Early Keratoconus Detection and Management
BY S. BARRY EIDEN, OD, FAAO
Corneal ectasia is a thinning disorder associated with progressive corneal steepening and surface irregularity. Keratoconus (KC) is a naturally occurring form of ectasia in which the cornea assumes a locally conical shape due to thinning and protrusion.
The frequency of KC is most commonly reported to be about 1 in 2,000. However, with newer technologies allowing for earlier diagnosis and detection of subtle and often “subclinical” cases, the true prevalence may be as common as 1 in 500 to 600 (Weissman, Medscape).
Advances in early KC diagnosis and in treatment strategies that can limit, if not halt, progression have resulted in a revolutionary paradigm shift in the contemporary management of the disease.
Is Keratoconus Hereditary?
Evidence of the hereditary nature of KC is becoming more compelling. A recent study utilized complex segregation analysis (CSA), a technique that determines whether there is evidence that a major gene underlies the distribution of a given phenotypic trait, to look at the hereditary aspects of KC (Kriszt et al, 2014). CSA also evaluates whether the implicated trait is inherited in a Mendelian dominant, recessive, or co-dominant manner.
Sixty keratoconus probands—212 family members and 212 age- and gender-matched healthy controls—underwent clinical and videokeratographic examination. In 145 relatives of probands, the estimated prevalence of manifest keratoconus was 7.6%, indicating strong familial aggregation. All examined videokeratography indices were able to differentiate between KC and non-KC family members as well as normal controls (anova p < 0.001). The researchers concluded that CSA points to a strong genetic contribution to the transmission of keratoconus. Inheritance is most probably due to a non-Mendelian major gene effect.
Advances in Early Detection
While detecting clinical signs and symptoms in the primary eyecare environment is important in managing these patients, new advanced technologies can detect KC and other ectasias well in advance of any subjective symptoms or traditional clinical findings. Screening high-risk patients, such as relatives of known KC patients as well as prospective and status-post (S/P) kerato-refractive patients, with these technologies has significant applications (Fernández Pérez et al, 2014).
Scheimpflug imaging tomography and associated software analysis programs look at both anterior and posterior corneal surfaces as well as at global pachymetry metrics and corneal aberrometry (Piñero et al, 2009; Ambrósio et al, 2011). Wavefront aberrometry indicates that higher-order aberrations are increased in patients who have KC or subclinical KC (Bühren et al, 2010). High-frequency corneal ultrasound (Artemis, ArcScan Inc.) has shown a consistent pattern of central epithelial thinning surrounded by paracentral thickening in what is described as a “doughnut pattern” in all KC patients studied. Early KC detection based on this pattern may be possible prior to other findings (Reinstein et al, 2010).
Corneal biomechanics appear to be effected in very early phases of KC and other forms of ectasia. Devices to measure corneal biomechanics are now becoming more clinically available. Systems such as the Ocular Response Analyzer (Reichert Inc.) and the Corvis ST (Oculus) have shown differentiating outcomes in KC and other ectatic corneas compared to normal corneas (Ali et al, 2014; Touboul et al, 2011).
New technologies have been confirmed in their ability to control KC progression and are dramatically altering treatment methods.
Corneal Cross-Linking (CXL) CXL is now considered a virtual standard of care in managing progressive or potentially progressive KC and other forms of progressive corneal ectasia. CXL was first and still is most commonly performed utilizing an “epithelium-off” (epi-off) approach whereby the central 7mm to 9mm of the corneal epithelium is removed prior to the application of riboflavin and ultraviolet (UV) light. The standard, or Dresden, protocol has been used and studied extensively worldwide (Wollensak et al, 2010).
A recent large-scale systematic review of the literature pertaining to epi-off CXL utilizing meta-analysis (Craig et al, 2014) identified 49 studies that were considered appropriate for inclusion in the meta-analyses. The majority of the studies (39/49) were graded as very low-quality evidence. Meta-analyses results were presented for changes in visual acuity, topography, refraction and astigmatism, and central corneal thickness (CCT). Statistically significant improvements were found in all efficacy outcomes at 12 months after the procedure. Common side effects were pain, corneal edema, and corneal haze, which usually resolved within a few days after the procedure. The authors stated that what remains uncertain is the duration of benefit to establish the procedure’s potential in avoiding or delaying disease progression and possibly reducing the need for corneal transplantation.
Due to the potential for numerous side effects and complications with epi-off CXL, many are now turning to transepithelial (or epi-on) CXL. Because the epithelium remains intact, epi-on CXL is typically far less painful, has faster healing and recuperation time, and a reduced propensity for treatment-related infection and inflammation. It is also less likely to result in endothelial cytotoxicity from the UV exposure in corneas with minimum thickness values lower than 400 microns.
But, is epi-on CXL as effective as epi-off CXL? A recent study looked at outcomes of epi-on CXL performed on patients who had progressive KC and CCT values below 400 microns (Khairy et al, 2014). This was a prospective, uncontrolled, interventional study that involved 32 eyes of 30 patients. Researchers concluded that epi-on CXL has potential as a method for treating patients who have progressive KC and CCT of less than 400 microns, in which standard epi-off CXL cannot be applied. Over 12 months of follow up, the epi-on CXL was safe and effective, with results comparable to the epi-off technique in thicker corneas, and it reduced rates of operative and postoperative discomfort.
A recent review article extracted data from 94 articles on methods to improve classic CXL treatment (Li et al, 2014). Reviewing techniques that ranged from modifications to the UV lamp to the use of new photo-active cross-linking agents that allow for “flash” CXL of only 30 seconds using the same power and wavelength of UV light, among many others, this article shows that CXL is an evolving technology.
Corneal Ring Segments Beyond CXL, corneal ring segments may also control progression as well as influence corneal shape, steepness, and visual outcomes. A retrospective study evaluated the long-term rate of progression of KC in eyes implanted with corneal ring segments at the five-year follow up. Data of 105 eyes from 85 patients who had undergone consecutive corneal ring segment implantation were studied for KC progression (Bedi et al, 2012); 92.9% of eyes that had documented preoperative progression demonstrated no progression between the one- and five-year follow up. Additionally, no statistically significant differences were noted in mean steep, flat, and average keratometry; manifest refraction spherical equivalent; and uncorrected and corrected distance visual acuity (p > 0.05) between the one- and five-year follow up.
The field of KC and corneal ectasia management is changing at an exponential rate. The importance of early detection and the application of evolving progression control methods is critical in preventing advanced disease. Those of us who are involved in managing KC patients must continually monitor the state-of-the-art care for these patients based on the most current research. CLS
For references, please visit www.clspectrum.com/references.asp and click on document #229.
Dr. Eiden is president and medical director of North Suburban Vision Consultants, president and founder of the International Keratoconus Academy of Eye Care Professionals, and co-founder of EyeVis Eye and Vision Research Institute. He is an adjunct faculty member at The University of Illinois Medical Center as well as at the Indiana and Illinois Colleges of Optometry and Pennsylvania College of Optometry at Salus University. He is also a consultant or advisor to CooperVision, Alcon, B+L, Visionary Optics, Alden Optical, Oculus, Oasis Medical, Paragon Vision Sciences, and SpecialEyes.