Five-year outcomes of treat and extend regimen using intravitreal aflibercept injection for treatment-naïve age-related macular degeneration.

PURPOSE: This study evaluated the long-term outcomes of eyes with neovascular age-related macular degeneration (nAMD) treated with aflibercept according to a treat-and-extend (T&E) regimen for up to 5 years. Methods This retrospective study included 112 eyes of 111 patients with nAMD who received aflibercept according to the T&E regimen. The patients received 3 monthly injections of aflibercept followed by a T&E regimen for at least 12 months. Data, including best-corrected visual acuity (BCVA), treatment interval, presence of exudation, central retinal thickness, and central choroidal thickness were analyzed. RESULTS: Of the 112 consecutive eyes, 66 completed the 5-year follow-up. After 5 years of treatment, BCVA (logMAR) was significantly better than baseline (0.29 ± 0.31 at baseline and 0.18 ± 0.23 at 5 years, P < 0.01). A mean of 7.0 ± 1.5 injections in the first year and 4.9 ± 2.2 injections per year thereafter were required. In eyes with subretinal hyperreflective material (SHRM) at baseline, BCVA at baseline and 5 years were significantly worse than in eyes without SHRM at baseline and 5 years. However, the eyes with SHRM required fewer injections and exhibited greater BCVA improvement. CONCLUSION: This retrospective study demonstrated the effectiveness of the T&E regimen with aflibercept in managing nAMD over a 5-year period, maintaining significant improvements in BCVA.

Predictive factors for outcomes of half-dose photodynamic therapy combined with aflibercept for pachychoroid neovasculopathy.

PURPOSE: To assess the effects of half-dose photodynamic therapy (PDT) combined with an intravitreous aflibercept (IVA) injection for pachychoroid neovasculopathy (PNV) and its predictive factors. METHODS: Clinical information of 43 patients (43 eyes) with PNV obtained before and 6 months after treatment with half-dose PDT combined with IVA was retrospectively analyzed. Patients were categorized into the sufficient (25 eyes, 58.1%) or insufficient (18 eyes, 41.9%) group based on resolution or persistence/recurrence of subretinal fluid (SRF), respectively, and clinical data were compared. Macular neovascularization (MNV) change was studied in 30 cases with available pre- and post-treatment optical coherence tomography angiography images. RESULTS: The sufficient group included younger patients with better baseline best-corrected visual acuity (BCVA), more treatment-naïve eyes, and smaller MNV lesions at baseline than the insufficient group (all, P < 0.047). Complete SRF resolution was 81.8% in treatment-naïve eyes and only 33.3% in previously treated eyes. MNV expanded after half-dose PDT was combined with IVA regardless of the treatment outcome (P = 0.003). CONCLUSION: Half-dose PDT combined with IVA was effective for PNV treatment, especially for younger patients with good baseline BCVA, treatment-naïve eyes, and small MNV sizes at baseline. MNV expanded after treatment regardless of the treatment outcomes.

LONG-TERM MORPHOLOGIC CHANGES IN MACULAR NEOVASCULARIZATION UNDER AFLIBERCEPT TREATMENT WITH A TREAT-AND-EXTEND REGIMEN.

PURPOSE: To examine the morphologic changes in macular neovascularization (MNV) secondary to age-related macular degeneration after 2 years of aflibercept treatment under a treat-and-extend (T&E) regimen. METHODS: This retrospective study analyzed the medical records for 26 eyes of 25 patients diagnosed with treatment-naive neovascular age-related macular degeneration and treated with aflibercept under a treat-and-extend regimen for 2 years. The areas of the MNV and vascular structures were assessed using swept-source optical coherence tomography angiography at baseline and after 2 years of treatment. RESULTS: The mean MNV area increased significantly from 0.65 ± 0.42 mm 2 at baseline to 0.78 ± 0.45 mm 2 at 2 years. At 2 years, the mean change in the MNV area from baseline was 22% (interquartile range: 4%-60%). The baseline MNV area was negatively correlated with the change ratio of the MNV areas at 2 years and baseline ( R = -0.68, P < 0.001). Nine of the 26 eyes (34.6%) showed newly formed mature vessels, and 7 eyes (26.9%) showed prominently developing preexisting mature vessels. CONCLUSION: Macular neovascularization expanded and showed vascular maturation under aflibercept treatment with a treat-and-extend regimen. The smaller the MNV at baseline, the greater is its expansion in 2 years.

