To test the hypothesis that tolerating some subretinal fluid (SRF) in patients with neovascular agerelated macular degeneration (nAMD) treated with ranibizumab using a treat-and-extend (T&E) regimen can achieve similar visual acuity (VA) outcomes as treatment aimed at resolving all SRF.Design: Multicenter, randomized, 24-month, phase 4, single-masked, noninferiority clinical trial.Participants: Participants with treatment-naïve active subfoveal choroidal neovascularization (CNV). Methods: Participants were randomized to receive ranibizumab 0.5 mg monthly until either complete resolution of SRF and intraretinal fluid (IRF; intensive arm: SRF intolerant) or resolution of all IRF only (relaxed arm: SRF tolerant except for SRF >200 mm at the foveal center) before extending treatment intervals. A 5-letter noninferiority margin was applied to the primary outcome.Main Outcome Measures: Mean change in best-corrected VA (BCVA), and central subfield thickness and number of injections from baseline to month 24.Results: Of the 349 participants randomized (intensive arm, n ¼ 174; relaxed arm, n ¼ 175), 279 (79.9%) completed the month 24. The mean change in BCVA from baseline to month 24 was 3.0 letters (standard deviation, 16.3 letters) in the intensive group and 2.6 letters (standard deviation, 16.3 letters) in the relaxed group, demonstrating noninferiority of the relaxed compared with the intensive treatment (P ¼ 0.99). Similar proportions of both groups achieved 20/40 or better VA (53.5% and 56.6%, respectively; P ¼ 0.92) and 20/200 or worse VA (8.7% and 8.1%, respectively; P ¼ 0.52). Participants in the relaxed group received fewer ranibizumab injections over 24 months (mean, 15.8 [standard deviation, 5.9]) than those in the intensive group (mean, 17 [standard deviation, 6.5]; P ¼ 0.001). Significantly more participants in the intensive group never extended beyond 4-week treatment intervals (13.5%) than in the relaxed group (2.8%; P ¼ 0.003), and significantly more participants in the relaxed group extended to and maintained 12-week treatment intervals (29.6%) than the intensive group (15.0%; P ¼ 0.005).Conclusions: Patients treated with a ranibizumab T&E protocol who tolerated some SRF achieved VA that is comparable, with fewer injections, with that achieved when treatment aimed to resolve all SRF completely.

IMPORTANCE Panretinal photocoagulation (PRP) for proliferative diabetic retinopathy (PDR) may lead to peripheral field loss that prevents driving. Anti-vascular endothelial growth factor agents are proposed as treatments for PDR that spare peripheral vision. If multispot lasers cause less visual field loss, continuing to perform PRP may be justified. OBJECTIVE To assess the effect of bilateral multispot laser PRP on retinal sensitivity and driving visual fields in PDR. DESIGN, SETTING, AND PARTICIPANTS This prospective nonrandomized interventional cohort analysis performed at a tertiary referral center included 43 laser-naive patients with PDR that required bilateral PRP. Participants were recruited from June 27, 2012, to October 14, 2013. At baseline and 6-month follow-up, patients underwent detailed static and kinetic perimetry, microperimetry, optical coherence tomography, wide-field color fundus photography, and fluorescein angiography. Quantitative change in retinal sensitivity was assessed by comparing the mean global retinal sensitivity before and after laser treatment and by comparing the modeled hill of vision by deriving a volumetric measure. Final follow-up was completed on May 21, 2014. INTERVENTIONS Multispot laser treatment was applied using standard parameters, until neovascularization regressed or complete retinal coverage was achieved. MAIN OUTCOMES AND MEASURES Participants who passed the Esterman binocular visual field test for driving in the United Kingdom (at least 120°horizontal field with no significant defects within the central 20°) and full-field and macular retinal sensitivity. RESULTS Of the 43 patients (17 men; 26 women; mean [SD] age, 46.6 [13.3] years), 38 (88%) completed the study. Before treatment, 41 of 43 patients (95%) passed the Esterman visual field test for driving; after completion of laser treatment, 35 of 38 patients (92%) passed. The mean (SD) change in retinal sensitivity on static perimetry was −1.4 (3.7) (95% CI, −2.7 to −0.1) dB OD and −2.4 (2.9) (95% CI, −3.4 to −1.4) dB OS. Mean (SD) 4°macular sensitivity decreased by 3.0 (5.2) dB OD and 2.6 (5.4) dB OS. CONCLUSIONS AND RELEVANCE This prospective study investigating the effects of multispot laser PRP on retinal sensitivity demonstrates a high likelihood of retaining eligibility to drive based on adequate visual field. A mild loss of retinal sensitivity was detected at 6 months after completion of laser treatment. Further change to visual fields may have occurred with longer follow-up. This study provides information that might be used to counsel patients requiring PRP and informs the debate regarding the role of anti-vascular endothelial growth factor therapy in patients with PDR who might otherwise receive laser treatment.