Topical Ocular Gene Therapy Restores Vision in Child With Cicatrizing Conjunctivitis

An adolescent boy with recurrent bilateral cicatrizing conjunctivitis from a rare a genetic disorder experienced sustained relief and significant visual improvement after ocular surface reconstruction and treatment with a first-of-its-kind topical collagen-delivering gene therapy.

Study Design

This case report describes a 13-year-old male patient with recurrent cicatrizing conjunctivitis in both eyes from dystrophic epidermolysis bullosa, a rare genetic disease caused by damaging variants in COL7A1, which encodes type VII collagen. With FDA compassionate-use approval, he received topical drops of beremagene geperpavec (B-VEC), a replication-deficient herpes simplex virus type 1–based gene therapy engineered to deliver functional human type VII collagen. A corneal-lesion model in healthy mice was first used to establish the safety of single and repeated topical B-VEC administration to the eye and the expression of human C7 in the corneal epithelium. In the patient, surgical symblepharon lysis with pannus removal was performed on the right eye, followed by immediate topical B-VEC application (1 drop of undiluted B-VEC biologic suspension [5 × 10⁹ plaque-forming units per milliliter]). Topical B-VEC was administered 3 times per week for the first 2 weeks and then once weekly.

Outcomes

In the mouse corneas, there was a lack of herpes stromal keratitis–related pathologic features and successful COL7A1 expression with topical B-VEC administration. In the patient, 8 months after surgery and treatment with 24 doses of topical B-VEC, visual acuity in the right eye improved from hand motion before surgery to 20/25 without correction, with no evidence of corneal abnormalities or recurrence of symblepharon.

Limitations

Limitations of this study include its single case sample size. There is a lack of molecular or genetic analysis of the patient's corneal epithelial cells before or after the surgery and the application of topical B-VEC. Aside from the clinically documented recurrence of the symblepharon after his previous 2 surgeries in the contralateral eye, there is not an untreated “control” eye for comparison.

Clinical Significance

This is the first topical ocular gene therapy ever reported. The remarkable clinical outcome (legally blind to 20/25 uncorrected) in this patient supports further investigation of topical B-VEC in the care of patients with dystrophic epidermolysis bullosa with ocular surface involvement. Use of replication-deficient herpes simplex virus type 1–based gene therapy may be promising for other ocular surface disorders.

Financial Disclosures: Dr. Neel Pasricha discloses financial relationships with Alcon Laboratories (Grant Support); Carl Zeiss Meditec, Iota Biosciences, Sanofi, Vanda Pharmaceuticals (Consultant/Advisor).