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Collagen Crosslinking Idea: The corneal collagen crosslinking procedure combines riboflavin (vitamin B2), which is a naturally occurring photosensitizer found in all human cells, and ultraviolet A (UVA) light to strengthen the biomechanical properties of the cornea. Although there may also be a slight flattening of the cornea, the most important effect of collagen crosslinking is that it appears to stabilize the corneal curvature and prevent further steepening and bulging of the corneal stroma. There is no significant change in the refractive index or the clarity of the cornea. Indications: 1) Prevent the progression of keratoconus and ectasia following corneal refractive surgery 2) corneal melts & infectious keratitis: to strengthen a collagenolytic cornea while UVA irradiation eliminates the infectious agent 3) corneal edema e.g. bullous keratopathy, Fuchs endothelial dystrophy Contra-indications: 1) 2) 3) 4) 5) 6) 7) Corneal thickness of less than 400 microns Prior herpetic infection Concurrent infection Severe corneal scarring or opacification History of poor epithelial wound healing Severe ocular surface disease (ex. dry eye) Autoimmune disorders Physical principle: Riboflavin alone has no crosslinking effect. Its function as a photosensitizer is to serve as a source for the generation of singlet oxygen and superoxide anion free radicals, which are split from its ring structure after exitation by the UV irradiation and which then lead to physical crosslinking of the corneal collagen fibers. In the presence of riboflavin, approximately 95% of the UVA light irradiance is absorbed superficially in the anterior 300 µm of the corneal stroma. Therefore, most studies require a minimal corneal thickness of 400 µm after epithelial removal in order to prevent corneal endothelial damage. Thinner corneas may be thickened temporarily with application of a hypotonic riboflavin formulation prior to UVA. treatment Technique: Corneal collagen crosslinking has been used successfully in combination with other treatment methods, such as intrastromal corneal ring segments, CK, and excimer laser photoablation 1) corneal epithelium is removed to increase UV penetration 2) 30-minute application of riboflavin (0.1% diluted in 20% dextran) every 2 minutes 3) 30-minute UVA treatment (370 nm; 3 m W/cm2 irradiation), with concomitant administration of topical riboflavin Complications: 1) 2) 3) 4) 5) 6) delayed epithelial healing, corneal haze (may be visually significant) decreased corneal sensitivity infectious keratitis, persistent corneal edema endothelial cell damage. Trans-epithelial CXL: A cross-linking procedure without epithelial removal would likely be less painful than one with the large diameter epithelial removal described above and would be ideal if it efficiently stabilized keratectasia. Several substances have been used to loosen the tight junctions of the epithelial layer and thus increase the penetration of riboflavin. One is a riboflavin solution containing benzalkonium chloride (BAK), the most commonly used preservative in ophthalmic medications. BAK is also a tensioactive substance, surfactant or an active surface agent that changes the surface tension value, and hence would facilitate the penetration of substances through the epithelium.