A novel RPE65 variant p.(Ala391Asp) in Leber congenital amaurosis: a case report and literature review in Japan.

Introduction: In Japan, inherited retinal dystrophy caused by biallelic variants of the RPE65 gene is exceedingly rare. The purpose of this study was to describe a Japanese male patient with a novel variant in RPE65 associated with Leber congenital amaurosis (LCA). Case report: The patient, diagnosed with LCA, exhibited infantile nystagmus and reported experiencing night blindness since early childhood. At 27 years of age, the patient underwent an ophthalmologically evaluation. Corrected visual acuity was Snellen equivalent 20/133 in the right eye and Snellen equivalent 20/100 in the left eye. Fundus examination revealed alterations in the retinal pigment epithelium characterized by hypopigmentation and narrowing of retinal vessels. Fundus autofluorescence imaging demonstrated a generally diminished autofluorescent signal. Full-field electroretinography identified a generalized dysfunction of both rod and cone systems in each eye. Whole exome sequencing identified a novel missense variant in RPE65 (NM_000329.3): c.1172C > A p.(Ala391Asp), which was classified as pathogenic, as well as a recurrent variant p.(Arg515Trp). Conclusion: This study provides valuable insights into the genotype-phenotype correlation of RPE65-associated LCA in Japanese patients, with critical implications for enhanced diagnostic accuracy and informed therapeutic decisions.

Visual field after anti-vascular endothelial growth factor therapy and laser treatment for retinopathy of prematurity.

PURPOSE: To evaluate the visual field after anti-vascular endothelial growth factor (VEGF) therapy and laser treatment for retinopathy of prematurity. METHOD: Retrospective cohort study. Infants with retinopathy of prematurity treated by anti-VEGF therapy or laser treatment were included in the study. Degrees of visual field in eight directions examined by Goldmann perimeter (intensity, 1000 apostilb; size, V4e = 64 mm2) were compared between the anti-VEGF therapy and laser treatment groups. The visual acuity (VA) and spherical equivalent refraction were also compared between the two groups. RESULTS: Nine eyes with anti-VEGF therapy and 12 eyes with laser treatment were enrolled in the analysis. The total, upper, nasal upper, nasal, nasal lower, temporal lower, and temporal upper visual fields were significantly wider in the eyes with anti-VEGF therapy than in those with laser treatment (496 vs 416, P = .002; 53 vs 45, P = .008; 56 vs 43, P = .003; 58 vs 39, P < .001; 55 vs 44, P = .01; 72 vs 65, P = .01; and 62 vs 56, P = .03, respectively). The logarithm of the minimum angle of resolution VA tended to be better in the eyes with anti-VEGF therapy than in those with laser treatment (0.01 vs 0.15, P = .06). Eyes with anti-VEGF therapy had significantly lower myopia than those with laser treatment (spherical equivalent refraction: -0.72 vs -5.7, P = .001). CONCLUSION: Anti-VEGF therapy may provide a wider visual field, better VA, and less myopia compared with laser treatment.

Genotype determination of the OPN1LW/OPN1MW genes: novel disease-causing mechanisms in Japanese patients with blue cone monochromacy.

Blue cone monochromacy (BCM) is characterized by loss of function of both OPN1LW (the first) and OPN1MW (the downstream) genes on the X chromosome. The purpose of this study was to investigate the first and downstream genes in the OPN1LW/OPN1MW array in four unrelated Japanese males with BCM. In Case 1, only one gene was present. Abnormalities were found in the promoter, which had a mixed unique profile of first and downstream gene promoters and a -71A > C substitution. As the promoter was active in the reporter assay, the cause of BCM remains unclear. In Case 2, the same novel mutation, M273K, was present in exon 5 of both genes in a two-gene array. The mutant pigments showed no absorbance at any of the wavelengths tested, suggesting that the mutation causes pigment dysfunction. Case 3 had a large deletion including the locus control region and entire first gene. Case 4 also had a large deletion involving exons 2-6 of the first gene. As an intact LCR was present upstream and one apparently normal downstream gene was present, BCM in Case 4 was not ascribed solely to the deletion. The deletions in Cases 3 and 4 were considered to have been caused by non-homologous recombination.

