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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 P P

To investigate short-term treatment outcomes of intravitreal brolucizumab (IVBr) for treatment-naïve neovascular age-related macular degeneration (AMD) in a Japanese multicenter study.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.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.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.

Purpose To determine the blood flow pattern of eyes before the development of type 3 macular neovascularization (MNV) by optical coherence tomography angiography (OCTA). Study design Retrospective study. Subjects 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. Methods 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. Results 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. Conclusions 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 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. Methods One-hundred eyes were studied; 53 eyes with CSC and 47 normal eyes. Volume scans of 12×12 mm square were obtained at the same time as the OCT angiographic (OCTA) scans (Plex Elite 9000 Swept-Source OCT®, 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. Results 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 Conclusions 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 evaluate the relationship between morphological changes and functional improvements assessed using focal macular electroretinograms after intravitreal aflibercept (IVA) injections in eyes with wet age-related macular degeneration. The clinical records of 42 eyes of 42 consecutive patients with naive, wet age-related macular degeneration received 3 monthly IVA were reviewed. The best-corrected visual acuity, central foveal thickness, outer retinal thickness, inner retinal thickness at baseline and 1 month after each IVA, and focal macular electroretinograms at baseline and 1 month after the first and third IVA were compared. Best-corrected visual acuity was improved after the third IVA (P = 0.0091). Central foveal thickness and outer retinal thickness showed decreases after every IVA (P < 0.001, respectively). Inner retinal thickness showed a decrease after the second IVA (P = 0.002), after and third IVA (P = 0.001). On focal macular electroretinograms, a- and b-wave amplitudes showed increases after the third IVA (P = 0.0028, P = 0.0012, respectively). Significant correlations were observed between best-corrected visual acuity and central foveal thickness, a-wave amplitude and outer retinal thickness, and b-wave amplitude and inner retinal thickness changes after the third IVA. All parameters significantly recovered after three monthly IVA, with a correlation between functional improvements and morphological changes.

To compare the 1-year results of initial or deferred photodynamic therapy (PDT) combined with intravitreal ranibizumab (IVR) for eyes with polypoidal choroidal vasculopathy.Prospectively, 72 men with treatment-naive polypoidal choroidal vasculopathy were randomized to initial or later PDT combined with IVR. In both groups, 2 additional monthly IVR followed. From Month 3, PDT and IVR were administered according to the retreatment criteria. Mean changes in the best-corrected visual acuity between baseline and Month 12 and central retinal thickness, the rate of eyes showing regression of polypoidal lesions, and number of additional treatments were compared.The best-corrected visual acuity increased by a mean of 8.1 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters in the initial PDT group and 8.8 ETDRS letters in the later PDT group, and there was a no significant difference (P = 0.59). The mean central retinal thickness decreased significantly in both groups but more so with combination therapy within the first 4 months; the difference was not significant at Month 12 (P = 0.30). The rate of eyes showing resolution of polypoidal lesions at 12 months was 62.1% in the initial PDT group and 54.8% in the later PDT group and again, there was no significant difference (P = 0.53). The mean number of additional IVR was 1.5 in initial PDT and 3.8 in later PDT; that of additional PDTs was 0.14 and 0.45, respectively, and they were significantly different (P0.001 and P = 0.013, respectively).Both initial and deferred PDT combined with IVR to treat polypoidal choroidal vasculopathy show the similar visual and anatomical improvements at 12 months. Initial PDT combination leads to significantly fewer additional treatments.

Purpose 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). Methods 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. Results LogMAR BCVA improved from 0.21±0.24 to 0.08±0.16 (P

To compare optical coherence tomographic angiography (OCTA) and indocyanine green angiography (ICGA) images for detecting polypoidal lesions (PLs) and branching vascular networks (BVNs), and to measure the polypoidal areas (PAs) in patients with polypoidal choroidal vasculopathy (PCV). All patients underwent ICGA, optical coherence tomography (OCT), and OCTA. We compared the detection sensitivity for PL and BVN, as evaluated by the ICGA and OCTA images. Furthermore, PA measured by ICGA was divided into two groups: one in which the area could be measured by OCTA (ICGA+OCTA+) and the other in which the area could not be measured by OCTA (ICGA+OCTA−). Twenty-one consecutive eyes of 21 patients (mean age, 73.8±9.8 years) were included. ICGA detected PL in all eyes (100%), whereas OCTA detected PL in 16 eyes (75.2%); ICGA detected BVN in 15 eyes (71.4%), whereas OCTA detected BVN in 20 eyes (95.2%). The mean PA in ICGA+OCTA+ and ICGA+OCTA− was 0.24±0.04 and 0.14±0.01 mm2, respectively; a significant difference was observed between ICGA+OCTA+ PA and ICGA+OCTA− PA (P

