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A Double-Blind Randomized Controlled Trial

Lagstein, Oded MD*,†; Ben-Artzi, Noa BMedSc; Achiron, Asaf MD*,†; Nemet, Achia BMedSc; Khreish, Maroun MD*; Bartov, Elisha MD*,†; Burgansky-Eliash, Zvia MD*,†

doi: 10.1097/IAE.0000000000001397
Original Study

Purpose: To evaluate the efficacy of topical apraclonidine in reducing pain and subconjunctival hemorrhage (SCH) after intravitreal injections (IViT).

Methods: A prospective, randomized, double-blinded study. Thirty-nine patients were examined twice, at each monthly IViT of 1.25 mg/0.05 mL bevacizumab. Patients were randomly assigned to receive either topical apraclonidine 0.5% or placebo to the treated eye, 30 minutes before the first IViT. At their second IViT, the intervention was switched. Thirty minutes after the injection, SCH size was measured by a slit lamp, and pain was assessed by the numerical rating scale (NRS-11).

Results: Mean pain score was 1.69 (SD ±1.44) in the apraclonidine group and 3.28 (SD ±2.27) in the control group (P < 0.001). Phakic patients had a greater pain reduction after topical apraclonidine (P < 0.001). Subconjunctival hemorrhage incidence was 41% in the apraclonidine group and 51.3% in the control group (P = 0.503). Mean SCH size was 1.71 mm2 (SD ±5.83) in the apraclonidine group and 3.25 mm2 (SD ±6.41) in the control group (P = 0.253). After topical apraclonidine, there was a smaller reduction in SCH size in patients with choroidal neovascularization or hypertension (P = 0.003 and 0.044, respectively), and a greater reduction in phakic patients (P = 0.048).

Conclusion: Topical apraclonidine 0.5%, administered 30 minutes before IViT, significantly decreased pain by a factor of 1.94. It did not decrease the incidence or size of SCH in the entire cohort, but only in several subpopulations.

Anti–vascular endothelial growth factor agents are a common and effective treatment for various retinal pathologies, but they are still delivered by intravitreal injections, making patient inconvenience and noncompliance potential barriers to treatment. Topical apraclonidine reduces pain after intravitreal injections and could increase patients' compliance and satisfaction.

*Department of Ophthalmology, The Edith Wolfson Medical Center, Holon, Israel;

The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; and

The Hebrew University Hadassah Medical School, Jerusalem, Israel.

Reprint requests: Oded Lagstein, MD, Department of Ophthalmology, The Edith Wolfson Medical Center, 62 Halochamim Street, Holon 58100, Israel; e-mail:

Presented at the 15th EURETINA Congress, Nice, France, September 17–20, 2015.

None of the authors has any financial/conflicting interests to disclose.

The study was performed with informed consent and following all the guidelines for experimental investigations required by the Institutional Review Board or Ethics Committee of the Wolfson Medical Center.

© 2017 by Ophthalmic Communications Society, Inc.