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Currently there is no effective treatment available for osteoarthritis (OA). We have recently developed Kyoto University Substances (KUSs), ATPase inhibitors specific for valosin-containing protein (VCP), as a novel class of medicine for cellular protection. KUSs suppressed intracellular ATP depletion, endoplasmic reticulum (ER) stress, and cell death. In this study, we investigated the effects of KUS121 on chondrocyte cell death. In cultured chondrocytes differentiated from ATDC5 cells, KUS121 suppressed the decline in ATP levels and apoptotic cell death under stress conditions induced by TNFα. KUS121 ameliorated TNFα-induced reduction of gene expression in chondrocytes, such as Sox9 and Col2α. KUS121 also suppressed ER stress and cell death in chondrocytes under tunicamycin load. Furthermore, intraperitoneal administration of KUS121 in vivo suppressed chondrocyte loss and proteoglycan reduction in knee joints of a monosodium iodoacetate-induced OA rat model. Moreover, intra-articular administration of KUS121 more prominently reduced the apoptosis of the affected chondrocytes. These results demonstrate that KUS121 protects chondrocytes from stress-induced cell death in vitro and in vivo, and indicate that KUS121 is a promising novel therapeutic agent to prevent the progression of OA.

ImportanceThere is no widespread effective treatment to halt the progression of retinitis pigmentosa. Consequently, adequate assessment and estimation of residual visual function are important clinically.ObjectiveTo examine whether deep learning can accurately estimate the visual function of patients with retinitis pigmentosa by using ultra-widefield fundus images obtained on concurrent visits.Design, Setting, and ParticipantsData for this multicenter, retrospective, cross-sectional study were collected between January 1, 2012, and December 31, 2018. This study included 695 consecutive patients with retinitis pigmentosa who were examined at 5 institutions. Each of the 3 types of input images—ultra-widefield pseudocolor images, ultra-widefield fundus autofluorescence images, and both ultra-widefield pseudocolor and fundus autofluorescence images—was paired with 1 of the 31 types of ensemble models constructed from 5 deep learning models (Visual Geometry Group–16, Residual Network–50, InceptionV3, DenseNet121, and EfficientNetB0). We used 848, 212, and 214 images for the training, validation, and testing data, respectively. All data from 1 institution were used for the independent testing data. Data analysis was performed from June 7, 2021, to December 5, 2022.Main Outcomes and MeasuresThe mean deviation on the Humphrey field analyzer, central retinal sensitivity, and best-corrected visual acuity were estimated. The image type–ensemble model combination that yielded the smallest mean absolute error was defined as the model with the best estimation accuracy. After removal of the bias of including both eyes with the generalized linear mixed model, correlations between the actual values of the testing data and the estimated values by the best accuracy model were examined by calculating standardized regression coefficients and P values.ResultsThe study included 1274 eyes of 695 patients. A total of 385 patients were female (55.4%), and the mean (SD) age was 53.9 (17.2) years. Among the 3 types of images, the model using ultra-widefield fundus autofluorescence images alone provided the best estimation accuracy for mean deviation, central sensitivity, and visual acuity. Standardized regression coefficients were 0.684 (95% CI, 0.567-0.802) for the mean deviation estimation, 0.697 (95% CI, 0.590-0.804) for the central sensitivity estimation, and 0.309 (95% CI, 0.187-0.430) for the visual acuity estimation (all P Conclusions and RelevanceResults of this study suggest that the visual function estimation in patients with retinitis pigmentosa from ultra-widefield fundus autofluorescence images using deep learning might help assess disease progression objectively. Findings also suggest that deep learning models might monitor the progression of retinitis pigmentosa efficiently during follow-up.

In glaucoma, retinal ganglion cells degenerate progressively, leading to visual field loss and blindness. Presently, the only treatment strategy for glaucoma is lowering the intraocular pressure. However, there are cases in which patients develop progressive visual field loss even though their intraocular pressures are within normal ranges. Therefore, the development of novel therapeutic strategies is an urgent endeavor. Besides high intraocular pressure, several other factors have been proposed to be associated with glaucoma progression, e.g., myopia, blood flow impairment, and amyloid β accumulation. We have previously reported that hop flower extracts possess γ-secretase inhibitory activities and reduce amyloid β deposition in the brains of Alzheimer’s disease model mice. In the current study, we showed that administration of hop flower extracts to glutamate-aspartate transporter (GLAST) knockout mice, the glaucoma model mice, attenuated glaucomatous retinal ganglion cell degeneration. Preservation of retinal ganglion cells in hop flower extract-administered mice was confirmed using optical coherence tomography, confocal scanning laser ophthalmoscopy, and retinal flatmount and histological evaluations. Hop flower extracts are, therefore, deemed a possible candidate as a novel therapeutic agent to treat glaucoma.

