Multimodal Imaging of Optic Nerve Head in Retinitis Pigmentosa.

BACKGROUND: A pallor optic nerve head (ONH) is one of the three features of retinitis pigmentosa (RP). This study aimed to assess the ONH prospectively by color tone, presence of hyper-reflective tissue, blood flow, retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) and investigate the change in these parameters with and without ONH pallor. METHODS: The presence of ONH pallor was assessed by three independent examiners through careful examination using fundus photographs. The presence of a hyper-reflective structure on the ONH was carefully evaluated using a volume scan optical coherence tomography (OCT). RNFL thickness and ellipsoid zone (EZ) width around the macula were also evaluated by OCT. Laser speckle flowgraphy was used to measure the mean blur rate of the entire ONH area, which was subsequently divided into the vessel area (MV) and tissue area (MT). RESULTS: Twenty-eight eyes of 28 patients with RP (55.4 ± 16.23 years of age) were included. The pale ONH was observed in 10 (35%) eyes. Hyper-reflective structures were observed in seven (25%) eyes. No significant correlation was found between the pale ONH and the presence of a hyper-reflective structure (Pearson's chi-squared test, p = .364). The average of the ONH area, MV, and MT was 8.65 ± 3.08 AU, 17.81 ± 7.54 AU, and 6.4 ± 2.66 AU, respectively, which significantly decreased in patients with pallor ONH (all p < .05). The global RNFL thickness was 73.54 ± 18.82 µm. The nasal and superior quadrants and global RNFL thickness in patients with a pale ONH were significantly thinner than in patients without a pale ONH (all p < .05). The global and superior and inferior GCC thickness in patients with a pale ONH were significantly thinner than in patients without a pale ONH(all p < .05).There was no difference in the EZ width between patients with and without a pale ONH (p = .107). CONCLUSION: We conducted multiple assessments of the ONH in RP patients and investigated its clinical significance. Our findings suggest that ONH pallor may indicate a comprehensive change that emerges alongside the progression of retinal degeneration in RP. TRIAL REGISTRATION: This trial was retrospectively registered in the UMIN Clinical Trial Registry (UMIN ID: 000048168).

Detailed Evaluation of Chromatic Pupillometry and Full-Field Stimulus Testing to Assess Ultralow Vision in Retinitis Pigmentosa.

Purpose: Novel therapeutic options, such as regenerative medicine and gene therapy, are now emerging as viable treatment options for patients with severe visual impairments, such as retinitis pigmentosa (RP). Gradable assessment of patients' visual function is essential to consider treatment options and to evaluate treatment outcomes; however, evaluation of visual function in patients with advanced low vision is often challenging because of patients' poor and sometimes unpredictable responses. In this study, we attempted to accurately assess visual capabilities and disease stage in patients with RP with a visual acuity (VA) of ≤ 0.01. Design: Retrospective analysis of visual function indicators, including VA, retinal thickness, full-field stimulus testing (FST), and chromatic pupillometry. Subjects: Overall, 43 patients (84 eyes) with advanced RP with a VA of ≤ 0.01 visited Kobe City Eye Hospital from 2019 to 2021. Methods: Hierarchical (multilevel) Bayesian modeling was used to estimate individual eye's pupil response and FST threshold, taking into account the ambiguity and randomness often observed in patients with ultralow vision. Using the estimated ability obtained from each test, the correlation between each test and retinal thickness was further analyzed to make a comprehensive assessment of the data. Main Outcome Measures: Visual acuity, retinal thickness, FST threshold, and pupil diameter change to different light stimuli. Results: Full-field stimulus testing and pupillometry measurements were moderately correlated with VA but exhibited a wide range of values within the same VA groups. Full-field stimulus testing was not correlated with central retinal thickness at counting fingers/hand motion VA range and seemed to reflect overall remaining photoreceptor function, including peripheral retina. Pupillometry may be able to distinguish between different levels of inner retinal function. Conclusions: The combination of pupillometry and FST allowed for graded evaluation of visual function within patients grouped in the same VA groups in patients with advanced RP with ultralow vision. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Use of ellipsoid zone width for predicting visual prognosis after cataract surgery in patients with retinitis pigmentosa.

