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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.

To determine parameters related to the size of the foveal avascular zone (FAZ) in healthy elderly eyes. We reviewed the medical records of 101 normal elderly eyes with a mean age of 64.2 ± 10.1 years. A 3 × 3 mm area centered on the fovea was analyzed in optical coherence tomography angiographic images. The center of FAZ and the center of foveal photoreceptors were identified, and the misalignment between the two center points was measured. The mean FAZ size was 0.35 ± 0.12 mm 2 . The distance between the center of the FAZ and the center of the foveal photoreceptors was 41.6 ± 21.1 μm. The misalignment distance between the center of the FAZ and the center of the foveal photoreceptors was not significantly correlated with the size of the FAZ ( r  = 0.091, P  = 0.3656). On the other hand, there was a significant correlation between the directionality of horizontal and vertical misalignments from the center of the foveal photoreceptors to the center of the FAZ and the FAZ size ( r = -0.264, P  = 0.0076 horizontal; r  = 0.212, P  = 0.0335, vertical). These results indicate that the larger the misalignment of the center of the FAZ from the center of the foveal photoreceptors in the temporal and superior directions, the larger the FAZ tended to be. In conclusion, analysis of parameters related to FAZ size in healthy elderly eyes may provide clues to age-related changes in macular microcirculation and early pathology in eyes with retinal diseases.

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.

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.

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.

PurposeThe purpose of this study was to compare the morphology of the central and peripheral choroid of eyes with central serous chorioretinopathy (CSC) to that of normal eyes using ultra-widefield optical coherence tomography (UWF-OCT).MethodsWe reviewed the medical records of 29 eyes of 25 patients (23 men, 2 women; average age 44.4 years) with CSC and 34 eyes of 22 healthy subjects (19 men, 3 women; average age, 49.5 years) with normal eyes. The images obtained by a prototype swept source UWF-OCT (Topcon, Tokyo, Japan) of about 31.5-mm wide and a depth of 10.9 mm were analyzed. The choroidal thickness was measured for each sector of the eye using the conventional automated layer analysis method. The local morphological differences were quantified by the maximum steepness (µm/deg) which was obtained by differentiating the changes in the choroidal thickness from the periphery to the fovea. Only the vertical scans were evaluated to avoid the influence of the optic disc.ResultsThe choroid was thicker in the macular area than the peripheral area in both normal and CSC eyes. The choroid at the subfovea was significantly thicker in the CSC eyes than that of the normal eyes (P < 0.0001); however, the difference at the periphery was not significant. The mean of the maximum steepness of the choroidal thickness was 20.8 ± 3.8 µm/deg in the CSC eyes which was significantly steeper than the 16.0 ± 4.6 µm/deg in healthy eyes (P < 0.0001).ConclusionThe choroid in CSC eyes has a steeper slope around the posterior pole. UWF-OCT can be used to evaluate the abnormalities of the choroidal structures from the posterior pole to the periphery in eyes with CSC.

To examine the foveal structure and vasculature in eyes with an idiopathic epiretinal membrane (ERM). Forty-nine eyes of 48 patients with an idiopathic ERM were studied. The superficial foveal avascular zone (FAZ) was measured by optical coherence tomography angiography (OCTA; RTVue XR Avanti, Optovue Inc., Fremont, CA), and the central foveal thickness (CFT) was measured by swept source OCT (DRI-OCT, Topcon, Japan). Twenty eyes underwent vitrectomy with internal limiting membrane (ILM) peeling, and the FAZ and CFT were evaluated pre- and postoperatively. Forty-nine eyes of 49 age-matched healthy subjects were also examined as control. The FAZ in eyes with an ERM was significantly smaller than that of the control eyes (0.188±0.16 mm2 vs 0.328±0.14 mm2, P<0.01). The CFT in eyes with an ERM was significantly thicker than that of control eyes (315±0.14 μm vs 193±0.14 μm, P<0.01). The size of the FAZ was strongly correlated with the CFT (ERM, R = -0.753; control, R = -0.61, both P<0.01). The postoperative size of the FAZ was not significantly different from the preoperative size (0.115 mm2 vs 0.128 mm2, P = 0.17) but the CFT was significantly thinner (370 μm vs 288 μm, P<0.01) after the vitrectomy with ILM peeling in 20 eyes. The results indicate that an ERM might affect the morphology and vasculature of not only the inner but also the outer retina before and after vitrectomy with ILM peeling. The FAZ area might have been affected by the ILM peeling.

To compare the efficacy of the subthreshold micropulse laser (SML) to conventional laser (CL) in treating focal leakages of the retinal pigment epithelium (RPE) in the eyes with central serous chorioretinopathy (CSC). Twenty-nine eyes of 28 patients with CSC and typical focal leakage were treated with CL or SML. Both treatments were made with a 577 nm yellow laser (CL: NIDEK MC-500, SML: IRIDEX IQ577). The percentage of eyes with a complete resolution, the distance of the laser burns from the fovea, and injury of the RPE after treatment were studied. A complete resolution was seen in 10 of 15 eyes (66.7%) after CL and 9 of 14 eyes (64.3%) after SML (P = 0.89). The average distance from the foveal center to the leakage point was 1282±596 μm for eyes treated with CL and 1271±993 μm for eyes treated with SML (P = 0.4). Only three eyes treated with SML had treatment sites within 500 μm of the fovea. RPE damage determined by fundus autofluorescence was found in all eyes treated with CL and only one eye treated with SML (P<.01). SML achieved equivalent therapeutic effects as CL but without RPE damage in eyes with CSC.

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.