EFFECTS OF HALF-DOSE PHOTODYNAMIC THERAPY ON CHRONIC CENTRAL SEROUS CHORIORETINOPATHY WITH OR WITHOUT MACULAR NEOVASCULARIZATION ASSESSED USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To assess the effects of half-dose photodynamic therapy on subretinal fluid and macular neovascularization (MNV) using optical coherence tomography angiography in patients with chronic central serous chorioretinopathy. METHODS: Clinical information on 168 patients (168 eyes) with chronic central serous chorioretinopathy obtained before and 6 months after treatment with half-dose photodynamic therapy was retrospectively analyzed. Patients were categorized into a success (145 eyes) or failure (23 eyes) group based on the absence or presence of subretinal fluid, respectively, and clinical data were compared between them. Macular neovascularization was studied in 147 cases with available optical coherence tomography angiography images. P < 0.05 indicated statistical significance. RESULTS: The success group showed a younger patient age, better posttreatment best-corrected visual acuity, and thicker pretreatment central choroidal thickness (all, P < 0.047) than did the failure group. Regarding MNV analysis, nine, eight, and 130 eyes had definite, possible, and no MNV, respectively, at baseline; among them, 100.0%, 75.0%, and 2.3%, respectively, had MNV at 6 months posttreatment. Patients with definite MNV at baseline were less likely to show successful subretinal fluid resolution. CONCLUSION: Although half-dose photodynamic therapy is generally effective for the treatment of chronic central serous chorioretinopathy, coexisting MNV may compromise the outcome; thus, optical coherence tomography angiography-based assessment of chronic central serous chorioretinopathy is important.

DIAGNOSTIC CHARACTERISTICS OF POLYPOIDAL CHOROIDAL VASCULOPATHY BASED ON B-SCAN SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AND ITS INTERRATER AGREEMENT COMPARED WITH INDOCYANINE GREEN ANGIOGRAPHY.

PURPOSE: To examine the characteristics of polypoidal choroidal vasculopathy using B-scan optical coherence tomography angiography (OCTA), and determine the diagnostic criteria of polypoidal choroidal vasculopathy based on OCTA. METHODS: This retrospective case series included patients diagnosed with treatment-naïve polypoidal choroidal vasculopathy who underwent indocyanine green angiography (ICGA) and swept-source OCTA at baseline. We compared the characteristics of the polyps detected using B-scan OCTA and ICGA. Then, the diagnostic concordance of each polypoidal lesion between ICGA and OCTA was evaluated. RESULTS: Among 54 eyes of 52 patients, all 54 eyes showed flow signals indicating polyps on both ICGA and B-scan OCTA. All polyps on B-scan OCTA were detected as round/ring-like flow signals inside pigment epithelial detachments, incomplete round/ring-like flow signals overlaid with round/ring-like OCT structures inside pigment epithelial detachments, or flow signals adjacent to a pigment epithelial detachment notch. Using B-scan OCTA, 94.7% of the polypoidal lesions were detected by an independent evaluator with an overall accuracy of 92.6% for counting the polypoidal lesions per eye relative to ICGA and a Kappa value of 0.82. CONCLUSION: Polyp detection on B-scan OCTA demonstrates high accuracy and is comparable to that obtained on ICGA. B-scan OCTA could replace ICGA for the diagnosis of polypoidal choroidal vasculopathy.

CHARACTERISTICS AND CLASSIFICATION OF TYPE 3 NEOVASCULARIZATION WITH B-SCAN FLOW OVERLAY AND EN FACE FLOW IMAGES OF OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To study B-scan flow overlay and en face flow optical coherence tomography angiography (OCT-A) images of Type 3 neovascularization (NV) and to characterize a staging system for Type 3 NV based on the OCT-A findings. METHODS: We retrospectively collected data on consecutive treatment-naive eyes with Type 3 NV. All eyes underwent fluorescein angiography, indocyanine green angiography, structural spectral domain OCT, and OCT-A (AngioPlex). Localization and extension of abnormal flows detected by B-scan flow overlay and en face OCT-A images were assessed. RESULTS: Of 24 eyes of 22 patients with Type 3 NV, B-scan flow overlay images showed that 4.2% had telangiectatic flow in the deep retinal layer without outer plexiform layer disruption (Stage 1), 8.3% had downward intraretinal flow and subretinal flow without retinal pigment epithelium disruption (Stage 2), and 87.5% had downward flow and retinal pigment epithelium disruption (Stage 3). Of the Stage 3 eyes, 95.2% showed flow signal penetrating at the site of the retinal pigment epithelium disruption on the B-scan flow overlay images. CONCLUSION: We showed the characteristics of Type 3 NV using B-scan flow overlay and en face OCT-A images. B-scan flow overlay OCT-A images seem useful to improve the detection and accurate diagnosis of Type 3 NV.