To evaluate the effect of half-dose verteporfin photodynamic therapy (hPDT) on the physiology of the macula determined by focal macular electroretinograms (FMERGs) in eyes with chronic central serous chorioretinopathy (CSC). Fourteen eyes of 13 patients with chronic CSC were treated with hPDT. The best-corrected visual acuity (BCVA) was measured, and optical coherence tomography (OCT) and FMERGs were performed at the baseline, and at 4 days, 1, 3, 6, and 12 months after the hPDT. The subreitnal fluid was resolved in 12 of the 14 eyes after the hPDT. The amplitude of the a-wave at 12 months was significantly increased by 1.28 times over that at the baseline. The amplitude of the b-wave was also increased but not significantly (P = 0.055). The implicit time of the a-wave was significantly reduced at 6 months, and that of the b-wave at 3 months. The amplitudes of the oscillatory potentials did not change significantly during the 12-month follow-up period. hPDT led to an improvement in the FMERGs for at least 12 months without a transient depression of the FMERGs in eyes with chronic CSC. hPDT can be used safely to treat eyes with CSC.

Purpose: We compared 1-year outcomes of 1 + pro re nata (PRN) versus 3 + PRN of intravitreal aflibercept injection (IAI) for age-related macular degeneration (AMD). Methods: Forty-two eyes with naïve AMD received 3 + PRN IAI treatment and 47 eyes with naïve AMD received 1 + PRN IAI treatment. Visual acuity (VA), central retinal thickness (CRT), and central choroidal thickness (CCT) and number of administered IAIs during 12 months were compared. Results: VAs improved, and CRTs reduced significantly at any given month from baseline in both groups (p < 0.01, respectively). CCT reduced significantly at 3 months in the 3 + PRN group (p = 0.024) but not in the 1 + PRN group. The 1 + PRN group received fewer injections than the 3 + PRN group (p < 0.01). Conclusions: Aflibercept leads to equivalent VA and morphologic retinal improvement without administering 3 injections.

PURPOSE: To determine how different intraoperative surgical procedures affect the midvitreous temperature. METHODS: The vitreous temperatures were monitored continuously with an intravitreal thermocouple in 87 eyes of 81 cases undergoing vitrectomy. Thirty-three eyes had diabetic retinopathy (DR), 35 eyes had an epiretinal membrane, and 19 eyes had an idiopathic macular hole. In eyes with DR, the correlation between the number of photocoagulations (PCs) and the change in temperature was analyzed. The temperature was also recorded before and after combined phacoemulsification and aspiration (PEA) and vitrectomy in 10 eyes. RESULTS: The average midvitreal temperature before the vitrectomy was 33.0 ± 1.3°C, 30.7 ± 1.7°C after core vitrectomy, 32.9 ± 1.3°C after membrane peeling, and 29.2 ± 1.4°C after peripheral vitrectomy. The temperature before PC was 29.8 ± 1.3°C, and it increased to 31.5 ± 1.9°C post-PC. The differences in the temperatures between consecutive procedures were significant (P < 0.01, respectively, Wilcoxon signed-rank test). The difference in the temperatures of the same procedures among the different diseases was not significant except after membrane peeling. A significant correlation was detected between the number of PCs and the duration of the PCs, and between the duration of PCs and the change in vitreous temperature after PC (r = 0.719, P = 0.0010, and r = 0.800, P = 0.0002, respectively, Spearman's rank correlation coefficient test). The temperature after PEA decreased significantly by 2.3°C. CONCLUSIONS: Our results showed that vitreous temperatures vary during different vitrectomy procedures.

The purpose of this paper is to report choroidal atrophy in a patient with cancer-associated retinopathy who had autoantibodies against the transient receptor potential cation channel, subfamily M, member 1 (TRPM1). A 69-year-old man visited our clinic in July 2010 with complaints of blurred vision and night blindness in both eyes. The full-field electroretinograms were negative type, indicating ON bipolar cell dysfunction. General physical examination revealed small cell carcinoma of the lung, and Western blot of the patient’s serum showed autoantibodies against TRPM1. We diagnosed this patient with cancer-associated retinopathy and retinal ON bipolar dysfunction due to anti-TRPM1 autoantibody. We followed him for more than 2 years from the initial visit and his symptoms have not changed. However, consistent with the choroidal hypopigmentation of the fundus, spectral domain optical coherence tomography showed a decrease in choroidal thickness of about one third over a 2-year follow-up period. We suggest that this case of gradually progressive choroidal atrophy was caused by the autoantibody against TRPM1 directly, because TRPM1 is expressed not only on ON bipolar cells but also on melanocytes. These findings indicate that we should be aware of choroidal thickness in patients with paraneoplastic retinopathy who have retinal ON bipolar dysfunction with the anti-TRPM1 antibody.