OCULAR MANIFESTATIONS IN TB, LEPROSY AND SYPHILIS

DR ANUMEHA

OCULAR TUBERCULOSIS
Caused by bacillus Mycobacterium tuberculosis PRIMARY : there are no other systemic lesions SECONDARY : infection resulting from contagious spread from adjacent structure or by hematogenous spread

EPIDEMOLOGY First described in eye by Maitre-Jan in 1711 who identified an iris lesion and attributed it to the disease Incidence: ranges from 1.4 - 5.74% No racial preferences No sexual predilection Elevated rates of TB infection are seen in individuals immigrating from Mexico, Philippines, Africa, Southeast Asia, the Caribbean, and Latin America.

Pathophysiology: M tuberculosis is a slow-growing obligate aerobe.Because of the unique ability to survive and proliferate within mononuclear phagocytes, M tuberculosis is able to invade local lymph nodes and spread to extrapulmonary sites, usually via hematogenous routes. Mycobacteria are highly antigenic, and they promote a vigorous, nonspecific immune response. Their antigenicity is due to multiple cell wall constituents, including glycoproteins, phospholipids, and wax D, which activate Langerhans cells, lymphocytes, and polymorphonuclear leukocytes.

C/F External ocular findings: 1) Eye lids: Lupus vulgaris -lids, lacrimal sac and conjunctiva lid abscesses tarsitis 2) Conjunctiva: chronic conjunctivitis Primary: Unilateral, < 20 yrs, lacrimation, mucoid secretion and conjunctival and lid oedema, with swelling and caseous preauricular and sub maxillary LN Conjunctiva becomes hypertrophied and large follicles appear which may break down and ulcerate.

Secondary: Bilateral, age > 20 yrs, previously infected pts. Results due to the infection of the conjunctiva from a contagious TB focus-TB lid, tarsus, orbit, lacrimal gland. No associated LN enlargement. May present in any 1 of the 6 forms: 1. Small millet seeded ulcers which may or may not coalesce 2. Small grayish sub conjunctival tubercles 3. A hypertrophic form, with proliferative changes and large cockscomb excrescences.

4. Pedunculated polyps arising from the tarsal or fornicial conjunctiva. 5. Lupus conjunctiva associated with lupus of the skin. 6. Tuberculoma of the conjunctiva.

Phlyctenulosis Allergic response to the Myco. TB Typically,seen in children On the bulbar conjunctiva, adjacent to the limbus. A leash of blood vessels may extend from the conjunctiva to the cornea giving the so-called fascicular keratitis. Photophobia, conjunctival injection and lacrimation are common symptoms. The child keeps his lids closed and tries to seek dark corners.

 Within 2-3 days the small greyish masses break down, small pits appear at the apex, the phlyctenules sink to the level of the conjunctiva and quickly epithelise over. They are often not solitary. Recurrences are very common. If cornea is not involved there is no scarring; full recovery occurs. Decreased vision may be due to dense corneal scarring with pannus. Corneal perforation is a very rare

Cornea: Sclero keratitis : Marginal keratitis with involvement of the contagious sclera. Arise either as an extension of TB scleritis or from the bacilli from the Schlemms canal producing corneal lesions Initially there is deep, vascular congestion at the limbus followed by the appearance of corneal infiltrates. This localized inflammation may later become intense. The attack may heal by corneal scarring or may progress to severe keratitis or kerato-uveitis and produce blindness

Sclero-keratitis

Interstitial keratitis
extend from sclero-keratitis or progression of disease from uveal focus. Gradual onset with slow involvement of the cornea, involving the lower 2/3rd. Peri-corneal inflammation-mild to moderate. Diffuse corneal infiltrates with intracorneal nodules real tubercles. Characteristic superficial vascularisation with occasional deep vascularisation Prolonged course with frequent exacerbation and remissions. Healing is by scarring or calcareous degeneration of the cornea causing loss of vision.

