Bilateral choroidal tuberculoma in a patient of miliary tuberculosis

Bilateral choroidal tuberculoma in a patient of miliary tuberculosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Bilateral choroidal tuberculoma in a patient of miliary tuberculosis Tanya Jain, Sachit Mahajan, Aishwaraya Kanagraj This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6434945/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Oct, 2025 Read the published version in Journal of Ophthalmic Inflammation and Infection → Version 1 posted 9 You are reading this latest preprint version Abstract Background Choroidal granuloma is one of the common manifestations of ocular tuberculosis. Tubercles indicate hematogenous dissemination of the disease. Tubercular granulomas respond to Anti Tubercular Treatment (ATT) and systemic corticosteroids. However, in some patients with large granulomas involving macula, adjunct treatment with intravitreal anti-VEGF may be required for prompt management of the granuloma. Findings: We report a case of bilateral Tubercular granuloma in a patient with miliary Tuberculosis (TB). The patient was an immunocompetent young female with miliary tuberculosis. Mantoux was positive. HRCT chest suggested miliary TB. The patient was already on ATT. Clinical examination showed multiple TB granulomas in both eyes, with a large granuloma involving the fovea in the left eye. She underwent intravitreal injection of the anti-VEGF drug bevacizumab (1.25 mg/0.05 mL) (off-label use) with moxifloxacin (500 µg/0.1 mL) (off-label use) in the left eye. She was continued on ATT and was started on oral steroids. After seven weekly intravitreal injections in the left eye at the second-month follow-up, lesions were consolidated and scarring. Optical coherence tomography showed a decrease in the size of the choroidal bump. Conclusion Weekly administration of intravitreal Anti-Vascular endothelial growth factor(VEGF) and moxifloxacin along with ATT and oral corticosteroids has controlled inflammation and has caused consolidation and scarring of TB granulomas in a patient with miliary TB. AntiVEGF TB granuloma miliary TB Figures Figure 1 Figure 2 Figure 3 Background Tuberculosis is caused by mycobacterium tuberculosis. It is well known to involve most ocular tissue, including the orbit and, most commonly, the uveal tissue, due to its high vascularity, which allows easy hematogenous spread of infection.( 1 ) The innate immunity limits the infection through a robust adaptive immune response by forming epithelioid cell granuloma with central areas of caseation necrosis. ( 2 , 3 ) Tuberculosis-related granulomas usually respond well to a combination of systemic steroids and specific antitubercular therapy (ATT).( 2 ) This case demonstrates a patient of miliary tuberculosis with bilateral tuberculous granulomas, managed with intravitreal moxifloxacin and intravitreal anti-VEGF, along with ATT and systemic steroids. Case Presentation A 21-year-old female presented with a history of diminished vision in both eyes (BE) for the past month. There was a history of shortness of breath and headache 2 months earlier. Her Mantoux test and TB gold test were positive, and her high-resolution computed tomography (HRCT) of the chest showed the presence of multiple tiny nodular lesions in bilateral lung fields with no evidence of cavitation suggestive of miliary tuberculosis. She was diagnosed with miliary tuberculosis and was started on ATT by the physician. The best-corrected visual acuity (BCVA) in the right eye (RE) was 6/12, N6, and 1/60, <N36 in the left eye (LE). Anterior segment examination showed conjunctival congestion in the RE. The rest of the anterior segment examination was unremarkable. The intraocular pressure was 14 mm Hg in the RE and 10 mm Hg in the LE (Goldmann applanation tonometer). Fundus examination of the RE showed a healthy optic disc with multiple subretinal yellowish lesions with ill-defined margins with central clearing varying in size from half-disc to two-disc diameters (Fig. 1 A). The LE fundus showed a subretinal elevated yellowish lesion with ill-defined margins and central clearing at the macula involving the fovea measuring around ten disc-diameters with multiple small subretinal yellowish lesions spread throughout the posterior pole and until the mid-periphery. (Fig. 1 B) Optical coherence tomography (OCT) of the RE showed normal foveal contour and elevation of retinal layers with an underlying choroidal bump with hyperreflectivity of the outer retinal layers at the lesion site (Fig. 2 B). OCT of the LE through the lesions revealed similar findings, with elevation of retinal layers and underlying dome-shaped choroidal bump with hyperreflectivity of outer retinal layers at the macula. (Figure- 3B) Mantoux test was positive, and HRCT chest showed bilateral diffuse multiple tiny nodular lesions in the lung parenchyma suggestive of