Blood flow alterations in cavernous sinus dural arteriovenous fistula: Optical coherence tomography angiography findings.

Purpose: This case report details the diagnostic process for a patient with an initial diagnosis of scleritis who was unresponsive to typical treatment modalities, culminating in the identification of a cavernous sinus dural arteriovenous fistula (CS-DAVF). The case highlights the role of anterior segment optical coherence tomography angiography (OCTA) in the diagnosis of this vascular anomaly and in monitoring the response to treatment. Observations: A 45-year-old man with persistently elevated intraocular pressure (IOP) and ocular congestion in the left eye was unresponsive to treatment for scleritis. The persistent ocular symptoms and new-onset tinnitus prompted further investigation. Anterior segment OCTA revealed vascular anomalies, and magnetic resonance imaging confirmed a CS-DAVF. The patient underwent endovascular treatment for the CS-DAVF. This intervention led to a significant reduction in IOP in the left eye and the resolution of ocular congestion. Conclusions and importance: This case highlights the diagnostic complexities of ophthalmic symptoms that mimic those of other conditions. Furthermore, it demonstrates the essential role of anterior segment OCTA in the accurate diagnosis and effective management of CS-DAVF and highlights the need for comprehensive diagnostic approaches in ophthalmology.

A case of Epstein-Barr virus-associated primary vitreoretinal lymphoma in an immunosuppressed patient.

PURPOSE: To describe a rare case of Epstein-Barr virus (EBV)-positive primary vitreoretinal lymphoma (PVRL) in an immunosuppressed patient. METHODS: Observational case report. RESULTS: A 64-year-old man under immunosuppressive therapy for rheumatic arthritis was referred for 2-month of blurred vision and decreased visual acuity in the right eye. Only mutton-fat keratic precipitates and mild vitreous opacity were found in the right eye without (sub-)retinal or sub-retinal pigment epithelial lesions. Vitreous biopsy and systemic workup suggested the diagnosis of PVRL of diffuse large B cell lymphoma (DLBCL) subform. Neoplastic cells stained positive for EBV antigens, EBV-encoded small RNA and Epstein-Barr nuclear antigen 2, consistent with EBV-positive DLBCL. Intravitreal methotrexate was effective in improving ocular symptoms. CONCLUSION: Our case provided evidence on the association of EBV infection with PVRL.

Association of Retinal Pigment Epithelium Reflectivity on Optical Coherence Tomography with Recurrence of Vogt-Koyanagi-Harada Disease: A Retrospective Observational Study.

Purpose: Despite the necessity of optical coherence tomography (OCT) for diagnosis and longitudinal monitoring in patients with Vogt-Koyanagi-Harada (VKH) disease, no studies have identified useful OCT markers for predicting recurrence in these patients. Although the precise reason for this remains unclear, one possibility is that infiltration of inflammatory cells into the choroid attenuates the OCT signal, making it difficult to precisely assess the structure of the choroid. Therefore, this study aimed to investigate changes in retinal pigment epithelium (RPE) reflectivity immediately above the choroid in eyes with acute VKH disease, as well as the association between RPE reflectivity and VKH disease recurrence. Patients and Methods: This single-centered retrospective observational study included 20 treatment-naïve patients with acute VKH disease presenting with serous retinal detachment (SRD) in the posterior pole at the initial visit between October 2015 and January 2020, as well as 15 healthy control eyes. All patients were followed up for at least 6 months and received treatment with intravenous methylprednisolone followed by oral administration of prednisolone. Swept-source OCT images through the fovea were used to measure central retinal thickness, central choroidal thickness, and RPE reflectivity. Results: During an observation period of 37.2 ± 30.8 months, recurrence of inflammation was observed in 11 patients (55.0%). Initial visual acuity was worse in patients who developed recurrence than in those who did not (P=0.024). On initial OCT images, RPE reflectivity differed significantly between patients with and without recurrence (1.75 ± 0.42 vs 1.35 ± 0.20; P=0.018), while there were no significant differences in other chorioretinal parameters, such as central retinal thickness and choroidal thickness. Conclusion: RPE reflectivity on OCT images may be useful for predicting the recurrence of inflammation in patients with VKH disease.

