Sarcoidosis of the central nervous system: Safety and efficacy of treatment, and experience of biological therapies.

OBJECTIVES: Neurological complications of sarcoidosis are uncommon and the natural history and optimal treatments under-researched. With the advent of biological therapies, it is important to define the clinical characteristics and immunopathology of the disease. PATIENTS AND METHODS: Patients referred to and treated within the Centre for Neurosarcoidosis over a 15 year period who had biopsy proven "highly probable" disease of the central nervous system were studied prospectively. RESULTS: Corticosteroids were used effectively in all patients, immunosuppression in 79 % and TNFα antagonists in 23 %. Treatment with steroids alone inevitably led to relapse, and low dose immunosuppression was ineffective in those with severe forms of the disease. Use of biological therapies substantially improved outcome. Patients with cranial neuropathy had an excellent outcome. Those with pachymeningitis had marked radiological abnormalities but less disablement. Those with leptomeningitis had an invasive, destructive disease which responded well to treatment but with residual neurological impairments. Treatment was required for many years, but the risk of relapse following treatment withdrawal was low. Infective complications arose in six. There were two deaths, neither directly related to the neurological disease, nor its treatment. CONCLUSIONS: This prospective study of the natural history and treatment response in neurosarcoidosis provides evidence that the use of high dose immunosuppression and early and prolonged use of biological therapies is associated with greatly improved outcomes and lower mortality. The data may be used to plan further studies and treatment trials, and provide class IV evidence for the effectiveness of biological agents in the treatment of Neurosarcoidosis.

Dyslipidemia, Dyslipidemia Treatment, and Open-angle Glaucoma in the Korean National Health and Nutrition Examination Survey.

PURPOSE: The purpose of this study was to investigate the association between dyslipidemia treatment and open-angle glaucoma (OAG). PATIENTS AND METHODS: We included 16,939 participants aged ≥40 years from the Korea National Health and Nutrition Examination Survey (2008 to 2012) and classified them into 2 groups based on current dyslipidemia treatment. The prevalence of OAG was determined using the modified International Society of Geographical and Epidemiological Ophthalmology criteria. The association between dyslipidemia treatment and OAG was evaluated using logistic mixed-effects model and propensity-score-weighted odds ratios. RESULTS: Analyses using the 2 abovementioned models revealed that dyslipidemia treatment was not associated with OAG (odds ratio, 1.08; 95% confidence interval, 0.75-1.56; P=0.838 and 1.03; 0.71-1.48; P=0.882, respectively), presence of optic disc hemorrhage (0.64; 0.15-2.73; P=0.648 and 1.10; 0.39-3.11; P=0.855), high vertical cup-to-disc ratio or asymmetry (1.02; 0.81-1.28; P=0.736 and 0.95; 0.75-1.20; P=0.650), presence of retinal nerve fiber layer defects (0.97; 0.67-1.42; P=0.857 and 1.03; 0.75-1.42; P=0.857), and presence of visual field defects (0.93; 0.55-1.54; P=0.931 and 0.97; 0.81-1.52; P=0.528). Total cholesterol and high-density lipoprotein cholesterol were also not associated with OAG. However, higher serum triglyceride levels were associated with OAG in the treated patients (1.31; 1.02-1.68; P=0.027) but not in the untreated patients (1.03; 0.93-1.14; P=0.079). CONCLUSIONS: In the Korean population, dyslipidemia treatment was not significantly associated with open-angle glaucoma. However, hypertriglyceridemia was associated with OAG in treated patients.

[OCT topographic characteristics of the optic nerve in patients clinically suspected to have large optic disc cupping in Togo]. / Les caractéristiques topographiques à l'OCT du disque optique chez des patients cliniquement suspects de grande excavation papillaire (GEP) au Togo.