To assess the characteristics of glaucoma patients who received systemic or topical steroid treatment. Patients who received steroid treatment were selected from a total of 4256 patients at our tertiary referral center of glaucoma management between August 2011 and October 2017. Clinical characteristics of the subjects were extracted from clinical records. To evaluate the factors influencing highest intraocular pressure during observation (max-IOP) or mean deviations (MDs) of visual field at the first and last visits, univariate and multivariate regression analyses were performed using a generalized estimating equation. Three hundred and eighty-two eyes of 196 patients were included in this study. The most frequent disease as the reason for steroid treatment was atopic dermatitis (58 eyes) followed by autoimmune diseases. The patients with atopic dermatitis were significantly younger (38.0 ± 11.2 years old, p < 0.001) and had lower MD (− 9.3 ± 9.1 dB at first visit, p = 0.01; − 10.6 ± 9.2 dB at last visit, p = 0.004) than those with other diseases. In multivariate regression analysis, age and MD at first visit, max-IOP, and atopic dermatitis were correlated with MD at last visit. The results of the present study suggest that patients with atopic dermatitis carry the risk of irreversible visual field loss even in youth. For earlier detection of high intraocular pressure, reinforcement of ophthalmological screening in management of atopic dermatitis should be recommended.

Inherited retinal dystrophy (IRD) patients often experience photophobia. However, its mechanism has not been elucidated. This study aimed to investigate the main wavelength of light causing photophobia in IRD and difference among patients with different phenotypes. Forty-seven retinitis pigmentosa (RP) and 22 cone-rod dystrophy (CRD) patients were prospectively recruited. We designed two tinted glasses: short wavelength filtering (SWF) glasses and middle wavelength filtering (MWF) glasses. We classified photophobia into three types: (A) white out, (B) bright glare, and (C) ocular pain. Patients were asked to assign scores between one (not at all) and five (totally applicable) for each symptom with and without glasses. In patients with RP, photophobia was better relieved with SWF glasses {“white out” (p

In glaucoma, retinal ganglion cells are damaged, leading to the progressive constriction of the visual field. We have previously shown that the valosin-containing protein (VCP) modulators, Kyoto University Substance (KUS)121 and KUS187, prevent the death of retinal ganglion cells in animal models of glaucoma, including the one generated by N-methyl-D-aspartate (NMDA)-induced neurotoxicity. KUSs appeared to avert endoplasmic reticulum (ER) stress by maintaining ATP levels, resulting in the protection of ganglion cells from cell death. To further elucidate the protective mechanisms of KUSs, we examined gene expression profiles in affected ganglion cells. We first injected KUS-treated mice with NMDA and then isolated the affected retinal ganglion cells using fluorescence-activated cell sorting. Gene expression in the cells was quantified using a next-generation sequencer. Resultantly, we found that KUS121 upregulated several genes involved in energy metabolism. In addition, we observed the upregulation of Zfp667, which has been reported to suppress apoptosis-related genes and prevent cell death. These results further support the suitability of KUS121 as a therapeutic drug in protecting retinal ganglion cells in ophthalmic disorders, such as glaucoma.

Acute kidney injury (AKI) is a life-threatening condition and often progresses to chronic kidney disease or the development of other organ dysfunction even after recovery. Despite the increased recognition and high prevalence of AKI worldwide, there has been no established treatment so far. The aim of this study was to investigate the renoprotective effect of Kyoto University substance 121 (KUS121), a novel valosin-containing protein modulator, on AKI. In in vitro experiments, we evaluated cell viability and ATP levels of proximal tubular cells with or without KUS121 under endoplasmic reticulum (ER) stress conditions. In in vivo experiments, the effects of KUS121 were examined in mice with AKI caused by ischemia-reperfusion injury. ER-associated degradation (ERAD)-processing capacity was evaluated by quantification of the ERAD substrate CD3delta-YFP. KUS121 protected proximal tubular cells from cell death under ER stress. The apoptotic response was mitigated as indicated by the suppression of C/EBP homologous protein expression and caspase-3 cleavage, with maintained intracellular ATP levels by KUS121 administration. KUS121 treatment suppressed the elevation of serum creatinine and neutrophil gelatinase-associated lipocalin levels and attenuated renal tubular damage after ischemia-reperfusion. The expression of inflammatory cytokines in the kidney was also suppressed in the KUS121-treated group. Valosin-containing protein expression levels were not altered by KUS121 both in vitro and in vivo. KUS121 treatment restored ERAD-processing capacity associated with potentiation of its upstream pathway, phosphorylated inositol-requiring enzyme-1α, and spliced X box-binding protein-1. In conclusion, these findings indicate that KUS121 can protect renal tubular cells from ER stress-induced injury, suggesting that KUS121 could be a novel and promising therapeutic compound for ischemia-associated AKI.