Deformation Texture of Bulk Cementite Investigated by Neutron Diffraction.

Understanding the deformation mechanism of cementite such as on a slip plane is important with regard to revealing and improving the mechanical property of steels. However, the deformation behavior of cementite has not been well investigated because of the difficulty of sample preparation given the single phase structure of cementite. In this study, by fabricating bulk single phase cementite samples using the method developed by the authors, the deformation texture formed by uniaxial compression was investigated using both electron back scatter diffraction and neutron diffraction. The fabricated sample had a random texture before the compression. After applying a compressive strain of 0.5 at 833 K, (010) fiber texture was formed along the compressive axis. It has been suggested from this trend that the primary slip plane of cementite is (010).

Anti-fumarase antibody promotes the dropout of photoreceptor inner and outer segments in diabetic macular oedema.

AIMS/HYPOTHESIS: In diabetic macular oedema (DMO), blood components passing through the disrupted blood-retinal barrier cause neuroinflammation, but the mechanism by which autoantibodies induce neuroglial dysfunction is unknown. The aim of this study was to identify a novel autoantibody and to evaluate its pathological effects on clinically relevant photoreceptor injuries. METHODS: Biochemical purification and subsequent peptide fingerprinting were applied to identify autoantigens. The titres of autoantibodies in DMO sera were quantified and their associations with clinical variables were evaluated. Two animal models (i.e. passive transfer of autoantibodies and active immunisation) were characterised with respect to autoimmune mechanisms underlying photoreceptor injuries. RESULTS: After screening serum IgG from individuals with DMO, fumarase, a Krebs cycle enzyme expressed in inner segments, was identified as an autoantigen. Serum levels of anti-fumarase IgG in participants with DMO were higher than those in diabetic participants without DMO (p < 0.001) and were related to photoreceptor damage and visual dysfunction. Passively transferred fumarase IgG from DMO sera in concert with complement impaired the function and structure of rodent photoreceptors. This was consistent with complement activation in the damaged photoreceptors of mice immunised with fumarase. Fumarase was recruited to the cell surface by complement and reacted to this autoantibody. Subsequently, combined administration of anti-fumarase antibody and complement elicited mitochondrial disruption and caspase-3 activation. CONCLUSIONS/INTERPRETATION: This study has identified anti-fumarase antibody as a serum biomarker and demonstrates that the generation of this autoantibody might be a pathological mechanism of autoimmune photoreceptor injuries in DMO.

Baerveldt or Ahmed glaucoma valve implantation with pars plana tube insertion in Japanese eyes with neovascular glaucoma: 1-year outcomes.

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.

Outer Plexiform Layer Elevations as a Marker for Prior Ocular Attacks in Patients With Behcet's Disease.

Purpose: Patients with Behcet's disease frequently have abnormal focal outer plexiform layer (OPL) bumps, which compress the inner nuclear layer. This study investigates the clinical relevance of these OPL elevations in Behcet's disease patients. Methods: Thirty-one consecutive patients (59 eyes) with Behcet's disease in remission and with available optical coherence tomography (OCT) images were included. The number of OPL bumps was counted using spectral-domain OCT images. The relationships between the number of bumps and visual acuity (VA), retinal thickness, choroidal thickness, disease duration, number of prior ocular attacks, and photoreceptor layer status (including external limiting membrane [ELM] and ellipsoid zone [EZ] continuity) were examined. Results: Eyes with more severe EZ or ELM disruptions had lower VA, more ocular attacks, and thinner retinas. Additionally, EZ line and ELM line status were significantly correlated with the number of OPL elevations. Eyes with OPL elevations had poorer VA, longer disease duration, more ocular attacks, and thinner retinas than those without OPL elevations. Additionally, the number of OPL elevations was strongly correlated with the number of ocular attacks in eyes with a preserved photoreceptor layer (R = 0.720, P < 0.0001). Conclusions: The number of OPL elevations was associated with the number of prior ocular attacks in eyes with preserved photoreceptor layers. Therefore, OPL elevations may be a marker of prior posterior ocular attacks, which is important when determining how best to manage Behcet's uveitis.

