Short-Term Real-World Outcomes of Intensive Aflibercept Injection for Refractory Neovascular Age-Related Macular Degeneration.

Background: The aim of this study is to report short-term outcomes after the shortening of the treatment interval to 4 weeks with a treat-and-extend (TAE) regimen (Si4w) of aflibercept in patients with refractory neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included 34 patients given aflibercept with a TAE regimen of a minimum of a 4-week interval when they had a limited response to bimonthly aflibercept. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) were compared before and after Si4w. The resolution of subretinal and intraretinal fluid before and after Si4w was also examined. The risk factors associated with persistent fluid were analyzed. Results: The average treatment duration until initiation of Si4w was 57.82 ± 28.59 months, with an average of 23.64 ± 12.40 injections administered. The BCVA was not significantly improved after Si4w. The CMT decreased significantly from 427.91 ± 125.74 µm to 336.38 ± 121.67 µm at the third visit (p < 0.001). Eighteen eyes (52.9%) showed complete resolution, and twenty-three eyes (67.6%) experienced complete resolution at least once during the three visits. The duration of fluid before Si4w was significantly associated with complete resolution (p = 0.011). Conclusions: Si4w of aflibercept showed satisfactory anatomical outcomes with complete resolution of fluid in patients with a limited response to bimonthly aflibercept injections, and should be considered as a useful treatment option.

Biosimilar candidate CT-P42 in diabetic macular edema: 24-week results from a randomized, active-controlled, Phase III study.

OBJECTIVE: To demonstrate the therapeutic similarity of CT-P42 compared to reference aflibercept (Eylea®) in adult patients with diabetic macular edema (DME). DESIGN: Randomized, active-controlled, double-masked, Phase III clinical trial PARTICIPANTS: Patients with a diagnosis of either type 1 or 2 diabetes mellitus (DM) with DME involving the center of the macula. METHODS: Patients were randomized (1:1) to receive either CT-P42 or reference aflibercept (2 mg/0.05 mL) by intravitreal injection every 4 weeks (5 doses) then every 8 weeks (4 doses) in the main study period. Results up to Week 24 are reported herein. MAIN OUTCOME MEASURES: The primary endpoint was mean change from baseline at Week 8 in best corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Equivalence between CT-P42 and reference aflibercept was to be concluded if the two-sided 95% confidence interval (CI) (global assumptions) and two-sided 90% CI (US Food and Drug Administration [FDA] assumptions) for the treatment difference fell entirely within the equivalence margin of ±3 letters, as assessed in the full analysis set. RESULTS: Overall, 348 patients were randomized (CT-P42: 173; reference aflibercept: 175). BCVA improved from baseline to Week 8 in both groups, with a least squares mean (standard error) improvement of 9.43 (0.798) and 8.85 (0.775) letters in the CT-P42 and reference aflibercept groups, respectively. The estimated between-group treatment difference was 0.58 letters, with the CIs within the pre-defined equivalence margin of ±3 letters (95% CI -0.73, 1.88 [global]; 90% CI -0.52, 1.67 [FDA]). Through Week 24, other efficacy results for the two groups, in terms of change in BCVA and retinal central subfield thickness, as well as ETDRS Diabetic Retinopathy Severity Scale score, supported therapeutic similarity. Pharmacokinetics, usability, safety (including the proportions of patients experiencing at least one treatment-emergent adverse event [CT-P42: 50.3%; reference aflibercept: 53.7%]), and immunogenicity were also comparable between groups. CONCLUSIONS: This study in patients with DME demonstrated equivalence between CT-P42 and reference aflibercept (2 mg/0.05 mL) in terms of efficacy, with similar pharmacokinetic, usability, safety, and immunogenicity profiles.

Prevalence and predictive value of sarcopenia in hospitalized patients with ischemic colitis.

