Adjunctive Intravitreal Anti-vascular Endothelial Growth Factor and Moxifloxacin Therapy in Management of Intraocular Tubercular Granulomas.

PURPOSE: To report pre and post treatment levels of VEGF-A in the aqueous humour of patients with intraocular tubercular granulomas and study the effect of a combined intravitreal anti-VEGF bevacizumab and moxifloxacin therapy on their regression. METHODS: Aqueous samples of 10 consecutive patients with intraocular tubercular granulomas obtained before and after initiating treatment were subjected to ELISA for analysing intraocular VEGF-A levels. Intravitreal injections of bevacizumab and moxifloxacin were given weekly till complete regression of these granulomas. All patients received the usual four-drug ATT and oral corticosteroids. RESULTS: Mean baseline VEGF-A level was 1004.27±411.40 pg/ml (401.32-1688.95) that reduced significantly to 27.62±46.86 pg/ml (6.9-131.83) at the last injection. Meannumber of intravitreal injections was 3.1 (2-4). We found significant correlation of decreasing levels of aqueous VEGF-A with the clinical regression of these tubercular granulomas. CONCLUSIONS: Intraocular TB granulomas have high levels of VEGF-A. Weekly intravitreal injections of anti-VEGF bevacizumab with moxifloxacin as an adjunct to the standard care may cause prompt regression of tubercular granulomas. ABBREVIATIONS: TB: Tuberculosis; IOTB: Intraocular tuberculosis; VEGF: Vascular endothelial growth factor; RD: Retinal detachment; Mtb: Mycobacterium tuberculosis; ATT: Antitubercular therapy; AMD: Age-related macular degeneration; SRF: Subretinal fluid; ELISA: Enzyme immunosorbent assay; PCR: Polymerase chain reaction; ONH: Optic nerve head; MDR-TB: Multidrug-resistant tuberculosis; pg/ml: picogram/milliliter; ESR: Erythrocyte sedimentation rate; CECT: Contrast enhanced computed tomography; DNA: Deoxyribonucleic acid; RNA: Ribonucleic acid; BSL: Biosafety level; BCVA: Best corrected visual acuity; HM: Hand movements; KP: Keratic precipitates; PSC: Posterior subcapsular cataract; PS: Posterior synechiae; CRA: Chorio-retinal atrophy; IVMP: Intravenous methyl prednisolone; OCT: Optical coherence tomography; RPE: Retinal pigment epithelium; FFA: Fundus fluorescein angiography; ICG: Indocyanine angiography; RAP: Retinal arterial proliferans.

Clinical Features and Outcomes of Patients With Tubercular Uveitis Treated With Antitubercular Therapy in the Collaborative Ocular Tuberculosis Study (COTS)-1.

Importance: Eradication of systemic tuberculosis (TB) has been limited by neglected populations and the HIV pandemic. Whereas ocular TB often presents as uveitis without any prior evidence of systemic TB, the existing uncertainty in the diagnosis of TB uveitis may perpetuate missed opportunities to address systemic TB. Objective: To examine the clinical features of TB uveitis and the associations with response to antitubercular therapy (ATT). Design, Setting, and Participants: This retrospective multinational cohort study included patients from 25 ophthalmology referral centers diagnosed with TB uveitis and treated with ATT from January 1, 2004, through December 31, 2014, with a minimum follow-up of 1 year. Main Outcomes and Measures: Treatment failure, defined as a persistence or recurrence of inflammation within 6 months of completing ATT, inability to taper oral corticosteroids to less than 10 mg/d or topical corticosteroid drops to less than 2 drops daily, and/or recalcitrant inflammation necessitating corticosteroid-sparing immunosuppressive therapy. Results: A total of 801 patients (1272 eyes) were studied (mean [SD] age, 40.5 [14.8] years; 413 [51.6%] male and 388 [48.4%] female; 577 [73.6%] Asian). Most patients had no known history (498 of 661 [75.3%]) of systemic TB. Most patients had bilateral involvement (471 of 801 [58.8%]). Common clinical signs reported include vitreous haze (523 of 1153 [45.4%]), retinal vasculitis (374 of 874 [42.8%]), and choroidal involvement (419 of 651 [64.4%]). Treatment failure developed in 102 of the 801 patients (12.7%). On univariate regression analysis, the hazard ratios (HRs) associated with intermediate uveitis (HR, 2.21; 95% CI, 1.07-4.55; P = .03), anterior uveitis (HR, 2.68; 95% CI, 1.32-2.35; P = .006), and panuveitis (HR, 3.28; 95% CI, 1.89-5.67; P < .001) were significantly higher compared with posterior distribution. The presence of vitreous haze had a statistically significant association (HR, 1.95; 95% CI, 1.26-3.02; P = .003) compared with absence of vitreous haze. Bilaterality had an associated HR of 1.50 (95% CI, 0.96-2.35) compared with unilaterality (HR, 1 [reference]), although this finding was not statistically significant (P = .07). On multivariate Cox proportional hazards regression analysis, the presence of vitreous haze had an adjusted HR of 2.98 (95% CI, 1.50-5.94; P = .002), presence of snow banking had an adjusted HR of 3.71 (95% CI, 1.18-11.62; P = .02), and presence of choroidal involvement had an adjusted HR of 2.88 (95% CI, 1.22-6.78; P = .02). Conclusions and Relevance: A low treatment failure rate occurred in patients with TB uveitis treated with ATT. Phenotypes and test results are studied whereby patients with panuveitis having vitreous and choroidal involvement had a higher risk of treatment failure. These findings are limited by retrospective methods. A prospectively derived composite clinical risk score might address this diagnostic uncertainty through holistic and standardized assessment of the combinations of clinical features and investigation results that may warrant diagnosis of TB uveitis and treatment with ATT.

