Identifying patients with autoimmune retinopathy

CAR was first reported in association with small cell lung cancer, but can occur with other malignancies including prostate, breast, and colon cancer.² Prompt diagnosis is important due to the possibility of an underlying malignancy in patients with CAR or MAR, and the correct diagnosis can lead to initiation of potentially life saving systemic treatment.

The classic anti-retinal antibody associated with CAR is directed against the 23 kDa protein, and detection of this antibody in the serum of a patient with acute vision loss should prompt a thorough systemic evaluation for an occult malignancy. However, in most case series the majority of patients with an autoimmune retinopathy will not have anti-recoverin antibodies or an underlying malignancy so the extent of the workup is controversial.

Autoimmune retinopathies are easily overlooked and can be difficult to diagnose. Patients classically present with acute to sub-acute vision loss, nyctalopia, scotomas and photopsias. However, visual complaints can be vague and nonspecific. The physical exam is often unremarkable with the most common findings being optic nerve pallor and vascular attenuation.

So how does the clinician decide when to pursue a patient's non-specific visual complaints with expensive and sometimes difficult to obtain tests like ERG and serum antibody analysis?

The first step is to expand the history. Some patients will have a recent diagnosis of cancer, or a history of prior malignancy. In patients with a non-paraneoplastic retinopathy, a personal or family history of autoimmunity can often be elicited.

Then a review of systems should be obtained to identify any pertinent positives that suggest an underlying malignancy such as unexplained weight loss or dyspnea. In addition, visual field testing is important for establishing an objective measure of vision loss. Concentric constriction is a classic finding, but the presence of any scotomata should heighten clinical suspicion.

Importance of imaging

Imaging technologies such as fundus autofluorescence (AF) and spectral domain optical coherence tomography (SD-OCT) are quickly becoming the most frequently ordered studies in ophthalmology, and they can provide important diagnostic information in conditions where the conventional exam is unremarkable. Using these imaging modalities, our group described fundus abnormalities in a group of seven patients with an autoimmune retinopathy.³

Using SD-OCT we found loss of outer retinal layers including the outer nuclear layer (ONL), the inner segment and outer segment junction (IS/OS) and external limiting membrane (ELM). The loss of these outer retinal structures was found within the macula, but spared the fovea. In one patient with CAR followed over eight months, these retinal changes progressed centripetally with a corresponding loss of vision by Goldman visual field testing. Lima et al. reported similar findings in a series of four patients with an autoimmune retinopathy.⁴ They also demonstrated a functional consequence associated with these imaging changes by microperimetry.

Another similar finding in both studies was the presence of abnormal fundus autofluorescence that corresponded with the boundaries of the structural changes noted on SD-OCT. In the areas of outer retinal loss, abnormal hyper-autofluorescence was seen acutely, but over time evolved to mottled hypo-autofluorescence. Typically, the area of hyper-autofluorescence formed a ring around the central area of preserved retinal architecture, but this was not a uniform finding.