Ischemic colitis (IC) and sarcopenia are associated with aging and multiple comorbidities. We aimed to investigate the prevalence and predictive role of sarcopenia in patients with IC. We retrospectively analyzed 225 hospitalized patients (median age, 72 years; women, 67.1%; severe IC, 34.2%) who were diagnosed with IC between January 2007 and February 2022. Sarcopenia was defined as the skeletal muscle index at the third lumbar vertebra determined by computed tomography. It was present in 49.3% (n = 111) of the patients and was significantly associated with severe IC compared to those without sarcopenia (48.6% vs. 20.2%, P < 0.001). Sarcopenia was associated with extended hospitalization (median: 8 vs. 6 days, P < 0.001) and fasting periods (4 vs. 3 days, P = 0.004), as well as prolonged antibiotic use (9 vs. 7 days, P = 0.039). Sarcopenia was linked to a higher risk of surgery or mortality (9.0% vs. 0%, P = 0.001) and independently predicted this outcome (odds ratio [OR], 11.17; 95% confidence interval [CI], 1.24‒1467.65, P = 0.027). It was prevalent among hospitalized patients with IC, potentially indicating severe IC and a worse prognosis. This underscores the importance of meticulous monitoring, immediate medical intervention, and timely surgical consideration.

Long-term efficacy and safety of brolucizumab in neovascular age-related macular degeneration: A multicentre retrospective real-world study.

PURPOSE: To investigate the long-term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age-related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow-up duration of ≥12 months. Changes in best-corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups. RESULTS: Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1 ± 8.6 years). 29 eyes (7.2%) were treatment naïve. The mean follow-up period was 15.3 ± 2.8 months; the mean number of BRZ injections within 1 year was 4.5 ± 1.7. BCVA was maintained during the follow-up period, and CST significantly improved from the first injection month and was maintained for 12 months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1 month and 42.9% at 12 months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes) and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5 ± 1.4 days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution. CONCLUSION: Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1 year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management.

Biosimilars of anti-vascular endothelial growth factor for ophthalmic diseases: A review.

The development of intravitreally injected biologic medicines (biologics) acting against vascular endothelial growth factor (VEGF) substantially improved the clinical outcomes of patients with common VEGF-driven retinal diseases. The relatively high cost of branded agents, however, represents a financial burden for most healthcare systems and patients, likely resulting in impaired access to treatment and poorer clinical outcomes for some patients. Biosimilar medicines (biosimilars) are clinically equivalent, potentially economic alternatives to reference products. Biosimilars approved by leading health authorities have been demonstrated to be similar to the reference product in a comprehensive comparability exercise, generating the totality of evidence necessary to support analytical, pre-clinical, and clinical biosimilarity. Anti-VEGF biosimilars have been entering the field of ophthalmology in the US since 2022. We review regulatory and scientific concepts of biosimilars, the biosimilar development landscape in ophthalmology, with a specific focus on anti-VEGF biosimilars, and discuss opportunities and challenges facing the uptake of biosimilars.

Biosimilar SB15 versus reference aflibercept in neovascular age-related macular degeneration: 1-year and switching results of a phase 3 clinical trial.

BACKGROUND/AIMS: To evaluate efficacy, safety, pharmacokinetics (PK) and immunogenicity of SB15 versus reference aflibercept (AFL), and switching from AFL to SB15 in neovascular age-related macular degeneration (nAMD). DESIGN: Prospective, double-masked, randomised, phase 3 trial. METHODS: Participants with nAMD were randomised 1:1 to receive SB15 (N=224 participants) or AFL (N=225). At week 32, participants either continued on SB15 (SB15/SB15, N=219) or AFL (AFL/AFL, N=108), or switched from AFL to SB15 (AFL/SB15, N=111). This manuscript reports 1-year and switching results of secondary efficacy endpoints such as changes from baseline to week 56 in best-corrected visual acuity (BCVA), central subfield thickness (CST, from internal limiting membrane (ILM) to retinal pigment epithelium), and total retinal thickness (TRT, from ILM to Bruch's membrane). Additional endpoints included safety, PK and immunogenicity. RESULTS: Efficacy results were comparable between groups. The least squares mean (LSmean) change in BCVA from baseline to week 56 was 7.4 letters for SB15/SB15 and 7.0 letters for AFL/AFL (difference (95% CI)=0.4 (-2.5 to 3.2)). The LSmean changes from baseline to week 56 in CST and TRT were -119.2 µm and -132.4 µm for SB15/SB15 and -126.6 µm and -136.3 µm for AFL/AFL, respectively (CST: difference (95% CI)=7.4 µm (-6.11 to 20.96); TRT: difference (95% CI)=3.9 µm (-18.35 to 26.10)). Switched and non-switched participants showed similar LSmean changes in BCVA from baseline to week 56 (AFL/SB15, 7.9 letters vs AFL/AFL, 7.8 letters; difference (95% CI)=0.0 (-2.8 to 2.8)). Safety, PK and immunogenicity were comparable between groups. CONCLUSIONS: Efficacy, safety, PK and immunogenicity were comparable between SB15 and AFL and between switched and non-switched participants.

