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Background: This study investigated factors associated with fellow eye horseshoe retinal tear (HST) development in consecutive patients with a presenting eye HST., Materials and Methods: Medical records were reviewed for patients with initial HSTs between 2015 and 2017 and 24 factors were analyzed. Logistic regression was used to assess factors associated with fellow eye HST development., Results: In total, 242 patients with an HST were identified with mean follow-up of 68.3 months. Four associations with fellow eye HST development were identified: (1) presence of fellow eye lattice degeneration, (2) subsequent presenting eye HSTs, (3) fellow eye vitreous hemorrhage at presenting eye HST occurrence, (4) OCT-determined stage 3 fellow eye posterior vitreous detachment at presenting eye HST occurrence., Conclusion: Four clinical findings associated with fellow eye HST development following presenting eye HST were identified. These factors may be important considerations during management patients with HST. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:338-345.] .

To assess the 52-week efficacy and safety of brolucizumab 6 mg administered every 4 weeks compared with aflibercept 2 mg dosed every 4 weeks in eyes with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid. Multicenter, randomized, double-masked phase 3a study. Participants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti–vascular endothelial growth factor treatment). Eyes were randomized (2:1) to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks up to and including week 100. The primary end point was analysis of noninferiority in mean best-corrected visual acuity (BCVA) change from baseline to week 52 (margin, 4 letters). Other key end points included change in central subfield thickness (CST) from baseline to week 52, fluid-free status (no intraretinal fluid and no subretinal fluid), and safety. At week 52, brolucizumab was noninferior to aflibercept in BCVA change from baseline (least squares mean difference, –0.6 Early Treatment Diabetic Retinopathy Study letters; 95% confidence interval [CI], –2.1 to 0.9; P < 0.001). A total of 4.8% and 1.7% of participants reported a 15-letter or more BCVA loss from baseline at week 52 in the brolucizumab and aflibercept groups, respectively. In eyes treated with brolucizumab compared with those treated with aflibercept, the CST was reduced significantly (P < 0.001), and a significantly greater proportion of eyes were fluid free at week 52 (40.4% brolucizumab vs. 19.0% aflibercept; 95% CI, 13.9–29.0; P < 0.001). Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, were 9.3% (0.8% and 2.0%) for brolucizumab versus 4.5% (0% and 0%) for aflibercept, respectively. Visual acuity outcomes in previously treated participants with nAMD and persistent retinal fluid receiving brolucizumab 6 mg dosed every 4 weeks were noninferior to aflibercept 2 mg dosed every 4 weeks, with superior anatomic outcomes. However, incidences of IOI, including retinal vasculitis and retinal vascular occlusion, also were higher, leading to study termination. [ABSTRACT FROM AUTHOR]

The article discusses the highlights of a 2014 roundtable discussion on the impact of anti-vascular endothelial growth factor (VEGF) treatments on naive age-related macular degeneration (AMD) patients conducted by the magazine "Retinal Physician." Topics discussed include the process of diagnosing a patient with AMD, the factors that retinal physicians are looking for on the optical coherence tomography (OCT) and the importance of discussing safety considerations to patients before treatment.