Comparative outcomes of trabeculotomy ab externo versus trabecular ablation ab interno for open angle glaucoma.

PURPOSE: To compare clinical outcomes between trabeculotomy ab externo (TLO) and trabecular ablation ab interno using a Trabectome (TAT) for open angle glaucoma (OAG). STUDY DESIGN: Prospective and retrospective cohort study. METHODS: We prospectively recruited 68 patients who underwent TAT between May 2013 and July 2015, and retrospectively recruited 59 patients who underwent TLO between April 2010 and May 2013. We included OAG patients who could be followed up for more than 12 months after surgery. Surgical outcomes were compared between groups. Kaplan-Meier analyses and Cox proportional hazards' models were used for four sets of criteria using postoperative intraocular pressures (IOP) ≤ 18 or ≤ 16 mmHg, and/or showing ≥ 20% reduction from baseline. RESULTS: Mean preoperative IOPs were 22.6 ± 7.4 mmHg in the TAT group and 24.3 ± 6.6 mmHg in the TLO group. Mean postoperative IOPs in the TAT group were 15.8 ± 3.6 mmHg at 12-months, and 15.7 ± 5.5 mmHg at 36-months, and 16.0 ± 3.4 mmHg at 12 months and 15.2 ± 3.8 mmHg at 36 months in the TLO group. Postoperatively, success rates at 36-months were significantly higher in the TLO group in some criteria; IOP reductions at 1- and 2- years were significantly higher in the TLO group; these differences were not significant after adjustment with other potential prognostic factors. The number of glaucoma medications were significantly higher in the TAT group, at 2-years (P < 0.001) but not at 3-years (P = 0.22). CONCLUSION: Surgical successes following TLO and TAT are not significantly different 3 years postoperatively after adjustment of potential prognostic factors.

Retinal Blood Flow Velocity Change in Parafoveal Capillary after Topical Tafluprost Treatment in Eyes with Primary Open-angle Glaucoma.

Although ocular circulation at the retina and optic disc is known to be associated with the pathology of glaucoma, direct measurement of blood flow velocity has been difficult to obtain. This prospective observational study enrolled 11 consecutive patients with treatment-naïve primary open-angle glaucoma (POAG) and 11 healthy subjects, and the effects of topical tafluprost treatment on ocular circulation were examined at baseline and at 1, 4, and 12 weeks after initiating treatment with topical tafluprost on POAG patients using multiple modalities, which include adaptive optics scanning laser ophthalmoscopy (AOSLO). Baseline mean intraocular pressure (IOP) was significantly higher and mean parafoveal blood flow velocity (pBFV) was significantly lower in POAG eyes than in healthy eyes. Mean IOP was significantly decreased (1 week, -19.1%; 4 weeks, -17.7%; and 12 weeks, -23.5%; all P < 0.001) and mean pBFV was significantly increased from the baseline at all follow-up periods after initiating treatment (1 week, 14.9%, P = 0.007; 4 weeks, 21.3%, P < 0.001; and 12 weeks, 14.3%, P = 0.002). These results reveal that tafluprost may not only lower IOP but may also improve retinal circulation in POAG eyes and AOSLO may be useful to evaluate retinal circulatory change after treatment.

Optical Coherence Tomography Angiography to Estimate Retinal Blood Flow in Eyes with Retinitis Pigmentosa.

Ophthalmologists sometimes face difficulties in identifying the origin of visual acuity (VA) loss in a retinitis pigmentosa (RP) patient, particularly before cataract surgery: cataract or the retinal disease state. Therefore, it is important to identify the significant factors correlating with VA. Nowadays, retinal blood flow in superficial and deep layers can be estimated non-invasively using optical coherence tomography angiography (OCTA). We estimated blood flow per retinal layer by using OCTA; investigated the correlation between VA and other parameters including blood flow and retinal thickness; and identified the most associated factor with VA in patients with RP. OCTA images in 68 of consecutive 110 Japanese RP patients were analysable (analysable RP group). Thirty-two age- and axial length-matched healthy eyes (control group) were studied. In the analysable RP group, the parafoveal flow density in superficial and deep layers was 47.0 ± 4.9% and 52.4 ± 5.5%, respectively, which was significantly lower than that in controls. Using multivariate analysis, we found that the parafoveal flow density in the deep layer and superficial foveal avascular area were the factors associated with VA. Non-invasive estimation of retinal blood flow per retinal layer using OCTA is useful for predicting VA in RP patients.