PURPOSE: To describe topographic characteristics of optic discs clinically suspected of large cupping. MATERIALS AND METHODS: This is retrospective study conducted from the January 2 to December 31 on the OCT registry and data base of a private ophthalmologic center in Lomé (Togo). We included records of patients with large cupping - CDR (cup-to-disc ratio) ≥ 0.4 -clinically observed and having undergone OCT-optic disc analysis. RESULTS: Three hundred and thirty-five patients (619 eyes) were studied, with a mean age of 41.87 years±17.51 years [6 years and 80 years] and a sex-ratio of 1.01 with a slight female predominance. The mean clinical CDR was 0.51±0.126 [0.4 and 0.9] (95 % CI [0.503 to 0.531]). The clinical CDR was ≥ 0.7 in 7.75 % of cases. The mean neuroretinal rim area was 1.63±0.43 mm2 [0.34 and 2.85 mm2]. The mean cup area was 1.43±0.54 mm2 [0.13 and 4.29 mm2], and the mean cup volume 0.47±0.28 mm3 [0.01 and 1.72 mm3]. The mean global CDR on OCT was 0.46±0.13 [0.21 and 0.87], of which 30.85 % (191 cases) had CDR <0.4. The CDR on OCT was >0.7 in 40 (6.46 %) eyes vs. 48 (7.75 %) eyes on clinical examination. CONCLUSION: On the average, optics discs exhibit large size and large cup volume. Topographic evaluation of the optic disc by the means of OCT offers important data and gives way to etiological research of large cupping in the black African.

Neuropatía óptica hereditaria de Leber: ¿de qué perspectivas terapéuticas disponemos? / Leber hereditary optic neuropathy: what are the therapeutic perspectives?

No disponible

Amiodarone-Associated Optic Neuropathy: A Nationwide Study.

PURPOSE: To investigate whether amiodarone use is associated with an increased risk of optic neuropathy. DESIGN: Retrospective population-based cohort study. PARTICIPANTS: Patients newly treated with amiodarone between 2005 and 2009 were identified from the Taiwan National Health Insurance Research Database. For each case patient, the study also included 4 age- and gender-matched control subjects who did not receive amiodarone treatment. METHODS: Cox multivariate regression analysis was used to assess the association between amiodarone and the occurrence of optic neuropathy. MAIN OUTCOME MEASURES: Hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The analysis included 6175 amiodarone-treated patients and 24 700 controls. The mean age was 66.7 years and 55.3% of subjects were male. The mean follow-up was 688 days. During the observational period, optic neuropathy developed in 17 amiodarone-treated patients (0.3%) and 30 control patients (0.1%; P = 0.006). Multivariate Cox regression analysis showed that amiodarone-treated patients had a 2-fold increased risk of optic neuropathy (HR, 2.09; 95% CI, 1.13-3.85; P = 0.02). After stratification by gender, amiodarone use remained a significant factor for optic neuropathy development among male subjects (HR, 3.05; 95% CI, 1.42-6.55; P = 0.004), but not among female subjects (HR, 1.15; 95% CI, 0.38-3.47; P = 0.81). Among amiodarone-treated patients, male gender was associated with a nearly 3-fold increased risk of optic neuropathy development compared with female gender (HR, 2.91; 95% CI, 0.94-9.01; P = 0.06). We also detected a trend of increased cumulative incidence of optic neuropathy with longer treatment duration (>41 vs. ≤41 days; HR, 3.46; 95% CI, 0.99-12.07; P = 0.05). However, higher daily dose did not increase the risk of optic neuropathy (HR, 0.96; 95% CI, 0.91-1.00; P = 0.07). CONCLUSIONS: These results demonstrated a higher risk of optic neuropathy in patients treated with amiodarone, especially in males and possibly in patients with longer duration of treatment.

Advanced glaucoma: management pearls.

A significant proportion of glaucoma patients present late, particularly in the developing world, and unfortunately, in an advanced stage of the disease. They are at imminent danger of losing remaining vision, and may also be afflicted with various socioeconomic and health challenges. The encounter with such a patient is typically characterized by anxiety/fear and sometimes hopelessness from the patient's perspective. The physician may also feel that they are in a difficult position managing the patient's disease. When dealing with such cases, we suggest a holistic, individualized approach taking into account the 'biopsychosociospiritual' (BPSS) profile of each patient. The BPSS model takes into account relevant ocular as well as systemic biology (factors such as the mechanism of glaucoma, level of intraocular pressure [IOP], rate of progression, life expectancy, general health), psychological considerations (e.g., fear, depression), socio-economic factors and spiritual/cultural values and beliefs before being able to decide with the patient and their care partner(s) what treatment goals should be and how they can best be approached. Treatment for advanced glaucoma can be highly effective, and patients and their care partners should be informed that aggressive IOP lowering to the low teens or even single digits offers the best chance of protecting remaining vision. This can be achieved safely and effectively in most cases with trabeculectomy (including an antimetabolite), and in some cases with medical and/or laser therapy. Vision rehabilitation and psychosocial support should also be considered in order to optimize remaining vision, replace fear with hope as appropriate, and thus improve the overall quality of life.

