Intraocular Tuberculosis

Reema Bansal; Aman Sharma; Amod Gupta

Disclosures

Expert Rev Ophthalmol. 2012;7(4):341-349. 

In This Article

Clinical Spectrum

Choroidal tubercles were one of the first signs described in intraocular TB. Clinical manifestations of intraocular TB are protean with wide spectrum.

Anterior Uveitis

Tuberculous anterior uveitis often presents as unilateral or bilateral chronic granulomatous disease which presents with large, mutton fat keratic precipitates. Iris nodules may be present near the pupillary border (Koeppe) or on the iris surface (Bussaca).[23] The anterior uveitis has an insidious onset and runs a chronic course, inevitably complicated by the development of cataract and posterior synechiae.[24] Broad posterior synechiae in patients with latent TB have been highly suggestive of tuberculous uveitis in India and Singapore.[24,25] Pigmented hypopyon may be seen rarely in TB anterior uveitis.[26] Anterior uveitis is often accompanied by vitritis.[23]

Intermediate Uveitis

Inflammatory cells from anterior uveitis may spillover into the vitreous cavity; however, vitreous may be the primary site of inflammation and present with moderate to severe cellular reaction in the vitreous cavity, including snowball opacities. Peripheral retinal vasculitis associated with discrete perivascular choroiditis/scars may indicate a tuberculous etiology.[24] In a North Indian population, TB was found to be an unusually common etiology of intermediate uveitis (46.7%).[27] Clinical signs in this series included vitritis in all eyes, snowballs (86.3%) and associated anterior segment inflammation (64.2%). The most frequent complications related to TB-uveitis included cystoid macular edema (40%) and cataract (38.9%). Other less common complications were epiretinal membrane, raised intraocular pressure, optic disc pallor, peripheral neovascularization, retinoschisis, retinal detachment and vitreous hemorrhage.[27]

Posterior Uveitis

Posterior uveitis is the most common presentation of intraocular TB, with lesions predominantly present in the choroid. Although uncommon, choroidal tubercles are the most well-recognized manifestation. However, serpiginous-like choroiditis (SLC) and retinal vasculitis were the most common clinical presentations of tubercular posterior uveitis in North India.[24]

Choroidal Tubercles

Choroidal tubercles are the most recognized lesions in intraocular TB, with both clinical and histopathologic descriptions available in the literature.[23,28–30] The tubercles are located deep in the choroid, presenting unilaterally (more commonly) or bilaterally as yellowish lesions, discrete with ill-defined borders and typically elevated centrally. Most commonly situated in the posterior pole, these are solitary or few in number. Inflammatory cells may be present in the anterior chamber or vitreous cavity. Subretinal fluid may be present. In HIV-infected individuals or those with miliary TB, choroidal tubercles may not be symptomatic and may not show any inflammatory signs. Choroidal tubercles may have associated retinal perivasculitis. On fundus fluorescein angiography (FFA), they exhibit hypofluorescence in early and hyperfluorescence in late phases. Histological examination reveals granulomatous inflammation, caseation necrosis and AFB. Varying degrees of marginal pigmentation and scar formation occur with their healing.[31]

If untreated, a choroidal tubercle may grow into a large tumor-like mass called tuberculoma. It is seen as a yellowish, elevated mass-like lesion mimicking an abscess that is subretinal, with surrounding retinal detachment (Figure 1A & B). Rapid bacillus multiplication, progressive liquefied caseation necrosis and tissue destruction lead to such an abscess. Neovascularization may develop in large-sized granulomas.

Figure 1.

Right eye fundus photograph of a 32-year-old male with choroidal granuloma and retinal vasculitis. (A) The visual acuity was counting fingers and the QuantiFERON-TB Gold test was positive. (B) After 9 months of antitubercular therapy and oral corticosteroids, the eye was quiescent with visual acuity 6/9.

Choroidal tubercles are localized in the choroid, but may rarely rupture the Bruch's membrane, and invade the subretinal space and the vitreous cavity, causing widespread intraocular inflammation, necessitating vitrectomy.[30] Poor vision at presentation may be due to tubercles located in and around the macula with surrounding subretinal fluid. Peripheral tubercles are usually asymptomatic unless associated with anterior segment inflammation. Nearly one-third of patients with choroidal tubercles may have associated disseminated TB and a negative tuberculin skin test (TST). HIV infection must be looked for in all patients presenting with choroidal tubercles. However, choroidal tubercles may occur without any systemic evidence of TB.[29]

Serpiginous-like Choroiditis

Classic SLC is a chronic inflammation of the choroid that is recurrent, and is believed to be immunogenic or, rarely, infective in origin. It shows relentless progression and responds to systemic corticosteroids and immunosuppressive agents. While it is typically solitary and peripapillary/juxtapapillary, tubercular SLC (TB-SLC) usually appears as multifocal lesions of choroiditis. The active lesions progress in a serpiginoid pattern and coalesce.[32,33] Individual lesions heal centrally and show a centrifugal spread in an amoeboid fashion. Subsequent to the introduction of this distinct clinical entity, TB-SLC has been identified and reported from various parts of the world.[10,17,23,24,33–37] TB-SLC predominantly affects young-middle aged males. The lesions are usually bilateral, noncontiguous to optic disc, and are commonly associated with mild vitreous inflammation. Two distinct patterns are seen: multifocal, discrete choroiditis lesions that are initially noncontiguous and later progress to form diffuse lesions with an active edge resembling serpiginous choroiditis (Figure 2A–D) and less commonly a solitary, diffuse plaque-like lesion with an amoeboid extension. Addition of antitubercular therapy (ATT) to the conventional oral corticosteroids significantly prevents recurrences. The lesions heal with significant scarring but, despite macular involvement, the fovea tends to be spared in the majority of eyes, leading to a good final visual acuity.[38]

Figure 2.