Screening for SLC7A14 gene mutations in patients with autosomal recessive or sporadic retinitis pigmentosa.

PURPOSE: In this study, we aimed to detect mutations in the SLC7A14 cationic transporter gene, which has recently been reported as a causative gene for retinitis pigmentosa (RP), in Japanese patients with autosomal recessive (AR) or sporadic RP. MATERIALS AND METHODS: We included 146 unrelated Japanese patients with AR or sporadic RP who lacked mutations in genes known to be associated with RP despite next-generation sequencing-based screening. We sequenced the seven SLC7A14 coding exons along with their flanking intronic DNA using the Sanger method. The detected polymorphisms were assessed for their pathogenicity with in silico prediction tools. For those who had heterozygous, nonsynonymous variants, we performed multiplex ligation-dependent probe amplification (MLPA) to search for additional deletion/duplication. RESULTS: We detected four distinct SLC7A14 polymorphisms excluding synonymous polymorphisms. Two of these polymorphisms were assessed as detrimental by in silico prediction tools. However, all of the mutations were heterozygous. Neither homozygous polymorphisms nor compound heterozygous polymorphisms, which are considered detrimental variants, were detected. Neither deletion nor duplication was found with MLPA in patients with heterozygous variants. CONCLUSIONS: The four SLC7A14 mutations detected herein were unlikely to be pathogenic in this Japanese cohort. The frequency and pathogenicity of SLC7A14 mutations may vary depending on ethnicity, and these mutations may be rare in Japanese patients.

Morphological features in anterior scleral inflammation using swept-source optical coherence tomography with multiple B-scan averaging.

BACKGROUND/AIMS: To determine the morphological features of anterior scleral inflammation using swept-source optical coherence tomography. METHODS: In this retrospective observational study, we examined 17 eyes of 14 patients with diffuse anterior scleral inflammation and 13 eyes of 13 young unaffected patients. We compared cross-sectional images of the conjunctiva, episclera and sclera obtained using swept-source optical coherence tomography equipped with a multiple B-scan averaging process between normal eyes and those with episcleritis and scleritis. RESULTS: Optical coherence tomography showed that the conjunctival stroma/episclera layer was notably swollen in diseased eyes. The eyes with diffuse anterior scleral inflammation had a significantly thicker conjunctival stroma/episclera than normal eyes (403.0 µm vs 288.0 µm, p=0.002). There was no significant difference in scleral stroma thickness between eyes with anterior scleral inflammation and normal eyes (464.7 µm vs 434.2 µm, p=0.11). We separately analysed 11 eyes with diffuse scleritis and 6 eyes with diffuse episcleritis. While the conjunctival epithelium and conjunctival stroma/episclera were thicker in eyes with diffuse scleritis than in those with diffuse episcleritis (78.9 µm vs 50.4 µm, p=0.003 and 445.5 µm vs 308.8 µm, p=0.033, respectively), the scleral stroma thickness in eyes with diffuse scleritis was comparable with normal eyes (465.5 µm vs 434.2 µm, p=0.43). CONCLUSIONS: The swelling of diffuse scleritis occurred within the episclera rather than in the scleral stroma. Since optical coherence tomography visualises the morphology of the episclera and sclera, it can be useful for evaluating inflammation activity and therapeutic effects in diffuse scleritis.

CHOROIDAL AND RETINAL ATROPHY OF BIETTI CRYSTALLINE DYSTROPHY PATIENTS WITH CYP4V2 MUTATIONS COMPARED TO RETINITIS PIGMENTOSA PATIENTS WITH EYS MUTATIONS.

