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.

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.

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.

ASYMMETRIC CONE DISTRIBUTION AND ITS CLINICAL APPEARANCE IN RETINITIS PIGMENTOSA.

PURPOSE: To report the characteristic changes of fundus autofluorescence in the nasal retina of patients with retinitis pigmentosa. METHODS: We investigated 113 eyes of 113 patients with retinitis pigmentosa. We obtained wide-field fundus autofluorescence images and evaluated the status of the retina nasal to the optic disk. The patients were divided into the following three groups: those without nasal sparing (advanced), those with nasal sparing, and those with larger intact areas in addition to the nasal retina (early). Visual acuity, visual field area, age, and the duration of the symptom were compared among the groups. RESULTS: Twenty eyes (17.7%), 51 (45.1%), and 42 (37.1%) were classified as early, nasal sparing, and advanced, respectively. The nasal retina was essentially preserved in the early group. The clinical characteristics' analysis suggested that the disease progression appears from that represented by early groups, then nasal sparing groups, and finally advanced groups. The authors found that the nasal sparing pattern bears a close resemblance to the previously reported cone photoreceptor distribution. CONCLUSION: Wide-field fundus autofluorescence imaging detected nasal sparing in retinitis pigmentosa. The characteristic fundus autofluorescence pattern should reflect cone photoreceptor distribution in the human retina. This finding may be an example of the clinical appearance of asymmetric photoreceptor distribution.

Wide-Field Fundus Autofluorescence for Retinitis Pigmentosa and Cone/Cone-Rod Dystrophy.

Retinitis pigmentosa and cone/cone-rod dystrophy are inherited retinal diseases characterized by the progressive loss of rod and/or cone photoreceptors. To evaluate the status of rod/cone photoreceptors and visual function, visual acuity and visual field tests, electroretinogram, and optical coherence tomography are typically used. In addition to these examinations, fundus autofluorescence (FAF) has recently garnered attention. FAF visualizes the intrinsic fluorescent material in the retina, which is mainly lipofuscin contained within the retinal pigment epithelium. While conventional devices offer limited viewing angles in FAF, the recently developed Optos machine enables recording of wide-field FAF. With wide-field analysis, an association between abnormal FAF areas and visual function was demonstrated in retinitis pigmentosa and cone-rod dystrophy. In addition, the presence of "patchy" hypoautofluorescent areas was found to be correlated with symptom duration. Although physicians should be cautious when interpreting wide-field FAF results because the peripheral parts of the image are magnified significantly, this examination method provides previously unavailable information.

Identification of a Dual Inhibitor of SRPK1 and CK2 That Attenuates Pathological Angiogenesis of Macular Degeneration in Mice.

Excessive angiogenesis contributes to numerous diseases, including cancer and blinding retinopathy. Antibodies against vascular endothelial growth factor (VEGF) have been approved and are widely used in clinical treatment. Our previous studies using SRPIN340, a small molecule inhibitor of SRPK1 (serine-arginine protein kinase 1), demonstrated that SRPK1 is a potential target for the development of antiangiogenic drugs. In this study, we solved the structure of SRPK1 bound to SRPIN340 by X-ray crystallography. Using pharmacophore docking models followed by in vitro kinase assays, we screened a large-scale chemical library, and thus identified a new inhibitor of SRPK1. This inhibitor, SRPIN803, prevented VEGF production more effectively than SRPIN340 owing to the dual inhibition of SRPK1 and CK2 (casein kinase 2). In a mouse model of age-related macular degeneration, topical administration of eye ointment containing SRPIN803 significantly inhibited choroidal neovascularization, suggesting a clinical potential of SRPIN803 as a topical ointment for ocular neovascularization. Thus SRPIN803 merits further investigation as a novel inhibitor of VEGF.

MMP20 and ARMS2/HTRA1 Are Associated with Neovascular Lesion Size in Age-Related Macular Degeneration.

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of severe visual impairment. Despite treatment, a central scotoma often remains. The size of the scotoma depends on the lesion size of the choroidal neovascular membrane and significantly affects the patient's quality of life, and the lesion size of neovascularization also affects response to treatments. The aim of this study was to identify genes associated with the neovascular lesion size in neovascular AMD. DESIGN: A genome-wide association study (GWAS). PARTICIPANTS: We included 1146 Japanese patients with neovascular AMD. METHODS: We performed a 2-stage GWAS for the lesion size of AMD as a quantitative trait among 1146 (first stage: 727, second stage: 419) Japanese patients with neovascular AMD. Lesion size was determined by the greatest linear dimension measured with fluorescein angiography examination before treatment. We examined the association between the genotypic distribution of each single nucleotide polymorphism (SNP) and the trait using an additive model adjusted for age and sex. To evaluate the associations between AMD development and SNPs associated with lesion size, we also performed a case-control study by using the genotype data from these 1146 Japanese patients as case subjects and the fixed dataset from the Nagahama Study as control subjects. MAIN OUTCOME MEASURES: Genes associated with the lesion size in neovascular AMD. RESULTS: In the discovery stage, rs10895322 in MMP20 showed a genome-wide significant P value of 6.95×10(-8), and rs2284665 in ARMS2/HTRA1 showed a P value of 1.55×10(-7). The associations of these 2 SNPs were successfully replicated in the replication stage, and a meta-analysis of both stages showed genome-wide significant P values (2.80×10(-9) and 4.41×10(-9), respectively). In a case-control study using 3248 Japanese subjects as controls, we could not find contribution of MMP20 rs10895322 for AMD development. Although MMP20 has been thought to be expressed only in dental tissues, we confirmed MMP20 expression in the human retina and retinal pigment epithelium/choroid with polymerase chain reaction. CONCLUSIONS: The growth of choroidal neovascularization in AMD would be affected by 2 genes: MMP20, a newly confirmed gene expressed in the retina, and ARMS2/HTRA1, a well-known susceptibility gene for AMD.

