The clinical diagnosis of endogenous fungal endophthalmitis has been well described in previous case series and case reports [1, 6, 14, 15]. While there have been descriptions of the differences between patients with yeast infection and patients with mold infection, no large head-to-head statistical comparisons of culture-proven cases have been previously reported .
In the current study, endogenous endophthalmitis caused by molds, consisting mainly of Aspergillus species, was frequently associated with history of iatrogenic immunosuppression and organ transplantation. In models of invasive aspergillosis impaired neutrophil function has been shown to play a major role in the development of infection, and prolonged steroid use or other immunosuppression may depress neutrophil function . Riddell et al. previously reported in a review of the literature that 43% of patients with endogenous Aspergillus endophthalmitis had received prior treatment with corticosteroids . The current study also demonstrated a significantly shorter duration of symptoms for patients presenting with endogenous endophthalmitis caused by molds. Infected eyes were also more likely to have a hypopyon. Aspergillus has been shown in histopathologic specimens to prominently invade through blood vessel walls in the choroid leading to necrosis and more rapid involvement of the vitreous . As such, infection with more virulent mold organisms has been shown in the literature to correlate with worse visual acuity outcomes and higher rates of enucleation, as it did in the current study [1, 6]. Given the fulminant course of mold infections, patients often require systemic antifungal therapy, as demonstrated in the current study.
In contrast, patients with endogenous endophthalmitis caused by yeast presented more indolently and with better visual acuities, matching descriptions in the literature . Shen et al. previously reported 29 eyes with endogenous fungal endophthalmitis, and none of the mold cases achieving final visual acuity of 20/200 or better; in contrast, 53% of Candida cases achieved that outcome . Due to less clear patient histories and nonspecific examination findings mimicking uveitis, misdiagnosis of Candida endophthalmitis has been reported to approach 50% . Thus, it is imperative to investigate for risk factors such as recent hospitalization, recent surgery, and intravenous drug use and entertain a diagnosis of fungal endophthalmitis when approaching the uveitis patient with progressive signs and symptoms.
Retinal detachment was a frequent event in the follow-up course for patients in both groups. Retinal detachment is associated with poor visual outcome and is a potential complication of vitrectomy for endophthalmitis [20, 21]. One proposed mechanism is post-operative peripheral vitreous contraction inducing retinal breaks . However, in the Endophthalmitis Vitrectomy Study, there was no significant difference in the rate of retinal detachment between patients undergoing needle tap and vitrectomy biopsy . It was recently postulated that early vitrectomy in endogenous endophthalmitis caused by yeast might reduce the incidence of retinal detachment . Sallam et al. reviewed 44 eyes with Candida endophthalmitis and reported that eyes that underwent vitrectomy within a week of presentation resulted in a retinal detachment rate of 8% versus 41% in those eyes with delayed vitrectomy.
Pars plana vitrectomy was frequently utilized as the initial management strategy for patients in both groups of the current study. It has been suggested that early vitrectomy is preferable for these patients since vitreous paracentesis may not obtain an adequate vitreous sample of the localized infection. Endogenous fungal endophthalmitis classically begins with choroidal seeding and eventually invades the vitreous cavity . In the current series, the most common isolate was C. albicans followed by Aspergillus fumigatus. This is in accordance with previously reported results [24, 25]. Of note, polymerase chain reaction (PCR) testing has shown to be more rapid and sensitive than traditional mycology cultures in diagnosing fungal endophthalmitis and is now employed at many medical centers .
In patients with a suspected infection, a diagnostic vitrectomy may be considered initially. Intravitreal therapy can be specifically targeted once appropriate stains and culture results are obtained. Oral antifungal therapy is also considered, usually fluconazole or voriconazole. Depending on the clinical response to initial treatment, intravitreal injections can be given until the infectious process resolves. Patients can be monitored closely for retinal detachment. Although there are early reports proposing the use of intravitreal corticosteroids as an adjunct, there is no well-designed prospective, comparative trial addressing this point and as such, intravitreal steroids are not recommended given the risk of inhibiting the host immune response [27, 28].
The current study is limited by its retrospective design as well its relatively small number of patients. Rapid and sensitive PCR testing was not available for clinical use at our institution during the entire study period. Patients had quite variable follow-up and data could be missing from the chart review. Patients were identified based on positive intraocular cultures and thus cases of presumed endogenous endophthalmitis in which cultures were not obtained may have been excluded. In spite of these limitations, this study demonstrates and reinforces key differences between endogenous endophthalmitis caused by molds compared to yeasts.