Optic neuropathy among a prison population in Papua New Guinea.

PURPOSE: To estimate the prevalence of optic neuropathy (ON) among prisoners in a provincial prison in Papua New Guinea, and to explore risk factors for this condition among this population. METHODS: Cross-sectional observation study of 148 male prisoners aged ≥18 years using an interview-based questionnaire, assessment of visual and nervous system function, ocular examination, and blood analysis (α-tocopherol, ß-carotene, lutein, folate, homocysteine, holotranscobalamin II, riboflavin, selenium, thiamin, and vitamins A, B(12) and C). Likelihood of the presence of ON was based on ordered groups determined by weighted combination of optic nerve head appearance and visual dysfunction (acuity, field, color perception). Main outcome measures were prevalence and associations of ON. RESULTS: Sample prevalence of clinical ON was 10.4% (95% confidence interval [CI], 6.2-16.8). No cases were found of unexplained non-visual nervous system dysfunction, including peripheral neuropathy. Increasing age (p = 0.001), length of current (p = 0.002) and lifetime (p = 0.03) incarceration, and duration of smoking by current smokers (p = 0.001) were associated with increased ON likelihood. However, when age-controlled, the smoking duration association was not maintained (p = 0.6). Prisoners were folate deficient. Adjusting for age and duration of current incarceration, whole blood (p = 0.02) and red blood cell (p = 0.04) folate concentrations were inversely associated with ON likelihood. No association was found for any other assessed demographic, lifestyle or biochemical measure. CONCLUSIONS: A cluster of ON associated with folate deficiency has been identified. Recommendations for dietary change and micronutrient supplementation have been made.

Age-related macular degeneration and optic disk cupping: the Beaver Dam Eye Study.

PURPOSE: To examine the association between presence, severity, and extent of lesions of age-related macular degeneration (AMD) and optic disk and cup diameters in a general population. DESIGN: Cross-sectional study. METHODS: setting: Population-based. study population: Adults aged 43 to 86 years participating in the Beaver Dam Eye Study. observation procedures: Fundus photographs were graded for lesions of AMD using standard protocols. The photographs were obtained during the baseline examination of the Beaver Dam Eye Study. main outcome measure: Optic disk cupping as related to presence, severity, and extent of lesions of AMD. RESULTS: There were no significant differences in the vertical optic disk and cup measurements or in the vertical cup to disk ratios by severity of lesions of AMD (P values all greater than .10). In those eyes with late lesions of AMD, there was no association of the size of the lesions or their distribution in the fundus and the extent of cupping. CONCLUSIONS: From a population perspective, there is no relationship of the presence or severity of AMD and optic disk cupping.

Superior segmental optic hypoplasia found in Tajimi Eye Health Care Project participants.

PURPOSE: To investigate the prevalence and characteristics of superior segmental optic hypoplasia in Japanese. METHODS: We studied 14 779 subjects, aged 40 years or older, who underwent IMAGEnet fundus photography as part of a large-scale eye disease screening project conducted in Tajimi, Japan. A single researcher reviewed all of the photographs for the presence of ocular abnormality in the optic nerve head and retina, paying special attention to the presence of superior segmental optic hypoplasia. RESULTS: Fundus photographs of 14 431 cases (28,396 eyes) were successfully reviewed. We found superior segmental optic hypoplasia in 37 cases (54 eyes; 0.3% of the cases and 0.2% of the eyes). Of the 37 cases, 23 (62%) showed the corresponding visual field defect in at least one eye. CONCLUSION: The prevalence of superior segmental optic hypoplasia is about 0.3% in the Japanese population.

Vitamin B intake and status in healthy Havanan men, 2 years after the Cuban neuropathy epidemic.

