Paraneoplastic ocular syndromes: a systematic review of epidemiology, diagnosis and outcomes (2010-2023)

Abstract

Background: Paraneoplastic ocular syndromes are rare, immune-mediated disorders triggered by malignancies. They may precede cancer diagnosis or signal its recurrence, highlighting their potential value as early warning signs. Their recognition is critical for timely diagnosis and appropriate management.

Methods: We performed a systematic review of case reports and case series published between 2010 and 2023 in PubMed database, focusing on six major syndromes: cancer-associated retinopathy (CAR), melanoma-associated retinopathy (MAR), bilateral diffuse uveal melanocytic proliferation (BDUMP), acute exudative polymorphous paraneoplastic vitelliform maculopathy (AEPPVM), paraneoplastic uveitis (PU), and paraneoplastic optic neuropathy (PON). We extracted demographic, clinical, immunologic, oncologic, therapeutic, and outcome-related data.

Results: A total of 132 articles comprising 147 patients were included: 53 with CAR, 22 with MAR, 26 with BDUMP, 16 with AEPPVM, 11 with PU, and 19 with PON. Visual impairment was bilateral in over 90% of cases. The most frequently associated malignancies were lung cancers (notably small-cell lung carcinoma), gynecological cancers, and melanoma. Onconeural autoantibodies were tested in serum-most commonly revealing anti-recoverin and anti-alpha-enolase in CAR, and anti-CRMP5 in PON-but were never assessed in cerebrospinal fluid (CSF), despite its potential diagnostic value. Therapeutic approach was highly heterogeneous and largely empirical, with systemic corticosteroids being the most commonly used treatment. Visual prognosis varied but was especially poor in CAR, for which 49.1% of patients experienced worsening vision. Notably, in CAR, an early oncologic diagnosis (within 6 months after symptom onset) was significantly associated with a favorable visual outcome (p = 0.03).

Conclusion: We identified a clinical profile of patients in whom paraneoplastic ocular syndromes should be suspected. These rare inflammatory disorders may serve as early indicators of malignancy. Further studies are needed to improve diagnostic pathways, optimize immunologic workup (including CSF testing), and guide therapeutic strategies.

Keywords: Acute exudative polymorphous vitelliform maculopathy (AEPPVM); Bilateral diffuse uveal melanocytic proliferation (BDUMP); Cancer-associated retinopathy (CAR); Melanoma-associated retinopathy (MAR); Paraneoplastic ocular syndromes; Paraneoplastic optic neuropathy (PON); Paraneoplastic uveitis (PU).

Fig. 1

Flow chart of reports selected according to PRISMA guidelines. CAR: Carcinoma associated retinopathy, MAR: Melanoma associated retinopathy, AEPPVM: Acute exudative paraneoplastic polymorphous vitelliform maculopathy, BDUMP: Bilateral diffuse uveal melanocytic proliferation, PU: paraneoplastic uveitis, PON: paraneoplastic optic neuropathy.