Clinical Evaluation of a Novel CRISPR-Cas12a-Based RID-MyC Assay for the Diagnosis of Fungal Endophthalmitis

Ophthalmol Retina. 2024 Nov 8:S2468-6530(24)00533-5. doi: 10.1016/j.oret.2024.11.003. Online ahead of print.

Abstract

Objective: This study evaluates the RID-MyC (Rapid Identification of Mycoses using CRISPR) assay, a CRISPR/Cas12a-based diagnostic tool, for its efficacy in diagnosing fungal endophthalmitis (FE), comparing it with panfungal PCR and culture methods.

Design: A comparative cross-sectional study assessing the performance of the RID-MyC assay against established diagnostic modalities for FE.

Subjects: The study included 133 intraocular samples from 117 patients with suspected microbial endophthalmitis.

Methods: The study compared the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the RID-MyC assay against panfungal PCR and culture. The Limit of Detection (LoD) for Aspergillus flavus and Candida albicans was determined for both RID-MyC and panfungal PCR across three different media: nuclease-free water (NFW), aqueous humor (AH), and vitreous humor (VH). Discrepancy analysis was conducted for discordant results, incorporating clinical outcomes and responses to antifungal treatment.

Main outcome measures: The study primarily assessed the sensitivity, specificity, PPV, and NPV for clinical samples. Time to diagnosis was also evaluated.

Results: The RID-MyC assay demonstrated a sensitivity of 88.24% (CI: 63.56% to 98.54%) and specificity of 93.1% (CI: 86.86% to 96.98%), with PPV and NPV of 65.22% (CI: 48.45% to 78.91%) and 98.18% (CI: 93.62% to 99.50%), respectively. Discrepancy analysis enhanced sensitivity to 90.48% (CI: 69.62% to 98.83%) and specificity to 96.43% (CI: 91.11% to 99.02%). The RID-MyC assay was 10 to 1000-fold more sensitive than panfungal PCR in detecting Aspergillus flavus and Candida albicans in intraocular specimens. The time to diagnosis with the RID-MyC assay was consistently under two hours.

Conclusions: The RID-MyC assay may advance the rapid and precise diagnosis of FE, with possible relevance to other invasive fungal conditions.