miliary TB. Human Immunodeficiency Virus (HIV) and Hepatitis B surface antigen (HbsAg) were nonreactive and the rest of uveitis workup was negative. Ultrasonography of the abdomen showed splenomegaly. The systemic and ocular investigations were suggestive of ocular tuberculosis (TB) in the form of bilateral choroidal granuloma and disseminated tubercles. Since the granuloma in the LE was significantly larger and involved the macula, we decided to inject the left eye with intravitreal anti-VEGF and moxifloxacin to facilitate early resolution. The granulomas of the RE were relatively small and discrete, and we decided to monitor their resolution with the commencement of the intensive phase of ATT and oral steroids (1mg/Kg body weight). After informed consent, she underwent intravitreal injection of the anti-VEGF drug bevacizumab (1.25 mg/0.05 mL) (off-label use) with moxifloxacin (500 µg/0.1 mL) (off-label use) in the LE under topical anaesthesia. One week after injection, the BCVA of the left eye remained the same at 1/60. However, the lesion appeared to be consolidating. She was continued on weekly intravitreal injections. At 3-week follow-up, her BCVA in the RE improved to 6/9 N6, and her BCVA in the LE improved to 2/60 < N36. The OCT through the granuloma in the LE showed a decrease in the choroidal bump and a reduction of subretinal fluid, suggesting consolidation of the lesion (Fig. 3 D). The lesions in the RE also appeared to be getting well-defined and healing (Fig. 2 C). The oral steroids were tapered, and the patient was continued on the intensive phase of ATT. However, on closer examination of the OCT of the LE, there were a few intraretinal cysts (Fig. 2 D) at the base of the granuloma, suggestive of continued activity, so it was decided to continue with the weekly intravitreal injections. After seven weekly intravitreal injections, her BCVA improved to 6/36, <N36 in the LE, and the choroidal bump decreased in size (Fig. 3 F). The intensive phase of ATT was stopped after 2 months, and the patient was shifted to the continuation phase for 9 months. The oral steroids were tapered in a weekly fashion and stopped after about 10 weeks of treatment. On the last follow-up 5, months after starting treatment, her systemic condition improved, with the healing of her pulmonary lesions. The ocular lesions appeared scarred, and the patient maintained a vision of RE 6/6, N6 and LE 6/24-, N18. The patient continued her continuation phase of ATT and is on two monthly follow-ups. Discussion and Conclusion Choroidal tuberculomas are usually large, unilateral, solitary, yellowish lesions at the posterior pole.Tuberculomas have predilection for the foveal and perifoveal area. They may vary in their presentation with features such as associated haemorrhage, striae, or exudative retinal detachment. Choroidal tubercules are generally small and multiple and have less defined borders than granulomas with more surrounding edema. They have an increased chance of association with central nervous system (CNS) TB.( 4 ) Mehta and associates found choroidal tubercles in 34.6% of 52 patients with neurotuberculosis. ( 5 ) Pathologically speaking, granulomas are chronic collections of inflammatory cells created by the immune system to prevent the dissemination of Mycobacterium tuberculosis. T cells bearing γδ T-cell receptors influence Th1/Th2 cells. The dominant T Helper 1 (Th1) cytokine bias leads to granuloma formation. Immune responses skewed towards T helper 2 (Th2) cells cross-inhibit protective responses such as granuloma formation, which may have a critical role in miliary tuberculosis, ( 6 ) Impaired expansion of γδ T-cells, presence of HLA-Bw15,75 HLA-DRB1*15/16, DRB1*13, and DQB1*0602,76 absence of HLA-Cw6, HLA-DRB1*10, and DQB1*0501 have been described to account for the propensity to develop disseminated tuberculosis. ( 6 ) In a study by Mehta et al. on the patterns of ocular inflammation in patients with miliary tuberculosis(TB), all 22 eyes of the patients with miliary TB included showed no signs of inflammation on slit lamp examination and single or multiple choroidal tubercles bilaterally in 7 patients and unilaterally in 4 patients with no associated vitritis or raised intraocular pressure. ( 7 ) In large TB granuloma, there is local ischemia leading to upregulation in vascular endothelial growth factor (VEGF) production at retinal pigment epithelium (RPE) and photoreceptor levels.