Impact of Delayed Time to Treatment on Visual Outcomes in Neovascular AMD: Data From the HARBOR Study.

BACKGROUND AND OBJECTIVE: To determine the potential impact on visual outcomes of delayed treatment initiation in patients with neovascular age-related macular degeneration (nAMD). PATIENTS AND METHODS: Post hoc analysis of anti-vascular endothelial growth factor treatment-naïve patients with nAMD from HARBOR. Time to treatment was defined as first ranibizumab injection date minus screening date. Comparisons were made between the prompt (≤ 6 days) versus delayed (> 10 days) treatment groups. Main outcome measures were best-corrected visual acuity (BCVA) change over time, BCVA, number of ranibizumab injections, and proportion of 3-line gainers/losers. RESULTS: In HARBOR, more than 50% of patients received their first injection within 7 days of screening, with mean (median) time to treatment of 4.6 (5) and 15.9 (14) days for the prompt and delayed treatment groups, respectively. Mean (95% confidence interval [CI]) BCVA change from baseline to Month 24 was 9.1 (7.4-10.8) and 8.8 (6.7-10.8) Early Treatment Diabetic Retinopathy Study letters in the prompt (n = 395) and delayed (n = 230) treatment groups, respectively. Mean (95% CI) total number of ranibizumab injections for the as-needed arms was 12.4 (11.6-13.3) and 11.4 (10.3-12.4) for the prompt and delayed treatment groups, respectively. CONCLUSION: In HARBOR, time from screening to first ranibizumab injection did not seem to significantly affect mean BCVA change or number of injections. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:62-69.].

The Value of Prior Response to Anti-Vascular Endothelial Growth Factor for Age-Related Macular Degeneration: A HARBOR Subanalysis.

PURPOSE: To evaluate disease activity-free intervals of patients with neovascular age-related macular degeneration (nAMD) in the pHase III, double-masked, multicenter, randomized, Active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg Ranibizumab administered monthly or on an as-needed Basis (PRN) in patients with subfoveal neOvasculaR age-related macular degeneration (HARBOR) to determine whether duration of response to previous treatment with ranibizumab informs future disease activity and need for subsequent injections. DESIGN: Retrospective subgroup analysis of the phase 3 HARBOR study (clinicaltrials.gov identifier, NCT00891735). PARTICIPANTS: Patients from the ranibizumab 0.5 mg pro re nata arm of the phase 3 HARBOR clinical trial who received all 3 loading injections and missed no more than 1 study visit (N = 217). METHODS: A disease activity-free interval was defined as a consecutive period in months when treatment was not required because the patient did not meet protocol retreatment criteria. Percentage of disease activity-free eyes at the next 1 and 2 months after a first disease activity-free interval of ≥2, ≥3, ≥4, ≥5, and ≥6 months was evaluated. Additionally, duration that eyes remained untreated after disease activity-free intervals was evaluated by Kaplan-Meier estimates. MAIN OUTCOME MEASURES: Key outcome measures included duration of the first treatment-free interval of ≥2, ≥3, ≥4, ≥5, and ≥6 months achieved by each patient; mean number of additional months patients remained treatment free after a treatment-free interval; and percentage of eyes requiring treatment within 2 months after each treatment-free interval. RESULTS: Percentage of eyes requiring retreatment the month after a treatment-free interval of ≥2, ≥3, ≥4, ≥5, and ≥6 months was 60% (90/151), 33% (33/100), 26% (20/77), 36% (24/66), and 19% (9/48), respectively. Percentage of eyes requiring retreatment within 2 months after a treatment-free interval of ≥2, ≥3, ≥4, ≥5, and ≥6 months was 73% (109/149), 53% (53/100), 53% (40/75), 47% (30/64), and 43% (20/46), respectively. After treatment-free intervals of ≥2, ≥3, ≥4, ≥5, and ≥6 months, mean (standard error of the mean) additional time treatment free was 1.3 months (0.17 month), 2.4 months (0.33 month), 2.9 months (0.44 month), 3.2 months (0.50 month), and 4.0 months (0.60 month), respectively. CONCLUSIONS: Longer treatment-free intervals may indicate longer future disease-free intervals; however, this association varies. Thus, although longer intervals suggest greater likelihood of not needing retreatment within 1 to 2 months, regular assessment is warranted owing to the unpredictability of nAMD disease activity.