Moxifloxacin: An Alternative to Ethambutol for the Treatment of Presumed Ocular Tuberculosis.

OBJECTIVE: To present moxifloxacin as an alternative treatment option to ethambutol in an anti-tubercular therapy (ATT) regime in patients with presumed ocular tuberculosis (TB). METHODS: We identified all cases in our hospital referred for treatment of presumed ocular TB between 2009 and 2013. Age, gender, ophthalmic examination, blood tests, treatment regimens, adverse drug reactions, and outcomes were collected and analyzed for the patients who had moxifloxacin as part of their ATT. RESULTS: Forty-three cases of presumed ocular TB were treated with moxifloxacin as a part of ATT. Mean age was 44.18 ± 12.47 years; 62.8% were male. A response to treatment, with no evidence of disease recurrence, was seen in 72.1% of cases. Shortened ATT duration was associated with increased risk of treatment failure (p = 0.02, 95% CI: -0.77 to -0.00). CONCLUSIONS: Moxifloxacin can be considered as a safe and effective alternative to ethambutol for the treatment of presumed ocular TB.

[Vasoproliferative tumor associated with presumed ocular tuberculosis: case report]. / Tumor vasoproliferativo associado à tuberculose ocular presumida: relato de caso.

PURPOSE: To describe a case of vasoproliferative tumor associated with presumed ocular tuberculosis treated with cryotherapy and intravitreal triamcinolone injection. STUDY DESIGN/PATIENT AND METHODS: Interventional case report. A 42-year-old female patient reported inflammation of the right eye 1 year ago, treated with oral prednisone for 30 days. She referred blurred vision in the right eye since childhood. Ophthalmologic examination showed 20/400 visual acuity in the right eye. Biomicroscopy and intraocular pressure were normal. Fundus examination showed vascularized elevated lesion, associated with serous retinal detachment and hard exudates at the inferior periphery. The lesion was surrounded by extensive area of hyperplastic retinal pigment epithelium. The macula showed attenuation of the foveal reflex. Ocular ultrasound showed a 2.25 mm height vascularized lesion. Serologic examination, hemogram and thorax RX were normal. PPD was considered strong reactor and tuberculosis was diagnosed after positive BK research. Considering the clinical aspects, the ocular diagnosis was vasoproliferative tumor associated with presumed ocular tuberculosis. Treatment with rifampicin, isoniazide and pyridoxine was started. We decided to treat the ocular tumor with cryotherapy and intravitreal triamcinolone injection (4 mg/ml). After 30 days, serous detachment was smaller and the tumor showed atrophic areas. Fluorescein angiography showed areas of vascular hyperfluorescence with slight extravasation and areas of blocked fluorescence due to RPE hyperplasia. Secondary vasoproliferative tumors are retinal glial proliferations and are associated with many ocular conditions that affect retina and choroid. Because of the great number of associated complications, with important visual loss, vasoproliferative tumors should be treated at the moment of diagnosis. Treatment of choice is cryotherapy. Intravitreal triamcinolone can be used as adjuvant treatment because of its angiogenic properties. Until the present moment, no ocular tuberculosis and vasoproliferative tumor association were reported in the literature. Treatment of secondary vasoproliferative tumors with cryoterapy and intravitreal triamcinolone appears as a new therapeutic choice. Further studies are necessary to prove the efficacy of this association.

