Introduction
Cataract surgery has been scrutinized for its potential role in the progression of nonneovascular age-related macular degeneration (AMD) to neovascular AMD (nAMD). However, conflicting reports challenge this association.1–3 This study aimed to assess the risk of nAMD following cataract surgery.
Methods
This retrospective cohort study used 2006 to 2025 data from TriNetX US Collaborative Network. The Western IRB deemed the study exempt from review and informed consent because it involved deidentified data and no participant interaction.
Two cohorts of adults 60 years or older without pseudophakia (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code Z96.1) were compared for their risk of nAMD diagnosis: (1) patients who underwent cataract extraction with intraocular lens implantation (Current Procedural Terminology [CPT] codes 66982, 66983, and 66984) and (2) controls with no record of cataract surgery. Index date was the procedure date for surgical patients and any ophthalmologic encounter date (CPT code 1012793) for controls. Secondary analysis of neovascular conversion risk was restricted to patients with nonneovascular AMD. Comparison between manual and mechanical cataract extraction was not feasible because these techniques lacked separate CPT codes.
Propensity score matching (PSM) balanced demographics and comorbidities (Supplement 1). Risk ratios (RRs) and 95% CIs were estimated at 1, 3, 6, 12, 18, and 24 months. Since TriNetX provides only 95% CIs and alternative levels cannot be specified, we predefined an association as significant when the 95% CI was lower than 0.90 or higher than 1.10 to account for multiple comparisons and reduce consequences of minor fluctuations, as performed in similar studies.4 eTable 2 in Supplement 1 provides query codes. Analysis was performed through TriNetX; the figure was generated using Python 3.11 (Python Software).
Results
Overall, 132 122 patients with cataract surgery and 407 579 controls were identified. After PSM, 122 384 individuals remained in each cohort (mean [SD] age, 70.9 [6.6] years; 142 925 females [58.4%]). The nonneovascular AMD subgroup comprised 14 340 surgical patients and 30 242 controls, with 14 049 per group after PSM.
Risk of nAMD was nonsignificant at all time points (Figure), starting at 0.11% in patients vs 0.11% in controls at 1 month (RR, 1.05; 95% CI, 0.82–1.33) and reaching 0.90% vs 0.79%, respectively, at 24 months (RR, 1.14; 95% CI, 1.04–1.24) (Table). The 95% CI remained within the predefined nonsignificance range, suggesting that the RR was likely a statistical variability rather than a true outcome. Among the nonneovascular AMD group, decreased conversion risk was observed at 3 months (RR, 0.71; 95% CI, 0.56–0.89), but this decline did not persist at subsequent time points. This pattern likely reflects small, early event differences and expected variability in this higher-risk subgroup rather than a true protective benefit.
Figure 1.
Risk ratios (RR) and 95% confidence intervals (shaded areas) for a new diagnosis of neovascular age-related macular degeneration (AMD) at 1, 3, 6, 12, 18, and 24 months following cataract surgery. The red line represents the overall population, while the green line represents patients with pre-existing dry AMD. The gray shaded area marks the non-significance zone (RR 0.9–1.1).
Table 1.
Number of patients, events, and risk ratios (RR) with 95% confidence intervals (CI) for new diagnoses of neovascular age-related macular degeneration (AMD) at 1, 3, 6, 12, 18, and 24 months after cataract surgery, shown for the overall population and for the subgroup of patients with pre-existing dry AMD.