SPONTANEOUS CLOSURE OF MACULAR HOLE AFTER VITRECTOMY FOR MYOPIC RETINOSCHISIS WITH FOVEAL DETACHMENT.

PURPOSE: To discuss a case of a macular hole formation after vitrectomy for myopic retinoschisis with foveal detachment and spontaneous closure, during long-term follow-up. METHODS: Case report. RESULTS: A 71-year-old man with myopic retinoschisis with foveal detachment had a vitrectomy with internal limiting membrane peeling combined with cataract surgery in the left eye. The preoperative best-corrected visual acuity was 8/20, and the axial length was 27.11 mm. A macular hole with foveal detachment was observed 1 month after surgery. However, the macular hole closed spontaneously with foveal detachment at 4 months of follow-up. Foveal detachment resolved, and the best-corrected visual acuity improved to 20/20 at nine months of follow-up. CONCLUSION: This case suggests that the macular hole formed after vitrectomy for myopic retinoschisis with foveal detachment with internal limiting membrane peeling can close spontaneously.

Displacement of the retina and changes in the foveal avascular zone area after internal limiting membrane peeling for epiretinal membrane.

PURPOSE: We investigated the differences in displacement of the outer and inner macular retina toward the optic disc after vitrectomy with internal limiting membrane (ILM) peeling for epiretinal membrane (ERM). Foveal avascular zone (FAZ) area changes were also investigated. STUDY DESIGN: Retrospective observational study METHODS: This retrospective observational case series included 45 eyes of 43 patients that underwent vitrectomy with ERM and ILM peeling for ERM and 38 normal eyes. The locations of the centroid of the FAZ (C-FAZ, center of the foveal inner retina) and foveal bulge (center of the foveal outer retina) were determined using 3×3mm superficial optical coherence tomography angiography. C-FAZ and foveal bulge displacements, and the pre- and postoperative FAZ areas and their associated factors, were investigated. RESULTS: Postoperative C-FAZ dislocated significantly more toward the optic disc than in pre-operative or normal eyes (P<0.001). C-FAZ and foveal bulge displaced toward the optic disc after surgery; C-FAZ showed significantly greater displacement than foveal bulge (P<0.001). The pre- and postoperative FAZ areas were correlated (P=0.01). Preoperative FAZ areas ≧0.10mm2 were reduced after surgery, and FAZ areas < 0.10mm2 were increased, independent of foveal displacement. CONCLUSION: ILM peeling during vitrectomy for ERM caused larger displacement of the inner and smaller displacement of the outer retinas, towards the optic disc. Postoperative changes in the FAZ area were dependent on the baseline FAZ area, but not on the foveal displacement. ILM may physiologically exert centrifugal tractional forces on the fovea.

Switching from aflibercept to brolucizumab for the treatment of refractory neovascular age-related macular degeneration.

PURPOSE: To examine the 16-week outcomes of switching to brolucizumab in eyes with neovascular age-related macular degeneration (nAMD) refractory to aflibercept. STUDY DESIGN: Retrospective observational study. METHODS: Data of eyes with nAMD who switched to brolucizumab because of resistance to aflibercept were collected. The best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative status on optical coherence tomography were analyzed. RESULTS: A total of 48 eyes of 48 patients were reviewed. At 4 to 7 weeks after switching, BCVA changed from 0.26 ± 0.19 to 0.25 ± 0.21 (not significant; P = 0.95), but CRT significantly decreased from 298.9 ± 108.4 µm to 241.9 ± 92.5 µm (P < 0.001) and CCT from 182.6 ± 89.3 µm to 169.7 ± 82.6 µm (P < 0.001). Of the 23 eyes refractory to monthly aflibercept injections, 12 (52.2%) achieved a dry macula, and 8 (34.8%) reduced exudative changes at 1 month. At 16 weeks, 31 eyes (64.6%) achieved the treatment interval ≥ 8 weeks. Two patients (4.2%) dropped out, 7 eyes (14.6%) developed intraocular inflammation (IOI), and 8 eyes (16.7%) switched back to aflibercept because of the failure to extend the treatment interval ≥ 8 weeks. CONCLUSION: Switching to brolucizumab in eyes refractory to aflibercept conferred favorable outcomes in controlling exudative changes. However, IOI and the regulation of the treatment interval to at least 8 weeks during the maintenance phase disrupted the continuation of brolucizumab treatment.

Choroidal hemodynamics in central serous chorioretinopathy after half-dose photodynamic therapy and the effects of smoking.