Tumor vasoproliferativo associado à tuberculose ocular presumida: relato de caso / Vasoproliferative tumor associated with presumed ocular tuberculosis: case report

OBJETIVO: Descrever um caso de tumor vasoproliferativo associado à tuberculose ocular tratado com crioterapia e injeção de triancinolona intravítrea. DESENHO DO ESTUDO/PACIENTES E MÉTODOS: Relato de caso intervencional. Paciente do sexo feminino, 42 anos, referia inflamação do olho direito havia 1 ano, não diagnosticada, tratada com prednisona oral por 30 dias. Relatava baixa visão com o olho direito (OD) desde a infância. Negava antecedentes pessoais e familiares. Ao exame ocular, apresentava acuidade visual menor que 20/400 com o OD. Não apresentava alterações à biomicroscopia e a pressão intra-ocular era normal em ambos os olhos. A fundoscopia do OD mostrava lesão vascularizada, elevada, associada ao descolamento seroso e exsudatos duros, localizada na periferia inferior da retina. A lesão era cercada por extensa área de pontos de hiperplasia do epitélio pigmentar. A mácula apresentava diminuição do reflexo foveal. No exame de ultra-som ocular, a lesão apresentava altura igual a 2,25mm e consistência sugestiva de lesão vascularizada. Foram solicitados exames sorológicos, hemograma, RX tórax e PPD. Os exames foram normais, com exceção do PPD, considerado forte reator. A paciente foi encaminhada ao infectologista, que diagnosticou tuberculose após exame de pesquisa de BK no escarro. Em face do quadro clínico, foi feito o diagnóstico de tumor vasoproliferativo da retina associado à tuberculose ocular presumida. Iniciou-se o tratamento com esquema tríplice (rifampicina, isoniazida e piridoxina). Optou-se por tratar o tumor com crioterapia e injeção intravítrea de triancinolona (4 mg/ml). Após 30 dias, a paciente apresentava diminuição do descolamento seroso e áreas atróficas na lesão tumoral. O aspecto angiofluoresceinográfico mostrava algumas áreas de enchimento precoce da trama vascular com discreto extravasamento tardio do contraste, sem áreas de oclusão capilar. A maior parte da lesão apresentava hipofluorescência por bloqueio (proliferação...

PURPOSE: To describe a case of vasoproliferative tumor associated with presumed ocular tuberculosis treated with cryotherapy and intravitreal triamcinolone injection. STUDY DESIGN/PATIENT AND METHODS: Interventional case report. A 42-year-old female patient reported inflammation of the right eye 1 year ago, treated with oral prednisone for 30 days. She referred blurred vision in the right eye since childhood. Ophthalmologic examination showed 20/400 visual acuity in the right eye. Biomicroscopy and intraocular pressure were normal. Fundus examination showed vascularized elevated lesion, associated with serous retinal detachment and hard exudates at the inferior periphery. The lesion was surrounded by extensive area of hyperplastic retinal pigment epithelium. The macula showed attenuation of the foveal reflex. Ocular ultrasound showed a 2.25 mm height vascularized lesion. Serologic examination, hemogram and thorax RX were normal. PPD was considered strong reactor and tuberculosis was diagnosed after positive BK research. Considering the clinical aspects, the ocular diagnosis was vasoproliferative tumor associated with presumed ocular tuberculosis. Treatment with rifampicin, isoniazide and pyridoxine was started. We decided to treat the ocular tumor with cryotherapy and intravitreal triamcinolone injection (4 mg/ml). After 30 days, serous detachment was smaller and the tumor showed atrophic areas. Fluorescein angiography showed areas of vascular hyperfluorescence with slight extravasation and areas of blocked fluorescence due to RPE hyperplasia. Secondary vasoproliferative tumors are retinal glial proliferations and are associated with many ocular conditions that affect retina and choroid. Because of the great number of associated complications, with important visual loss, vasoproliferative tumors should be treated at the moment of diagnosis. Treatment of choice is cryotherapy. Intravitreal triamcinolone can be used as adjuvant treatment...