Abstract
Purpose :
To report the characteristics of inflammatory findings in patients with USH2A-associated retinal degeneration.
Methods :
We retrospectively identified 75 subjects (M=38/F=37, age 4-84) with confirmed disease-causing USH2A gene mutations, all of whom had a complete eye exam, including visual acuity (VA), visual fields (VFs), full field electroretinograms, macular (n=75) and optic nerve (n=40) spectral domain optical coherence tomography (SD-OCT), fluorescein angiography (FA) (n=31), and CLIA-certified testing (n=35) for circulating auto-antibodies (AAbs) against retinal and/or retrobulbar optic nerve (ON) antigens by immunoblot, Western blot, and retinal immunohistochemistry (IHC).
Results :
Of the 62 tested eyes with FA, 38 eyes had leakage of optic nerve head, vascular arcades, macula, or a combination thereof. The nerve fiber layer (NFL) was thickened on SD-OCT, most often sectorally, in 49 of 80 eyes, and correlated well with FA leakage, helping explain disproportionate VA losses compared to foveal SD-OCT findings. Cystoid macular edema (CME) was seen by SD-OCT in 47 of 150 eyes. Anti-retinal AAbs were found in 32 of the 35 tested patients [most often against carbonic anhydrase II (16/35) and enolase (15/35)]. AAbs recognizing anti-ON antigens were found in 28 of 34 tested patients. Retinal IHC showed positive staining in 28 of 34 cases, labeling predominantly photoreceptors (26/34) and less frequently ganglion cells (GC=11/34) and NFL (8/34). Altogether, 66.7% (50/75) of patients exhibited clinical signs of inflammation, which correlated directly with the presence of circulating AAbs in 25 of them. These patients received intravitreal and/or sub-Tenon steroid injections, with both subjective and measurable increase in vision (VA, VF, or both), associated with improved OCT and FA characteristics in most cases.
Conclusions :
Secondary autoimmunity (affecting optic nerve, NFL, and/or GC) and clinical inflammation involving retina and/or optic disc appear to be common yet underdiagnosed features of USH2A-associated retinal degeneration. Clinical inflammatory manifestations that can be readily detected with macular OCT, disc OCT, and FA affected 2/3 of the patients. Clinical suspicion can be further confirmed by AAb/IHC testing. Identification of these complications is clinically and prognostically important, as meaningful vision improvements can be achieved with treatment.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.