eTable. Comparisons of Participants Included in and Excluded From This Study
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Park SJ, Lee JH, Ahn S, Park KH. Cataract Surgery and Age-Related Macular Degeneration in the 2008-2012 Korea National Health and Nutrition Examination Survey. JAMA Ophthalmol. 2016;134(6):621–626. doi:10.1001/jamaophthalmol.2016.0453
In the past, concern has been raised that cataract surgery may be associated with the incidence or progression of age-related macular degeneration (AMD); inconsistent findings from previous studies have puzzled clinicians. In addition, data addressing this association in Asian populations and in the era of phacoemulsification are scarce.
To determine the associations between cataract surgery and AMD in a representative Korean population.
Design, Setting, and Participants
This cross-sectional study used a multistage, probability-cluster survey sample to produce nationally representative estimates. Data were analyzed from the Korea National Health and Nutrition Examination Survey (KNHANES), which included results for cataract surgery status and AMD grading from 2008 to 2012. A total of 20 419 participants 40 years or older were included. Data were analyzed from February 5 to August 20, 2015.
Main Outcomes and Measures
The association between cataract surgery and AMD was assessed in each right and left eye using logistic regression models and in both eyes using generalized estimating equation models. Sample weights were applied to adjust for survey design, nonresponse, and stratification to generate nationally representative population-based results.
From the 20 419 eligible individuals (11 642 women [51.9%] and 5777 men [48.1%]; mean [SE] age, 55.83 [0.14] years), 17 987 had information regarding cataract surgery status and gradable fundus photographs of at least 1 eye. A total of 34 863 eyes (17 616 right eyes and 17 247 left eyes) underwent analysis. Of these, 1264 right eyes (5.5%) and 1235 left eyes (5.4%) had cataract surgery. Of 1056 right eyes and 949 left eyes with any AMD (early or late), 167 right eyes (15.2%) and 147 left eyes (13.7%) had cataract surgery. The analyses did not show any association between cataract surgery and any form of AMD (early, late, and all) except in left eyes, where cataract surgery was associated with late AMD (odds ratio, 2.34; 95% CI, 1.13-4.85).
Conclusions and Relevance
The results suggest that the association between cataract surgery and AMD is uncertain in the current era of phacoemulsification. The association for left eyes might be a chance finding.
Cataract and age-related macular degeneration (AMD) are the leading causes of visual impairment and blindness worldwide.1,2 Given the aging population, cataract and AMD have emerged as public health concerns during the last decade.1,2 Because both conditions are quite common and often coexist, concerns have been raised that cataract surgery may be associated with the occurrence and progression of AMD. However, contradictory results from previous studies that have investigated the association between cataract surgery and AMD have puzzled clinicians: early cohort and case-control studies suggested an association,3-11 whereas other studies did not (Table 1).12-15
In addition, these results have been derived primarily from white populations; a paucity of data addresses the potential association in Asian populations.16,17 In addition to inherent differences, such as iris color and retinal pigment epithelial darkness, which may influence AMD pathogenesis in relation to cataract surgery, AMD characteristics are quite different between Asian and white individuals. Early signs of AMD (eg, drusen) are less common in Asian than in white patients, and polypoidal choroidal vasculopathy, a distinct subtype of exudative AMD, accounts for 20% to 55% of exudative AMD in Asian populations, whereas it accounts for only 8% to 13% in white populations.18-20 A recent study also showed differences between Asian and white patients in the genetic architecture of AMD.21
Uncertainty regarding the association between cataract surgery and AMD specifically in Asian populations led us to conduct the present study. South Korea is a newly industrialized country in East Asia and one of the most populous countries in the world. The Korea National Health and Nutrition Examination Survey (KNHANES) is a nationwide, government-led survey that can provide nationally representative estimates of the prevalence of various health conditions.20,22-24 Using the KNHANES database, we aimed to elucidate the association between cataract surgery and AMD in the Korean population.
Question Is cataract surgery associated with a risk for age-related macular degeneration (AMD) in the 2008-2012 Korea National Health and Nutrition Examination Survey (KNHANES)?
Findings In this cross-sectional study of 17 987 participants with 34 863 eyes, analyses showed no association between cataract surgery and any form of AMD (early, late, and all) except in left eyes, where cataract surgery was associated with late AMD.
Meaning The association between cataract surgery and AMD in KNHANES is not clear in the current era of phacoemulsification.