OBJECTIVE: To predict the visual prognosis of cataract surgery in patients with retinitis pigmentosa by measuring ellipsoid zone (EZ) width using spectral-domain optical coherence tomography. METHODS: This retrospective study included patients with retinitis pigmentosa who underwent uncomplicated cataract surgery between December 2017 and June 2020. Preoperative best-corrected visual acuity (BCVA) and the best postoperative BCVA during follow-up were collected. EZ width was measured on preoperative cross-sectional optical coherence tomography images along the horizontal/vertical meridian through the fovea. RESULTS: Thirty-eight eyes of 38 patients (22 female; mean [±standard deviation] age, 62.1 ± 11.8 years) were included. The median preoperative logarithm of the minimum angle of resolution BCVA of 0.52 (range, 0.00-3.00) significantly improved to 0.07 (range, -0.18-3.00) after surgery (P < 0.001). On preoperative spectral-domain optical coherence tomography images, the median horizontal, vertical, and average EZ widths were 783 (range, 0-9837), 761 (range, 0-10 250), and 769 (range, 0-10 043) µm, respectively. Postoperative BCVA significantly correlated with the horizontal (r = -0.784, P < 0.001), vertical (r = -0.777, P < 0.001), and average EZ widths (r = -0.777, P < 0.001). The area under the receiver operating characteristic curve for the ability of the horizontal, vertical, and average EZ widths to discriminate eyes with and without postoperative BCVA ≤ 0.3 was 0.971, 0.960, and 0.963, respectively, with best cut-off values of 513, 608, and 515 µm, respectively. CONCLUSIONS: EZ width measurement can help predict the visual prognosis of cataract surgery in patients with retinitis pigmentosa. A preferable visual acuity prognosis can be expected in patients with an EZ width of approximately 600 µm.

Retinal pigment epithelium melanin imaging using polarization-sensitive optical coherence tomography for patients with retinitis pigmentosa.

This study aimed to evaluate the distribution of retinal pigment epithelium (RPE) melanin in patients with retinitis pigmentosa (RP) using entropy measurements by custom-made polarization-sensitive optical coherence tomography (PS-OCT) images, and compare entropy with the intensity of short-wavelength (SW) and near-infrared (NIR) autofluorescence (AF). We retrospectively reviewed the retinal images, including PS-OCT, SW-AF, and NIR-AF of patients with RP who had a hyperautofluorescent ring on AF. A total of 12 eyes of 12 patients (8 women and 4 men; mean age: 37.9 years) were included. There was a strong positive correlation between entropy value and NIR-AF intensity (r = 0.626, p < 0.001), and there was a very weak negative correlation between entropy value and SW-AF (r = - 0.197, p = 0.001). The mean values of the entropy in the foveal, temporal (2 mm from the fovea), and nasal (2 mm from the fovea) sections were 0.41 (± 0.09), 0.29 (± 0.08), and 0.26 (± 0.08), respectively. The entropy was significantly higher in the foveal section than in the temporal and nasal sections (p = 0.002 and p = 0.003, respectively). There was no significant difference between the entropies values for the temporal and nasal sections (p = 0.157). Age, logMAR best-corrected visual acuity, ellipsoid zone width, and central retinal thickness were not correlated with foveal entropy. We presented RPE melanin imaging in patients with RP using PS-OCT for the first time. PS-OCT can be a useful tool for monitoring patients with RP.

Characteristics of astigmatism before and 1 month after blepharoptosis surgery in patients with acquired ptosis.

