Recent Advances and Ongoing Challenges in the Diagnosis of Culture Negative Endophthalmitis

Background: Culture negative (CN) but presumed infectious endophthalmitis poses a huge diagnostic challenge in terms of clinical management. This article outlines the current state of knowledge of infectious endophthalmitis with negative cultures and summarizes the recommendations for the work up of this condition along with providing a simple algorithm, by putting into context the recent concerns about over-diagnosing endophthalmitis. Methods: We searched the PubMed and Scopus databases for large hospital based studies on diagnosis of endophthalmitis, with emphasis on culture-negative infections in October 2021. Only clinical studies written in English were included. Basic science studies, letters to the editor and case reports on endophthalmitis were excluded. Results: Twenty studies were included in this study. The prevalence of CN endophthalmitis ranged from 40% to 70%. Recent advances in PCR along with high throughput sequencing have helped identify the etiological agent in most cases but these technologies are not easily available, requires advanced bioinformatic analysis and are not cost effective. Role of other inflammatory and relatively low-cost biomarkers in diagnosing a presumed infection is yet to be validated clinically but hold promise in helping ophthalmologists identify the causative agent. Conclusions: CN endophthalmitis is a relatively frequent finding and should not be labelled as sterile endophthalmitis. Recent advances provide a new perspective for ophthalmologist in diagnosis of presumed infectious endophthalmitis and further studies are needed to confirm their utility in clinical settings.