epiretinal tissue [27]. Classically, there are four described stages:

I. Mild periphlebitis

II.Widespread periphlebitis involving larger vessels and adjacent arterioles

III.Neovascularization with retinal and vitreal hemorrhages

IV. Fibrovascular proliferations with recurrent vitreous hemorrhages

The usual presentation is of unilateral vitre- oushemorrhage-inducedvisualloss.Examination of the fellow eye reveals the characteristic peripheral retinal periphlebitis. Resolution of the vitreous hemorrhage shows hemorrhages and exudates along the peripheral vessels. The visual loss may be reversible as a result of vitreous hemorrhages or may be permanent due to anatomical changes in macular architecture or tractional retinal detachments. A fundus fluorescein angiographic examination helps to assess the severity of vasculitis and study the extent of ischemia and neovascularization. Laser photocoagulation may be needed in patients with extensive peripheral ischemia or neovascularization. Non-clearing vitreous hemorrhages may need a core vitrectomy, laser photocoagulation with additional management as needed for fibrous proliferations or tractional detachments. The medical management includes the use of systemic or periocular corticosteroids for the control of the vasculitis. There is no consensus on the need to use antitubercular therapy in these patients.

In contrast, tubercular retinal vasculitis is associated with active systemic tuberculosis. This form of vasculitis is usually a direct result of infection with M. tuberculosis or may be a combination of direct infection with an associated hypersensitivity. Rosen et al. described a series of 12 patients of ocular tuberculosis of whom 9 patients had retinal vasculitis. The common clinical picture was of an acute retinal periphlebitis with a moderate grade of vitreous infiltrate tending to develop a peripheral ischemia and neovascularization. Clinical systemic disease was seen in three patients, but all had strongly positive Mantoux tests [28]. PCR techniques are

increasingly being used to identify tubercular retinal vasculitis. In one series, Gupta et al. used this technique to arrive at a diagnosis in 13 patients of retinal vasculitis, and the consistent presence of areas of active or healed choroiditis in these patients led the authors to suggest that presence of these areas may tend to suggest a tubercular etiology [29]. A fundus fluorescein angiographic examination reveals the presence and extent of ischemia and possible neovascularization. Appropriate laser photocoagulation may be necessary for areas of extensive peripheral ischemia or in cases with established retinal neovascularization. The vasculitis may require systemic/periocular corticosteroids, and antitubercular therapy is necessary.

Tubercular retinitis is rare and may result by a process of contiguous spread from the choroid or via hematogenous dissemination and is seen as a focal or diffuse retinitis often accompanied by vitreous opacification.

Tuberculous Panophthalmitis

Rarely, a granulomatous inflammation may affect all the coats of the eye, producing a panophthalmitis. Most case reports describe a painless and progressive disease process with defective vision, ophthalmoplegia, corneal haze and hypotony. Tubercular panophthalmitis is thought to be more common in children, malnourished adults, or in patients with systemic tubercular disease. The histopathological features have been described recently by Chawla et al. in the case of a 12-year-old girl. She presented with a painless and progressive reduction in vision and had corneal vascularization, iris nodules, and scleral necrosis. The eye was enucleated, and examination showed a necrotizing granulomatous inflammation consisting of epithelioid cell granulomas along with areas of caseous necrosis. In the opinion of the authors, the absence of pain, eyeball nodules, and a tendency to perforation may point to a tubercular infection [30]. Antitubercular therapy may be helpful in earlier-stage disease but may be of limited value

in end-stage disease, when enucleation may be necessary to establish the diagnosis.

Neuro-ophthalmological Aspects

Neurotuberculosis is a common presentation of systemic tubercular disease, and as a result, neuro-ophthalmological findings are common and varied. In perspective, 67 (67%) of 100 Indian patients with tubercular meningoencephalitis had neuro-ophthalmic findings, commonly optic neuritis (32% with about half progressing to optic atrophy), gaze palsy (20%), third and sixth nerve palsy, conjugate deviation, primary optic atrophy, and complete ophthalmoplegia [31].

The findings depend in part on the specific clinical pattern of neurotuberculosis in the individual patient. Tuberculous meningitis is the most common pattern and is characterized by the formation of thick exudates at the base of the brain often extending to the basal cisterns and the sylvian fissure. An accompanying vasculitis of the adjacent smalland medium-sized vessels is the norm as is an inflammation of any underlying brain parenchyma. This vasculitis is responsible for the observed cranial nerve involvement including the optic and oculomotor nerves.

Involvement of the optic nerve in tubercular meningitis is common and is responsible for the majority of the ocular morbidity associated with this condition. A primary optic atrophy often ensues in varying degrees. In patients presenting in the acute stages of the disease, an early diagnosis is often possible, moreover, if patients complain of visual loss, but often diagnosis is late as patients who have been critically ill or comatose are unable to articulate visual symptoms. Simultaneous use of systemic corticosteroids along with the antitubercular therapy may reduce this complication. In one clinical trial, 27 patients with tuberculous meningitis were treated with ethambutol, isonicotinic acid hydrazide, streptomycin, and dexamethasone versus a control group of 28 who were treated with triple antituberculous drugs only. Ocular complications were seen in two of the combined dexamethasone

and antitubercular therapy group as compared to seven of the group not receiving dexamethasone [32]. However, larger and more controlled doubleblind studies are required. Girgis et al. have hypothesized that suggested that the concurrent use of dexamethasone in tuberculous meningitis may reduce the ocular morbidity but may not reverse established damage.

