Rotational stability and clinical outcomes of a new one piece toric intraocular lens with anchor-wing haptics.

BACKGROUND: To evaluate the safety and efficacy of a new toric intraocular lens (IOL) with anchor-wing haptics. METHODS: The new toric IOL with anchor-wing haptics (NS60YT, NIDEK Co., Ltd.) was implanted in eligible patients with age-related cataracts with preoperative corneal astigmatism of 1.0 D or greater at a university hospital and two private hospitals in Japan. The following IOL cylinder powers were evaluated: 1.50 D (NS60YT3), 2.25 D (NS60YT4), 3.00 D (NS60YT5) and 4.50 D (NS60YT7). All patients were assessed out to 12 months postoperatively. The primary endpoint was visual acuity (VA) with spherical addition at 6 months postoperatively, and the primary analysis calculated the proportion of eyes with VA with spherical addition of 0.1 logMAR or better. The magnitude of rotation was compared to the intended axis of IOL implantation at each postoperative examination. Adverse events were evaluated for the safety analysis. RESULTS: This study enrolled 64 eyes of 53 patients. At 6 months postoperatively, for all IOL powers, VA with spherical addition of 0.1 logMAR or better was achieved in 90% [95% confidence interval (CI): 80-96] of eyes. The mean IOL rotation was 5.3 ± 4.3° at 12 months postoperatively. The mean magnitude of rotation ranged from 1.9° to 2.5° between each postoperative examination from 1 day to 12 months. There were no vision-threatening intraoperative or postoperative complications for the duration of the study. CONCLUSIONS: The NS60YT IOL remained stable after implantation and was efficacious for treating 1.00 D or greater astigmatism in patients with senile cataracts. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov ( NCT03242486 ) on August 8, 2017 - Retrospectively registered.

Early postoperative evaluation of retinal function by electroretinography after vitreous surgery for idiopathic epimacular membrane.

PURPOSE: In this study, we used the PuREC to carry out electroretinography (ERG) measurements using skin electrodes to assess changes before and after microincision vitreous surgery (MIVS) for epiretinal membrane (ERM) and evaluate the stress on retinal function soon after MIVS. METHODS: The study subjects were 18 eyes of 18 patients who underwent MIVS for ERM simultaneously with cataract surgery. ERG measurements were performed using a skin electrode on the day before vitreous surgery, on the day after surgery, and 1 week later. The amplitude and implicit time of each waveform were measured, and the changes between preoperative results and those 1 day and 1 week postoperatively were investigated. RESULTS: Preoperatively, the dark-adapted (DA) 0.01 ERG, the DA 3.0 ERG a-wave amplitude, and the light-adapted (LA) 3.0 ERG b-wave amplitude were significantly smaller in affected eyes compared with their fellow eyes (P < 0.05, Wilcoxon's signed-rank test). The day after surgery, all-wave amplitude showed no significant difference compared to preoperatively (repeated-measures analysis of variance (ANOVA) post hoc test). One week after surgery, the LA 3.0 ERG for b-waves and flicker ERG amplitude had improved from the value on the day after surgery (P < 0.05, ANOVA post hoc test). CONCLUSIONS: Cone ERG components have improved within 1 week after surgery by MIVS for ERM.

Effects of photodynamic therapy plus intravitreal aflibercept with subtenon triamcinolone injections for aflibercept-resistant polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the outcome of triple therapy of photodynamic therapy combined with injections of intravitreal aflibercept (IVA) and subtenon triamcinolone acetonide for polypoidal choroidal vasculopathy (PCV) resistant to IVA. METHODS: A retrospective chart review at a single institution was conducted to identify patients with PCV resistant to treatment with IVA who were switched to treatment with triple therapy. In total, 13 eyes from 13 patients were included in the study. Demographic data, visual acuities, central retinal thickness (CRT) and height of pigment epithelial detachment (PED) on optical coherence tomography (OCT), complications, and number of injections were reviewed. RESULTS: The patients had a mean age of 68 years (range 53-83). The number of prior injections with IVA ranged from 5 to 10. At 12 months follow-up after triple therapy, there was a significant improvement in visual acuity (P = 0.0039), a significant decrease in CRT (P = 0.003), and a significant reduction of the height of PED (P = 0.015). Only one patient had retinal pigment epithelium tear. CONCLUSIONS: Triple therapy improved visual and anatomical outcomes in patients with PCV with recurrent or resistant retinal fluid and PED after multiple injections with IVA.