Sensitivity and specificity for detecting early glaucoma in eyes with high myopia from normative database of macular ganglion cell complex thickness obtained from normal non-myopic or highly myopic Asian eyes.

PURPOSE: We aimed to determine the sensitivity and specificity of the normative database of non-myopic and highly myopic eyes of the macular ganglion cell complex (mGCC) thickness embedded in the NIDEK RS-3000 spectral-domain optical coherence tomography (SD-OCT) for detecting early glaucoma in highly myopic eyes. METHODS: Forty-seven highly myopic eyes (axial length ≥26.0 mm) of 47 subjects were studied. The SD-OCT images were used to determine the mGCC thickness within a 9-mm diameter circle centered on the fovea. The sensitivity and specificity of the non-myopic database were compared to that of the highly myopic database for distinguishing the early glaucomatous eyes from the non-glaucomatous eyes. The mGCC scans were classified as abnormal if at least one of the eight sectors of the significance map was < 1 % of the normative thickness. RESULTS: Twenty-one eyes were diagnosed to be non-glaucomatous and 26 eyes to have early glaucoma. . The average mGCC thickness was significantly thinner (80.9 ± 8.5 µm) in the early glaucoma group than in the non-glaucomatous group (91.2 ± 7.5 µm; p <1 × 10(-4)). The sensitivity was 96.2 % and specificity was 47.6 % when the non-myopic database was used, and the sensitivity was 92.3 % and the specificity was 90.5 % when the highly myopic database was used. The difference in the specificity was significant (p < 0.01). CONCLUSIONS: The significantly higher specificity of the myopic normative database for detecting early glaucoma in highly myopic eyes will lead to fewer false positive diagnoses. The database obtained from highly myopic eyes should be used when evaluating the mGCC thickness of highly myopic eyes.

Severe Circulatory Disturbance in Optic Disc, Retina, and Choroid Following Sub-Tenon Triamcinolone Acetonide Injection for Posterior Scleritis.

PURPOSE: To report a rare case of optic disc and chorioretinal vascular occlusions in the right eye following sub-Tenon injection of triamcinolone acetonide (STTA) in an older male patient with scleritis and to discuss the associated risk factors and potential alternative therapies. METHODS: The medical history and clinical examination, including fundoscopy, fluorescein angiography (FA), and indocyanine green angiography (ICGA), were conducted to diagnose and evaluate the extent of vascular occlusion after STTA. An extensive literature review was undertaken to ascertain the associated risks and consider other treatment options for scleritis. RESULTS: Severe circulatory disturbances in the optic disc and chorioretinal regions of the right eye developed after STTA for exacerbated scleritis, as confirmed by FA and ICGA, resulting in a significant decrease in visual acuity. A complex medical history encompassing ophthalmic and systemic health issues may have contributed to this negative outcome. A literature review pointed out the potential complications of STTA and highlighted alternative approaches to scleritis management. CONCLUSIONS: Cautious application of STTA in treating scleritis is crucial, especially in patients with pre-existing vascular or ocular conditions. Thus, a multidisciplinary approach and a careful assessment of various treatment options are vital to minimize the risk of severe complications and improve patient outcomes.

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.

Frequency-doubling technology and retinal measurements with spectral-domain optical coherence tomography in preperimetric glaucoma.

BACKGROUND: To determine the relationship between visual fields and retinal structures measured with spectral-domain optical coherence tomography in preperimetric glaucoma (PPG). METHODS: Twenty-six eyes of 26 patients with PPG and 20 healthy eyes of 20 volunteers were included. All patients underwent Heidelberg retina tomography-2 (HRT2), standard automated perimetry (SAP), frequency-doubling technology (FDT) perimetry, and RTVue-100. SAP and FDT indices, HRT parameters, and circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (mGCC) thicknesses were correlated using Pearson's test. Areas under the receiver operating characteristic curves (AUROCs) and sensitivity/specificity based on each parameter's definition of abnormalities were compared between parameters. RESULTS: Significant differences were found in FDT-MD, FDT-PSD, SAP-PSD, cpRNFL, and mGCC parameters (p < 0.001-0.015), but not in SAP-MD or HRT parameters, between PPG and control groups. Significant correlations were not found between visual field indices and structural parameters, except between FDT-MD and HRT rim area (r = 0.450, p = 0.021) and between FDT-PSD and temporal cpRNFL thickness (r = 0.402, p = 0.021). AUROCs for cpRNFL (p = 0.0047-0.033) and mGCC (p = 0.0082-0.049) parameters were significantly better than those of HRT parameters, whereas significant differences were not found between FDT indices and cpRNFL or mGCC parameters or between cpRNFL and mGCC parameters. Adding average cpRNFL or mGCC thickness to FDT-MD significantly increased sensitivity compared to single parameters (p = 0.016-0.031). CONCLUSIONS: Structural and functional parameters were poorly correlated but complementary for glaucoma detection in PPG. Combining these parameters may improve PPG diagnosis.

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).

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.

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.

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.

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.

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.

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.