Purpose: To report 36-month outcomes of RIDE (NCT00473382) and RISE (NCT00473330), trials of ranibizumab in diabetic macular edema (DME). Design: Phase III, randomized, multicenter, double-masked, 3-year trials, sham injection–controlled for 2 years. Participants: Adults with DME (n=759), baseline best-corrected visual acuity (BCVA) 20/40 to 20/320 Snellen equivalent, and central foveal thickness (CFT) ≥275 μm on optical coherence tomography. Methods: Patients were randomized equally (1 eye per patient) to monthly 0.5 mg or 0.3 mg ranibizumab or sham injection. In the third year, sham patients, while still masked, were eligible to cross over to monthly 0.5 mg ranibizumab. Macular laser was available to all patients starting at month 3; panretinal laser was available as necessary. Main Outcome Measures: The proportion of patients gaining ≥15 Early Treatment Diabetic Retinopathy Study letters in BCVA from baseline at month 24. Results: Visual acuity (VA) outcomes seen at month 24 in ranibizumab groups were consistent through month 36; the proportions of patients who gained ≥15 letters from baseline at month 36 in the sham/0.5 mg, 0.3 mg, and 0.5 mg ranibizumab groups were 19.2%, 36.8%, and 40.2%, respectively, in RIDE and 22.0%, 51.2%, and 41.6%, respectively, in RISE. In the ranibizumab arms, reductions in CFT seen at 24 months were, on average, sustained through month 36. After crossover to 1 year of treatment with ranibizumab, average VA gains in the sham/0.5 mg group were lower compared with gains seen in the ranibizumab patients after 1 year of treatment (2.8 vs. 10.6 and 11.1 letters). Per-injection rates of endophthalmitis remained low over time (∼0.06% per injection). The incidence of serious adverse events potentially related to systemic vascular endothelial growth factor inhibition was 19.7% in patients who received 0.5 mg ranibizumab compared with 16.8% in the 0.3 mg group. Conclusions: The strong VA gains and improvement in retinal anatomy achieved with ranibizumab at month 24 were sustained through month 36. Delayed treatment in patients receiving sham treatment did not seem to result in the same extent of VA improvement observed in patients originally randomized to ranibizumab. Ocular and systemic safety was generally consistent with the results seen at month 24. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

PURPOSE: To evaluate intravitreal aflibercept injections (IAI; also called VEGF Trap-Eye) for patients with macular edema secondary to central retinal vein occlusion (CRVO). DESIGN: Randomized controlled trial. METHODS: This multicenter study randomized 189 patients (1 eye/patient) with macular edema secondary to CRVO to receive 6 monthly injections of either 2 mg intravitreal aflibercept (IAI 2Q4) (n [ 115) or sham (n[74). From week 24 to week 52, all patients received 2 mg intravitreal aflibercept as needed (IAI 2Q4D PRN and sham D IAI PRN) according to retreatment criteria. The primary endpoint was the proportion of patients who gained ‡15 ETDRS letters from baseline at week 24. Additional endpoints included visual, anatomic, and quality-of-life NEI VFQ-25 outcomes at weeks 24 and 52. RESULTS: At week 24, 56.1% of IAI 2Q4 patients gained ‡15 letters from baseline compared with 12.3% of sham patients (P < .001). At week 52, 55.3% of IAI 2Q4 D PRN patients gained ‡15 letters compared with 30.1% of sham D IAI PRN patients (P < .001). At week 52, IAI 2Q4 D PRN patients gained a mean of 16.2 letters of vision vs 3.8 letters for sham D IAI PRN (P < .001). The most common adverse events for both groups were conjunctival hemorrhage, eye pain, reduced visual acuity, and increased intraocular pressure. CONCLUSIONS: Monthly injections of 2 mg intravitreal aflibercept for patients with macular edema secondary to CRVO resulted in a statistically significant improvement in visual acuity at week 24, which was largely maintained through week 52 with intravitreal aflibercept PRN dosing. Intravitreal aflibercept injection was generally well tolerated. [ABSTRACT FROM AUTHOR]

