Ophthalmology

Genetic testing is clinically relevant for the following indications, including but not limited to:

• Patients with clinically suspected inherited retinal disease or otherwise unexplained progressive vision loss
• Suspected syndromic retinal disease, where retinal degeneration occurs with features such as hearing impairment in
• Patients assessed for eligibility for gene-directed therapies or clinical trials, such as RPE65-associated retinal disease
• Families seeking genetic counselling, recurrence-risk clarification or cascade testing of relatives

Testing is typically requested by ophthalmologists, paediatricians, optometrists, and clinical geneticists.

Genetic testing is used when a heritable eye disorder is suspected, where a precise molecular diagnosis guides treatment decisions. For example, in a predominantly pediatric cohort of 193 patients with negative electroretinograms, comprehensive genetic testing established the diagnosis in 91.7%, spanning 41 genes.

• A pathogenic or likely pathogenic variant establishes the specific molecular diagnosis, identifying the causative gene and condition.
• A variant of uncertain significance (VUS) cannot currently be classified as likely benign or likely pathogenic, and reanalysis can be offered after a few years as evidence accumulates.
• In other cases, no pathogenic variant is detected in the analyzed genes; a pathogenic variant cannot, however, be entirely excluded, as the causative change may lie in a gene not yet linked to the condition or in a regulatory region that current methods cannot reliably capture.
• Each variant is classified according to criteria.

A confirmed pathogenic finding secures the diagnosis and can refine prognosis, guiding the timing of low-vision support and, where syndromic features are present, surveillance for extraocular involvement. It clarifies inheritance and recurrence risk, enabling cascade and predictive testing of relatives. For eligible genotypes such as RPE65-associated disease, it can establish access to approved gene-directed therapy or clinical trials.

is an important part of the testing process. It helps patients and families understand the test, interpret results, and make well-informed medical decisions, and it supports physicians in delivering informed care. Availability of genetic counselling services may vary by country. Please to check out access in your region.

Testing is based on , combined with virtual multi-gene panels for each clinical entity. Gene content can be customized upon customer request.

• Marques JP, Soares CA, Carvalho AL, Estrela-Silva S, Santos LC, Ramos L, et al. Portuguese Society of Ophthalmology and Portuguese Society of Human Genetics Joint Clinical Practice Guidelines for Genetic Testing in Inherited Retinal Dystrophies. Clin Genet. . 2025;107(6):600-611. doi: 10.1111/cge.14691. PMID: . PMCID: PMC12050251.
• Lam BL, Leroy BP, Black G, Ong T, Yoon D, Trzupek K. Genetic testing and diagnosis of inherited retinal diseases. Orphanet J Rare Dis.. 2021;16(1):514. doi: 10.1186/s13023-021-02145-0. PMID: . PMCID: PMC8670140.
• Sodi A, Banfi S, Testa F, Della Corte M, Passerini I, Pelo E, et al. RPE65-associated inherited retinal diseases: consensus recommendations for eligibility to gene therapy. Orphanet J Rare Dis. 2021;16(1):257. doi: 10.1186/s13023-021-01868-4. PMID: . PMCID: PMC8176684.
• Bahena P, Daftarian N, Maroofian R, Linares P, Villalobos D, Mirrahimi M, et al. Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment. Hum Genet. 2022;141(3-4):785-803. doi: 10.1007/s00439-021-02303-1. PMID: . PMCID: PMC9035000.
• Zaslavsky K, Tumber A, Millar E, Boginskaia O, MacDonald H, Klatt R, et al. Genetic Spectrum of Negative Electroretinograms in a Predominantly Pediatric Cohort of 177 Patients. Invest Ophthalmol Vis Sci. 2025;66(15):19. doi: 10.1167/iovs.66.15.19. PMID: . PMCID: PMC1269769