In this study, we aimed to evaluate the characteristics of astigmatism preoperatively and 1 month postoperatively in patients with age-related ptosis (AP) and contact lens-related ptosis (CLP), and investigate surgery-induced astigmatism (SIA) using the Jaffe vector analysis and the Cravy method. Consecutive patients who underwent blepharoptosis surgery between January 2019 and December 2019 were included. The patients were divided into AP and CLP groups. Computerized corneal topography was used to assess the magnitude and axis of corneal astigmatism. Astigmatism was classified as with-the-rule (WTR), against-the-rule (ATR), or oblique astigmatism (OA) pre- and postoperatively. SIA was calculated by vector analysis using the Cravy and Jaffe methods. The correlation between SIA and margin reflex distance (MRD) was calculated. One hundred and eight eyes from 58 patients (AP group: 85 eyes from 45 patients, CLP group: 23 eyes from 13 patients) were included. The AP group (73.8±7.6 years) was significantly older than the CLP group (47.7±6.6 years). The MRD increased significantly after treatment in both groups. The proportions of WTR, ATR, and OA were 52%, 22%, and 25%, and 86%, 9%, and 4% in the AP and CLP groups, respectively. A shift in astigmatism type was observed in 41% and 13% of patients in the AP and CLP groups, respectively. The average SIA measured using the Cravy method was 0.11±1.22 D in the AP group and -0.28±1.07 D in the CLP group (WTR astigmatism). The SIA calculated using the Jaffe method was 0.78±0.70 D in the AP group and 0.82±0.88 D in the CLP group. There was no significant correlation between SIA calculated using the Cravy and Jaffe methods and MRD. ATR was most common in age-related ptosis and WTR was most common in contact lens-related ptosis. Upper eyelid re-positioning may affect visual functions due to astigmatic changes in the short term postoperatively.

Decrease in choroidal blood flow after half and one-third dose verteporfin photodynamic therapy for chronic central serous chorioretinopathy.

BACKGROUND: The effect of various reduced doses of verteporfin photodynamic therapy (PDT) on choroidal blood flow in chronic central serous chorioretinopathy (CSC) remains unclear. Therefore, this study aimed to evaluate choroidal blood flow after half-dose PDT (1/2PDT) and one-third dose PDT (1/3PDT) with verteporfin for chronic CSC using laser speckle flowgraphy and spectral-domain optical coherence tomography. METHODS: Twenty-seven eyes of 27 patients with serous retinal detachment (SRD) caused by chronic CSC for more than 6 months were included in this study. Patients were divided into the 1/2PDT (n = 12; January 2018 to July 2019) and 1/3PDT (n = 15; August 2016 to December 2017) groups based on the treatment period. The best-corrected visual acuity (BCVA), central retinal thickness (CRT), central choroidal thickness (CCT), and mean blur rate in the macular area (m-MBR) and optic nerve head (ONH-MBR) were obtained using laser speckle flowgraphy and evaluated at baseline (pre-treatment), and 2 weeks, 1 month, 3 months, and 6 months after treatment. RESULTS: We found that SRD disappeared after 1 month in 92 and 93% of patients' eyes in the 1/2PDT and 1/3PDT groups, respectively. Recurrence of SRD was observed in one eye at the 6-month follow-up after 1/2PDT and two eyes at the 3-month follow-up after 1/3PDT. No significant improvement was observed in baseline BCVA in the 1/3PDT and 1/2PDT groups. The average m-MBR against baseline significantly decreased at 2 weeks and 1, 3, and 6 months in the 1/2PDT group. The average m-MBR against baseline decreased significantly only at the 2 weeks follow-up in the 1/3PDT group. The average rate of change in the CCT against baseline decreased significantly throughout for up to 6 months in the 1/2PDT group and for up to 3 months in the 1/3PDT group. No significant fluctuation was observed in the ONH-MBR. CONCLUSIONS: Here, PDT significantly affected choroidal blood flow depending on the verteporfin dose in chronic CSC. TRIAL REGISTRATION: This trial was retrospectively registered ( UMIN000026850 ; Approval date 03/04/2017).

Correlation between tangential distortion of the outer retinal layer and metamorphopsia in patients with epiretinal membrane.

