*3.1. Patient Description*

The patient initially presented to the neuro-ophthalmology service at the age of 51 for evaluation of decreased peripheral visual fields and photopsias in both eyes. He had no family history of inherited retinal degeneration. At presentation, his visual acuity was 20/20 in each eye, but he was found to have peripheral visual field loss. Ophthalmoscopic examination early in his disease course showed granular juxtapapillary pigmentary changes and mild vascular attenuation in both eyes. Electroretinogaphy (ERG) at presentation was consistent with widespread retinal dysfunction a ffecting both rods and cones. He experienced relatively rapid progression of his visual field loss and was seen by the inherited retinal degeneration service with concern for retinitis pigmentosa versus autoimmune retinopathy (AIR). Cancer-associated retinopathy was also considered, but his workup for malignancy was negative and his ERG was felt to be inconsistent with a paraneoplastic process at that time.

He ultimately developed peripheral bone-spicule-like pigmentary changes in both eyes (Figure 1A,B, 7 years after initial presentation) and progressive visual field constriction (Figure 1C,D, 8 years after initial presentation). Molecular evaluation for an inherited retinal degeneration, including whole exome sequencing, was performed but failed to identify a genetic etiology for his condition (for methods see [2]). He developed colon cancer several years after presentation, but this was thought to

be unrelated to his ocular disease. He was given a presumed diagnosis of autoimmune retinopathy and ultimately required treatment for cystoid macular edema with intravitreal steroids.

**Figure 1.** Clinical findings in a patient with retinal degeneration. (**A**,**B**): Montage color fundus photographs of the right (**A**) and left (**B**) eyes. There was granular, retinal pigment epithelial atrophy in the mid-periphery of both eyes, in addition to peripheral bone-spicule-like pigmentary changes and pigment clumps in both eyes. Arteriolar attenuation was notable in both eyes. (**C**,**D**): Goldman visual fields of the right (**C**) and left (**D**) eyes. There was severe constriction of the peripheral visual field in both eyes.

At the time of his last follow up with the retina service at the age of 69, his visual acuity was 20/40 + 1 in the right eye and 20/100 in the left eye with stable peripheral pigmentary changes in both eyes, and no cystoid macular edema. At age 70, the patient expired and donated his eyes for ophthalmic research. Evaluation of the patient's serum with Western blotting revealed the presence of antibodies that reacted with a 23 kilodalton protein in human retina.
