Recent Advances in Corneal Collagen Crosslinking
Reham Tarek Farrag Hussein;
Abstract
Summary
The structural characteristics of the cornea facilitate its essential functions, specifically to serve as both a transparent barrier and the predominant refractive element of the eye.
The cornea is formed of keratocytes which represent the predominant cellular components of the corneal stroma, collagen that constitutes more than 70% of the dry weight of the cornea.And proteoglycans forms the major component of ECM and located in the spaces among major collagen fibers in the stroma of the cornea.The orientation of successive collagen fibril layers throughout the entire cornea is an important factor determining the mechanical properties of the cornea.
The metrics of biomechanical properties of the cornea is evaluated by stress strain relationship which in biological tissues typically exhibit a nonlinear response named Young’s modulus of elasticity.
The constitutive representations of the cornea can be useful in predicting the corneal biomechanical response to various types of surgical manipulations or to controlled deformation in order to measure intraocular pressure (IOP). They include viscoelastic and hydration models and finite element models.
There are various methods of clinical testing of corneal biomechanical properties these include:
The Ocular Response Analyzer (ORA),the Corneal Visualization Scheimpflug Technology (Corvis ST), dynamic corneal surface topography, swept source ocular coherence tomography (ssOCT) combined with an air puff, brillouin optical microscopy, quantitative ultrasonic spectroscopy (QUSi), corneal transient elastography(CTE), radial shearing speckle pattern interferometry(RSSPI), dynamic corneal imaging (DCI) , optical coherence tomography elastography.
Collagen cross linking is commonly used to treat keratectasias such as keratoconus, corneal ectasia after refractive surgery, and pellucid marginal degeneration (PMD) and works by halting the progression of the condition. However, the anti-edematous and antimicrobial properties can be helpful in the auxiliary treatment of bullous keratopathy and infectious keratitis.
Management of keratoconus, PMD and post-surgery ectasia depends on their severity and the extent of irregular astigmatism. Mild cases are correctable with spectacles and soft toric contact lenses. However, with progressive disease, the cornea becomes more irregular and rigid gas permeable lenses are required.In 15-20% of keratoconic patients, surgery, typically keratoplasty, becomes necessary, as a result of contact lens intolerance, corneal scarring and thinning.None of these interventions, while often successful in terms of visual rehabilitation, treat the underlying causes of kerectasia and its progression. It is only with the advent of corneal collagen cross-linking (CXL) that a hope to slow, stop or even to a limited extent reverse keratoconus is started.
Riboflavin has a modest affinity fornucleic acid and its absorption of UV-A leads to theoxidation of guanine bases, thus preventing the replicationof the viral and bacterial genome. Thiseffect is synergistic with any direct antimicrobialeffect of UV-A irradiation itself and with any damageto microbial cell membranes and DNA caused byoxygen radicals.The antimicrobialefficacy of the combination of riboflavin andUV-A against a range of common bacterial pathogenscausing infectious keratitis has now been well demonstratedin vitro. Also the treatment responses of the infectious ulcers indicatethat photochemically activated riboflavin could be used forfuture management of infectious keratitis, allowing for lessfrequent application of topical antibiotics and fewer patientvisits. Use of the method might reduce the frequency ofcomplications associated with corneal infections andincrease the healing rate in the treatment of microbial keratitis.
Corneal collagen cross-linking has also been suggestedas a treatment for corneal oedema. Thisconcept is supported by changes in the hydrationbehaviour of the porcine cornea after CXL and theobservation that stromal compaction follows CXL ina similar experimental model.
Corneal collagen cross-linking with riboflavin is a method to increase the biomechanical stability of the cornea by inducing additional cross-links between or within collagen fibers using UV-A light and riboflavin as photomediators. The first patients were treated in 1998by Prof. Theo Seiler and Prof. Eberhard Spoerl at the University of Dresden, Germany. Currently, the classical corneal collagen cross-linking (CXL) protocol is strictly formulated. Various new methods for epithelial disruptions were introduced to the classical technique.
