Efficacy and Safety of Brolucizumab for Diabetic Macular Edema: The KINGFISHER Randomized Clinical Trial.

Importance: Despite the effectiveness of existing anti-vascular endothelial growth factor (VEGF) therapies, a need remains for further treatment options to improve response rates and/or reduce injection or monitoring frequency in patients with diabetic macular edema (DME). Objective: To evaluate the efficacy and safety of brolucizumab vs aflibercept dosed every 4 weeks in participants with DME. Design, Participants, and Setting: This 52-week, double-masked, phase 3 randomized clinical trial included treatment-naive adults and adults who had previously received anti-VEGF therapy. Data were collected from September 2019 to March 2020, and data were analyzed from April 2020 to February 2021. Intervention: Brolucizumab, 6 mg, intravitreal injection every 4 weeks or aflibercept, 2 mg, intravitreal injection every 4 weeks. Main Outcomes and Measures: Participants were randomized 2:1 to brolucizumab, 6 mg, or aflibercept, 2 mg. The primary end point was change from baseline in best-corrected visual acuity at week 52. Secondary end points were the proportion of participants with a 2-step improvement or greater from baseline in Diabetic Retinopathy Severity Scale score, the proportion of eyes with absence of both subretinal fluid and intraretinal fluid, change from baseline in central subfield thickness, and safety at week 52. Results: A total of 517 participants were randomized to brolucizumab (n = 346) or aflibercept (n = 171); 299 (57.8%) were male, and the mean (SD) age was 60.7 (10.2) years. Brolucizumab was noninferior to aflibercept in best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study letter score) change from baseline at week 52 (brolucizumab, 12.2-letter improvement; aflibercept, 11.0-letter improvement; difference, 1.1; 95% CI, -0.6 to 2.9; noninferiority margin, 4; P < .001). Brolucizumab was superior to aflibercept for the proportion of eyes without subretinal and intraretinal fluid (brolucizumab, 144 of 346 [41.6%]; aflibercept, 38 of 171 [22.2%]; difference, 20.0%; 95% CI, 12.5to 28.6; P < .001) and mean central subfield thickness change from baseline at week 52 (brolucizumab, -237.8 µm; aflibercept, -196.5 µm; difference, -41.4; 95% CI, -58.9 to -23.8; P < .001). Incidence of intraocular inflammation was 4.0% (14 of 346) in the brolucizumab arm and 2.9% (5 of 171) in the aflibercept arm, incidence of retinal vasculitis was 0.9% (3 of 346) and 0.6% (1 of 171), respectively, and incidence of retinal vascular occlusion was 0.3% (1 of 346) and 0.6% (1 of 171). One participant in the brolucizumab arm had retinal artery occlusion. Conclusions and Relevance: In these study participants with DME, no clinically meaningful differences in visual outcomes were noted between the brolucizumab and aflibercept arms; some superior anatomic improvements were noted in the brolucizumab arm. No new safety concerns were identified. Trial Registration: ClinicalTrials.gov Identifier: NCT03917472.

Short-term Efficacy and Safety of Ranibizumab for Neovascular Age-related Macular Degeneration in the Real World: A Post-marketing Surveillance Study.

PURPOSE: To investigate the short-term efficacy and safety of ranibizumab in the routine clinical setting in patients with neovascular age-related macular degeneration and to analyze the associated factors for visual outcome. METHODS: This was a post-hoc analysis of a ranibizumab regulatory post-marketing surveillance study in which 4,136 patients were enrolled and followed for 12 weeks. Change in best-corrected visual acuity (BCVA), size of choroidal neovascularization, and the presence of hemorrhage and exudate were analyzed and the association between BCVA change and baseline characteristics were investigated. Data on ocular and systemic adverse events were collected. RESULTS: Mean BCVA improved significantly and mean BCVA change was the logarithm of the minimal angle of resolution 0.13 ± 0.01 (p < 0.001). A lower baseline BCVA and younger age were significant predictive factors for visual improvement or maintenance (≥0 lines). For greater visual acuity gain (≥3 lines), no treatment history, lower baseline BCVA, younger age, and classic-type choroidal neovascularization were significant predictive factors. No new safety signals were found. CONCLUSIONS: In this study, conducted in real-world clinical practice with a large number of neovascular age-related macular degeneration patients, visual and anatomical outcomes improved significantly after three monthly ranibizumab treatments. Treatment-naive patients had a higher chance of greater visual gain (≥3 lines) than non-naive patients.

Delayed Absorption of Subretinal Fluid after Retinal Reattachment Surgery and Associated Choroidal Features.