Deep central keratitis Arise from the bacilli in the aqueous which penetrate the corneal endothelium, Descemets membrane and parenchyma of the cornea. Infiltration confined to the deep layers of the central cornea, which gradually spreads to the upper and middle layers leaving a marginal peripheral area clear. Corneal sensations +++ Characteristic deep vascularisation which may proceed to superficial layers in the late stages. Healing is by scarring or calcareous degeneration of the cornea

infiltrates of the cornea

Seen in older age groups. Appear as small, localised, whitish infiltrates with illdefined borders and often an opaque halo which merges into clear cornea. These infiltrates may either undergo necrosis, ulceration and sloughing or healing by severe scarring with loss of vision

corneal ulcers
Exremely rare condition. Progressive, relentless and destructive ulcer extending from the limbus with sloping edges and have a caseous base. TB bacilli are found in the scrapings. Secondary infection of the ulcer is common. Ulcer may progress and perforate the cornea leading to loss of vision

Sclera May cause episcleritis or scleritis Anterior Scleritis Most frequent type Appears as a deep, purplish-red congestion which does not fade on the injection of ephedrine into the conjunctival sac. Involves characteristically 1 sector of the sclera. In the malignant form, there is brawny scleritis, a diffuse, succulent oedematous inflammation of both the sclera and episclera. Scleral perforation does not occur.

Posterior scleritis
Affects the sclera posterior to the equator + Tenons capsule = sclero-tenonitis. Characterised by lid oedema, little or no anterior inflammation, mild-moderate proptosis and decreased eye movts. Moderate pain during the acute stage of tenonitis. Proptosis and ocular immobility disappear as the secondary tenonitis fades

uveal tract A TB focus may probably be the starting point from

which all the other types of endogenous ocular TB arise. Mode of spread = haematogenous spread. Both the Anterior and the posterior uvea may be involved independently

Anterior TB Uveitis: Tuberculous granulomatous uveitis:

Slow onset Peri-corneal congestion, thickened iris, loss of normal iris pattern and iris lustre, severe post. Synechiae, muttonfat KPs, prescence of the Koeppes nodules at the pupillary margin. Capsular clouding of the lens and secondary glaucoma occurs.

Anterior uveitis

Nodular Tuberculous Iritis

miliary tubercles on the iris. Occur in pts with low sensitivity to tuberculin Insidious onset with minimal inflammation Tubercles appear as small greyish nodules, either in the superficial iris or in the iris stroma with little surrounding inflammatory reaction

Conglomerate tubercle of the iris

Rare condition Results either from a forward extension of ciliary tubercle or from the fusion of miliary tubercles Appears as a large, invasive malignant tumour located at the angle of the AC. Pain is constant Very poor prognosis

Posterior TB uveitis Circumscribed choroiditis

Usually affects the individual > 20 yrs age Has a predilection to involve macula. Initially ill defined lesion in the posterior pole In 6 wks, the lesion becomes more well defined, becomes circumscribed and healing appear with pigment around the lesion and secondary gliosis. Within 3-4 mths the lesions appear healed. Recurrences are frequent, appear at the periphery of the old lesion

Spreading choroiditis Devastating form of choroiditis seen in<20 yrs having high sensitivity and low immunity. rapid inflammation and exudations, starting as a small focus spreading over the entire fundus and overlying retina. There is clouding of the vitreous and decreased vision. Necrosis and caseation always occur Finally, there is wide spread atrophic choroiditis, with pigment heaping, gliosis of the choroid and retina and exposure of the choroidal vessels.

Miliary TB of the Choroid

Terminal complication of the TB meningitis. multiple, 1-3 or more in number, appear as small yellowish- pink nodules with little or no evidence of surrounding inflammation. Characteristically seen in the posterior pole of the eye

Solitary tubercles of the Choroid

in adults having low sensitivity and high immunity.pearlywhite or greyish masses Little or no vitreous clouding is seen. Tubercles usually heal by hyalinization, the inflammatory reaction may become intense and a conglomerate tubercle of the posterior segment may form.

Conglomerate tubercle of the posterior segment

Extremely rare, break down of a solitary tubercle, appears as a large mass covered with exudate and Hhages, retina becomes detached and vitreous clouding is present. Necrosis and caseation are rapid.

Vitreous findings Anterior vitreous cell with the development of

cellular aggregates known as "snowballs" in the anterior and inferior vitreous. Pars plana "snowbanking" or granulomas can be seen.