Predictors of treatment outcomes following treat-and-extend regimen with aflibercept for branch retinal vein occlusion: post-hoc analysis of the PLATON trial.

We investigated predictors of visual outcomes and injection interval in macular edema (ME) secondary to branch retinal vein occlusion (BRVO) treated with a treat-and-extend (TAE) regimen. All 48 patients in a multicenter study were followed for 52 weeks and received three monthly intravitreal aflibercept injections before the TAE regimen, with treatment intervals adjusted by 4 weeks, up to a maximum of 16 weeks. Various laboratory biomarkers and optical coherence tomography parameters were evaluated. Patients were classified into the extension failure group if they had ≥ 1 treatment interval decreased due to an increase in the central macular thickness compared to the previous visit and 18 patients were assigned to this group. In multivariate logistic analyses, presence of microaneurysms and prominent middle limiting membrane (p-MLM) sign, increased initial external limiting membrane (ELM) disruption, and higher total cholesterol were correlated with inhibiting a sustained extension in the injection interval (P = 0.015, P = 0.032, P = 0.037, P = 0.009, respectively). Therefore, in the patients with ME secondary to BRVO with these risk factors, early consideration of frequent injection may improve treatment outcome.

Efficacy and Safety of the Aflibercept Biosimilar SB15 in Neovascular Age-Related Macular Degeneration: A Phase 3 Randomized Clinical Trial.

Importance: Aflibercept biosimilars can expand available treatment options in retinal diseases and have the potential to improve patient access to safe and effective therapy. Objective: To establish equivalence in efficacy and similarity in safety, pharmacokinetics, and immunogenicity of SB15 and reference aflibercept (AFL) in neovascular age-related macular degeneration (nAMD). Design, Setting, and Participants: This was a randomized double-masked parallel group phase 3 trial conducted at 56 centers in 10 countries from June 2020 to March 2022, including follow-up through 56 weeks. Of 549 screened participants, 449 participants 50 years and older with treatment-naive nAMD were included and randomly assigned to SB15 (n = 224) or AFL (n = 225). Key exclusion criteria included considerable scarring, fibrosis, atrophy, and hemorrhage. This report includes results up to the end of the parallel group period at week 32. Of the 449 randomized participants, 438 (97.6%) completed week 32 follow-up. Intervention: Participants were randomized 1:1 to receive 2 mg of SB15 or AFL every 4 weeks for the first 12 weeks (3 injections), followed by dosing every 8 weeks up to week 48, with final assessments at week 56. Main Outcomes and Measures: The primary end point was the change in best-corrected visual acuity (BCVA) from baseline to week 8 with predefined equivalence margins of -3 letters to 3 letters. Other key end points were changes in BCVA and central subfield thickness up to week 32, safety, pharmacokinetics, and immunogenicity. Results: The mean (SD) age among the 449 included participants was 74.0 (8.1) years, and 250 participants (55.7%) were female. Baseline demographic characteristics and most disease characteristics were comparable between treatment groups. The least squares mean change in BCVA from baseline to week 8 in the SB15 group was equivalent to that in the AFL group (6.7 letters vs 6.6 letters, respectively; difference, 0.1 letters; 95% CI, -1.3 to 1.4). Comparable efficacy between treatment groups was maintained up to week 32 (least squares mean change from baseline in BCVA: SB15, 7.6 letters vs AFL, 6.5 letters; least squares mean change from baseline in central subfield thickness: SB15, -110.4 µm vs AFL, -115.7 µm). No clinically relevant differences were observed in the incidence of treatment-emergent adverse events (TEAEs) (SB15, 107/224 [47.8%] vs AFL, 98/224 [43.8%]) and ocular TEAEs in the study eye (SB15, 41/224 [18.3%] vs AFL, 28/224 [12.5%]). The serum concentration profiles and cumulative incidences of overall antidrug antibody positive participants were comparable. Conclusions and Relevance: In this phase 3 randomized clinical trial, SB15 and AFL showed equivalent efficacy and comparable safety, pharmacokinetics, and immunogenicity in participants with nAMD. Trial Registration: ClinicalTrials.gov Identifier: NCT04450329.

