Prospective Study of Corneal Sensitivity in Patients Treated With Proton Therapy for Extraocular Tumors

Several cases of radio-induced neurotrophic keratitis had been observed after proton therapy delivering a mean corneal dose of ≥50 GyRBE. We conducted a prospective exploratory study to assess corneal sensitivity in subsequent patients undergoing proton therapy for cephalic extraocular tumors.

Forty-three patients (85 eyes) treated with high-energy proton therapy were included in this prospective, single-center, observational cohort study. All patients had their corneal sensitivity measured using Cochet-Bonnet esthesiometer, before and average 6 months after irradiation. Ocular surface was clinically assessed for stromal opacity, corneal thinning, corneal perforation, superficial punctate keratitis graded according to Oxford classification, and tear break-up time. Cornea and extraocular sensitive innervation structures of cornea were contoured and their dose metrics assessed.

No severe corneal damage was detected. Corneal sensitivity, superficial punctate keratitis according to Oxford classification, and tear break-up time did not vary significantly after irradiation. The mean value of maximal dose to cornea and extraocular sensory innervation of cornea were 10.7 GyRBE and 42.0 GyRBE, respectively. Doses to cornea and its innervation structures were not associated with significant changes in corneal sensitivity ( P = 0.423 and P = 0.614). A dose per fraction greater than 2 GyRBE was significantly associated ( P = 0.033) with a decrease of corneal sensitivity after proton therapy.

This pilot study showed no excess risk of damage to corneal sensitivity 6 months after proton therapy, as doses to the cornea could be minimized. However, based on prior neurotrophic keratitis cases for corneal doses above 50 GyRBE, further investigation is needed to establish the impact of high-dose proton therapy on corneal sensitivity.