interest, the Rotterdam Study documented that only carriers of the CFH-Y402H risk allele had a significantly increased risk of developing GA after cataract surgery or in association with the pseudophakic state.12 Although longer-term follow-up (at least 5 years) is needed to further clarify this important question, our findings seem to indirectly support the speculation that the risk of AMD is higher among surgical patients than among generally healthy older persons (who were the controls in population-based studies), regardless of cataract surgery status. In a patient-to-patient comparison (which is the case in clinic-based studies), a difference may not be detected. However, a difference may be evident when patients are compared with generally healthy older persons living in the community (which is the case in population-based studies). There may be differences between patient samples and population-based controls but not between surgical and nonsurgical states. The different distributions of comorbidities between clinic-based and population-based samples highlight the importance of study sample and control group selection to the research question under investigation and to the appropriate interpretation of study findings.19 The strengths of this study, in addition to the paired eye comparison of the same patients enabling the exact match for systemic AMD risk profile between the 2 comparison groups (operated and nonoperated eyes), include photographic documentation of the macula before or shortly after surgery and
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annually after surgery for up to 3 years. A limitation of the study is the self-reported nature of most of the ocular and systemic conditions, even though validation was undertaken from clinic notes. In conclusion, paired eye comparison of this older surgical cohort showed a 50% higher risk of detecting or developing retinal pigment changes in surgical eyes over 3 years, but no increased risk of developing late or early AMD or soft/reticular drusen. We also documented that the distribution of early AMD lesions was more frequent among patients undergoing cataract surgery than among their age peers in the older population. Our study findings may provide a partial explanation for the inconsistent observations on the potential links between cataract surgery and AMD from population- and clinic-based studies. Future studies are needed to assess whether cataract surgery or postsurgical ocular status jointly with other AMD risk factors contributes to a greater risk of late AMD in cataract surgical patients.
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Wang et al 䡠 AMD 3 Years after Cataract Surgery 12. Ho L, Boekhoorn SS, Liana, et al. Cataract surgery and the risk of aging macula disorder: the Rotterdam Study. Invest Ophthalmol Vis Sci 2008;49:4795– 800. 13. Armbrecht AM, Findlay C, Aspinall PA, et al. Cataract surgery in patients with age-related macular degeneration: oneyear outcomes. J Cataract Refract Surg 2003;29:686 –93. 14. Sutter FK, Menghini M, Barthelmes D, et al. Is pseudophakia a risk factor for neovascular age-related macular degeneration? Invest Ophthalmol Vis Sci 2007;48:1472–5. 15. Baatz H, Darawsha R, Ackermann H, et al. Phacoemulsification does not induce neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci 2008;49:1079 – 83. 16. Chew EY, Sperduto RD, Milton RC, et al. Risk of advanced age-related macular degeneration after cataract surgery in the Age-Related Eye Disease Study: AREDS report 25. Ophthalmology 2009;116:297–303. 17. Dong LM, Stark WJ, Jefferys JL, et al. Progression of agerelated macular degeneration after cataract surgery. Arch Ophthalmol 2009;127:1412–9. 18. Kaiserman I, Kaiserman N, Elhayany A, Vinker S. Cataract surgery is associated with a higher rate of photodynamic therapy for age-related macular degeneration. Ophthalmology 2007;114:278 – 82. 19. Klein BE. Is the risk of incidence or progression of age-related macular degeneration increased after cataract surgery? Arch Ophthalmol 2009;127:1528 –9. 20. Cugati S, de Loryn T, Pham T, et al. Australian prospective study of cataract surgery and age-related macular degeneration: rationale and methodology. Ophthalmic Epidemiol 2007;14:408 –14. 21. Klein R, Davis MD, Magli YL, et al. The Wisconsin AgeRelated Maculopathy Grading System. Ophthalmology 1991; 98:1128 –34. 22. Mitchell P, Smith W, Attebo K, Wang JJ. Prevalence of age-related maculopathy in Australia: the Blue Mountains Eye Study. Ophthalmology 1995;102:1450 – 60. 23. Mitchell P, Wang JJ, Foran S, Smith W. Five-year incidence of age-related maculopathy lesions: the Blue Mountains Eye Study. Ophthalmology 2002;109:1092–7. 24. International ARM Epidemiological Study Group, Bird AC, Bressler NM, Bressler SB, et al. An international classification and grading system for age-related maculopathy and age-related macular degeneration. Surv Ophthalmol 1995;39:367–74. 25. Pollack A, Marcovich A, Bukelman A, Oliver M. Age-related macular degeneration after extracapsular cataract extraction with intraocular lens implantation. Ophthalmology 1996;103:1546–54.