PURPOSE: To compare atrophy of the choroid and retina between Bietti crystalline dystrophy (BCD) patients and EYS-related retinitis pigmentosa (RP) patients with a similar degree of central visual field defects, age, and axial length (AL). METHODS: Nine eyes of nine BCD patients with CYP4V2 mutations (BCD group) were examined. Moreover, we selected 10 eyes of 10 RP patients with EYS mutations matched for age, axial length, and mean deviation (measured with the 10-2 SITA standard program; EYS-RP group), and 10 eyes of 10 normal volunteers matched for age and axial length (control group). Macular thicknesses of the choroid and retina were measured via swept-source optical coherence tomography. RESULTS: The macular choroid was significantly thinner in the BCD group than in the EYS-RP and control groups, although the thickness did not significantly differ between the EYS-RP and control groups. The macular retina was significantly thinner in the BCD and EYS-RP groups than in the control group, although the thickness did not significantly differ between the BCD and EYS-RP groups at most sites. CONCLUSION: Bietti crystalline dystrophy patients with CYP4V2 mutations showed more severe macular choroid atrophy as compared to EYS-related RP patients. These different damage patterns suggest differences in choroidal expression between CYP4V2 and EYS.

Longitudinal change in choroidal thickness after trabeculectomy in primary open-angle glaucoma patients.

PURPOSE: To investigate longitudinal changes in intraocular pressure (IOP), axial length (AL), and choroidal thickness (ChT) in primary open-angle glaucoma (POAG) eyes after trabeculectomy and to evaluate the parameters that might influence those changes. METHODS: In this prospective observational study, we recruited 28 patients with POAG (28 eyes) scheduled for trabeculectomy. The average macular ChTs and foveal retinal thicknesses along 6-mm segments centered on the fovea were examined preoperatively and postoperatively (at 1, 3, and 6 months) using swept-source optical coherence tomography. The IOP, AL, and mean deviation (MD) of standard automated perimetry (SAP) were also analyzed as independent variables. RESULTS: Results from 16 patients were included in the final analysis. A significant increase in ChT with respect to the preoperative value was observed at every postoperative stage (1 month, P < 0.001; 3 months, P < 0.001; 6 months, P = 0.011), whereas the retinal thickness showed no significant change over the study period. The ChT increase and IOP reduction were sustained throughout the 6-month period without further significant changes. Stepwise multivariate analyses showed significant correlations between the percentage decrease in IOP and the percentage increase in ChT at 1 and 6 months postoperatively. The percentage increase in ChT was also significantly correlated with a better MD of the SAP at 1 month (ß = 0.01; P = 0.009). CONCLUSIONS: The ChT increase following trabeculectomy was sustained at 1, 3, and 6 months postoperatively. The percentage increase in ChT was significantly correlated with the percentage change in IOP and (more weakly) with better SAP MD values.

Magnetic scattering in the simultaneous measurement of small-angle neutron scattering and Bragg edge transmission from steel.

Pulsed neutron sources enable the simultaneous measurement of small-angle neutron scattering (SANS) and Bragg edge transmission. This simultaneous measurement is useful for microstructural characterization in steel. Since most steels are ferromagnetic, magnetic scattering contributions should be considered in both SANS and Bragg edge transmission analyses. An expression for the magnetic scattering contribution to Bragg edge transmission analysis has been derived. The analysis using this expression was applied to Cu steel. The ferrite crystallite size estimated from this Bragg edge transmission analysis with the magnetic scattering contribution was larger than that estimated using conventional expressions. This result indicates that magnetic scattering has to be taken into account for quantitative Bragg edge transmission analysis. In the SANS analysis, the ratio of magnetic to nuclear scattering contributions revealed that the precipitates consist of body-centered cubic Cu0.7Fe0.3 and pure Cu, which probably has 9R structure including elastic strain and vacancies. These results show that effective use of the magnetic scattering contribution allows detailed analyses of steel microstructure.

Influence of high myopia on outcomes of trabeculectomy with mitomycin C in patients with primary open-angle glaucoma.