Are Dilated Fundus Examinations Needed for OCT-Guided Retreatment of Exudative Age-Related Macular Degeneration?

PURPOSE: To determine whether presence of macular hemorrhage on dilated fundus examination (DFE) or fundus photography influences vision outcomes with OCT-guided pro re nata (PRN) ranibizumab retreatment in patients with neovascular age-related macular degeneration (nAMD), we investigated whether hemorrhage without OCT-detectable fluid impacted vision outcomes. DESIGN: Post hoc analysis of prospectively collected data from the 24-month pHase III, double-masked, multicenter, randomized, Active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg Ranibizumab administered monthly or on an as-needed Basis (PRN) in patients with subfoveal neOvascular age-related macular degeneration (HARBOR) trial (ClinicalTrials.gov identifier, NCT00891735). PARTICIPANTS: This post hoc analysis examined 1097 patients from the intention-to-treat population of HARBOR. METHODS: Dilated fundus examination and fundus photography were evaluated for hemorrhage, and spectral-domain (SD) OCT images from HARBOR participants were analyzed for macular fluid secondary to macular neovascularization. Agreement between methods was determined for each time point. Visual outcomes were evaluated for 82 patients with evidence of hemorrhage on DFE or fundus photography at 3 months and no evidence of SD-exudative activity requiring retreatment at month 3. MAIN OUTCOME MEASURES: Pooled data from the intention-to-treat population of HARBOR were analyzed for hemorrhage on DFE or fundus photography and exudative activity on SD OCT. A subgroup of PRN patients were analyzed for best-corrected visual acuity gains at 24 months. RESULTS: Most study eyes (89% [973/1095]) showed macular hemorrhages at baseline, declining to 31% (319/1042) at month 3 and stabilizing at 11% (111/989) by month 6 of follow-up. After baseline, exudative activity was detected on SD-OCT in more than 89% of eyes when hemorrhage was present on DFE or fundus photography. Patients not requiring a month 3 PRN ranibizumab injection achieved similar visual gains over 24 months, regardless of month 3 hemorrhage presence versus absence: 9.4 and 8.7 Early Treatment Diabetic Retinopathy Study letter scores, respectively (P = 0.74). CONCLUSIONS: After 3 initial ranibizumab injections, SD-OCT detected nAMD activity in 89% of eyes when hemorrhage was present on fundus photography. Ranibizumab retreatment guided by monthly SD-OCT achieved similar vision gains with or without injection when hemorrhage was present without OCT-detectable fluid. This suggests that macular hemorrhages without OCT-detectable macular fluid may not require treatment and DFE may not be needed at every visit. These conclusions should be confirmed in a prospective randomized trial before firm recommendations regarding clinical practice can be made.

Five-year outcomes of intravitreal drug therapy for neovascular age-related macular degeneration in eyes with baseline vision 20/60 or better.

OBJECTIVE: To assess outcomes in treatment-naive eyes with neovascular age-related macular degeneration (nAMD) and good baseline visual acuity (VA) treated using a treat-and-extend (T&E) regimen with intravitreal aflibercept, ranibizumab, or bevacizumab. DESIGN: Single center, retrospective, observational case series. PARTICIPANTS: Ninety-one patients (93 eyes) with nAMD and baseline VA ≥20/60 followed for ≥1 year after the first intravitreal injection. Minimum of 6 (first year) and 3 (subsequent years) and maximum of 12 injections per 12 calendar months. INTERVENTION: Intravitreal aflibercept 2.0 mg, ranibizumab 0.5 mg, or bevacizumab 1.25 mg. Three monthly injections. Treatment interval extended in 2-week increments after resolution of macular edema and reduced in 2-week increments if edema recurred; maximum interval of 12 weeks. Medication changed if edema recurred during and persisted after three monthly injections of original agent. MAIN OUTCOME MEASURES: VA maintenance over time. Total number of injections received by year of treatment. RESULTS: Ninety-three eyes were analyzed. Pretreatment VA was 20/20-20/25 (N=16), 20/30-20/40 (N=47), and 20/50-20/60 (N=30). Mean follow-up was 3.2 years. Follow-up by year was 93, 73, 65, 44, and 26 eyes for years 1-5, respectively. Mean number of injections during years 1-5 was 7.9, 5.9, 5.6, 5.9, and 6.0, respectively; mode number of injections was 7, 5, 3, 6, and 4, respectively. For years 1-5, percent of all eyes at or above baseline was 70%, 66%, 65%, 59%, and 58%, respectively; percent ≥20/60 was 86%, 88%, 86%, 84%, and 77% for years 1-5. For eyes with baseline VA ≥20/40, percent of eyes at or above baseline was 83%, 82%, 81%, 68% and 76% for years 1-5, respectively. CONCLUSION: Using a T&E intravitreal injection protocol, more than 75% of treatment-naive eyes with nAMD and baseline VA ≥20/60 can maintain VA ≥20/60 over 5 years.

