Kumiko Nakao

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.

A novel splice site mutation in the tissue inhibitor of the metalloproteinases-3 gene in Sorsby's fundus dystrophy with unusual clinical features

Abstract Sorsby’s fundus dystrophy (SFD) is an autosomal dominant macular dystrophy which is developed usually in the third or fourth decade of life, and is characterized by central visual loss and nyctalopia due to fundus changes of exudative or atrophic macular lesions. Its functional prognosis is usually poor because of disciform macular scars and peripheral chorioretinal atrophies. To date, five different mutations in the tissue inhibitor of the metallo-proteinases-3 (TIMP3) gene have been identified in families of a wide geographic origin, all of which are missense mutations that cause replacement by cysteine of conserved amino acids in the C-terminus of exon 5 of TIMP3. We have studied two Japanese families with SFD, the first report from the Eastern world, and identified a novel 3’ splice site mutation in the TIMP3 gene, namely a single base insertion at the intron 4/exon 5 junction which converts the consensus sequence CAG to CAAG in the splice acceptor site. In addition, our patients displayed a distinctive clinical expression in that they developed macular dystrophies at an approximately 30-year later age of onset and preserved functional vision until later life with essentially uninvolved peripheral retina. The present findings may provide some insight into the genotype–phenotype relationship in SFD.

Relationship between position of peak retinal nerve fiber layer thickness and retinal arteries on sectoral retinal nerve fiber layer thickness.

PURPOSE We determined the relationship between the position of the peak of the retinal nerve fiber layer (RNFL) thickness, and the retinal arteries, axial length (AL), and sectoral RNFL thickness in healthy eyes. METHODS A prospective, observational cross-sectional study (registration number, UMIN000006040) of 50 healthy right eyes (mean age 25.8 ± 3.7 years) was performed. The RNFL thickness was measured by optical coherence tomography in twelve 30° sectors (clock hours) around the optic disc. The RNFL nasal-superior-temporal-inferior-nasal curves and fundus photographs were used to measure the angles between the supratemporal and infratemporal peak RNFL positions (peak angle), and the retinal artery angle (artery angle), respectively. The relationships between the peak angle, artery angle, AL, and sectoral RNFL thickness were investigated by linear regression analyses. RESULTS The peak angles were highly correlated with the artery angle (r = 0.92, P < 0.001) and correlated negatively with the AL (r = -0.49, -0.38; P < 0.01). After excluding the effect of the AL, the peak and artery angles were correlated significantly with the sectoral RNFL thickness in 8 sectors. After excluding the effect of the peak angle, the AL was correlated significantly with the sectoral RNFL thicknesses in only one sector. CONCLUSIONS The temporal RNFL thickness increased as the superior and inferior RNFL peaks, and retinal arteries shifted toward the fovea, whereas an inverse relationship was observed for the inferior and supranasal areas. The sectoral RNFL thickness is correlated better with the peak and artery angles than the axial length. (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary &recptno=R000007154&language=J number, UMIN000006040.).

Vitreomacular adhesion and the defect in posterior vitreous cortex visualized by triamcinolone-assisted vitrectomy

Purpose: To study the vitreomacular adhesion and the contractile force of posterior hyaloid, which are shown in triamcinolone acetonide (TA)-assisted pars plana vitrectomy (PPV). Design: Interventional case series. Methods: Twenty-eight eyes with diabetic macular edema (DME) without posterior vitreous detachment (PVD) received TA-assisted PPV. Surgical PVD was performed by an aspiration of vitrectomy probe, and the dynamic changes of posterior vitreous cortex and residual vitreous cortex were evaluated. Results: A premacular defect was formed in the detached posterior vitreous cortex during surgical PVD in 27 of 28 eyes. Immediately thereafter, the small defect expanded into a large hole in the detached posterior vitreous cortex in all cases. A residual vitreous cortex was left on the macula in 22 eyes. Conclusions: These observations demonstrate a firm vitreoretinal adhesion in the central macula and suggest that the enlargement of the defect of posterior vitreous cortex may be extrusion of vitreous out through the premacular dehiscence into the preretinal space, or a tangentially contractile force may exist in the posterior vitreous cortex. Both macular adhesion and the traction of vitreous cortex might contribute to the pathogenesis of DME and other vitreomacular disease.