Synthesis of chiral malonates by α-alkylation of 2,2-diphenylethyl tert-butyl malonates via enantioselective phase-transfer catalysis.

An efficient synthetic approach for chiral malonates was established via enantioselective phase transfer catalysis. The α-alkylation of 2,2-diphenylethyl tert-butyl α-methylmalonates with (S,S)-3,4,5-trifluorophenyl-NAS bromide as a phase-transfer catalyst under phase-transfer catalytic conditions successfully produced corresponding α-methyl-α-alkylmalonates; these compounds are versatile chiral building blocks containing a quaternary carbon center in high chemical yields (up to 99%) with excellent enantioselectivities (up to 98% ee). α,α-Dialkylmalonates were selectively hydrolyzed to the corresponding chiral malonic monoacids under basic (KOH/MeOH) and acidic conditions (TFA/CH2Cl2), showing the practicality of the method.

Clinical implications of choroidal vascular brightness using ultra-widefield indocyanine green angiography in polypoidal choroidal vasculopathy.

Polypoidal choroidal vasculopathy (PCV) is characterized by choroidal vascular abnormalities including polypoidal lesion and branching vascular networks. Not only choroidal structural changes, but also choroidal hyperpermeability and congestion are also thought to be involved in pathogenesis of PCV. We investigated choroidal vascular brightness intensity (CVB) using ultra-widefield indocyanine green angiography (UWF-ICGA) images and analyzed its association with clinical features in patients with PCV. In this study, 33 eyes with PCV and 27 eyes of age-matched controls were included. CVB was measured by extracting the enhanced pixels of choroidal vessels after the reference brightness across the images was adjusted to be uniform. Associations between choroidal vascular features and the clinical features of PCV were also determined. The mean CVB was higher in PCV than control eyes, regardless of the segmented region (all p < 0.001). CVB was also higher at the posterior pole than at the periphery, and the inferior quadrants were brighter than the superior quadrants in both the PCV and control group (all p < 0.05). In affected eyes, CVB was higher than in unaffected fellow eyes at the posterior pole, whereas there was no difference at the periphery. Posterior pole CVB correlated significantly with subfoveal choroidal thickness (r = 0.502, p = 0.005), polyp number (r = 0.366 p = 0.030), and the greatest linear dimension (r = 0.680, p = 0.040). Greatest linear dimension was positively correlated with CVB at posterior pole (p = 0.040), whereas SFCT or CVD in all regions didn't show the significant correlation. The UWF ICGA results showed an increase in CVB at the inferior quadrants and posterior pole, suggesting venous outflow congestion in PCV eyes. CVB might provide more substantial information on the phenotype than other choroidal vascular features.

Neurologic Dysfunction Assessment in Parkinson Disease Based on Fundus Photographs Using Deep Learning.

Importance: Until now, other than complex neurologic tests, there have been no readily accessible and reliable indicators of neurologic dysfunction among patients with Parkinson disease (PD). This study was conducted to determine the role of fundus photography as a noninvasive and readily available tool for assessing neurologic dysfunction among patients with PD using deep learning methods. Objective: To develop an algorithm that can predict Hoehn and Yahr (H-Y) scale and Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score using fundus photography among patients with PD. Design, Settings, and Participants: This was a prospective decision analytical model conducted at a single tertiary-care hospital. The fundus photographs of participants with PD and participants with non-PD atypical motor abnormalities who visited the neurology department of Kangbuk Samsung Hospital from October 7, 2020, to April 30, 2021, were analyzed in this study. A convolutional neural network was developed to predict both the H-Y scale and UPDRS-III score based on fundus photography findings and participants' demographic characteristics. Main Outcomes and Measures: The area under the receiver operating characteristic curve (AUROC) was calculated for sensitivity and specificity analyses for both the internal and external validation data sets. Results: A total of 615 participants were included in the study: 266 had PD (43.3%; mean [SD] age, 70.8 [8.3] years; 134 male individuals [50.4%]), and 349 had non-PD atypical motor abnormalities (56.7%; mean [SD] age, 70.7 [7.9] years; 236 female individuals [67.6%]). For the internal validation data set, the sensitivity was 83.23% (95% CI, 82.07%-84.38%) and 82.61% (95% CI, 81.38%-83.83%) for the H-Y scale and UPDRS-III score, respectively. The specificity was 66.81% (95% CI, 64.97%-68.65%) and 65.75% (95% CI, 62.56%-68.94%) for the H-Y scale and UPDRS-III score, respectively. For the external validation data set, the sensitivity and specificity were 70.73% (95% CI, 66.30%-75.16%) and 66.66% (95% CI, 50.76%-82.25%), respectively. Lastly, the calculated AUROC and accuracy were 0.67 (95% CI, 0.55-0.79) and 70.45% (95% CI, 66.85%-74.04%), respectively. Conclusions and Relevance: This decision analytical model reveals amalgamative insights into the neurologic dysfunction among PD patients by providing information on how to apply a deep learning method to evaluate the association between the retina and brain. Study data may help clarify recent research findings regarding dopamine pathologic cascades between the retina and brain among patients with PD; however, further research is needed to expand the clinical implication of this algorithm.