Serum levels of lipid metabolites in age-related macular degeneration.

Age-related macular degeneration (AMD) is a neurodegenerative disease that causes adult-onset blindness. There are 2 forms of this progressive disease: wet and dry. Currently there is no cure for AMD, but several treatment options have started to emerge making early detection critical for therapeutic success. Analysis of the eyes of Abca4(-/-)Rdh8(-/-) mice that display light-induced retinal degeneration indicates that 11-cis-retinal and docosahexaenoic acid (DHA) levels were significantly decreased as compared with the eyes of control dark-adapted C57BL/6J mice. In addition, exposure to intense light correlated with higher levels of prostaglandin G2 in the eyes of Abca4(-/-)Rdh8(-/-) mice. Intense light exposure also lowered DHA levels in the eyes of wild-type C57BL/6J mice without discernible retinal degeneration. Analysis of human serum from patients with AMD recapitulated these dysregulated DHA levels and revealed dysregulation of arachidonic acid (AA) levels as well (∼32% increase in patients with AMD compared with average levels in healthy individuals). From these observations, we then built a statistical model that included levels of DHA and AA from human serum. This model had a 74% probability of correctly identifying patients with AMD from controls. Addition of a genetic analysis for one of the most prevalent amino acid substitutions in the age-related maculopathy susceptibility 2 gene linked to AMD, Ala(69)→Ser, did not improve the statistical model. Thus, we have characterized a reliable method with the potential to detect AMD without a genetic component, paving the way for a larger-scale clinical evaluation. Our studies on mouse models along with the analysis of human serum suggest that our small molecule-based model may serve as an effective tool to estimate the risk of developing AMD.

Atypical presentation of primary intraocular lymphoma.

BACKGROUND: In 2014, Pang et al. reported three cases with vitelliform submaculopathy as a preceding lesion of primary intraocular lymphoma (PIOL). Here, we report a case with an atypical presentation of PIOL who initially presented with vitelliform submaculopathy, vitreous haze and preripheral retinal focus. CASE PRESENTATION: A 73-year-old female initially visited another hospital with a chief complaint of acute reduced vision in the right eye. Funduscopic examination of the right eye showed a yellowish retinal lesion at the fovea with vitreous haze and retinal foci scattered in the peripheral region. Spectral-domain optic coherence tomography (SD-OCT) revealed a hyperreflective subretinal debris above the retinal pigment epithelium (RPE) at the fovea, suggesting vitelliform submaculopathy. Vitrectomy was performed to improve visualization of the retinal lesions and for examination of PIOL. Vitreous cytology was class III and cytokine analysis of vitreous fluid showed increased IL-10 and an IL-10/IL-6 ratio >1, suggesting PIOL. Thereafter, there was a sub-RPE infiltration of presumed lymphoma in the nasal retina, and PCR analysis of anterior chamber fluid indicated IgH gene rearrangement, leading to diagnosis of PIOL. Three months later, there was complete disappearance of the vitelliform submacular lesion, with resultant disruption and thinning of the outer retinal layers on SD-OCT images. CONCLUSIONS: Clinicians should be aware of atypical manifestations of PIOL such as vitelliform submaculopathy and peripheral retinal foci with vitreous haze. The patient's unusual funduscopic changes are findings that have not reported in patients with PIOL.

Expression pattern of Ccr2 and Cx3cr1 in inherited retinal degeneration.

