Ophthalmic involvement of chronic lymphocytic leukemia: A systematic review of 123 cases

To identify clinical presentations, main causes, and prognosis of ophthalmic involvement in chronic lymphocytic leukemia (CLL), we performed a systematic review of articles describing CLL ophthalmic involvement in January 2019, using the PubMed database. We found 86 articles describing 123 cases of patients with ophthalmic involvement associated with CLL. Ophthalmic symptoms were CLL's first manifestation in 25.6% of patients and revealed Richter transformation in 11.0%. There were three main causes of ophthalmic features: CLL-infiltration (52.0%), lymphoma (26.0%), and infection (15.4%), with specific clinical and radiological characteristics. CLL-infiltration was mostly bilateral, whereas lymphoma was usually unilateral (P = 0.02). Optic neuropathy was always secondary to CLL-infiltration, and in those cases, cerebrospinal fluid immunophenotyping was a potential alternative to invasive biopsy as it confirmed the diagnosis in 4 patients (36.4%). On the contrary, lymphoma usually presented as adnexal involvement (P = 0.04), particularly as an orbital mass (P = 0.004). Infections concerned mostly patients previously treated for CLL (P < 0.0001), and main presentations included posterior uveitis (P = 0.0002) and retinal infiltrates (P < 0.0001). Overall, the prognosis was poor, as 29.3% of the patients died within 36 months of follow-up, and 26.1% had a partial or total visual loss. Eye infections were associated with the poorest prognosis as 47% of patients died, with a 6-month-median survival.