Aqueous microRNA profiling in age-related macular degeneration and polypoidal choroidal vasculopathy by next-generation sequencing.

Although many studies demonstrated the differences of clinical features, natural course, and response to treatment between typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV), differential microRNAs (miRNAs) expression in the aqueous humor (AH) between them has not been reported yet. We investigated the roles of miRNAs in the AH of patients with typical AMD and PCV using next-generation sequencing (NGS) and quantitative PCR (qPCR). Target genes and predicted pathways of miRNAs were investigated via pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes database. A total of 161 miRNAs from eyes with typical AMD and 185 miRNAs from eyes with PCV were differentially expressed. 33 miRNAs were commonly upregulated, and 77 miRNAs were commonly downregulated in both typical AMD and PCV groups. Among them, hsa-miR-140-5p, hsa-miR-374c-3p, and hsa-miR-200a-5p were differentially expressed and were predicted to regulate proteoglycans in cancer, p53 signaling pathway, Hippo signaling pathway, and adherens junction. The differential expression profiles and target gene regulation networks of AH miRNAs may contribute to the development of different pathological phenotypes in typical AMD and PCV. The results of this study provide novel insights into the pathogenesis, associated prognostic biomarkers, and therapeutic targets in AMD and PCV.

Short-Term Safety and Efficacy of Intravitreal Brolucizumab Injections for Neovascular Age-Related Macular Degeneration: A Multicenter Retrospective Real-World Study.

INTRODUCTION: The aim of the study was to determine the short-term real-world safety and efficacy of intravitreal brolucizumab injections in Korean patients with neovascular age-related macular degeneration (nAMD). METHODS: This multicenter retrospective study involved 294 eyes (treatment naïve 20 eye [6.8%] and nontreatment naïve 274 eyes [93.2%]) of 290 patients from 13 hospitals or retinal centers in South Korea. Patients with nAMD who received brolucizumab injection(s) between April 1 and November 30, 2021, with a follow-up ≥1 month, were included. Primary outcomes were safety, incidence of intraocular inflammation (IOI), and potential risk factors. The secondary outcome was efficacy, i.e., change in best-corrected visual acuity (BCVA) and optical coherence tomography-measured macular thickness and retinal fluid. RESULTS: The mean age was 71.63 ± 8.66. The follow-up period was 2.38 ± 0.79 months. The mean number of brolucizumab injections during the follow-up was 1.52 ± 0.58. The overall incidence of IOI was 13.9% (n = 41 eyes). Most IOI cases were of anterior uveitis (8.8%, 26 eyes), followed by retinal vasculitis (2.4%, seven eyes) and occlusive retinal vasculitis (0.3%, one eye). Most eyes showed IOI resolution (n = 40, 97.5%) and BCVA restoration (n = 39, 95.1%) with or without corticosteroid treatment during the follow-up. Age, sex, IOI history, or other anti-vascular endothelial growth factor injection histories were not associated with the occurrence of IOI. However, only thin subfoveal choroidal thickness (SFCT) was associated with the occurrence of IOI (odds ratio = 0.995, p = 0.020). BCVA at 1 month improved from baseline (baseline 0.518 ± 0.356 vs. 1 month 0.503 ± 0.383, p = 0.023), but the improvement was not maintained. Anatomical improvement was significant after 3 months. CONCLUSION: In Korean patients with nAMD, the incidence of IOI following brolucizumab injections was 13.9%. IOI was well-controlled with or without steroid treatment. Most IOI eyes (95.1%) were restored to the level of vision before. IOI occurrence and occlusive vasculitis was rare. In the short term, brolucizumab injection effectively improved vision at 1 month and dried retinal fluid for 3 months.