BACKGROUND: Though accumulating evidence suggests that microglia, resident macrophages in the retina, and bone marrow-derived macrophages can cause retinal inflammation which accelerates photoreceptor cell death, the details of how these cells are activated during retinal degeneration (RD) remain uncertain. Therefore, it is important to clarify which cells play a dominant role in fueling retinal inflammation. However, distinguishing between microglia and macrophages is difficult using conventional techniques such as cell markers (e.g., Iba-1). Recently, two mouse models for visualizing chemokine receptors were established, Cx3cr1 (GFP/GFP) and Ccr2 (RFP/RFP) mice. As Cx3cr1 is expressed in microglia and Ccr2 is reportedly expressed in activated macrophages, these mice have the potential to distinguish microglia and macrophages, yielding novel information about the activation of these inflammatory cells and their individual roles in retinal inflammation. METHODS: In this study, c-mer proto-oncogene tyrosine kinase (Mertk) (-/-) mice, which show photoreceptor cell death due to defective retinal pigment epithelium phagocytosis, were employed as an animal model of RD. Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice were established by breeding Mertk (-/-) , Cx3cr1 (GFP/GFP) , and Ccr2 (RFP/RFP) mice. The retinal morphology and pattern of inflammatory cell activation and invasion of Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice were evaluated using retina and retinal pigment epithelium (RPE) flat mounts, retinal sections, and flow cytometry. RESULTS: Four-week-old Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice showed Cx3cr1-GFP-positive microglia in the inner retina. Cx3cr1-GFP and Ccr2-RFP dual positive activated microglia were observed in the outer retina and subretinal space of 6- and 8-week-old animals. Ccr2-RFP single positive bone marrow-derived macrophages were observed to migrate into the retina of Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice. These invading cells were still observed in the subretinal space in 18-week-old animals. CONCLUSIONS: Cx3cr1-GFP-positive microglia and Ccr2-RFP-positive macrophages were distinguishable in the retinas of Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice. In addition, Ccr2 expression in Cx3cr1 positive microglia is a feature of microglial activation in RD. Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice enabled observation of microglial activation over time during RD and may be useful for developing inflammation-targeted treatment strategies for RD in the future.

Somatic instability of expanded CAG repeats of ATXN7 in Japanese patients with spinocerebellar ataxia type 7.

PURPOSE: Spinocerebellar ataxia type 7 (SCA7) is a disease characterized by progressive ataxia syndrome and retinal degeneration. SCA7 is caused by expansion of CAG repeats in the ataxin 7 gene. The purpose of this study was to describe the clinical and genetic features in a two-generation Japanese family with SCA7. METHODS: The female proband underwent systemic examinations that included neurological and ophthalmic examinations and magnetic resonance imaging (MRI) scans. We interviewed her affected mother about the clinical history at the bedside. Genomic DNA was purified from peripheral blood lymphocytes. The number of CAG repeats in the proband, and her affected mother was determined by a polymerase chain reaction-based assay that used the GeneScan analysis software. RESULTS: Neurological examinations showed limb ataxia, truncal ataxia, explosive speech, and hyperactive deep tendon reflexes. The MRI scans showed atrophy of the cerebellum and fundus of pons and tegmentum. Ophthalmologically, loss of visual acuity, macular degenerations, and central scotomas were observed in both eyes. Full-field electroretinography revealed reduced cone responses with preserved rod responses. The mother had hand-motion vision. Genetic analysis revealed that various expanded CAG repeat lengths (43-57) and the peak number of repeats (47 and 48) were the same in both patients. CONCLUSIONS: The proband exhibited a typical phenotype of SCA7, which includes cone dystrophy and spinocerebellar ataxia. Genetic analysis demonstrated somatic instability of the CAG repeats in the blood lymphocytes and suggested that there was no genetic anticipation through the maternal transmission.

Multimodal imaging of a case of peripheral cone dystrophy.

PURPOSE: To characterize the peripheral cones in the images obtained by spectral-domain optical coherence tomography (OCT), swept source OCT, and adaptive optics fundus camera in a patient with peripheral cone dystrophy. METHODS: A 28-year-old Japanese man underwent detailed ophthalmic evaluations including high-resolution imaging of the fundus of both eyes. RESULTS: The decimal best-corrected visual acuity was 1.2 in both eyes. The results of slit-lamp biomicroscopy and ophthalmoscopy were essentially normal. Fluorescein and indocyanine green angiographies did not show any hyper- or hypofluorescent areas of the retina. Goldmann perimetry showed full peripheral visual fields but relative central scotomas within the central 20°. The results of the Humphrey Visual Field Analyzer showed a limited preservation of the central sensitivity. Color vision tests showed no errors in both eyes. Spectral-domain OCT showed attenuation of both the ellipsoid and interdigitation zones throughout the macular region except the center of the fovea. The scotopic full-field ERGs were normal, but the photopic ERGs were markedly reduced. Regular cone mosaics were not observed especially more than 450 µm radius from the fovea in the adaptive optics retinal images. The parafoveal cone densities were severely decreased in both eyes. CONCLUSIONS: Our findings indicate that the peripheral cone dystrophy diagnosed by full-field ERGs and perimetry is due to a reduction in the density of parafoveal and peripheral cones.

Influence of silicone oil tamponade on self-sealing sclerotomy using 25-gauge transconjunctival sutureless vitrectomy: a retrospective comparative study.

