Presented by Malini Veerappan Pasricha, MD
A 40-yo Mongolian man presented with progressive blurring of vision in his right eye.
Figure 1A: Wide-field color photo of the right eye. Dense vitritis is present as well as a posible focal areas of retinitis inferotemporally and inferonasally.
Figure 1B: Wide-field color photo of the left eye. This eye is normal.
The patient noted progressive blurry vision, pain, redness, and photophobia in his right eye two weeks prior to presentation at an outside facility. He denied any flashes, floaters, metamorphopsia, or headaches. His past ocular history was otherwise unremarkable. Family history was noncontributory. He reported having started smoking cigarettes two weeks prior to onset of symptoms, and denied use of illicit substances. Review of systems was negative. At presentation to an outside facility, he was noted to have significant anterior chamber granulomatous inflammation and pupil synechiae limiting view of the posterior pole. He was started on atropine and prednisolone eye drops for anterior uveitis. He returned to the outside facility one week later, with an improved view of the posterior pole, and examination revealed new concern for retinitis. An anterior chamber tap was performed, intravitreal foscarnet was administered, oral valacyclovir was initiated, and the patient was referred to us for further evaluation and management.
On examination in our office, his best corrected Snellen visual acuity measured 20/125 in the right eye (OD) and 20/40 in the left eye (OS). Intraocular pressures were 14 mmHg OD and 10 mmHg OS. The left eye examination and imaging were unremarkable. Anterior segment examination of the right eye was notable for mild conjunctival injection, trace endothelial folds, trace anterior chamber flare, focal posterior synechiae and pigment on the anterior lens capsule. The posterior examination of the right eye showed dense vitritis, with a questionable patch of focal retinitis inferonasally (Figure 1A). Fluorescein angiography (FA) of the right eye showed diffuse vasculitis, optic disc leakage, and peripheral non-perfusion (Figures 2A and B).
Figure 2A: Wide-field fluorescein angiogram of the right eye. Widespread vasculitis is present as well as optic nerve leakage. Note the peripheral area of nonperfusion.
Figure 2B: Wide-field later phase fluorescein angiogram of the right eye. Extensive vascular leakage is present as well as a large area of inferotemporal nonperfusion.
The patient had a positive QuantiFERON test on initial workup. Though the chest xray was negative, a follow-up CT chest showed signs of reactive lymphadenopathy. A focused review of systems was negative for fevers, chills, night sweats, and cough. The patient denied oral and genital ulcers. His sexual preference is women, and he denied any IV drug use.
Additional lab testing was ordered. Results were negative for RPR, FTA-ABS, HIV, HLA-B27, CBC, CMP, PT/INR, COVID-19, influenza, ACE, lysozyme, Lyme, ESR, CRP, ANCA panel, rheumatoid factor, CCP, C3/C4 complement. The anterior chamber tap from presentation at the outside facility was negative for HSV, VZV and CMV.
Diagnostic testing including a positive QuantiFERON test, reactive lymphadenopathy on CT chest, retinal vasculitis with peripheral non-perfusion on FA indicated probable tuberculosis as an etiology. The patient was referred to a TB clinic for further evaluation and initiated on quadruple therapy (rifampin, isoniazid, pyrazinamide, ethambutol). One week later, his vision improved to 20/80 and we initiated oral prednisone 60mg. The following week, his vision further improved to 20/25 and exam revealed significant improvement in panuveitis (Figure 3). The patient continues to be compliant with his TB therapy and is currently on a steroid taper. We will continue to follow him in our retina clinic.
Figure 3: Fundus photo of the right eye approximately two weeks following beginning quadruple TB therapy and one week after beginning oral steroids. Note the marked improvement in inflammation.
