May-Yung Yen

Leber's hereditary optic neuropathy: a multifactorial disease.

Lebers hereditary optic neuropathy (LHON) is a maternally transmitted disease characterized by acute or subacute visual loss predominantly affecting young men. The majority of LHON cases are caused by one of the three primary mitochondrial DNA (mtDNA) mutations: G3460A/ND1, G11778A/ND4, or T14484C/ND6. Although the primary etiological factor of LHON is a mtDNA mutation, the presence of a primary mtDNA mutation does not necessarily lead to visual loss. The pathogenesis of LHON remains unclear. The marked incomplete penetrance and gender bias indicate that additional genetic (nuclear or mitochondrial) and epigenetic factors may also be involved. Deficiency in respiratory chain function and reactive oxygen species (ROS) are believed to play a pivotal role in the pathophysiology of the disease.

Systemic lupus erythematosus-associated optic neuritis: clinical experience and literature review.

Purpose:  This study aimed to evaluate the visual outcome of optic neuritis in patients with systemic lupus erythematosus (SLE).

Visual acuity and contrast sensitivity in different types of posterior capsule opacification

Purpose: To compare the visual acuity (VA) and contrast sensitivity in 2 types of posterior capsule opacification (PCO) in pseudophakic eyes before and after neodymium:YAG (Nd:YAG) capsulotomy and to evaluate vision test results after Nd:YAG capsulotomy. Setting: Department of Ophthalmology, Taipei Veterans General Hospital, National Yang‐Ming University, Taipei, Taiwan. Methods: Fourteen eyes with fibrosis‐type PCO and 15 eyes with Elschnig‐pearl‐type PCO were enrolled prospectively. Before and 1 week after Nd:YAG capsulotomy, VA and contrast sensitivity were assessed using the illiterate E version of the Bailey‐Lovie chart and the Vistech VCTS 6000 chart, respectively. Results: Before capsulotomy, the mean logMAR acuity in the group with Elschnig‐pearl‐type PCO was 0.47 ± 0.32 (SD) and in the group with fibrosis‐type PCO, 0.17 ± 0.07. The difference between the 2 groups was significant (P = .002). After capsulotomy, there was no significant between‐group difference (P gt; .05). Before capsulotomy, the contrast sensitivity was significantly worse (P < .01) at all spatial frequencies in the group with pearl‐type PCO, especially at 6 cycles per degree. After capsulotomy, there was no significant between‐group difference (P gt; .05) at any spatial frequency. Conclusions: After cataract surgery, patients with pearl‐type PCO had lower VA and contrast sensitivity than those with fibrosis‐type PCO. An Nd:YAG capsulotomy improved the VA and contrast sensitivity in patients with both types of PCO.

Pathogenesis and neuroprotective treatment in Purtscher's retinopathy

Purtschers retinopathy is characterized by sudden visual loss in severely traumatized patients and is associated with multiple areas of superficial retinal whitening located primarily in the posterior pole. Visual outcome in Purtschers retinopathy is variable, and there is no well-defined treatment. We report on a patient with immediate blurred vision in the right eye after a traffic accident. Ophthalmoscopy revealed multiple whitish patches scattered over the macular and peripapillary areas in the right eye. Fluorescein angiography showed multifocal retinal arteriolar occlusion in the early phase and staining of the involved retinal vessels and optic nerve head in the late phase. Indocyanine green angiography (ICG) showed rarefaction of choroidal vessels in the peripapillary area of the right eye at early phase. The late phase ICG study revealed multifocal hypofluorescent patches in the macular and peripapillary areas. Megadose steroid therapy was given with good visual response in the first 2 weeks, and the patients vision had recovered completely when followed-up 10 months later.

Leber's Hereditary Optic Neuropathy—The Spectrum of Mitochondrial DNA Mutations in Chinese Patients

PURPOSE To investigate the spectrum of mitochondrial DNA (mtDNA) mutations in Chinese patients with Lebers hereditary optic neuropathy (LHON), optic atrophy of unknown etiology, and optic neuropathy of known etiology. METHODS Twenty-seven patients from 25 LHON pedigrees, 22 patients with bilateral optic atrophy of unknown etiology, 21 patients with optic neuropathy of known etiology, and 25 normal healthy controls were included in this study. Twelve pairs of primers that covered the 21 reported mtDNA mutations were utilized. Single-strand conformation polymorphism analysis and DNA sequencing were used to detect base substitutions in mtDNA. RESULTS Twenty-three LHON pedigrees (92%) had the 11778 mtDNA primary mutation. Two pedigrees (8%) had the 14484 mutation. No 3460 mutations were detected in this group. Thirteen other sequence changes were found in these patients, but only the 4216 mutation had been reported previously. Thirteen pedigrees had multi-mutation patterns consisting of one primary mutation together with other sequence changes. No primary mutations were found in patients with optic atrophy of unknown etiology or in patients with optic neuropathy of known etiology. CONCLUSIONS High frequency of 11778 mtDNA mutation was found in Chinese patients with LHON. No specific multi-mutation pattern such as the European mtDNA haplogroup J was found.

