Tanzania Endemic Optic Neuropathy
Key Points at a Glance
Section titled “Key Points at a Glance”1. Tanzanian Endemic Optic Neuropathy
Section titled “1. Tanzanian Endemic Optic Neuropathy”Tanzanian Endemic Optic Neuropathy (TEON) is an endemic optic neuropathy of unknown cause first reported in Dar es Salaam, Tanzania, in 1991. It is characterized by bilateral irreversible vision loss, color vision abnormalities, sensorineural hearing loss, and peripheral neuropathy, primarily affecting young adults.
Age of onset is 10–39 years, with a median of 20 years, and no sex difference is observed. The prevalence is estimated at 0.3–2.4% among young adults in Dar es Salaam. Geographically, it is limited to coastal cities in Tanzania, including Dar es Salaam, with only one reported case from inland areas. No clustering by occupation or school has been observed.
The clinical picture is similar to the epidemic optic neuropathy that occurred in Cuba from 1991 to 1993, but differs in that the Cuban epidemic affected tens of thousands of people, mainly middle-aged and older adults, whereas TEON is limited to young adults and occurs continuously.
Both diseases are similar in clinical presentation (bilateral painless vision loss and color vision impairment) and extensive vitamin B complex deficiency, but in Cuba, the disease mainly affected adults to the elderly on a scale of tens of thousands over a short period. In Cuba, the epidemic ended in 1993 with vitamin B complex supplementation for all residents, but TEON continues to occur sporadically, mainly in younger individuals, and the cause remains undetermined.
2. Main Symptoms and Clinical Findings
Section titled “2. Main Symptoms and Clinical Findings”Subjective Symptoms
Section titled “Subjective Symptoms”Typical Ocular Symptoms
- Vision loss: Simultaneous, bilateral, and painless onset. It may progress over 2 to 12 weeks. In rare cases, vision loss continues for up to 6 months after onset.
- Central scotoma and centrocecal scotoma: The central part of the visual field becomes difficult to see.
- Color vision deficiency: Accompanied by color vision impairment that makes it difficult to distinguish red and green.
Relatively rare ocular symptoms
- Pain on eye movement
- Photophobia (light sensitivity)
Extraocular symptoms
- Sensorineural hearing loss: A notable complication observed in approximately 50% of patients.
- Sensory peripheral neuropathy: Painful neuropathy in the hands and feet.
Rare symptoms
- Gait ataxia, weight loss, stomatitis
Clinical findings (findings confirmed by physician examination)
Section titled “Clinical findings (findings confirmed by physician examination)”- Visual acuity: Corrected visual acuity of 6/9 or worse in both eyes. Symmetric visual impairment with a difference of no more than 2 lines on the Snellen chart between eyes.
- Color vision: Misreading of at least one plate on the Ishihara color vision test (reduced color vision).
- Fundus findings: Bilateral optic disc pallor with symmetric temporal optic atrophy.
- OCT findings: Reduction of the retinal nerve fiber layer (RNFL) localized to the papillomacular bundle, with other areas often preserved. Changes are mostly severe and symmetrical between eyes. In a few cases, microcystic changes are observed on the nasal side of the macula.
- Pupillary light reflex: In toxic and nutritional optic neuropathies, the pupillary light reflex is preserved, and relative afferent pupillary defect (RAPD) is generally negative.
Sensorineural hearing loss (about 50%) and painful sensory peripheral neuropathy of the hands and feet are typical extraocular symptoms. Rarely, gait ataxia, weight loss, and stomatitis may also occur. These extraocular symptoms are characteristic of this disease and provide important clues for differential diagnosis.
3. Causes and Risk Factors
Section titled “3. Causes and Risk Factors”The specific cause of TEON remains undetermined. The following risk factors have been identified in studies, but none have established a causal relationship.
Nutrition-related factors
- Low folate intake: Vitamin B deficiency is widely observed in both patient and control groups.
- Vitamin B deficiency is a common factor with Cuban epidemic optic neuropathy, but it has not been established as a sole cause.
Environmental factors
- Increased exposure to indoor pollution: Exposure to smoke from charcoal and wood used for cooking.
- Heavy metals: High levels of manganese, cobalt, and tin have been detected in toenails.
Socioeconomic factors
- Low socioeconomic status has been suggested as an independent risk factor.
Genetic factors ruled out
- Leber hereditary optic neuropathy (LHON)-associated mitochondrial DNA mutations (G11778A, G3460A, T14484C) were not detected, making an association with hereditary optic neuropathy unlikely.
- Cassava consumption was considered a risk factor in Cuba, but there is no evidence of cyanide poisoning in Tanzania.
B vitamin deficiency is common in patients, but it alone is not established as a cause. Multiple factors are suggested, including increased exposure to indoor pollution, heavy metals (manganese, cobalt, tin), low folate intake, and low socioeconomic status. Rather than a single cause, it is considered a multifactorial disease process in nutritionally deficient populations.
4. Diagnosis and Testing Methods
Section titled “4. Diagnosis and Testing Methods”There is no established consensus on diagnostic criteria for TEON. Many studies define it as cases meeting “progressive, symmetric, bilateral vision loss with central or cecocentral scotoma” and “color vision deficiency.” Sensorineural hearing loss and sensory neuropathy are common but not required for diagnosis.
History Taking (Important)
Section titled “History Taking (Important)”Collect the following information systematically.
