INJECTION FREQUENCY OF AFLIBERCEPT VERSUS RANIBIZUMAB IN A TREAT-AND-EXTEND REGIMEN FOR CENTRAL RETINAL VEIN OCCLUSION: A Randomized Clinical Trial.

PURPOSE: To prospectively investigate the injection frequency of aflibercept and ranibizumab in the treatment of macular edema in central retinal vein occlusion. METHODS: Patients with treatment-naive central retinal vein occlusion and macular edema were randomized to receive intravitreal injections with aflibercept (n = 22) or ranibizumab (n = 23) in a treat-and-extend regimen with a follow-up time of 18 months. After 3 loading doses, the treatment intervals were extended by 2 weeks to a maximum of 12 weeks. Intervals were shortened by 2 weeks if macular edema recurred. RESULTS: The number of injections was significantly lower in the aflibercept group with a mean of 10.9 injections (95% confidence interval, 9.6-12.3) compared with 14.4 in the ranibizumab group (95% confidence interval 12.7-16.1) at study completion (P = 0.0017). The mean treatment interval was significantly longer in the aflibercept group compared with the ranibizumab group 10.0 (95% confidence interval, 8.7-11.3) and 6.6 (95% confidence interval, 5.2-8.0) weeks, respectively (P < 0.001). No significant difference between the groups regarding visual acuity or central retinal thickness was observed. CONCLUSION: Patients with macular edema secondary to central retinal vein occlusion required significantly fewer intravitreal injections of aflibercept compared with ranibizumab when treated with a treat-and-extend regimen. This may reduce the treatment burden and, to some extent, the need for close monitoring of patients.

LONG-TIME OUTCOME IN PATIENTS TREATED WITH RANIBIZUMAB FOR DIABETIC MACULAR EDEMA: A 4-Year Study.

PURPOSE: To investigate the long-time visual outcome in patients with diabetic macular edema treated with ranibizumab in an ordinary clinical setting. METHODS: One hundred two eyes of 80 patients were followed for 4 years. All patients received a loading dose of 3 monthly ranibizumab 0.5-mg injections. From Month 3 to Month 48, patients received ranibizumab reinjections pro re nata based on disease activity. RESULTS: Excluding deaths, the 4-year visit was completed by 82% of the study eyes. The best-corrected visual acuity improved by 6.6 Early Treatment Diabetic Retinopathy Study letters at 4 years (P < 0.001). The patients received a mean of 7.7 ± 3.4 ranibizumab injections for 4 years. The number of injections (mean ± SD) given were 4.7 (1.1), 1.4 (1.4), 0.7 (1.1), and 0.9 (1.4) during Years 1 to 4, respectively. No difference in the injections needed was seen between patients who had previously received focal/grid laser and treatment-naive subjects. CONCLUSION: The gain in the best-corrected visual acuity achieved after the initial loading dose was sustained over time with a pro re nata regimen. The number of injections needed to maintain the best-corrected visual acuity was low during the study period.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE FOVEAL MICROVASCULATURE IN GEOGRAPHIC ATROPHY.

PURPOSE: To examine the retinal and choroidal foveal and parafoveal vasculature in patients with bilateral geographic atrophy (GA) secondary to age-related macular degeneration using optical coherence tomography angiography (OCTA). METHODS: Fourteen eyes from 7 patients with and without fovea-sparing bilateral GA at St. Erik Eye Hospital. All patients were examined by optical coherence tomography angiography, en face OCT and fundus autofluorescence (FAF). Segmented optical coherence tomography angiography flow scans were obtained from the superficial retinal vascular layer (SL) and the choriocapillaris (CC) and correlated with areas of retinal pigment epithelial (RPE) loss on fundus autofluorescence. The foveal avascular zone (FAZ) was measured on superficial retinal vascular layer scans and compared to the GA area of each patient. RESULTS: No significant correlation (r = -0.17, P = 0.58) was found between superficial retinal vascular layer foveal avascular zone (0.49 mm ± 0.23 mm) and GA area (7.36 mm ± 4.36 mm). Absent or severely impaired CC flow was observed inside all GA lesions and to varied extent outside the GA margins including areas of fovea sparing. A high level of symmetry was observed in CC flow between fellow eyes. CONCLUSION: In this cross-sectional study, no relation was found between superficial retinal vascular layer foveal avascular zone and GA area. CC flow inside the GA was severely impaired, whereas CC flow outside the GA correlated poorly with both RPE integrity and visual acuity. Fellow eye symmetry suggests that CC monitoring may be a relevant clinical end point in interventional GA studies.

NEAR VISION OUTCOME IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION TREATED WITH AFLIBERCEPT.

PURPOSE: The aim of this study was to investigate the outcome in near vision and the best-corrected visual acuity in patients with wet, age-related macular degeneration treated with aflibercept in a fixed bimonthly regimen in an ordinary clinical setting. METHODS: The study was a retrospective, nonrandomized consecutive case series including 85 patients with wet, age-related macular degeneration followed for 18 months. During the first year all the patients received aflibercept injections in a fixed regimen at the following time points: Month 0, 1, 2, 4, 6, 8, 10, and 12. From Month 12 to Month 18, patients were treated with a treat and extend algorithm. RESULTS: The median near visual acuity improved from 12 points (95% confidence interval [CI] 10.5-13.4) at baseline to 5 points both at Month 12 (95% CI 3.8-6.2) and at Month 18 (95% CI 3.6-6.4) (P < 0.0001). At the 18-month visit, 58% (42/73) of the patients had a near visual acuity of at least 5 points compared with 7% (6/85) (P < 0.0001) at baseline. Best-corrected visual acuity improved from 60.9 letters (Snellen 20/63) (95% CI 58.4-63.4) at baseline to 68.1 letters (20/40) (95% CI 65.3-70.9) (P < 0.001) at Month 12 and 69.6 letters (20/40) (95% CI 66.7-72.5) (P < 0.001) at Month 18. CONCLUSION: Significant improvements were found in near vision and best-corrected visual acuity. The improvement in near vision was comparably greater than the change in best-corrected visual acuity. Monitoring near vision can contribute additional information when managing the patient with wet, age-related macular degeneration.

