Findings from a recent study published in Ophthalmology found that eyes receiving repeated intravitreal anti-vascular endothelial growth factor (VEGF) injections are at significantly increased risk of developing cataracts requiring surgery.
The 10-year cumulative incidence of cataract surgery reached 40.7% in injected eyes, compared with just 7.2% in the untreated fellow eyes of the same patients.
Give me some background first.
Anti-VEGF injections are the mainstay of treatment for multiple retinal diseases, including wet age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO).
The agents—which include bevacizumab, ranibizumab, aflibercept, and brolucizumab—are administered directly into the vitreous cavity, often on a monthly or near-monthly basis for years at a time.
Cataract formation has long been recognized as a known complication of intravitreal injections.
Go on ..
But the direct relationship between anti-VEGF treatment and cataract development has been hard to pin down clinically, in part because the patients receiving these injections tend to be older adults who are already at high risk of cataracts on their own.
- The open question: Is it the injections themselves driving lens changes, or is it simply an overlap in demographics?
This study set out to isolate the injection variable by using each patient's untreated fellow eye as the control.
Now, talk about the study.
A team based in South Korea designed a retrospective, interventional case series to evaluate the association between intravitreal anti-VEGF injections and incident cataract surgery.
The approach: Investigators selected patients who were phakic in both eyes at baseline but received unilateral anti-VEGF injections (≥12 injections in one eye only).
- This allowed them to compare outcomes between the injected eye and the fellow eye within the same individual, controlling for systemic risk factors like age, diabetes status, and medication use.
Electronic medical records were analyzed using Kaplan-Meier survival analysis to assess cumulative incidence of cataract surgery over time. Lens opacity grades at the time of surgery and changes in best-corrected visual acuity (BCVA) were also evaluated.
Who was included in the study?
The study included 603 bilateral phakic patients who received ≥12 unilateral anti-VEGF injections. Data spanned 15 years, from 2010 to 2025, and was obtained through electronic medical records.
- Follow-up: Median follow-up was 74 months.
- Indications: 79.6% of participants had wet AMD, while 20.4% presented with macular edema secondary to RVO.
- Anti-VEGF injections included bevacizumab, ranibizumab, aflibercept, or brolucizumab
- Frequency: Administered as three loading doses a month, followed by either an as-needed or treat-and-extend regimen.
Findings?
Of the 603 patients, 225 received cataract surgery. Of those, 194 (32.2%) were operated on in only the injected eye, eight (1.3%) in the non-injected eye, and 23 (3.8%) in both eyes.
The headline number: The 10-year cumulative incidence of cataract surgery was 40.7% (95% CI, 35.9 to 45.1) in injected eyes versus 7.2% (95% CI, 4.1 to 10.3) in fellow eyes. Roughly a six-fold difference.
On hazard analysis, the injected eye carried a hazard ratio (HR) of 8.174 (95% CI, 5.767 to 11.586) for cataract surgery compared with the fellow eye.
- Older age was also independently associated with increased risk (HR, 1.069; 95% CI, 1.052 to 1.086).
Tell me more.
At the time of surgery, all lens opacity grades, including nuclear, cortical, and posterior subcapsular, were significantly higher in injected eyes (all p < 0.001).
- The greatest difference was observed in posterior subcapsular opacity.
Why?
Posterior subcapsular cataracts are the type most commonly associated with inflammation and trauma.
That pattern aligns with the proposed mechanism here: repeated needle entry into the eye causing inadvertent contact with the lens or zonules.
Any limitations?
This was a retrospective case series from a single institution, which limits the ability to draw causal conclusions. There was also no randomization, and selection of which eye received injections was determined by disease status, not controlled assignment.
Other considerations:
- The study used cataract surgery as a surrogate for clinically significant cataract development
- Patients who developed cataracts but did not proceed to surgery would not have been captured
- Individual injection counts, agent switches, and retreatment intervals were not reported as stratified variables, limiting the ability to assess whether certain protocols carry more risk than others
Expert opinion?
The authors attributed the association to several possible causes:
- They pointed to inadvertent physical trauma to the lens or zonules during the injection procedure as a primary mechanism.
- Intraocular inflammation (uveitis), which they noted as a well-established risk factor for cataract development, was also flagged as a contributing pathway.
Their position: Retina specialists should become more attentive to how they administer injections, and the injection process itself may need refinement to reduce the risk of mechanical damage to the lens.
Anything else?
The within-patient study design is a notable strength.
Because both the injected and fellow eyes came from the same individual, systemic confounders like age, cardiovascular status, and metabolic disease were inherently controlled.
- That makes the six-fold difference harder to dismiss as coincidence.
And the bigger picture?
These findings add to a growing body of evidence on the downstream effects of repeated anti-VEGF injections.
T2D A large Canadian study presented at the 2024 American Academy of Ophthalmology (AAO) annual meeting analyzed over 163,000 patients with retinal conditions who underwent cataract surgery and found that those with a prior anti-VEGF injection history faced higher rates of complications during the procedure itself, including vitreous hemorrhage, retained lens fragments, and retinal detachment.
How interesting … and now: the takehome.
For retina specialists administering repeated anti-VEGF injections: cataract development in the treated eye appears to be a real and dose-dependent risk, not just an age-related coincidence.
Counseling patients about this possibility, particularly those on long-term injection protocols, is warranted.
In practice: When these patients do present for cataract surgery, their injection history is worth flagging for the cataract surgeon, given the accumulating evidence of both increased cataract incidence and higher surgical complication rates in this population.