Objective: Two similarly designed, phase-3 studies (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD [VIEW 1, VIEW 2]) of neovascular age-related macular degeneration (AMD) compared monthly and every-2-month dosing of intravitreal aflibercept injection (VEGF Trap-Eye; Regeneron, Tarrytown, NY, and Bayer HealthCare, Berlin, Germany) with monthly ranibizumab. Design: Double-masked, multicenter, parallel-group, active-controlled, randomized trials. Participants: Patients (n = 2419) with active, subfoveal, choroidal neovascularization (CNV) lesions (or juxtafoveal lesions with leakage affecting the fovea) secondary to AMD. Intervention: Patients were randomized to intravitreal aflibercept 0.5 mg monthly (0.5q4), 2 mg monthly (2q4), 2 mg every 2 months after 3 initial monthly doses (2q8), or ranibizumab 0.5 mg monthly (Rq4). Main Outcome Measures: The primary end point was noninferiority (margin of 10%) of the aflibercept regimens to ranibizumab in the proportion of patients maintaining vision at week 52 (losing <15 letters on Early Treatment Diabetic Retinopathy Study [ETDRS] chart). Other key end points included change in best-corrected visual acuity (BCVA) and anatomic measures. Results: All aflibercept groups were noninferior and clinically equivalent to monthly ranibizumab for the primary end point (the 2q4, 0.5q4, and 2q8 regimens were 95.1%, 95.9%, and 95.1%, respectively, for VIEW 1, and 95.6%, 96.3%, and 95.6%, respectively, for VIEW 2, whereas monthly ranibizumab was 94.4% in both studies). In a prespecified integrated analysis of the 2 studies, all aflibercept regimens were within 0.5 letters of the reference ranibizumab for mean change in BCVA; all aflibercept regimens also produced similar improvements in anatomic measures. Ocular and systemic adverse events were similar across treatment groups. Conclusions: Intravitreal aflibercept dosed monthly or every 2 months after 3 initial monthly doses produced similar efficacy and safety outcomes as monthly ranibizumab. These studies demonstrate that aflibercept is an effective treatment for AMD, with the every-2-month regimen offering the potential to reduce the risk from monthly intravitreal injections and the burden of monthly monitoring. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Objective: To evaluate the biologic effects and safety of vascular endothelial growth factor (VEGF) Trap-Eye during a 12-week fixed-dosing period in patients with neovascular (wet) age-related macular degeneration (AMD). Design: Multicenter, prospective, randomized, double-masked clinical trial with initial 12-week fixed dosing period. Data were analyzed to week 16. Participants: We included 159 patients with subfoveal choroidal neovascularization secondary to wet AMD. Methods: Patients were randomized 1:1:1:1:1 to VEGF Trap-Eye during the fixed-dosing phase (day 1 to week 12): 0.5 or 2 mg every 4 weeks (0.5 mg q4wk, 2 mg q4wk) on day 1 and at weeks 4, 8, and 12; or 0.5, 2, or 4 mg every 12 weeks (0.5 mg q12wk, 2 mg q12wk, or 4 mg q12wk) on day 1 and at week 12. Main Outcome Measures: The primary endpoint was change from baseline in central retinal/lesion thickness (CR/LT) at week 12; secondary outcomes included change in best-corrected visual acuity (BCVA), proportion of patients with a gain of ≥15 letters, proportion of patients with a loss of >15 letters, and safety. Results: At week 12, treatment with VEGF Trap-Eye resulted in a significant mean decrease in CR/LT of 119 μm from baseline in all groups combined (P<0.0001). The reduction in CR/LT with the 2 mg q4wk and 0.5mg q4wk regimens was significantly greater than each of the quarterly dosing regimens. The BCVA increased significantly by a mean of 5.7 letters at 12 weeks in the combined group (P<0.0001), with the greatest mean gain of >8 letters in the monthly dosing groups. At 8 weeks, BCVA improvements were similar with 2 mg q4wk and 2 mg q12wk dosing. After the last required dose at week 12, CR/LT and visual acuity were maintained or further improved at week 16 in all treatment groups. Ocular adverse events were mild and consistent with safety profiles reported for other intraocular anti-VEGF treatments. Conclusions: Repeated monthly intravitreal dosing of VEGF Trap-Eye over 12 weeks demonstrated significant reductions in retinal thickness and improvements in visual acuity, and was well-tolerated in patients with neovascular AMD. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Objective: The 2-year, phase III trial designated Anti-vascular endothelial growth factor (VEGF) Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization (CNV) in Age-related Macular Degeneration (ANCHOR) compared ranibizumab with verteporfin photodynamic therapy (PDT) in treating predominantly classic CNV. Design: Multicenter, international, randomized, double-masked, active-treatment-controlled clinical trial. Participants: Patients with predominantly classic, subfoveal CNV not previously treated with PDT or antiangiogenic drugs. Intervention: Patients were randomized 1:1:1 to verteporfin PDT plus monthly sham intraocular injection or to sham verteporfin PDT plus monthly intravitreal ranibizumab (0.3 mg or 0.5 mg) injection. The need for PDT (active or sham) retreatment was evaluated every 3 months using fluorescein angiography (FA). Main Outcome Measures: The primary, intent-to-treat efficacy analysis was at 12 months, with continued measurements to month 24. Key measures included the percentage losing <15 letters from baseline visual acuity (VA) score (month 12 primary efficacy outcome measure), percentage gaining ≥15 letters from baseline, and mean change over time in VA score and FA-assessed lesion characteristics. Adverse events were monitored. Results: Of 423 patients (143 PDT, 140 each in the 2 ranibizumab groups), the majority (≥77% in each group) completed the 2-year study. Consistent with results at month 12, at month 24 the VA benefit from ranibizumab was statistically significant (P<0.0001 vs. PDT) and clinically meaningful: 89.9% to 90.0% of ranibizumab-treated patients had lost <15 letters from baseline (vs. 65.7% of PDT patients); 34% to 41.0% had gained ≥15 letters (vs. 6.3% of PDT group); and, on average, VA was improved from baseline by 8.1 to 10.7 letters (vs. a mean decline of 9.8 letters in PDT group). Changes in lesion anatomic characteristics on FA also favored ranibizumab (all comparisons P<0.0001 vs. PDT). Overall, there was no imbalance among groups in rates of serious ocular and nonocular adverse events. In the pooled ranibizumab groups, 3 of 277 (1.1%) patients developed presumed endophthalmitis in the study eye (rate per injection = 3/5921 [0.05%]). Conclusions: In this 2-year study, ranibizumab provided greater clinical benefit than verteporfin PDT in patients with age-related macular degeneration with new-onset, predominantly classic CNV. Rates of serious adverse events were low. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Purpose: To evaluate the efficacy and safety of ranibizumab administered monthly for three months and then quarterly in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Design: Phase IIIb, multicenter, randomized, double-masked, sham injection-controlled trial in patients with predominantly or minimally classic or occult with no classic CNV lesions. Methods: Patients were randomized 1:1:1 to 0.3 mg ranibizumab (n = 60), 0.5 mg ranibizumab (n = 61), or sham (n = 63) treatment groups. The primary efficacy endpoint was mean change from baseline visual acuity (VA) at month 12. Results: Mean changes from baseline VA at 12 months were −16.3, −1.6, and −0.2 letters for the sham, 0.3 mg, and 0.5 mg groups, respectively (P ≤ .0001, each ranibizumab dose vs sham). Ranibizumab arrested CNV growth and reduced leakage from CNV. However, the treatment effect declined in the ranibizumab groups during quarterly dosing (e.g., at three months the mean changes from baseline VA had been gains of 2.9 and 4.3 letters for the 0.3 mg and 0.5 mg doses, respectively). Results of subgroups analyses of mean change from baseline VA at 12 months by baseline age, VA, and lesion characteristics were consistent with the overall results. Few serious ocular or nonocular adverse events occurred in any group. Conclusions: Ranibizumab administered monthly for three months and then quarterly provided significant VA benefit to patients with AMD-related subfoveal CNV and was well tolerated. The incidence of serious ocular or nonocular adverse events was low. [Copyright &y& Elsevier]

The article describes the case of one patient who suffers from distortion of vision and another who has wet age-related macular degeneration (AMD). Topics discussed include central retinal vein occlusion (CRVO) as the final diagnosis for the patient who suffered from vision distortion, effect of ranibizumab on the patient's eyesight and other drugs prescribed to the patient. Also discussed is the treatment method recommended to the AMD patient.

A response by Philip J. Rosenfeld, David M. Brown and Susan Schneider to a letter to the editor about the results of their Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age-Related Macular Degeneration (MARINA) study and the Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration (ANCHOR) study in the October 5, 2006 issue is presented.

