BLOG: Evolving use of hypotonic photosensitizing solutions in cross-linking
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In corneal cross-linking, the cornea is saturated with a photosensitizing drug that is activated by UVA light to strengthen and stiffen collagen bonds.
In the U.S., there are two riboflavin solutions that have been studied in clinical trials and approved for use by the FDA: Photrexa Viscous (riboflavin 5’-phosphate in 20% dextran ophthalmic solution) and Photrexa (riboflavin 5’-phosphate ophthalmic solution), both from Glaukos. Other solutions have been used only for investigational protocols in the U.S. but may be in clinical use outside the U.S.
Photrexa Viscous is typically the starting point in all cross-linking procedures. Drops are applied every 2 minutes for 30 minutes, and then pachymetry is performed to verify corneal thickness just before applying UVA light with the KXL System (Glaukos). If the corneal thickness is greater than 400 µm, the irradiation can proceed; otherwise, the hypotonic Photrexa solution (without dextran) should be used for about 10 minutes to swell the cornea, with cycles of solution application and measurements repeated until the stroma is greater than 400 µm.
This 400-µm threshold is somewhat arbitrary. It was used in the U.S. clinical trials and is viewed as a reasonable threshold to ensure that the corneal endothelium and other ocular structures are protected from photochemical damage during cross-linking. But switching to the hypotonic solution 30 minutes into the procedure adds significantly to the total case time.
Now, after several years of corneal cross-linking experience, I know that it is not all unusual to see patients thin to less than 400 µm, especially if they started out somewhat borderline, in the range of 450 µm before removing epithelium. Because of this, my own protocol has shifted over time. If the cornea starts out very close to 400 µm, I go straight to Photrexa from the start. And if it is borderline, around 450 µm, I will often alternate between the two photosensitizing solutions to make sure the corneal thickness remains over 400 µm when I’m ready to start applying the UVA light.
We should also acknowledge that pachymetry measurements can themselves be imprecise in a keratoconic eye. If the measurement is taken exactly on the steepest and thinnest part of the cone, it might be 380 µm, but just off the peak of the cone, the same cornea could measure 420 µm. So, if your measurement is off just a little, you might not be in the “safe” zone when you think you are. For this reason, some cornea specialists use Photrexa in every case, reasoning that it can only help. There is no significant downside to a thicker cornea, only a thin one.
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