Simulating an Anti-Vascular Endothelial Growth Factor Switch in Neovascular Age-Related Macular Degeneration: A HARBOR Subanalysis.

PURPOSE: A simulated switching study assessed the effects of continuing the same anti-vascular endothelial growth factor (VEGF) treatment among patients who typically are considered for a therapy switch. Post hoc analysis of data from HARBOR was undertaken. Patients with neovascular age-related macular degeneration who demonstrated a suboptimal response after 3 or 6 months of ranibizumab treatment were identified as switching candidates. Rather than switching, however, patients continued on ranibizumab treatment, and visual and anatomic outcomes from the point of the hypothetical switch were examined. DESIGN: Post hoc analysis of the phase 3 HARBOR clinical trial. PARTICIPANTS: Patients were included in 3- and 6-month switcher analyses if they received 3 of 3 initial monthly ranibizumab doses and 5 of 6 initial monthly ranibizumab doses, respectively, and met all the following: 5-letter or fewer gain from baseline, best-corrected visual acuity (BCVA) 20/40 or worse, and intraretinal or subretinal fluid with central foveal thickness (CFT) equal to or greater than central subfield thickness. METHODS: Patient data were examined at months 3 and 6 to identify those who met predetermined switching criteria. Best-corrected visual acuity and CFT were examined from the point at which switching criteria were met through months 6, 12, 18, and 24 of HARBOR and compared with those who did not meet the criteria. MAIN OUTCOME MEASURES: Outcome measures included mean BCVA and CFT change over time from the point (month 3 or 6) at which switching criteria were met. RESULTS: By months 3 and 6, only 44 of 1059 patients (4.2%) and 37 of 769 patients (4.8%), respectively, met the inclusion criteria for hypothetical switching. Patients who met switching criteria at month 3 gained, on average, 5.3 letters from months 3 to 12 and 2.7 letters from months 3 to 24. Month 6 switchers gained, on average, 1.6 letters from months 6 to 12 and 1.8 letters from months 6 to 24. Both groups experienced significant CFT reductions over 24 months. CONCLUSIONS: Month 3 hypothetical switchers achieved vision and anatomic improvement while continuing their original ranibizumab treatment. Month 6 switcher outcomes replicated those commonly reported in published anti-VEGF switching studies: stable vision or nominal improvements in vision with continued substantial anatomic improvement.

Online education improves pediatric residents' understanding of atopic dermatitis.

BACKGROUND/OBJECTIVES: Pediatricians manage skin conditions such as atopic dermatitis (AD) but report that their dermatologic training is inadequate. Online modules may enhance medical education when sufficient didactic or clinical teaching experiences are lacking. We assessed whether an online module about AD improved pediatric residents' knowledge and changed their clinical management of AD. METHODS: Target and control cohorts of pediatric residents from two institutions were recruited. Target subjects took a 30-question test about AD early in their residency, reviewed the online module, and repeated the test 6 months and 1 year later. The control subjects, who had 1 year of clinical experience but had not reviewed the online module, also took the test. The mean percentage of correct answers was calculated and compared using two-sided, two-sample independent t tests and repeated-measures analysis of variance. For a subset of participants, clinical documentation from AD encounters was reviewed and 13 practice behaviors were compared using the Fisher exact test. RESULTS: Twenty-five subjects in the target cohort and 29 subjects in the control cohort completed the study. The target cohort improved from 18.0 ± 3.2 to 23.4 ± 3.4 correctly answered questions over 1 year (P < .001). This final value was greater than that of the control cohort (20.7 ± 4.5; P = .01). Meaningful differences in practice behaviors were not seen. CONCLUSION: Pediatric residents who reviewed an online module about AD demonstrated statistically significant improvement in disease-specific knowledge over time and had statistically significantly higher scores than controls. Online dermatology education may effectively supplement traditional clinical teaching.