Plasma Antiretinal Autoantibody Profiling and Diagnostic Efficacy in Patients With Autoimmune Retinopathy.

PURPOSE: To evaluate plasma antiretinal autoantibody (ARA) profiling and diagnostic efficacy for autoimmune retinopathy (AIR). DESIGN: A multicenter, diagnostic evaluation study. METHODS: Forty-nine patients with a clinical diagnosis of AIR, disease controls including 20 patients with retinitis pigmentosa (RP), and 30 normal controls were included. Plasma samples from patients were analyzed for the presence of 6 ARAs, including recoverin, α-enolase, carbonic anhydrase II, heat shock protein 60, aldolase C, and cone-rod homeobox/cone-rod retinal dystrophy 2 using western blotting. RESULTS: Autoantibody detection rates against cone-rod homeobox/cone-rod retinal dystrophy 2, heat shock protein 60, and aldolase C in AIR were 67.3%, 40.8%, and 42.9%, respectively, which were higher than those in RP and normal controls (P < .001, P < .001, and P = .007, respectively), but recoverin, α-enolase, and carbonic anhydrase II were not different from other control groups (P = .117, P = .774, and P = .467, respectively). Among ARAs, antirecoverin antibody was the most specific, as it was found in 3 (6.1%) patients with AIR and none of the control groups. As the number of detected ARAs increased, the probability of AIR increased (odds ratio: 1.913; P < .001; 95% confidence interval: 1.456-2.785). The positive number of ARAs was significantly higher when photoreceptor disruption was observed on optical coherence tomography, or severe dysfunction was observed in electroretinography (P = .022 and P = .029, respectively). CONCLUSIONS: The profiles of ARAs in the AIR group were different from those in the RP and normal controls. The higher number of positive ARAs suggests a higher possibility of AIR diagnosis. ARAs should be used as adjunct tools for the clinical diagnosis of AIR.

MULTIMODAL IMAGING FEATURES AND TREATMENT RESPONSES OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To investigate features of central serous chorioretinopathy with choroidal neovascularization (CNV) on multimodal imaging and analyze their association with treatment response. METHODS: A total of 37 patients with chronic central serous chorioretinopathy complicated by CNV were divided into bevacizumab and photodynamic therapy groups, and each group was subdivided into responders and nonresponders according to subretinal fluid status at 3 months. We assessed multimodal imaging parameters (subfoveal choroidal thickness; vortex vein engorgement; choroidal vascular hyperpermeability; and CNV morphologic pattern, area, and vessel density) and analyzed their association with treatment responses. RESULTS: Responders in the bevacizumab group showed thinner subfoveal choroidal thickness (384.0 ± 103.2 vs. 398.3 ± 87.1 µm, P = 0.042), smaller CNV area (0.512 ± 0.267 vs. 1.323 ± 0.481 mm2, P = 0.007), open-circuit pattern (84.6% vs. 12.5%, P < 0.001), and capillary fringe (69.2% vs. 37.5%, P = 0.001) than nonresponders. Responders in the photodynamic therapy group had thicker subfoveal choroidal thickness (420.1 ± 93.5 vs. 395.7 ± 6.5 µm, P = 0.021), more quadrants with engorged vortex veins extending to the macula (P = 0.012), and intense choroidal vascular hyperpermeability (57.1% vs. 50.0%, P = 0.026) than nonresponders. Choroidal neovascularization showing closed-circuit pattern (85.7% vs. 0%, P = 0.001) and peripheral loop (64.3% vs. 0%, P = 0.001) demonstrated a good response to photodynamic therapy. CONCLUSION: Heterogeneous features of choroidal hyperpermeability, thickness, and CNV morphology in CNV accompanying central serous chorioretinopathy are associated with different therapeutic responses to bevacizumab and photodynamic therapy treatments.