A diagnostic rule has been formulated that tracks five variables (optic atrophy, focal neurological deficit, symptoms lasting longer than 6 days, abnormal movements, and neutrophils constituting less than 50% of CSF neutrophils), and it has a diagnostic sensitivity of 98% and a specificity of 44% when one feature was present and a diagnostic sensitivity of 55% and specificity of 98% when three or more features are present [33].

Involvement of the oculomotor nerves is also well known with the VI being the most commonly involved followed by the III and the IV [34]. In a review of tuberculous meningitis, up to 30–40% of patients had a VI nerve palsy as compared to 5–15% with a III nerve palsy [35]. Oculomotor nerve palsies may either recover fully or may be a part of permanent neurological sequel.

Other patterns of neurotuberculosis include the avascular spherical granulomatous lesions termed as tuberculomas. Tuberculomas may directly compress any part of the visual pathway (commonly the optic nerve) or any of the oculomotor nerves producing either visual loss or oculomotor palsies.

Intracranial tuberculosis in any pattern can cause a raised intracranial pressure that is visible clinically as papilledema or unilateral or bilateral VI nerve palsy. This raised pressure is due to the exudates associated with tubercular meningitis that tend to block the normal outflow channels of the cerebrospinal fluid at the foramen of Luschka and Magendie or is due to the spaceoccupying lesion effects of large tuberculomas. A secondary optic atrophy often supervenes if untreated.

Intraocular findings are also frequent including chorioretinitis and tubercles, and retinal vasculitis. As part of the hematogenous dissemination that is

the cause of the neurotuberculosis, choroidal tubercles may occur. The prevalence of such tubercles depends on the extent and pattern of the neurotuberculosis and systemic tuberculosis that is present. In a series of 52 patients with tubercular meningitis, Kennedy et al. detected choroidal tubercles in 2% (1 of 52) of patients [36]. Tubercles are virtually pathognomonic of and more prevalent in patients with miliary tuberculosis, and their presence has been suggested as a diagnostic guideline. Up to 10% of patients with miliary tuberculosis–induced neurotuberculosis may show choroidal tubercles [37]. In recent studies, Mehta et al. have shown that a finding of choroidal tubercles in patients of neurotuberculosis indicates the presence of a concurrent systemic focus of tuberculous infection (usually pulmonary) [38].

Ocular Tuberculosis in HIV-Positive

Patients

The epidemic of HIV infection has led to a marked resurgence of systemic tuberculosis. In hyperendemic areas, mycobacterial infections are a common superinfection and may occur due to a reactivation of preexisting latent tuberculosis or due to fresh infections. The prevalence of systemic tuberculosis has increased 20-fold to 8% from the 0.4% normally seen in immunocompetent individuals [39]. This has been termed “the cursed duet”. The occurrence of systemic tuberculosis is considered as an AIDS-defining disease and occurs at CD4 counts <500 cells/mm [3]. The manifestations are protean and often difficult to diagnose due to atypical clinical presentations or difficulties in the interpretation of routine investigations such as the Mantoux tests/ X-rays/tomography.

Several studies have documented ocular lesions in patients with HIV/AIDS. In one study, 46 AIDS patients were prospectively examined, 17 had systemic tuberculosis, and four of these patients (23.5%) had ocular disease including choroidal tubercles (three patients) (Fig. 5.5) and chorioretinitis (one

Fig. 5.5 The left eye of a 32-year-old male patient showing a large yellow-white tuberculoma and an associated exudative detachment. The patient had acquired immune deficiency syndrome and pulmonary tuberculosis

patient). The mean CD4 count was 250 cells/ mm3 and disseminated tuberculosis was seen in all these patients [11]. Within a large cohort of 766 patients, ocular tuberculosis was seen in 19 eyes of 15 patients (1.95%). Observable lesions included choroidal granulomas (10 eyes), subretinal abscess/panophthalmitis (seven eyes), and conjunctival abscess/panophthalmitis (one eye each). The mean CD4 count was 160.85 cells/mm3 and pulmonary tuberculosis was seen in all these patients [40]. The detected ocular tuberculosis largely affects the posterior uvea in the form of tubercles and is part of a disseminated tubercular disease with low CD4 counts (<250 cells/mm [3]). Other reported presentations include conjunctival lesions such as masses, eyelid lesions that mimic chalazia, corneal stromal infiltrates with or without scleritis, ulcers, granular masses or pedunculated polypoid tumors [41].

The techniques of diagnosis are similar to immunocompetent patients, but the interpretation of common tests is difficult. The preexisting immunosuppression can return false-negative Mantoux tests, and chest and abdominal radiography often have atypical findings. The diagnosis often needs a high index of suspicion and cultures or PCR studies of aqueous/vitreous/ocular tissue may be needed to confirm a diagnosis. Due care needs to be given to rifampicin-protease inhibitor interactions to avoid therapeutic failures, and