Most patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency develop pathological or subnormal retinal function.

AIM: There have been few studies on long-term electroretinographic findings in patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). This study correlated long-term electroretinographic findings with age, metabolic control and clinical symptoms. METHODS: We examined 12 Swedish patients with LCHADD. Visual acuity testing, fundus examinations, optical coherence tomography and electroretinography were performed. The results were correlated to age, the levels of 3-hydroxyacylcarnitine and acylcarnitine and clinical metabolic control. RESULTS: Blindness or moderate visual impairment was found in two patients. Retinal pigmentation, atrophy and fibrosis were present in 11, seven and one of the patients, respectively, and optical coherence tomography showed retinal thinning in three of the six patients examined. Electroretinography was performed on 11 of the 12 patients. It was pathological, with reduced rod and cone responses, in five patients, subnormal in four and was related to poor clinical metabolic control and severe neonatal symptoms. Repeated electroretinographies revealed reduced function with increasing age. CONCLUSION: More than 80% of the LCHADD patients developed pathological or subnormal retinal function. This was more pronounced in patients with neonatal symptoms, but ameliorated by strict dietary treatment. Annual ophthalmological follow-ups, with electroretinography every second or third year, are recommended.

Recurrent Neovascular Age-Related Macular Degeneration after Discontinuation of Vascular Endothelial Growth Factor Inhibitors Managed in a Treat-and-Extend Regimen.

PURPOSE: To investigate the recurrence rate of active macular neovascularization in patients with neovascular age-related macular degeneration (nAMD) previously followed up in a treat-and-extend (TE) regimen in which treatment had been stopped because of disease stability. DESIGN: Prospective cohort study. PARTICIPANTS: One hundred five patients with nAMD previously followed up in a TE regimen treated with aflibercept injections. METHODS: All patients with a dry macula on 3 consecutive visits 12 weeks apart were eligible to participate in the study. Patients were examined at baseline and then monitored for disease recurrence 4, 6, 8, 10, and 12 months after the last injection. MAIN OUTCOME MEASURES: The proportion of patients with recurrent disease within 12 months after the last injection. Change in best-corrected visual acuity (BCVA) at the time of recurrence and after resumed therapy. RESULTS: Evidence of recurrent nAMD was seen in 54 of 102 patients (52.9%) after 12 months of follow-up. The mean time to recurrence after the last injection was 6.7 ± 2.2 months. The BCVA decreased from 71.7 ± 10.0 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline to 68.1 ± 11.1 ETDRS letters at the recurrence (P = 0.12). After treatment resumed, BCVA increased to 71.4 ± 10.0 ETDRS letters (P = not significant compared with baseline). Patients with a pigment epithelial detachment (PED) at baseline showed a 74% (14/19) recurrence rate compared with 48% (40/83) in patients without a PED (P < 0.05). Only 22 of 54 patients (40.7%) with recurrent disease showed symptoms of visual loss or metamorphopsia. CONCLUSIONS: Recurrent nAMD is common in previously stable patients for whom anti-VEGF injections have been suspended. It is difficult to predict which patients will experience a recurrence, and most of these patients do not show symptoms in the early stages of reactivation. Long-term follow-up is important, and early detection of recurrent disease can improve the chances for maintained visual function.

Optical Coherence Tomography Angiography in Central Retinal Vein Occlusion: Correlation Between the Foveal Avascular Zone and Visual Acuity.

PURPOSE: To investigate the relationship between best-corrected visual acuity (BCVA) and the foveal avascular zone (FAZ) in patients with central retinal vein occlusion (CRVO) evaluated with optical coherence angiography (OCT-A). METHODS: The study was a prospective consecutive case series including 24 patients with CRVO. All patients received either aflibercept or ranibizumab intravitreal injections prior to analysis. Best-corrected visual acuity and FAZ were evaluated in eyes without macular edema. The FAZ areas were evaluated with OCT-A in both the superficial and deep capillary plexus layers by using 3 × 3-mm images of the macula. Disruption of the ellipsoid zone (EZ) was also analyzed. RESULTS: The mean superficial FAZ area measured 0.76 mm2 (95% confidence interval [CI] 0.50-1.13). The mean deep FAZ area measured 1.12 mm2 (95% CI 0.77-1.47). In a multivariable analysis a negative correlation was found between the BCVA and the superficial FAZ area (r = -0.54, P = 0.03). The correlation between the BCVA and deep FAZ area did not meet statistical significance (r = -0.43, P = 0.09). In a multivariable analysis, disruption of the ellipsoid zone was significantly correlated to a larger superficial FAZ area (r = 0.68, P = <0.001) and poor visual acuity (r = 0.75, P < 0.001). CONCLUSIONS: Optical coherence tomography-A is a novel technique that allows segmented evaluation of the FAZ in patients with CRVO providing additional prognostic information. The FAZ areas were enlarged both in the superficial and the deep capillary networks. A significant correlation was found between BCVA and the FAZ area in CRVO patients without macular edema (ClinicalTrials.gov, number NCT02274259).