Ocular adverse events from pharmacological treatment in patients with multiple sclerosis—A systematic review of the literature

Abstract

Purpose The aim of this study was to review the scientific evidence and describe the ocular treatment-emergent adverse events (TEAEs) related to pharmacological treatment in patients with multiple sclerosis. Methods A systematic review of literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines in the MEDLINE, LILACS, EMBASE, and COCHRANE databases. Articles were filtered based on title and abstract considering the selection criteria and subsequently filtered by full-text reading. The resulting articles were evaluated using the Joanna Briggs Institute Quality Tools. Study characteristics and results were extracted and presented in structured tables to conduct a narrative synthesis. Results A total of 2852 published articles were extracted using our strategy. After removing duplicates, 2841 articles were screened based on title and abstract, 102 articles were evaluated using quality tools, and 69 articles were filtered by full-text reading. Through this search strategy, 60 articles met all the inclusion criteria and seven articles, through a search update conducted in the same manner, were included. This resulted in 67 articles meeting the inclusion criteria, of which 11 were experimental and 56 were observational. The therapies related to ocular TEAEs were alemtuzumab, amantadine, fingolimod, steroids, CTLA-4 Ig, estriol, interferon β, natalizumab, hyperbaric oxygen, rituximab, siponimod, teriflunomide, and tovaxin. Fingolimod and siponimod were commonly associated with macular edema, interferon β was associated with retinopathy, alemtuzumab was associated with thyroid eye disease, amantadine was associated with corneal edema, and steroids were associated with acute retinal necrosis. Opportunistic infections were also found, and there was one life-threatening case. Conclusions Our search revealed different methodological assessments of the topic. However, longitudinal studies regarding ocular TEAEs related to multiple sclerosis therapy are necessary to provide evidence-based recommendations, especially in understudied regions such as Latin America and Africa. Physicians should monitor ocular symptoms in patients being treated for multiple sclerosis and consider an interdisciplinary approach. Systematic review registration PROSPERO ID CRD42020106886

Drugs Causing Cystoid Macular Edema: Pathogenesis, Diagnosis, and Treatment

“…[65] Fingolimod kullanımı ile ilişkili makuler ödem gelişimini bildiren çok sayıda rapor bulunmaktadır. [66,67] Fingolimod henüz bilinmeyen bir mekanizma ile kan-retina bariyerini yıkarak ve vasküler geçirgenliği artırarak makuler ödem oluşumuna neden olmaktadır. [68] Amerikan İlaç ve Gıda Ajansı (FDA) fingolimod kullanan hastalarda oküler bulguların yakından takibini önermektedir.…”

Ponesimod-Associated Macular Edema: Onset and Resolution

“…At the direction of her neurologist, ponesimod was stopped and the patient was switched to teriflunomide-a pyrimidine synthesis inhibitor known to have lower ophthalmological risk. 7 Concurrently, her topical 1% prednisolone acetate dose was increased to twice daily while her topical bromfenac was maintained at a daily dose.…”

“…Older S1P structural analogues, namely fingolimod, have similarly been implicated in ophthalmological pathologies, termed fingolimod-associated macular edema (FAME). [6][7][8] Fortunately, FAME occurs in only approximately 0.5% of patients and typically resolves after medication cessation. We report a case of macular edema in a patient with RRMS being treated with ponesimod.…”

A narrative review of neuro-ophthalmologic disease in African Americans and Hispanics with multiple sclerosis

“…It was originally hypothesized that S1P3 modulation at the orbital journals.sagepub.com/home/taj TherapeuTic advances in chronic disease vascular endothelial junctions was directly responsible, although macular edema has been reported as an adverse event with ponesimod, a highly selective S1P1 modulator. 47,48 In addition, MME has been encountered in S1P modulation in other non-neurological conditions, such as ulcerative colitis, which argues against a direct neuroinflammatory effect underlying its pathogenesis. There are data to suggest that nonselective S1P modulation may be associated with an increase in macular volume, which could represent subclinical macular edema, although this hypothesis was limited by the single-center design, and did not report measures of the INL, where the majority of MME presents.…”