( 3 ) Due to increased VEGF production, TB granulomas are associated with high vascularity and angiogenesis. ( 2 ) Hence, for the effective treatment of these granulomas, specifically, larger granulomas, macula involving or threatening granulomas, we must treat the infection and the inflammation. Combining this treatment along with ATT and systemic steroids is recommended as intravitreal treatment aids in the direct attack on the inflammation and infection, hastening recovery. ( 3 ) Due to increased vascular endothelial growth factor (VEGF) production, TB granulomas are associated with high vascularity and angiogenesis. ( 1 ) However tuberculomas resist both ATT and oral steroid combination due to abnormal vascularization maintaining the inflammatory process. Production of VEGF occurs as a part of inflammation to promote vessel dilation and in response to hypoxia. VEGF is a known biomarker for active disease in pulmonary and extrapulmonary sites. ( 8 ) Anti-VEGF therapy has been used to treat TB granulomas, which are highly vascular, associated with exudation or massive serous retinal detachment, and refractory to conventional ATT and corticosteroids. ( 8 ) Parallel reduction of VEGF with clinical regression of the granuloma has been reported. ( 7 ) There was a significant correlation between decreasing levels of aqueous VEGF-A and the clinical regression of these tubercular granulomas. ( 9 ) Moxifloxacin belongs to the fluoroquinolone group, which consists of second-line ATT drugs. ( 9 ) High concentrations of VEGF in these patients warrant a frequent administration of intravitreal anti-VEGF. The half-life of bevacizumab has a mean of 4.9 days. ( 10 )These factors suggest a weekly dose of anti-VEGF and moxifloxacin to control the disease process. In a study by Agarwal et al. ( 11 ), weekly intravitreal injections of anti-VEGF bevacizumab with moxifloxacin in addition to the standard treatment with oral steroids and ATT caused prompt resolution of tubercular granulomas in a series of 10 patients with a mean number of injections of 3.1. In conclusion, we report a rare manifestation of a case of miliary tuberculosis with bilateral multiple TB granulomas. We highlight the prompt response in both the eyes with ATT and oral steroids and emphasize the adjuvant role of weekly intravitreal anti-VEGF and moxifloxacin in achieving faster resolution in these challenging patients. Abbreviations ATT Anti Tubercular Treatment TB tuberculosis HRCT High-Resolution Computed Tomography VEGF Vascular Endothelial Growth Factor BCVA Best Corrected Visual Acuity Declarations Authors’ contributions T.J and S.M analysed and interpreted the patient data. The manuscript was written by A.K and S.M and substantively revised by T.J. All authors read and approved the final manuscript. Funding No funding was received. Availability of data and materials All data generated or analysed during this study are included in this published article. Ethics approval and consent to participate This brief report has been performed in accordance with the ethical standards laid down by the Declaration of Helsinki and its later amendments Consent for publication Consent for publication was obtained from the patient. Competing interests The authors declare that they have no competing interests. References Gupta A, Sharma A, Bansal R, Sharma K (2015) Classification of Intraocular Tuberculosis. Ocul Immunol Inflamm 23(1):7–13 Via LE, Lin PL, Ray SM, Carrillo J, Allen SS, Eum SY et al (2008) Tuberculous Granulomas Are Hypoxic in Guinea Pigs, Rabbits, and Nonhuman Primates. Infect Immun 76(6):2333 Cangemi FE, Friedman AH, Josephberg R (1980) Tuberculoma of the choroid. Ophthalmology 87(3):252–258 Aysu E, Betül TU, Cu, Soysal A, Yüksel B et al Choroidal Tuberculoma in Two Cases With Multiple Intracranial Tuberculomas. In 2011 [cited 2024 Oct 21]. Available from: https://www.semanticscholar.org/paper/Choroidal-Tuberculoma-in-Two-Cases-With-Multiple-Aysu-En/cae328922b1663d3a3f8a75dae2ccfdfc8683955 Mehta S, Chauhan V, Hastak S, Jiandani P, Dalal P (2006) Choroidal Tubercles in Neurotuberculosis: Prevalence and Significance. Ocul Immunol Inflamm 14(6):341–345 Sharma SK, Mohan A, Sharma A, Mitra DK (2005) Miliary tuberculosis: new insights into an old disease. Lancet Infect Dis 5(7):415–430 Mehta S (2017) Patterns of ocular inflammation in patients with miliary tuberculosis. F1000Research 6:412 Thayil SM, Albini TA, Nazari H, Moshfeghi AA, Parel JMA, Rao NA et al (2011) Local Ischemia and Increased Expression of Vascular Endothelial Growth Factor Following Ocular Dissemination of Mycobacterium tuberculosis. Cardona PJ, editor. PLoS ONE. ;6(12):e28383 Agarwal M, Gupta C, Mohan KV, Upadhyay PK, Jha V (2020) Correlation of vascular endothelial growth factor with the clinical regression of tubercular granuloma. Indian J Ophthalmol 68(9):2037 Moisseiev E, Waisbourd M, Ben-Artsi E, Levinger E, Barak A, Daniels T et al (2014) Pharmacokinetics of bevacizumab after topical and intravitreal administration in human eyes. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Klin Exp Ophthalmol 252(2):331–337 Agarwal M, Gupta C, Mohan KV, Upadhyay PK, Dhawan A, Jha V (2023) Adjunctive Intravitreal Anti-vascular Endothelial Growth Factor and Moxifloxacin Therapy in Management of Intraocular Tubercular Granulomas. Ocul Immunol Inflamm 31(1):158–167 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 24 Oct, 2025 Read the published version in Journal of Ophthalmic Inflammation and Infection → Version 1 posted Editorial decision: Revision requested 09 May, 2025 Reviews received at journal 07 May, 2025 Reviewers agreed at journal 24 Apr, 2025 Reviews received at journal 23 Apr, 2025 Reviewers agreed at journal 23 Apr, 2025 Reviewers invited by journal 15 Apr, 2025 Editor assigned by journal 15 Apr, 2025 Submission checks completed at journal 15 Apr, 2025 First submitted to journal 12 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6434945","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":447320548,"identity":"c41824ab-da9c-4402-8965-3212b6c1a05f","order_by":0,"name":"Tanya Jain","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIiWNgGAWjYNACHiBkYGB8wMBwgBjFcC3MzAYkaAEDZjYJorTYs589JvFDxk7GnIH/WDVPzR05fgbmh49u4LOFJy9NsocnmceygZntNs+xZ8aSDWzGxjl4HZZjJsHDw8xjcACkhe1w4oYDPGzSeLXwvzGT/MNTD9ZSzPOPGC0SOWbSPDyHwVqYeduI0XLjjbG1DM9xkBZjybl9h40lmwn4hb0/x/Dm255qe4MDjA8/vPl2WI6fvfnhY3xagIBFgrEHSMk/YGACxxIzfuVgJR8YfkBYjD8Iqx4Fo2AUjIIRCADxOkIiwhfycgAAAABJRU5ErkJggg==","orcid":"","institution":"Dr Shroff’s Charity Eye Hospital","correspondingAuthor":true,"prefix":"","firstName":"Tanya","middleName":"","lastName":"Jain","suffix":""},{"id":447320550,"identity":"8e5d74fb-2839-4c20-b0fb-06483b4320b5","order_by":1,"name":"Sachit Mahajan","email":"","orcid":"","institution":"Dr Shroff’s Charity Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sachit","middleName":"","lastName":"Mahajan","suffix":""},{"id":447320551,"identity":"9cb1d76e-52af-47f5-acac-fdfe868b025e","order_by":2,"name":"Aishwaraya Kanagraj","email":"","orcid":"","institution":"Dr Shroff’s Charity Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Aishwaraya","middleName":"","lastName":"Kanagraj","suffix":""}],"badges":[],"createdAt":"2025-04-12 13:53:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6434945/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6434945/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12348-025-00509-2","type":"published","date":"2025-10-24T16:17:17+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82168391,"identity":"144d44cd-d001-42aa-9730-3d85a14b8d54","added_by":"auto","created_at":"2025-05-07 09:27:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":678896,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Right eye fundus photo showing multiple choroidal granulomas in the macula (B) Left eye fundus photo showing a large choroidal granuloma in the macula\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6434945/v1/5e39ab5d59c07736189b6531.png"},{"id":82166003,"identity":"fb0115ab-850a-4f5a-84cf-571043ad5bf9","added_by":"auto","created_at":"2025-05-07 09:11:23","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":415037,"visible":true,"origin":"","legend":"\u003cp\u003eRight eye fundus photo showing multiple choroidal granulomas (B) OCT scan through the tubercle along the inferior arcade showing choroidal bump and subretinal fluid. (C) Fundus photo showing regression of the granuloma on 4th week follow up (D) OCT scan through the lesion showing\u0026nbsp; decrease in choroidal bump and with subretinal fluid. (E) Fundus photo showing completely regressed granuloma on 2\u003csup\u003end\u003c/sup\u003e month follow up (F) \u0026nbsp;OCT scan through the granuloma showing regression of choroidal bump.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6434945/v1/8af9c50ba811273df3d3d552.png"},{"id":82166006,"identity":"547b1527-c7a3-44de-8870-43bf9b434280","added_by":"auto","created_at":"2025-05-07 09:11:23","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":362983,"visible":true,"origin":"","legend":"\u003cp\u003eLeft eye fundus photo showing a large choroidal granuloma 5*3 mm (B) OCT macular scan showing choroidal bump and subretinal fluid (red arrow). (C) Fundus photo showing regression of the granuloma on 4th week follow up (D) OCT macular scan showing choroidal bump with intraretinal cystic spaces and with subretinal fluid. (E) Fundus photo showing completely regressed granuloma on 2\u003csup\u003end\u003c/sup\u003e month follow up (F) \u0026nbsp;OCT scan through the granuloma showing regression of choroidal bump.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6434945/v1/c1dd54faaa2c498e99653853.png"},{"id":94490304,"identity":"6512a93d-ab09-43de-a458-89a6e0c9d89a","added_by":"auto","created_at":"2025-10-27 17:09:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2223674,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6434945/v1/84123693-8088-4294-aa4a-11cc1bde3f7f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Bilateral choroidal tuberculoma in a patient of miliary tuberculosis","fulltext":[{"header":"Background","content":"\u003cp\u003eTuberculosis is caused by mycobacterium tuberculosis. It is well known to involve most ocular tissue, including the orbit and, most commonly, the uveal tissue, due to its high vascularity, which allows easy hematogenous spread of infection.