uveitis causes and treatment
Infectious Posterior Uveitis
Posterior uveitis has a broad differential diagnosis which can be grouped into infectious, inflammatory and neoplastic causes. Infectious posterior uveitis accounts for majority of the cases of uveitis . The differential diagnosis of infectious posterior uveitis is broad and it includes various microorganisms and their clinical presentations. Many of these results in morbidity and mortality, thus, appropriate, timely management is required to save the eye and life of the patient. Thorough clinical evaluation gives a clue to the diagnosis which is confirmed by various laboratory investigations. The common infectious causes include syphilis, toxoplasmosis, tuberculosis and viral causes. This review highlights the clinical features, diagnosis and treatment options of these causes.
Ocular syphilis can cause any type of uveitis, and has to be ruled out as it is the most common intraocular bacterial infection and re-emerging in various forms, especially with AIDS (about 1-2% of HIV positive cases are found to have ocular syphilis).
Ocular syphilis has been regarded as ” the great imitator ” as it may involve any ocular structures with features of either conjunctivitis, scleritis, interstitial keratitis, iridocyclitis or postrior uveitits (vitritis, chorioretinitis, serous retinal detachment, vasculitis). Syphilis can present with placoid choroidal lesions in which there are large, solitary, grey-white or pale yellowish placoid subretinal lesions . It gives a pattern of coarsely stippled hyperpigmentation seen on fundus autofluorescene.
Syphilitic uveitis can be the first presentation of systemic disease. Syphilitic punctate inner retinitis is a typical presentation of syphilitic posterior uveitis which have very distinct inner retinal and preretinal white spots associated with inner retinitis and arteriolitis. Syphilis also presents with optic nerve vasculitis with leakage of lipid and protein and exudate accumulating in the peripapillary outer plexiform layer. Serous component of the exudate reabsorbs and a lipidrich deposit precipitates in the outer plexiform layer of Henle’s layer, resulting in a typical macular star appearance (Figure 1) classically associated with cat scratch disease.
DIAGNOSIS– Diagnosis can be divided into 2 categories. Non treponemal tests include Venereal Disease Research Laboratory(VDRL) and rapid plasma reagin (RPR). These use cardiolipinlecithin-cholesterol antigen to test there activity of human IgG and IgM. The test has low sensitivity.
Treponemal tests include Treponema pallidum particle agglutination(TP-PA) and fluorescent treponemal antibody absorption(FTA-Abs).These are more sensitive and specific, thus, considered as confirmatory tests .
TREATMENT- Ocular syphilis is treated same as neurosyphilis with aqueous penicillin G (2-5 million units IV every 4 hrs for 10-14 days). Alternatively , one may use penicillin G procaine 2.4 million units IM dailly with 500 mg probenecid orally QID for 0-14 day.
OCULAR TOXOPLASMOSIS Ocular toxoplasmosis is the most common infective cause of posterior uveitis in immunocompetent patients. Earlier it was considered to be a congenital infection, but new evidence suggests that acquired disease are becoming much more common. The characteristic lesion is focal necrotisisng retinochoroiditis along with vitritis (HEADLIGHT IN FOG appearance). Initial lesion starts in superficial retina, gradually involving full thickness . These lesions remain active for up to 16 weeks and then resolve, leaving a hyperpigmented scar (Figure 2). Vascular involvemnent may be seen near active lesion presenting as diffuse or segmental vasculitis.
D I A G N O S I S – D i a g n o sis o f o c u l a r toxoplasmosis is almost always clinical with investigations like FFA, ICG and OCT being complimentary. An acute T.gondii infection can be demonstrated by detection of specific IgM or IgAantibodies, or both, in the blood. PCR and real time PCR are rapid and sensitive technique for the diagnosis of ocular toxoplasmosis.
TREATMENT- It consists of pyrimethaminesulfadiazine combination and corticosteroids. An initial dose of 75-100 mg of pyrimethamine is given daily for 2 days, followed by 25-50 mg dose daily and 2-4 g sulfadiazine daily for 2 days, followed by 500mg to 1 g dose every 6 hrs as well s 5 mg folinic acid daily for 4-6 weeks. Oral prednisolone is given (1mg/kg) from the 3rd day of therapy and tappered over 2-6 weeks. Other treatment includes quadruple drug therapy( classic regimen +clindamycin).
