Jared T. Sokol, MD, MBA
Massachusetts Eye and Ear
Day 2 of the Atlantic Coast Retina Club was filled with fascinating mystery cases presented by leading retina faculty. Below are highlights from Session F, moderated by Dr. Ninel Z. Gregori, MD (Bascom Palmer Eye Institute) and Dr. Lucy Young, MD, PhD (Mass Eye and Ear)
Dr. David J. Ramsey presented the first case of a 73-year-old male with progressive vision loss in both eyes over the last few months. He has a previous diagnosis of early AMD and family history positive for AMD receiving anti-VEGF injections. Vision was 20/400 OD and 20/60 OS. Exam was notable for RPE changes OU, few drusen OU, blonde fundus OU, and reticular degeneration OU. Work-up was notable for significant retinal thinning, IS/OS loss on OCT, enlarged deep foveal avascular zone on OCTA, mild visual field constriction on Goldmann perimetry, and changes on photopic full-field ERG. Genetic testing was notable for a heterozygous pathologic sequence variant of Crumbs homolog 1 (CRB1), which has been implicated in a wide range of inherited retinal diseases. The patient seemed to have findings of both an IRD and AMD and it was posed that CRB1 could be acting as a modifier gene in AMD.
The next case was presented by Dr. Jose Pulido of a 54-year-old male with a history of lupus, lupus nephritis, rheumatoid arthritis, and Hashimoto’s disease referred for a possible inherited retinal disease. The patient had a family history of retinitis pigmentosa and came to clinic with a previously performed negative retinitis pigmentosa genetic panel. The patient’s exam was significant for pigment changes in the posterior pole of both eyes. Autofluorescence was significant for hypoautofluorescence in the posterior pole with a surrounding ring of hyperautofluorescence in the midperiphery. Full-field ERG showed diminished rod and cone function in both eyes. An autoinflammatory disease was suspected so genetic testing for ALPK1 was sent and a pathologic variant in ALPK1 was identified. The patient was diagnosed with retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache (ROSAH syndrome), which is an inherited NF κB–mediated autoinflammatory disease with retinal dystrophy.
Dr. Nitish Mehta shared a case of a 31-year-old female who presented with a yellow spot in her vision centrally in the left eye. She had decreased visual acuity of 20/60 in the left eye and endorsed a mild headache. OCT was notable for an elevation of the subfoveal outer retina with loss of photoreceptors. Laboratory work-up was negative and oral prednisone was started, which resulted in worsening of the lesion so this was stopped. The differential diagnosis was thought to include acute idiopathic maculopathy, acute macular neuroretinopathy, or myopic neovascularization. Over the next 6 months the lesion diminished. The diagnosis remained unclear and after 1 year the patient was 20/20 with complete resolution of the lesion.
Next, Dr. Jason I. Comander presented a 30-year-old female with a long-standing diagnosis of retinitis pigmentosa. Her OCT was notable for loss of outer retinal layers peripherally and normal retinal layers centrally. Full-field ERG was better than expected based on the diagnosis. A review of the records revealed that the patient was originally diagnosed with RP at age 2 after presenting with nyctalopia. ERG at her original diagnosis was severely diminished and when comparing ERGs over time, the amplitudes seem to have improved. The question of this being RP was posed to the audience. Genetic testing revealed a pathogenic variant in RPE65. The patient was treated with Luxturna gene therapy, with the patient having a subjective improvement in night vision. Our visual field remained stable in the treated eye while it worsened in the fellow eye. Her diagnosis was thought to be RPE65 disease with a mild RP phenotype.
Dr. Yasha S. Modi presented a case of a 27-year-old female with Leber congenital amaurosis (biallelic mutation in RPE65). The patient also had a 25-year-old sister with LCA. Baseline OCT demonstrated a small area of ellipsoid zone preserved at the fovea and otherwise diffuse outer retinal loss. She underwent Luxturna gene therapy treatment in both eyes. Post-operatively she endorsed brighter vision, but shortly after she developed a headache, painful red eyes, and bilateral loss of vision. Her exam was notable for vitritis, bilateral serous retinal detachment, and choroidal infiltrates. Her presentation was thought to be a VKH-sympathetic ophthalmia like picture. It was questioned if exposure of ocular antigens during surgery, unrelated inflammatory response, or an autoimmune response to the gene therapy was the cause of her presentation. HLA-typing was performed with 3 SO-VKH “risk alleles”. The patient received corticosteroid treatment and was transitioned to systemic immunosuppression; she continued to have poor vision in both eyes. This was thought to be a severe case of inflammation after Luxturna gene therapy with HLA-typing suggesting that she was “at risk” for SO-VKH like disease.