Extensive Chorioretinal Atrophy in Vogt–Koyanagi–Harada Disease

PURPOSE To report extensive chorioretinal atrophy during the long-term course of Vogt-Koyanagi-Harada (VKH) disease not treated properly in the initial phase. CASES Four patients with VKH disease were examined more than 10 years after onset of the disease. OBSERVATIONS They presented initially with classic features of VKH disease, except 1 patient who had developed bilateral, acute angle-closure glaucoma as the initial sign. Two patients received systemic corticosteroid therapy at the acute phase of the disease. During the follow-up of 13-34 years subsequent to onset, these patients had chronic recurrent anterior uveitis with apparently stable depigmented fundus. Eventually, they developed diffuse, extensive chorioretinal atrophy that resulted in severe visual loss. One patient had an unusual familial occurrence of the disease. CONCLUSIONS Failure to prescribe proper corticosteroid therapy in the initial phase of VKH disease may lead to chronic recurrent uveitis. Long-standing uveitic reactions may eventually result in severe visual loss due to extensive chorioretinal degeneration.

Inflammatory cytokine of basal and reflex tears analysed by multicytokine assay

Tear cytokine has a major role in various pathophysiological conditions of the ocular surface. So far, studies on tear cytokines have shown significant progress in providing an understanding of ocular surface diseases.1–3 The information that could be acquired from each subject, however, until recently has been severely hampered by limited sample volume and assay sensitivity. More importantly, it has become apparent that the relative balance between various cytokines and combinations of cytokines could be more important than absolute concentrations. Previous studies showed that the composition of basic and reflex tears was different, which made it more difficult to understand the ocular surface disorder correctly or to treat the patients suitably.4,5 Cytometric bead array (CBA) is a microparticle based flow cytometric assay that allows us to quantify multiple molecules from a very small sample.3,6,7 Using this method, we evaluated the inflammatory cytokines of basal and reflex tears from a single sample of individual eyes. Twenty three normal volunteers (11 males and 12 females, 22–44 years of age, average 28 years) were recruited for this …

Clinical course of HTLV-I-associated uveitis

PURPOSE To define the long-term clinical course and visual outcome of human T-cell lymphotrophic virus type I (HTLV-I)-associated uveitis (HAU). METHODS We reviewed the clinical data on 96 eyes of 70 patients, 26 men and 44 women, with HAU, with specific reference to recurrence of the disease and long-term visual outcome. The mean follow-up period was 83 months (range, 12-276 months). RESULTS The mean age of onset was 42.8 years (range, 7-78 years of age), with men presenting at a significantly younger age. Forty-seven patients had isolated HAU; in 10 patients, HTLV-I-associated myelopathy occurred before or after the onset of HAU; in 14 patients, hyperthyroidism had preceded HAU. A single episode of mild to moderate acute uveal inflammation with resolution in a few weeks or more occurred in 44 (62.9%) patients, and multiple episodes in 26 (37.1%), with a mean interval of 16 months (range, 1-250 months), which affected the same eye, fellow eye, or both. The majority of patients had favorable visual outcome at the last examination, whereas only a few patients suffered poor vision resulting from steroid cataract and retinochoroidal degeneration. CONCLUSIONS The clinical course of HAU is virtually benign and its visual outcome is favorable, although its recurrence is common. The uveitis is usually isolated and affects a portion of otherwise unremarkable HTLV-I carriers, but it may sometimes be manifest as a symptom of syndromic diseases such as HTLV-I-associated myelopathy or hyperthyroidism. This study describes for the first time cases of HAU that occurred many years before manifestation of HTLV-I-associated myelopathy.