Low Conversion Rate to Multiple Sclerosis in Idiopathic Optic Neuritis Patients in Taiwan

PurposeTo investigate the clinical characteristics of patients with idiopathic optic neuritis (ON) in Taiwan and to assess the conversion rate to multiple sclerosis (MS) in these patients.MethodsWe studied the medical records of a total of 109 patients with a clinical diagnosis of idiopathic ON treated in the Taipei Veterans General Hospital during the period from January 1986 to May 2003. Clinical characteristics, management, and disease courses were retrospectively reviewed. Our main focus was on the development of multiple sclerosis after an ON attack. Univariate and multivariate analyses were used to evaluate the risk indicators for MS conversion.ResultsThe patients (58 women, 51 men) had a mean age of 41.2 years at onset. ON was retrobulbar in 46.8% of the patients. Management with or without pulse therapy did not affect the final visual outcome. Female sex, retrobulbar type ON, recurrent cases, elevated cerebrospinal fluid (CSF) IgG index, and central nervous system (CNS) imaging abnormalities were identified as risk indicators for the development of MS (P < 0.05). The 2-year cumulative probability of developing MS was 5.92%, and the 5-year cumulative probability was 14.28%. The conversion rate to MS did not differ among treatment groups.ConclusionsIdiopathic ON patients in Taiwan have an older age at onset and a higher percentage of optic disc edema than reported in previous literature. The characteristic features of ON patients associated with a high risk of developing MS are female sex, retrobulbar type ON, CNS imaging abnormalities, elevated CSF IgG index, and recurrence. Idiopathic ON patients in Taiwan display a significantly lower conversion rate to MS. Jpn J Ophthalmol 2006;50:170–175

Increase of mitochondrial DNA in blood cells of patients with Leber’s hereditary optic neuropathy with 11778 mutation

Aims: To investigate the change of mitochondrial DNA (mtDNA) content in Leber’s hereditary optic neuropathy (LHON) with 11778 mutation. Methods: Mitochondrial DNA content in 27 LHON patients with 11778 mutation, 26 asymptomatic maternal relatives, and 23 normal controls was measured using a competitive polymerase chain reaction (PCR) method. Results: The mean relative content of mtDNA (with respect to the β actin gene) in LHON patients, asymptomatic maternal relatives, and normal controls was 245.5 (162.3), 238.2 (118.4), and 156.5 (61.6), respectively. There was a statistically significant difference between patients and controls and between relatives and controls. However, no statistically significant difference between patients and unaffected relatives was found. There was no statistically significant difference in the relative content of mtDNA between all males and females carrying 11778 mtDNA mutation Conclusion: The results suggest that the increase in mtDNA content in LHON patients with 11778 mtDNA mutation may be due to a compensatory effect for respiratory chain defects of mitochondria. However, the increase of mtDNA content is the result rather than the cause of defective mtDNA. It still cannot explain the pathogenesis of LHON.

Leukaemic infiltration of the optic nerve as the initial manifestation of leukaemic relapse.

Leukaemic infiltration of the optic nerve as the initial manifestation of leukaemic relapse

Compensatory elevation of complex II activity in Leber's hereditary optic neuropathy.

AIMS: To evaluate the mitochondrial respiratory enzyme activities in blood cells of Lebers hereditary optic neuropathy (LHON) with 11778 point mutation of mitochondrial DNA. METHODS: Assays for the activities of NADH-cytochrome c reductase (complex I+complex III), succinate-cytochrome c reductase (complex II+complex III), and cytochrome c oxidase (complex IV) on blood cell mitochondria of seven LHON patients and 15 normal controls. RESULTS: There was no statistically significant difference in NADH-cytochrome c reductase and cytochrome c oxidase activities between LHON patients and controls, but activities of succinate-cytochrome c reductase in LHON patients was significantly elevated compared with normal controls. CONCLUSION: The observations that the activity of NADH-cytochrome c reductase is normal but that of succinate-cytochrome c reductase is increased in LHON patients with 11778 point mutation of mitochondrial DNA indicate an elevation of complex II activity, which may be due to a nuclear compensatory effect for defects of the respiratory function of mitochondria.

The effect of photo-oxidative stress and inflammatory cytokine on complement factor H expression in retinal pigment epithelial cells.

PURPOSE Genetic variation in complement factor H (CFH) has been implicated as a major risk factor for age-related macular degeneration (AMD). The reduction in CFH amount or its complement-modulating activity may lead to inadequate control of complement-driven inflammation at the outer retina. We explored the effect of photo-oxidative stress and inflammatory cytokine on the expression of CFH in retinal pigment epithelial (RPE) cells. METHODS Cultured human RPE cells were exposed to blue light in the presence of interferon-γ (IFN-γ). CFH expression in cell lysate was examined by Western blot and the secretory CFH in culture medium was analyzed by ELISA. RPE cells were treated with vitamin C and exogenous superoxide dismutase mimetic (Tempol) before photo-oxidative treatments. The intracellular reactive oxygen species were examined by flow cytometry. RESULTS IFN-γ increased CFH expression in RPE and the expression was suppressed significantly under concomitant blue light illumination. The secretory CFH level also decreased significantly under blue light illumination, which was related to the decreased intracellular mRNA and protein expressions of CFH. The suppression was mediated through an oxidative mechanism, and was particularly related to superoxide anion generation. The suppression of CFH expression in RPE under blue light illumination was abrogated by vitamin C and Tempol. CONCLUSIONS Photo-oxidative stress reduces the ability of IFN-γ to increase CFH expression in RPE. Apart from reducing the oxidative damage, vitamin C reduces the suppression of CFH under photo-oxidative stress. These results suggest a new perspective of the interaction between oxidative stress and inflammation, and provide a potential novel treatment strategy for age-related macular degeneration.