26. Pollack A, Marcovich A, Bukelman A, et al. Development of exudative age-related macular degeneration after cataract surgery. Eye (Lond) 1997;11:523–30. 27. Pham TQ, Wang JJ, Rochtchina E, et al. Systemic and ocular comorbidity of cataract surgical patients in a western Sydney public hospital. Clin Experiment Ophthalmol 2004;32:383–7. 28. Riley AF, Malik TY, Grupcheva CN, et al. The Auckland cataract study: co-morbidity, surgical techniques, and clinical outcomes in a public hospital service. Br J Ophthalmol 2002;86:185–90. 29. Reeves SW, Tielsch JM, Katz J, et al. A self-administered health questionnaire for the preoperative risk stratification of patients undergoing cataract surgery. Am J Ophthalmol 2003; 135:599 – 606. 30. Desai P, Minassian DC, Reidy A. National cataract surgery survey 1997-8: a report of the results of the clinical outcomes. Br J Ophthalmol 1999;83:1336 – 40. 31. McKibbin M. The pre-operative assessment and investigation of ophthalmic patients. Eye (Lond) 1996;10:138 – 40. 32. Gilvarry A, Eustace P. The medical profile of cataract patients. Trans Ophthalmol Soc U K 1982;102:502– 4. 33. Klein R, Deng Y, Klein BE, et al. Cardiovascular disease, its risk factors and treatment, and age-related macular degeneration: Women’s Health Initiative Sight Exam ancillary study. Am J Ophthalmol 2007;143:473– 83. 34. Wong TY, Tikellis G, Sun C, et al. Age-related macular degeneration and risk of coronary heart disease: the Atherosclerosis Risk in Communities Study. Ophthalmology 2007; 114:86 –91. 35. Tan JS, Mitchell P, Smith W, Wang JJ. Cardiovascular risk factors and the long-term incidence of age-related macular degeneration: the Blue Mountains Eye Study. Ophthalmology 2007;114:1143–50. 36. Fraser-Bell S, Wu J, Klein R, et al, Los Angeles Latino Eye Study Group. Cardiovascular risk factors and age-related macular degeneration: the Los Angeles Latino Eye Study. Am J Ophthalmol 2008;145:308 –16. 37. Wang JJ, Rochtchina E, Lee AJ, et al. Ten-year incidence and progression of age-related maculopathy: the Blue Mountains Eye Study. Ophthalmology 2007;114:92– 8. 38. Buch H. Fourteen-year incidence of age-related maculopathy and cause-specific prevalence of visual impairment and blindness in a Caucasian population: the Copenhagen City Eye Study. Acta Ophthalmol Scand 2005;83:400 –1.
Footnotes and Financial Disclosures Originally received: March 20, 2012. Final revision: June 14, 2012. Accepted: July 5, 2012. Available online: September 5, 2012.
Manuscript no. 2012-403.
1
Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Sydney, Australia.
2
Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia.
3 4
The study was supported by the Australian National Health & Medical Research Council, Canberra Australia (Grant ID 302010, 2004 –2006) and Retina Australia (2005). JJW is funded by a National Health & Medical Research Council Senior Research Fellowship (Grant IDs 358702, 2005– 2009, and 632909, 2010 –2014). J.J.W. and E.R. had full access to all the data in this study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Marsden Eye Specialists, Parramatta, New South Wales, Australia.
Centre for Clinical Epidemiology & Biostatistics, University of Newcastle, Newcastle, Australia. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Correspondence: Jie Jin Wang, MMed, PhD, Centre for Vision Research, Department of Ophthalmology, Westmead Millennium Institute, University of Sydney, Westmead Hospital, Hawkesbury Rd, Westmead, NSW Australia, 2145. E-mail: [email protected].
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