Intrastromal corneal ring implants for corneal thinning disorders: an evidence-based analysis.

OBJECTIVE: The purpose of this project was to determine the role of corneal implants in the management of corneal thinning disease conditions. An evidence-based review was conducted to determine the safety, effectiveness and durability of corneal implants for the management of corneal thinning disorders. The evolving directions of research in this area were also reviewed. SUBJECT OF THE EVIDENCE-BASED ANALYSIS: The primary treatment objectives for corneal implants are to normalize corneal surface topography, improve contact lens tolerability, and restore visual acuity in order to delay or defer the need for corneal transplant. Implant placement is a minimally invasive procedure that is purported to be safe and effective. The procedure is also claimed to be adjustable, reversible, and both eyes can be treated at the same time. Further, implants do not limit the performance of subsequent surgical approaches or interfere with corneal transplant. The evidence for these claims is the focus of this review. The specific research questions for the evidence review were as follows: SafetyCorneal Surface Topographic Effects:Effects on corneal surface remodellingImpact of these changes on subsequent interventions, particularly corneal transplantation (penetrating keratoplasty [PKP])Visual AcuityRefractive OutcomesVISUAL QUALITY (SYMPTOMS): such as contrast vision or decreased visual symptoms (halos, fluctuating vision)Contact lens toleranceFunctional visual rehabilitation and quality of lifePatient satisfaction:Disease Process:Impact on corneal thinning processEffect on delaying or deferring the need for corneal transplantation

CLINICAL NEED: TARGET POPULATION AND CONDITION Corneal ectasia (thinning) comprises a range of disorders involving either primary disease conditions such as keratoconus and pellucid marginal corneal degeneration or secondary iatrogenic conditions such as corneal thinning occurring after LASIK refractive surgery. The condition occurs when the normally round dome-shaped cornea progressively thins causing a cone-like bulge or forward protrusion in response to the normal pressure of the eye. Thinning occurs primarily in the stoma layers and is believed to be a breakdown in the collagen network. This bulging can lead to an irregular shape or astigmatism of the cornea and, because the anterior part of the cornea is largely responsible for the focusing of light on the retina, results in loss of visual acuity. This can make even simple daily tasks, such as driving, watching television or reading, difficult to perform. Keratoconus (KC) is the most common form of corneal thinning disorder and is a noninflammatory chronic disease process. Although the specific causes of the biomechanical alterations that occur in KC are unknown, there is a growing body of evidence to suggest that genetic factors may play an important role. KC is a rare condition (<0.05% of the population) and is unique among chronic eye diseases as it has an early age of onset (median age of 25 years). Disease management for this condition follows a step-wise approach depending on disease severity. Contact lenses are the primary treatment of choice when there is irregular astigmatism associated with the disease. When patients can no longer tolerate contact lenses or when lenses no longer provide adequate vision, patients are referred for corneal transplant. Keratoconus is one of the leading indications for corneal transplants and has been so for the last three decades. Yet, despite high graft survival rates of up to 20 years, there are reasons to defer receiving transplants for as long as possible. Patients with keratoconus are generally young and life-long term graft survival would be an important consideration. The surgery itself involves lengthy time off work and there are potential complications from long term steroid use following surgery, as well as the risk of developing secondary cataracts, glaucoma etc. After transplant, recurrent KC is possible with need for subsequent intervention. Residual refractive errors and astigmatism can remain challenging after transplantation and high refractive surgery rates and re-graft rates in KC patients have been reported. Visual rehabilitation or recovery of visual acuity after transplant may be slow and/or unsatisfactory to patients.