For this study, we analyzed the 5-year (2008-2012) data from the KNHANES, which included the Korean Ophthalmological Society–designed 5-year ophthalmic survey. Detailed survey information has been published.20,22-26 Briefly, the KNHANES is an ongoing population-based, cross-sectional survey in South Korea conducted by the Korea Centers for Disease Control and Prevention and the Korean Ministry of Health and Welfare.20,22-26 For the 2008-2012 KNHANES, 3840 to 4600 households were selected randomly on an annual basis in 192 to 200 postal codes that represented the civilian, noninstitutionalized South Korean population. A rolling sample design yielded a multistage, probability-cluster survey. The KNHANES consists of health interview, health examination, and nutrition surveys20,22,24-26; for this study, we analyzed data from the first 2 surveys. The institutional review board of the Seoul National Bundang Hospital approved this study, which was conducted in accordance with the Declaration of Helsinki.27 Informed consent was waived for this survey-based study.
Using structured slitlamp examinations (BQ-900; Haag-Streit AG), KNHANES ophthalmologists classified cataract status as phakia and postoperative status, including pseudophakia and aphakia (category 1), and as phakia, pseudophakia, and aphakia (category 2).26 Fundus photographs were taken with a nonmydriatic fundus camera (TRC-NW6S, Topcon). Grading of AMD was performed in participants 40 years or older. Participants were defined as having early AMD when the fundus photograph demonstrated the presence of soft indistinct or reticular drusen or the presence of hard or soft distinct drusen with pigmentary abnormalities (increased pigmentation or hypopigmentation of the retinal pigment epithelium) in the absence late AMD signs. Late AMD included the presence of signs of wet AMD or geographic atrophy. Wet AMD was defined as retinal pigment epithelial detachment or serous detachment of the sensory retina, subretinal or sub–retinal pigment epithelial hemorrhages, and subretinal fibrous scars. Geographic atrophy was defined as a discrete circular area (≥175 µm in diameter) of retinal depigmentation with visible choroidal vessels in the absence of wet AMD signs. Each fundus photograph was graded at least twice using the International Age-related Maculopathy Epidemiological Study Group protocol.26,28 Details of AMD grading describing the resolution of discrepancies and interrater reliability have been published.20,24 The Epidemiologic Survey Committee of the Korean Ophthalmological Society verified the ophthalmic survey, including the slitlamp examination results and AMD grading.20,23-25
Data were analyzed from February 5 to August 20, 2015. For the present study, we included participants 40 years or older who had cataract surgery status determined by the slitlamp examination and a gradable fundus photograph of at least 1 eye. Statistical analysis was performed with SAS software (version 9.2; SAS Institute Inc). Multivariate adjusted odds ratios and 95% CIs were assessed separately for the right and left eyes using logistic regression models. For these analyses, KNHANES sample weights were applied to adjust for survey design, nonresponse, and stratification to generate nationally representative population-based results.20,22,24,25 Similar multivariate-adjusted odd ratios and 95% CIs were assessed for right and left eyes combined using generalized estimating equation models, which address correlations of findings within the same participant. Statistical significance was set at P < .05.
Covariates for statistical models were determined based on related studies.20,24,25 The early AMD covariates included age, sex, smoking status (never, former, or current smoker), equalized gross household income (>50% or ≤50% household income according to equalized gross household incomes), educational level (high school or higher or middle school or lower), occupation (white collar, blue collar, or unemployed), medical history of diabetes mellitus and dyslipidemia, body weight (body mass index [calculated as weight in kilograms divided by height in meters squared] ≥25 or <25), presence of hepatitis B surface antigens, and anemia (hemoglobin level, <13 g/dL in men or <12 g/dL in women [to convert to grams per liter, multiply by 10.0]). The late AMD covariates included age, sex, smoking status, and body weight. The analyses for all AMD (early and late AMD) included all covariates for early AMD.
A total of 20 419 eligible individuals 40 years or younger (11 642 women [51.9%] and 5777 men [48.1%]; mean [SE] age, 55.83 [0.14]) participated in the KNHANES during the study period; of these participants, 17 987 had information regarding cataract surgery status and gradable fundus photographs of at least 1 eye. Comparisons between participants who were included and excluded in this study are provided in the eTable in the Supplement. Briefly, excluded participants tended to be older, to have lower income and educational levels, to be unemployed, and to have comorbidities including diabetes mellitus, history of stroke, and anemia compared with participants included in the analyses; the sex ratio, smoking status, history of dyslipidemia, and body weight did not differ between groups.