BACKGROUND: Characteristic complications have been reported for transconjunctival sutureless vitrectomy, such as postoperative sclerotomy leakage and postoperative hypotony. Particular attention to sclerotomy closure is required in cases of silicone oil tamponade, because postoperative supplementation of silicone oil implies reoperation, whereas postoperative supplement of gas is comparatively easy. This study investigated sclerotomy closure in cases of silicone oil tamponade using 25-gauge transconjunctival sutureless vitrectomy. METHODS: We enrolled 19 consecutive eyes with silicone oil injection (Group A, self-sealing sclerotomies, n = 10) (Group B, sutured sclerotomies, n = 9) and 10 eyes with silicone oil removal (Group C, self-sealing sclerotomies) using 25-gauge TSV. Postoperative intraocular pressure was compared between Groups A and B, and between Groups A and C using repeated-measures analysis of variance (ANOVA), one-way factorial ANOVA, and the Tukey-Kramer test. RESULTS: No significant differences in age or axial length were seen among groups, but surgical time differed significantly between Group C and the other groups. Mean duration of silicone oil tamponade was 3.2 ± 1.4 months in Group C, and no sclerotomies in Group A or C required suture placement. Postoperative silicone oil leakage to the subconjunctival space was not encountered in Group A. No cases showed postoperative hypotony (defined as intraocular pressure <5 mmHg). Significant differences in intraocular pressure within the same postoperative period were not identified between Groups A and B. Conversely, significant differences in intraocular pressure within the same postoperative period were identified at postoperative days 1 and 2, although not at postoperative week 1 or postoperative month 1 between Groups A and C. CONCLUSIONS: The procedure for sclerotomy closure seems to have little influence on postoperative intraocular pressure in eyes with silicone oil tamponade using 25-gauge transconjunctival sutureless vitrectomy, because silicone oil tamponade may avoid postoperative hypotony by decreasing sclerotomy leakage in the early postoperative period.

Focal choroidal excavation associated with focal retinochoroiditis.

PURPOSE: To describe detailed spectral-domain optical coherence tomography (OCT) findings for two patients with focal choroidal excavation (FCE) associated with focal retinochoroiditis. CASE REPORT: Three eyes from two patients with FCE associated with focal retinochoroiditis were evaluated by funduscopy, fluorescence angiography, indocyanine green angiography, and spectral-domain OCT during follow-up. Both patients with focal retinochoroiditis developed new FCE after oral steroid treatment and two eyes showed regression of the FCE during the follow-up. Both eyes from one patient transformed from the conforming to the nonconforming type and neither of the eyes were stable during the follow-up. Ultimately, all eyes exhibited the conforming-type FCE. CONCLUSIONS: Focal choroidal excavation can be seen as a tomographic phenotype after the treatment of focal retinochoroiditis. Spectral-domain OCT was useful for detecting the development of FCE after the treatment and for observing FCE regression.

Improved Photoreceptor Function in Male Acute Zonal Occult Outer Retinopathy.

PURPOSE: To describe male acute zonal occult outer retinopathy (AZOOR) patients with improvement of photoreceptor structure and visual function. CASE SERIES: Medical records for eight eyes in seven patients (mean age, 36.9 years; range, 22 to 57 years) with AZOOR were reviewed retrospectively. Of the seven patients, four were treated with high-dose methylprednisolone therapy and three were not treated. All patients presented with photopsias and severe vision loss in the affected eyes. Visual acuity ranged from 0.2 to 1.5 on a Snellen decimal scale and Humphrey visual field testing showed blind spot enlargement or ring scotomas. Fundus and angiographic examinations found no specific abnormalities, leading to a diagnosis of AZOOR. Spectral domain optical coherence tomography showed attenuation of the photoreceptor inner segment ellipsoid zone. Multifocal electroretinography demonstrated that there were decreased responses at the site of the spectral domain optical coherence tomography abnormalities and corresponding visual field loss. Three patients had a spontaneous resolution with restoration of photoreceptor structure and visual function, and four patients had a visual improvement with restoration of photoreceptor structure and visual function after steroid pulse therapy. CONCLUSIONS: These results suggest that male AZOOR patients may have a tendency of visual improvement both with and without treatment.

Treatment of experimental autoimmune uveoretinitis with peroxisome proliferator-activated receptor α agonist fenofibrate.

