Norio Ohba

Clinicopathological correlation of polypoidal choroidal vasculopathy revealed by ultrastructural study

Aims: To describe the clinical and histopathological findings in a patient with polypoidal choroidal vasculopathy. Methods: A 76 year old Japanese man had a discrete, orange-red lesion of 1 disc diameter in the macula, with the fluorescein and indocyanine green angiographic and optical coherence tomographic findings compatible with polypoidal choroidal vasculopathy. He underwent a surgical removal of the macular lesion, followed by light and electron microscopic examinations. Results: The histopathological examination revealed that the specimen consisted of degenerated retinal pigment epithelium-Bruch’s membrane-choriocapillaris complex and inner choroid. A tortuous, unusually dilated venule was present adjacent to an arteriole with marked sclerotic changes, appearing to form arteriovenous crossing. These vessels seemed to represent native inner choroidal vessels, and had haemorrhage per diapedesis. Blood cells and fibrin filled the lumina of the vessels and accumulated in the extravascular spaces, indicating vascular stasis. Conclusion: Hyperpermeability and haemorrhage due to stasis of a dilated venule and an arteriole involved by sclerosis at the site where they cross in the inner choroid might cause oedema and degeneration of the tissue. Voluminous accumulation of blood cells and fibrin might generate elevation of tissue pressure sufficient to displace the weakened lesion anteriorly. The result suggests that the polypoidal vessels in this case represent abnormality in the inner choroidal vasculature.

Genetic association of manganese superoxide dismutase with exudative age-related macular degeneration

PURPOSE To elucidate whether any polymorphic genes for xenobiotic-metabolizing and antioxidant enzymes are associated with the development of exudative age-related macular degeneration. METHODS A hospital-based case-control study was performed on a consecutive series of 102 Japanese patients with the exudative form of age-related macular degeneration who were recruited between 1993 and 1998 in the Kagoshima University Hospital. Controls were 200 systemically healthy individuals who had no senescent ocular disorders and were over 50 years of age. There was no evidence of age-related macular degeneration in the 200 controls. Genomic DNA from peripheral bloods was examined using polymerase chain reaction and defined for the genetic polymorphisms of cytochrome P-450 1A1, glutathione S-transferases, microsomal epoxide hydrolase, and manganese superoxide dismutase. RESULTS We found a significant association of manganese superoxide dismutase gene polymorphism, valine/alanine polymorphism at the targeting sequence of the enzyme, with age-related macular degeneration. The patients had an increased frequency of alanine allele and alanine/alanine genotype (odds ratio = 10.14, 95% confidence interval = 4.84 to 2.13; P =.0005 after Bonferroni correction). We also observed a weak association of microsomal epoxide hydrolase exon-3 polymorphism with age-related macular degeneration (odds ratio = 2.20, 95% confidence interval = 4. 02 to 1.20; P =.020 after Bonferroni correction). Cytochrome P-450 1A1, glutathione S-transferases, and microsomal epoxide hydrolase exon-4 were polymorphic, but their genotype frequency distributions did not show a statistically significant difference between the patients and controls. CONCLUSIONS The results suggest that manganese superoxide dismutase gene polymorphism is associated with exudative age-related macular degeneration. Microsomal epoxide hydrolase is another enzyme that may be associated with the disease. The exudative form of age-related macular degeneration may have genetic risk factors against oxidative stress and/or effects of xenobiotics. Further association studies in other polymorphic genes for xenobiotic-metabolizing enzymes are needed to elucidate the environmental-genetic interaction in the underlying cause of age-related macular degeneration.

Anatomic and visual outcomes after indocyanine green-assisted peeling of the retinal internal limiting membrane in idiopathic macular hole surgery

