Secondary Ophthalmic Features Represent Diagnostic Clues and Potential Points of Intervention for Inherited Retinal Diseases (Target 5000 Report 3)

Authors

• Kirk A.J. Stephenson, Mater Misericordiae University Hospital
• Julia Zhu, Mater Misericordiae University Hospital
• Marcus Conway, Mater Misericordiae University Hospital
• Bridget Moran, Mater Misericordiae University Hospital
• Adrian Dockery, Mater Misericordiae University Hospital
• Laura Whelan, The Provost, Fellows, Foundation Scholars & The Other Members Of Board, Of The College Of The Holy & Undivided Trinity Of Queen Elizabeth Near Dublin
• Jacqueline Turner, Mater Misericordiae University Hospital
• James J. O’Byrne, Mater Misericordiae University Hospital
• D. Ian Flitcroft, School of Physics, Clinical and Optometric Sciences
• G. Jane Farrar, The Provost, Fellows, Foundation Scholars & The Other Members Of Board, Of The College Of The Holy & Undivided Trinity Of Queen Elizabeth Near Dublin
• David J. Keegan, Mater Misericordiae University Hospital

ORCID

• D. Ian Flitcroft: 0000-0002-7004-6026

Abstract

Background/Objective: Inherited retinal degenerations (IRDs) are the leading cause of blind registration in children and adults, yet 30–40% of cases remain genetically unresolved. Deep ophthalmic phenotyping may help to address this shortfall by identifying characteristic phenotypes. We describe the ophthalmic features of patients with stationary or progressive inherited retinal diseases other than outer retinal degeneration (i.e., secondary ophthalmic features, SOFs). Methods: This is a retrospective review of all patients attending an ophthalmic genetics clinic with a genetically confirmed IRD focusing on SOFs including refractive error, cataract, retinal detachment (RRD), cystoid macular lesions (CML) and epiretinal membrane (ERM). These features were assessed in the context of phenotype and genotype. Results: In a cohort of 429 genotyped patients, ≥1 SOFs were seen in 70.2% of patients, with 36.6% being affected by multiple SOFs. Refractive error (63.3%) and cataract (43.4%) were the most common secondary features, with a subset affected by CML (14.7%), ERM (10%) and RRD (4.7%). Conclusions: SOFs are common in patients with IRDs and most are amenable to therapeutic intervention even when no primary treatment (e.g., gene therapy) is available. We highlight patterns associated with genotypes and disease groups which may aid harmonisation of clinical and genetic diagnoses.

Keywords

cataract, cystoid macular lesions, inherited retinal degenerations, myopia, retinal detachment

DOI Link

10.3390/genes16121433

Publication Date

2025-01-01

Publication Title

Genes

Volume

16

Issue

12

Deposit Date

2026-11-05

Funding

This project received funding from Fighting Blindness Ireland (FB16FAR, FB18CRE, FB20DOC), The Health Research Board Ireland (POR/2010/97), Health Research Charities Ireland (HRCI-HRB-2020-007; MRCG-2013-8, MRCG-2016-14) and Science Foundation Ireland (16/1A/4452).

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Additional Links

https://www.scopus.com/pages/publications/105026140152

Recommended Citation

Stephenson, K., Zhu, J., Conway, M., Moran, B., Dockery, A., Whelan, L., Turner, J., O’Byrne, J., Flitcroft, D., Farrar, G., & Keegan, D. (2025) 'Secondary Ophthalmic Features Represent Diagnostic Clues and Potential Points of Intervention for Inherited Retinal Diseases (Target 5000 Report 3)', Genes, 16(12). Available at: 10.3390/genes16121433