N. Greben¹*, I. Gavryliak¹, V. Bilous²,
V. Korsa², A. Tykhomyrov²

¹Department of Ophthalmology, Bogomolets National Medical University, Kyiv, Ukraine;
²Department of Enzyme Chemistry and Biochemistry,
Palladin Institute of Biochemistry, Kyiv, Ukraine;
*e-mail: nkgreden@ukr.net

Received: 03 June 2025; Revised: 17 September 2025;
Accepted: 28 November 2025; Available on-line: 29 December 2025

Ocular tuberculosis (TB) is a vision-threatening condition that frequently manifests as corneal neovascularization and stromal keratitis, which triggers a cascade of inflammatory and hypoxia-driven responses. Conventional therapeutic approaches, including corticosteroids and antimicrobial agents, often fail to halt disease progression. Here, we report a case of a 50-year-old patient diagnosed with TB-associated keratitis, unresponsive to standard treatment. The aim of the study was to evaluate the effectiveness of the alternative therapeutic strategy involving topical administration of angiostatin, a natural anti-angiogenic polypeptide derived from the autologous plasminogen. Solution of angiostatin fragment containing the first three kringle domains (K1-3) was applied in a two doses of eye drops (~15 μg per administration) five times daily for 2 months, with a cumulative exposure of approximately 4.5 mg. Treatment efficacy was monitored using both standard ophthalmologic assessments and non-invasive biochemical indicators such as the levels of hypoxia-inducible factor HIF-1α, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP-9), fibrinogen/fibrin (Fg/Fb) and lactoferrin measured the in tear fluid across treatment time points (Day 0, 14, and 61) using Western blot analysis. The high intensity of HIF-1 α, VEGF and MMP-9 expression, Fg/Fb accumulation and the presence of low-molecular-weight fragments of lactoferrin were detected in the tear fluid prior to the treatment. Following angiostatin therapy, the patient exhibited marked regression of corneal neovascularization and restoration of corneal transparency, complemented with normalization of HIF-1α, VEGF, and MMP-9 levels, reduced Fg/Fb accumulation and the presence of intact lactoferrin in the tear fluid. The data obtained demonstrated a multifactorial mechanism of angiostatin action that extends beyond classical anti-angiogenic pathways. The convergence of clinical and molecular indicators of recovery underscores the potential of angiostatin application as a safe and effective therapeutic alternative for managing corneal complications in ocular TB, particularly in cases resistant to conventional treatment.

Keywords: angiostatin, corneal injury, HIF-1α, lactoferrin, MMP-9, ocular tuberculosis, tear fluid, VEGF