PURPOSE: The peroxisome proliferator-activated receptor α (PPARα) agonist has been approved for treating hypercholesterolemia and lipid abnormalities. Researchers have recently discovered that an anti-inflammatory effect of PPAR agonist may have the potential to treat autoimmune disease. This study aims to investigate the therapeutic effects of fenofibrate on experimental autoimmune uveoretinitis (EAU). METHODS: EAU was induced in Lewis rats using bovine S-antigen (S-Ag) peptide. Fenofibrate was suspended in 3% arabic gum and administered orally at a high dose of 100 mg/kg and at a low dose of 20 mg/kg every day. Fenofibrate treatment was initiated after the clinical onset once daily for 14 days. The rats were examined every other day for clinical signs of EAU. The histological scores and delayed-type hypersensitivity (DTH) were evaluated on day 28 post-immunization. Morphologic and immunohistochemical examinations were performed with light and confocal microscopy, respectively. Lymphocyte proliferation was measured with [3H] thymidine incorporation into antigen-stimulated T cells from inguinal lymph nodes. RESULTS: Clinical and histological scores of EAU were decreased in the fenofibrate-treated groups. The expression of inflammatory cytokines and Müller cell proliferation were inhibited in the fenofibrate-treated groups. DTH was significantly inhibited in the fenofibrate-treated groups, compared with the vehicle-treated groups (controls). Lymphocyte proliferation assay demonstrated decreased proliferation in the presence of 25 mg/ml S-Ag peptide in the fenofibrate-treated groups compared with controls. CONCLUSIONS: The current results indicate that fenofibrate administered orally following clinical onset has therapeutic effect in EAU. Fenofibrate may be useful for treating intraocular inflammation.

Autosomal recessive cone-rod dystrophy associated with compound heterozygous mutations in the EYS gene.

BACKGROUND: EYS mutations have been identified only in patients with autosomal recessive retinitis pigmentosa (arRP). This study was conducted to describe clinical and genetic features of a Japanese patient with autosomal recessive cone-rod dystrophy (arCRD) and EYS mutations. METHODS: We performed complete ophthalmic examinations including full-field electroretinography (ERG). Genetic analysis using whole-exome sequencing and Sanger sequencing was performed to identify the disease-causing mutation in a 31-year-old male patient. RESULTS: At the initial visit, the patient's decimal best-corrected visual acuity (BCVA) was 0.9 and 0.6 in his right and left eyes, respectively. Funduscopy indicated retinal degenerations were predominantly affected within the vascular arcades and preserved retinal vessels in the mid-periphery in both eyes. Visual field testing showed there were relative central scotomas and preserved peripheral visual fields in both eyes. ERG indicated there was a decreased pattern for both the rod and cone responses. At the age of 36 years, his BCVA decreased to 0.2 in both eyes. Optical coherence tomography showed marked retinal thinning of the macular regions in both eyes. Genetic analysis identified compound heterozygous truncating mutations (p.Y2935X and p.S1653KfsX2) in the EYS gene. His unaffected parents were heterozygous for each mutation. CONCLUSIONS: Our results demonstrated that EYS mutations can be the cause of not only arRP but also arCRD. Our findings extend the phenotypic spectrum of patients with EYS mutations.

OAT mutations and clinical features in two Japanese brothers with gyrate atrophy of the choroid and retina.

BACKGROUND: Gyrate atrophy (GA) of the choroid and retina is an extremely rare inherited chorioretinal dystrophy. Ornithine aminotransferase (OAT) gene mutations are identified in patients with GA. The purpose of this study was to report a novel deletion mutation of the OAT gene and describe clinical features of two brothers with GA in a Japanese family. METHODS: We performed ophthalmic examinations, including best-corrected visual acuity, slit-lamp biomicroscopy, dilated funduscopy, fundus autofluorescence imaging, optical coherence tomography, visual field testing, and full-field electroretinography (ERG). Serum ornithine concentrations and OAT activities were analyzed. Mutation screening of the OAT gene was performed using Sanger sequencing. RESULTS: Both brothers had compound heterozygous mutations (p.K169DfsX10 and p.R426X), one of which was novel. Their unaffected parents carried one of the mutations heterozygously. An arginine-restricted diet was started in the younger brother at the age of 2 years, while the diet was not initiated in the older brother until the age of 6 years. After more than 15 years of follow-up, the dietary treatment seemed to slow the progression of the chorioretinal lesions in the younger brother. However, when compared at the same age, the younger brother had more reduced ERG amplitudes and constricted visual fields than his older brother. CONCLUSIONS: We identified a novel frameshift mutation (p.K169DfsX10) in the OAT gene. While an early arginine-restricted dietary treatment suppressed the fundus changes of GA to some degree in the younger brother, the efficacy of suppressing the progression of visual function loss could not be clearly determined.

