Staged intrastromal delivery of riboflavin with UVA cross-linking in advanced bullous keratopathy: laboratory investigation and first clinical case.

Purpose: To evaluate the safety and efficacy of staged ultraviolet A (UVA) cross-linking following intrastromal 0.1% riboflavin administration in eyes with advanced corneal edema.
Methods: Ten eye bank corneas divided in two groups (n = 5) were placed on a pressurized artificial anterior chamber following Descemet's membrane stripping. Two consecutive corneal pockets (350- and 150-microm depth) were sequentially created using a femtosecond laser. Sequential intrastromal injections of 0.1% riboflavin (0.2 mL) followed by either UVA irradiation (15 mW/cm2) for 7 minutes or exposure to air were performed for each pocket. Corneal clarity and central thickness were measured before and after the two UVA cross-linking steps. The same steps were clinically applied in an 84-year-old woman with bullous keratopathy prior to corneal transplantation and followed for 6 months.
Results: The corneal clarity improved in the treated but not the control eyes. The mean central corneal thickness was significantly reduced by 256 microm (ultrasound, P = .0002) and 273 miccrom (Scheimpflug, P = .0004) in treated eyes, but only 100 microm (ultrasound, P = .048) and 107 microm (Scheimpflug, P = .075) in the control eyes. The clinical treatment of corneal edema showed improved clarity and reduced central corneal thickness from 675 to 550 microm (ultrasound) and 696 to 571 microm (Scheimpflug) at 1 month. Best spectacle-corrected visual acuity improved from finger counting to 20/80 at 1 week and beyond, postponing corneal transplantation for > 6 months.
Conclusions: Staged UVA cross-linking (15 mW/cm2) with femtosecond laser facilitated intrastromal 0.1% riboflavin administration may be a safe (no corneal scarring) and effective (marked reduction of edema) temporizing alternative method for managing bullous keratopathy.