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      Keratoconus: Overview and Update on Treatment

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          Abstract

          Keratoconus is a non-inflammatory, progressive thinning process of the cornea. It is a relatively common disorder of unknown etiology that can involve each layer of the cornea and often leads to high myopia and astigmatism. Computer- assisted corneal topography devices are valuable diagnostic tools for the diagnosis of subclinical keratoconus and for tracking the progression of the disease. The traditional conservative management of keratoconus begins with spectacle correction and contact lenses. Several newer, more invasive, treatments are currently available, especially for contact lens-intolerant patients. Intrastromal corneal ring segments can be used to reshape the abnormal cornea to improve the topographic abnormalities and visual acuity. Phakic intraocular lenses such as iris-fixated, angle-supported, posterior chamber implantable collamer and toric lenses are additional valuable options for the correction of refractive error. Corneal cross-linking is a relatively new method of stiffening the cornea to halt the progression of the disease. The future management of keratoconus will most likely incorporate multiple treatment modalities, both simultaneous and sequential, for the prevention and treatment of this disease.

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          Increased resistance of crosslinked cornea against enzymatic digestion.

          Collagen-crosslinking using combined riboflavin/ UVA treatment has been developed by us as a new treatment for keratoconus by stiffening the collagenous matrix. Recently, we have started to use the same method for the treatment of corneal ulcers. The aim of the present study was to evaluate the influence of the crosslinking treatment on the resistance of the cornea against enzymatic degradation. 60 enucleated porcine eyes were treated with the photosensitizer riboflavin and UVA-irradiation (370 nm; irradiance of 1, 2 or 3 mW/cm2) for 30 minutes and compared with 20 untreated control eyes. After crosslinking treatment, the corneal buttons were trephined and exposed to pepsin, trypsin and collagenase solutions. The extent of the corneal digestion was monitored daily. Selected cases were examined by light microscopy. The corneal buttons crosslinked with riboflavin/ UVA at 3 mW/cm2 were dissolved only by day 13 following pepsin digestion and by day 14 following collagenase treatment versus 6 days in the untreated control corneas. Digestion by trypsin was observed on day 5 in buttons crosslinked at 3 mW/cm2 compared to day 2 in the control corneas. Microscopically, a prolonged preservation especially of the anterior portion of the crosslinked corneas could be demonstrated. Photochemical crosslinking of the cornea using riboflavin and UVA results in a markedly increased resistance versus collagen digesting enzymes. The findings support the use of the new method in the treatment of corneal ulcers.
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            Keratoconus.

            Keratoconus is a bilateral noninflammatory corneal ectasia with an incidence of approximately 1 per 2,000 in the general population. It has well-described clinical signs, but early forms of the disease may go undetected unless the anterior corneal topography is studied. Early disease is now best detected with videokeratography. Classic histopathologic features include stromal thinning, iron deposition in the epithelial basement membrane, and breaks in Bowman's layer. Keratoconus is most commonly an isolated disorder, although several reports describe an association with Down syndrome, Leber's congenital amaurosis, and mitral valve prolapse. The differential diagnosis of keratoconus includes keratoglobus, pellucid marginal degeneration and Terrien's marginal degeneration. Contact lenses are the most common treatment modality. When contact lenses fail, corneal transplant is the best and most successful surgical option. Despite intensive clinical and laboratory investigation, the etiology of keratoconus remains unclear. Clinical studies provide strong indications of a major role for genes in its etiology. Videokeratography is playing an increasing role in defining the genetics of keratoconus, since early forms of the disease can be more accurately detected and potentially quantified in a reproducible manner. Laboratory studies suggest a role for degradative enzymes and proteinase inhibitors and a possible role for the interleukin-1 system in its pathogenesis, but these roles need to be more clearly defined. Genes suggested by these studies, as well as collagen genes and their regulatory products, could potentially be used as candidate genes to study patients with familial keratoconus. Such studies may provide the clues needed to enable us to better understand the underlying mechanisms that cause the corneal thinning in this disorder.
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              Changes in collagen orientation and distribution in keratoconus corneas.

              To map the collagen orientation and relative distribution of collagen fibrillar mass in keratoconus corneal buttons. Structural analysis was performed by obtaining synchrotron x-ray scattering patterns across the samples at 0.25-mm intervals. The patterns were analyzed to produce two-dimensional maps of the orientation of the lamellae and of the distribution of total and preferentially aligned lamellae. Compared with normal corneas, in keratoconus the gross organization of the stromal lamellae was dramatically changed, and the collagen fibrillar mass was unevenly distributed, particularly around the presumed apex of the cone. The development of keratoconus involves a high degree of inter- and probably intralamellar displacement and slippage that leads to thinning of the central cornea and associated changes in corneal curvature. This slippage may be promoted by a loss of cohesive forces and mechanical failure in regions where lamellae bifurcate.
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                Author and article information

                Journal
                Middle East Afr J Ophthalmol
                MEAJO
                Middle East African Journal of Ophthalmology
                Medknow Publications (India )
                0974-9233
                0975-1599
                Jan-Mar 2010
                : 17
                : 1
                : 15-20
                Affiliations
                Department of Ophthalmology, Tulane University, New Orleans, LA, USA
                [1 ]North Carolina University, Chapel Hill, NC USA
                Author notes
                Corresponding Author: Dr. Ladan Espandar, 1430 Tulane Ave, 5 th Floor, Ophthalmology Department, Tulane University, New Orleans, LA, USA. E-mail: lespanda@ 123456tulane.edu
                Article
                MEAJO-17-15
                10.4103/0974-9233.61212
                2880369
                20543932
                af8ee897-471c-4516-a3ad-4dd8252a5780
                © Middle East African Journal of Ophthalmology

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Cornea/Refractive Update

                Ophthalmology & Optometry
                keratoconus,phakic intraocular lens,intacs,collagen cross-linking
                Ophthalmology & Optometry
                keratoconus, phakic intraocular lens, intacs, collagen cross-linking

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