Mycobacterium tuberculosis is one of the important infectious agent responsible for intermediate uveitis. It was thought that eye shows hypersensitivity to the non-viable or tubercular bacilli DNA causing such uveitis. For definite diagnosis of aetiology, isolation of the MTB bacilli from vitreous sample, aqueous paracentesis or retinal biopsy is required.
Our study provided the clinical spectrum and visual outcome of patients with intermediate uveitis with positive PCR of intraocular fluids for MTB. Pubmed search did not show any study on Real Time/nested Quantitative PCR positivity for MTB in intermediate uveitis. PCR has emerged as a powerful tool for rapid detection of the mycobacterial genome, with a high specificity and a variable sensitivity. The utility of PCR analysis lies in important facts like ocular samples usually are tested negative for the acid fast bacilli (AFB) with direct smear and culture due to paucibacillary nature of the disease and the systemic involvement may not be present at the time of ocular disease, causing delay in diagnosis and management.[9]
PCR has a very low false-positive rate on intraocular fluids. External contamination leads to false-positive and polymorphism, specimen degradation, or failure to sample in the acute stages of disease causes false-negative results.19 Arora et al. evaluated the role of PCR for detection of Mycobacterium tuberculosis in aqueous humour samples obtained from eyes with active uveitis and showed that it can be effectively used for the diagnosis of intraocular tuberculosis which was supported by the review report by Gupta et al.20 In our study we performed PCR testing for presumed tubercular intermediate uveitis. As culture is difficult and time consuming, presently, the use of real-time PCR can be done to establish tubercular aetiology, our study also proved PCR to be an important tool for rapid detection of the mycobacterial genome in suspected tubercular intermediate uveitis cases.
According to COTS-2 guidelines either one or both immunologic tests (purified protein derivative) PPD, interferon gamma release assay IGRA) along with high resolution computed tomography (HRCT) of chest suggestive of healed TB infections were candidates for ATT treatment.16
Parchand et al discussed the clinical profile of intermediate uveitis in Indian population and concluded that addition of anti-tuberculosis therapy in cases of intermediate uveitis of presumed tubercular origin can reduce the recurrences.10 According to them, patients were diagnosed as intermediate uveitis of presumed tubercular aetiology if there was a documented positive tuberculin skin test (10 mm of induration or more) at 48–72 hours with evidence of vitritis, snowballs, or snow banking; and all known causes of infectious uveitis except TB and known non-infectious uveitis syndromes were ruled out. Madhavan et al. proved the presence of tuberculosis genome in the vitreous chamber fluid and the epiretinal membrane in Eales disease. They found that 5 out of 14 vitreous (20.8%) fluid samples were positive for tuberculosis genome. In our study we found that about 64% of the patients showed positivity for TB genome in nested PCR and 48 percent cases showed positivity in real time PCR in intermediate uveitis. The PCR results showcased circulating antigens of tuberculosis leading to an inflammatory response. In our study, fundus evaluation of patients with positive PCR (AC tap or Vitreous tap) demonstrated features snow ball opacities and vitritis. Our study provides clinical profile of cases of intermediate uveitis with documented evidence of MTB DNA in ocular fluids. Of note is that 48 % of patients in the study had actively multiplying copies of MTB DNA by Real-time PCR. In cases with signs and symptoms of intermediate tubercular uveitis but not fitting into COTS 2 criteria, ocular fluids PCR testing can also be considered as diagnostic modality for appropriate diagnosis and treatment. Figueira et al. described the role of anti- tuberculosis treatment in inflammatory diseases suggestive of tubercular aetiology. 21 The consensus was that the positively screened patients should be treated for active tuberculosis with 4 drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) for 6–9 months. Patients should be reviewed at end of initiation phase which is 2 months and the end of treatment which is 9 months. Sixteen percent of our patients had recurrences in one year period.
The major limitations of the study include small sample size, retrospective nature, lack of comparison with other causes of intermediate uveitis with intraocular fluids negative for PCR and relatively short follow up, lack of standardization of PCR and low sensitivity. Further studies are needed to find out the role of PCR in intermediate uveitis of tubercular origin.