Optical coherence tomography angiography (OCTA) is a new technique for non-invasive imaging of blood vessels, allowing combined evaluation of both deep and surface vessels. The purpose of this study was to evaluate the post-trabeculectomy longitudinal changes in complete avascular area (CAA) of filtering blebs using anterior segment (AS-) OCTA and their association with surgical outcomes. This study included 57 eyes of 53 patients who had undergone trabeculectomy with mitomycin C. AS-OCTA images of filtering bleb were acquired at 3 and 6 months after trabeculectomy, and at 1 month in possible cases. CAAs, regions where complete blood flow was not depicted in AS-OCTA images, were evaluated for their presence, extent, and change over time. CAAs were detected in 37 eyes (65%) and 33 eyes (58%) at 3 and 6 months postoperatively, respectively. The extent of CAAs reduced over time after surgery in most cases. No parameters related to CAAs were significantly associated with surgical success (i.e., intraocular pressure (IOP) ≤ 12 mmHg and IOP reduction > 20% without medication). In conclusion, although it is difficult to predict surgical success by CAA itself, AS-OCTA may be useful for the objective evaluation of the vascularity of filtering blebs.

We have established a stepwise method to differentiate induced pluripotent stem cells (iPSCs) into retinal pigment epithelium (RPE) (iPSC-RPE), which enables efficient isolation and purification of patient-derived iPSC-RPE cells with high quality. Here, we describe in detail the process of differentiating iPSCs into iPSC-RPE.

We performed a prospective, longitudinal study to investigate the association between the preoperative intrascleral vasculature assessed using anterior segment (AS)-optical coherence tomography angiography (OCTA) and surgical outcomes of trabecular meshwork-targeted micro- or minimally invasive glaucoma surgery (MIGS). We included 37 patients with primary open-angle glaucoma. Preoperative AS-OCTA images of the sclero-conjunctiva of the nasal corneal limbus were acquired in the superficial (conjunctival) and deep (intrascleral) layers. The vessel densities (VDs) of each layer were measured separately in the entire area, limbal side, and fornix area. Surgical success was determined by postoperative intraocular pressure (IOP) and IOP reduction. Twenty-three and 14 eyes were classified as having successful and unsuccessful outcomes, respectively. The deep VDs of the entire area and fornix area were significantly lower in the successful group (P = 0.031 and P = 0.009). The success rate was significantly higher for eyes with a lower deep VD than for eyes with a higher deep VD. A greater IOP reduction was significantly associated with lower deep VD in the fornix area (P = 0.022) and higher preoperative IOP (P, 前眼部OCTAを用いた線維柱帯切開術効果予測 --房水主流出路の可視化による緑内障手術予後予測の可能性--. 京都大学プレスリリース. 2021-09-09.

Purpose To investigate conjunctival and intrascleral vasculature in glaucoma eyes using anterior segment (AS)-optical coherence tomography angiography (OCTA) and assess the factors contributing to the vessel density in AS-OCTA images. Design Prospective, cross-sectional study. Methods Thirty-four patients with primary open-angle glaucoma and 20 healthy subjects were included. A swept-source OCT system was used to obtain the AS-OCTA images of the corneoscleral limbus at the nasal and temporal quadrants. Vessel densities were measured in the superficial (from the conjunctival epithelium to a depth of 200 μm) and deep (from a depth of 200 to 1000 μm) layers. The vessel density was compared between healthy and glaucoma eyes, and the associations of the vessel density with possible confounding factors were analyzed using univariable and multivariable analyses. Results The vessel density was not significantly different between healthy eyes and eyes with glaucoma. There was a significant association of superficial vessel density with the use of a prostaglandin analog (P = .007) and with nasal location (P = .016) in eyes with glaucoma. Deep vessel density was significantly smaller with advancing age (P = .029) in healthy eyes and greater with higher intraocular pressure (P = .021) in eyes with treated glaucoma. Conclusions AS-OCTA images may be useful for the objective assessment of conjunctival hyperemia and helpful for understanding the pathophysiology of post-trabecular aqueous humor outflow.

