Purchase this article with an account.
Lynn K. Stanwyck, Emily Place, Jason Comander, Rachel M Huckfeldt, Lucia Sobrin; Predictive value of genetic testing for inherited retinal diseases in patients with suspected atypical autoimmune retinopathy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4208.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The clinical features of autoimmune retinopathy (AIR) can resemble and be difficult to differentiate from inherited retinal disorders (IRD). Misdiagnosis of an IRD as AIR causes unnecessary treatment with immunosuppressive agents. In this retrospective case series, we calculate the predictive value of genetic testing for IRD in patients with suspected AIR, and provide productive examples of this testing in clinical practice.
This study was approved by the Massachusetts Eye and Ear Infirmary (MEEI) institutional review board and conformed to the provisions of the Declaration of Helsinki. We identified patients seen at MEEI between April 2013 and January 2017 for whom the differentiation of AIR vs. IRD was difficult based on clinical assessment alone. All patients had some atypical features for AIR, but tested positive for anti-retinal antibodies. We further identified the subset of these patients who had genetic testing for IRDs with Genetic Eye Disease panel for Retinal genes (GEDi-R). We recorded clinical characteristics and ancillary testing results. We calculated the positive predictive value (PPV) and negative predictive value (NPV) of genetic testing in a population with about equal numbers of IRD and AIR patients.
Of the seven patients for whom it was difficult to distinguish between IRD and AIR on a clinical basis, six had genetic testing: 4 women and 2 men with a mean age of 62 years. In two of these six patients, genetic diagnoses were made based upon the identification of known pathogenic variants in the common IRD genes USH2A and RHO. Two patients had variants of unknown significance within IRD genes, and the other two had no relevant genetic findings. Given the 51% sensitivity for GEDi-R testing and assuming a 50% pre-test probability of having an IRD based on clinical data, the PPV for GEDi-R for detecting IRD in this patient population is 91% and the NPV is 67%.
In patients for whom the differential diagnosis of AIR and IRD is unclear based on clinical information, genetic testing can be a valuable tool when it identifies an IRD, thus sparing the patient unnecessary treatment with immunosuppressive agents. However, the test has a low negative predictive value, meaning that a negative genetic testing result does not confidently exclude IRD as the true diagnosis.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
This PDF is available to Subscribers Only