Background: Ranibizumab — a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A — has been evaluated for the treatment of neovascular age-related macular degeneration. Methods: In this multicenter, 2-year, double-blind, sham-controlled study, we randomly assigned patients with age-related macular degeneration with either minimally classic or occult (with no classic lesions) choroidal neovascularization to receive 24 monthly intravitreal injections of ranibizumab (either 0.3 mg or 0.5 mg) or sham injections. The primary end point was the proportion of patients losing fewer than 15 letters from baseline visual acuity at 12 months. Results: We enrolled 716 patients in the study. At 12 months, 94.5% of the group given 0.3 mg of ranibizumab and 94.6% of those given 0.5 mg lost fewer than 15 letters, as compared with 62.2% of patients receiving sham injections (P<0.001 for both comparisons). Visual acuity improved by 15 or more letters in 24.8% of the 0.3-mg group and 33.8% of the 0.5-mg group, as compared with 5.0% of the sham-injection group (P<0.001 for both doses). Mean increases in visual acuity were 6.5 letters in the 0.3-mg group and 7.2 letters in the 0.5-mg group, as compared with a decrease of 10.4 letters in the sham-injection group (P<0.001 for both comparisons). The benefit in visual acuity was maintained at 24 months. During 24 months, presumed endophthalmitis was identified in five patients (1.0%) and serious uveitis in six patients (1.3%) given ranibizumab. Conclusions: Intravitreal administration of ranibizumab for 2 years prevented vision loss and improved mean visual acuity, with low rates of serious adverse events, in patients with minimally classic or occult (with no classic lesions) choroidal neovascularization secondary to age-related macular degeneration. (ClinicalTrials.gov number, NCT00056836.) N Engl J Med 2006;355:1419-31. [ABSTRACT FROM AUTHOR]

Background: We compared ranibizumab — a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A — with photodynamic therapy with verteporfin in the treatment of predominantly classic neovascular age-related macular degeneration. Methods: During the first year of this 2-year, multicenter, double-blind study, we randomly assigned patients in a 1:1:1 ratio to receive monthly intravitreal injections of ranibizumab (0.3 mg or 0.5 mg) plus sham verteporfin therapy or monthly sham injections plus active verteporfin therapy. The primary end point was the proportion of patients losing fewer than 15 letters from baseline visual acuity at 12 months. Results: Of the 423 patients enrolled, 94.3% of those given 0.3 mg of ranibizumab and 96.4% of those given 0.5 mg lost fewer than 15 letters, as compared with 64.3% of those in the verteporfin group (P<0.001 for each comparison). Visual acuity improved by 15 letters or more in 35.7% of the 0.3-mg group and 40.3% of the 0.5-mg group, as compared with 5.6% of the verteporfin group (P<0.001 for each comparison). Mean visual acuity increased by 8.5 letters in the 0.3-mg group and 11.3 letters in the 0.5-mg group, as compared with a decrease of 9.5 letters in the verteporfin group (P<0.001 for each comparison). Among 140 patients treated with 0.5 mg of ranibizumab, presumed endophthalmitis occurred in 2 patients (1.4%) and serious uveitis in 1 (0.7%). Conclusions: Ranibizumab was superior to verteporfin as intravitreal treatment of predominantly classic neovascular age-related macular degeneration, with low rates of serious ocular adverse events. Treatment improved visual acuity on average at 1 year. (ClinicalTrials.gov number, NCT00061594.) N Engl J Med 2006;355:1432-44. [ABSTRACT FROM AUTHOR]

