Clinical and Histopathologic Correlates of Asymmetric Retinitis Pigmentosa

Question  What additional information can we obtain about nonsyndromic asymmetric retinitis pigmentosa (RP) from studying human pathology samples?

Findings  This case report compared clinical imaging with histopathology and sequencing DNA extracted from autopsied eyes of a deceased patient with asymmetric RP. No additional pathogenic variants were found using this approach.

Meaning  This approach may provide a multimodal perspective into functional, cellular, and molecular phenotyping; in this case, an ultrarare presentation of asymmetric RP that can be applied to other rare mendelian diseases.

Importance  Asymmetric retinitis pigmentosa (RP) is a rare presentation of a normally symmetric condition. Histopathologic evidence should be examined to see if this asymmetry extends to the tissue and cellular levels.

Objective  To determine whether additional information can be obtained about asymmetric RP from studying clinical imaging and pathology correlates, including pathology samples from autopsied eyes.

Design, Setting, and Participants  In this case report, clinical and postmortem histopathological characteristics were compared in 2 eyes of a patient in her 50s with asymmetric RP. Individuals with rare mendelian diseases, such as RP, were studied using data from the curated National Eye Institute Eye Pathology collection.

Main Outcome and Measures  Results of clinical evaluation, multimodal retinal imaging, histopathology, and molecular genetic testing in a case of nonsyndromic asymmetric RP using resources from the ocular pathology collection.

Results  Eyes from a deceased patient in her 50s with nonsyndromic asymmetric RP found within the ocular pathology collection were studied. The patient was diagnosed with RP as an adolescent and presented in her 50s to the eye clinic with advanced RP, with the left eye affected much more severely than the right. The patient’s phenotype was studied using in vivo imaging and postmortem histopathology to identify interocular differences in tissue degeneration. Extraction of blood-derived DNA and formalin-fixed paraffin-embedded DNA from autopsied eyes analyzed using next-generation sequencing did not yield a definitive molecular diagnosis nor significant tissue differences.

Conclusions and Relevance  This study demonstrates newly reported histopathological and molecular correlates in asymmetric RP. This report also highlights the relevance of studying previously seen patients and reevaluating their conditions using resources within the ocular pathology collection to gain further insight on their disease.