Sequential multiple retinal vein occlusions and transient ischemic attack in MTHFR polymorphism and protein S deficiency

Background The C677T variant of the MTHFR (5,10‐Methylenetetrahydrofolate reductase) gene is associated with increased susceptibility to homocystinuria (OMIM#236250), neural tube defects (OMIM#601634), schizophrenia (OMIM#181500), thromboembolism (OMIM#188050), and vascular diseases. 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 MTHFR C677T variant and protein S deficiency. Methods We performed 8 years of continuous ophthalmic follow‐up 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‐field color fundus photography, spectral domain optical coherence tomography, and fluorescein angiography. Results Sequential retinal vein occlusions and a transient ischemic attack were observed during the follow‐up period. Targeted gene sequencing by PCR identified the homozygous MTHFR C677T variant. The metabolic profile indicated low‐protein S activity, high levels of vitamin B6, and LDL cholesterol consistent with her hypercoagulable state. Prescription of low‐dose aspirin and atorvastatin for hypercholesterolemia resulted in no further neovascularization, leakage, or vein occlusion. Conclusion Retinal vein occlusions associated with the MTHFR C677T variant and protein S deficiency may signal impending systemic thromboembolic episodes and warrant aggressive preventative measures. In this report, we describe a case of sequential retinal vein occlusions followed by a transient ischemic attack in a 51‐year old Asian woman secondary to both homozygous MTHFR mutations and protein S deficiency despite controlled plasma homocysteine level. Fluorescein angiography of the right eye at the initial visit demonstrated the presence of a hypofluorescent punctate blocking defects in the superior temporal arcade along with hyperfluorescent window defect at the temporal periphery. With adequate coagulation control, the blocking defects resolved at the follow‐up visit.