PURPOSE: The aim of this study was to investigate the incidence and associated clinical factors of delayed absorption of subretinal fluid (SRF) after surgery for rhegmatogenous retinal detachment. METHODS: This study involved 36 eyes of 36 consecutive patients who underwent successful surgery for rhegmatogenous retinal detachment. A complete ophthalmologic evaluation, including clinical fundus examination, optical coherence tomography, and indocyanine green angiography, was conducted before and after surgery. Delayed absorption was defined as the presence of residual concave SRF or an SRF bleb at 6 months after surgery. Clinical factors and choroidal features on indocyanine green angiography were compared according to the presence and absence of delayed absorption. RESULTS: Eighteen of 36 eyes (50%) showed delayed absorption. Macular involvement and worse preoperative visual acuity were significantly related to the presence of delayed absorption (p = 0.001 and p = 0.034, respectively). On indocyanine green angiography, preoperative choroidal vascular hyperpermeability was noted in 70% of eyes with delayed absorption and in 14% of eyes without it (p = 0.010). CONCLUSIONS: Delayed absorption of SRF after retinal reattachment surgery was not rare, with a 50% of incidence in this study. Macula-off status was significantly related to the incidence of delayed SRF absorption, and choroidal features such as choroidal vascular hyperpermeability might be responsible in part, possibly through the resultant exudative property of choroid.

Optical Coherence Tomographic Features and Prognosis of Pneumatic Displacement for Submacular Hemorrhage.

PURPOSE: To identify prognostic factors, including optical coherence tomographic features, of visual outcome in exudative age-related macular degeneration with submacular hemorrhage treated with pneumatic displacement. METHODS: This retrospective interventional case series included 37 eyes with exudative age-related macular degeneration and submacular hemorrhage, all of which underwent pneumatic displacement. The best-corrected visual acuity (BCVA) was measured at diagnosis and at 3 and 6 months after treatment. In addition to demographic and funduscopic parameters, tomographic features such as reflectance of the submacular hemorrhage were analyzed with regard to BCVA at 6 months. RESULTS: After pneumatic displacement and a subsequent treatment such as laser or anti-vascular endothelial growth factor therapy, the BCVA at 3 and 6 months improved significantly (P < 0.001, respectively). Higher baseline BCVA (P < 0.001), shorter symptom duration (P = 0.007), and younger age (P = 0.014) were significant positive prognostic factors on regression analysis. Among optical coherence tomography characteristics, reflectance of the submacular hemorrhage, the shortest radius of the submacular hemorrhage centered on the fovea, and defects in the ellipsoid zone, and external limiting membrane affected the BCVA at 6 months (P < 0.05). CONCLUSION: A favorable visual outcome was demonstrated after initial pneumatic displacement and subsequent treatment for submacular hemorrhage. The submacular hemorrhages exhibiting lower reflectance on optical coherence tomography and a smaller shortest radius from the foveal center were found to be good candidates for pneumatic displacement.

Anterior Diabetic Retinopathy Studied by Ultra-widefield Angiography.

PURPOSE: To evaluate the prevalence of anterior type diabetic retinopathy (DR) using ultra-widefield fluorescein angiography and to identify the factors associated with anterior type DR incidence. METHODS: A retrospective case review was used in this study. Patients with non-proliferative diabetic retinopathy (NPDR) underwent examination by ultra-widefield fluorescein angiography, and were classified into anterior, posterior, or diffuse DR groups. Anterior DR was defined if diabetic retinal changes were noted only at the location anterior to the imaginary circle bordered by the Early Treatment Diabetic Retinopathy Study seven-standard fields. Correlations between demographic data, as well as systemic and ocular factors, and the incidence of NPDR types were evaluated. RESULTS: Among the 234 eyes of 234 patients with NPDR, 25 eyes (10.7%) demonstrated anterior DR. Anterior DR was observed in 10 eyes (30.3%) of patients having mild NPDR, three eyes (4.8%) of moderate NPDR patients, and in 12 eyes (7.1%) of severe NPDR patients (p < 0.001). The incidence of anterior DR positively correlated with lower hemoglobin A1c levels and with greater high-density lipoprotein levels following multiple logistic regression analysis (p < 0.001). The mean hemoglobin A1c level was 7.03 ± 0.99% in anterior DR, 7.99 ± 1.74% in posterior DR, and 7.94 ± 1.39% in diffuse DR patients (p = 0.003). The mean high-density lipoprotein level was 51.2 ± 12.5 mg/dL in anterior, 49.7 ± 15.2 mg/dL in posterior, and 45.2 ± 13.1 mg/dL in diffuse DR patients (p = 0.010). CONCLUSIONS: Diabetic retinal changes confined to an anterior location were more frequently noted in earlier stages of NPDR. The incidence of DR sparing posterior retinal involvement was related to favorable blood sugar and lipid profiles.

Macular ischemia and outcome of vitrectomy for diabetic macular edema.

