Although KC is defined as a non-inflammatory condition it has long been my view that inflammation must play a role in the condition. KC progression is associated with allergy, vigorous eye rubbing, and even contact lens wear. We know that all of these situations can cause inflammation so my question is why has the role of this inflammatory process not been further investigated in the pathogenesis of KC? In our practice we aggressively treat the allergy (and rubbing) associated with KC in an attempt to prevent further progression. So far our results have been good with documented changes in corneal topography and Pentacam scans (although not reported in the literature). Your views on this issue will be appreciated.
In my opinion you are standing at the beginning of new scientific approach to KC pathogenesis and latter on new treatment. I agree with you that inflammatory cascade initiated by different causes, which you have mentioned will start, as in case of age-related macular degeneration .
GOOD LUCK AND FURTHER FRUITFUL WORK
Prof. Marianne Shahsuvaryan
Dear Dirk
I hope these articles may be useful for you
1) Expert Opin Drug Metab Toxicol. 2013 Dec;9(12):1613-24.
Keratoconus and crosslinking: pharmacokinetic considerations.
Chan CC1, Squissato V.
2) Clin Ophthalmol. 2013;7:2019-2030.
Keratoconus: current perspectives.
Vazirani J1, Basu S
I learnt two bases for KC. The first, biomechanical and the second, biochemical. If I am to mention something on the biochemical basis, then I have to state that there occurs some change in collagen type VI expression. An increased level of proteolytic activity alongside the changes in the composition of proteoglycan composition may possibly be associated with KC. Reports of increased cathepsin B and G activity and gelatinase A have been published. Immunolocalized antiproteases have been found to be decreased in KC corneas. Some studies also put forward the view that KC might occur due to the structural change in the epithelium. And eye rubbing excessively might be one of the many reasons for the change brought about to the epithelium. And IL-1 mechanism leading to the tissue loss is not unknown, and this helps with apoptotic cell death.
Dirk, just as our ability to detect evermore subtle morphological signs of corneal distortion in keratoconus have advanced, so too has our ability to understand corneal inflammation. What once defined classic clinical signs of inflammation: rubor, dolor, calor, tumor, is rather gross by clinical and laboratory capabilities today. There are many who are challenging this conventional notion and I believe we are in the midst of redefining at least some aspects of this condition. However, consider glaucoma. This disease is a very large collection of different etiologies and mechanisms that lead to a common clinical manifestation: retinal ganglion cell degeneration. This is also possible for corneal ectatic diseases, i.e. their may be several routes (genetic, inflammatory, etc) that all lead to similar clinical manifestations that we define as keratoconus. As our understanding advances, we may have new therapeutic options that more specifically target the causal mechanism for a particular individual.
Thank Michael
Hopefully we will get more information in future which may lead to better therapy for these patients. Using a RGP lens to correct the irregular astigmatism must cause more inflammation which can further contribute to the progression of the disease. Are you aware of any clinical tests currently available that we can use to check for corneal inflammation in KC patients other than what we currently rely on? Or is there something on the horizon from your department at Houston - I believe Jan works from there?
Hi Dirk, yes, Jan Bergmanson is here, as is Alan Burns, Rachel Redfern and Allison McDermott. We each have a keen interest in different aspects of corneal inflammation, wound healing, anatomy and structure. I am not aware of any clinical tests to address your question, but there are several laboratory candidates that may be pursued. There was a nice review in Eye recently (2014; http://www.nature.com/eye/journal/v28/n2/full/eye2013278a.html ) on the pathogenesis of KC that you may wish to look up if you have not already. It does address some of these new ideas. I wish I had more to offer, but you are at the edge of what we know. Cheers.
Hi Dirk,
I do agree that there is a role of inflammation in the pathogenesis of Keratoconus. For long it has been categorized as a non-inflammatory ectasia. Currently we are evaluating the role of inflammation in the pathogenesis of keratoconus. However, the inflammation in this condition will not be that "calor, dolor, rubor" type of inflammation but rather it will be the subtle type of inflammation manifested by expression of inflammatory cytokines.
Thanks Omer
I tend to agree with you and think the process is similar to that of dry eye disease which we now know has a large inflammatory component. Hopefully we can address this and some of the serious consequences of KC
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