PURPOSE: To evaluate tangential morphological changes in the outer retina and assess their correlation with the degree of metamorphopsia in patients with idiopathic epiretinal membrane (ERM). METHODS: This retrospective study included patients with idiopathic ERM who underwent vitrectomy between January 2018 and December 2019. We evaluated the preoperative examination results. Using cross-sectional spectral-domain optical coherence tomography (OCT) images along the horizontal/vertical meridian through the fovea, we defined a new parameter, tangential displacement (TD), as the tangential component of the position vector of the distorted outer nuclear layer caused by ERM. Visual function measurements included M-CHARTS results (vertical/horizontal metamorphopsia score [MV/MH]) and best-corrected visual acuity (BCVA). The correlations among the OCT parameters including TD and central foveal thickness (CFT) with visual function measurements were determined. RESULTS: Overall, 78 eyes of 76 patients (49 females; mean age, 67.9 [± standard deviation, 7.5 years]) were included. The mean horizontal TD was 24.0 ± 73.9 µm, which was significantly different from 0 (p = 0.005). The mean vertical TD was 6.0 ± 76.2 µm, which was not significantly different from 0. The absolute value of horizontal TD was significantly correlated with MV (r = 0.513, p < 0.01) and MH (r = 0.423, p < 0.01). The absolute value of vertical TD was also significantly correlated with MV (r = 0.274, p = 0.02) and MH (r = 0.413, p < 0.01). However, neither value was significantly correlated with BCVA. Multiple regression analysis showed that the horizontal absolute TD was an independent factor associated with both MV (ß = 0.635, p < 0.001) and MH (ß = 0.259, p = 0.048). CONCLUSION: We found that ERM tended to distort the outer retinal layer toward the temporal side of the fovea. The tangential distortion of this layer was associated with the degree of metamorphopsia, suggesting that misalignment of parafoveal photoreceptors causes metamorphopsia in patients with ERM.

Melanin concentration and depolarization metrics measurement by polarization-sensitive optical coherence tomography.

Imaging of melanin in the eye is important as the melanin is structurally associated with some ocular diseases, such as age-related macular degeneration. Although optical coherence tomography (OCT) cannot distinguish tissues containing the melanin from other tissues intrinsically, polarization-sensitive OCT (PS-OCT) can detect the melanin through spatial depolarization of the backscattered light from the melanin granules. Entropy is one of the depolarization metrics that can be used to detect malanin granules in PS-OCT and valuable quantitative information on ocular tissue abnormalities can be retrived by correlating entropy with the melanin concentration. In this study, we investigate a relationship between the melanin concentration and some depolarization metrics including the entropy, and show that the entropy is linearly proportional to the melanin concentration in double logarithmic scale when noise bias is corrected for the entropy. In addition, we also confirm that the entropy does not depend on the incident state of polarization using the experimental data, which is one of important attributes that depolarization metrics should have. The dependence on the incident state of polarization is also analyzed for other depolarization metrics.

HLA-Matched Allogeneic iPS Cells-Derived RPE Transplantation for Macular Degeneration.

Immune attacks are key issues for cell transplantation. To assess the safety and the immune reactions after iPS cells-derived retinal pigment epithelium (iPS-RPE) transplantation, we transplanted HLA homozygote iPS-RPE cells established at an iPS bank in HLA-matched patients with exudative age-related macular degeneration. In addition, local steroids without immunosuppressive medications were administered. We monitored immune rejections by routine ocular examinations as well as by lymphocytes-graft cells immune reaction (LGIR) tests using graft RPE and the patient's blood cells. In all five of the cases that underwent iPS-RPE transplantation, the presence of graft cells was indicated by clumps or an area of increased pigmentation at 6 months, which became stable with no further abnormal growth in the graft during the 1-year observation period. Adverse events observed included corneal erosion, epiretinal membrane, retinal edema due to epiretinal membrane, elevated intraocular pressure, endophthalmitis, and mild immune rejection in the eye. In the one case exhibiting positive LGIR tests along with a slight fluid recurrence, we administrated local steroid therapy that subsequently resolved the suspected immune attacks. Although the cell delivery strategy must be further optimized, the present results suggest that it is possible to achieve stable survival and safety of iPS-RPE cell transplantation for a year.

Polarization-sensitive optical coherence tomography for estimating relative melanin content of autologous induced stem-cell derived retinal pigment epithelium.