The structural characteristics of the cornea facilitate its essential functions, specifically to serve as both a transparent barrier and the predominant refractive element of the eye.
The cornea is formed of keratocytes which represent the predominant cellular components of the corneal stroma, collagen that constitutes more than 70% of the dry weight of the cornea.And proteoglycans forms the major component of ECM and located in the spaces among major collagen fibers in the stroma of the cornea.The orientation of successive collagen fibril layers throughout the entire cornea is an important factor determining the mechanical properties of the cornea.
The metrics of biomechanical properties of the cornea is evaluated by stress strain relationship which in biological tissues typically exhibit a nonlinear response named Young’s modulus of elasticity.
The constitutive representations of the cornea can be useful in predicting the corneal biomechanical response to various types of surgical manipulations or to controlled deformation in order to measure intraocular pressure (IOP). They include viscoelastic and hydration models and finite element models.
There are various methods of clinical testing of corneal biomechanical properties these include:
The Ocular Response Analyzer (ORA),the Corneal Visualization Scheimpflug Technology (Corvis ST), dynamic corneal surface topography, swept source ocular coherence tomography (ssOCT) combined with an air puff, brillouin optical microscopy, quantitative ultrasonic spectroscopy (QUSi), corneal transient elastography(CTE), radial shearing speckle pattern interferometry(RSSPI), dynamic corneal imaging (DCI) , optical coherence tomography elastography.
Collagen cross linking is commonly used to treat keratectasias such as keratoconus, corneal ectasia after refractive surgery, and pellucid marginal degeneration (PMD) and works by halting the progression of the condition. However, the anti-edematous and antimicrobial properties can be helpful in the auxiliary treatment of bullous keratopathy and infectious keratitis.
Management of keratoconus, PMD and post-surgery ectasia depends on their severity and the extent of irregular astigmatism. Mild cases are correctable with spectacles and soft toric contact lenses. However, with progressive disease, the cornea becomes more irregular and rigid gas permeable lenses are required.In 15-20% of keratoconic patients, surgery, typically keratoplasty, becomes necessary, as a result of contact lens intolerance, corneal scarring and thinning.None of these interventions, while often successful in terms of visual rehabilitation, treat the underlying causes of kerectasia and its progression. It is only with the advent of corneal collagen cross-linking (CXL) that a hope to slow, stop or even to a limited extent reverse keratoconus is started.
Riboflavin has a modest affinity fornucleic acid and its absorption of UV-A leads to theoxidation of guanine bases, thus preventing the replicationof the viral and bacterial genome. Thiseffect is synergistic with any direct antimicrobialeffect of UV-A irradiation itself and with any damageto microbial cell membranes and DNA caused byoxygen radicals.The antimicrobialefficacy of the combination of riboflavin andUV-A against a range of common bacterial pathogenscausing infectious keratitis has now been well demonstratedin vitro. Also the treatment responses of the infectious ulcers indicatethat photochemically activated riboflavin could be used forfuture management of infectious keratitis, allowing for lessfrequent application of topical antibiotics and fewer patientvisits. Use of the method might reduce the frequency ofcomplications associated with corneal infections andincrease the healing rate in the treatment of microbial keratitis.
Corneal collagen cross-linking has also been suggestedas a treatment for corneal oedema. Thisconcept is supported by changes in the hydrationbehaviour of the porcine cornea after CXL and theobservation that stromal compaction follows CXL ina similar experimental model.
Corneal collagen cross-linking with riboflavin is a method to increase the biomechanical stability of the cornea by inducing additional cross-links between or within collagen fibers using UV-A light and riboflavin as photomediators. The first patients were treated in 1998by Prof. Theo Seiler and Prof. Eberhard Spoerl at the University of Dresden, Germany. Currently, the classical corneal collagen cross-linking (CXL) protocol is strictly formulated. Various new methods for epithelial disruptions were introduced to the classical technique.
Other data
| Title | Recent Advances in Corneal Collagen Crosslinking | Other Titles | التطورات الحديثة في تشابك كولاجين القرنية | Authors | Reham Tarek Farrag Hussein | Issue Date | 2015 |
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