The right eye analysis included 17 616 eyes, and the left eye analysis included 17 247 eyes. Among these, 1264 right eyes (5.5%) and 1235 left eyes (5.4%) had cataract surgery, and 1056 right eyes (5.0%) and 949 left eyes (4.5%) had signs of any AMD. Table 2 shows detailed characteristics of the participants included in each analysis for the right and left eyes. Thirteen right eyes and 11 left eyes were aphakic; only 1 aphakic right eye showed early AMD, and no other aphakic eyes showed any signs of AMD. Therefore, our analysis could not provide results using category 2 cataract status (phakia, pseudophakia, and aphakia).
An association between cataract surgery and late AMD was observed in the left eyes (odds ratio, 2.34; 95% CI, 1.13-4.85) but not in the right eyes. Cataract surgery was not associated with early AMD or all AMD across all analyses conducted in the right or left eyes using logistic regression models. Cataract surgery was not associated with early, late, or all AMD in both eyes combined using the generalized estimating equation models. Detailed results from category 1 cataract status (phakia and postoperative status) are provided in Table 3.
We assessed the association between cataract surgery and AMD in a nationwide representative sample of the Korean population 40 years and older. To the best of our knowledge, the present study is one of the largest population-based studies in Asian or Anglo-European populations. Our findings suggest that cataract surgery is not associated with AMD; 8 of 9 sets of analysis did not show any association. Although our observed association in left eyes might be owing to chance, large, well-known eye disease cohorts and case-control and cross-sectional studies have suggested that an association between cataract surgery and late AMD exists (Table 1). The Beaver Dam Eye Study3,4 and the Blue Mountains Eye Study5 reported that cataract surgery was associated with AMD progression, particularly for incidences of late AMD, in their follow-up studies and pooled analysis.6 Pollack et al7 reported a higher rate of progression to exudative AMD in eyes that had cataract surgery compared with fellow eyes that did not undergo surgery in their nonrandomized clinical trial, and Kaiserman et al8 reported similar results in a retrospective study.
Cross-sectional studies also reported the association between cataract surgery and late AMD, which included the results of a pooled analysis of 3 cross-sectional studies (the Salisbury Eye Evaluation, the Proyecto VER, and the Baltimore Eye Survey)9 and the Los Angeles Latino Eye Study.10 Conversely, the Rotterdam Study,11 a cohort study, found that cataract surgery increased the risk for dry AMD, unlike the results from the Blue Mountains Eye Study and the Beaver Dam Eye Study. Cataracts, particularly nuclear cataracts, may have a protective effect on AMD development29,30 based on blue light toxicity studies and may be one explanation for the observed different associations.31 Another explanation is that of cataract surgery–related inflammatory responses, which is a cornerstone of AMD pathogenesis.20
However, other studies with primarily clinic-based patient samples have not found an association between cataract surgery and AMD, as the present results suggest (Table 1).12-14 A prospective study by Armbrecht et al12 showed no increased risk for AMD progression after cataract surgery among patients with AMD within 1 year. Similarly, a randomized clinical trial by Hooper et al14 showed no increased 6-month risk for AMD progression among patients with early AMD. Recently, the Age-Related Eye Disease Study, a large, well-known disease-based cohort, could not show a clear effect of cataract surgery on the risk for progression to late AMD.13 In addition, the Australian Cataract Surgery and AMD Study15 investigated this association by paired comparisons between eyes undergoing surgery and fellow eyes that did not in each patient, which inherently addresses between-persons confounding factors; the study also showed no increased risk for developing any AMD (early or late) in eyes undergoing cataract surgery. Wang et al15 suggested that the discrepancies between the results of these studies may derive from differences in comorbidity distributions between clinic-based samples and population-based participants, which may be attributed to a systematic bias of the selected populations in these studies. In cohort studies, relatively low recall rates and mortality on follow-up examinations may be a threat to generalization, and in clinic-based studies, sampled participants may be more prone to have AMD than the healthy general population living in the community.15 The present study, in contrast, analyzed a nationally representative population from the KNHANES, which could minimize any selection bias. In addition, the KNHANES provided comprehensive information for comorbidities for every participant, which helped to address the risk for bias. Therefore, the present results could not be explained by these biases.
