Cancer-associated retinopathy (ORPHA:71505)
A rare paraneoplastic disease of the eye characterized by the presence of extraocular malignancy and circulating autoantibodies against retinal proteins.
Epidemiology
Cancer-associated retinopathy (CAR) is a rare visual syndrome and its prevalence is still unknown. Females are affected twice as commonly as men. The average age of a CAR patient is about 66 years old.
Clinical description
The disease is progressive; visual symptoms and sudden vision loss can manifest before diagnosis of cancer. The disease is highly heterogeneous and patients differ in their clinical presentation and antibody profiles. Different antiretinal antibodies frequently coexist in a single patient, creating antibody-profiles related to the syndrome, with each disease progression stage having its own unique autoantibody signature. Patients typically present with rapidly progressive visual loss, scotomas, dyschromotopsia, nyctalopia, photoaversion, and prolonged dark adaptation. Although the disease is bilateral, initial asymmetry is not uncommon. Deterioration of visual acuity and visual field changes (scotoma, or central constriction) are common, attenuated retinal arteriole, in addition to the presence of serum autoantibodies against retinal proteins, are crucial for diagnosis. The electroretinogram (ERG) typically shows marked reduction or loss of rod and cone-mediated responses. The most common malignancies related to CAR are carcinomas, including breast carcinomas, small cell carcinoma of the lung, non-small cell carcinoma, endometrial, ovarian, cervical, prostate, and colon carcinomas, and cutaneous melanomas.
Etiology
The exact etiology remains unknown but an autoimmune mechanism may contribute to the development of retinal degeneration. No known genetic association has been reported.
Diagnostic methods
Initial absence of clinical findings makes the diagnosis challenging. The diagnostic evaluation should include electroretinography (ERG) in patients with unexplained visual glare and subacute visual loss. Optical coherence tomography (OCT) is useful to provide information on the presence of cystoid macular edema (CME) and loss of outer retinal layers, which may include disruption of the ellipsoid zone (EZ). Areas around the macula can show loss of inner and outer segments. The presence of CME is associated to decreased ERG amplitudes and faster EZ loss. Predisposed cancer patients may develop autoantibodies cross-reacting with photoreceptor proteins.
Differential diagnosis
The main differential diagnosis is non-paraneoplastic autoimmune retinopathy. Other differential diagnoses include white dot syndrome spectrum disorders, retinal degenerative disorders (such as retinitis pigmentosa and cone-rod dystrophy), posterior uveitis, acute zonal occult outer retinopathy (AZOOR) and retinal toxicities from medications such as chemotherapy agents and vitamin deficiencies.
Management and treatment
Early diagnosis and treatment are critical to lower the risk of irreversible immunological damage to the retinal cells. Treatment involves modulation of the immune system to reduce autoimmune response and systemic antibody levels. Importantly, care for patients with cancer should be consulted with oncologist prior to applying immunosuppressive therapies. Patients with less severe retinal disease or earlier disease can benefit from rituximab monotherapy or with an adjunctive antimetabolite, which may be also added to other immunosuppression like intravenous methylprednisolone, sodium succinate and hydroxyzine as a pretreatment regimen before each rituximab infusion. Response to treatments varies when patients were treated at late stages of retinal disease. Cyclophosphamide or IVIg adjunctive therapies can be applied to patients with more severe or rapidly advancing disease.
Prognosis
The ophthalmological prognosis varies depending on the clinical course of CAR, ranging from progressive visual loss to blindness. The overall prognosis varies depending on the type of cancer present. It is difficult to achieve an improvement in vision in patients who had advanced disease before immunosuppressive treatments were initiated.

                            Last update: 
                            August 2023


                            - Expert reviewer(s): 
                            Dr Grazyna ADAMUS