Transplantation of autologous human induced pluripotent stem cell-derived retinal pigment epithelial (hiPSC-RPE) sheets is a promising therapy for age-related macular degeneration (AMD). As melanin content is a representative feature of healthy RPE, we used polarization-sensitive optical coherence tomography (PS-OCT) to estimate the relative melanin content of RPE in diseased and non-diseased area, and in human iPSC-RPE sheets in vitro and in vivo by evaluating the randomness of polarization (entropy). Two aged Japanese women, one with neovascular AMD that underwent transplantation of an autologous hiPSC-RPE cell sheet and another with binocular dry AMD, were selected for this study. Entropy value was minimal in cells containing no melanin, whereas that of human RPE and hiPSC-RPE sheets was high. En face entropy of the cultured hiPSC-RPE sheet was compared with its grey-scale photo and its values were found to be inversely correlated with the extent of absence of pigmentation in vitro. En face entropy maps were compared to colour fundus photographs, fundus autofluorescence images, and fluorescein angiography images from patients. Entropy values of intact and defective RPEs and of iPSC-RPE transplant areas were determined in vivo using PS-OCT B-scan images. PS-OCT was found to be applicable in the estimation of relative melanin content of cultured and transplanted RPEs in regenerative medicine.

Bilateral retinitis after influenza virus infection in a case report.

PURPOSE: To report 2 years' longitudinal retinal changes using spectral domain optical coherence tomography (SD-OCT) images in a case of retinitis after influenza virus infection. OBSERVATIONS: A 48-year-old female complained of scotoma in the central visual field after influenza virus infection. Her best visual acuity was 20/16, her fundus examination was normal, and fluorescein angiography demonstrated no evident leakage in either the retina or the optic disc. However, SD-OCT images showed a disrupted, blurred inner-segment ellipsoid zone in the macula of both eyes. Two steroid pulse therapy sessions in the first 3 months showed temporary improvement of the central scotoma. However, atrophy of the photoreceptor layer at the juxta fovea gradually progressed in OCT images during the follow-up period. In contrast, the fovea itself was mostly intact and visual acuity was maintained in the 2-year period. CONCLUSIONS AND IMPORTANCE: We experienced a unique case of retinitis after influenza infection, in whom progressive atrophy of the photoreceptor layer was observed in SD-OCT images.

Optical Coherence Tomography-Based Deep-Learning Models for Classifying Normal and Age-Related Macular Degeneration and Exudative and Non-Exudative Age-Related Macular Degeneration Changes.

INTRODUCTION: The use of optical coherence tomography (OCT) images is increasing in the medical treatment of age-related macular degeneration (AMD), and thus, the amount of data requiring analysis is increasing. Advances in machine-learning techniques may facilitate processing of large amounts of medical image data. Among deep-learning methods, convolution neural networks (CNNs) show superior image recognition ability. This study aimed to build deep-learning models that could distinguish AMD from healthy OCT scans and to distinguish AMD with and without exudative changes without using a segmentation algorithm. METHODS: This was a cross-sectional observational clinical study. A total of 1621 spectral domain (SD)-OCT images of patients with AMD and a healthy control group were studied. The first CNN model was trained and validated using 1382 AMD images and 239 normal images. The second transfer-learning model was trained and validated with 721 AMD images with exudative changes and 661 AMD images without any exudate. The attention area of the CNN was described as a heat map by class activation mapping (CAM). In the second model, which classified images into AMD with or without exudative changes, we compared the learning stabilization of models using or not using transfer learning. RESULTS: Using the first CNN model, we could classify AMD and normal OCT images with 100% sensitivity, 91.8% specificity, and 99.0% accuracy. In the second, transfer-learning model, we could classify AMD as having or not having exudative changes, with 98.4% sensitivity, 88.3% specificity, and 93.9% accuracy. CAM successfully described the heat-map area on the OCT images. Including the transfer-learning model in the second model resulted in faster stabilization than when the transfer-learning model was not included. CONCLUSION: Two computational deep-learning models were developed and evaluated here; both models showed good performance. Automation of the interpretation process by using deep-learning models can save time and improve efficiency. TRIAL REGISTRATION: No15073.

Evaluation of Transplanted Autologous Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium in Exudative Age-Related Macular Degeneration.