To compare the efficacy and safety of intravitreal aflibercept + anti–platelet-derived growth factor receptor β (PDGFRβ) combination with intravitreal aflibercept injection (IAI) monotherapy in patients with treatment-naïve neovascular age-related macular degeneration (nAMD). Phase 2, randomized, double-masked study. A total of 505 patients (eyes) with nAMD. Patients were randomized 1:2:2 to low-dose combination intravitreal anti-PDGFRβ 1 mg and aflibercept 2 mg (LD combo), high-dose combination intravitreal anti-PDGFRβ 3 mg and aflibercept 2 mg (HD combo), or IAI alone every 4 weeks through week 12. At week 12, patients in the HD combo and IAI groups were re-randomized to continue as assigned or switch to HD combo → IAI or IAI → HD combo and dosed every 4 weeks through week 28. During weeks 28 to 52, patients received treatment as needed per prespecified criteria. This report presents efficacy through week 28 and safety through week 52. Mean best-corrected visual acuity (BCVA) change from baseline at week 12 (primary end point). At week 12, mean BCVA gains from baseline were 5.8, 5.8, and 7.5 letters with LD combo, HD combo, and IAI, respectively (P = 0.21 for LD combo and P = 0.10 for HD combo vs. IAI). The corresponding proportions of eyes that gained ≥15 letters were 12%, 19%, and 22%, respectively. Mean reductions in central retinal thickness from baseline were 126.1, 127.1, and 126.9 μm, respectively. Proportions of eyes with complete resolution of fluid from baseline were 35%, 24%, and 42%, respectively. Vision and anatomic outcomes at week 28 were consistent with the week 12 results. Through week 52, the incidence of intraocular inflammation was 1.0%, 7.5%, 2.1%, 2.1%, and 0%, respectively. The incidence of Anti-Platelet Trialists' Collaboration–defined arterial thromboembolic events was 1.9%, 0.9%, 1.1%, 2.1%, and 1.9%, respectively. Intravitreal aflibercept + anti-PDGFRβ did not improve BCVA over IAI alone. Anatomic outcomes evaluating complete fluid resolution favored IAI. Adverse events were consistent with the reported IAI safety profile, except for a higher frequency of intraocular inflammation in the HD combo group. [ABSTRACT FROM AUTHOR]

Geographic atrophy (GA), a late stage of age-related macular degeneration (AMD), is a major cause of blindness. Even while central visual acuity remains relatively well preserved, GA often causes considerable compromise of visual function and quality of life. No treatment currently exists. We evaluated the safety and efficacy of pegcetacoplan, a complement C3 inhibitor, for treatment of GA. Prospective, multicenter, randomized, sham-controlled phase 2 study. Two hundred forty-six patients with GA. Patients with GA were assigned randomly in a 2:2:1:1 ratio to receive intravitreal injections of 15 mg pegcetacoplan monthly or every other month (EOM) or sham intravitreal injections monthly or EOM for 12 months with follow-up at months 15 and 18. Area and growth of GA were measured using fundus autofluorescence imaging. The primary efficacy end point was mean change in square root GA lesion area from baseline to month 12. Secondary outcome measures included mean change from baseline in GA lesion area without the square root transformation, distance of GA lesion from the fovea, best-corrected visual acuity (BCVA), low-luminance BCVA, and low-luminance visual acuity deficit. The primary safety end point was the number and severity of treatment-emergent adverse events. In patients receiving pegcetacoplan monthly or EOM, the GA growth rate was reduced by 29% (95% confidence interval [CI], 9–49; P = 0.008) and 20% (95% CI, 0–40; P = 0.067) compared with the sham treatment group. Post hoc analysis showed that the effect was greater in the second 6 months of treatment, with observed reductions of 45% (P = 0.0004) and 33% (P = 0.009) for pegcetacoplan monthly and EOM, respectively. Two cases of culture-positive endophthalmitis and 1 case of culture-negative endophthalmitis occurred in the pegcetacoplan monthly group. New-onset investigator-determined exudative AMD was reported more frequently in pegcetacoplan-treated eyes (18/86 eyes [20.9%] and 7/79 eyes [8.9%] in monthly and EOM groups, respectively) than in sham-treated eyes (1/81 eyes [1.2%]). Local C3 inhibition with pegcetacoplan resulted in statistically significant reductions in the growth of GA compared with sham treatment. Phase 3 studies will define the efficacy and safety profile further. [ABSTRACT FROM AUTHOR]

