Ocular and Orbital Involvement in Extranodal Natural Killer/T-cell Lymphoma: A Systematic Review of Clinical Outcomes and Prognostic Factors

Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare and aggressive malignancy, with ocular and orbital involvement representing an uncommon but clinically important presentation. Many cases are frequently misdiagnosed due to their ability to mimic common inflammatory and infectious eye conditions, resulting in delayed diagnosis and poorer clinical outcomes. This systematic review aimed to evaluate clinical outcomes and prognostic factors in ocular and orbital ENKTL. A PRISMA-compliant systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD420261348194) and conducted using PubMed, MEDLINE, Embase, and Cochrane Library from database inception to 19 March 2026. Twenty-eight studies comprising approximately 429 patients were included. Data were extracted on patient demographics, treatment, survival, and prognostic factors, and analysed using a narrative synthesis. Median survival ranged from six to 17 months, with high mortality and frequent reports of rapid clinical deterioration. Delayed diagnosis, advanced disease, central nervous system involvement, and relapse were associated with poorer outcomes. Non-anthracycline, asparaginase-based regimens were associated with improved disease control compared with conventional therapies, although outcomes remained poor overall. Visual outcomes were similarly unfavourable. Improved survival was associated with early recognition, prompt biopsy, and timely initiation of appropriate treatment.