Cataract-related inflammation has decreased significantly from the era of extracapsular/intracapsular cataract surgery to the era of phacoemulsification, and with advances in cataract surgery technique, aphakic cataract surgery has also sharply decreased with increasing intraocular lens replacement during cataract surgery. In addition, UV-blocking intraocular lenses have been used widely since the mid-1980s.32 These changes may help to address blue light toxicity and cataract surgery–related inflammatory responses, which have been used to explain the association between cataract surgery and AMD. Moreover, recent advances in diagnostic tools, especially optical coherence tomography, facilitate the evaluation of the retina in individuals with decreased visual acuity. Hence, the likelihood of cataract surgery might decrease in someone with AMD mistakenly believed to have cataract. In addition, ethnic differences may provide another biological explanation, because very little is known about Asian populations regarding the association between cataract surgery and AMD. Darker irises and retinal pigment epitheliums may affect AMD progression in eyes with cataract surgery, although these associations were not clearly confirmed.33 Moreover, clinical characteristics of Asian AMD (uncommon drusen in early AMD and a higher proportion of polypoidal choroidal vasculopathy in exudative AMD) might be associated with AMD pathogenesis as related to cataract surgery status.18-20
The strengths notwithstanding, the present study has several limitations. First, the study design is cross-sectional in nature, which could not address the temporal relationship of cataract surgery and AMD. The present results cannot be interpreted as a causal relationship. Second, the KNHANES included only noninstitutionalized individuals, and of these participants, the present study included the participants who had cataract surgery and AMD grading. Therefore, the eligibility criteria of the KNHANES and this study might affect the analyses of association. Third, among eligible participants, those younger than 50 years were expected to have a low prevalence of AMD and cataract surgery, which might affect the analyses of association. However, although AMD and cataract surgery are scarce among persons in their 40s, numerous cohort and cross-sectional studies included the participants 40 years or older in their analyses for the association.4,9,16,17,34 In addition, the KNHANES provides AMD grading in participants 40 years or older so that all studies regarding AMD epidemiology using the KNHANES database set the eligible participants to 40 years or older, as in our present study and previous studies.20,24 Moreover, the KNHANES classified any geographic atrophy, not central geographic atrophy, as late AMD according to the grading protocol and did not provide the raw data (eg, fundus photographs) to the researchers. Thus, all published AMD epidemiologic studies using the KNHANES database used the same AMD grading,20,23,25,26 as was the case for our analyses. Fourth, we estimated the association between cataract surgery and AMD while accounting for person-level covariates through generalized estimating equation models. However, we did not implement survey weights in these models because the standard survey procedure of the SAS software does not support paired-eye analysis. Fifth, individuals with unrecognized AMD might undergo the cataract surgery when incorrectly attributing decreased visual acuity to cataract. This event might influence the analyses to a certain degree, although it might not weaken the present results. Sixth, the analyses could not assess the effect of aphakia because aphakic eyes were scarce in the database. However, given advances in cataract surgery techniques and intraocular lenses, aphakic condition effects have become less important, as discussed above.
The association between cataract surgery and AMD was not clear in this representative Korean population. Because recent studies reported that most patients with AMD had better visual function and quality of life after undergoing cataract surgery,35 we expect the results of the present study to help guide cataract surgery in Asian patients with AMD. Further longitudinal studies are warranted to assess the causal association between cataract surgery and AMD in Asian populations.
Corresponding Author: Kyu Hyung Park, MD, PhD, Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam-Si, Gyeonggi-Do, 463-707, South Korea (firstname.lastname@example.org).
Submitted for Publication: November 17, 2015; final revision received February 4, 2016; accepted February 8, 2016.
Published Online: March 31, 2016. doi:10.1001/jamaophthalmol.2016.0453.
Author Contributions: Dr S. J. Park and Ms Lee contributed equally to this work. Drs S. J. Park and K. H. Park had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: S. J. Park, Lee.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: S. J. Park, Lee.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: S. J. Park, Lee, Ahn.
Obtained funding: S. J. Park, Lee.
Administrative, technical, or material support: S. J. Park, Lee, K. H. Park.
Study supervision: S. J. Park, Lee, K. H. Park.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Funding/Support: This study was supported by grant NRF-2015R1D1A1A02062194 from the National Research Foundation of Korea, awarded by the Ministry of Education, Science, and Technology.
Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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