PURPOSE: To report the results after 4 years of follow-up in a previously presented first case of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) sheet autologous transplantation using multimodal imaging. DESIGN: Follow-up of a single case. PARTICIPANT: A patient with exudative age-related macular degeneration and polypoidal choroidal vasculopathy. METHODS: Transplantation of an autologous iPSC-derived RPE cell sheet after removal of choroidal neovascularization (CNV) in September 2014. MAIN OUTCOME MEASURES: The function of the graft was assessed 4 years after surgery by color fundus photography, spectral-domain (SD) OCT, fluorescein angiography, indocyanine green angiography, and an adaptive optics (AO) retinal camera. RESULTS: At the 4-year follow-up, the transplanted autologous iPSC-derived RPE sheet had survived beneath the retina with slight expansion of the pigmented area and no adverse events. The outer nuclear layer above and adjacent to the graft showed acceptable thickness and an organized structure. Fluorescein angiography and SD OCT suggested the presence of vessel-like structures confined to the grafted area associated with the remaining trunk vessel of preoperative polypoidal choroidal vasculopathy but with no exudative changes. Visual acuity has been stable with no additional injections of anti-vascular endothelial growth factor agent. The choroidal volume at the graft site is relatively preserved when compared with the volume outside this site without RPE after removal of the CNV. Indocyanine green angiography revealed a preserved choriocapillaris around the iPSC-derived RPE sheet. Dark cell-like structures with a predominantly hexagonal arrangement were observed by AO imaging in an area located near the margin of the graft sheet. The average intercell distance was found to be stable over time. CONCLUSIONS: Thus far, the grafted iPSC-derived RPE sheet has survived for 4 years and seems to support photoreceptors and choroidal vessels. The morphologic characteristics of the RPE are observed at the transplant site.

Tilted Disc Syndrome Associated with Serous Retinal Detachment: Long-term Prognosis. A Retrospective Multicenter Survey.

PURPOSE: This study evaluated the long-term visual prognosis of a serous retinal detachment (SRD) secondary to tilted disc syndrome with or without an SRD at the final visit and the interventions. DESIGN: A retrospective, observational case series. METHODS: This was a multicenter study with an enrollment of 48 eyes of 41 treatment-naïve patients (14 men, 27 women) in whom tilted disc syndrome-related SRD was diagnosed at the first visit. Investigators at each institution decided whether to observe the patients without interventions or to treat with intravitreous injections of antivascular endothelial growth factor agents, photodynamic therapy, or both therapies combined. The patients were followed for at least 12 months. Main outcome measurements were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline. RESULTS: Analyses of all eyes showed improvement from baseline when BCVA was measured (P < 0.0001), although last BCVA was similar to BCVA at baseline (P = 0.46). CRT significantly improved from that at baseline at the final visit (P < 0.0001). When eyes with or without SRD at the final visit were analyzed, baseline BCVAs (P = 0.22) were similar, whereas BCVA (P = 0.05) and last BCVA (P = 0.005) were significantly better in eyes without SRD. When eyes with or without the interventions were analyzed, baseline (P = 0.70), best (P = 0.99), and last (P = 0.70) BCVAs were similar. Last CRT significantly decreased from baseline CRT in eyes that had undergone interventions (P < 0.0001). CONCLUSIONS: The visual prognosis of SRD secondary to tilted disc syndrome was better when SRD resolved but was not influenced by the treatments.

Assessment of the deformation of the outer nuclear layer in the Epiretinal membrane using spectral-domain optical coherence tomography.

BACKGROUND: We aimed to investigate the deformation of the outer nuclear layer using optical coherence tomography in patients with epiretinal membrane (ERM) and its relationship with metamorphopsia. METHODS: Thirty-nine eyes from 39 patients with ERM were included in the study. Patients with the subtypes of pseudo macula hole and lamellar hole were excluded. Twenty-one fellow eyes without macular disease were included as normal controls. Forty-nine B-scan images were obtained in the range of 20 degrees around the macula using SD-OCT. The outer nuclear layer (ONL) was evaluated as a three-dimensional image (3D-ONL) reconstructed using the distance between the ONL and retinal pigment epithelium (RPE) line. The deformation of the ONL was figured at the reference plane and evaluation plane (ONL-B). The characteristic parameters of the ONL-B were defined as circularity, area ratio, and axis ratio. The correlations between these parameters and visual acuity and MCHART score ratio (MH/MV) were then evaluated. RESULTS: ONL height was significantly higher in ERM patients than in normal controls (54.1 ± 5.3 µm and 84.1 ± 12.9 µm, respectively; P < 0.001). In ERM patients, the MV score was 0.53 ± 0.50, the MH score was 0.71 ± 0.61, and the distance from the RPE line to the ONL-B was 153.5 ± 13.5 µm. The axis of the ONL-B in normal controls and ERM patients was - 6.25 ± 21.8 and - 1.28 ± 29.1, respectively, which indicates that the ONL is horizontally long in both normal individuals and ERM patients. The circularity and area ratio were significantly smaller in ERM patients than in normal controls. In all ERM patients, MH/MV had a significant correlation with axis (r = - 0.29, p = 0.034), circularity (r = - 0.28, p = 0.044), and area ratio (r = - 0.47, p = 0.001). Moreover, we found that the correlation was more significant if the subjects had an axis of the ONL within ±10 degrees (n = 16); the correlations of MH/MV with axis (r = - 0.29, p = 0.034), circularity (r = - 0.53, p = 0.021), and area ratio were more significant (r = - 0.78, P < 0.0001). CONCLUSION: The ONL is horizontally long in normal individuals and ERM patients. The direction of metamorphopsia is correlated with the direction of ONL deformation.

