Non-paraneoplastic autoimmune retinopathy that developed in fellow eye 10 years after onset in first eye: a case report

Autoimmune retinopathy (AIR) consists of a group of inflammation-mediated retinal disorders which are characterized by a reduction in vision, defects in the visual field, dysfunction of the photoreceptors, and presence of antiretinal antibodies. Cancer-associated retinopathy, first reported in 1976, is characterized by vision reduction due to photoreceptor degeneration and the presence of a cancerous lesion [1]. AIR without the detection of a malignancy is called non-paraneoplastic retinopathy (npAIR), and it was first reported in 1997 [2]. Despite the many case reports since this report, the diagnosis, management, and treatment of AIR is still a challenge because the clinical diagnostic criteria and treatment methods have not been definitively established. In addition, there are still many unanswered questions on the long-term prognosis of npAIR.

Thus, the purpose of this report is to present our findings in a case of npAIR that developed in the fellow eye 10 years after the onset of npAIR in the first eye.

It has been reported that photophobia and photosensitivity are characteristic symptoms of AIR [4]. Our case had bilateral photophobia since the onset in the first eye. However, AIR usually develops bilaterally [5] which was different from our case.

Enolase is a 46-kDa glycolytic enzyme that is expressed in both the retina and the optic nerve [6]. Anti-enolase antibodies have been reported to be positive not only in systemic autoimmune diseases [7] but also in patients without a tumor and 10% of healthy subjects [8]. However, considering the reported diagnostic criteria for AIR and the clinical characteristics of α-enolase antibody-positive autoimmune retinopathy, we believe that this antibody affected the development and clinical symptoms of retinopathy in our case. The clinical manifestations of anti-α-enolase antibody-positive paraneoplastic AIR patients were reported to be relatively mild, and the progression was comparatively slow [9]. The findings in our case are consistent with these earlier cases in which α-enolase antibodies were positive and the progression was slow. The clinical features of Japanese patients with anti-α-enolase antibody-positive AIR were recently published [10]. The authors reported that OCT showed drusen of various sizes with domed-shaped hyperreflective spots under the retinal pigment epithelium corresponding to the drusen in 48% of the cases. However, neither the fundus photographs nor the OCT images showed any obvious drusen in our case. The authors also reported that the BCVA improved or was maintained in 80% of the eyes during the follow-up period. However, their study period was at least two months, making it difficult to compare their findings with that of our case. Saito et al. presented a case with small cell lung carcinoma that developed bilateral neuroretinitis with unilateral focal outer retinitis that was positive for autoantibodies against recoverin, CRMP-5, and α-enolase [11]. They reported that the recoverin-mediated autoimmune retinopathies and ophthalmic findings in their case had inflammatory features. Although similar to our case by the presence of inflammation, the response to treatment was different. It is not known why there was a difference in the response to treatment, however their case was associated with a tumor which could be treated. Adamus et al. reported that a rebound of the anti-recoverin autoantibody titer was associated with exacerbations of the visual symptoms. However, anti-recoverin antibody was not detected throughout the clinical course of our case [12]. In addition, Ferreyra et al. reported that there was an improvement in vision in only 19% of npAIR without CME and in 25% of npAIR with CME after treatment [3]. The authors also showed that the subgroup most responsive to immunosuppression treatment was the paraneoplastic AIR group and the least responsive was the npAIR group [13]. A case of unilateral TRPM1-positive CAR associated with adenocarcinoma of the right ovary has been reported [14]. The patient was treated with rituximab, monoclonal antibody, and corticosteroids which resulted in a visual acuity of 20/20, symptomatic improvements, and normalization of the ERGs. Although there are differences from our case, such as the type of antibody, the presence of a tumor or method of treatment, further long-term follow-up of the patient is necessary. A case of CAR more similar to our case was reported by Saito et al. [15]. Goldmann perimetry and ERGs of their case showed retinitis pigmentosa–like findings in the right eye and a normal appearance in the left eye at the first onset. Eight years later, the left eye also presented with a visual field defect and ERG abnormalities, and immunoblot analyses detected anti-recoverin antibodies. The differences from our case are that in their case a bronchioloalveolar carcinoma was detected and treated, that anti-recoverin antibodies were detected, and that the visual prognosis was good only with 40 mg/g of oral administration of prednisolone. Their case report indicates that regular screening for tumors is necessary even in cases where no tumor was detected as in our case.

It is not clear why the disease initially developed in only one eye, and why it took 10 years to develop in the fellow eye. In addition, we could not determine why the response to treatment was poor. Our case was not treated with biologics such as anti-CD20 monoclonal antibody, e.g., Rituximab, or intravenous immunoglobulin. The treatment consisted of only steroids at the initial onset. Therefore, the clinical course might have been different if further treatments had been given at that time.

In summary, we presented our findings in a case of npAIR that developed in the fellow eye more than10 years after its onset in the first eye. Our case had differences in the clinical findings, characteristics, and course compared to earlier cases. Because our case was resistant to treatment and had poor visual functional outcome, cases such as ours require careful follow-up. There is still no established evidence-based treatment for cases of npAIR, and it varies among physicians, regions, and facilities. Sharing the history of this case will help to reaffirm the importance of follow-up examinations in patients with npAIR and in considering treatment options.