PURPOSE: Endogenous fungal endophthalmitis (EFE) is a rare, sight-threatening intraocular infection with heterogeneous clinical presentations. Candida and Aspergillus species are the most common etiologic agents and may manifest with retinochoroiditis lesions that can be challenging to differentiate clinically. Accurate identification of the causative organism is essential for targeted antifungal therapy, anticipating disease progression, and optimizing outcomes. This study aimed to differentiate the etiology of EFE-associated retinochoroiditis using detailed clinical and optical coherence tomography (OCT) analysis. DESIGN: International, multicenter, retrospective comparative case series. METHODS: Demographic information, clinical characteristics, fundus photography, and OCT scans of patients with culture-proven Candida or Aspergillus EFE presenting with retinochoroiditis lesions were collected from eight tertiary-care centers worldwide. Lesion morphology (size, location, multifocality, and associated features) and OCT patterns (vitreal changes, vitreoretinal interface abnormalities, inner/outer retinal infiltration, and choroidal involvement) were compared between groups. Student's t-tests were used for continuous variables and Fisher's exact tests for categorical variables. Multivariable logistic regression and a random forest classifier were applied to identify the features most predictive of fungal species. RESULTS: Thirty-eight eyes of 30 patients (mean age: 64.7±15 years) were included: 28 with Candida and 10 with Aspergillus EFE. Foveal involvement occurred only in Candida cases (28.6% eyes). Compared with Aspergillus, Candida EFE showed significantly more multifocal lesions (p=0.008), mid-peripheral/peripheral involvement (p=0.004), satellite lesions (p=0.001), and "string-of-pearls" vitreous exudates (p=0.05). Aspergillus eyes had larger lesions (2.4 vs. 1.2 disc-diameters; p=0.001), more pre-/subretinal hemorrhage (p=0.03), and higher rates of occlusive vasculitis (p=0.008). On OCT, Candida eyes demonstrated more vitreous condensations/rain-cloud sign (p=0.03), preretinal aggregates (p=0.02), and intraretinal fluid (IRF) (p=0.04). Aspergillus infections more commonly exhibited full-thickness involvement with dense shadowing (p=0.001) and choriocapillaris alteration (p=0.008). Multivariable regression and random forest analysis identified lesion size, multifocality, satellite lesions, hemorrhage/vasculitis, IRF, and choriocapillaris alteration as the most discriminative features. These features allowed species differentiation with ∼85% accuracy using machine-learning classification. CONCLUSIONS: Candida and Aspergillus EFE presenting with retinochoroiditis exhibit distinct features that allow reliable differentiation between these fungal etiologies. These OCT-based biomarkers may inform early organism-specific management while awaiting microbiological confirmation.
Agarwal et al. (Fri,) studied this question.