We have previously shown that maintenance of ATP levels is a promising strategy for preventing neuronal cell death, and that branched chain amino acids (BCAAs) enhanced cellular ATP levels in cultured cells and antagonized cell death. BCAAs attenuated photoreceptor degeneration and retinal ganglion cell death in rodent models of retinal degeneration or glaucoma. This study aimed to elucidate the mechanisms through which BCAAs enhance ATP production.Intracellular ATP concentration was measured in HeLa cells under glycolysis and citric acid cycle inhibited conditions. Next, glucose uptake was quantified in HeLa cells and in 661W retinal photoreceptor-derived cells under glycolysis inhibition, endoplasmic reticulum stress, and glucose transporters (GLUTs) inhibited conditions, by measuring the fluorescence of fluorescently labeled deoxy-glucose analog using flow cytometry. Then, the intracellular behavior of GLUT1 and GLUT3 were observed in HeLa or 661W cells transfected with enhanced green fluorescent protein-GLUTs.BCAAs recovered intracellular ATP levels during glycolysis inhibition and during citric acid cycle inhibition. BCAAs significantly increased glucose uptake and recovered decreased glucose uptake induced by endoplasmic reticulum stress or glycolysis inhibition. However, BCAAs were unable to increase intracellular ATP levels or glucose uptake when GLUTs were inhibited. Fluorescence microscopy revealed that supplementation of BCAAs enhanced the translocation of GLUTs proteins to the plasma membrane over time.BCAAs increase ATP production by promoting glucose uptake through promotion of glucose transporters translocation to the plasma membrane. These results may help expand the clinical application of BCAAs in retinal neurodegenerative diseases, such as glaucoma and retinal degeneration.

To investigate the association between the use of topical β-blockers and subsequent asthma attacks in glaucoma patients with asthma. This was a retrospective longitudinal cohort study using an administrative claims database. All patients aged 20 years or older who were registered in the health insurance claims database updated and managed by JMDC Inc. (Tokyo, Japan). Patients who were newly prescribed eye drops for glaucoma treatment were identified between 2011 and 2017. The patients with glaucoma were divided into two groups: β-blocker users and non-β-blocker users, based on the presence of a β-blocker in the prescribed eye drops. We investigated whether the incidence of asthma attacks in patients with previously treated asthma differed between the two groups. We categorized 17,666 patients in the β-blocker-user group and 12,609 patients in the non-β-blocker-user group. A total of 580 patients in the β-blocker group (3.28%) and 847 in the non-β-blocker group (6.72%) underwent asthma treatment before the prescription of anti-glaucoma eye drops (P

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Concentric retinitis pigmentosa (RP), in which retinal degeneration is limited in the periphery, is rare and little information exists to date on the subject. Herein, we describe the clinical and genetic characteristics of this atypical form of RP. We retrospectively reviewed our database and identified 14 patients with concentric RP. Additionally, 14 patients with age-matched typical RP were also included. Patients with concentric RP had better visual acuity (logarithm of minimum angle of resolution −0.04 vs. 0.32, p = 0.047) and preserved ellipsoid zones (7630 µm vs. 2646 µm, p &lt, 0.001) compared to typical RP. The electroretinogram showed subnormal but recordable responses in patients with concentric RP. Genetic testing was done in nine patients with concentric RP and revealed causative mutations in the EYS gene in one patient and the RP9 gene in one patient. Two patients had myotonic dystrophy and the diagnosis was revised as myotonic dystrophy-associated retinopathy. Concentric RP is a rare, atypical form of RP with better visual function. There is some overlap in the causative genes in concentric and typical RP. Myotonic dystrophy-associated retinopathy is an important differential diagnosis.

We have established a stepwise method to differentiate induced pluripotent stem cells (iPSCs) into retinal pigment epithelium (RPE) (iPSC-RPE), which enables efficient isolation and purification of patient-derived iPSC-RPE cells with high quality. Here, we describe in detail the process of differentiating iPSCs into iPSC-RPE.