A prospective epidemiological study was carried out over 1 year to evaluate vitamin B complex dietary intake and status in Cuba, 2 years after the Cuban neuropathy epidemic of 1993. Of the 199 healthy middle-aged men selected, 141 completed the study. Volunteers were followed up every 3 months for 1 year. Dietary intake and status of thiamin, riboflavin, vitamin B6, folate and vitamin B12 were assessed each time. The dietary intake of vitamin B complex was low, particularly in June and July (folate), and October (thiamin). A deficient status was observed for vitamin B complex, except for vitamin B6. Vitamin B complex intake and status varied over the year. However, dietary intake and status were poorly related. The results prove that healthy Cuban men represent a vulnerable population in terms of vitamin B complex status and stress the necessity to both promote preventive multivitamin supplementation and produce local food rich in vitamin B complex.

Frequency of sustained glaucomatous-type visual field loss and associated optic nerve cupping in Beaver Dam, Wisconsin.

PURPOSE: To determine the prevalence of persisting glaucomatous-type visual field loss in a Midwestern American adult population, in association with four grades of disc cupping. METHODS: On two separate occasions (1988-1990 and 1993-1995) 2955 predominantly Caucasian adults aged 43-84 provided medical history, underwent applanation tonometry, slit-lamp examination, quantitative suprathreshold perimetry and stereoscopic disc analysis as part of the National Institutes of Health-sponsored Beaver Dam Eye Study. Those demonstrating evidence of glaucomatous-type visual field loss at both visits were the subject of the present analysis. Among these individuals, associations were determined for four categories of optic disc cupping (vertical cup/disc < 0.5, > 0.5, > 0.6, > 0.8), intraocular pressure, blood pressure, cardiovascular pathology and prior glaucoma diagnosis. RESULTS: Of the 2955 subjects assessed, 120 (4%; 57 women, 63 men) demonstrated glaucomatous-type visual field defects at each visit. Fifty-five of these 120 (2% of the tested population) also exhibited some degree of disc cupping in a related eye at both visits. Among these 2%, positive associations relating the extent of field loss, cupping and intraocular pressure were confirmed, but the majority in each cupping category had normal eye pressures. Only seven of the 120 were aware of the presence or suspicion of eye disease prior to the screening. CONCLUSIONS: A majority of those found to have visual field loss and optic nerve cupping persisting together in the same eye after 3-5 years had normal pressures in each eye at both visits. Despite good access to medical care, very few who demonstrated persisting cupping and field loss (even among those with elevated eye pressure) were aware of their ocular condition through prior contact with an eye care professional.

Biochemical evidence of thiamine depletion during the Cuban neuropathy epidemic, 1992-1993.

During an epidemic outbreak of neuropathy in Cuba during 1992-1993, blood and urine samples were collected from 107 persons with confirmed neuropathy, from 106 control subjects without clinical abnormality who were broadly matched with the affected persons by age and domicile, and from 537 unmatched subjects, also free from clinical abnormality. The unmatched subjects lived in two locations in Cuba; at each location they were drawn from two age ranges: 11-15-y-old secondary school students and 16-64-y-old adults. Measurements of urinary thiamine and blood transketolase and its activation with thiamine pyrophosphate were made. For the neuropathy subjects, these measurements were repeated after 3 wk of rehabilitation. All groups showed biochemical evidence of thiamine depletion affecting 30-70% of their members, which is a high prevalence. Severity of biochemical depletion was, however, no greater in the neuropathy subjects than in the control subjects (P > 0.05). However, it was greater in Pinar del Rio, where the incidence of disease was higher, than in the city of Havana, where less disease was seen. Although the majority of the affected subjects responded biochemically to a daily oral multivitamin supplement containing thiamine (P < 0.001), in some cases normal biochemical status was not achieved even after 3 wk of intensive treatment. In the affected group, thiamine status was inversely correlated with the amount of alcohol consumed (P = 0.007). Thiamine status at the outset was correlated with clinical outcome after treatment. Although neither thiamine depletion nor alcohol abuse were likely to have been the sole cause of the neuropathy epidemic, they may have been contributory factors. Thiamine supplementation or food fortification may therefore be necessary in Cuba.

Epidemic optic neuropathy in Cuba--clinical characterization and risk factors.