(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) The innate immunity limits the infection through a robust adaptive immune response by forming epithelioid cell granuloma with central areas of caseation necrosis. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Tuberculosis-related granulomas usually respond well to a combination of systemic steroids and specific antitubercular therapy (ATT).(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) This case demonstrates a patient of miliary tuberculosis with bilateral tuberculous granulomas, managed with intravitreal moxifloxacin and intravitreal anti-VEGF, along with ATT and systemic steroids.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 21-year-old female presented with a history of diminished vision in both eyes (BE) for the past month. There was a history of shortness of breath and headache 2 months earlier. Her Mantoux test and TB gold test were positive, and her high-resolution computed tomography (HRCT) of the chest showed the presence of multiple tiny nodular lesions in bilateral lung fields with no evidence of cavitation suggestive of miliary tuberculosis. She was diagnosed with miliary tuberculosis and was started on ATT by the physician.\u003c/p\u003e \u003cp\u003eThe best-corrected visual acuity (BCVA) in the right eye (RE) was 6/12, N6, and 1/60, \u0026lt;N36 in the left eye (LE). Anterior segment examination showed conjunctival congestion in the RE. The rest of the anterior segment examination was unremarkable. The intraocular pressure was 14 mm Hg in the RE and 10 mm Hg in the LE (Goldmann applanation tonometer). Fundus examination of the RE showed a healthy optic disc with multiple subretinal yellowish lesions with ill-defined margins with central clearing varying in size from half-disc to two-disc diameters (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). The LE fundus showed a subretinal elevated yellowish lesion with ill-defined margins and central clearing at the macula involving the fovea measuring around ten disc-diameters with multiple small subretinal yellowish lesions spread throughout the posterior pole and until the mid-periphery. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOptical coherence tomography (OCT) of the RE showed normal foveal contour and elevation of retinal layers with an underlying choroidal bump with hyperreflectivity of the outer retinal layers at the lesion site (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). OCT of the LE through the lesions revealed similar findings, with elevation of retinal layers and underlying dome-shaped choroidal bump with hyperreflectivity of outer retinal layers at the macula. (Figure- 3B)\u003c/p\u003e \u003cp\u003eMantoux test was positive, and HRCT chest showed bilateral diffuse multiple tiny nodular lesions in the lung parenchyma suggestive of miliary TB. Human Immunodeficiency Virus (HIV) and Hepatitis B surface antigen (HbsAg) were nonreactive and the rest of uveitis workup was negative. Ultrasonography of the abdomen showed splenomegaly. The systemic and ocular investigations were suggestive of ocular tuberculosis (TB) in the form of bilateral choroidal granuloma and disseminated tubercles. Since the granuloma in the LE was significantly larger and involved the macula, we decided to inject the left eye with intravitreal anti-VEGF and moxifloxacin to facilitate early resolution. The granulomas of the RE were relatively small and discrete, and we decided to monitor their resolution with the commencement of the intensive phase of ATT and oral steroids (1mg/Kg body weight).\u003c/p\u003e \u003cp\u003eAfter informed consent, she underwent intravitreal injection of the anti-VEGF drug bevacizumab (1.25 mg/0.05 mL) (off-label use) with moxifloxacin (500 \u0026micro;g/0.1 mL) (off-label use) in the LE under topical anaesthesia. One week after injection, the BCVA of the left eye remained the same at 1/60. However, the lesion appeared to be consolidating. She was continued on weekly intravitreal injections. At 3-week follow-up, her BCVA in the RE improved to 6/9 N6, and her BCVA in the LE improved to 2/60\u0026thinsp;\u0026lt;\u0026thinsp;N36. The OCT through the granuloma in the LE showed a decrease in the choroidal bump and a reduction of subretinal fluid, suggesting consolidation of the lesion (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD). The lesions in the RE also appeared to be getting well-defined and healing (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). The oral steroids were tapered, and the patient was continued on the intensive phase of ATT. However, on closer examination of the OCT of the LE, there were a few intraretinal cysts (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD) at the base of the granuloma, suggestive of continued activity, so it was decided to continue with the weekly intravitreal injections. After seven weekly intravitreal injections, her BCVA improved to 6/36, \u0026lt;N36 in the LE, and the choroidal bump decreased in size (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eF). The intensive phase of ATT was stopped after 2 months, and the patient was shifted to the continuation phase for 9 months. The oral steroids were tapered in a weekly fashion and stopped after about 10 weeks of treatment.