PURPOSE: To investigate the effect of vitrectomy on the treatment of diabetic macular edema (DME) refractory to nonsurgical therapies and to determine the preoperative prognostic factors related to surgical outcomes. METHODS: Seventy-seven eyes from 74 patients who had undergone vitrectomy and macular photocoagulation 2 weeks after vitrectomy for nontractional DME refractory to anti-vascular endothelial growth factor or steroid injection and/or macular grid/focal photocoagulation were included. The eyes were divided into the responsive group (group 1) and the unresponsive group (group 2) according to the postoperative changes in central subfield thickness (CST). The changes in best-corrected visual acuity (BCVA) and CST were compared. Potential preoperative predictors including the size of the foveal avascular zone (FAZ) were assessed. RESULTS: In group 1 (N = 51), the mean logarithm of the minimum angle of resolution BCVAs at baseline was 0.60 ± 0.30; 6 months after vitrectomy, 0.47 ± 0.28 (vs. baseline, p < 0.001); 12 months after vitrectomy, 0.38 ± 0.28 (vs. baseline, p < 0.001). However, in group 2 (N = 26), no significant change in BCVA was noted. Among the preoperative factors, only the size of the FAZ showed a significant difference between the two groups (0.45 ± 0.17 mm(2) in group 1 vs. 0.59 ± 0.26 mm(2) in group 2; p = 0.020). The enlarged FAZ was also significantly correlated with worse BCVA at the postoperative 6-month follow-up (r = 0.256, p = 0.025). CONCLUSIONS: Vitrectomy is an effective treatment modality for DME refractory to nonsurgical therapies, especially in cases without enlarged FAZ. Preoperative evaluation of the perfusion status of the macula seems helpful to selecting candidates for vitrectomy.

Visual Impairment of Korean Population: Prevalence and Impact on Mental Health.

PURPOSE: We identified the prevalence and sociodemographic characteristics of people with visual impairment (VI), and determined the relationship between VI and mental health in the Korean population. METHODS: This is a cross-sectional study using the database of the Korean National Health and Nutrition Examination Survey from 2008 through 2012. A total of 28,392 participants at 19 years of age or older with data of visual acuity and mental health questionnaire was included. Prevalence of VI and its association with sociodemographic factors were analyzed. Multivariate regression analyses were conducted to determine the association of VI with mental health. RESULTS: Estimated prevalence of VI was 0.43% (95% confidence interval [CI], 0.35-0.52%) in adults aged 19 years and over. After adjusting for sex, the VI group was significantly older (P < 0.001). After adjusting for age and sex, the VI group showed increased odds ratios (ORs) for diabetes mellitus (P < 0.001), lower education (P < 0.001), no occupation (P = 0.046), restricted daily activity (P < 0.001), and being single (P = 0.002) compared to the control group. After adjusting for covariates, VI was not associated with any of mental health parameters (OR, 0.88 [95% CI, 0.53-1.47] for depressive symptom; 1.38 [0.91-2.09] for suicidal ideation; 1.26 [0.82-1.94] for perceived stress). However, restricted daily activity was the strongest risk factor for poor mental health (OR, 2.49 [2.22-2.79] for depressive symptom; 2.77 [2.51-3.06] for suicidal ideation; 2.30 [2.09-2.54] for perceived stress). CONCLUSIONS: Visually impaired people showed significantly unfavorable sociodemographic status. Although VI was not directly associated with mental health, restricted daily activity and poor sociodemographic factors found in visually impaired people increased risk for poor mental health.

Changing trends in surgery for retinal detachment in Korea.

PURPOSE: To analyze trends in rhegmatogenous retinal detachment (RRD) surgery among the members of the Korean Retina Society from 2001 to 2013. METHODS: In 2013, surveys were conducted by email and post to investigate the current practice patterns regarding RRD treatment. Questions included how surgeons would manage six cases of hypothetical RRD. Results were compared to those reported in 2001. RESULTS: A total of 133 members (60.7%) in 2013 and 46 members(79.3%) in 2001 responded to the survey. Preference for pneumatic retinopexy has decreased in uncomplicated primary RRD (p = 0.004). More respondents in 2013 selected vitrectomy as the primary procedure when mild vitreous hemorrhage (p = 0.001), myopia (p = 0.044) and history of successful scleral buckling on the fellow eye (p = 0.044) were added to the primary scenario. Vitrectomy was over twice as popular in cases of pseudophakic, macula-off RRD with posterior capsular opacity (p = 0.001). CONCLUSIONS: For RRD with myopia, pseudophakia and media opacity, surgical interventions over the last decade have drastically shifted from scleral buckling and pneumatic retinopexy to vitrectomy.

Change in subfoveal choroidal thickness after argon laser panretinal photocoagulation.

AIM: To evaluate changes in subfoveal choroidal thickness (SFCT) and macular thickness as measured by enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT) after argon laser panretinal photocoagulation (PRP) in patients with severe diabetic retinopathy. METHODS: This prospective, comparative case series included 21 patients (28 eyes) with severe diabetic retinopathy. All patients underwent three sessions of PRP. The SFCT and macular thickness were measured using EDI-OCT at baseline and one week after completion of 3 sessions of PRP. RESULTS: SFCT before PRP was (318.1±96.5)µm and increased to (349.9±108.3)µm (P=0.001) after PRP. Macular thickness significantly increased at one week after PRP (from 273.1±23.9µm at baseline vs 295.8±25.3µm at one week; P<0.001). No significant relationship between the changes in macular thickness and SFCT was observed (r=-0.13, P=0.52). CONCLUSION: PRP induced increases in both SFCT and macular thickness. Changes in SFCT did not correlate with changes in macular thickness.