BACKGROUND: From 1991 to 1993, epidemic optic and peripheral neuropathy affected more than 50,000 people in Cuba. The number of new cases decreased after the initiation of vitamin supplementation in the population. In September 1993, Cuban and U.S. investigators conducted a study to characterize and identify risk factors for the optic form of the syndrome. METHODS: We conducted ophthalmologic and neurologic examinations, assessed exposure to potential toxins, administered a semiquantitative food-frequency questionnaire, and assessed serum measures of nutritional status in 123 patients with severe optic neuropathy, matched for sex and age to randomly chosen normal subjects. RESULTS: In the case patients, prominent clinical features were subacute loss of visual acuity with field defects, diminished color vision, optic-nerve pallor, and decreased sensitivity to vibration and temperature in the legs. Tobacco use, particularly cigar smoking, was associated with an increased risk of optic neuropathy. The risk was reduced among subjects with higher dietary intakes of methionine, vitamin B12, riboflavin, and niacin and higher serum concentrations of antioxidant carotenoids. The risk was also reduced among subjects who raised chickens at home or had relatives living overseas--factors that may be indirect measures of increased food availability. CONCLUSIONS: The epidemic of optic and peripheral neuropathy in Cuba between 1991 and 1993 appears to be linked to reduced nutrient intake caused by the country's deteriorating economic situation and the high prevalence of tobacco use.

An epidemic in Cuba of optic neuropathy, sensorineural deafness, peripheral sensory neuropathy and dorsolateral myeloneuropathy.

An epidemic outbreak of peripheral neuropathy affected Cuba in 1992-93 resulting in 50,862 cases (national cumulative incidence rate (CIR) 461.4 per 100,000). Clinical forms included retrobulbar optic neuropathy, sensory and dysautonomic peripheral neuropathy, dorsolateral myeloneuropathy, sensorineural deafness, dysphonia and dysphagia, spastic paraparesis, and mixed forms. For epidemiological purposes, cases were classified as optic forms (CIR 242.39) or peripheral forms (CIR 219.25). Increased risk was found among smokers (odds ratio (OR) 4.9), those with history of missing meals (OR 4.7) resulting in lower intake of animal protein, fat, and foods that contain B-vitamins, combined drinking and smoking (OR 3.5), weight loss (OR 2.8), excessive sugar consumption (OR 2.7) and heavy drinking (OR 2.3). Optic neuropathy was characterized by decreased vision, bilateral and symmetric central or cecocentral scotomata, and loss of color vision due to selective lesion of the maculopapillary bundles. Peripheral neuropathy was a distal axonopathy lesion affecting predominantly large myelinated axons. Deafness produced selective high frequency (4-8 kHz) hearing loss. Myelopathy lesions combined dorsal column deficits and pyramidal involvement of lower limbs with spastic bladder. Clinical features were those of Strachan syndrome and beriberi. Intensive search for neurotoxic agents, in particular organophosphorus esters, chronic cyanide, and trichloroethylene intoxication, yielded negative results. Treatment of patients with B-group vitamins and folate produced rewarding results. Most patients improved significantly and less than 0.1% of them remained with sequelae; there were no fatal cases. Supplementation of multivitamins to the entire Cuban population resulted in curbing of the epidemic. Overt malnutrition was not present, but a deficit of micronutrients, in particular thiamine, cobalamine, folate and sulfur amino acids appears to have been a primary determinant of this epidemic.

Food shortages and an epidemic of optic and peripheral neuropathy in Cuba.

From late 1991 to mid-1993, cases of optic neuropathy of unknown etiology, which first appeared in unusual numbers in a western province of Cuba, spread and multiplied throughout the island. The dominant symptoms changed, becoming increasingly those of peripheral neuropathy. Incidence rates peaked in April 1993. An estimated 50,000 cases were reported. The majority were adult men and women (aged about 25-65), with comparatively few children or elderly people being affected. The cause has yet to be delineated. However, food shortages and radical changes in diet resulting from the longstanding US trade embargo and the recent loss of Eastern Europe as Cuba's trading partner have compromised nutritional status, especially B-vitamin sufficiency, and appear to be related to the neuropathic illnesses. In April 1993, the Cuban government began distributing vitamin supplements to every citizen. Causal hypotheses include tobacco-alcohol or "nutritional" amblyopia; cyanide toxicity from cassava; toxic legumes introduced as supplements to scarce flour; other toxins, for example pesticides, or a "blue mold" on tobacco; enterovirus; and a hereditary enzyme deficiency in affected persons. None of these factors appears to be present in all cases, but it is generally believed that an interaction of some toxin or toxins, in combination with nutritional deficiency, is likely to be the major cause.