Ocular TB can be primary (eye is initial site of entry) or secondary (organism spreads to eye hematogenously). Hypersenstivity reaction to tuberculous protein can also cause retinal vasculitis. It may involve any ocular structure causing any type of uveitis, with posterior uveitis being the most common. In the posterior segment, TB may manifest as choroidal tubercles or tuberculoma , subretinal abscess, serpiginous choroiditis (SC), or retinal vasculitis (Figure 3). Choroid tubercles is the earliest sign presenting as small yellow nodules with indistinct borders. Tuberculomas are larger, solitary, tumor-like masses with overlying hemorrhage, exudate, or sub- retinal fluid. Choroidal mass may be seen typically elevated accompanied with retinal detachment. Subretinal abscess is formed prgressively from choroid tubercle. In serpiginous-like choroiditis (SLC), there is hypersensitivity in the choroid or retinal pigment epithelium (RPE), resulting in multifocal plaquelike choroiditis .
DIAGNOSIS – In common clinical practise, diagnosis include tuberculin senstivity test (TST), interferon-gamma release assay and chest X-ray or HRCT. For definitive diagnosis , PCR for M.tuberculosis from aqueous or vitreous tap can be done. Angiography confirms activity in choroiditis and shows ring of fire appearance in the subretinal abscess/choroidal granuloma.
TREATMENT- Anti-tubercular therapy (ATT) should be started by an infectious disease specialist once tubercular etiology is confirmed and may include isoniazid, rifampicin, pyrazinamide, and ethambutol for 9-12 months . Concomitant systemic steroids for 4-6 weeks is given in tapering dose as it protects against tissue damage from delayed type of hypersenstivity .
Viral retinitis is predominantly caused by the herpes family of viruses (VZV, HSV, CMV). Herpetic eye disease is among the most common cause of infectious uveitis.Posterior uveitis caused by herpes virus may appear as part of herpetic disease elsewhere (skin,brain) or as an isolated finding. Most forms of herpetic posterior uveitits is acute and fulminant, often causing serious complications like retinal detachment and proliferative vitreoreinopathy. Acute retinal
necrosis (ARN ) is most often found in an immunocompetent host, whereas progressive outer retinal necrosis (PORN) and CMV are seen in an immunocompromised host. ARN is characterised by clinical triad of severe vitritis, arteritis and periphlebitis. Confluent peripheral retinal necrosis is diagnostic of ARN(figure 4) , presenting as panuveitis. Necrotisisng retinitis, confluent areas of outer retinal whitening with minimal vitritis involving the posterior pole and sparing of retinal vessels at early stage, gives a typical ”cracked mud appearance” , and is diagnostic of PORN. CMV retinitis has a characteristic granular or pizza pie appearnce and a typical brushfire pattern of spread along the blood vessels .
DIAGNOSIS- Diagnosis is basically clinical, aqueous humor aspirate may be analyzed for local production of antibodies against HSV or VZV by the ELISAmethod.
TREATMENT- Treatment is given with topical corticosteroids and cycloplegics and systemic antiviral drugs. IV acyclovir is treatment of choice for ARN. Regimen consist of 15 mg/kg/day IV acyclovir for 3 divided dose for 7- 10 days, followed by oral antiviral either acyclovir (800 mg five time a day) or valacyclovir (1 gmthree times a day) for upto 6 weeks. 3 drugs are approved for treatment of CMV retinis : gancyclovir ,foscarnet and cidofovir. Systemic therapy started with 2 weeks of twicw daily IV gancyclovir 5mg/kg or foscarnet 90mg/kg or once we ekly c idofovir 5mg/kg, follwed by maintenance therapy of once daily gancyclovir 5mg/kg or foscarnet 90-120 mg/kg or cidofovir 5mg /kg every 2 weeks.
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