Introduction
Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents have become the gold standard for treating various retinal vascular diseases, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). While these therapies are highly effective in preserving and improving visual acuity, their long-term safety profile regarding the anterior segment remains a subject of investigation. This report analyzes the clinical impact of chronic anti-VEGF administration on the development and progression of cataracts leading to surgical intervention.
Patient Information
The study cohort comprised 603 patients who were phakic (retaining their natural crystalline lens) in both eyes at the start of treatment. These patients were monitored over a median follow-up period of 74 months. Inclusion criteria required patients to have received a minimum of 12 unilateral anti-VEGF injections (ranibizumab or aflibercept) in a designated “injected eye,” while the “fellow eye” remained untreated, serving as an internal control for each patient. The demographic profile included a broad age range, with statistical analysis accounting for the influence of aging on cataract formation.
Diagnosis
The primary diagnosis addressed is the development of clinically significant cataract secondary to, or accelerated by, chronic intravitreal injections. Diagnosis was confirmed through slit-lamp biomicroscopy, where lens opacities were graded using standardized clinical scales. The study specifically identified a dramatically higher 10-year cumulative incidence of cataract surgery in injected eyes (40.7%; 95% CI, 35.9-45.1) compared to fellow eyes (7.2%; 95% CI, 4.1-10.3). The diagnosis was further characterized by the distribution of opacity types, with injected eyes showing significantly higher grades of nuclear, cortical, and posterior subcapsular opacities.
Differential Diagnosis
In evaluating the progression of cataracts in these patients, several differential factors were considered:
- Primary Age-Related Cataract: While aging is the most common cause of cataracts, the significant disparity between the injected and fellow eyes (Hazard Ratio [HR] of 8.174) suggests that age alone does not account for the accelerated progression in the treated eye.
- Corticosteroid-Induced Cataract: Patients receiving adjunctive steroid treatments for retinal conditions often develop posterior subcapsular cataracts. This was ruled out or controlled for by focusing on the specific impact of anti-VEGF monotherapy.
- Diabetic Cataract: Metabolic changes in diabetic patients can accelerate lens clouding; however, the unilateral nature of the treatment in this cohort allowed for the isolation of the injection process as the primary variable.
- Traumatic Cataract: Direct needle-to-lens trauma during the injection procedure is a known complication, though rare in experienced hands.
Treatment and Management
The management protocol involved continuous monitoring of lens clarity during the course of anti-VEGF therapy. When cataract progression reached a point where it significantly impaired the patient’s visual acuity or interfered with the monitoring of the underlying retinal pathology, surgical intervention was performed. The treatment of choice was phacoemulsification with intraocular lens (IOL) implantation. Management also included optimizing the ocular surface and ensuring stable intraocular pressure post-injection. The decision-making process for surgery was based on the balance between the benefits of improved anterior segment clarity and the potential risks of exacerbating macular edema during the perioperative period.
Outcome and Prognosis
The long-term outcome revealed a substantial increase in the necessity for cataract surgery in eyes receiving chronic anti-VEGF treatment. The injected eye was associated with a Hazard Ratio of 8.174 (95% CI 5.767-11.586) for undergoing surgery. Older age was also a significant risk factor (HR, 1.069). Interestingly, at the time of surgery, the most pronounced difference in opacity type was found in the posterior subcapsular (PSC) region (p < 0.001). Following cataract surgery, patients generally experienced a significant improvement in best-corrected visual acuity (BCVA), assuming the underlying retinal condition remained stable.
Discussion
The findings of this large-scale retrospective series suggest a strong association between the frequency and duration of anti-VEGF injections and the development of surgically significant cataracts. Several mechanisms may explain this phenomenon. First, the mechanical trauma or the transient increase in intraocular pressure during repeated injections may disrupt lens metabolism. Second, the suppression of VEGF—which is naturally present in the aqueous humor—may interfere with the normal homeostasis of the lens, as VEGF is thought to play a role in the health of the anterior segment vasculature and nutrient exchange. The specific prevalence of posterior subcapsular opacities is particularly noteworthy, as this type of cataract typically has a more rapid impact on visual function and is frequently associated with secondary causes, such as medications or trauma.
Clinicians should be aware of this increased risk when counseling patients starting long-term anti-VEGF therapy. Regular monitoring of lens status is essential, and patients should be informed that while the injections are necessary to save their central vision, they may hasten the need for cataract surgery. Future research should focus on whether specific anti-VEGF agents or different injection intervals carry varying levels of risk.
References
- Choi J, Choi E, Kang SW, et al. Impact of intravitreal anti-vascular endothelial growth factor injections on cataract development. Ophthalmology. 2026. PMID: 41825596.
- American Academy of Ophthalmology. Preferred Practice Patterns: Age-Related Macular Degeneration.
- Rosenfeld PJ, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006.