Tanzanian Endemic Optic Neuropathy

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Tanzanian endemic optic neuropathy is a disorder of unknown etiology that first appeared in Dar es Salaam, Tanzania in 1991 [8]. This disease primarily affects people ages 10-39 [5]. The typical presentation includes irreversible bilateral loss of visual acuity and color vision, sensorineural hearing loss, and peripheral neuropathy [7, 8].

Disease Entity

Disease Epidemiology

Age of onset is typically between ages 10-39, with a median age of 20 [5]. The disease prevalence is estimated to be between 0.3 and 2.4% of young adults in Dar es Salaam. There has been no significant sex predilection identified [7].

The disease is isolated to the coastal towns of Tanzania, with only one case reported inland. There is no significant clustering by place of occupation or school [10].

Etiology

To date, no specific cause has been identified. However, B-vitamin deficiency was found to be widespread in Dar es Salaam in both those affected by optic neuropathy and the control population [4]. This mirrors the widespread B-vitamin deficiency in the Cuban epidemic of optic neuropathy, a disease with near identical presentation save a significantly older age distribution. Interestingly, efforts by the Cuban Ministry of Public Health to instigate population-wide vitamin B supplementation were able to curb the epidemic in 1993 [3]. The presence of widespread B-vitamin deficiency in both the Tanzanian and Cuban optic neuropathy epidemics suggests a multifactorial disease process in a nutrient deficient population [1, 4, 5].

Risk Factors

Specific risk factors that have been identified include low folate consumption, increased indoor pollution exposure, higher levels of heavy metals (manganese, cobalt, and tin) found in toenails, and lower socioeconomic status. However, no causal relationships have been established to date [2, 6, 8].

Although cassava consumption was a significant risk factor for the Cuban epidemic [3], no evidence of cyanide poisoning was found in those afflicted by Tanzanian endemic optic neuropathy. Mitochondrial DNA analysis did not find any of the common mutations (G11778A, G3460A, T14484C) associated with Leber Hereditary Optic Neuropathy [9].

Pathophysiology

As the causative mechanism has yet to be discovered, the pathophysiologic mechanism by which Tanzanian endemic optic neuropathy develops is unknown.

Diagnosis

While there is no consensus for the diagnostic criteria, most studies define the disease by the presence of progressive, symmetric, bilateral vision loss with central or cecocentral scotomas and impaired color vision. Other neurological findings such as sensorineural hearing loss and sensory neuropathy are common but not necessary for diagnosis [10].

History

Although Tanzanian endemic optic neuropathy is a regionally defined disorder, a detailed history is important to elucidate possibly significant exposures and to rule out other possible causes of vision loss in this population.

  • Pertinent occupational or environmental toxin exposures
  • Diet/cassava consumption
  • Cooking and use of charcoal/firewood indoors
  • Smoking history
  • Alcohol abuse
  • Previous cancer diagnosis
  • Previous demyelinating disease
  • Sexual history
  • Family history of hereditary optic neuropathies

Physical examination

  • Snellen visual acuity: Visual impairment is present bilaterally, with a corrected Snellen visual acuity of 6/9 or worse. The interocular difference in visual acuity is typically two lines on a Snellen chart or less.
  • Ishihara pseudoisochromatic plates: Reduced color vision is present, with only one unseen plate being required for diagnosis [7].
  • Amsler grid to assess for macular degeneration or central visual field scotoma
  • Humphrey visual field testing to rule out peripheral retinal disease
  • Swinging flashlight to assess for monocular vs. bilateral optic lesion

Ocular Findings

Slit lamp and dilated fundus examination can be used to rule out anterior segment pathology or abnormalities typical of other known diseases, such as glaucoma [7].

Fundoscopic findings of Tanzanian endemic optic neuropathy can include bilateral optic disc pallor with symmetric temporal optic atrophy [7, 10].

Symptoms

  • Typical ophthalmologic symptoms include [4, 10]:
    • Simultaneous, bilateral, and painless vision loss
    • Central or centrocecal scotomas
    • Progresses of ocular symptoms over the course of 2-12 weeks
    • Reduced color vision
  • Less commonly identified ophthalmologic symptoms include [4, 10]:
    • Pain with eye movement
    • Photophobia
    • Continued progression of vision loss up to 6 months post onset
  • Common non-ophthalmologic symptoms include [8, 10]:
    • Sensorineural hearing loss, present in approximately 50% of cases studied
    • Painful sensory neuropathy
  • Rare cases included [1, 10]:
    • Gait ataxia
    • Weight loss
    • Stomatitis

Diagnostic Procedures

Optical coherence tomography typically displays retinal nerve fiber layer (RNFL) loss, with the majority of cases graded as severe RNFL loss and over 90% of imaged individuals having concordance in the severity grading bilaterally. The RNFL loss is localized to the papillomacular bundle, or cecocentral projection, and spares other regions [7].

