ADVANCED AMD

The Age-Related Eye Disease Study 2 (AREDS2) provides no evidence that cataract surgery increases the risk of progression to late age-related macular degeneration (AMD) in eyes at high risk, reported Emily Y Chew MD at the 2015 annual meeting of the Association for Research in Vision and Ophthalmology in Denver, USA.

“Understanding if cataract surgery affects the risk of progression to advanced AMD is important for us to move forward with our clinical recommendations for patients with AMD, and the data from AREDS2 are reassuring,” said Dr Chew, chair of AREDS2, and Deputy Director, Division of Epidemiology and Clinical Applications and Deputy Clinical Director, National Eye Institute, Bethesda, Maryland, USA.

“Still, patients who are at risk for developing advanced AMD must be warned about their risk for progression regardless of cataract surgery. The opportunity for vision improvement with anti-VEGF therapy for neovascular AMD makes it compelling for us to watch these patients very carefully after cataract surgery,” she said.

The AREDS2 analyses included only eyes that were phakic and without late AMD at baseline. In addition, cases (eyes that underwent cataract surgery) had to be free of late AMD at the time of surgery and have at least two years of follow-up after surgery. The controls were eyes that never had cataract surgery during the study.

Three different approaches were used for the analyses – matched pair, Cox proportional hazard models with time-dependent covariates, and logistic regression using general estimating equations. For each type of analysis, four different outcomes were investigated – progression to any late AMD, neovascular AMD, central geographic atrophy, or any geographic atrophy. In addition, the Cox proportional hazards regression model looked separately at right and left eyes.

The matched pair analysis included 912 cases matched to the same number of controls based on multiple criteria: age group at time of surgery, smoking status, gender, race, AREDS assignment to lutein/zeaxanthin, AMD status at baseline and severity at surgery (cases only), neovascular AMD status in the fellow eye before cataract surgery, and length of follow-up after surgery.

The results of the matched pair analysis were consistent in showing no harmful effect of cataract surgery. For all four outcomes, there were far fewer eyes with progression among the cases compared to the controls. In all of the other analyses as well, no statistically significant differences emerged that would suggest cataract surgery adversely affected the risk of progression to late AMD or any of its components, Dr Chew reported.

Reviewing the literature

Previous studies examining whether cataract surgery affects the risk of progression to late AMD provided conflicting results. Population-based epidemiologic studies, including the Beaver Dam Eye Study, Blue Mountains Eye Study, Baltimore Eye Survey, Rotterdam Eye Study, and others, suggested that cataract surgery was a risk factor. In contrast, Dr Chew and colleagues found no strong evidence that cataract surgery increased the risk of progression to late AMD when analysing data from the AREDS using almost the same statistical approaches employed in the AREDS2 analyses.

“In AREDS, the totality of the evidence suggested there was no major deleterious effect of cataract surgery on the risk of progression to late AMD,” she said.

The Australian Cataract Surgery and Age-related Macular Degeneration Study also found no harmful effect of cataract surgery on progression to advanced AMD. It was a prospective study designed to specifically address the question of whether cataract surgery increased risk of progression to advanced AMD and used a paired eye comparison, including patients who had cataract surgery in one eye and remained phakic in the fellow eye for at least two years.

Resolving the conflicts

Dr Chew offered several possible explanations for why the AREDS2 results differ from the findings in the population-based research. She noted the potential for unadjusted confounding in the latter studies and differences in their pool of “cases”. Cases in some of the epidemiologic studies were eyes with a history of cataract surgery at enrolment, and in the epidemiologic studies that looked at eyes with incident cataract surgery, it is presumed the recommendation for cataract surgery was made by a general ophthalmologist.

“In AREDS2, patients were examined by a retina specialist who may have not recommended cataract surgery for a patient
whose vision loss was thought to be related to retinal disease,” Dr Chew explained.

Cataract surgery and intraocular lens (IOL) technology have also changed over the years. “Clearly, in AREDS2 we were in a different age in terms of better cataract surgery techniques, and patients in AREDS2 are also more likely to have been implanted with a UVB-blocking IOL, which may have an effect on AMD progression,” Dr Chew said.

As another difference, the participants in AREDS2 are healthy volunteers. “The AREDS2 population may be different than the participants in a population-based study, and perhaps a limitation of AREDS2 is that it is not a population-based cohort,” Dr Chew said.

Regardless of the results of the studies, such patients are at high risk for developing advanced AMD and should be followed vigilantly following cataract surgery.

Emily Y Chew: echew@nei.nih.gov