Corneal Myofibromatous and Pterygium-Like Changes in a Family With a PDGFRB Variant.

Abstract

Purpose: To report the clinical, pathologic, and genetic findings in a family with early-onset pterygia, corneal vascularization, and corneal myofibromatous lesions.

Methods: We performed clinical, pathologic, and genetic analysis of 12 members of a family originating in Puebla Mexico, who manifested with pterygia/pseudopterygia and corneal opacification transmitted in an autosomal-dominant inheritance pattern. Three unaffected family members also were evaluated.

Results: Clinical findings included isolated pterygia, isolated corneal subepithelial and anterior stromal opacities associated with varying degree of corneal vascularization, and a combination of pterygia and corneal opacities. Nine patients (17 eyes) underwent surgical procedures, including penetrating keratoplasty (9/17), superficial keratectomy (7/17), and pterygium excision (7/17). Five patients (eight eyes) had more than one surgery for recurrence of pterygia (2/8), recurrent corneal opacities obscuring the visual axis (3/8), penetrating keratoplasty failure (1/8), and indication not known (2/8). Documented recurrences occurred early, within 1 to 2 years of surgery. Histopathology of 21 specimens available for evaluation (nine penetrating keratoplasty corneas, seven superficial keratectomies, and five conjunctival-corneal tissues from pterygium/pseudopterygium excision) from seven patients showed varying degrees of myofibroblastic proliferation. Exome sequencing identified a heterozygous c.1610C>A (p.Ala537Asp) variant in the platelet-derived growth factor receptor beta (PDGFRB) gene in all 11 affected family members tested and in one of three unaffected family members.

Conclusions: The combined clinical presentation, histopathologic features, and genetic findings suggest an autosomal dominantly inherited predisposition to exuberant corneal myofibroblastic proliferation, driven by the platelet-derived growth factor receptor activation.