Pharmacological prevention of radiation-induced dry eye-an experimental study in a rabbit model

To evaluate the radioprotective effect of lidocaine, amifostine and pilocarpine on lacrimal glands.

Twenty-five rabbits were randomized into five groups: the control, irradiated/sham-treated, irradiated/lidocaine-pretreated, irradiated/amifostine-pretreated and irradiated/pilocarpine-pretreated groups. One week before irradiation, 72 h and 1 month afterward, the inferior lacrimal gland was investigated histomorphologically, immunohistochemically [tenascin-C and alpha smooth muscle actin (alpha-SMA)] and functionally using scintigraphy and the Schirmer test.

Compared with control animals, the lacrimal ejection fraction (LEF) in the irradiated/sham-treated group was significantly reduced 72 h afterwards. Pilocarpine- as well as amifostine-pretreated animals showed a slightly lower reduction. Lidocaine stabilized the LEF. Immunohistochemically, a significant loss of alpha-SMA and an up-regulation of tenascin-C expression in irradiated/untreated glands were evident. Pretreatment with lidocaine and amifostine-but not with pilocarpine-induced lower up-regulation of TN-C expression 72 h after radiation. One month after irradiation a reduction of the immunhistochemical changes at all was found. Ultrastructural damage was observed in irradiated/non-treated and pilocarpine-pretreated glands, whereas lidocaine and amifostine preserved the ultrastructure.

Morphologic and functional findings could prove a prevailing protection profile of amifostine and especially of lidocaine on lacrimal glands. This may provide a prophylactic approach in the radioprotection of the lacrimal glands during radiotherapy of the orbital region.