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To determine the clinical properties of pachychoroid neovasculopathy (PNV) that differ from conventional neovascular age-related macular degeneration (nAMD) and suggest that they are different clinical entities. To accomplish this, we reviewed the medical records of 100 consecutive patients diagnosed with nAMD. All of the patients were Japanese, and their mean age was 75.5 years. There were 72 men and 28 women. For the bilateral cases, only the right eye was analyzed. An eye was diagnosed with PNV when a macular neovascularization (MNV) was detected just above the dilated choroidal vessels. The Indocyanine green angiographic (ICGA) and en face optical coherence tomographic (OCT) images were used to assess the vertical symmetry of the medium and large choroidal vessels. The subfoveal choroidal thickness (SCT) was also measured manually in the OCT images. After reclassification, there were 29 (29%) patients with typical nAMD (25 with type 1 MNV, 4 with type 2 MNV), 43 (43%) with PNV, 21 (21%) with polypoidal choroidal vasculopathy, and 7 (7%) with retinal angiomatous proliferation. Of the 43 PNV, 17 (39.5%) had polypoidal lesions and 26 (60.5%) had no polypoidal lesions. The percentage of eyes with vertical asymmetry of the medium and large choroidal vessels was significantly greater in the 35 PNV (81.4%) than in the 16 non-PNV (28.1%; P  < 0.01) cases. The mean SCT was significantly thicker in the PNV eyes than in the non-PNV eyes (298 ± 96 μm vs. 228 ± 82 μm; P  < 0.01). The response of PNV to anti-vascular endothelial growth factor treatments was better than that of non-PNV eyes [higher dry macula rate after the loading period (90.9% vs. 59.1%), fewer total number of injections (11.0 ± 2.9 vs. 13.4 ± 3.2), and longer treatment intervals for the anti-VEGF therapy (8.4 ± 3.1 vs. 13.4 ± 3.2 weeks) at 2 years (all P  < 0.01)]. These differences in the morphology and response to anti-VEGF treatments suggest that PNV is a separate clinical entity to conventional nAMD.

This multicenter study aimed to assess the short-term effectiveness and safety of faricimab in treatment-naïve patients with wet age-related macular degeneration (wAMD) in Japan. We retrospectively reviewed 63 eyes of 61 patients with wAMD, including types 1, 2, and 3 macular neovascularization as well as polypoidal choroidal vasculopathy (PCV). Patients received three consecutive monthly intravitreal injections of faricimab as loading therapy. Over these 3 months, visual acuity improved gradually compared to baseline. Moreover, the central foveal thickness decreased significantly at 1, 2, and 3 months compared to baseline ( p  < 0.0001). At 3 months after initiation of faricimab therapy, a dry macula (defined as absence of intraretinal or subretinal fluid) was achieved in 82% of the eyes. Complete regression of polypoidal lesions was observed in 52% of eyes with PCV. Subfoveal choroidal thickness also decreased significantly at 1, 2, and 3 months compared to baseline ( p  < 0.0001). Although retinal pigment epithelium tears developed in two eyes, there were no other ocular or systemic complications observed during the 3 months of loading therapy. In conclusion, loading therapy using faricimab resulted in improved visual acuity and retinal morphology in Japanese patients with wAMD without particular safety issues.

To diagnose central serous chorioretinopathy (CSC) by deep learning (DL) analyses of en face images of the choroidal vasculature obtained by optical coherence tomography (OCT) and to analyze the regions of interest for the DL from heatmaps. One-hundred eyes were studied; 53 eyes with CSC and 47 normal eyes. Volume scans of 12x12 mm square were obtained at the same time as the OCT angiographic (OCTA) scans (Plex Elite 9000 Swept-Source OCT.sup.®, Zeiss). High-quality en face images of the choroidal vasculature of the segmentation slab of one-half of the subfoveal choroidal thickness were created for the analyses. The 100 en face images were divided into 80 for training and 20 for validation. Thus, we divided it into five groups of 20 eyes each, trained the remaining 80 eyes in each group, and then calculated the correct answer rate for each group by validation with 20 eyes. The Neural Network Console (NNC) developed by Sony and the Keras-Tensorflow backend developed by Google were used as the software for the classification with 16 layers of convolutional neural networks. The active region of the heatmap based on the feature quantity extracted by DL was also evaluated as the percentages with gradient-weighted class activation mapping implemented in Keras. The mean accuracy rate of the validation was 95% for NNC and 88% for Keras. This difference was not significant (P >0.1). The mean active region in the heatmap image was 12.5% in CSC eyes which was significantly lower than the 79.8% in normal eyes (P<0.01). CSC can be automatically diagnosed by DL with high accuracy from en face images of the choroidal vasculature with different programs, convolutional layer structures, and small data sets. Heatmap analyses showed that the DL focused on the area occupied by the choroidal vessels and their uniformity. We conclude that DL can help in the diagnosis of CSC.