Two similarly designed phase 3 trials (HAWK and HARRIER) compared brolucizumab, a single-chain antibody fragment that inhibits vascular endothelial growth factor-A, with aflibercept to treat neovascular age-related macular degeneration (nAMD). Double-masked, multicenter, active-controlled, randomized trials. Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye. Patients were randomized to intravitreal brolucizumab 3 mg (HAWK only) or 6 mg or aflibercept 2 mg. After loading with 3 monthly injections, brolucizumab-treated eyes received an injection every 12 weeks (q12w) and were interval adjusted to every 8 weeks (q8w) if disease activity was present; aflibercept-treated eyes received q8w dosing. The primary hypothesis was noninferiority in mean best-corrected visual acuity (BCVA) change from baseline to Week 48 (margin: 4 letters). Other key end points included the percentage of patients who maintained q12w dosing through Week 48 and anatomic outcomes. At Week 48, each brolucizumab arm demonstrated noninferiority to aflibercept in BCVA change from baseline (least squares [LS] mean, +6.6 [6 mg] and +6.1 [3 mg] letters with brolucizumab vs. +6.8 letters with aflibercept [HAWK]; +6.9 [brolucizumab 6 mg] vs. +7.6 [aflibercept] letters [HARRIER]; P < 0.001 for each comparison). Greater than 50% of brolucizumab 6 mg–treated eyes were maintained on q12w dosing through Week 48 (56% [HAWK] and 51% [HARRIER]). At Week 16, after identical treatment exposure, fewer brolucizumab 6 mg–treated eyes had disease activity versus aflibercept in HAWK (24.0% vs. 34.5%; P = 0.001) and HARRIER (22.7% vs. 32.2%; P = 0.002). Greater central subfield thickness reductions from baseline to Week 48 were observed with brolucizumab 6 mg versus aflibercept in HAWK (LS mean −172.8 μm vs. −143.7 μm; P = 0.001) and HARRIER (LS mean −193.8 μm vs. −143.9 μm; P < 0.001). Anatomic retinal fluid outcomes favored brolucizumab over aflibercept. Overall, adverse event rates were generally similar with brolucizumab and aflibercept. Brolucizumab was noninferior to aflibercept in visual function at Week 48, and >50% of brolucizumab 6 mg–treated eyes were maintained on q12w dosing interval through Week 48. Anatomic outcomes favored brolucizumab over aflibercept. Overall safety with brolucizumab was similar to aflibercept (ClinicalTrials.gov ; NCT02307682 , NCT02434328). [ABSTRACT FROM AUTHOR]

Purpose: To compare aqueous levels of fluocinolone acetonide (FAc) after administration of FAc inserts or FAc implants (Retisert; Bausch & Lomb, Rochester, NY). Design: Comparison of pharmacokinetics from 2 prospective, interventional, clinical trials. Participants: Thirty-seven patients with diabetic macular edema (DME) (Fluocinolone Acetonide in Human Aqueous [FAMOUS] Study, C-01-06-002) and 7 patients with uveitis (NA-00019318). Methods: Aqueous FAc was measured after administration of FAc implants or 0.2 μg/day (low dose, ILUVIEN; Alimera Sciences Inc., Alpharetta, GA) or 0.5 μg/day (high dose) FAc inserts. Main Outcome Measures: The primary end point was aqueous levels of FAc. Results: At 1 month after administration for subjects who received 1 treatment, mean aqueous FAc levels were 2.17 (low dose) and 3.03 ng/ml (high dose) for FAc inserts and 6.12 ng/ml for FAc implants with maximum levels of 3.83, 6.66, and 13.50 ng/ml, respectively. At 3 months, mean FAc levels were 1.76, 2.15, and 6.12 ng/ml, respectively. Between 6 and 36 months after low-dose inserts, aqueous levels of FAc were remarkably stable, ranging from 1.18 to 0.45 ng/ml. After high-dose inserts, mean FAc levels were stable between 6 and 24 months, ranging from 1.50 to 0.84 ng/ml and then decreasing to 0.35 ng/ml at 30 months and 0.15 ng/ml at 36 months. In implant-containing eyes, mean FAc levels remained >6 ng/ml through 15 months, the last time point with measurements from at least 6 eyes. Conclusions: Low- and high-dose FAc inserts both provide stable long-term release of FAc with comparable peak levels in the aqueous: slightly >2 ng/ml for approximately 3 months followed by steady-state levels between 1.0 and 0.5 ng/ml through 36 months for low-dose inserts versus levels between 1.5 and 1.1 ng/ml through 24 months for high-dose inserts. Steady-state aqueous levels after FAc implants were >6 ng/ml. These results provide new insights that aid in the interpretation of efficacy trials and indicate that there is a dose effect for steroid-induced ocular hypertension. In susceptible patients, prolonged aqueous levels of FAc >1 ng/ml moderately increased the risk of glaucoma and levels >6 ng/ml posed a markedly increase risk. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Objective: To evaluate anatomic outcomes and vision, injection frequency, and safety during the as-needed (PRN) treatment phase of a study evaluating a 12-week fixed dosing period followed by PRN dosing to week 52 with vascular endothelial growth factor (VEGF) Trap-Eye for neovascular (wet) age-related macular degeneration (AMD). Design: Multicenter, randomized, double-masked trial. Participants: We included 159 patients with subfoveal choroidal neovascularization (CNV) secondary to wet AMD. Methods: Patients were randomly assigned to 1 of 5 intravitreal VEGF Trap-Eye treatment groups: 0.5 mg or 2 mg every 4 weeks or 0.5, 2, or 4 mg every 12 weeks during the fixed-dosing period (weeks 1–12). From weeks 16 to 52, patients were evaluated monthly and were retreated PRN with their assigned dose (0.5, 2, or 4 mg). Main Outcome Measures: Change in central retinal/lesion thickness (CR/LT), change in total lesion and CNV size, mean change in best-corrected visual acuity (BCVA), proportion of patients with 15-letter loss or gain, time to first PRN injection, reinjection frequency, and safety at week 52. Results: The decrease in CR/LT at week 12 versus baseline remained significant at weeks 12 to 52 (−130 μm from baseline at week 52) and CNV size regressed from baseline by 2.21 mm2 at 48 weeks. After achieving a significant improvement in BCVA during the 12-week, fixed-dosing phase for all groups combined, PRN dosing for 40 weeks maintained improvements in BCVA to 52 weeks (5.3-letter gain; P<0.0001). The most robust improvements and consistent maintenance of visual acuity generally occurred in patients initially dosed with 2 mg every 4 weeks for 12 weeks, demonstrating a gain of 9 letters at 52 weeks. Overall, a mean of 2 injections was administered after the 12-week fixed-dosing phase, and the mean time to first reinjection was 129 days; 19% of patients received no injections and 45% received 1 or 2 injections. Treatment with VEGF Trap-Eye was generally safe and well tolerated, with few ocular or systemic adverse events. Conclusions: PRN dosing with VEGF Trap-Eye at weeks 16-52 maintained the significant anatomic and vision improvements established during the 12-week fixed-dosing phase with a low frequency of reinjections. Repeated dosing with VEGF Trap-Eye was well tolerated over 52 weeks of treatment. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Purpose: To compare Iluvien intravitreal inserts that release 0.2 or 0.5 μg/day of fluocinolone acetonide (FA) in patients with diabetic macular edema (DME). Design: Prospective, randomized, interventional, multicenter clinical trial. Participants: We included 37 patients with DME. Methods: Subjects with persistent DME despite ≥1 focal/grid laser therapy were randomized 1:1 to receive an intravitreal insertion of a 0.2- or a 0.5-μg/day insert. Main Outcome Measures: The primary end point was aqueous levels of FA throughout the study with an important secondary outcome of the change from baseline in best-corrected visual acuity (BCVA) at month 12. Results: The mean aqueous level of FA peaked at 3.8 ng/ml at 1 week and 1 month after administration of a 0.5-μg/day insert and was 3.4 and 2.7 ng/ml 1 week and 1 month after administration of a 0.2-μg/day insert. For both inserts, FA levels decreased slowly thereafter and were approximately 1.5 ng/ml for each at month 12. The mean change from baseline in BCVA was 7.5, 6.9, and 5.7 letters at months 3, 6, and 12, respectively, after administration of a 0.5 μg/day-insert and was 5.1, 2.7, and 1.3 letters at months 3, 6, and 12, respectively, after administration of a 0.2-μg/day insert. There was a mild increase in mean intraocular pressure after administration of 0.5-μg/day inserts, but not after administration of 0.2-μg/day inserts. Conclusions: The FA intravitreal inserts provide excellent sustained intraocular release of FA for ≥1 year. Although the number of patients in this trial was small, the data suggest that the inserts provide reduction of edema and improvement in BCVA in patients with DME with mild effects on intraocular pressure over the span of 1 year. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]