Comparison of treatment methods for submacular hemorrhage in neovascular age-related macular degeneration: conservative versus active surgical strategy.

The optimal treatment of submacular hemorrhage (SMH) following neovascular age-related macular degeneration (nAMD) is controversial. This study aimed to compare visual outcomes of conservative versus active surgical treatment. Two hundred thirty-six eyes of 236 patients with SMH (≥ 1 disc diameter) were stratified into four groups: observation (n = 21); anti-vascular endothelial growth factor (VEGF) monotherapy (n = 161); non-surgical gas tamponade (n = 31); and subretinal surgery (n = 23). The primary outcome was best-corrected visual acuity (BCVA) at 12 months. The baseline BCVAs of the observation, anti-VEGF monotherapy, non-surgical gas tamponade, and subretinal surgery groups were 1.50 ± 0.70, 1.09 ± 0.70, 1.31 ± 0.83, and 1.62 ± 0.77 logarithm of minimal angle resolution (LogMAR), respectively. The mean BCVAs at 12 months were 1.39 ± 0.84, 0.90 ± 0.83, 1.35 ± 0.88, and 1.44 ± 0.91 LogMAR, respectively. After adjusting for age, baseline BCVA, SMH size, and the number of intravitreal anti-VEGF injections before SMH, the mean BCVA showed no significant difference among treatments at 12 months (P = 0.204). The anti-VEGF monotherapy group showed better mean BCVA significantly at 3 months (P < 0.001). Only baseline BCVA was associated with VA gain at 12 months (Odds ratio = 3.53, P < 0.001). This study demonstrated that there was no difference in 12 month visual outcomes among treatments and a better early visual outcome can be expected with anti-VEGF monotherapy.

A real-world study assessing the impact of retinal fluid on visual acuity outcomes in patients with neovascular age-related macular degeneration in Korea.

To evaluate the real-world treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) in Korea, focusing on retinal fluid resolution. This multi-institutional retrospective chart review study, analyzed medical records of patients with nAMD (age ≥ 50 years) who received their first anti-vascular endothelial growth factor (VEGF) treatment in ophthalmology clinics across South Korea between January 2017 and March 2019. The primary endpoint was the proportion of patients with retinal fluid after 12 months of anti-VEGF treatment. The association between fluid-free period and VA gains was also evaluated. A total of 600 patients were enrolled. At baseline, 97.16% of patients had retinal fluid; after 12 months of anti-VEGF treatment, 58.10% of patients had persistent retinal fluid. VA improvements were relatively better in patients with absence of retinal fluid compared with presence of retinal fluid (+ 12.29 letters vs. + 6.45 letters at month 12; P < .0001). Longer duration of absence of retinal fluid over first 12 months correlated with better VA gains at month 12 (P < .01). More than half of the study patients with nAMD had retinal fluid even after 12 months of treatment with their current anti-VEGF. Presence of retinal fluid was associated with relatively worse VA outcomes.

Clinical significance of metabolic quantification for retinal nonperfusion in diabetic retinopathy.

Diabetic retinopathy (DR) is characterized by microvascular changes including ischemia. Degradation and metabolic changes of various retinal cells occur during ischemia. Ischemic region containing more cells will lead to greater metabolic impairment. We analyzed the non-perfusion region (NPR) by integrating histologic mapping with ultra-widefield fluorescein angiography (UWF FA) images. We also investigated the correlations of the weighted ischemic index (ISI) considering the regional distribution of retinal cells with cytokines, macular edema (ME), and neovascularization (NV). In this study, 32 patients with treatment-naïve DR and 21 age-matched control participants were included. The difference between the non-weighted and weighted ISI of NPR with leakage was greatest at the posterior region. The weighted ISI of NPR with leakage was correlated with MCP-1, IL-8, IL-6, PlGF, and VEGF-A levels, while the non-weighted ISI of NPR with leakage was correlated with IL-8 and IL-6 levels. The presence of baseline ME or NV in patients with DR was associated with the weighted ISI, with a stronger association when cones and rods were weighted. The weighted ISI reflecting both metabolic activity and cell distribution demonstrated a better correlation with clinical features and was more valuable in NPR with leakage than non-weighted ISI, which previous studies conventionally used.