Ophthalmic
for inherited retinal diseases, congenital cataracts, and optic atrophy with gene panels and whole genome sequencing
System Profile
Yield Comparison
Clinical Dimensions
- Cataracts
- Retinal disease
- Coloboma
- Strabismus
- Nystagmus
- Early visual loss
- Retinitis pigmentosa
- Leber congenital amaurosis
- Congenital cataracts
- Aniridia
- Coloboma
- Optic nerve hypoplasia
- Stickler ocular disease
- Strabismus
- Cataracts
- Coloboma
- Retinal pigment changes
- Nystagmus
- Ptosis
- Optic nerve hypoplasia
- Absent red reflex
- Blurry vision
- Night blindness
- Photophobia
- Wandering eye
- Progressive vision loss
- Missing objects in periphery
- Color vision issues
- Elevated lactate during neuro-ophthalmic symptoms
- Abnormal peroxisomal markers
- Elevated phytanic acid
- VLCFA elevation
- Retinal imaging with bone-spicule pigmentation
- Optic nerve hypoplasia
- Coloboma
- Cataracts on slit-lamp
- Foveal hypoplasia
- Retinal thinning
- ERG abnormal (retinal dystrophy)
- OCT with thinning
- VEP delayed
- Slit-lamp showing cataracts
- Fundus photography showing RP patterns
- Steroid eye drops
- Intraocular meds
- Long-term ocular pressure meds
- Vitamin supplements in retinal dystrophy
- Severe ocular surface reactions to topical meds
- Prolonged inflammation after minor exposures
- Cataract removal in infancy
- Strabismus surgery
- Glaucoma surgeries
- Retinal reattachment or laser procedures
- Low-vision therapy
- Orientation and mobility training
- Visual aids and accommodations
- Low-vision aids
- Magnifiers
- Special lenses
- Prisms
- Occlusion patches
- Pediatric ophthalmology/retina specialists
- Low vision services
- Ophthalmologist noting syndromic ocular findings and suggesting genetic workup
- Retinitis pigmentosa
- Early-onset blindness
- Congenital cataracts
- Coloboma
- Optic nerve anomalies
- Strabismus running in family
- No trauma or screen overuse explaining visual loss
- Visual problems present since infancy
- No occupational exposure to toxins
- Congenital cataracts
- Coloboma
- Microphthalmia
- Nystagmus
- Poor visual tracking
- Absent red reflex
Red Flag Combinations
Clinical patterns that should prompt consideration of genetic testing
Retinal dystrophy + ataxia
Cataracts + hearing loss
Coloboma + CHD (CHARGE)
Optic nerve hypoplasia + pituitary/endocrine issues
Screening Decision Pathway
When to consider genetic testing for ophthalmic presentations
graph TD
START["Patient Presents with\nOphthalmic Concerns"] --> SCREEN{"Screen for\nRed Flags"}
SCREEN --> RF1["Failed vision screens"]
SCREEN --> RF2["Abnormal red reflex"]
SCREEN --> RF3["Early screening showing strabismus or acuity defic..."]
RF1 --> EVAL{"Multiple\nFlags Present?"}
RF2 --> EVAL{"Multiple\nFlags Present?"}
RF3 --> EVAL{"Multiple\nFlags Present?"}
EVAL -->|Yes| TEST["Order Genetic Testing\n(ES/GS)"]
EVAL -->|No| MONITOR["Continue Monitoring\nRe-evaluate if New Findings"]
TEST --> DX["Molecular Diagnosis\n49-92% yield"]
style TEST fill:#dcfce7,stroke:#16a34a,color:#14532d
style DX fill:#bbf7d0,stroke:#16a34a,color:#14532d
style MONITOR fill:#fef3c7,stroke:#d97706,color:#92400e
Screening Red Flags
Findings on routine screening that may indicate genetic etiology
- Failed vision screens
- Abnormal red reflex
- Early screening showing strabismus or acuity deficits
Exome / Genome Sequencing Indications
Clinical scenarios supporting ES/GS as a diagnostic approach
- Retinal dystrophy
- Congenital cataracts
- Coloboma
- Optic nerve anomalies
- Progressive childhood vision loss, particularly with systemic features or family history
Key Evidence
Published studies supporting genetic testing for ophthalmic conditions
| Study | Year | Type | Sample | Yield | Key Finding |
|---|---|---|---|---|---|
| Comprehensive Genetic Study of Retinitis Pigmentosa and Ushe... | 2021 | Cohort | 591 | 37.4-55.2% | Genetic screening of 591 Italian RP/Usher probands achieved 37.4-55.2% diagnosti... |
| 100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Ca... | 2021 | Cohort | 2183 | 25% | 25% diagnostic yield in 2183 rare disease families; monogenic disorders 35% vs c... |
| Clinical and Genetic Re-Evaluation of Inherited Retinal Dege... | 2022 | Cohort | None | 70-92% | 70-80% diagnostic yield with targeted IRD panels, rising to 92% with WGS as seco... |
| Clinician-Driven Exome Sequencing Reanalysis for Inherited R... | 2024 | Cohort | 264 | 71.2% | 62.9% initial ES diagnostic yield + 8.3% additional from clinician-driven reanal... |
| Whole-Genome Sequencing Added Value for Inherited Retinal Dy... | 2024 | Cohort | 66 | 28.8% | 28.8% WGS yield in 66 WES-negative IRD families; true added value 9.6% overall (... |
| Determinants of Diagnostic Yield in a Multi-Ethnic Asian Inh... | 2025 | Cohort | None | 49.2% | 49.2% diagnostic yield in 506 IRD probands with panel testing; 69 genes, ABCA4/U... |
| Long-Read Genome Sequencing for Inherited Retinal Dystrophie... | 2025 | Case Report | 3 | 100% | 3/3 previously unsolved IRD cases solved with long-read GS (PacBio Revio): deep ... |
Updated: 2026-02-25
Curated by: human
Status: human reviewed