Quantitative Analysis of Inflammation in Orbital Fat of Thyroid-associated Ophthalmopathy Using MRI Signal Intensity.

We quantitatively analyzed inflammation in orbital fat from cases of thyroid-associated ophthalmopathy (TAO) using short-tau inversion recovery (STIR) sequences from magnetic resonance imaging. The signal intensity ratios (SIRs) of orbital fat as well as the superior rectus (SR), inferior rectus (IR), lateral rectus (LR), medial rectus (MR), and superior oblique (SO) muscles on STIR images were measured in 70 eyes from 70 treatment-naive TAO patients (active TAO group, 19 patients; inactive TAO group, 51 patients) and 20 eyes from 20 controls. The mean SIR in the active TAO group was significantly higher than that in the inactive TAO group and controls (P < 0.001). The SIR of orbital fat in all TAO patients was significantly (P < 0.001) positively correlated with that of the extraocular muscles: SR (r = 0.64), IR (r = 0.55), LR (r = 0.58), MR (r = 0.71), and SO (r = 0.65). The SIR of orbital fat had a significant positive correlation with the CAS (r = 0.53, P < 0.001). The measurements of SIRs in orbital fat may be useful in evaluating the activity in tissues of TAO patients.

Changes in the anterior segment after cycloplegia with a biometer using swept-source optical coherence tomography.

The aim of this study was to investigate changes in the anterior segment of the eye after cycloplegia. A biometer combined with swept-source optical coherence tomography (SSOCT) was used for measurements. Patients with strabismus or amblyopia who underwent cycloplegia were included. The axial length, central corneal thickness, anterior chamber depth, and lens thickness were measured with the biometer-SSOCT system before and after cycloplegia. Altogether, 10 eyes of 10 patients (mean age 7.20 ± 3.08 years, range 4-14 years) were evaluated. The mean measurements before cycloplegia were 22.75 ± 0.96 mm axial length, 516 ± 33 µm central corneal thickness, 3.40 ± 0.21 mm anterior chamber depth, and 3.77 ± 0.26 mm lens thickness. The corresponding values after cycloplegia were 22.75 ± 0.95 mm, 519 ± 34 µm, 3.68 ± 0.16 mm, and 3.42 ± 0.20 mm, respectively. The mean lens thickness had significantly decreased (P < 0.001) after cycloplegia, and the mean anterior chamber depth had significantly increased (P < 0.001). The means of the axial length (P = 0.66) and central corneal thickness (P = 0.17) had not changed significantly. The change in lens thickness was significantly correlated with the change in anterior chamber depth (r = -0.73, P = 0.02). The new biometer-SSOCT combination proved useful for accurately detecting changes in the anterior segment of the eye after cycloplegia in pediatric patients. The biometer's measurements indicated increased anterior chamber depth and decreased lens thickness after cycloplegia. The anterior chamber depth increased relative to the decrease in lens thickness.

Successful medical treatment with danazol after failed embolization of uterine arteriovenous malformation.

BACKGROUND: Transcatheter arterial embolization has been the therapy of choice for uterine arteriovenous malformations, whereas medical therapy has not been popular because of patient propensity to bleed. CASE: A 29-year-old woman, gravida 3, para 0, was diagnosed with uterine arteriovenous malformation. Because initial treatment with uterine artery embolization was unsuccessful, she was ultimately treated with danazol. Resolution of the lesion after 2 weeks of danazol therapy was observed. As of follow-up at 16 months, she has remained free from further abnormal bleeding episodes and recurrence of the lesion. CONCLUSION: Danazol has the potential for medical management of uterine arteriovenous malformations in hemodynamically stable patients who do not respond to embolization.