Areas of uncertainty in endophthalmitis care.

Endophthalmitis remains one of the most feared presentations in ophthalmic practice, not only because of its potential for rapid and irreversible vision loss but also due to the substantial diagnostic, therapeutic, and prognostic uncertainty that accompanies its management. Despite landmark trials, advances in vitreoretinal surgery, antimicrobial therapy, imaging, and molecular diagnostics, many aspects of endophthalmitis care continue to rely on clinical judgment rather than uniformly applicable, high-quality evidence. This review synthesizes contemporary areas of uncertainty spanning disease definition, diagnosis, treatment, antimicrobial resistance, and outcome prediction. We highlight the conceptual challenges in distinguishing infectious endophthalmitis from sterile or immune-mediated intraocular inflammation, particularly in culture-negative cases and post-intravitreal injection scenarios. Diagnostic ambiguity is compounded by limited microbiological yield, evolving molecular techniques with uncertain clinical interpretation, and supportive but non-specific imaging findings. Treatment-related uncertainties include the optimal timing and extent of vitrectomy in the era of small-gauge surgery, selection and dosing of intravitreal antimicrobials amid rising resistance and geographic variability, the contentious role of adjunctive corticosteroids, and management strategies for fungal and culture-negative endophthalmitis. Prognostication remains imprecise, with anatomical success often failing to predict functional recovery. Rather than reiterating established guidelines, this review focuses on real-world clinical gray zones and unresolved questions. Endophthalmitis is best viewed as a heterogeneous clinical syndrome shaped by microbial, host, and treatment-related factors. Recognizing uncertainty as an inherent feature of care underscores the need for individualized, adaptive decision-making and highlights priorities for future research, including standardized endpoints, region-specific surveillance, and integration of emerging imaging, molecular, and computational tools.