TB is an important diagnosis in the differential of pars planitis syndrome, especially if it is unilateral.

TB retina
secondary to choroidal TB 2 forms : 1. Superficial multiple or single exudates in the retina 2. TB periphlebitis

Exudative retinitis
haematogenous spread in adults having low moderate tuberculin hypersensitivity superficial, multiple rather circumscribed exudates

Periphlebitis:
Most frequent cause of Eales disease Common in India & middle east M>F 20-30 yrs 80-90% BL

extensive vascular sheathing

Clinical course:
Stage of inflammation Stage of ischemia/ non perfusion Stage of neovascularization with/ without sequalae Etiology: Unknown Assoc with TB, focal sepsis , thrombangitis oblterans

C/f Stage of inflammation:

Vascular sheathing Exudates Retinal hage Vitreous cells Macular oedema Epiretinal membrane AC flare KP

Stage of nonperfusion
Obliterated vessels A-V shunts BRVO Demarcation bet perfused and non perfused areas

Stage of neovascularization:
NVD NVE Haemorrhages Fibrovascular proliferation Tractional retinal detachment

Management AIMS:
Reducing vasculitis and vitritis Reducing risk of vit hage Removing nonresolving vit hage

Mainstay of t/t is STEROIDS

Topicals , sub tenons, systemic Used in inflammatory phase

Steroids: Topicals: predacetate 1% Dexamethasone 0.1%

Peribulbar Triamcinolone

Oral Prednisolone 1-1.5 mg/kg/day

capillary closure, vascular leakage, venous beading and early NVE

Optic nerve TB optic neuritis

complication of TB meningitis in 10-60% of the cases. Tubercles are found along the pial coat and may even be present along the intra septal pial extensions into the nerve substance. Necrosis and caseation follow with complete destruction of the nerve occurs ultimately leading to complete optic atrophy TB optic neuritis may occur following retinal periphlebitis as well

Papillar edema

Neuro-ophthalmic disease: Tuberculous meningitis Raised ICT will lead to VI and III CN palsies, Optic atrophy occurs with progressive necrosis and caseation of the optic nerve.

INVESTIGATIONS:
DEFINITIVE DIAGNOSIS PRESUMPTIVE DIAGNOSIS

DEFINITIVE DIAGNOSIS:

1) Microscopy:
easiest but least sensitive test. Requires density of 5,000 to 10,000 bacilli per ml. aqueous or vitreous specimens are used

2) Culturing:

more sensitive and can detect densities of 10-100 bacilli per ml

Colonies of myco tuberculosis on L-J medium

Acid fast stain

3) PCR:to amplify mycobacterial DNA Presumptive diagnosis relies on a combination of features including the clinical picture, evidence of disease elsewhere and evidence of previous tuberculous infection. 1)Radiology: can show both active and old pulmonary tuberculosis 2) Extra-ocular tissue specimens : serial sputum samples, broncho-alveolar lavage, transbronchial biopsy. sent for microscopy, culture and PCR

3) Tuberculin skin testing: Mantoux test: reaction depends on delayed-type hypersensitivity and therefore is testing whether the patient has an acquired specific immune response to the bacillus

4) OCT : choroidal lesions highlights an elevated choroid with localized contact of the choriocapillaris-retinal pigment epithelial complex with subretinal fluid.
5) Other tests: Interferon gamma titers

6) Indocyanin green angiography: both for diagnosis and monitoring the effect of t/t

Hypofluorescent spots

Ophthalmologists are involved in three aspects of tuberculosis (TB) management: 1. Screening known tuberculosis patients for ocular manifestations of the disease. 2. Diagnosing ocular tuberculosis in patients presenting with eye problems. 3. Assessing the ocular complications of anti- tuberculous medication.

Treatment: Medical t/t

1) Patients ocular inflammation and who have a recent skin test conversion, positive sputum cultures, chest x-ray, or systemic findings consistent with TB clearly need t/t of pulmonary TB. Ocular inflammation improves with systemic treatment. A 4-drug regimen is given:Isoniazid, rifampin, ethambutol, and pyrazinamide for 2 months, then ethambutol and pyrazinamide are discontinued. Isoniazid and rifampin are continued for an additional 4-7 months for a total duration of therapy of 6-9 months.