This retrospective study aimed to evaluate choroidal hemodynamics after half-dose photodynamic therapy (PDT) for central serous chorioretinopathy (CSC) and the effects of smoking using laser speckle flowgraphy. This study included 29 eyes of 29 patients treated with half-dose PDT for CSC, who were followed-up for at least 6 months. The mean blur rate (MBR) in the PDT irradiation area (whole area), the pachyvessel (PV) area, non-PV (NPV) area, and filling delay (FD) area were assessed at baseline and 1, 3, and 6 months post-PDT, respectively. The MBR was also assessed by smoking status. The MBR significantly decreased from baseline in the whole, PV, NPV, and FD areas at all time points (P < 0.001). Of the 29 patients, 6 were never smokers, 13 were past smokers, and 10 were current smokers. At baseline, no significant difference was found in the MBR in the whole, PV, NPV, and FD areas among never, past, and current smokers. The MBR changes showed a significantly smaller decrease in current smokers than in never smokers in the whole (P = 0.021), PV (P = 0.009), and NPV (P = 0.034) areas, but not in the FD area (P = 0.172). Half-dose PDT for CSC reduced choroidal blood flow in the PDT-irradiated area, which was blunted by current smoking status.

Three cases of brolucizumab-associated retinal vasculitis treated with systemic and local steroid therapy.

PURPOSE: To describe three Japanese cases of retinal vasculitis that occurred following intravitreal brolucizumab injections and the systemic and local steroid treatment administered. CASES: Three patients developed intraocular inflammation (IOI) and retinal vasculitis following the first injection of brolucizumab for age-related macular degeneration. For two eyes, monthly aflibercept injections did not control exudation, and therapy was changed to brolucizumab; one eye was treatment-naïve. All three patients noticed blurry vision and floaters 11-18 days after brolucizumab injections, and the treated eyes exhibited anterior chamber cells, fine keratic precipitates, vitreous cells, and vitreous haze. Ultra-widefield color images of the fundus showed retinal hemorrhage in the peripheral retina and, in two cases vascular sheathing. Ultra-widefield fluorescein angiography (FA) showed segmental vascular leakage in all eyes and leakage from the optic disc in two eyes. Vascular filling defects were noted in the peripheral retinae of two eyes. Brolucizumab-associated retinal vasculitis was diagnosed, and treated with 30 mg/day of oral prednisolone, subtenon triamcinolone acetonide injection (20 mg/0.5 ml), and 0.1% betamethasone sodium phosphate solution. After 1 week, color fundus images and FA showed improvements in vascular sheathing, leakage from retinal vessels, and optic disc leakage, but the vascular filling defects remained. Visual acuity was restored in all three eyes 6 weeks after the onset. CONCLUSION: Brolucizumab-associated IOI, including retinal vasculitis and retinal occlusion, is a rare but important adverse event that can cause severe vision loss. Prompt diagnosis with FA and treatment with systemic or local steroids should be considered.

Prevalence of and factors associated with dilated choroidal vessels beneath the retinal pigment epithelium among the Japanese.

Pachyvessels are pathologically dilated large choroidal vessels and are associated with the pathogenesis of several pachychoroid-related disorders, including central serous chorioretinopathy. We aimed to investigate the prevalence of and risk factors for pachyvessels in the Japanese population. We included 316 participants (aged ≥ 40 years) with normal right eyes. The presence of pachyvessels (vertical diameter > 300 µm, distance to the retinal pigment epithelium < 50 µm) was determined using 6 × 6 mm macular swept-source optical coherence tomography images, and associated risk factors were investigated. Subfoveal choroidal thickness was measured, and its associated risk factors investigated. The overall prevalence of pachychoroids was 9.5%. Regression analysis showed that a younger age, shorter axial length, male sex, and smoking were significantly associated with the presence of pachyvessels (p = 0.047; odds ratio [OR] 0.96 per year, p = 0.021; OR 0.61 per 1 mm, p = 0.012; OR 3.08 vs. female, and p = 0.011; OR 3.15 vs. non-smoker, respectively) and greater choroidal thickness (p < 0.001, p < 0.001, p < 0.003, and p < 0.017, respectively). The results were consistent with other research findings which showed that pachychoroid-related disorders such as central serous chorioretinopathy were associated with younger age, male sex, shorter axial length, and smoking. Smoking may be associated with choroidal circulatory disturbance in the Japanese population.

Association Between Retinal Layer Thickness and Perfusion Status in Extramacular Areas in Diabetic Retinopathy.

