Bevacizumab and rapamycin can decrease corneal opacity and apoptotic keratocyte number following photorefractive keratectomy

Invest Ophthalmol Vis Sci. 2012 Nov 15;53(12):7645-53. doi: 10.1167/iovs.12-10494.

Abstract

Purpose: We investigated the effects of bevacizumab and rapamycin on central corneal opacity and apoptotic keratocyte number after photorefractive keratectomy (PRK) followed by ultraviolet B (UV-B) irradiation.

Methods: A total of 60 right eyes of Sprague-Dawley rats in four groups (n = 15 each) underwent PRK ablation to 80 μm with a 3-mm zone. Sponges soaked with 0.02% mitomycin C (MMC), 2.5% bevacizumab, 0.01% rapamycin, and balanced saline solution were applied for 2 minutes to these eyes in the MMC, bevacizumab, rapamycin, and control groups, respectively. At 3 weeks after PRK, all right eyes were exposed to 100 mJ/cm(2) UV-B irradiation. Biomicroscopy was used to determine the amount of haze, and TUNEL staining for apoptosis and histology were performed at 3, 6, and 12 weeks.

Results: Contrary to the results at 3 weeks, central corneal haze, and apoptotic keratocyte and keratocyte number decreased significantly in the MMC, bevacizumab, and rapamycin groups compared to the control group, and the keratocyte number was lower in the MMC group than the bevacizumab and rapamycin groups at 6 weeks (all P < 0.05). At 12 weeks, the apoptotic keratocyte number was lower in the MMC, bevacizumab, and rapamycin groups than the control group, and the keratocyte number was significantly lower in the MMC than the rapamycin and control groups (all P < 0.05).

Conclusions: Intraoperative bevacizumab and rapamycin administration decreases central corneal haze and apoptotic keratocyte number after PRK. Bevacizumab and rapamycin may be safe alternatives to MMC during refractive surgery to prevent postoperative corneal opacity less affecting the keratocyte number.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Apoptosis / drug effects*
  • Bevacizumab
  • Cell Count
  • Corneal Keratocytes / drug effects*
  • Corneal Keratocytes / pathology
  • Corneal Opacity / drug therapy*
  • Corneal Opacity / etiology
  • Corneal Opacity / pathology
  • Disease Models, Animal
  • Immunosuppressive Agents / pharmacology
  • In Situ Nick-End Labeling
  • Microscopy, Acoustic
  • Photorefractive Keratectomy / adverse effects*
  • Rats
  • Rats, Sprague-Dawley
  • Sirolimus / pharmacology*
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Immunosuppressive Agents
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Sirolimus