Clues behind keratocyte density

Topography shows positive keratoconus screening findings
Source: Journal of Cataract & Refractive Surgery, reproduced with permission

Some researchers have measured keratocyte density as a way to analyze the role of these cells in corneal healing after refractive surgery and in diseased corneas. A recent study brings new, and to some extent surprising, insight into keratocyte density among these groups of patients.
Researchers looked at four groups of patients: those with keratoconus (22 patients), post-LASIK keratectasia (24 clear corneas from 17 cases), uncomplicated post-LASIK cases (12 corneas from 7 cases), and normal unoperated cases (26 corneas from 13 cases). What they found wasn’t quite what one would expect.
For starters, there was no difference in mean keratocyte density between keratoconus patients and those with normal corneas. Then there was the fact that even in uncomplicated LASIK patients, keratocyte density was still lower than in the normal virgin eye group.
In fact, the keratocyte density was, overall, no different between uncomplicated LASIK patients and those with post-LASIK keratectasia.
One has to delve much deeper into the study to find out why the results likely presented in such a fashion, which at times seem “contradictory,” in the words of lead study author Mohammad Ali Javadi, M.D., Ophthalmic Research Center and Ophthalmology Department, Labbafinejad Medical Center, Tehran, Iran.
It’s important to analyze keratocyte density by stromal layers, which begins to make better sense of some of the results, which were published in the August 2009 issue of Cornea.

Break it down

Dr. Javadi and colleagues studied keratocyte density in three sections of the stroma: the anterior, middle, and posterior layers. In doing so, they found there were variations in layer density between uncomplicated LASIK patients and post-LASIK keratectasia ones.
“In post-LASIK keratectasia, there was a meaningful difference in keratocyte density between the anterior and posterior and between the middle and posterior stromal layers; such a difference was not observed in the uncomplicated post-LASIK cases,” Dr. Javadi reported. “It seems that despite a general reduction in keratocyte density in both post-LASIK groups, there may be a heterogeneous distribution of stromal keratocytes in post-LASIK keratectasia, which is in contrast to a more homogenous distribution in uncomplicated post-LASIK cases. It is unclear why the distribution of keratocytes is different between the 2 mentioned groups, but it may be explained by predisposition to corneal ectasia before surgery in the post-LASIK keratectasia group.”
Further, Dr. Javadi suggested that a homogenous distribution of keratocytes in uncomplicated LASIK patients could be important in stopping ectasia from occurring.
Dr. Javadi remarked that this appears to be the first study to measure post-LASIK keratectasia keratocyte density and compared this group to virgin corneas as well.
“Cell density in this group was significantly lower than that in normal unoperated corneas in the anterior and posterior 10% of stroma but not in the middle (33%–67%) layer, which included the retroablation zone,” Dr. Javadi reported. “This could be explained by the possible redistribution of keratocytes in the middle stroma posterior to the ablation zone.”
Dr. Javadi also explained, in the context of previous research, why keratocyte density was similar between keratoconus eyes and normal corneas.
“Such contradictory results could be explained by the high rate of keratocyte turnover in keratoconus and the balance between apoptosis, reactive cell proliferation, and lateral migration and/or redistribution of keratocytes,” Dr. Javadi reported. “In a study by [other researchers] the full-thickness keratocyte density in non-contact lens wearer keratoconic corneas was not significantly different from controls, although it was decreased in the anterior and posterior stroma of keratoconic subjects who wore contact lenses.”
Why does Dr. Javadi believe uncomplicated LASIK patients still had lower keratocyte density than unoperated corneas? “It has also been reported that corneal epithelial injury induces cytokines release and consequently leads to keratocytes apoptosis after LASIK,” Dr. Javadi reported.
John D. Sheppard, M.D., professor of ophthalmology, microbiology, and immunology, Eastern Virginia Medical School, Norfolk, Va., meanwhile, believes there is wide variability when it comes to keratocyte density among people—regardless of whether they have undergone surgery or not.
“Obviously we are not all the same and there is a wide distribution of different types of collagen, matrix material, and keratocytes from one human to another,” Dr. Sheppard said. “There are a lot of factors involved here that we don’t fully understand.”
Because of that variability, surgeons must be trained to expect the unexpected after surgery, Dr. Sheppard said. “Similar patients having the same surgeon, same procedure, and same corneal thickness have different responses to corneal healing,” Dr. Sheppard said. “There are a host of variables to explain different responses to surgery.”
That said, Dr. Sheppard agrees that making scientific insights into keratocytes and other cellular material will advance the aims of prevention and treatment related to corneal disorders.
“If we better characterize different phenotypes of different intracellular matrix proteins and keratocytes, we may be able to better prevent or treat keratectasia,” Dr. Sheppard said. “In 10 years, we’ll not only have a clearer understanding of who is going to develop bad keratectasia but also how to treat it.”

Editors’ note: Dr. Javadi has no financial interests related to this study. Dr. Sheppard has no financial interests related to his comments.

Contact information

Javadi: ma_javadi@yahoo.com
Sheppard: 757-622-2200, docshep@hotmail.com