To determine the blood flow pattern of eyes before the development of type 3 macular neovascularization (MNV) by optical coherence tomography angiography (OCTA). Retrospective study. Ten eyes of 10 patients (4 men and 6 women, mean age 80.4 years) diagnosed with unilateral Type 3 MNV who developed type 3 MNV in the fellow normal eye during the follow-up period were studied. The time of onset of type 3 MNV was defined as the time when retinal exudation was detected by OCT. The blood flow of a 3 x 3 mm or 6 x 6 mm area in the deep capillary plexus (DCP) and the outer retina (OR) including the central fovea were assessed at the onset and at 6 months prior to the onset of the type 3 MNV. All MNVs that developed in the fellow eye were type 3 MNVs. Abnormal blood flow signals in the MNVs were detected in the DCP and/or the OR by OCTA at the onset in all cases. Eight of the 10 eyes had OCTA recordings prior to the development of the MNV: 3 eyes had non-exudative MNVs only in the DCP and 5 eyes had non-exudative MNVs in the DCP and OR. The exudation appeared on the average 3.5 months after the non-exudative MNV was observed in the fellow eyes. A non-exudative MNV in the fellow eyes can already be observed by OCTA in eyes before the onset of the exudation. Knowing this will help clinicians not only how to treat these eyes appropriately but will also help in determining the origin of the MNV.

Purpose To assess 6-month outcomes of switching from aflibercept to faricimab in eyes with refractory neovascular age-related macular degeneration (nAMD) previously requiring monthly injections. Methods This multicenter retrospective study examined nAMD eyes receiving monthly aflibercept injections switched to faricimab administered monthly up to 4 injections followed by injections at a minimum of 2-month intervals as per drug labeling. Data regarding age, sex, number of previous injections, treatment intervals, and best-corrected visual acuity (BCVA) were collected. Central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), and maximal pigment epithelial detachment (PED) height were measured by optical coherence tomography. Results The study included 130 eyes of 124 patients. At 6 months, 53 eyes (40.8%) continued on faricimab treatment (Group 1), while 77 eyes (59.2%) discontinued faricimab for various reasons (Group 2) the most common being worse exudation. There were no significant differences between the two groups at baseline. In Group 1, CRT and SFCT significantly decreased at 1 month ( P = 0.013 and 0.008), although statistical significance was lost at 6 months ( P = 0.689 and 0.052). BCVA and maximal PED height showed no significant changes; however, mean treatment intervals were extended from 4.4 ± 0.5 weeks at baseline to 8.7 ± 1.7 weeks at 6 months ( P < 0.001) in Group 1. No clear predictors of response were identified. Conclusion Switching from aflibercept to faricimab allowed for extension of treatment intervals from monthly to bimonthly in roughly 40% of eyes, suggesting that faricimab may be considered in refractory nAMD cases.

Background To report a case of intraocular inflammation (IOI) after intravitreal injection of aflibercept 8 mg for treatment-refractory neovascular age-related macular degeneration. Case presentation An 80-year-old man with diabetes mellitus had neovascular age-related macular degeneration refractory to treatment with aflibercept 2 mg. Despite ten injections of faricimab, the exudation remained, and we switched to brolucizumab, which resulted in a mild IOI. The IOI improved with only topical steroids, and we switched back to aflibercept 2 mg for the exudation. However, the exudation remained, and we decided to switch to aflibercept 8 mg after careful discussion with the patient. Two weeks later, he experienced minor ocular pain and photophobia. One month later, although a dry macula was achieved, severe visual impairment occurred due to anterior chamber inflammation, retinal vasculitis, and retinal vascular occlusion. We diagnosed the severe IOI following aflibercept 8 mg and immediately started steroid eye drops and a sub-Tenon injection of triamcinolone acetonide. Although the inflammation resolved, his visual acuity did not improve. Conclusions This case demonstrated a potential dose-dependent inflammatory response following aflibercept 8 mg, which did not occur with aflibercept 2 mg in patients with a history of intraocular inflammation.