A minority of cases also have microcystic macular changes on macular FastMap imaging, more prominently in the nasal macula [7].

Laboratory test & Imaging

Laboratory testing can be used to exclude other known causes of optic neuropathy. This testing may include serum folate, vitamin B12, RPR, serum thiocyanate levels, HIV antibodies, HTLV-1 antibodies, and mitochondrial DNA analysis [8, 10].

MRI imaging may be indicated in cases of isolated bilateral optic neuropathy to rule out demyelinating diseases.

Differential diagnosis

  • B-vitamin deficiency
  • Congenital optic neuropathies
  • Drug/toxin exposure
  • Infectious etiology
  • Demyelinating diseases
  • Vascular diseases

Management & Outcomes

Management of Tanzanian endemic optic neuropathy is generally supportive with poor outcomes[8]. Vitamin supplementation has shown some success in treatment of acute cases but needs to be administered early in the disease course to be effective[4].

References

1. Bourne, R. R., Dolin, P. J., Mtanda, A. T., Plant, G. T., & Mohamed, A. A. (1998). Epidemic optic neuropathy in primary school children in Dar es Salaam, Tanzania. British Journal of Ophthalmology, 82(3), 232–234. https://doi.org/10.1136/bjo.82.3.232

2. Bowman, R. J. C., Wedner, S., Bowman, R. F., Masanja, H., Bunce, C., Wood, M. L., & Gilbert, C. (2010). Optic neuropathy endemic in secondary school children in Dar es Salaam, Tanzania. British Journal of Ophthalmology, 94(2), 146–149. https://doi.org/10.1136/bjo.2009.160713

3. Cuba Neuropathy Field Investigation Team. (1995). Epidemic optic neuropathy in Cuba—Clinical characterization and risk factors. The New England Journal of Medicine, 333(18), 1176–1182. https://doi.org/10.1056/NEJM199511023331803

4. Dalmar, A. A., Hodson, K. E., & Plant, G. T. (2011). Epidemic Optic Neuropathy Is Evident in the Somalian Population. Journal of Neuro-Ophthalmology, 31(2), 127–130. https://doi.org/10.1097/WNO.0b013e31820d1604

5. Dolin, P. J., Mohamed, A. A., & Plant, G. T. (1998). Epidemic of Bilateral Optic Neuropathy in Dar es Salaam, Tanzania. New England Journal of Medicine, 338(21), 1547–1548. https://doi.org/10.1056/NEJM199805213382115

6. Hodson, K. E., Bowman, R. J., Mafwiri, M., Wood, M., Mhoro, V., & Cox, S. E. (2011). Low folate status and indoor pollution are risk factors for endemic optic neuropathy in Tanzania. The British Journal of Ophthalmology, 95(10), 1361–1364. https://doi.org/10.1136/bjo.2010.197608

7. Kisimbi, J., Shalchi, Z., Mahroo, O. A., Mhina, C., Sanyiwa, A. J., Mabey, D., Mohamed, M., & Plant, G. T. (2013). Macular spectral domain optical coherence tomography findings in Tanzanian endemic optic neuropathy. Brain, 136(11), 3418–3426. https://doi.org/10.1093/brain/awt221

8. Massawe, E. R., Moshi, N., Ren, J., Rieke, C. C., Magohe, A. K., Fellows, A. M., Arega, E. A., Niemczak, C. E., Jackson, B. P., Karagas, M. R., & Buckey, J. C. (2021). Unexplained multi-sensory neuropathy syndrome in young Tanzanian adults. Journal of Global Health Reports, 5, e2021013. https://doi.org/10.29392/001c.21360

9. Plant, G. T., Dolin, P., Mohamed, A. A., & Mlingi, N. (1997). Confirmation that neither cyanide intoxication nor mutations commonly associated with Leber’s Hereditary Optic Neuropathy are implicated in Tanzanian Epidemic Optic Neuropathy. Journal of the Neurological Sciences, 152(1), 107–108. https://doi.org/10.1016/S0022-510X(97)00132-9

10. Plant, G. T., Mtanda, A. T., Arden, G. B., & Johnson, G. J. (1997). An epidemic of optic neuropathy in Tanzania: Characterization of the visual disorder and associated peripheral neuropathy. Journal of the Neurological Sciences, 145(2), 127–140. https://doi.org/10.1016/S0022-510X(96)00162-1

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