Tuberculosis (TB) is an infection caused by a rod-shaped, non spore-forming, aerobic bacterium called Mycobaceteria tuberculosis.1 Bacilli are spread primariliy by inhalation. In the majority of healthy people, the immune system quickly contains the infection.2 If the infection is not contained, local spread throughout the lungs and spread to regional lymph nodes occur over the next 3-8 weeks.1 Subsequent spread to other organs results in extrapulmonary TB. Organs affected in extrapulmonary TB include the central nervous system (including eyes), skin, cardiovascular system, musculoskeletal system, genitourinary tract, and gastrointestinal tract.3 While pulmonary TB patients may experience cough, dyspnea, hemoptysis, night sweats, weight loss, anorexia, and fatigue, patients with extrapulmonary TB may present with abdominal pain, diarrhea, infertility, monoarticular joint pain, headaches, or lymphadenopathy.1
Ocular TB is a form of extrapulmonary TB and its prevalence among those with active TB varies significantly, from 1% in pulmonary TB patients to 20% in extrapulmonary TB.2 The predominant route of infection to ocular tissues is by hematogenous spread from the lung. However, patients with ocular TB may have a normal chest radiograph and no pulmonary symptoms and/or may have evidence of other forms of extrapulmonary TB.1 Ocular TB is either unilateral or asymmetrically bilateral, and has a chronic and insidious course. It may present as anterior, intermediate, posterior or pan uveitis, and is more often granulomatous than non-granulomatous uveitis. The table below shows the many clinical manifestations of ocular tuberculosis.1,4
Ocular Manifestations of Tuberculosis (Adapted from Ryan's Retina)
|Primary Site of Inflammation||Clinical Signs|
|Lids, adnexa, sclera, cornea||Lupus vulgaris
|Lacrimal apparatus||Lacrimal gland adenitis
|Anterior Uveitis||Nongranulomatous/granulomatous uveitis
Anterior chamber granulomas
|Intermediate Uveitis||Recurrent, granulomatous|
|Posterior Uveitis||Choroidal tubercles/tuberculoma
Perivascular healed chorioretinal scars
Exudative retinal vasculitis
|Optic nerve||Optic disc granuloma
Classic posterior uveitis findings are choroidal tubercles, subretinal abscesses, choroidal tuberculoma, serpiginous-like choroiditis, and retinal vasculitis and non-perfusion.3 Choroidal tubercles are small (1/4 to 1 disc diameter in size) grayish yellow choroidal lesions, that appear similar to sarcoid lesions.3 Subretinal abscesses arise from liquefaction of caseous material due to rapid multiplication of bacilli, and may result in necrosis, chorioretinal anastomoses, and subretinal neovascularization.3 Choroidal tuberculomas are large yellow-white solitary, elevated choroidal masses, sometimes with overlying retinal folds and retinal hemorrhages.3 Serpiginous-like choroiditis can present as a multifocal choroiditis that progresses to become confluent with several advancing edges, or an initial plaque-like lesion with ameboidal spread, or inactive scars that show new activity at their edges.3,5,6 Of note, patients with presumed serpiginous choroiditis who worsen with steroid treatment should undergo prompt workup for TB.3 Lastly, tubercular retinal vasculitis, which was the predominant retinal finding in our patient, is active leakage around the veins and sometimes arteries, associated with retinal hemorrhages, lipid exudation, and focal chorioretinitis. This should be differentiated from sarcoid vasculitis and Behcet’s disease, which are more arteriolar than venular. It is unclear whether the vasculitis is infectious or a hypersensitivity response to the M. tuberculosis antigen. Consequent retinal non-perfusion and neovascularization of the retina may warrant laser ablation of the ischemic retina.3
Diagnostic evaluation of ocular TB includes molecular biology techniques such as intradermal injection of tuberculin purified protein derivative (PPD), interferon gamma release assays such as QuantiFERON blood testing, and imaging such as chest radiograph. Chest x-ray may reveal infiltrations, cavitations, hilar lymphadenopathy, pleural effusion, fibrotic or calcific lesions, or non-specific lymphadenopathy.1 Isolation of M. tuberculosis by culture remains the gold standard for diagnosis. However, isolation from inflamed ocular tissues or aqueous/vitreous sample is often not possible due to the relatively large specimen size required.1,7
Antitubercular therapy is effective in treating and reducing the risk of recurrence of ocular TB. The World Health Organization recommends patients with new active pulmonary or extrapulmonary TB to be treated with a four-drug regimen, commonly referred to as RIPE (rifampin 10mg/kg daily, isoniazid 5mg/kg daily, pyrazinamide 20-25mg/kg daily, ethambutol 15 mg/kg daily). Oral corticosteroids are beneficial in patients with ocular TB, as well as tubercular pericarditis and meningitis.1,8 Co-management with an infectious disease specialist is recommended for systemic management of TB and drug side effect monitoring.
TB continues to be a major global health concern. TB is endemic in Africa (280 in 100,000 persons), Southeast Asia (183 in 100,000 persons), and India (168 in 100,000 persons), and is one of the most common causes of infectious uveitis in these regions.2 It is also the most common opportunistic infection in HIV positive patients.1 Current challenges in managing TB are multi-drug resistant and extensively drug resistant TB, as well as the emergence of non-tubercular mycobacterial infections. The latter occurs in both immunocompetent and immunocompromised persons, in previously unrecognized settings (such as soil, water, and dust), and with new clinical manifestations, such as endophthalmitis after uncomplicated cataract surgery, LASIK, endothelial keratoplasty, intravitreal injections, and scleral buckling. Lack of laboratory tools for differentiation, resistance to routine antitubercular treatment, and lack of treatment guidelines all present challenges in management of non-tubercular infections.1