Glaucoma is a multifactorial optic neuropathy, possibly involving vascular dysfunction, leading to the death of retinal ganglion cells and their axons. Disc hemorrhage (DH) is known to be closely associated with the widening of retinal nerve fiber layer defect (NFLD); however, it has not been well elucidated how DH affects retinal microvasculature. We aimed to investigate the association between DH history and longitudinal changes in superficial retinal microvasculature in NFLD. We enrolled 15 glaucoma patients with DH history (32 glaucomatous NFLD locations, with or without DH history). NFLD-angle, superficial retinal vessel density (VD), and decreased superficial retinal microvasculature (deMv)-angle were assessed using optical coherence tomography angiography for at least three times over time. The mean follow-up period and OCT/OCTA scan interval were 21.3 ± 5.4 months (range, 12–28) and 6.8 ± 0.4 months (range, 2–18), respectively. Linear mixed-effects models showed that the presence of DH history was significantly associated with an additional NFLD-angle widening of 2.19 degree/year (P = 0.030), VD decrease of 1.88%/year (P = 0.015), and deMv-angle widening of 3.78 degree/year (P P

Background: To investigate the short-term effects of different types of anti-glaucoma eyedrop on sclero-conjunctival vasculatures and their associations with intraocular pressure (IOP) reduction. Methods: This was a prospective study including 20 healthy subjects. A single instillation of ripasudil or bimatoprost was introduced into the right eyes of the participants. The superficial (conjunctival) and deep (intrascleral) vasculatures of the corneal limbus using anterior-segment optical coherence tomography angiography (OCTA) and IOP were examined in both eyes at baseline and 15 min and 2 h after instillation. Results: In the ripasudil group, the vessel density (VD) (median) at baseline (deep, 13.1%, superficial, 28.5%) significantly increased in both layers at 15 min (deep, 19.9%, superficial, 37.3%) and the deep layer at 2 h (deep, 14.8%, superficial, 31.6%). In the bimatoprost group, the superficial VD significantly changed over time, but the deep VD did not. The greater effect of ripasudil on IOP reduction was significantly associated with a lower baseline VD in the deep layer (at 15 min, p = 0.004, at 2 h, p = 0.018). Conclusions: Differences in the timing, depth, and extent of the effects on vasculature after instillations, could be detected using OCTA. The IOP-lowering effects of ripasudil might be associated with the deep vasculature.

Next-generation sequencing (NGS) has greatly advanced the studies of causative genes and variants of inherited diseases. While it is sometimes challenging to determine the pathogenicity of identified variants in NGS, the American College of Medical Genetics and Genomics established the guidelines to help the interpretation. However, as to the genetic screenings for patients with retinitis pigmentosa (RP) in Japan, none of the previous studies utilized the guidelines. Considering that EYS is the major causative gene of RP in Japan, we conducted stepwise genetic screening of 220 Japanese patients with RP utilizing the guidelines. Step 1–4 comprised the following, in order: Sanger sequencing for two major EYS founder mutations; targeted sequencing of all coding regions of EYS; whole genome sequencing; Sanger sequencing for Alu element insertion in RP1, a recently determined founder mutation for RP. Among the detected variants, 2, 19, 173, and 1 variant(s) were considered pathogenic and 8, 41, 44, and 5 patients were genetically solved in step 1, 2, 3, and 4, respectively. Totally, 44.5% (98/220) of the patients were genetically solved, and 50 (51.0%) were EYS-associated and 5 (5.1%) were Alu element-associated. Among the unsolved 122 patients, 22 had at least one possible pathogenic variant.

