Bilateral Atypical Retrobulbar Optic Neuritis Associated With Tuberculosis in an Immunocompetent Patient

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Gour Wang, MD Bilateral Atypical Retrobulbar Optic Neuritis Associated With Tuberculosis in an Immunocompetent Patient Timothy H. M. Fung, FRCOphth, Archana Pradeep, FRCOphth CASE REPORT A previously healthy Afro-Caribbean 31-year-old man was referred from the medical team to the emergency eye department for a 9-week history of gradually progressive painless reduction of vision in both eyes. Two weeks before evaluation in the emergency eye department, he was admitted to the hospital for investigation of his shortness of breath, which was associated with a productive cough, weight loss, loss of appetite, and night sweats. General and central nervous system examination was normal. There was no family or past medical history and no history of ocular diseases or injuries. There was no history of contact with tuberculosis (TB) patients or travel in an endemic country. The patient did not take any regular medications. On examination, visual acuity was counting fingers (CF) in both eyes. There was no relative afferent pupillary defect (RAPD). There was no anterior chamber or vitreous inflammation present in either eye. Intraocular pressure was 20 mm Hg in both eyes. Fundus examination of both eyes was within normal limits. Optical coherence tomography of the macula and optic discs was unremarkable in both eyes. The chest x-ray (Fig. 1) showed grossly abnormal upper zone and mid zone lung parenchyma with multiple ring shadows, with some frank areas of thick-walled cavitation. Baseline hematological and inflammatory markers were normal. Serum testing for retroviruses, herpes viruses, syphilis, hepatitis, cytomegalovirus, borrelia, toxoplasma, and human T-lymphotropic virus was within normal limits. He was referred to the eye outpatient clinic for further evaluation of his vision loss. Two days after evaluation in the emergency eye department, he was commenced by the medical team on Rifater (rifampicin 120 mg, isoniazid 50 mg, and pyrazinamide 300 mg) 6 tablets once a day, pyridoxine 10 mg once a day, moxifloxacin 800 mg once a day (substituted for ethambutol), and oral prednisolone 60 mg once a day after a positive sputum culture for mycobacterium TB. Two days after starting anti-TB medications he was seen in the eye outpatient clinic. His vision remained CF in both eyes. There was no RAPD. Anterior segment examination was normal in both eyes. The vitreous was quiet in both eyes. Intraocular pressure was 16 mm Hg in both eyes. Fundus examination of both eyes was within normal limits. There was no optic disc swelling or optic disc pallor. Fundus fluorescein angiography, optical coherence tomography of the macula and optic discs, and indocyanine green angiography of both eyes were unremarkable. Urgent electrodiagnostic testings (EDTs) including pattern and flash visual evoked potential (VEP), full field electroretinogram (ffERG), pattern ERG (pERG), and multifocal ERG (mfERG) were requested as well as neuroimaging. Four days later, the mfERG and ffERG results were normal in both eyes and did not show evidence of macular/central cone retinal or generalized retinal dysfunction in either eye. The pattern VEP was almost absent The Queens Medical Centre, EENT Centre, Department of Ophthalmology, Nottingham, United Kingdom. The authors report no conflicts of interest. Address correspondence to Timothy H. M. Fung, FRCOphth, The Queens Medical Centre, EENT Centre, Department of Ophthalmology, Nottingham, NG7 2UH, United Kingdom; E-mail: [e-mail] e174 FIG. 1. Chest x-ray at presentation showing grossly abnormal lung parenchyma with multiple ring shadows, and some frank areas of thick-walled cavitation. Evidence of an upper zone volume loss. Fung and Pradeep: J Neuro-Ophthalmol 2021; 41: e174-e176 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence bilaterally. The flash VEP was of low amplitude on the right eye and not measurable on the left eye. The N95 component of pERG was reduced more than the P50 component that was of shorter latency, suggesting retrograde degeneration of retinal ganglion cell function. The combination of VEP and ERG findings suggested bilateral optic neuropathy affecting the left eye slightly more than the right eye. The findings from EDTs were correlated with findings from neuroimaging (Fig. 2), which showed bilateral retrobulbar optic neuritis with an abnormal shortT1 inversion recovery high signal in the posterior aspect of the optic nerves from the level of the optic canal to the chiasm. He was continued on anti-TB medications and a high-dose oral prednisolone. Six weeks later in clinic, he reported improvement in his pulmonary symptoms but his vision remained unchanged at CF in both eyes. Both eyes were quiet with no signs of inflammation in the anterior or posterior segment. There was disc pallor present in both eyes. He was registered as severely sight impaired and was continued on his anti-TB medications with a tapering course of oral prednisolone. DISCUSSION TB is one of the most prevalent infectious disease in many developing countries (1), with ocular TB