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Protein S deficiency is also associated with an increased risk of thromboembolism from reduced thrombin generation. In this report, we describe the case of a patient who presented with multiple retinal vein occlusions likely caused by an underlying combination of a homozygous<jats:italic>MTHFR<\/jats:italic>C677T variant and protein S deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed 8\u00a0years of continuous ophthalmic follow\u2010up of one patient diagnosed with central retinal vein occlusion. Peripheral blood was collected for metabolic evaluation and hypercoagulability assessment. Targeted gene sequencing was used for genetic diagnosis. Examination of the retinal vasculature was performed through dilated funduscopic examination, digital color fundus and ultrawide\u2010field color fundus photography, spectral domain optical coherence tomography, and fluorescein angiography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sequential retinal vein occlusions and a transient ischemic attack were observed during the follow\u2010up period. Targeted gene sequencing by PCR identified the homozygous<jats:italic>MTHFR<\/jats:italic>C677T variant. The metabolic profile indicated low\u2010protein S activity, high levels of vitamin B6, and LDL cholesterol consistent with her hypercoagulable state. Prescription of low\u2010dose aspirin and atorvastatin for hypercholesterolemia resulted in no further neovascularization, leakage, or vein occlusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Retinal vein occlusions associated with the<jats:italic>MTHFR<\/jats:italic>C677T variant and protein S deficiency may signal impending systemic thromboembolic episodes and warrant aggressive preventative measures.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1273","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T06:00:10Z","timestamp":1588140010000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sequential multiple retinal vein occlusions and transient ischemic attack in<i>MTHFR<\/i>polymorphism and protein S deficiency"],"prefix":"10.1002","volume":"8","author":[{"given":"Ahra","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Columbia University New York NY USA"},{"name":"Institute of Human Nutrition Vagelos College of Physicians and Surgeons New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara D.","family":"Ragi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Columbia University New York NY USA"},{"name":"Institute of Human Nutrition Vagelos College of Physicians and Surgeons New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Kyun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Columbia University New York NY USA"},{"name":"State University of New York at Downstate Medical Center Brooklyn NY USA"},{"name":"Jonas Children's Vision Care and Bernard &amp; 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