INTRAVITREAL AFLIBERCEPT INJECTION FOR CHOROIDAL NEOVASCULARIZATION DUE TO PRESUMED OCULAR HISTOPLASMOSIS SYNDROME The HANDLE Study

Purpose: To evaluate intravitreal aflibercept injection (IAI) in patients with presumed ocular histoplasmosis syndrome and choroidal neovascularization. Methods: Open-label randomized Phase I/II study of IAI in patients with presumed ocular histoplasmosis syndrome-related choroidal neovascularization. Thirty-nine eyes from 39 patients were randomized in a 1:1 ratio to 2 groups. The Sustained Group eyes (n = 19) underwent monthly IAI for 3 months, then mandatory IAI every 2 months for 12 months (with an option for monthly PRN dosing, if needed). The PRN Group eyes (n = 20) received 1 IAI at randomization, then monthly PRN IAI for 12 months. Results: Thirty-nine eyes (19 eyes Sustained Group and 20 eyes PRN Group) were randomized. Average age of participants was 50 years (19-75), with 16 men and 23 women. Ten, 12, and 17 eyes demonstrated extrafoveal, juxtafoveal, and subfoveal choroidal neovascularization, respectively. All eyes in both groups received IAI at baseline, with the Sustained and PRN groups receiving on an average 7.5 (5-11) and 4.6 (1-10) injections, respectively, over the 12 months. At baseline, overall average visual acuity was 68 letters (13-87 letters) with Snellen equivalent of 20/42 (20/20-20/160). At 12-month follow-up, Sustained Group's average visual acuity was 84.9 letters (74-94) and Snellen equivalent was 20/21 (20/13-20/32), indicating an average improvement of 12 letters (6 letters loss to 36 letters gain) (P < 0.01). The PRN Group's 12-month average visual acuity was 80.9 letters (60-94) and Snellen equivalent was 20/26 (20/13-20/63), indicating an average gain of 19 letters (4-75) (P < 0.01). Mean baseline central subfield thickness (CST) was 374 mu m and mean 1-year CST was 260 mu m (P < 0.01) among all study participants. The Sustained Group's mean baseline CST was 383 mu m and mean 12-month CST was 261 mu m (P < 0.01). Mean baseline CST of the PRN Group was 360.8 mu m with the final mean CST of 260.5 mu m (P < 0.01). No reported endophthalmitis, retinal tears, detachments, vitreous hemorrhage, nor adverse thrombotic events were reported. Conclusion: Intravitreal aflibercept resulted in improved visual and anatomical outcomes with a favorable safety profile. PRN IAI dosing required less injections with similar visual and anatomical outcomes compared with sustained dosing.