Abstract: TH-PO0588
Temporal Retinal Thinning as a Preclinical Marker of Alport Syndrome in Cases of Genetic Uncertainty
Session Information
- Monogenic Kidney Diseases: Glomerular
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Ibrahim, Abdelrahman, University of Utah Health, Salt Lake City, Utah, United States
- Mekki, Ossama, University of Utah Health, Salt Lake City, Utah, United States
- Nwaduru, Chinedu Elvis, University of Utah Health, Salt Lake City, Utah, United States
- Revelo Penafiel, Monica Patricia, University of Utah Health, Salt Lake City, Utah, United States
- Al-Rabadi, Laith, University of Utah Health, Salt Lake City, Utah, United States
Background
Genetic testing is central to diagnosing Alport syndrome (AS) and COL4-related nephropathies. However, some patients remain genetically inconclusive or harbor variants of uncertain significance (VUS). We hypothesized that the Temporal Thinning Index (TTIMax), derived from retinal OCT, may serve as a reliable preclinical marker in such cases.
Methods
We analyzed TTIMax in patients with suspected AS who either lacked definitive genetic findings or carried VUS. Retinal OCT was assessed using ETDRS grids. TTIMax was calculated and compared with renal biopsy findings and ClinVar variant reclassification timelines to evaluate its predictive value.
Results
In two biopsy-proven AS cases with inconclusive genetic testing, TTIMax values of 8.4% and 8.9% revealed early structural abnormalities consistent with AS, confirmed by FSGS and basement membrane changes on electron microscopy. Separately, five patients with variants initially classified as VUS (e.g., COL4A3 c.4421T>C, COL4A5 c.3686G>A) demonstrated consistent TTIMax elevations years before their variants were reclassified as pathogenic. OCT abnormalities remained stable despite shifting variant interpretations, underscoring their diagnostic reliability.
Conclusion
TTIMax is a robust imaging biomarker that complements genetic testing by identifying AS-related structural changes in cases of diagnostic uncertainty. Its predictive value—both in the absence of genetic confirmation and potentially prior to variant reclassification—supports its integration into multimodal diagnostic pathways for COL4-related nephropathies.