Phlyctenulosis

The presence of an allergen within corneal or conjunctival tissue may occasionally produce a nonspecific immune reaction termed as phlyctenular keratoconjunctivitis. The association between tuberculosis and phlyctenulosis was hypothesized in the early twentieth century by several researchers, but the first large series was collected by Gibson (1918), who examined and investigated 92 such patients with phlyctenular keratoconjunctivitis. The overwhelming majority (90%) had positive Mantoux tests, but detectable systemic disease was found in only 26%. In distinction, other large cohorts of 1,073 patients and 105 contacts and another of 600 patients, phlyctenulosis was found in only two patients in either series. However, epidemiological data suggest a strong link between phlyctenulosis and tuberculoprotein hypersensitivity, particularly in areas where tuberculosis is endemic. The common presentation is in malnourished children who display single or multiple grayish limbal nodules of 1–3 mm in size. The overlying epithelium occasionally becomes necrotic and may ulcerate. These ulcers may migrate toward the cornea usually dragging a small leash of superficial blood vessels along with it producing photophobia and watering. Topical steroids are recommended for the ocular inflammation and systemic antitubercular therapy if any systemic disease is detected. The disease tends to be recurrent throughout the patients childhood.

Corneal Tuberculosis

Tubercular infection tends to produce both immune reactions as well as direct infection. The most common immune reaction is interstitial keratitis that is usually a unilateral infiltrate in the peripheral stroma with its accompanying vascularization. The deposition of mycobacterial antigens within corneal tissues is thought to induce a hypersensitivity reaction. Topical steroids are required to resolve these infiltrates as is systemic antitubercular therapy for any associated systemic disease. Other findings include infiltrations and

ulcerations. In the recent decades, the growing popularity and numbers of refractive surgery procedures have led to increasing numbers of corneal infections. Patients undergoing laserassisted intrastromal keratomileusis (LASIK) may be infected with atypical mycobacteria, mainly M. chelonae, and these infections usually present as haziness at the flap-corneal interface or even as corneal abscesses in severe cases. Treatment consists of frequent use of fourthgeneration fluoroquinolones or, in severe cases, flap excision.

Uveal Tuberculosis

The hallmark manifestation of ocular tuberculosis is infection or inflammation of the uveal layer of the eye.

Anterior Uveitis

Tubercular anterior uveitis produces the prototype granulomatous inflammation along with syphilis and leprosy. This term describes the classically described large and greasy keratic precipitates that appear like “mutton-fat” globules but may be fine and white in some instances. The anterior uveitis may present in an acute fashion but is commonly chronic. Frequently, it may be recurrent in nature. The intensity may range from mild to severe with broad-based dense posterior synechiae. Translucent nodules may occur at the pupillary margins (Koeppe nodules, that are thought to mark the sites of future posterior synechiae) or grayish nodules may form on the iris surface or in the superficial stroma (Busacca nodules). These iris nodules probably represent a form of iris tubercle. Treatment is with topical or periocular steroids and systemic antitubercular drugs (if a focus of systemic tuberculosis is present).

Intermediate Uveitis

Tuberculous infection can also present as a smoldering low-grade chronic intermediate uveitis. There is generally an associated vitritis, snowball opacities (Fig. 5.1), pars plana exudates, and peripheral vascular sheathing. Treatment is with topical or periocular steroids and systemic

Fig. 5.1 The right eye of a 40-year-old female patient showing multiple white fluffy opacities in the vitreous (snowballs). The patient had associated mediastinal tuberculosis

Fig. 5.2 The right eye of a 32-year-old female patient showing a yellow-white tubercle in the inferior retina. The patient had associated pulmonary and central nervous system tuberculosis

antitubercular drugs (if a focus of systemic tuberculosis is present).

Posterior Uveitis (Choroidal Tuberculosis)

Choroidal tubercles and tuberculomas (largersized lesions) are the most common manifestations of ocular tuberculosis (Figs. 5.2 and 5.3). The prevalence varies from 1.4% in patients with isolated pulmonary tuberculosis to 60% in the disseminated forms of tuberculosis. Tubercles are yellow-white in color and usually have an overlying and surrounding serous retinal detachment in the acute phases. They range from ¼ disc diameter (DD) to several DDs in size and are commonly found in the posterior pole. The number of tubercles varies from 1 to 50 with five being the average. Histopathology of uveal tissue specimens reveals classical caseating granulomas that are characterized by stromal destruction with swelling of the adjacent choroid and infiltration with round cells, epithelioid cells, and giant cells. Appropriate staining techniques have revealed the presence of mycobacteria within the tubercle, suggesting a direct tissue infection. Fundus fluorescein angiography of these tubercles has a distinctive appearance with an early hypofluorescence or minimal hyperfluorescence within the tubercle that increases in the later

Fig. 5.3 The right eye of a 28-year-old female patient showing multiple large tuberculomas with a surrounding exudative detachment in the posterior pole. The patient had associated miliary tuberculosis

phases. Significant peritubercular fluorescence is seen in all the phases of the angiogram giving a “ring of fire” picture [20], suggesting that the inflammatory activity may extend beyond the boundaries of the visible tubercle. Optical coherence tomography studies reveal attachments between the retinal pigment epithelial-choriocapillaris layer and the overlying neurosensory retina. There is an associated surrounding subretinal