PURPOSE: This study was performed to investigate the association between changes in retinal layer thickness and perfusion status in the extramacular areas of eyes with diabetic retinopathy. DESIGN: Retrospective cross-sectional study. METHODS: The medical records of 70 eyes from 55 patients with diabetes were reviewed. The status of retinal perfusion in extramacular areas was evaluated using swept-source optical coherence tomography angiography. Retinal layer thickness was measured in nonperfused areas (NPA) larger than 2 optic disc areas, areas of sparse capillaries (SC), and perfused areas (PA-DR) in eyes with diabetic retinopathy. Retinal layer thickness was also measured in perfused areas in eyes without diabetic retinopathy (PA-NDR), and the thicknesses were then compared. In addition, swept-source optical coherence tomography angiography images and retinal thickness maps were compared to investigate the distribution of retinal thickness changes and spatial relationships to areas of retinal perfusion. RESULTS: The inner retinal thickness in NPA was significantly thinner than the inner retinal thicknesses in SC, PA-DR, and PA-NDR (all P < .001), and the inner retinal thickness in PA-NDR and SC was significantly thinner than that in PA-DR (P = .006 and .031, respectively). In a distribution analysis of the extramacular areas, NPA spatially overlapped with areas of severe retinal thinning in all locations. Local thickening with smooth shapes and gentle borders overlapped with areas of capillary abnormalities. Neovascularization was present at sites of local thickening with irregular shapes and unnatural clear borders. CONCLUSIONS: Changes in retinal layer thickness were associated with perfusion status, suggesting that retinal thickness maps can reflect perfusion status.

Analysis of macular curvature in normal eyes using swept-source optical coherence tomography.

PURPOSE: To evaluate macular shape in normal eyes using swept-source optical coherence tomography (SS-OCT). STUDY DESIGN: Retrospective cross-sectional study. METHODS: We retrospectively evaluated 77 normal eyes of 48 subjects. Curvature of retinal pitment epithelium (RPE) and choroid/scleral interface (CSI) was measured in vertical and horizontal SS-OCT 16-mm scanned images. After correcting the optical distortion of OCT images, curvatures of superior, central, and inferior sectors in the vertical scan, and temporal, central, and nasal sectors in the horizontal scan (each 4-mm length) were compared. Factors associated with overall RPE and CSI curvatures were investigated. RESULTS: RPE and CSI curvatures of superior, central, and inferior sectors in the vertical scan were 16.6±3.1, 13.8±2.1, 17.7±3.2 and 17.8±3.0, 13.8±3.3, 18.4±3.3 (×10-5 µm-1), respectively. Central curvature was significantly flatter than superior and inferior curvatures in both RPE and CSI (all P<0.001). The RPE and CSI curvatures of temporal, central, and nasal sectors in the horizontal scan were 17.2±2.3, 15.2±2.5, 18.8±2.7 and 18.3±2.7, 16.7±2.9,14.4±2.9 (×10-5 µm-1), respectively. While central curvature was significantly flatter than nasal and temporal curvatures in RPE (P<0.001 and P=0.025), nasal curvature was significantly flatter than central and temporal curvatures (P=0.027 and P<0.001) in CSI. Overall CSI curvature was significantly associated with axial length (AL) (P<0.001), whereas overall RPE curvature was significantly associated with overall CSI curvature (P<0.001), choroidal thickness (P<0.001), and AL (P=0.038) CONCLUSIONS: This study revealed that RPE curvature is associated with CSI curvature, choroidal thickness, and AL, suggesting that choroidal and scleral structures affect macular RPE curvature.

Vascular maturity of type 1 and type 2 choroidal neovascularization evaluated by optical coherence tomography angiography.

PURPOSE: Vessel maturation is considered to proceed by pruning branches resulting in less branching vessels. This study investigated the vessel junction densities of type 1 and type 2 choroidal neovascularizations (CNVs) using optical coherence tomography angiography (OCTA). METHODS: We collected consecutive data from treatment-naïve eyes diagnosed with typical age-related macular degeneration (AMD). The OCTA images with CNV were analyzed to calculate vessel areas, vessel lengths, and vessel junction densities. RESULTS: Of 60 eyes in 60 patients, type 1 CNV diagnoses had been made in 40 eyes, and type 2 CNV in 20 eyes. We found no significant difference in vessel areas between type 1 CNV and type 2 CNV (type 1 CNV, 0.44 ± 0.37 mm2; type 2 CNV, 0.37 ± 0.48 mm2), and no significant difference in vessel lengths (type 1 CNV, 18.24 ± 15.96 mm; type 2 CNV, 16.13 ± 21.45 mm). However, the vessel junction density of type 1 CNV was significantly lower than that of type 2 CNV by 16.0% (P = 0.008). CONCLUSION: OCTA revealed that the vessel junction densities of type 1 CNVs were lower than those of type 2 CNVs, suggesting type 1 CNV vessels are more mature than type 2 CNV vessels.