PURPOSE: To determine the clinical characteristics and surgical outcomes of highly myopic (HM) eyes with an axial length (AL) of ≥26.0 mm that underwent trabeculectomy with mitomycin C (MMC). METHODS: This was a retrospective study of 63 eyes of 54 patients with primary open-angle glaucoma that underwent trabeculectomy with MMC. The characteristics and surgical outcomes of 19 HM eyes were compared with those of 44 non-HM eyes. Surgical success was defined as an high intraocular pressure (IOP) of ≤21 mmHg (criterion A), ≤18 mmHg (criterion B), or ≤15 mmHg (criterion C), with a lower IOP cutoff of 6 mmHg and a >20 % reduction regardless of the use of antiglaucoma medication. Cox regression analyses were performed to evaluate the effect of each pretreatment and surgical factor on the success rate. RESULTS: Patients with HM eyes were significantly younger than those with non-HM eyes (mean age 64.1 ± 9.9 vs. 69.1 ± 9.5 years; P < 0.05). The 3-year qualified success rates for HM eyes and non-HM eyes did not differ significantly for the three criteria. Younger age [hazard ratio (HR) for a 1-year increase 0.93, P < 0.005], preoperative pseudophakia (HR 3.88, P < 0.005), and shorter AL (HR for a 1-mm increase 0.72, P < 0.05) were found to be significant risk factors for trabeculectomy failure based on an IOP of ≤15 mmHg (criterion C). Age and pseudophakia also had significant effects on trabeculectomy failure based on criteria A and B, and the AL had a significant influence based on criterion A. CONCLUSIONS: In our patient cohort a longer AL was not a risk factor for trabeculectomy failure, but it may be a success factor for trabeculectomy with MMC.

Clustering of Combined 24-2 and 10-2 Visual Field Grids and Their Relationship With Circumpapillary Retinal Nerve Fiber Layer Thickness.

PURPOSE: The purpose of this study was to cluster the test points of the combined 24-2 and 10-2 visual fields (VFs) and circumpapillary retinal nerve fiber layer thickness (cpRNFLT) sectors using explanatory factor analyses (EFAs). The correlations between the VF clusters and cpRNFLT clusters were determined, and a new function-structure relationship map was determined. METHODS: Two hundred fifty-four eyes of 166 subjects (13 normal eyes and 241 eyes with glaucoma) were studied retrospectively. All eyes had an axial length <27 mm and had undergone 24-2 and 10-2 VF tests using the Swedish Interactive Threshold Algorithm (SITA-standard) and cpRNFLT examinations by spectral domain optical coherence tomography within a 3-month period. Explanatory factor analysis was performed to group the 116 test points of the combined 24-2/10-2 VF test grids into a smaller number of VF clusters. Another EFA was performed to cluster the 24 cpRNFLT sectors. The correlations between the VF clusters and the cpRNFLT clusters were evaluated by Pearson's correlation analysis. RESULTS: The combined 24-2/10-2 VF test grids were grouped into seven VF clusters by EFA. Another EFA grouped the cpRNFLT sectors into 11 clusters. The correlation coefficients between the corresponding VF and cpRNFLT clusters ranged from 0.304 (P < 1 × 10-6) to 0.794 (P < 2.2 × 10-16). CONCLUSIONS: Explanatory factor analysis revealed detailed patterns of glaucomatous VF defects and glaucomatous cpRNFL thinning. Their significant correlations indicate that they have common latent factors that might be derived from a developing pattern of glaucomatous optic neuropathy. These findings support the function-structure relationship theory in glaucoma.

Microvascular Density in Glaucomatous Eyes With Hemifield Visual Field Defects: An Optical Coherence Tomography Angiography Study.