Occult macular dystrophy with bilateral chronic subfoveal serous retinal detachment associated with a novel RP1L1 mutation (p.S1199P).

PURPOSE: The purpose of this study was to present an atypical case of occult macular dystrophy (OMD) with bilateral chronic subfoveal serous retinal detachment (SRD). METHODS: A 53-year-old man was ophthalmologically evaluated because of decreased visual acuity in both eyes. Genomic DNA was extracted from venous blood samples. Mutational analysis of the retinitis pigmentosa 1-like 1 (RP1L1) gene was performed by Sanger sequencing. RESULTS: Best-corrected visual acuity (BCVA) was 0.1 logMAR in both eyes until the age of 53, after which it gradually declined. Full-field electroretinography (ERG) was unremarkable, while multifocal ERG revealed a reduced central response in both eyes. Optical coherence tomography showed subfoveal SRD in both eyes, and fundus fluorescein angiography yielded unremarkable results. His brother and cousin had similar subjective symptoms. At age 58, his logMAR BCVA was 0.532 (OD) and 0.347 (OS). He was given 23 administrations of intravitreal bevacizumab (IVB; 1.25 mg) in both eyes alternately over a 2-year period and also underwent reduced-fluence photodynamic therapy in both eyes. Two years after the first administration of IVB, a reduction in SRD was obtained, and IVB was therefore discontinued. Three years after the first administration, logMAR BCVA was 0.155 (OD) and 0.523 (OS). Mutational analysis revealed a novel heterozygous missense mutation (p.S1199P). CONCLUSIONS: We describe in detail a case of bilateral chronic subfoveal SRD in an atypical OMD patient carrying a novel heterozygous RP1L1 mutation (p.S1199P). Our results further extend the phenotypic spectrum of RP1L1-associated OMD.

Remodelling of retinal on- and off-bipolar cells following experimental retinal detachment.

BACKGROUND: To study the response of ON and OFF bipolar cells in experimental retinal detachment. METHODS: Domestic cat retinas were detached for 7 days. The retinas were prepared for immunocytochemical staining with antibodies to Go alpha (α), glutamate transporter GLT-1, protein kinase C and rod opsin, which serve as markers for ON bipolar cells, OFF bipolar cells, rod bipolar cells and rod photoreceptors, respectively. Both sections and whole-mounts were labelled with antibodies to Goα and GLT-1. RESULTS: Following 7 days of detachment, ON bipolar cell processes extended into the outer nuclear layer and had neurites extending beyond their target layer into the inner plexiform layer. In contrast, OFF bipolar cell processes were reduced in the outer plexiform layer following detachment. CONCLUSION: ON and OFF bipolar cells undergo significant remodelling of their processes in response to retinal detachment, and the ON and OFF pathways may be differentially affected. The remodelling may be due to morphological changes that have previously been shown to occur in photoreceptor synaptic terminals or as a result of loss of synaptic connections due to photoreceptor cell death.

[Correlation of intraocular pressure variation after visual field examination with 24-hour intraocular pressure variations in primary open-angle glaucoma].

OBJECTIVES: We retrospectively examined intraocular pressure variations after visual field examination in primary open angle glaucoma (POAG), together with its influencing factors and its association with 24-hour intraocular pressure variations. SUBJECTS AND METHODS: Subjects were 94 eyes (52 POAG patients) subjected to measurements of 24-hour intraocular pressure and of changes in intraocular pressure after visual field examination using a Humphrey Visual Field Analyzer. Subjects were classified into three groups according to the magnitude of variation (large, intermediate and small), and 24-hour intraocular pressure variations were compared among the three groups. Factors influencing intraocular pressure variations after visual field examination and those associated with the large variation group were investigated. RESULTS: Average intraocular pressure variation after visual field examination was -0.28 ± 1.90 (range - 6.0(-) + 5.0) mmHg. No significant influencing factors were identified. The intraocular pressure at 3 a.m. was significantly higher in the large variation group than other two groups (p < 0.001). Central corneal thickness was correlated with the large variation group (odds ratio = 1.04; 95% confidence interval, 1.01-1.07 ; p = 0.02). CONCLUSION: No particular tendencies in intraocular pressure variations were found after visual field examination. Increases in intraocular pressure during the night might be associated with large intraocular pressure variations after visual field examination.