To evaluate the long-term efficacy and factors involved in the recurrence and persistence of subretinal fluid (SRF) after half-dose photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSC). In this retrospective observational case series, 79 eyes (73 patients) with chronic CSC were treated with half-dose PDT and followed up for at least 3 years. They were divided into successful (64 eyes) and unsuccessful (15 eyes) groups based on SRF absorption and disease recurrence after one PDT session. Age, best-corrected visual acuity (BCVA), central foveal thickness, neuroretinal thickness, height of SRF, subfoveal choroidal thickness, window defect area detected by fluorescein angiography, and PDT spot area were compared between the groups. Factors associated with PDT success and BCVA at 3 years were investigated. LogMAR BCVA improved from 0.21±0.24 to 0.08±0.16 (P<0.001) at 3 years after PDT. Compared with the unsuccessful group, the successful group had a significantly younger mean age (50.5±9.7 vs. 56.5±9.1 years, P = 0.032) and better baseline BCVA (0.18±0.23 vs. 0.32±0.25, P = 0.034). Other parameters were not significantly different. Multivariate analyses showed that unsuccessful PDT was significantly associated with lower baseline BCVA (P = 0.026) and older age (P = 0.029) and that BCVA at 3 years after PDT was positively associated with baseline BCVA (P<0.001). Half-dose PDT has a long-term efficacy in chronic CSC. Relatively early PDT may improve anatomic and functional outcomes of chronic CSC.

This multicentre retrospective study evaluated the 1-year outcomes and safety profile of faricimab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD). Fifty-five patients (57 eyes) underwent loading therapy comprising three monthly faricimab injections. If dryness was achieved by the third month, subsequent treat-and-extend (TAE) follow-up continued at a minimum 8-week interval thereafter. If wet macula persisted at the third month, a fourth dose was administered, followed by the TAE regimen. After 1 year, improvements in visual acuity (0.44 ± 0.46 [baseline] to 0.34 ± 0.48; p < 0.01) and central foveal thickness (326 ± 149 [baseline] to 195 ± 82 μm; p < 0.0001) were significant. Dry macula, characterised by the absence of intraretinal or subretinal fluid, was achieved in 65% of cases. Treatment intervals varied, ranging from 8 to 16 weeks, with 44% of eyes extending to a 16-week interval, followed by 33% at 8 weeks, 16% at 12 weeks, 5% at 14 weeks, and 2% at 10 weeks. Notably, 50% of the polypoidal choroidal vasculopathy patients exhibited complete regression of polypoidal lesions between 12 and 15 months. Faricimab treatment in nAMD patients induced significant improvements in central vision and retinal morphology. Two cases of retinal pigment epithelial tears and one case of iritis were reported as ocular complications.

Purpose To investigate short-term treatment outcomes of intravitreal brolucizumab (IVBr) for treatment-naïve neovascular age-related macular degeneration (AMD) in a Japanese multicenter study. Study design Retrospective case control study Methods The subjects were 58 eyes of 57 patients with neovascular AMD (43 men and 14 women, mean age 74.6 years) of whom 43 eyes of 42 patients completed initial loading of 3 monthly IVBr injections and were followed for more than 3 months. Best-corrected visual acuity (BCVA) changes, anatomical outcomes, and complications were investigated. Results Of the 43 eyes that completed loading doses, the AMD subtype was type 1 and type 2 macular neovascularization (MNV) in 51%, polypoidal choroidal vasculopathy (PCV) in 42%, and type 3 MNV in 7%. At 3 months after initiating treatment, BCVA significantly improved (P = 0.002) and central retinal thickness significantly decreased (P < 0.0001). At 3 months, complete retinal and subretinal fluid resolution was achieved in 91% of all eyes and complete regression of polypoidal lesions was achieved in 82% of PCV eyes. Iritis occurred in 8 eyes of 8 patients (14%), but resolved using topical or subtenon corticosteroid injection without visual loss in all cases. Conclusions IVBr for treatment-naïve neovascular AMD was effective in the short-term, achieving significantly improved BCVA, good retinal fluid resolution, and a high rate of polypoidal lesion regression. However, iritis was noted in 14% of patients which may limit use of this drug.