Comparison of pretreatment measurements of anterior segment parameters in eyes with acute and chronic primary angle closure.

PURPOSE: To compare pretreatment anterior segment parameters between eyes with acute primary angle closure (APAC) and chronic primary angle closure (CPAC), and to identify the characteristics of eyes with APAC. STUDY DESIGN: Retrospective. METHODS: We measured pretreatment anterior chamber depth (ACD), iris convexity (IC), and pupil diameter in eyes with APAC and CPAC using anterior segment optical coherence tomography. The risk of APAC associated with anterior segment parameters was investigated using multiple logistic regression. Eyes with APAC were discriminated from eyes with CPAC using the receiver-operating characteristic (ROC) curve and area under the curve (AUC). The best cutoff for these variables was determined. RESULTS: Thirty-four eyes with APAC and 60 eyes with CPAC were included. The mean intraocular pressure was 52.3 ± 12.6 mmHg in APAC and 15.5 ± 3.5 mmHg in CPAC (P < .001). Eyes with APAC had a shallower ACD (1.407 ± 0.301 mm vs. 1.960 ± 0.205 mm, P < .001) and less IC (0.233 ± 0.087 mm vs. 0.294 ± 0.068 mm, P < .001) than eyes with CPAC. In multivariate analysis, significant variables associated with APAC were ACD (P < .001) and IC (P = .001). The AUC for ACD was 0.931 and for IC, 0.742. The best cutoff for ACD was 1.699 mm (sensitivity 0.824, specificity 0.917) and for IC, 0.282 mm (sensitivity 0.853, specificity 0.533). CONCLUSIONS: Eyes with APAC had a shallower ACD and less IC. Eyes with an ACD < 1.7 mm may be at risk for APAC.

Deep Learning Classification Models Built with Two-step Transfer Learning for Age Related Macular Degeneration Diagnosis.

The objective of this study was to build deep learning models with optical coherence tomography (OCT) images to classify normal and age related macular degeneration (AMD), AMD with fluid, and AMD without any fluid. In this study, 185 normal OCT images from 49 normal subjects, 535 OCT images of AMD with fluid, and 514 OCT mages of AMD without fluid from 120 AMD eyes as training data, while 49 normal images from 25 normal eyes, 188 AMD OCT images with fluid and 154 AMD images without any fluid from 77 AMD eyes as test data, were enrolled. Data augmentation was applied to increase the number of images to build deep learning models. Totally, two classification models were built in two steps. In the first step, a VGG16 model pre-trained on ImageNet dataset was transfer learned to classify normal and AMD, including AMD with fluid and/or without any fluid. Then, in the second step, the fine-tuned model in the first step was transfer learned again to distinguish the images of AMD with fluid from the ones without any fluid. With the first model, normal and AMD OCT images were classified with 0.999 area under receiver operating characteristic curve (AUC), and 99.2% accuracy. With the second model, AMD with the presence of any fluid, and AMD without fluid were classified with 0.992 AUC, and 95.1% accuracy. Compared with a transfer learned VGG16 model pre-trained on ImageNet dataset, to classify the three categories directly, higher classification performance was achieved with our notable approach. Conclusively, two classification models for AMD clinical practice were built with high classification performance, and these models should help improve the early diagnosis and treatment for AMD.