A Novel Truncating Mutation of Cytochrome P4501B1 (CYP1B1) Gene in Primary Infantile Glaucoma

PURPOSE To report a novel mutation of the CYP1B1 gene in a Japanese patient with primary infantile glaucoma. METHODS DNA was extracted from leukocytes of six unrelated patients with primary infantile glaucoma. The coding regions of the CYP1B1 gene were amplified by polymerase chain reaction, examined by agarose gel separation and heteroduplex methods, and directly sequenced. RESULTS One of the patients with primary infantile glaucoma had a mutation of the CYP1B1 gene, with an abnormal shift in agarose gel separation and heteroduplex analysis. Direct sequencing disclosed a homozygous insertion of guanine at nucleotide 1620 of exon 3, which produced a frameshift leading to premature termination of amino acid translation. The patient was male and had sporadic, classic primary infantile glaucoma. None of the other five patients with infantile glaucoma, the 30 patients with primary adult-onset glaucoma, or the 70 healthy control subjects showed any abnormalities in the CYP1B1 gene. CONCLUSIONS This is the first report of CYP1B1 gene mutation in primary infantile glaucoma from the Eastern world. CYP1B1 gene mutation for primary infantile glaucoma spreads worldwide, but its prevalence may have ethnic or geographic differences.

Optic disc swelling in Vogt-Koyanagi-Harada disease.

PURPOSE This retrospective observational study was designed to evaluate the frequency of, and the factors associated with, optic disc swelling in Vogt-Koyanagi-Harada disease (VKH). METHODS A retrospective observational study was conducted. We analyzed 116 eyes of 58 patients with VKH. Demographic and clinical differences between patients with and without disc swelling were analyzed. RESULTS Thirty-two eyes (27.6%) of 16 VKH patients had disc swelling. The mean age of the patients with disc swelling was higher than that of those without disc swelling (58.9 vs. 41.4, P = 0.0001). The disc-macula distance to disc diameter (DM/DD) ratio of the eyes with disc swelling was higher than that of those without disc swelling (2.81 vs. 2.59, P = 0.0007). The cup to disc (C/D) ratio of the eyes with disc swelling was smaller than that of those without disc swelling (0.18 vs. 0.32, P = 0.000001). The intraocular pressure was lower (P = 0.0084), and the refractive error was larger (P = 0.019), in eyes with disc swelling than in those without. There was no significant association between the presence of disc swelling and the range of retinal detachment, cerebrospinal fluid cell count, recurrence rate of VKH, or the incidence of sunset glow fundus. Among the eyes with disc swelling, 13 eyes of 7 patients had visual field defects even after the inflammation subsided, and these patients were older, had a higher DM/DD ratio, and had a smaller C/D ratio than those without visual field defects. CONCLUSIONS The occurrence of disc swelling in VKH was significantly correlated with age and disc morphology, rather than the severity of inflammation. Some VKH patients with disc swelling develop visual field defects from optic disc involvement.

Long-term outcomes of visual field defects after indocyanine green-assisted macular hole surgery.

Purpose: To evaluate the long-term course of visual field defects after intravitreal injection of indocyanine green (ICG) during vitrectomy. Methods: Retrospective observational case series. The medical records of seven eyes of seven patients with visual field defects after the adjunctive use of ICG during macular hole surgery were studied. All of the surgeries were performed between February 2001 and January 2002. Humphrey static perimetry and best-corrected visual acuity were examined periodically, and the main outcome measure was the mean deviation (MD) determined by the Humphrey (30-2) SITA-Fast program. Results: All patients were observed for more than 4.5 years, for a mean of 60.7 months and a range of 54 to 66 months. The preoperative MD was −3.5 ± 3.1 dB (mean ± SD), and the postoperative MD was −13.3 ± 4.9 dB at 1 year, −13.4 ± 4.6 dB at 2 years, −16.2 ± 5.1 dB at 3 years, and −15.6 ± 5.1 dB at 4 years. The decrease in the mean MD between 1 and 3 years after surgery was significant (P < 0.05). Optic disk pallor in five eyes showed a decrease in the MD between 1 year and 3 years after the surgery. There was no significant difference in the postoperative best-corrected visual acuity at any time. Conclusions: The visual field defect in eyes that had undergone vitrectomy with staining of the internal limiting membrane with ICG can continue to deteriorate for at least 3 years. Eyes receiving intravitreal ICG during vitrectomy should be followed for a longer period to determine the long-term effect of ICG.