For ocular TB with extrapulmonary involvement and without pulmonary involvement, t/t same, except ethambutol may be left off and t/t is required for 9 months.

2) Patients with uveitis: ocular inflammation positive

TB skin test with no systemic associations, and negative chest x-ray anti -TB antibiotic t/t is considered.

o If the uveitis is severe, progressive, or difficult to manage with local and systemic immunosuppressive drugs or if the uveitis is sight threatening, then anti-TB therapy should be considered. o There is need of a bacteriocidal agent and a sterilizing agent. Isoniazid initially decreases bacterial load by bacteriocidal activity, while rifampin and pyrazinamide may be used for sterilization.

3) With no other evidence of TB other than ocular with positive PPD, a 2-drug regimen of isoniazid (300 mg/d) and rifampin (600 mg/d) for 9-12 months is advocated . For iris nodules/ciliary body masses, the addition of pyrazinamide is done

Ocular toxicity of anti-TB drugs Ethambutol:

causes dose dependent optic neuritis (focal areas of papillomacular axonal swelling and occasional demyelination, scotomas) pts with renal insufficiency at risk gout or hyperuricemia, GI disturbances, headache, confusion, and disorientation, and peripheral neuritis

Rifampin: Liver damage in pre-existig liver disease INH:

may cause optic neuritis but is rare,chr alcoholics and malnourished people at risk. administer pyridoxine (vitamin B-6) in individuals with poor nutrition or predisposed to developing neuropathy

OCULAR LEPROSY
The ocular lesions of leprosy can be classified into 4 categories: direct invasion of the eye by M. leprae sensitization of ocular tissue to M. leprae antigens and due to formation of intravascular immune complexes Secondary lesions following granulomatous infiltration of the V and VII cranial nerves Secondary lesions following granulomatous infiltration of contiguous structures eyebrows, eyelids, lid glands, lacrimal drainage system.

 Caused by M. Leprae Seen mostly in tropics and subtropical areas 25% cases show ocular involvement
2 main types: Tuberculoid leprosy (TT) Lepromatous leprosy (LL)

s/s common with the lepromatous type of leprosy Grading of Eye signs: Grade-I:Insensitivity of cornea is sight threatening lesions (STL) but not very severe in itself Grade-II :Lagophthalmos ,not serious but causes exposure keratitis Grade III : Keratitis, Iritis, Scleritis Grade IV : perforation of cornea, iridocyclitis, secondary glaucoma Grade-V : burnt out disease, development of unilateral or bilateral phthisis bulbi

Lids & conjunctiva

Chronic conjunctivitis severe lagophthalmos Loss of lashes (Madarosis) Trichiasis Tylosis
Tylosis

Bilateral total loss of brows and madarosis

Corneal signs: exposure keratitis due to the paralysis of one or both orbicularis muscles as the facial nerve is affected, Superficial punctate keratitis in LL Grey spots of infiltration The minute grains of chalk appearance in the cornea : pathognomonic of leprosy chronic interstitial keratitis may develop Corneal sensations are lost Leprous pannus corneal nerves thickening or beading earliest detectable ocular findings

Superficial punctuate keratitis

Beading of corneal nerves

Episclera and sclera

Episcleritis Small episcleral nodules at the limbus

Iris 1) Iridocyclitis : of chronic nature pathognomonic sign: glistening iris pearls at the pupillary margin. pearls slowly enlarge and coalesce become pedunculated and drop into AC Iris atrophy and miotic pupil caused by the immune complex deposition in the uvea associated with systemic symptoms such as fever and swelling of skin lesions large granuloma, leproma may occur in AC Poor prognosis

scleritis

iridocyclitis

Iris atrophy and miotic pupil

Specific grey spots in iris

Other features
Small nodules may be seen in the periphery in the anterior choroid occasionally Lacrimal glands are occasionally enlarged leading to lepromatous dacryoadenitis Secondary cataract and glaucoma

Diagnosis: