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Show Low Prevalence of Bilateral (Presumed Nutritional) Optic Neuropathy as a Cause of Blindness in The Gambia Abdirisak A. Dalmar, MD, PhD, Katherine E. Hodson, MSc, Gordon T. Plant, MD, FRCP, FRCOphth Objective: Previous reports of epidemics of optic neuropa-thy in Africa have mainly focused on eastern and central areas. Our study aimed to measure the prevalence of optic neuropathy in The Gambia, a West African country, and compare this prevalence with a simultaneously occurring epidemic of optic neuropathy, now considered endemic, in Tanzania. Methods: The sample population, derived from the Gam-bian National Blindness Survey (1996), was selected using simple random sampling. Thirty-three cases of low vision/ blindness were identified where optic neuropathy was the sole cause of visual loss. Within a month, 31 cases were located and these patients underwent ophthalmic and peripheral nerve assessment and completed lifestyle ques-tionnaires. Results: Five of the 31 individuals were found to have bilateral symmetrical optic neuropathy. Although it was not possible to fully ascertain etiology, the phenotype is compatible with epidemic, presumed nutritional, optic neuropathy described in Tanzania. Comparative prevalence data suggest a prevalence of 0.07% in The Gambia based on a total sample size of 6873 vs 2.4% in Tanzania. Conclusion: Our data indicate that bilateral optic neuropa-thy is nonepidemic in The Gambia. Rare vitamin B12 and folate deficiencies reported in rural Gambians may explain the low prevalence because previous epidemics were due to nutrient deficiency. Our study is the only available estimate of epidemic optic neuropathy in The Gambia and, as such, provides an important contribution to our knowledge in iden-tifying characteristics that may cause specific populations to be more susceptible to this public health burden. Journal of Neuro-Ophthalmology 2013;33:256-259 doi: 10.1097/WNO.0b013e31829b4240 © 2013 by North American Neuro-Ophthalmology Society Strachan (1) was among the first to extensively record an optic neuropathy epidemic in the West Indies toward the end of the 19th century. Hundreds of patients were documented with dimness of vision and painful "burning" sensations of the lower limbs, a clinical entity that was later named Strachan syndrome and linked to nutritional defi-ciency in prisoners of war during World War II (2). In Africa, over the past 80 years, there are reports of outbreaks of Tropical Ataxic Neuropathy (TAN) in Nigeria (3), and a form of acute paralysis known as "Konzo" in Democratic Republic of Congo (formerly Zaire) (4), Mozambique (5), and Tanzania (6). First reported in 1988, the most recent epidemic, also occurred in Tanzania, appeared to be endemic within the secondary school population of Dar es Salaam (7). Patients presented with bilateral, simultaneous, usually painless, visual loss over 2-12 weeks and were found to have impaired color vision, central or cecocentral scotomas, and, in many cases, peripheral neuropathy (8-10). This epi-demic was distinct from TAN and Konzo but resembled Cuban Epidemic Optic Neuropathy (11). Low levels of die-tary B-vitamin were thought to be responsible for the Cuban epidemic, and widespread B-vitamin supplementation largely resolved the outbreak (11). Likewise, a similar etiology is suspected in Tanzania. Preliminary biochemical analyses indi-cate B-vitamin deficiencies, although a similar deficiency was seen in healthy controls (A.A. Dalmar, MD, PhD, personal communication, 2012). Therefore, a multifactorial etiology has been proposed, including nutritional, genetic, and envi-ronmental factors. Such a hypothesis is supported by the most recent data from Tanzania, in which folate status and indoor smoke pollution were identified as risk factors (12). Interest in epidemic optic neuropathy, especially in Africa, has been largely reignited by these Tanzanian cases. A study has confirmed that the condition may also be at epidemic levels in Somalia (13). Previous reports in Africa have focused on eastern and central African countries, with little data from the western area of the continent. Our goal was to measure the prevalence National Hospital for Neurology and Neurosurgery, London, United Kingdom. Supported by Sight Savers International and the British Council for Prevention of Blindness. The authors report no conflicts of interest. Address correspondence to Gordon T. Plant, MD, FRCP, FRCOphth, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom; E-mail: gordon@plant. globalnet.co.uk 256 Dalmar et al: J Neuro-Ophthalmol 2013; 33: 256-259 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. of optic neuropathy in The Gambia as part of a 1996 national survey on the impact of a national eye care program on blindness and low vision prevalence. In addition, comparisons with a parallel prevalence study in the Tanza-nian epidemic were undertaken. METHODS The Gambia In 1996, the National Blindness Survey was conducted in The Gambia, a West African country. The sample population was selected using multistage random sampling. The country was stratified into 7 health regions, and districts from each region were randomly selected using proportional probability sampling (PPS). Settlements were selected from each district, also using PPS, with stratification by settlement size (small ,400 residents and large $400 residents). A compound-to-compound census was then undertaken to provide a current sampling frame for subsequent compound selection. All residents in a com-pound were examined, resulting in a sample size of 6873 individuals (14). A 2-part ophthalmic examination was carried out: Part 1: Visual acuity was measured in all subjects aged 5 years and older, and the anterior segment was examined with a focused light and ·2 loupe. All those who were 35 years and older, and any younger person with a visual acuity of G/18 (20/60) or less in either eye, were referred for detailed examination by an experienced ophthalmologist. Visual fields were screened (Henson CFA3000 visual field analyser; Henson Instruments, Redditch, UK), intraocular pressure was measured (Schiotz tonometer; Akriti, Hyderabad, India), and the optic disc was inspected. Thirty-three cases of low vision or blindness in which optic neuropathy was a sole cause of visual loss were identified during the initial study. Part 2: Within 1 month, investigators returned and invited each patient with optic neuropathy to a local clinic to undergo additional testing. 1. Visual acuity (Snellen chart) and color vision (Ishihara plates). 2. Visual fields (Henson field analyser) and tangent screen color fields using a red target (laser pointer). 3. Peripheral nerve function (knee and ankle jerk reflexes: temperature, pain, touch, and joint position sensation; movement coordination). 4. Hearing (whisper and Rinne test). 5. Standard ophthalmic examination. Tanzania A parallel prevalence survey in Tanzania was also conducted (15). Stratified systematic sampling was used to select a sam-ple of 1078 people, based on stratification of the 21 resi-dential areas of Dar es Salaam. The study was powered to obtain statistically significant confidence intervals, account-ing for study design and assumed prevalence rate. Clinical examination included assessment of visual acuity (Snellen chart), color vision (Ishihara plates), and fundus examina-tion using direct ophthalmoscopy. The Gambia and Tanzanian patients were asked about their clinical history and lifestyle. The case definition for bilateral optic neuropathy used in each study is identical to that used in previous studies: bilateral simultaneous visual loss over at least 3 days (the interocular differences in visual acuity being no greater than 2 lines on the Snellen chart) impaired color vision, bilateral central or cecocentral scotomas at onset, and temporal pallor of the optic discs (8). Data Handling Estimates of prevalence and 95% confidence interval were calculated using SPSS software (IBM Software, Portsmouth, UK), adjusting for excess sampling error (extrabinomial variation) arising from the study design. Ethics Ethical approval was provided by the Gambia Government/ Medical Research Council Joint Ethics Committee. RESULTS A high response rate was achieved. Thirty-one of 33 (93.9%) individuals initially identified as having optic neuropathy in the 1996 Gambia National Blindness Survey were traced and examined. From these, 5 cases were identified as bilateral (presumed nutritional) optic neuropathy. Of those presenting with bilateral optic neuropathy, the mean age was 42 (±7.5) years and 3 of the 5 cases were women. All patients displayed temporal pallor of the optic discs and some level of color vision impairment (unable to read at least 1 Ishihara plate). On ophthalmoscopy, abnormalities of the nerve fiber layer were detected in all cases, particularly involving the papil-lomacular bundle (Fig. 1). All individuals had been suffer-ing from optic neuropathy for over 2 years and some more than 2 years, at the time of the survey. None used alcohol, and 2 were current smokers. At time of symptom onset, 4 of the 5 patients admitted to cassava consumption ranging from daily to once per week consumption. No other die-tary factors or medicinal uses were identified. Table 1 sum-marizes the additional characteristics of the patients with optic neuropathy. All patients lived in rural areas of The Gambia, and 3 reported receiving previous treatment with eye drops, although it was not possible to determine the composition of the drops. No treatment involved vitamin supplements, and only 1 patient reported any improve-ment in symptoms. Based on the survey totaling 6873 persons, the overall prevalence of bilateral optic neuropathy in The Gambia was 0.07%. Dalmar et al: J Neuro-Ophthalmol 2013; 33: 256-259 257 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. DISCUSSION A clinical review of bilateral optic neuropathy cases from the 1996 National Blindness Survey in The Gambia identified 5 individuals likely to be suffering from the clinical entity seen in Tanzania termed "epidemic optic neuropathy." No lifestyle factors were common to the cases other than cassava consumption at the time of symptom onset in 4 of 5 cases. Given its widespread use in West Africa, cassava is unlikely to have been a specific risk factor for Gambian bilateral optic neuropathy. This would be consistent with findings from Tanzania (16), although the absence of a control group makes it difficult to draw definitive conclusions. The chronic nature of the cases also limits our knowledge of exposures at the time of optic neuropathy onset, and the long duration between the onset of disease clinical evalua-tion makes recall bias and lifestyle changes probable. In addition, the duration of bilateral optic neuropathy in our patients could not be accurately determined. We set out to provide prevalence data on Gambian bilateral optic neuropathy to assess any potential undetected burden on the country. Bilateral optic neuropathy in Dar es Salaam, Tanzania, was 34 times higher than in The Gambia in 1996 (Table 2). This indicates that the cases of bilateral optic neuropathy were nonepidemic in The Gambia. How-ever, there were limitations in our study. Although identical case definitions were used in comparing the populations of The Gambia and Tanzania, our ability to standardize meth-odologies was limited given that The Gambian study was conducted within a larger national survey. Yet, if any cases were excluded, this should have occurred synonymously in each study given that identical case criteria were used. Dif-ferences in the age distribution of the 2 populations may account for some of the difference in the prevalent rates. Also, while The Gambian survey was conducted on a coun-trywide level, the survey in Tanzania included only the city of Dar es Salaam. Finally, we did not exclude other poten-tial causes of bilateral optic neuropathy, such as Leber hereditary optic neuropathy and neuromyelitis optica. Our results provide for the first time a prevalence estimate of optic neuropathy in a coastal West African country. Data on B-vitamin status indicate rare deficiencies in vitamin B12 and folate in the rural Gambian population FIG. 1. Fundus photographs of presumed nutritional optic neuropathy. There is temporal pallor of the optic discs and thinning of the nerve fiber layer in the papillomacular bundle (arrows). TABLE 1. Characteristics of cases from The Gambia presenting with bilateral optic neuropathy Clinical Characteristic N Visual acuity* 6/24-3/60 4 ,3/60 1 Severely impaired color vision† 3 Abnormalities of retinal nerve fiber layer 5 Numbness/burning of lower limbs 3 Reported weight loss at symptom onset 2 Breast-feeding (of the 3 women) 2 Consuming meat at least once per week 3 Memory loss 0 *WHO classification: 6/9-6/18 (20/30-20/60), adequate vision; 6/24-3/60 (20/80-20/400), impaired vision; ,3/60 (,20/400), blind. †Able to read a maximum of 4 of 15 Ishihara plates. TABLE 2. Prevalence comparison of bilateral optic neuropathy in The Gambia and Tanzania Country n Prevalence (%) 95% CI The Gambia 6873 0.07 0.04-0.08 Tanzania (15) 1078 2.4 1.7-3.0 CI, confidence interval. 258 Dalmar et al: J Neuro-Ophthalmol 2013; 33: 256-259 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. at the time of the survey (17), which may, at least in part, explain the low prevalence of bilateral optic neuropathy, in The Gambia compared with Tanzania. (10,12,18,19). ACKNOWLEDGMENTS The authors acknowledge the support provided by the Gambian eye care program staff, their chairman Dr Hannah Faal, and all those involved in the original blindness survey. REFERENCES 1. Strachan H. On a form of multiple neuritis prevalent in the West Indies. Practitioner. 1897;59:477-484. 2. Fisher C. Residual neuropathological changes in Canadians held prisoners of war by the Japanese (Strachan's Disease). Can Serv Med J. 1955;11:157-199. 3. Osuntokun BO. Cassava diet, chronic cyanide intoxication and neuropathy in Nigerian Africans. World Rev Nutr Diet. 1981;36:141-173. 4. Carton H, Kazadi K, Kabeya O, Billiau A, Maertens K. Epidemic spastic paraparesis in Bandundu (Zaire). J Neurol Neurosurg Psychiatry. 1986;49:620-627. 5. Ministry of Health, Mozambique. Mantakassa: an epidemic of spastic paraparesis associated with chronic cyanide intoxication in a cassava staple area of Mozambique. Epidemiology and clinical laboratory findings in patients. Bull World Health Organ. 1984;62:477-484. 6. Howlett WP, Brubaker GR, Mlingi N, Rosling H. Konzo, an epidemic upper motor neuron disease studied in Tanzania. Brain. 1990;113(pt 1):223-235. 7. Bowman RW, Wedner S, Bowman RF, Masanja H, Bunce C, Wood ML, Gilbert C. Optic neuropathy endemic in secondary school children in Dar es Salaam, Tanzania. Br J Ophthalmol. 2010;94:146-149. 8. Plant GT, Mtanda AT, Arden GB, Johnson GJ. An epidemic of optic neuropathy in Tanzania: characterization of the visual disorder and associated peripheral neuropathy. J Neurol Sci. 1997;145:127-140. 9. Plant GT, Perry H. The anatomical basis of the caecocentral scotoma. New observations and a review. Brain. 1990;113:1441-1457. 10. Johnson GJ, Mtanda AT, Kinabo NN, Sangawe JLF, Masesa DE, Negral AD. Optic nerve and macular atrophy of unknown origin in Tanzania. Arch Public Health. 1993:51;561-571. 11. The Cuba Neuropathy Field Investigation Team. Epidemic optic neuropathy in Cuba-Clinical Characterization and Risk Factors. N Engl J Med. 1995;333:1176-1182. 12. Hodson KE, Bowman RJ, Mafwiri M, Wood M, Mhoro V, Cox SE. Low folate status and indoor pollution are risk factors for endemic optic neuropathy in Tanzania. Br J Ophthalmol. 2011;95:1361-1364. 13. Dalmaar AA, Hodson KE, Plant GT. Epidemic optic neuropathy is evidence in the Somalian population. J Neuroophthalmol. 2011;31:127-130. 14. Faal H, Minassian D, Dolin P, Mohamed A, Ajewole A, Johnson G. Evaluation of a national eye care programme: re-survey after 10 years. Br J Ophthalmol. 2000;84:948-951. 15. Dolin PJ, Mohamed AA, Plant GT. Epidemic of bilateral optic neuropathy in Dar es Salaam, Tanzania. N Engl J Med. 1998;338:1547-1548. 16. Plant GT, Dolin P, Mohamed AA, Mlingi N. Confirmation that neither cyanide intoxication nor mutations commonly associated with Leber's Hereditary optic neuropathy are implicated in Tanzanian epidemic optic Neuropathy. J Neurol Sci. 1997;152:107-108. 17. Moore SE, Azam Mansoor M, Bates CJ, Prentice AM. Plasma homocysteine, folate and vitamin B12 compared between rural Gambian and UK adults. Br J Nutr. 2006;96:508-515. 18. Macias-Matos C, Rodriguez-Ojea A, Chi N, Jimenez S, Zulueta D, Bates CJ. Biochemical evidence of thiamine depletion during the Cuban neuropathy epidemic, 1992-1993. Am J Clin Nutr. 1996;64:347-353. 19. Bourne RR, Dolin PJ, Mtanda AT, Plant GT, Mohamed AA. Epidemic optic neuropathy in primary school children in Dar es Salaam, Tanzania. Br J Ophthalmol. 1998;82:232-234. Dalmar et al: J Neuro-Ophthalmol 2013; 33: 256-259 259 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