Long-term follow-up of penile glans necrosis due to paraphimosis.

INTRODUCTION: Paraphimosis is a urologic emergency in which the foreskin of the penis becomes trapped behind the coronal sulcus and forms a tight band of constricting tissue. Surgical or conservative release of this constriction is required for the treatment. Delayed treatment will cause devastating outcomes, such as penile glans necrosis. A few studies have reported penile glans necrosis/gangrene, but long-term follow-up of the recovery from glans necrosis due to paraphimosis has not been previously reported. CASE PRESENTATION: A 25-year-old man who experienced glans necrosis following paraphimosis was not treated promptly with circumcision. The patient underwent conservative treatment with debridement of necrotic tissue and cystostomy for urethral meatal necrosis. We were able to prevent partial penectomy. His penile glans was covered with healthy epithelium and retained its natural shape and voiding and erectile functions were normal 2 years after the treatment. CONCLUSION: We report successful conservative management of penile glans necrosis.

Frequencies of human leukocyte antigen alleles and haplotypes among Japanese patients with age-related macular degeneration.

PURPOSE: Stem cell therapy is a potential treatment for retinal disorders. We are currently exploring treating HLA matched patients of age-related macular degeneration (AMD) by using allogenic retinal pigment epithelium cells derived from induced pluripotent stem cells (iPS-RPE) from human leukocyte antigen (HLA) homozygote donors. The purpose of this study was to investigate the frequency of HLA class I and II alleles and haplotypes in Japanese patients with AMD. STUDY DESIGN: Cross-sectional observation clinical study. METHODS: A total of 138 consecutive patients diagnosed with neovascular AMD (mean age, 76.0 ± 7.8 years, 105 men) and 300 controls were included in the study. The frequencies of HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 alleles were determined using illumina MiSeq platform. Frequencies of HLA alleles at six loci in patients with AMD were compared with those of the controls. RESULTS: The alleles with the highest prevalence at each locus were A*24:02 (29.7%), B*52:01 (15.5%), C*12:02 (16.1%), DRB1*09:01 (19.1%), DQB1*06:01 (23.2%), and DPB1* 05:01 (40.5%). There were no significant associations between the HLA alleles and AMD. The most common haplotype was A*24:02-B*52:01-C*12:02-DRB1*15:02-DQB1*06:01-DPB1*09:01, with a 9.8% genetic frequency among all haplotypes, detected in 18.8% of the patients. CONCLUSION: The genotype of HLA in patients with AMD was not different from that in the Japanese control population. Thus, therapy with iPS-RPEof the most frequent HLA haplotype could be a feasible alternative for AMD in a wider population.

Development of a molecular diagnostic test for Retinitis Pigmentosa in the Japanese population.

PURPOSE: Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy caused by different genetic variants. More than 60 causative genes have been identified to date. The establishment of cost-effective molecular diagnostic tests with high sensitivity and specificity can be beneficial for patients and clinicians. Here, we developed a clinical diagnostic test for RP in the Japanese population. STUDY DESIGN: Evaluation of diagnostic technology, Prospective, Clinical and experimental study. METHODS: A panel of 39 genes reported to cause RP in Japanese patients was established. Next generation sequence (NGS) technology was applied for the analyses of 94 probands with RP and RP-related diseases. After interpretation of detected genetic variants, molecular diagnosis based on a study of the genetic variants and a clinical phenotype was made by a multidisciplinary team including clinicians, researchers and genetic counselors. RESULTS: NGS analyses found 14,343 variants from 94 probands. Among them, 189 variants in 83 probands (88.3% of all cases) were selected as pathogenic variants and 64 probands (68.1%) have variants which can cause diseases. After the deliberation of these 64 cases, molecular diagnosis was made in 43 probands (45.7%). The final molecular diagnostic rate with the current system combining supplemental Sanger sequencing was 47.9% (45 of 94 cases). CONCLUSIONS: The RP panel provides the significant advantage of detecting genetic variants with a high molecular diagnostic rate. This type of race-specific high-throughput genotyping allows us to conduct a cost-effective and clinically useful genetic diagnostic test.