representing an important form of extrapulmonary infection. Typical presentation is usually in the form of a granulomatous uveitis. Other typical manifestations include episcleritis, scleritis, interstitial keratitis, subretinal abscess, optic disc granuloma, retinal vasculitis, choroiditis, chorioretinitis, and choroidal granuloma (2). On atypical occasions, ocular TB can present in the form of an optic neuropathy that develops from either direct infection of the nerve induced by the mycobacteria or from a hypersensitivity reaction to the infectious agent (2). Optic nerve involvement in TB can be diverse, with approximately 50% of cases typically taking the form of a painless unilateral papillitis (3). In an immunocompromised patient with miliary TB described by Jaafar et al, optic neuropathy presented in the form of bilateral optic disc swelling, which was associated with the presence of multiple foci of choroiditis in the peripheral retina (4). In an extremely rare case of a patient with a histologically and bacteriologically confirmed primary tuberculous osteomyelitis, optic neuropathy presented in the form of a unilateral painless retrobulbar optic neuritis (5). To the best of our knowledge, this is the first report of an immunocompetent patient with confirmed pulmonary TB with a concurrent bilateral retrobulbar optic neuritis without the presence of any uveitis. There are certain points in this case that deserves attention. First, neuroimaging and EDTs may be necessary to diagnose an optic neuropathy in a patient with confirmed pulmonary TB who presents with bilateral painless visual loss without any clinical signs on examination. Second, despite revolutionary advances in diagnostic technologies, establishing a definite diagnosis of TB as the cause of the retrobulbar optic neuritis is challenging. There are no diagnostic criteria for tuberculous retrobulbar optic neuritis, and no specific diagnostic test is available. Optic nerve sheath biopsy FIG. 2. Axial STIR MRI images showing an abnormal STIR high signal in the posterior aspect of the bilateral optic nerves from the level of the optic canal to the chiasm. STIR, short-T1 inversion recovery. Fung and Pradeep: J Neuro-Ophthalmol 2021; 41: e174-e176 e175 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence may provide a pathological confirmation of granulomatous inflammation with acid-fast bacilli. However, it is obviously challenging to perform and carries a significant risk of permanent visual loss. Third, there is still an unanswered question on what is the correct treatment regimen for tuberculous retrobulbar optic neuritis. Are patients with tuberculous retrobulbar optic neuritis who are treated with isoniazid and/or ethambutol at an increased risk of medication-induced optic nerve toxicity, given an already compromised optic nerve status? We did not observe any deterioration in visual acuity in our patient on follow-up visits to suggest the presence of medicationinduced optic neuropathy. However, color vision and visual fields monitoring were not possible in our patient given his poor visual acuity. Adjunctive systemic corticosteroid is frequently added to antimicrobial medications in the management of extrapulmonary TB, especially for cases of tubercular meningitis and pericarditis (3). We found no improvement in visual acuity for our patient despite 6 weeks of treatment with anti-TB medications combined with a high-dose systemic corticosteroid. In summary, as demonstrated in our case, bilateral retrobulbar optic neuritis may present in an immunocompetent patient with confirmed pulmonary TB. It is therefore important to strongly consider the diagnosis in this patient e176 group particularly if they present with bilateral loss of vision with no findings on clinical examination. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: T.H.M. Fung and A. Pradeep; b. Acquisition of data: T.H.M. Fung and A. Pradeep; c. Analysis and interpretation of data: T.H.M. Fung and A. Pradeep. Category 2: a. Drafting the manuscript: T.H.M. Fung and A. Pradeep; b. Revising it for intellectual content: T.H.M. Fung and A. Pradeep. Category 3: a. Final approval of the completed manuscript: T.H.M. Fung and A. Pradeep. REFERENCES 1. Narayanan S, Prakash D, Subramaniam G. Bilateral primary optic neuropathy as the presenting manifestation of tuberculosis in an immunocompetent patient. IDCases. 2019;18:e00579. 2. Gupta V, Gupta A, Rao NA. Intraocular tuberculosis—an update. Surv Ophthalmol. 2007;52:561–587. 3. Davis EJ, Rathinam SR, Okada AA, Tow SL, Petrushkin H, Graham EM, Chee SP, Guex-Crosier Y, Jakob E, Tugal-Tutkun I, Cunningham ET Jr, Leavitt JA, Mansour AM, Winthrop KL, Hills WL, Smith JR. Clinical spectrum of tuberculous optic neuropathy. J Ophthal Inflamm Infect. 2012;2:183–189. 4. Jaafar J, Hitam WH, Noor RA. Bilateral atypical optic neuritis associated with tuberculosis in an immunocompromised patient. Asian Pac J Trop Biomed. 2012;2:586–588. 5. Miller BW, Frenkel M. Report of a case of tuberculous retrobulbar neuritis and osteomyelitis. Am J Ophthalmol. 1971;71:751–756. Fung and Pradeep: J Neuro-Ophthalmol 2021; 41: e174-e176 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.