Defective regeneration of the epithelial basement accounts for most late haze following injury to the epithelium and anterior stroma, according to Steven E. Wilson, MD.
“Refractive surgeons have called this late haze, but it’s fibrosis,” said Dr. Wilson, professor of ophthalmology and director of corneal research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH.
Surgeons performing photorefractive keratectomy (PRK) can reduce the risk of the scarring that causes this haze by properly maintaining their lasers, he said, adding that future treatments might provide “missing elements” that aid in complete healing of the epithelial basement membrane.
The fibrosis can occur not only with PRK, but at the edge of LASIK flaps, corneal transplants, and after infections that cause ulcers.
“If you have the right kind of injury, it could happen to any patient,” Dr. Wilson said.
A rough stromal surface or the destruction of many keratocytes can interfere with epithelial membrane regeneration, he noted.
Growth factor influence
Defects in the epithelial basement membrane allow two epithelium-derived growth factors, TGF-beta and PDGF, to penetrate the stroma and drive the development of myofibroblasts. The cells depend on high levels of TGF-beta to prevent autocrine interleukin-1 from triggering apoptosis of myofibroblasts.
Myofibroblasts produce small amounts of the crystallins that create a disordered extracellular matrix, causing opacities which patients experience as late haze.
“They secrete massive amounts of collagen and other extracelluar matrices that aren’t normally in the cornea,” he said.
In higher myopia corrections, haze is greater because of the rough stromal surface and greater apoptosis of keratocytes. In a human PRK model, it only occurs if there is a high-level PRK without mitomycin C, he said.
Some patients may have genetic abnormalities affecting epithelial basement membrane regeneration, but only 2% to 5% of human patients will develop this severe fibrosis without mitomycin C treatment, he said.
“There are likely some genetic factors we don’t understand yet," he added. "There is also the possibility the extent of injury in one 9 D PRK may not be the same in another -9 D PRK.”