Post-traumatic osteoarthritis (PTOA) is a major cause which hinders patients from the recovery after intra-articular injuries or surgeries. Currently, no effective treatment is available. In this study, we showed that inhibition of the acute stage chondrocyte death is a promising strategy to mitigate the development of PTOA. Namely, we examined efficacies of Kyoto University Substance (KUS) 121, a valosin-containing protein modulator, for PTOA as well as its therapeutic mechanisms. In vivo, in a rat PTOA model by cyclic compressive loading, intra-articular treatments of KUS121 significantly improved the modified Mankin scores and reduced damaged-cartilage volumes, as compared to vehicle treatment. Moreover, KUS121 markedly reduced the numbers of TUNEL-, CHOP-, MMP-13-, and ADAMTS-5-positive chondrocytes in the damaged knees. In vitro, KUS121 rescued human articular chondrocytes from tunicamycin-induced cell death, in both monolayer culture and cartilage explants. It also significantly downregulated the protein or gene expression of ER stress markers, proinflammatory cytokines, and extracellular-matrix-degrading enzymes induced by tunicamycin or IL-1β. Collectively, these results demonstrated that KUS121 protected chondrocytes from cell death through the inhibition of excessive ER stress. Therefore, KUS121 would be a new, promising therapeutic agent with a protective effect on the progression of PTOA., 京大開発の薬剤「KUS121」の変形性膝関節症への効果を確認 --外傷性変形性関節症の治療薬として臨床応用へ--. 京都大学プレスリリース. 2020-12-17.

OBJECTIVES: We investigated in vivo light-induced photoreceptor damage in retinitis pigmentosa (RP) using spectral-domain optical coherence tomography (SD-OCT) images. METHODS: We retrospectively reviewed patients with genetic diagnosis of EYS-associated RP. The outer nuclear layer (ONL) thickness under retinal vessels was measured on SD-OCT vertical scans. As a control, we measured adjacent ONL thickness 100 μm superior and inferior from the vessel. Same measurements were performed in healthy subjects. We calculated the ratio of ONL thickness under vessel divided by the average of adjacent ONL thickness and defined as ONL preservation ratio. In patients with RP, the length of ellipsoid zone (EZ) from the fovea was also measured with SD-OCT vertical scans. RESULTS: Thirty EYS-associated RP patients and 25 healthy subjects were included. In both groups, ONL thickness overshadowed by retinal vessels was not significantly different from that of adjacent area. However, ONL preservation ratio of RP was larger than that of healthy control in both superior and inferior retina (1.03 vs 0.97; p

Epidemiological studies indicate that the daily intake of antioxidants from a traditional Asian diet reduces the risk of developing age-related macular degeneration. Many of the phytochemicals that are abundant in whole grains exhibit a wide variety of biological activity such as antioxidant, anti-inflammatory, and neuroprotective effects. Ferulic acid (FA) is a phenolic acid found in vegetables and grains that has therapeutic potential for diabetes mellitus, Alzheimer’s disease, and other diseases. We investigated the retinal protective effect of FA in a sodium iodate (NaIO3)-induced model of retinal degeneration. In a human retinal pigment epithelial cell line, FA attenuated H2O2-induced injury and lipopolysaccharide- or 7-ketocholesterol-induced inflammation. In mice, the oral administration of FA or its analog, ethyl ferulate, attenuated the morphological and functional features of NaIO3-induced retinal degeneration according to optical coherence tomography and electroretinography. Our results demonstrate that the oral administration of FA provides protective effects to the retina, suggesting that the intake of FA as a daily supplement or daily healthy diet containing rich vegetables and whole grains may prevent age-related macular degeneration.

Masayo Suda, Hideo Nakanishi, Tadamichi Akagi, Tomoaki Murakami, Kiyoshi Suzuma, Kenji Suda, Takanori Kameda, Satoshi Morooka, Hanako Ohashi Ikeda, Akitaka Tsujikawa Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan Purpose: To describe the 1-year surgical outcomes of both Baerveldt glaucoma implant (BGI) and the Ahmed glaucoma valve (AGV) implant with pars plana tube insertion in Japanese eyes with neovascular glaucoma (NVG). Patients and methods: This was a retrospective study of 21 eyes of 18 patients who had undergone BGI (10 eyes) or AGV (11 eyes) implantation. The 1-year surgical outcomes in the two groups were compared. Surgical success was defined as an intraocular pressure (IOP) of 6–21 mmHg (criterion A) or 6–18 mmHg (criterion B) with >20% reduction regardless of the use of antiglaucoma medications. Results: The mean preoperative IOP was 33.9±6.6 mmHg in the BGI group and 30.9±5.3 mmHg in the AGV group (P=0.31). The IOP at 1-year was lower in the BGI group at 10.3±5.9 mmHg than in the AGV group at 14.8±3.3 mmHg (P=0.044). The mean number of glaucoma medications at 1 year was 1.0±1.3 in the BGI group and 1.4±1.4 in the AGV group (P=0.57). The incidence of postoperative complications during the 1-year follow-up was not statistically different between the two groups; however, one eye in the BGI group lost light perception after additional surgery for Hoffman elbow exposure. The 1-year success rates of the BGI group was 60.0% and that in the AGV group was 90.9% based on criterion A (P=0.095), and 50.0% and 81.8% based on criterion B (P=0.074). Conclusions: Significant reductions of the IOP and number of glaucoma medications were achieved at 1 year after both types of implants in Japanese eyes with NVG. Keywords: neovascular glaucoma, Baerveldt, Ahmed, glaucoma drainage device, pars plana tube insertion

