Treatment of Sorsby fundus dystrophy with anti-tumor necrosis factor-alpha medication

Purpose Tissue inhibitor of matrix metalloproteinase (TIMP)-3 has many functions, including preventing the constituent formation of tumor necrosis factor-alpha (TNF alpha) in tissue. Sorsby macular dystrophy is caused by a mutation in the gene responsible for TIMP-3, suggesting a potential treatment. Methods Comprehensive ophthalmologic examination with multimodal imaging to include optical coherence tomography (OCT) and OCT angiography were used to evaluate a patient with Sorsby fundus dystrophy treated first with intravitreal triamcinolone, then with adalimumab. Results A 35-year-old woman presented in 2003 with aggressive macular neovascularization in both eyes related to Sorsby macular dystrophy c.610A>T (p.Ser204Cys). Her visual acuity was 20/25 in the right and 20/400 in the left eye. She was treated with periodic intravitreal injections of 4 mg triamcinolone, which caused the neovascularization to become inactive. When switched to intravitreal bevacizumab, she showed disease activity. She was switched back to intravitreal triamcinolone with minimal signs of exudation and hemorrhage. Because of the high lifetime risk of complication, she was switched to subcutaneous adalimumab and in follow-up over 18 months had no signs of disease activity. The visual acuity in the right eye was 20/20. Conclusions TIMP3 has numerous effects including controlling local TNF alpha production. It is possible with the mutation in the gene for TIMP-3, abnormally high tissue levels of TNF alpha are produced in the eye. Direct inhibition of TNF alpha action by adalimumab offers a molecularly targeted approach to the disease pathophysiology and merits increased study.

Automated summary

The mutation in the gene responsible for TIMP-3 in patients with Sorsby macular dystrophy may lead to abnormally high levels of TNF alpha in the eye. Adalimumab's direct inhibition of TNF alpha offers a targeted approach to the disease pathophysiology and shows promising efficacy.