PURPOSE: To investigate microcirculation of peripapillary retina and optic disc in eyes with primary open-angle glaucoma (POAG) and hemifield visual field (VF) defects. DESIGN: Prospective observational case series with normal comparison group. METHODS: Sixty eyes with POAG (41 with superior and 19 with inferior hemifield VF defects) and 21 normal eyes were included in this study. Optical coherence tomography (OCT) angiography was used to acquire 3 × 3-mm optic disc cubes, and circumpapillary retinal nerve fiber layer thickness was also measured using OCT. Vessel densities in the peripapillary superficial retina and whole-signal-mode optic disc were individually analyzed based on the sectorial division. RESULTS: The peripapillary vessel densities were significantly reduced at the corresponding location of the VF defects in both non-highly myopic (P < .001, P = .006) and highly myopic glaucomatous eyes (P < .001, P = .005) compared with the normal eyes. Vessel densities of the optic discs were significantly reduced at locations corresponding to the VF defects in eyes without high myopia but with inferior hemifield VF defects (P = .006), but not in the other eyes. The vessel densities in the peripapillary retina were significantly associated with visual field total deviation values at their corresponding sides. The choroidal microvascular reduction in the peripapillary area extended to the α-peripapillary atrophy (PPA) as well as ß-PPA zones. CONCLUSIONS: Microvascular reduction was associated with VF defects in a region-specific manner: significantly and partially in the peripapillary retina and optic disc, respectively.

Next-generation sequencing-based comprehensive molecular analysis of 43 Japanese patients with cone and cone-rod dystrophies.

PURPOSE: To investigate the efficacy of targeted exome sequencing for mutational screening of Japanese patients with cone dystrophy (CD) or cone-rod dystrophy (CRD). METHODS: DNA samples from 43 Japanese patients with CD or CRD were sequenced using an exome-sequencing panel targeting all 193 known inherited eye disease genes and next-generation sequencing methodologies. Subsequently, candidate variants were screened using systematic data analyses, and their potential pathogenicity was assessed using distinct filtering approaches, which included the frequency of the variants in normal populations, in silico prediction tools, and cosegregation. RESULTS: Causative mutations were detected in 12 patients with CD or CRD (27.9%). In total, 14 distinct mutations were identified in the genes ABCA4, CDHR1, CRB1, CRX, GUCY2D, KCNV2, PROM1, PRPH2, and RDH5, including four novel mutations, c.3050+1G>A in ABCA4, c.386A>G in CDHR1, c.652+1_652+4del in CRB1, and c.454G>A in KCNV2. Moreover, a putative pathogenic mutation was identified in RGS9BP, a gene recognized as the source of bradyopsia. CONCLUSIONS: Targeted exome sequencing effectively identified causative mutations in Japanese patients with CD or CRD. The results confirmed the heterogeneity of the genes responsible for CD and CRD in Japanese populations, as well as the efficacy of targeted exome sequencing-based screening of patients with inherited retinal degeneration.

Efficacy of Column Scatter Plots for Presenting Retinitis Pigmentosa Phenotypes in a Japanese Cohort.

PURPOSE: We evaluated the efficacy of column scatter plots to describe genotype-phenotype correlations in a Japanese cohort with retinitis pigmentosa (RP). METHODS: Clinical records of 121 patients with RP with identified causative mutations were reviewed. Visual acuity, central and peripheral visual fields, electroretinography (ERG), lens status, and measurements of optical coherence tomography were evaluated according to causative genes using column scatter plots. Values for three common genes (EYS, USH2A, and RHO) were compared statistically. RESULTS: All patients with PDE6B, PRPH2, and RPGR mutations, those 55 years old or younger with RP1L1 and USH2A mutations, and those 45 years old or younger with EYS and RHO mutations retained visual acuity of at least 0.1. All patients with RPGR mutations showed at least -20 dB mean deviation. Goldmann perimeter measures of 4/6 patients with RHO mutations showed remaining peripheral visual fields. Dark-adapted 0.01 and 3.0 ERGs were extinguished for most genes. Half of the patients with RHO RP maintained cone responses in light-adapted 3.0 and 3.0 flicker ERG. All patients with PRPH2, those 55 years old or younger with USH2A and RP1L1, and those 45 years old or younger with PDE6B and EYS mutations maintained subfoveal ellipsoid zones. No differences were identified between EYS and USH2A or RHO and USH2A. CONCLUSIONS: Column scatter plots enabled comparisons of the associated severities and illustration of the ophthalmological measurements for every RP causative gene. TRANSLATIONAL RELEVANCE: Analysis of mutations in specific genes may be helpful for determining visual prognoses in the clinical setting.