Fundus images autofluorescence of a 45-year-old female with multifocal active lesions of serpiginous-like choroiditis. (A) Left eye fundus photograph and (B) fundus autofluorescence. The lesions are (C) hypofluorescent in early and (D) hyperfluorescent in late phases. The center of the lesion shows transmission hyperfluorescence, both in early as well as in late phases.

In SLC, FFA helps in differentiating active from inactive lesions. The active edge/lesion is hypofluorescent during the dye transit (Figure 2C) and shows hyperfluorescence in the late phase (Figure 2D). Healed areas show transmission defects. On indocyanine green angiography, the active lesions appear hypofluorescent in both early as well as late phases. However, the active lesions may show a subtle area of hypoperfusion of choriocapillaris in the initial frames.[39] The fundus autofluorescence pattern reveals characteristic changes as the lesions evolve from an initial acute stage to the healed stage.[35] In acute stage, a subtle halo of increased autofluorescence (hyperautofluorescence) corresponds to the lesion that looks amorphous (stage 1). As healing begins, a thin border of decreased autofluorescence (hypoautofluorescence) surrounds the lesions. The lesion itself appears well-defined and predominantly hyperautofluorescent with a stippled pattern (stage 2). As it heals further, the hypoautofluorescence progresses and the lesions appear predominantly hypoautofluorescent with stippled pattern (stage 3). When complete healing occurs, the lesions appear hypo autofluorescent throughout (stage 4). As fundus autofluorescence is a useful tool for in vivo imaging of the outer retinal complex, it is best suited to evaluate SLC that primarily involves the choriocapillaries and RPE. This noninvasive modality is reliable for detecting specific high-risk characteristics such as progression or recurrence of SLC.[35]

High-resolution spectral domain-optical coherence tomography scans reveal a progressively changing pattern in eyes of patients with SLC.[36] In the acute lesions, a localized, fuzzy area of hyper-reflectivity is seen in the outer retinal layers involving the RPE, photoreceptor outer segment tips, photoreceptor inner segment–outer segment junction, external limiting membrane and the outer nuclear layer. As the lesions start healing, the spectral domain-optical coherence tomography scan shows irregular, hyper-reflective knobbly elevations of the outer retinal layers with ultimate loss of RPE, photoreceptor outer segment tips, inner segment-outer segment junction and external limiting membrane.

Retinal Vasculitis

Inflammation of the retinal vessels is a well-known association of systemic TB, more commonly involving the veins than arteries. In eyes with evidence of intraocular TB by a positive PCR, active vasculitis was seen as severe perivascular cuffing, infiltrates, retinal hemorrhages, moderate vitritis, snowball opacities, neuroretinitis and focal choroiditis.[40–42] Presence of perivascular choroiditis lesions (active or healed) is a strong indicator of tubercular etiology (Figure 3A & B).[23] On FFA, extensive peripheral capillary nonperfusion areas that lead to retinal/optic disc neovascularization characterize TB retinal vasculitis. Thus patients with TB retinal vasculitis may first present with vitreous/preretinal hemorrhage. It has been long speculated that patients of idiopathic retinal vasculitis, the so-called Eales' disease, may indeed be tuberculous retinal vasculitis. Eales' disease was first described in 1880 as recurrent retinal and vitreous hemorrhage in apparently young and healthy adult males, associated with constipation and epistaxis. Interestingly, presence of MTB DNA was demonstrated in epiretinal membranes of patients with Eales' disease who underwent vitreous surgery.[43,44]

Figure 3.

Left eye fundus photograph of a 21-year-old male with retinal vasculitis, optic disc edema and perivascular choroiditis scars along lower temporal vessels. (A) The visual acuity was counting fingers and tuberculin skin test was 13 × 18 mm. (B) After 10 months of antitubercular therapy and oral corticosteroids, the eye was quiescent with visual acuity 6/6.

Endophthalmitis, Panophthalmitis or Neuroretinitis

Hypopyon is rarely noted in intraocular TB.[45] A pigmented hypopyon in an immunosuppressed patient has been reported in biopsy- and culture-proven intraocular TB.[26] Atypical presentations may be seen in patients with immunocompromised status. Direct exudation into the vitreous cavity and anterior chamber from rupture of a subretinal abscess may produce endophthalmitis or panophthalmitis.[30,46,47] AFB has been demonstrated in an eye enucleated for acute granulomatous uveitis, glaucoma and exophthalmos in a patient without any systemic evidence of TB. In patients with HIV infection, intraocular TB is rare, but can have varied presentations including choroidal granuloma, subretinal abscess or panophthalmitis.[48]

Unilateral neuroretinitis has been reported in an asymptomatic woman with latent TB, followed by bilateral multifocal choroiditis and exudative retinal detachment.[49] Optic neuropathy due to TB is uncommon but an important sign in endemic areas.[50] In recent data collected from nine different countries by various authors on tuberculous optic neuropathies, the clinical spectrum included papillitis, neuroretinitis, optic nerve tubercle, compressive optic neuropathy, retrobulbar neuritis, optic neuritis and anterior ischemic optic neuropathy.[50]

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