- Occupational and environmental toxin exposure history
- Dietary history (cassava intake, vitamin B complex status)
- Indoor use of charcoal or firewood
- Smoking history and alcohol abuse history
- History of malignant tumors and demyelinating diseases
- Sexual history (to rule out infectious optic neuropathy)
- Family history of hereditary optic neuropathy
Ophthalmic examination
Section titled “Ophthalmic examination”- Snellen visual acuity test: confirmation of best-corrected visual acuity of 6/9 or worse in both eyes
- Ishihara color vision test: Color vision deficiency confirmed by at least one misread plate
- Amsler grid: Evaluation of central scotoma
- Humphrey visual field test: Exclusion of peripheral retinal disease
- Swinging flashlight test: RAPD is negative in bilateral optic neuropathy
- Optical coherence tomography (OCT): Confirmation of retinal nerve fiber layer (RNFL) thinning (localized to papillomacular bundle)
Visual evoked potentials (VEP) are useful in the evaluation of optic neuropathy; optic neuropathy shows reduced amplitude, generally without prolonged latency.
Clinical Tests
Section titled “Clinical Tests”The following tests are performed to rule out other optic neuropathies.
| Test Item | Purpose |
|---|---|
| Serum folate and vitamin B12 | Assessment of vitamin deficiency |
| RPR (syphilis serology) | Rule out infectious optic neuropathy |
| HIV antibody, HTLV-1 antibody | Rule out infectious etiology |
| Serum thiocyanate | Rule out cyanide poisoning |
| Mitochondrial DNA analysis | Exclusion of LHON-associated mutations |
If necessary, add MRI (to rule out demyelinating disease).
Differential diagnosis
Section titled “Differential diagnosis”- Vitamin B complex deficiency: Assessed by dietary history and serum tests
- Leber hereditary optic neuropathy (LHON): Bilateral near-simultaneous onset can be misdiagnosed as toxic/nutritional optic neuropathy. Presence or absence of pain is an important distinguishing feature; in LHON, peripapillary capillary dilation and tortuosity are seen in the acute phase. Differentiation is confirmed by mitochondrial DNA mutation analysis.
- Optic neuropathy due to drug/toxin exposure: ethambutol, methanol, etc.
- Infectious etiology: syphilis, HTLV-1-associated optic neuropathy
- Demyelinating diseases: multiple sclerosis often presents with pain on eye movement and unilateral onset
- Vascular diseases: ischemic optic neuropathy is more common in elderly patients and those with cardiovascular risk factors
5. Standard treatment
Section titled “5. Standard treatment”Management of TEON is generally symptomatic, and no established specific treatment exists. The prognosis is generally poor.
Vitamin supplementation
Acute-phase vitamin supplementation has achieved some success, but it must be administered early in the disease course. In the Cuban epidemic, supplementation with B vitamins for the entire population in 1993 brought the outbreak to an end. There is no treatment that completely stops optic atrophy, but oral vitamin B12 may be given for long-standing optic atrophy.
Treatment principles
The principles of treatment for toxic and nutritional optic neuropathy include discontinuation of the causative agent and adequate nutritional intake.
Early administration has been reported to have some effect, but in advanced cases, vision loss may become irreversible. There is no established specific treatment, and symptomatic therapy is the mainstay. In the Cuban epidemic, early vitamin B complex supplementation for the entire population contributed to the end of the outbreak, but vision recovery in individual patients cannot be guaranteed.
6. Pathophysiology and Detailed Pathogenesis
Section titled “6. Pathophysiology and Detailed Pathogenesis”The pathophysiological mechanism of TEON remains unclear. The widespread vitamin B complex deficiency observed in both the Cuban and Tanzanian epidemics suggests a multifactorial disease process in undernourished populations, but a single etiology has not been identified.
No LHON-associated mitochondrial DNA mutations have been detected, and the mechanism of hereditary optic neuropathy is ruled out.
As the pathophysiology of toxic and nutritional optic neuropathy, it is presumed that among retinal ganglion cells, P cells (which form the papillomacular bundle) with high ATP consumption are predominantly damaged. This is consistent with the observation that RNFL thinning on OCT is localized to the papillomacular bundle.
In a recent spectral-domain OCT study (Kisimbi 2013), microcystic changes mainly in the inner nuclear layer were found in about 12.5% of 128 TEON patients, reported as a nonspecific finding secondary to ganglion cell death. This is similar to changes observed in other optic nerve diseases such as multiple sclerosis.
Elucidation of the causative mechanism and development of more effective treatment strategies remain important future challenges.
References
Section titled “References”- 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(2):127-140. PMID: 9094040
- Dolin PJ, Mohamed AA, Plant GT. Epidemic of bilateral optic neuropathy in Dar es Salaam, Tanzania. N Engl J Med. 1998;338(21):1547-1548. PMID: 9599114
- 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(3):232-234. PMID: 9602617
- 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. 2012;96(2):223-226. PMID: 21733919
- Kisimbi J, Shalchi Z, Mahroo OA, Mhina C, Sanyiwa AJ, Mabey D, Mohamed M, Plant GT. Macular spectral domain optical coherence tomography findings in Tanzanian endemic optic neuropathy. Brain. 2013;136(Pt 11):3418-3426. PMID: 24018312
- Adamolekun B. Neurological disorders associated with cassava diet: a review of putative etiological mechanisms. Metab Brain Dis. 2011;26(1):79-85. PMID: 21327546