DESCRIPTION OF TECHNOLOGY/THERAPY: INTACS® (Addition Technology Inc. Sunnyvale, CA, formerly KeraVision, Inc.) are the only currently licensed corneal implants in Canada. The implants are micro-thin poly methyl methacrylate crescent shaped ring segments with a circumference arc length of 150 degrees, an external diameter of 8.10 mm, an inner diameter of 6.77 mm, and a range of different thicknesses. Implants act as passive spacers and, when placed in the cornea, cause local separation of the corneal lamellae resulting in a shortening of the arc length of the anterior corneal curvature and flattening the central cornea. Increasing segment thickness results in greater lamellar separation with increased flattening of the cornea correcting for myopia by decreasing the optical power of the eye. Corneal implants also improve corneal astigmatism but the mechanism of action for this is less well understood. Treatment with corneal implants is considered for patients who are contact lens intolerant, having adequate corneal thickness particularly around the area of the implant incision site and without central corneal scarring. Those with central corneal scarring would not benefit from implants and those without an adequate corneal thickness, particularly in the region that the implants are being inserted, would be at increased risk for corneal perforation. Patients desiring to have visual rehabilitation that does not include glasses or contact lenses would not be candidates for corneal ring implants. Placement of the implants is an outpatient procedure with topical anesthesia generally performed by either corneal specialists or refractive surgeons. It involves creating tunnels in the corneal stroma to secure the implants either by a diamond knife or laser calibrated to an approximate depth of 70% of the cornea. Variable approaches have been employed by surgeons in selecting ring segment size, number and position. Generally, two segments of equal thickness are placed superiorly and inferiorly to manage symmetrical patterns of corneal thinning whereas one segment may be placed to manage asymmetric thinning patterns. Following implantation, the major safety concerns are for potential adverse events including corneal perforation, infection, corneal infiltrates, corneal neovascularization, ring migration and extrusion and corneal thinning. Technical results can be unsatisfactory for several reasons. Treatment may result in an over or under-correction of refraction and may induce astigmatism or asymmetry of the cornea. Progression of the corneal cone with corneal opacities is also invariably an indication for progression to corneal transplant. Other reasons for treatment failure or patient dissatisfaction include foreign body sensation, unsatisfactory visual quality with symptoms such as double vision, fluctuating vision, poor night vision or visual side effects related to ring edge or induced or unresolved astigmatism.

EVIDENCE-BASED ANALYSIS METHODS: The literature search strategy employed keywords and subject headings to capture the concepts of 1) intrastromal corneal rings and 2) corneal diseases, with a focus on keratoconus, astigmatism, and corneal ectasia. The initial search was run on April 17, 2008, and a final search was run on March 6, 2009 in the following databases: Ovid MEDLINE (1996 to February Week 4 2009), OVID MEDLINE In-Process and Other Non-Indexed Citations, EMBASE (1980 to 2009 Week 10), OVID Cochrane Library, and the Centre for Reviews and Dissemination/International Agency for Health Technology Assessment. Parallel search strategies were developed for the remaining databases. Search results were limited to human and English-language published between January 2000 and April 17, 2008. The resulting citations were downloaded into Reference Manager, v.11 (ISI Researchsoft, Thomson Scientific, U.S.A), and duplicates were removed. The Web sites of several other health technology agencies were also reviewed including the Canadian Agency for Drugs and Technologies in Health (CADTH), ECRI, and the United Kingdom National Institute for Clinical Excellence (NICE). The bibliographies of relevant articles were scanned.

INCLUSION CRITERIA: English language reports and human studiesAny corneal thinning disorderReports with corneal implants used alone or in conjunction with other interventionsOriginal reports with defined study methodologyReports including standardized measurements on outcome events such as technical success, safety, effectiveness, durability, vision quality of life or patient satisfactionCase reports or case series for complications and adverse events

EXCLUSION CRITERIA: Non-systematic reviews, letters, comments and editorialsReports not involving outcome events such as safety, effectiveness, durability, vision quality or patient satisfaction following an intervention with corneal implantsReports not involving corneal thinning disorders and an intervention with corneal implants

SUMMARY OF FINDINGS: In the MAS evidence review on intrastromal corneal ring implants, 66 reports were identified on the use of implants for management of corneal thinning disorders. Reports varied according to their primary clinical indication, type of corneal implant, and whether or not secondary procedures were used in conjunction with the implants. Implants were reported to manage post LASIK thinning and/or uncorrected refractive error and were also reported as an adjunctive intervention both during and after corneal transplant to manage recurrent thinning and/or uncorrected refractive error. (ABSTRACT TRUNCATED)