Clinical Characteristics and Chronic Immunotherapy in Idiopathic Recurrent Neuroretinitis and Idiopathic Recurrent Papillitis: Describing a Potential New Phenotype.

Background: Idiopathic cases of recurrent optic disc edema, which we termed idiopathic recurrent papillitis (IRP), share similar features with idiopathic recurrent neuroretinitis (IRN). This raises the possibility that they may be in the same spectrum of disease, in which long-term immunotherapies have been suggested to reduce relapses. We sought to characterize IRN and IRP, including the treatment effects of immunotherapy.

Methods: This retrospective, multicenter cohort study included patients with either IRN or papillitis (all without retrobulbar optic nerve enhancement on MRI during the acute attack) who were diagnosed at Mayo Clinic or University of Minnesota between January 2015 and October 2023. Demographics, age at first attack, and annualized relapse rates (ARRs) on and off long-term immunotherapy for patients on immunotherapy >6 months were recorded.

Results: Among 30 patients, 17 (56.7%) patients had a neuroretinitis attack at least once, out of whom 10 (58.8%) patients had both neuroretinitis and papillitis attacks. Thirteen (43.3%) patients had only papillitis attacks. The median age of first attack was 34 years (interquartile range [IQR] 28-42) in neuroretinitis and 38 years (IQR 28-49) in papillitis (P = 0.91). The median number of attacks for all patients was 3.5 (IQR 3-5). Out of 15 patients who were on immunotherapy for 6 months or longer, 10 (66.7%) patients had at least 1 relapse with a median ARR on therapy of 0.28 attacks/year (IQR 0-0.54), which was not significantly different from off therapy (P = 0.74). Among immunotherapies, mycophenolate mofetil had the lowest median ARR (0 attacks/year, IQR 0-0.29), followed by intravenous immunoglobulin (0.49 attacks/year, IQR 0.25-0.74), methotrexate (0.49 attacks/year, IQR 0.29-0.87), rituximab/ocrelizumab (0.68 attacks/year, IQR 0.34-1.47), and azathioprine (0.75 attacks/year, IQR 0-2.17).

Conclusions: There is significant overlap between IRN and IRP, suggesting they are in the same spectrum of disease. Most long-term immunotherapies other than mycophenolate did not seem to be effective in reducing the number of relapses, although further prospective studies are required to assess this.