W e read with great interest the study by Agarwal et al., which presents a multicenter optical coherence tomography (OCT)-based analysis of culture-proven Candida and Aspergillus endogenous fungal endophthalmitis (EFE). The authors should be commended for assembling a rare international cohort and for proposing imaging features that may assist etiologic differentiation while microbiological confirmation is pending.
Several aspects may warrant further clarification to define the clinical scope of these biomarkers. First, some OCT findings may reflect not only fungal species but also disease stage and treatment timing. EFE is a heterogeneous, sight-threatening infection in which ocular findings are shaped by systemic source, immune status, pathogen virulence, and the interval between systemic infection and ocular involvement. , Vitreous condensations, preretinal aggregates, dense shadowing, hemorrhagic vasculitis, and choriocapillaris alterations could evolve with lesion progression or after systemic or intravitreal antifungal therapy. Stratifying OCT findings by the interval from ocular symptom onset, systemic diagnosis, and antifungal initiation to imaging, and ideally incorporating serial OCT/OCTA, would help distinguish organism-related signatures from stage-related changes.
Second, the cohort appears to represent lesion-visible and OCT-accessible EFE. This design is well suited to detailed phenotyping, but it may limit applicability to patients seen at initial presentation with dense vitritis, poor media clarity, or early diffuse inflammation without discrete retinochoroidal lesions. Explicitly framing the proposed biomarkers as most applicable to imageable retinochoroiditis would help prevent overextension to the full clinical spectrum of EFE.
Third, the source of microbiological confirmation deserves consideration. Although positive blood cultures are highly relevant in endogenous infection, ocular imaging biomarkers may be most directly anchored to cases confirmed by aqueous or vitreous culture. Sensitivity analyses stratified by blood-culture-only vs intraocular-fluid-confirmed cases would strengthen confidence that the observed phenotypes reflect intraocular pathogen-specific disease rather than concurrent systemic fungemia with variable ocular expression.
Finally, host context may modify imaging appearances. Immunosuppression, sepsis, transplant status, renal disease, and infection source may influence fungal burden, vascular invasion, inflammatory response, and lesion evolution. Hemorrhagic vasculitis and choriocapillaris alteration are biologically plausible manifestations of the angioinvasive behavior of Aspergillus , but their frequency and severity may also be shaped by host-related vascular and immune factors.
In summary, Agarwal et al. provide an important step toward noninvasive, organism-oriented assessment of fungal EFE. Prospective studies using standardized serial OCT/OCTA protocols, predefined grading criteria, and stratification by disease timing, microbiological confirmation source, and host systemic status would further clarify when these biomarkers can safely inform early management.
CRediT authorship contribution statement
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