PURPOSE The purpose of this study was to investigate the lamina cribrosa (LC) microvasculature using swept-source optical coherence tomography angiography (OCTA) images that have been processed using multiple image averaging and a projection-resolved algorithm. OCTA has recently gained popularity for assessing retinal and choroidal microvasculature. However, it is not known if the LC microvasculature, which likely holds important information for further understanding of glaucoma, can be visualized with OCTA. METHODS One normal subject and 1 glaucomatous subject were enrolled and optic disc 3×3 mm swept-source OCTA cubic images were obtained for each subject. Anterior LC slab frames were developed, and the averaged images were created using 3 frames. Images were examined both with and without removal of projection artifacts. RESULTS The OCTA images of anterior LC slabs before projection artifact removal contained information on superficial and deep layer vessel blood flow. However, after projection artifact removal, fewer blood flow signals remained. These en face OCTA images showed flow signals on or immediately adjacent to lamina beams, but not inside lamina pores. The glaucomatous eye had a sectoral reduction in LC microvasculature blood flow that was not detected in normal eye. CONCLUSIONS This is the first demonstration of imaging of the inner LC microvasculature, which, in agreement with previous histologic reports, was arranged in a polygonal pattern. Furthermore, glaucomatous eye had decreased flow signals in comparison with normal eye. Therefore, future imaging studies with OCTA may be helpful for identifying and better understanding LC pathologic changes associated with glaucoma.

In retinitis pigmentosa (RP), peripheral visual-field loss starts in early stages, whereas central vision loss occurs in advanced stages. Sensory strabismus gradually occurs in RP. We investigated the relationship between ocular deviation and visual function and explored for sensory strabismus risk factors in 119 consecutive patients with RP at various stages. We assessed ocular deviation at far and near distances, that is the central visual field, using the mean deviation (MD) value and visual acuity (VA), and the residual binocular field area, using Goldmann perimetry (GP), in 33 patients. The horizontal ocular deviation at near distance was >10° in 30% patients and correlated with residual visual function. Although there was no effective cut-off value for central visual function, a cut-off residual GP area of 40 cm2 distinguished patients with a larger from those with a smaller horizontal ocular deviation at far distance (P = 0.04). Our findings suggest that visual function is negatively associated with ocular deviation in patients with RP and that the sensory strabismus risk is relatively high for patients with a binocular visual field 2. Thus, screening for ocular alignment may be necessary for patients with RP-associated severe vision loss as part of their comprehensive care.

Purpose: To compare the detection sensitivities of the progression of retinitis pigmentosa (RP) by automated perimetry to obtain the mean deviation (MD) and total point score and by optical coherence tomography (OCT) to determine the residual ellipsoid zone (EZ) length and thickness of retinal layers. Methods: Twenty-two eyes of 22 patients with RP who underwent annual automated perimetry (Humphrey Field Analyzer 10-2) and OCT examinations during the same period more than four times were included. Disease progression was evaluated using linear regression analysis with the least-squares method. The disease progression speed and interinspection fluctuations for the different examinations were compared using standardized values. The progression detection ability factor, defined as the average of the least squares divided by the square of annual change, was used to compare the sensitivities of the examinations for detecting the progression of RP. Results: EZ length showed a high correlation with MD (R = 0.87; P = 1.12E-07) at baseline. Disease progression was detected more frequently using EZ length (12/22 eyes) than using MD (3/22 eyes; P = 0.004) or central retinal thickness (1/11 eyes; P = 0.012). Linear regression using standardized values showed that the EZ length had the fastest annual change, with the smallest least absolute values. EZ length was more sensitive for detecting RP progression than MD, total point score, visual acuity, or central retinal thickness. Conclusions: EZ measurement was sensitive for detecting RP progression, and the results of this study indicate that EZ length is appropriate for end points in clinical trials. Translational Relevance: The study provides a basis for conducting future clinical trials.