PURPOSE To report anatomic and visual outcomes after vitrectomy and adjunctive retinal internal limiting membrane (ILM) peeling with and without intravitreal indocyanine green for idiopathic macular hole repair. DESIGN Retrospective comparative study of consecutive case series. METHODS Three consecutive groups of idiopathic macular hole cases underwent modifications of surgical technique. Group I (48 eyes of 47 patients) underwent a standard vitrectomy, fluid/gas exchange, and 1 weeks face-down positioning, group II (21 eyes of 21 patients) an adjunctive ILM peeling without use of indocyanine green, and group III (28 eyes of 28 patients) an adjunctive peeling of ILM stained with intravitreal application of 0.1 to 0.2 ml of 0.5% indocyanine green dye. RESULTS Three groups of patients had comparable clinical characteristics as to age, gender, estimated duration of macular hole, preoperative visual acuity, and follow-up time. The rate of macular hole closure after a single surgery, as determined by optical coherence topography was 85.4% in group I, 85.7% in group II, and 100% in group III. Groups I and II showed a statistically significant visual improvement, but group III did not show significant visual acuity improvement as the mean logarithm of the minimal angle of resolution visual acuity was from 0.767 (20/120) preoperatively to 0.691 (20/100) postoperatively (P =.342). Eight cases in group III developed within a few postoperative months of optic disk pallor and irreversible peripheral visual field loss, predominantly affecting the nasal field. CONCLUSIONS Intravitreal indocyanine green-assisted ILM peeling improves anatomic success in macular hole surgery, but it may potentially lead to unfavorable visual acuity outcome and peripheral visual field loss.

Spontaneous closure of traumatic macular hole

PURPOSE To report eight cases of spontaneous closure of traumatic macular hole. DESIGN Consecutive observational case series. PATIENTS AND METHODS In a consecutive series of 18 eyes of 18 patients with traumatic macular hole, eight patients achieved spontaneous closure of traumatic macular hole. Clinical records of the eight eyes of eight patients were reviewed, together with the results of optical coherence tomography performed in three eyes. RESULTS All eight patients with spontaneous closure of traumatic macular hole were males, with a mean age of 14.6 years (range, 11-21 years). The major cause of blunt trauma was sports-related accidents. Six eyes developed visual symptoms immediately after trauma and two eyes 10 to 12 days later. In all eight eyes, contact lens biomicroscopy revealed a small, full-thickness macular hole not complicated by epiretinal membrane, cuff of subretinal fluid, or posterior vitreous detachment. The macular hole closed spontaneously 1 week to 4 months after trauma. All eight eyes had visual acuity improvement with the final best-corrected visual acuity of 0.5 or better in four (50%) eyes. Optical coherence tomography in three eyes revealed two distinct abnormalities. Two eyes presented with acute foveal dehiscence without involvement of the posterior vitreous cortex. The remaining eye showed at presentation perifoveal vitreous detachment with residual vitreous adhesion to the edge of updrawn fovea and developed release of the vitreofoveal adhesion at the time of hole closure. CONCLUSIONS Spontaneous closure of traumatic macular hole is not uncommon. An observation for a period of up to four months may be a management of choice for traumatic macular hole. There may be clinically and pathogenetically two distinct mechanisms of traumatic macular formation; one type that causes immediate visual loss due to primary dehiscence of the fovea, and the other type that leads to delayed visual loss due to dehiscence of the fovea secondary to persistent vitreofoveal adhesion.

Baseline Features of Idiopathic Optic Neuritis as Determined by a Multicenter Treatment Trial in Japan

BACKGROUND An optic neuritis treatment trial was conducted at 30 clinical centers in Japan using the same protocol. Patient participation was based on: age range of 14-55 years; acute symptoms indicative of unilateral optic neuritis of unknown or demyelinating origin; visual symptoms of 14-day duration or less; relative afferent pupillary defect in affected eye; and normal or swollen optic disc of affected eye. CASES Initially, 102 patients qualified for participation; baseline data were obtained for analysis from 70 of these patients. Demographic characteristics of Japanese patients with optic neuritis were clarified and compared with those in a US study. OBSERVATIONS The incidence of ocular or periocular pain and the presence of periventricular plaques were noted to be lower, and the incidence of disc swelling higher, in the Japanese patients, suggesting racial differences in the characteristics of the disease. Such differences may possibly be related to the lower incidence of multiple sclerosis in Japanese patients. The results of visual function tests were virtually the same in both studies. The nonaffected eyes of more than half the patients showed abnormal mean deviation in Humphrey field analysis, as also noted in the US study. CONCLUSIONS The baseline clinical features of optic neuritis in the Japanese patients have been defined. Some racial differences in the characteristics of the disease may exist.

Anatomical and visual outcomes after episcleral macular buckling compared with those after pars plana vitrectomy for retinal detachment caused by macular hole in highly myopic eyes.

