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Background: The purpose of this study was to report on the incidence and treatment outcomes of endogenous endophthalmitis among newborns in the neonatal intensive care unit (NICU) of a single medical center. Methods: This was a noncomparative, retrospective case series of endogenous endophthalmitis among infants at the Jackson Memorial Hospital NICU treated between March 1, 2002 and March 1, 2007. Results: Of 4323 infants admitted to the NICU, seven eyes of six (0.139%) infants (two males, four females) were diagnosed with endophthalmitis during the study period. Four patients were born prematurely with a mean gestational age of 27.5 weeks and a mean birth weight of 1153 g. Retinopathy of prematurity was reported in two of the six patients. Mean follow-up was 3.5 years. The diagnosis was confirmed by positive cultures or polymerase chain reaction testing at a median age of 34 postnatal days. Positive cultures included Candida albicans (n = 4), Pseudomonas aeruginosa (n = 1), and Herpes simplex type 2 (n = 1). All patients received systemic treatment and five received adjunctive ophthalmic interventions, including intravitreal antibiotics in five eyes of four patients and vitrectomy with pars plana lensectomy in three eyes. One patient underwent primary enucleation and another had delayed evisceration. In the remaining five eyes, there was a normal appearing posterior segment and normal intraocular pressures at last follow-up. Conclusion: Endogenous endophthalmitis is a rare complication in infants in the NICU, but may occur in patients with candidemia, bacteremia, retinopathy of prematurity, and low birth weight. Despite early and appropriate treatment, involved eyes may have poor outcomes. [ABSTRACT FROM AUTHOR]