Extrapolating from research by Wollensak et al., which showed that the cytotoxic UVA irradiance dose for keratocytes is 0.5 to 0.7 mW/cm2 , Dr Kanellopoulos suggested that possibly, an equivalent amount of light would be needed to kill bacteria within the cornea.
Knowing that the amount of UVA fluence delivered dissipates as the light penetrates deeper into the cornea suggests the possibility
that using a higher fluence for the light treatment might increase its sterilizing effect.
In this regard, Dr Kanellopoulos noted that the standard protocol for CXL, as introduced by Seiler and colleagues in Dresden,
uses a light fluence of 3 mW/cm2 delivered for 30 minutes. Beginning in 2005 at his centre, Dr Kanellopoulos began using a higher UVA fluence protocol in
which the riboflavinsoaked cornea is irradiated with UVA 6 mW/cm2 for 15 minutes, 10 mW/cm2 for 10 minutes, or 30 mW/cm2 for 3 minutes. Recently, he began using a fluence of 45 mW/cm2 for 2 minutes to treat infections.
"Based on our research in cadaver corneas and then in clinical use for over 6 years, Avedro has brought to the market a UVA
treatment device (KXL) that allows customized fluence settings of up to 45 mW/cm2 with a total radiance restriction of 10 J in the cornea," Dr Kanellopoulos said. "This device is CE marked and can be used
for a variety of CXL applications, most notably, 'LASIK Xtra', which is the addition of prophylactic CXL in routine LASIK
cases that we introduced several years ago."
Other technique modifications to increase delivery of UV light and riboflavin in the treatment of infectious keratitis also
can be considered. For example, Dr Kanellopoulos said he has been performing CXL in combination with topography-guided PRK
in ectatic eyes needing corneal strengthening and regularization. Removal of Bowman's membrane, as is done in this procedure,
is thought to increase the extent of crosslinking by enhancing the penetration of UV light and riboflavin.
As an additional option, riboflavin delivery might be enhanced using a higher concentration of topically applied solution,
or optimized through direct instillation of the riboflavin solution into a femtosecond laser-created pocket at the level of
infection. Dr Kanellopoulos said he has also used the latter technique when performing CXL for the treatment of bullous keratopathy.
"However, in considering these modifications, we cannot ignore there may be increased toxicity from increasing the light fluence
and riboflavin concentration, and we cannot overlook the potential for harm to limbal stem cells and goblet cells as a bystander
to the CXL procedure," Dr Kanellopoulos said.
Another safety issue to consider when using CXL as a treatment for infectious keratitis is that the keratocyte apoptosis induced
by the procedure may make the cornea more susceptible to infection during the interval until there is repopulation of stromal
keratocytes, he added.
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