AIM: To determine the spectrum of uveitis, causes of visual loss in systemic tuberculosis (TB), role of investigations and outcome after anti-TB therapy (ATT). METHODS: A retrospective study was conducted on 250 patients with systemic TB at a referral center in Chennai, South India from April 2016 to May 2019. Systemic workup comprised of Mantoux, chest X-ray, polymerase chain reaction (PCR) and QuantiFERON (QFT) TB Gold. Aqueous humor analysis by nested PCR or real time PCR (RT-PCR) and ancillary ophthalmic investigations such as fundus fluorescein angiography, optical coherence tomography were performed. RESULTS: Multifocal choroiditis and vasculitis were the most common manifestations (39% and 24% respectively) together accounting for 61% of cases and they had a higher risk of recurrence (3%). Pulmonary tuberculosis (PTB) was more frequently associated with uveitis (18%). Among those with extra-pulmonary tuberculosis (EPTB), uveitis occured in miliary TB (2%), bone (1%) and abdominal TB (1%). Complications such as cystoid macular edema, choroidal neovascular membranes and macular scarring caused visual loss. Aqueous humor analysis detected mycobacterium TB antigen. Collectively, systemic investigations such as chest X-ray, Mantoux test and those performed on blood samples such as PCR and QFT were positive in 39% of patients. In inconclusive patients, nested PCR and/or RT-PCR were done on aqueous humor samples and were diagnostic in 96%. A combination of tests was diagnostic in 92%. ATT in isolation in 71% and combined with corticosteroids in 29% was used for treatment of which signs of resolution and improvement in vision started as early as 6wk in those who were started immediately on corticosteroids and ATT and longer than 3mo in those on ATT alone. Prompt treatment with ATT and corticosteroids improved vision in 23% of our patients within 2mo. Vitritis with choroiditis causes cystoid macular oedema and requires longer duration of ATT. Vision improved in 69%. Complete resolution occurred in 75% and worsening in 12%. CONCLUSION: A combination of investigations guided by clinical suspicion helps in precise diagnosis. In diagnostic dilemmas analysis of ocular samples is reliable and confirmatory. Screening all patients and a multidisciplinary approach in TB (active, healed or during treatment) is recommended.