Purpose: To report anatomical and visual outcomes after episcleral macular buckling (EMB) and pars plana vitrectomy (PPV) for retinal detachment caused by macular hole in highly myopic eyes with posterior staphyloma. Patients and Methods: This retrospective, interventional case series included 58 eyes of 58 patients with retinal detachment caused by macular hole in highly myopic eyes with posterior staphyloma and geographic chorioretinal atrophy. The cases were assigned to 2 groups according to the surgical technique: the EMB group (30 eyes) underwent posterior episcleral buckling using a solid silicone plate specifically designed for macular indentation, and the PPV group (28 eyes) underwent PPV combined with fluid–gas exchange. Baseline clinical data including age, sex, refractive errors, and degree of retinal detachment did not differ between EMB and PPV groups. Main outcome measures included ophthalmoscopy findings, three-mirror contact lens biomicroscopy results, and visual acuity at the end of follow-up (mean follow-up, 52.8 months in the EMB group and 44.1 months in the PPV group). Optical coherence tomography was performed in selected cases in the EMB group. Results: In the EMB group, the retinal reattachment rate was 93.3% after primary surgery and 100% after secondary surgery. In the PPV group, the retinal reattachment rate was 50% after primary surgery and 86% after secondary surgery using the EMB procedure, thus indicating a better anatomical success rate after primary EMB than after primary PPV. The mean logarithm of the minimum angle of resolution (logMAR) visual acuity ± SD in the EMB group increased significantly from 1.45 ± 0.50 before surgery to 0.92 ± 0.42 at the end of follow-up (P < 0.001). The mean logMAR visual acuity in the PPV group increased significantly from 1.70 ± 0.45 before surgery to 1.35 ± 0.61 at the end of follow-up (P < 0.02). Visual acuity improvement at the end of follow-up was significantly better after EMB than after PPV (P < 0.005). Optical coherence tomography revealed that 10 of 12 eyes with successful indentation of the macular hole area after EMB had complete closure of the macular hole as well as reattachment of the retina, and the remaining 2 eyes had persistent retinal reattachment with the foveal defect. Conclusions: EMB is a preferred surgical procedure for the repair of retinal detachment and macular hole closure in highly myopic eyes with posterior staphyloma.

A long-term follow-up study of severe variant of central serous chorioretinopathy.

Purpose To facilitate understanding of the long-term course and visual outcome of a severe variant of central serous chorioretinopathy. Design Consecutive observational case series. Patients and Methods The authors reviewed 25 patients with multifocal posterior pigment epitheliopathy and bullous retinal detachment, who had a mean follow-up time of 10.6 years (range, 6–22 years), with reference to the demographic feature, fundus changes, recurrence, and final anatomic and visual outcome. Two patients underwent optical coherence tomography. Results The patients were 21 men and 4 women, with a mean age at disease onset of 43.1 years (range, 30–63 years). Twenty-one patients were otherwise healthy, and four developed ocular disease during systemic corticosteroid therapy for metabolic or autoimmune diseases including systemic lupus erythematosus. The disease was bilateral in 21 patients (84%). Nine patients (36%) presented initially with classic central serous chorioretinopathy, followed by its severe variant 7 months to 9 years later. Active disease was characterized by multifocal exudative lesions in the posterior pole and bullous retinal detachment with shifting subretinal fluid in the inferior periphery. Optical coherence tomography of exudative lesions disclosed cloudy and fibrinous subretinal fluid. The exudative lesions were self-limited or responded to photocoagulation. During the follow-up period, 13 patients (52%) showed 1 to 5 recurrent disease, but the disease eventually became quiescent with multifocal atrophic scars in the posterior pole with or without atrophic tracts in the inferior periphery. Final best-corrected visual acuity was 20/20 or better in 24 of 46 affected eyes (52%) of 25 patients and 20/40 or better in 37 eyes (80.4%). Conclusions A severe variant of central serous chorioretinopathy characterized by multifocal posterior exudations and bullous inferior retinal detachment with shifting subretinal fluid may affect otherwise healthy, middle-aged males or individuals receiving systemic corticosteroid therapy for metabolic or autoimmune diseases. Exudative chorioretinal lesions are self-limited or respond to photocoagulation. Recurrence is common, but the disease eventually becomes quiescent with favorable visual acuity unless the macula is damaged.

Localization of fluorescence-labeled lectin binding sites on photoreceptor cells of the monkey retina

The binding of eight fluorescence-labeled lectins to the photoreceptors of the monkey retina was investigated using a post-embedding staining method. Concanavalin A (specific for mannosyl and glucosyl residues) bound to the outer and inner segments of both rods and cones, while the degree of staining was more intense in the rods. The rod outer segments showed patchy fluorescence and the proximal portions of the inner segments were diffusely stained. Wheat germ agglutinin (specific for sialyl and N-acetylglucosaminyl residues) bound preferentially to the surface of the outer and inner segments of both rods and cones. Ricinum communis agglutinin-1 (specific for galactosyl residues) stained the rod outer segments in patches, particularly strongly in the region dividing the outer and inner segments. The cones were also stained, although faintly, in the same pattern as the rods. The distal halves of the rods and cones showed diffuse weak staining and their proximal halves stained spotty. Peanut agglutinin (specific for Gal beta 1 leads to 3GalNAc sequence) bound preferentially to the cones and only scarcely to the rods. The external surface of both outer and inner segments of cones were uniformly stained; the interior of the cone outer segments was also stained, while the interior of the inner segments was not. Two lectins specific for fucosyl residues, namely, Ulexeuropaeus agglutinin-1 and Lotustetragonolobus agglutinin, bound diffusely to the distal halves of the inner segments of both rods and cones. Lectins reacting with N-acetyl-galactosamine residue, i.e. Dolichos biflorus agglutinin and soybean agglutinin, bound weakly to the distal portions of rods and cones.

Multicenter Clinical Trial for Evaluating Methylprednisolone Pulse Treatment of Idiopathic Optic Neuritis in Japan

BACKGROUND A randomized, controlled clinical trial was conducted in 1991 to compare an intravenous megadose of methylprednisolone with a control drug (mecobalamin) for treating acute idiopathic optic neuritis. CASES Sixty-six cases from 22 clinical centers throughout Japan were examined to evaluate the treatment on visual function parameters, such as visual acuity, visual field, color vision, contrast sensitivity, and critical flicker frequency. OBSERVATIONS The methylprednisolone pulse treatment group showed faster recovery of visual function, particularly the visual acuity at 1 week (P<.05), Humphrey field analyzer mean deviation at 3 weeks (P<.05), and color vision at 1 week (P<.05). Recovery of contrast sensitivity at several different spatial frequencies was significant in the pulse treatment group at 1 (P<.01), 2 (P<.05), and 4 weeks (P<.05) after the start of treatment. Visual function test results at 12 weeks and 1 year were essentially the same in the two treatment groups. Side effects appeared more frequently in the pulse treatment group than in the control (P<.05). CONCLUSIONS Pulse treatment does not appear effective for idiopathic optic neuritis even though visual function in the pulse treatment group of this trial recovered more quickly during the initial phase compared to the controls. More effective and specific treatment should be established for optic neuritis.

Specialization of the interphotoreceptor matrices around cone and rod photoreceptor cells in the monkey retina, as revealed by lectin cytochemistry

The binding sites of two lectins, peanut agglutinin (PNA) and wheat germ agglutinin (WGA), in the interphotoreceptor matrix (IPM) and photoreceptor plasma membranes of the Japanese monkey (Macaca fuscata) retina were localized using a pre-embedding staining method with ferritin-conjugated (Fer) lectins as well as a postembedding staining method with fluorescence-labeled (FITC) lectins. FITC-PNA, but not WGA, stained cylindrical domains of the IPM around cone outer and inner segments, while the IPM around rods stained with FITC-WGA but not PNA. When the intact (not detached) retinal tissues were incubated with Fer-lectin, the lectin generally labeled neither the IPM nor photoreceptor plasma membranes, but labeled only those structures in detached portions occurring at the edges of occasional retinal tissue blocks. Thus, the neural retinas physically isolated from the retinal pigment epithelium (RPE) were utilized principally here. Ultrastructurally, the IPM in the intact retina consisted of granular and filamentous materials; the IPM in the isolated neutral retina also retained those components, although somewhat loosely organized, and the IPM around cones appeared to be preserved better than did the IPM around rods. Fer-PNA bound to the IPM associated with cones, but not rods; Fer-WGA bound to the rod- but not cone-associated IPM. The ferritin particles were found to lie close to the granular and filamentous materials. Those photoreceptor-associated IPMs extended to the apical surface of the RPE in detached portions or to the apical villi of the RPE which were frequently found in the isolated neural retinas. Also, Fer-PNA labeled the cone, but not rod, plasma membranes; Fer-WGA bound heavily to the plasma membranes of rod and cone outer segments, but sparsely to those of their inner segments. These results suggest that the IPM comprises chemically and physically differential domains specialized for cone and rod photoreceptor cells, and that these specialized IPM are structurally so stable that may be involved in isolating photoreceptor cells physicochemically from each other and in the interactions between the photoreceptors and the RPE, such as retinal adhesion.