| Cohort | Patients in cohort | Patients with outcome | Risk Ratio (95% CI) | ||
|---|---|---|---|---|---|
| 1 Month | |||||
| Overall | Cataract Surgery | 118,713 | 136 | 1.05 (0.82–1,33) | |
| Control | 118,640 | 130 | |||
| Dry AMD | Cataract Surgery | 11,677 | 56 | 0.67 (0.48–0.94) | |
| Control | 11,483 | 82 | |||
| 3 Months | |||||
| Overall | Cataract Surgery | 118,713 | 303 | 1.14 (0.97–1.35) | |
| Control | 118,640 | 265 | |||
| Dry AMD | Cataract Surgery | 11,677 | 123 | 0.71 (0.56–0.89) | |
| Control | 11,483 | 171 | |||
| 6 Months | |||||
| Overall | Cataract Surgery | 118,713 | 471 | 1.25 (1.10–1.44) | |
| Control | 118,640 | 375 | |||
| Dry AMD | Cataract Surgery | 11,677 | 215 | 0.80 (0.67–0.96) | |
| Control | 11,483 | 264 | |||
| 12 Months | |||||
| Overall | Cataract Surgery | 118,713 | 696 | 1.16 (1.04–1.30) | |
| Control | 118,640 | 598 | |||
| Dry AMD | Cataract Surgery | 11,677 | 361 | 0.83 (0.73–0.96) | |
| Control | 11,483 | 426 | |||
| 18 Months | |||||
| Overall | Cataract Surgery | 118,713 | 893 | 1.14 (1.04–1.26) | |
| Control | 118,640 | 780 | |||
| Dry AMD | Cataract Surgery | 11,677 | 494 | 0.85 (0.76–0.96) | |
| Control | 11,483 | 570 | |||
| 24 Months | |||||
| Overall | Cataract Surgery | 118,713 | 1,064 | 1.14 (1.04–1.24) | |
| Control | 118,640 | 935 | |||
| Dry AMD | Cataract Surgery | 11,677 | 577 | 0.87 (0.78–0.97) | |
| Control | 11,483 | 652 | |||
RRs <0.90 or >1.10 were considered statistically significant.
Discussion
The association between cataract surgery and neovascular AMD progression remains debated.2,5 Some studies have proposed that cataract removal increases retinal exposure to blue and UV light, potentially promoting oxidative stress, or that surgery may cause a proinflammatory microenvironment, facilitating the migration of proangiogenic factors to the macula.1 Although a meta-analysis deemed its data insufficient to draw definitive conclusions,5 most studies have found no significant risk increase.2,3,6 A study comparing operated vs fellow eyes reported no increased risk over a 3-year period.6 Furthermore, the Age-Related Eye Disease Study (AREDS) and AREDS2 trials concluded that cataract surgery did not affect progression to nAMD.3
Study limitations include our dependence on ICD-10 and CPT code accuracy because TriNetX lacks detailed imaging, disease severity, and laterality data. Thus, unmeasured factors (eg, external cataract surgery; AREDS supplements use) could not be accounted for and may have affected outcomes.
Our findings are consistent with studies that found no increased risk of AMD progression following cataract surgery.2,3,6 While some ophthalmologists may hesitate to recommend surgery to patients with advanced AMD due to concerns about disease progression but limited visual gains, we found those concerns may be unwarranted. Further, even retrospective, studies might inform clinicians’ advice to patients.
Supplementary Material
Online Supplemental Materials: Baseline cohort characteristics after propensity score matching (Supplemental Table 1). List of Common Procedural Terminology (CPT) and International Classification of Diseases, Tenth Revision (ICD-10) codes used for inclusion/exclusion criteria, assessing outcomes, and propensity matching (Supplemental Table 2).
Acknowledgments
a. Funding/Support:
This project was supported in part by the Clinical and Translational Science Collaborative (CTSC) of Cleveland which is funded by the National Institutes of Health (NIH), National Center for Advancing Translational Science (NCATS), Clinical and Translational Science Award (CTSA) grant, UL1TR002548.
b. Financial Disclosures:
DCK reports consulting fees from Dynavax Technologies Corporation. SKS reports grants from Regeneron, Eyevensys, Eyepoint, and Gilead, and consulting fees from Adverum, Novartis, Zeiss, and Bausch and Lomb. SS reports consulting fees from 4DMT, Alimera, Abbvie, Apellis, Astellas, Bausch and Lomb, Clearside, Eyepoint, Harrow, Genetech/Roche, Kodiak, Merck, Regeneron, RegenXBio, Ripple, Volk, and Zeiss with contracted research support from Acelyrin, Gilead, Genetech/Roche, Santen, IONIS, and Kodiak. All other authors declare no financial disclosures or conflicts of interest.
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