<p>Incidence of Glaucoma or Ocular Hypertension After Repeated Anti-Vascular Endothelial Growth Factor Injections for Macular Degeneration</p>

Abstract

Purpose: To estimate the risk of glaucoma or sustained ocular hypertension (OHT) related to anti-vascular endothelial growth factor (VEGF) injections for age-related macular degeneration (AMD). Design: Retrospective chart review. Subjects: Patients who received unilateral anti-VEGF injections for AMD at the Wheaton Eye Clinic (IL). Methods: Chart analysis was performed on 1095 patients, without prior glaucoma or OHT, who received unilateral anti-VEGF injections for AMD from 2005 to 2012, with data collected through 2013. Data collection included demographics, lens status, date and medication type of each injection, and the date of diagnosis of glaucoma or OHT by a treating glaucoma specialist, which was the main outcome measure. Rare events logistic regression was performed to determine the risk of disease development based on sex, lens status, and injection frequency. Results: Unilateral glaucoma or sustained OHT developed in 42 patients over the course of follow-up, with 40 events in the injected eye only, 2 in the contralateral eye only. Statistical modeling predicted elevated risk for onset of glaucomatous disease with a higher maximum frequency of injections (p < 0.0001, odds ratio [OR] 2.18 for each additional injection over the most injection-intense 6 months for a given subject) and with phakic lens status (p = 0.0009, OR 0.33 for pseudophakia). Conclusion: Our results show a significant risk for glaucoma or OHT development in patients undergoing repeated treatments with intravitreal anti-VEGF injections for AMD, establishing the first reliable connection between disease development and a period of highfrequency injections. In addition, we show a significantly increased risk of disease development in phakic patients, which we believe points to a mechanical explanation for this type of secondary glaucoma.

Intraocular Pressure–Related Events After Anti–Vascular Endothelial Growth Factor Therapy for Macular Edema Due to Central Retinal Vein Occlusion or Hemiretinal Vein Occlusion

“…Patients in the present study underwent a less intensive pattern of injection therapy compared with the patients reported by Wingard et al The latter study also showed a higher frequency of events in phakic individuals, and the present report shows a similar trend ( P = .07; Table 1). Wingard and colleagues hypothesize that repeated intravitreal anti-VEGF injections lead to a pressure imbalance between the anterior and posterior segments in individuals with a phakic lens and that this strains the eye’s outflow system, leading to compromised outflow facility. This issue deserves further study because individuals with a phakic lens may require closer monitoring in the setting of intravitreal injection therapy.…”

“…The present study did not find a significant association between the cumulative number of anti-VEGF injections and the proportion of eyes with an IOP-related event, but we did find a greater number of IOP-related events in individuals who received intravitreal anti-VEGF therapy beyond 12 months. Wingard and colleagues 18 predicted an elevated risk for glaucoma or ocular hypertension with higher injection frequency using statistical modeling. Patients in the present study underwent a less intensive pattern of injection therapy compared with the patients reported by Wingard et al 18 The latter study also showed a higher frequency of events in phakic individuals, and the present report shows a similar trend (P = .07; Table 1).…”

“…Wingard and colleagues 18 predicted an elevated risk for glaucoma or ocular hypertension with higher injection frequency using statistical modeling. Patients in the present study underwent a less intensive pattern of injection therapy compared with the patients reported by Wingard et al 18 The latter study also showed a higher frequency of events in phakic individuals, and the present report shows a similar trend (P = .07; Table 1). Wingard and colleagues 18 hypothesize that repeated intravitreal anti-VEGF injections lead to a pressure imbalance between the anterior and posterior segments in individuals with a phakic lens and that this strains the eye's outflow system, leading to compromised outflow facility.…”

Ocular adverse events associated with anti-VEGF therapy: A pharmacovigilance study of the FDA adverse event reporting system (FAERS)

“…Clinical ophthalmologists are also concerned about the increase of intraocular pressure after the administration of anti-VEGF drugs. A retrospective study estimated the risk of glaucoma or sustained ocular hypertension related to anti-VEGF treatment for neovascular AMD, and found that the rate of injection and lens status are associated with intraocular pressure (Wingard et al, 2019). As the zonular system attached to the lens is fragile, the presumption is that the anterior chamber volume compresses with anterior movement of the lens and iris and thus, may strain the outflow apparatus, and cause increase in intraocular pressure (Kerimoglu et al, 2015).…”

Prophylaxis with intraocular pressure lowering medication and glaucomatous progression in patients receiving intravitreal anti-VEGF therapy

“…Some recent studies align with the mechanical theory that injections could damage the outflow apparatus through repeated compressions of the anterior chamber (AC) volume, straining the outflow system particularly in phakic eyes. Wingard et al [25] reported that an elevated risk of glaucomatous disease was associated with higher injection frequency and phakic lens status. Studies by Wen et al [26] and Arslan et al [27] showed that post-injection AC angle narrowing and decrease in AC depth were related to phakic lens status, and that outflow facility was reduced by 12% in eyes receiving 20 or more injections compared to fellow untreated eyes.…”