Enolase autoantibodies and retinal function in multiple sclerosis patients.

BACKGROUND: Electroretinographic (ERG) abnormalities have been reported in multiple sclerosis (MS), as well as the presence of circulating antiretinal antibodies. We and others have reported cases of impaired vision and diminished ERGs in MS patients with alpha-enolase autoantibodies. Anti-enolase antibodies have been implicated in autoimmune retinopathy. We performed this study to further explore the relationship between antiretinal antibodies and ERG changes in patients with MS. METHODS: Patients with clinically definite MS and normal visual acuity were recruited for this study, along with healthy controls. All patients and controls had ERG testing done according to ISCEV standards. Patient and control sera were analyzed for the presence of antiretinal antibodies using Western blot and ELISA techniques, and HLA class II typing was performed using polymerase chain reaction. RESULTS: We found a statistically significant difference between MS patients and controls in the rod-cone b-wave implicit time (p < 0.005). We found autoantibodies against alpha-enolase in 38% of MS patients and 11% of controls (p < 0.02). There was no statistically significant difference between ERG parameters of MS patients with alpha-enolase autoantibodies compared to those without alpha-enolase antibodies. Furthermore, the presence of alpha-enolase did not associate with a particular HLA haplotype. CONCLUSIONS: Factors affecting the retina other than alpha-enolase antibodies may account for the delayed rod-cone b-wave implicit times observed in MS patients in this study. Anti-enolase antibodies are likely an epiphenomenon of autoimmune disease, and are not causing retinopathy in MS patients with normal visual acuity. However, the possibility of rare cases of patients with pathogenic alpha-enolase autoantibodies can not be excluded. The pathogenic contribution of these antibodies in MS patients with visual impairment deserves further investigation.

Electroretinographic abnormalities in multiple sclerosis: possible role for retinal autoantibodies.

BACKGROUND: Multiple sclerosis (MS) has been associated with inflammation of the uveal tract, suggesting an immunological link between the uvea and central nervous system (CNS) in this disease. The retina is embryologically derived from the CNS, and it is conceivable that retinal antigens may also be recognized by the immune system in MS. Electroretinographic abnormalities, as well as retinal autoantibodies, have previously been described in MS. We performed this study to further explore the possibility of retinal autoimmunity in MS. METHODS: Thirty-four patients with clinically definite MS and thirty-seven healthy controls were recruited. All patients and controls had standard electroretinographic (ERG) testing done, as well as a brightflash ERG protocol to isolate rod photoreceptor function. Patient and control sera were analyzed for the presence of antiretinal antibodies using Western blot techniques. RESULTS: We found statistically significant differences between MS patients and controls in four ERG parameters. In the MS group, implicit times of the rod-cone b-wave response, cone b-wave response, and rod photoreceptor response were increased. The amplitudes of the photopic oscillatory potentials were reduced in the MS group. Patients with the highest titres of retinal autoantibodies had delayed rod-cone b-wave implicit times and diminished photopic oscillatory potential amplitudes. CONCLUSIONS: We report ERG evidence of retinal dysfunction in patients with MS. We also report the first use of the brightflash ERG protocol in MS, which demonstrated rod photoreceptor dysfunction. Patients with the highest antiretinal antibody titres had abnormal ERG recordings. Retinal autoimmunity is a possible explanation for these observed ERG abnormalities in MS patients.

Utility of the National Eye Institute VFQ-25 questionnaire in a heterogeneous group of multiple sclerosis patients.

PURPOSE: To investigate the utility of the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25) in assessing visual function in a heterogeneous group of multiple sclerosis (MS) patients and to identify correlations of VFQ-25 scores with clinically relevant objective visual parameters. DESIGN: Comparative cohort study. METHODS: The VFQ-25 was distributed to 34 patients with clinically definite MS. Patients underwent a comprehensive ophthalmic examination, including Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (V(A)), Pelli-Robson contrast sensitivity (CS), Humphrey visual field 30 to 2 (HVF), and Farnsworth-Munsell 100-Hue color vision (100-Hue). Expanded Disability Status Scores (EDSS) were recorded for each patient. Comparative analyses using chi2 tests and t tests were performed. Spearman rank correlation coefficients were computed to identify relationships between VFQ-25 scores and the aforementioned visual parameters. RESULTS: In comparison with a published reference group without ocular disease, MS patients had considerably worse VFQ-25 composite scores (P < .01), being similar to published cohorts of glaucoma and cataract patients. VFQ-25 composite scores were found to be modestly and significantly correlated with several clinical parameters, including: V(A) (r = -0.63, P < .001), CS (r = 0.60, P < .001), HVF (r = 0.53, P = .003), and 100-Hue (r = -0.48, P = .01). EDSS scores, the use of disease modifying agents, and having a history of previous optic neuritis did not correlate significantly with VFQ-25 composite scores. CONCLUSIONS: The VFQ-25 questionnaire is a sensitive and useful tool in assessing visual function in MS patients. Such patients have quality of life indices similar to glaucoma and cataract patients, underscoring the significance of visual symptoms in MS.