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOn the last follow-up 5, months after starting treatment, her systemic condition improved, with the healing of her pulmonary lesions. The ocular lesions appeared scarred, and the patient maintained a vision of RE 6/6, N6 and LE 6/24-, N18. The patient continued her continuation phase of ATT and is on two monthly follow-ups.\u003c/p\u003e "},{"header":"Discussion and Conclusion","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003cp\u003eChoroidal tuberculomas are usually large, unilateral, solitary, yellowish lesions at the posterior pole.Tuberculomas have predilection for the foveal and perifoveal area. They may vary in their presentation with features such as associated haemorrhage, striae, or exudative retinal detachment. Choroidal tubercules are generally small and multiple and have less defined borders than granulomas with more surrounding edema. They have an increased chance of association with central nervous system (CNS) TB.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Mehta and associates found choroidal tubercles in 34.6% of 52 patients with neurotuberculosis. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003ePathologically speaking, granulomas are chronic collections of inflammatory cells created by the immune system to prevent the dissemination of Mycobacterium tuberculosis.\u003c/p\u003e \u003cp\u003eT cells bearing γδ T-cell receptors influence Th1/Th2 cells. The dominant T Helper 1 (Th1) cytokine bias leads to granuloma formation. Immune responses skewed towards T helper 2 (Th2) cells cross-inhibit protective responses such as granuloma formation, which may have a critical role in miliary tuberculosis, (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Impaired expansion of γδ T-cells, presence of HLA-Bw15,75 HLA-DRB1*15/16, DRB1*13, and DQB1*0602,76 absence of HLA-Cw6, HLA-DRB1*10, and DQB1*0501 have been described to account for the propensity to develop disseminated tuberculosis. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn a study by Mehta et al. on the patterns of ocular inflammation in patients with miliary tuberculosis(TB), all 22 eyes of the patients with miliary TB included showed no signs of inflammation on slit lamp examination and single or multiple choroidal tubercles bilaterally in 7 patients and unilaterally in 4 patients with no associated vitritis or raised intraocular pressure. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn large TB granuloma, there is local ischemia leading to upregulation in vascular endothelial growth factor (VEGF) production at retinal pigment epithelium (RPE) and photoreceptor levels.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Due to increased VEGF production, TB granulomas are associated with high vascularity and angiogenesis. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eHence, for the effective treatment of these granulomas, specifically, larger granulomas, macula involving or threatening granulomas, we must treat the infection and the inflammation. Combining this treatment along with ATT and systemic steroids is recommended as intravitreal treatment aids in the direct attack on the inflammation and infection, hastening recovery. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eDue to increased vascular endothelial growth factor (VEGF) production, TB granulomas are associated with high vascularity and angiogenesis. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) However tuberculomas resist both ATT and oral steroid combination due to abnormal vascularization maintaining the inflammatory process. Production of VEGF occurs as a part of inflammation to promote vessel dilation and in response to hypoxia. VEGF is a known biomarker for active disease in pulmonary and extrapulmonary sites. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) Anti-VEGF therapy has been used to treat TB granulomas, which are highly vascular, associated with exudation or massive serous retinal detachment, and refractory to conventional ATT and corticosteroids. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) Parallel reduction of VEGF with clinical regression of the granuloma has been reported. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) There was a significant correlation between decreasing levels of aqueous VEGF-A and the clinical regression of these tubercular granulomas. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) Moxifloxacin belongs to the fluoroquinolone group, which consists of second-line ATT drugs. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) High concentrations of VEGF in these patients warrant a frequent administration of intravitreal anti-VEGF. The half-life of bevacizumab has a mean of 4.9 days. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)These factors suggest a weekly dose of anti-VEGF and moxifloxacin to control the disease process. In a study by Agarwal et al. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e), weekly intravitreal injections of anti-VEGF bevacizumab with moxifloxacin in addition to the standard treatment with oral steroids and ATT caused prompt resolution of tubercular granulomas in a series of 10 patients with a mean number of injections of 3.1.\u003c/p\u003e \u003cp\u003eIn conclusion, we report a rare manifestation of a case of miliary tuberculosis with bilateral multiple TB granulomas. We highlight the prompt response in both the eyes with ATT and oral steroids and emphasize the adjuvant role of weekly intravitreal anti-VEGF and moxifloxacin in achieving faster resolution in these challenging patients.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eATT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAnti Tubercular Treatment\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etuberculosis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHRCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHigh-Resolution Computed Tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVEGF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVascular Endothelial Growth Factor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBCVA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBest Corrected Visual Acuity\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eT.J and S.M analysed and interpreted the patient data. The manuscript was written by A.K and S.M and substantively revised by T.J. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis brief report has been performed in accordance with the ethical standards laid down by the Declaration of Helsinki and its later amendments\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent for publication was obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGupta A, Sharma A, Bansal R, Sharma K (2015) Classification of Intraocular Tuberculosis. Ocul Immunol Inflamm 23(1):7\u0026ndash;13\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVia LE, Lin PL, Ray SM, Carrillo J, Allen SS, Eum SY et al (2008) Tuberculous Granulomas Are Hypoxic in Guinea Pigs, Rabbits, and Nonhuman Primates. Infect Immun 76(6):2333\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCangemi FE, Friedman AH, Josephberg R (1980) Tuberculoma of the choroid. Ophthalmology 87(3):252\u0026ndash;258\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAysu E, Bet\u0026uuml;l TU, Cu, Soysal A, Y\u0026uuml;ksel B et al Choroidal Tuberculoma in Two Cases With Multiple Intracranial Tuberculomas. In 2011 [cited 2024 Oct 21]. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.semanticscholar.org/paper/Choroidal-Tuberculoma-in-Two-Cases-With-Multiple-Aysu-En/cae328922b1663d3a3f8a75dae2ccfdfc8683955\u003c/span\u003e\u003cspan address=\"https://www.semanticscholar.org/paper/Choroidal-Tuberculoma-in-Two-Cases-With-Multiple-Aysu-En/cae328922b1663d3a3f8a75dae2ccfdfc8683955\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMehta S, Chauhan V, Hastak S, Jiandani P, Dalal P (2006) Choroidal Tubercles in Neurotuberculosis: Prevalence and Significance. Ocul Immunol Inflamm 14(6):341\u0026ndash;345\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharma SK, Mohan A, Sharma A, Mitra DK (2005) Miliary tuberculosis: new insights into an old disease. Lancet Infect Dis 5(7):415\u0026ndash;430\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMehta S (2017) Patterns of ocular inflammation in patients with miliary tuberculosis. F1000Research 6:412\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThayil SM, Albini TA, Nazari H, Moshfeghi AA, Parel JMA, Rao NA et al (2011) Local Ischemia and Increased Expression of Vascular Endothelial Growth Factor Following Ocular Dissemination of Mycobacterium tuberculosis. Cardona PJ, editor. PLoS ONE. ;6(12):e28383\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAgarwal M, Gupta C, Mohan KV, Upadhyay PK, Jha V (2020) Correlation of vascular endothelial growth factor with the clinical regression of tubercular granuloma. Indian J Ophthalmol 68(9):2037\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoisseiev E, Waisbourd M, Ben-Artsi E, Levinger E, Barak A, Daniels T et al (2014) Pharmacokinetics of bevacizumab after topical and intravitreal administration in human eyes. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Klin Exp Ophthalmol 252(2):331\u0026ndash;337\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAgarwal M, Gupta C, Mohan KV, Upadhyay PK, Dhawan A, Jha V (2023) Adjunctive Intravitreal Anti-vascular Endothelial Growth Factor and Moxifloxacin Therapy in Management of Intraocular Tubercular Granulomas. Ocul Immunol Inflamm 31(1):158\u0026ndash;167\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-ophthalmic-inflammation-and-infection","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joii","sideBox":"Learn more about [Journal of Ophthalmic Inflammation and Infection](http://joii-journal.springeropen.com)","snPcode":"12348","submissionUrl":"https://submission.nature.com/new-submission/12348/3","title":"Journal of Ophthalmic Inflammation and Infection","twitterHandle":"@SpringerOpen","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"AntiVEGF, TB granuloma, miliary TB","lastPublishedDoi":"10.21203/rs.3.rs-6434945/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6434945/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eChoroidal granuloma is one of the common manifestations of ocular tuberculosis. Tubercles indicate hematogenous dissemination of the disease. Tubercular granulomas respond to Anti Tubercular Treatment (ATT) and systemic corticosteroids. However, in some patients with large granulomas involving macula, adjunct treatment with intravitreal anti-VEGF may be required for prompt management of the granuloma.\u003c/p\u003e\u003ch2\u003eFindings:\u003c/h2\u003e \u003cp\u003eWe report a case of bilateral Tubercular granuloma in a patient with miliary Tuberculosis (TB). The patient was an immunocompetent young female with miliary tuberculosis. Mantoux was positive. HRCT chest suggested miliary TB. The patient was already on ATT. Clinical examination showed multiple TB granulomas in both eyes, with a large granuloma involving the fovea in the left eye. She underwent intravitreal injection of the anti-VEGF drug bevacizumab (1.25 mg/0.05 mL) (off-label use) with moxifloxacin (500 \u0026micro;g/0.1 mL) (off-label use) in the left eye. She was continued on ATT and was started on oral steroids. After seven weekly intravitreal injections in the left eye at the second-month follow-up, lesions were consolidated and scarring. Optical coherence tomography showed a decrease in the size of the choroidal bump.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eWeekly administration of intravitreal Anti-Vascular endothelial growth factor(VEGF) and moxifloxacin along with ATT and oral corticosteroids has controlled inflammation and has caused consolidation and scarring of TB granulomas in a patient with miliary TB.\u003c/p\u003e","manuscriptTitle":"Bilateral choroidal tuberculoma in a patient of miliary tuberculosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-07 09:11:19","doi":"10.21203/rs.3.rs-6434945/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-09T15:12:06+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-07T10:24:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"252027539185482877408596118847436910316","date":"2025-04-24T07:47:34+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-24T03:00:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"269813527714009477603419227420574767753","date":"2025-04-24T02:34:29+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-15T22:40:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-15T09:42:19+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-15T09:38:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Ophthalmic Inflammation and Infection","date":"2025-04-12T13:41:16+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-ophthalmic-inflammation-and-infection","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joii","sideBox":"Learn more about [Journal of Ophthalmic Inflammation and Infection](http://joii-journal.springeropen.com)","snPcode":"12348","submissionUrl":"https://submission.nature.com/new-submission/12348/3","title":"Journal of Ophthalmic Inflammation and Infection","twitterHandle":"@SpringerOpen","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"37323007-0241-46b5-bf09-fa7e163f40b2","owner":[],"postedDate":"May 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-27T16:28:26+00:00","versionOfRecord":{"articleIdentity":"rs-6434945","link":"https://doi.org/10.1186/s12348-025-00509-2","journal":{"identity":"journal-of-ophthalmic-inflammation-and-infection","isVorOnly":false,"title":"Journal of Ophthalmic Inflammation and Infection"},"publishedOn":"2025-10-24 16:17:17","publishedOnDateReadable":"October 24th, 2025"},"versionCreatedAt":"2025-05-07 09:11:19","video":"","vorDoi":"10.1186/s12348-025-00509-2","vorDoiUrl":"https://doi.org/10.1186/s12348-025-00509-2","workflowStages":[]},"version":"v1","identity":"rs-6434945","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6434945","identity":"rs-6434945","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}