Retinal Ganglion Cell Loss in X-linked Adrenoleukodystrophy with an ABCD1 Mutation (Gly266Arg).

The authors here report a single case of a 10-year-old male patient who presented with severe vision loss associated with progressive demyelination. The patient was diagnosed with X-linked childhood cerebral adrenoleukodystrophy (ALD). Genetic analysis demonstrated a missense mutation (Gly266Arg) in exon 1 of the ABCD1 gene. His corrected visual acuity confirmed the absolute lack of light perception in both eyes. Funduscopy revealed severe pallor of the optic disc in both eyes. Spectral-domain optical coherence tomography showed thinning of the retinal ganglion cell and inner plexiform layers (GCL and IPL). Thinning of the GCL and IPL may be due to transneuronal retrograde degeneration of ganglion cells secondary to optic tract demyelination.

Genetic polymorphisms associated with endothelial function in nonarteritic anterior ischemic optic neuropathy.

PURPOSE: To examine the relationship between nonarteritic anterior ischemic optic neuropathy (NAION) and genetic polymorphisms of enzymes influencing endothelial function. METHODS: The subjects were 34 patients with NAION (mean age, 62.4 years old; 59% male) and 102 controls (mean age, 63.8 years old; 66% male). Genetic polymorphisms were investigated in three candidate genes associated with endothelial function: endothelin-1 (ET-1), angiotensin-converting enzyme (ACE), and methylenetetrahydrofolate reductase (MTHFR). The genotype distributions in the patients with NAION were compared with those in the controls. RESULTS: There were no significant differences in the genotype distributions of the ACE I/D and MTHFR C677T polymorphisms between the NAION and control groups (p=0.261 and p=0.354, respectively), whereas the genotype distribution of the G/T (Lys198Asn) polymorphism of the ET-1 gene varied significantly between the groups (p=0.009). After adjusting for covariates, individuals with the TT genotype of the Lys198Asn polymorphism were more likely to develop NAION compared with those with the GG genotype (odds ratio=4.43, 95% confidence interval 1.33-14.73, p=0.015). CONCLUSIONS: We found an increased prevalence of a G/T polymorphism of the ET-1 gene in patients with NAION. Our data suggest that this polymorphism may be an important risk factor in developing NAION in the Japanese population.

Whole-exome sequencing identifies a novel ALMS1 mutation (p.Q2051X) in two Japanese brothers with Alström syndrome.

PURPOSE: No mutations associated with Alström syndrome (AS), a rare autosomal recessive disease, have been reported in the Japanese population. The purpose of this study was to investigate the genetic and clinical features of two brothers with AS in a consanguineous Japanese family. METHODS: Whole-exome sequencing analysis was performed on two brothers with AS and their unaffected parents. We performed a complete ophthalmic examination, including decimal best-corrected visual acuity, slit-lamp and funduscopic examination, visual-field and color-vision testing, full-field electroretinography, and optical coherence tomography. Fasting blood tests and systemic examinations were also performed. RESULTS: A novel mutation (c.6151C>T in exon 8) in the Alström syndrome 1 (ALMS1) gene that causes a premature termination codon at amino acid 2051 (p.Q2051X), was identified in the homozygous state in the affected brothers and in the heterozygous state in the parents. The ophthalmologic findings for both brothers revealed infantile-onset severe retinal degeneration and visual impairment, marked macular thinning, and severe cataracts. Systemic findings showed hepatic dysfunction, hyperlipidemia, hypogonadism, short stature, and wide feet in both brothers, whereas hearing loss, renal failure, abnormal digits, history of developmental delay, scoliosis, hypertension, and alopecia were not observed in either brother. The older brother exhibited type 2 diabetic mellitus and obesity, whereas the younger brother had hyperinsulinemia and subclinical hypothyroidism. CONCLUSIONS: A novel ALMS1 mutation was identified by using whole-exome sequencing analysis, which is useful not only to identify a disease causing mutation but also to exclude other gene mutations. Although characteristic ophthalmologic findings and most systemic findings were similar between the brothers, the brothers differed slightly in terms of glucose tolerance and thyroid function.