Inherited Retinal Disease: Advances in Diagnosis and Management

Overview

Inherited retinal diseases (IRDs) are increasingly diagnosable and manageable in general optometric practice due to advances in imaging and genetic testing. A case of a 60-year-old male initially diagnosed with dry AMD was reclassified as pseudo-Stargardt pattern dystrophy after multimodal imaging and genetic testing revealed a PRPH2 gene mutation.

Background

Inherited retinal diseases have traditionally required referral to specialized centers due to their complexity. Recent technological advances, including widefield imaging, fundus autofluorescence, optical coherence tomography, and genetic testing, have made IRD diagnosis and management more accessible in community practice. IRDs often mimic other retinal conditions such as age-related macular degeneration, complicating diagnosis. Genetic testing now enables precise genotype identification, prognosis, and eligibility for emerging therapies.

Data Highlights

The patient’s visual acuity was 20/50 in the right eye and 20/30 in the left eye despite advanced retinal changes. Fundus autofluorescence showed patchy central hypoFAF with symmetric hyperFAF flecks extending beyond the vascular arcades, atypical for AMD. OCT revealed large areas of atrophy and abnormal deposits anterior to the RPE, inconsistent with drusen. Genetic testing identified a pathogenic variant in the PRPH2 gene, confirming pseudo-Stargardt pattern dystrophy.

Key Findings

• Multimodal imaging techniques such as FAF, OCT, and widefield photography are critical for differentiating IRDs from AMD.
• Symmetric hyperautofluorescent flecks beyond the macula suggest an IRD rather than typical AMD.
• OCT findings of deposits anterior to the RPE and extensive atrophy support an IRD diagnosis.
• Full-field electroretinography and dark adaptation testing can aid early IRD detection but were not used in this case.
• Genetic testing confirmed a PRPH2 mutation causing pseudo-Stargardt pattern dystrophy, an autosomal dominant IRD with variable expression.
• Absence of family history does not exclude IRD due to variable penetrance and expressivity.

Clinical Implications

Optometrists should consider IRDs in patients with atypical retinal findings or poor response to standard AMD treatments. Incorporating multimodal imaging and genetic testing into practice facilitates accurate diagnosis, prognosis, and identification of patients eligible for clinical trials. Early detection of choroidal neovascularization in IRDs allows timely anti-VEGF therapy to improve outcomes.

Conclusion

Advances in imaging and genetic testing have transformed IRD diagnosis and management, enabling community-based clinicians to identify and treat these complex conditions more effectively. Recognizing IRD masqueraders such as pseudo-Stargardt pattern dystrophy is essential for appropriate patient care and access to emerging therapies.

References

1. Author/Source/2024 -- Digging in to Inherited Retinal Disease