Nobuo Ishida

Leu518Pro mutation of the βig-h3 gene causes lattice corneal dystrophy type I

Abstract PURPOSE: To describe a Japanese family with lattice corneal dystrophy type I, which segregates with a novel mutation, Leu518Pro of the βig-h3 gene. METHODS: DNA was extracted from leukocytes in four members (three affected and one unaffected) of a Japanese family with lattice corneal dystrophy type I. Exon 12 of the βig-h3 gene was amplified and analyzed with a molecular biologic method. Clinical data were also collected. RESULTS: Three generations of this family have been positively diagnosed with lattice corneal dystrophy, indicating autosomal dominant inheritance. We found a heterozygous point mutation that segregates with the disease phenotype. It was a single base-pair transition (CTG to CCG, Leu to Pro). CONCLUSIONS: Although it is extremely rare compared with the Arg124Cys mutation of the βig-h3 gene, Leu518Pro mutation of the βig-h3 also causes lattice corneal dystrophy type I.

Six different mutations of TGFBI (betaig-h3, keratoepithelin) gene found in Japanese corneal dystrophies.

Purpose. To investigate mutations of the human transforming growth factor beta-induced gene (TGFBI), transforming growth factor–beta-induced gene product (&bgr;ig-h3, keratoepithelin), in Japanese patients with Avellino corneal dystrophy (ACD), lattice corneal dystrophy (LCD), granular corneal dystrophy (GCD), and Reis-Bücklers corneal dystrophy (RBCD). Methods. Genomic DNA was extracted from the peripheral blood of 75 patients and 7 unaffected relatives from 60 families with ACD, 34 patients and 8 unaffected relatives from 21 families with LCD, 4 patients and 4 unaffected relatives from 4 families with GCD, and 4 patients and an unaffected relative from 3 families with RBCD. Fifty normal volunteers served as controls. Exons 4, 11, and 12 of the TGFBI gene were amplified by polymerase chain reaction and were directly sequenced. Results. Six different heterozygous missense mutations were detected in codons R124, L518, L527, and R555 of the TGFBI gene in the 117 patients from 88 families. A R124H mutation was detected in the patients with ACD. A R124C mutation was detected in the patients with LCD type 1 (LCD1), L518P was in atypical LCD1, and L527R in LCD with opacities deep in stroma. A R555W mutation was detected in the patients with GCD. A R555Q mutation was detected in the patients with RBCD. Conclusions. We conclude that codons R124 and R555 of the TGFBI gene are also hot spots in Japanese patients with ACD, LCD, GCD, and RBCD. Many Japanese patients with CD had ACD with R124H mutation. GCD with R555W mutation was rare.

Corneal endothelium in a case of mitochondrial encephalomyopathy (Kearns-Sayre syndrome).

A case of mitochondrial encephalomyopathy (Kearns-Sayre syndrome) with corneal endothelial abnormality is reported. A 22-year-old woman had retinitis pigmentosa, external ophthalmoplegia, complete heart block, ataxia, muscle weakness, dementia, sensorineural hearing loss, and was of short stature. Renal dysfunction, diabetes mellitus, and amenorrhea were also observed. Biopsy revealed decreased cytochrome c oxidase (complex IV) activity in muscle mitochondria. The corneal endothelium examined by specular microscope showed decreased cell density, severe polymegathism, and pleomorphism in both eyes. To our knowledge, this is the first report concerning primary corneal endothelial abnormality in a case with mitochondrial encephalomyopathy. The corneal endothelium is one of the tissues that could be affected by the enzyme deficiency present in this disease.

Ocular ball bullet injury: detection of gonioscopically unrecognisable cyclodialysis by ultrasound biomicroscopy

Editor,—Ocular ball bullet (BB) injuries are vision threatening and more than 1200 people every year are reported to sustain these injuries in the United States.1  Fewer cases with BB injuries have been reported in Japan.2-4Ultrasound biomicroscopy (UBM) is useful in the morphological evaluation of the anterior segment of the eye.5 We report a 13 year old boy who sustained cyclodialysis from a BB injury, which was not revealed by gonioscopy but was by UBM. To our knowledge, this is the first report describing detection of cyclodialysis from BB injury by UBM. ### CASE REPORT A 13 year old boy sustained an ocular BB injury in his left eye and visited us the following day. The boy was accidentally shot by his elder brother. The BB was made of plastic. His best corrected visual acuity was right eye, 1.2 and left eye, 0.06. Intraocular pressure was right eye, 17 mm Hg and left eye, 11 mm Hg. Slit lamp examination …

Long-term results of non-valved Glaucoma drainage implant surgery and glaucoma drainage implant combined with trabeculectomy

Purpose: The purpose was to investigate the efficacy and complications of nonvalved glaucoma drainage implant (GDI) surgery and GDI combined with trabeculectomy. Subjects and Methods: Serial Japanese patients who received GDI were retrospectively investigated. The survival rate of eyes was analyzed using the Kaplan-Meier method, defining death as: (1) Intraocular pressure (IOP) <6 mmHg, or ≥22 mmHg, and <20% reduction of preoperative IOP, (2) additional glaucoma surgery, (3) loss of light perception. Prognostic factors of age, sex, previous surgery, type of glaucoma, synechial closure, preoperative IOP, type of GDI (single-, double-plate Molteno, Baerveldt 350) and GDI combined with trabeculectomy were investigated employing proportional hazards analysis. Results: One hundred and twenty-four eyes of 109 patients aged 53.3 ± 7.8 years old were analyzed. Types of GDI were single-plate (15.3%), double-plate Molteno (71.8%), and Baerveldt 350 (12.9%). The results of survival rate analysis were 86.1, 71.1, 71.1, and 64.6% for 1, 3, 5, and 10 years respectively. Thirty-four eyes (27.4%) died because of uncontrolled IOP (19.4%), loss of light perception (5.6%), and additional glaucoma surgery (2.4%). Single-plate Molteno was the only risk factor for failure. Persistent unphysiological hypotony (0.8%) and bullous keratopathy (5.6%) were observed. Conclusion: Nonvalved GDI surgery and GDI combined with trabeculectomy using nonabsorbable tube ligature proved to be an excellent device for any type of glaucoma in Japanese patients. Hypotony and corneal endothelial loss are the most serious complication in the long-term results of our patients.

Mitochondrial DNA mutations in Japanese patients with optic neuropathy unassociated with a mutation at nucleotide position 11,778

AbstractWe examined for mitochondrial DNA (mtDNA) mutations at nucleotide positions(nt) 3460, 14,484, 9438, 9804, and 15,257 in ten Japanese patients with idiopathic optic neuropathy unassociated with a mutation at nt11,778. The mtDNAs were amplified by polymerase chain reaction (PCR), the products were digested with restriction enzymes, and the sizes of the fragments were analyzed on 8% polyacrylamide gel. Of the ten patients, one had an mtDNA mutation at nt3460 and another patient had a mutation at nt14,484. We suggest that mtDNA mutations in Japanese patients with optic neuropathy unassociated with a mutation at nt11,778 should be further investigated.

Retinal Photocoagulation Density in the Treatment of Neovascular Glaucoma due to Diabetic Retinopathy

Purpose: The risk factors for pan-retinal photocoagulation (PRP) failure and the efficacy of achieving a PRP burn density of ≥ 40% in the mid-periphery against diabetic neovascular glaucoma (NVG) were retrospectively evaluated.Methods: All eyes were treated in order to exceed more than 40% PRP density by fluorescein fundus angiography before and after PRP. Risk factors for failed IOP control (≤22 mmHg or baseline) were evaluated by dividing into two groups; eyes received previous retinal photocoagulation (RP) before NVG (group I) and eyes with no RP before NVG (group II).Results: Thirty one eyes of 25 patients were used (group I: 12 eyes, group II: 19 eyes).RP density before NVG in all eyes in group I was less than 40%. Risk factors for failed IOP control were prolonged PRP treatment of more than 12 months in group I (p=0.00053), and higher IOP at the diagnosis of NVG (p=0.01157), preexisting glaucoma or ocular hypertension (OH) (p=0.04664) and the persistence of optic disc neovascularization (NVD) in group II (p=0.01766).Conclusion: Eyes with RP density of less than 40% may have a risk for later development of NVG. The prompt initiation of PRP, a PRP burn density of greater than 40%, and the completion of PRP within 6 months are strongly recommended for the treatment of NVG. Special care should be taken in NVG-affected eyes with small pupils, preexisting glaucoma or OH, or persistent NVD as well as those that are subjected to PRP for more than 12 months.