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Newer technologies, improved diagnostics altering treatment of corneal ectasia
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Corneal ectasia is an important corneal pathology, and like so many other diseases, its diagnosis and treatment are currently evolving rapidly. Corneal ectasia includes keratoconus, pellucid marginal degeneration, posterior keratoconus and post-laser refractive surgery ectasia. Estimates of the number of patients with this diagnosis vary widely. The classic prevalence number is 1:2,000, meaning that there are about 180,000 patients with keratoconus in the U.S. I think this number is low, and some sources have suggested a prevalence as high as 1:400, which would increase the number to 900,000. If we include the so-called forme fruste keratoconus or keratoconus suspect, the number may be higher yet.
Large LASIK centers and practices report that at least 10% of patients are denied laser refractive surgery because of a cornea that is too thin or has an atypical topography that makes the surgeon nervous. Because only myopes and hyperopes are usually seen at these centers, the number might be smaller for the overall population, but in my opinion, as much as 1% to 2% of the population may fit into the forme fruste keratoconus or keratoconus suspect category. That moves the number of at-risk patients in the U.S. up to 3.6 million to 7.2 million. This makes the patient with frank corneal ectasia or risk factors for ectasia more common than classically taught, and as treatment options become safer and more readily available, clinicians will need to decide which of these patients deserve treatment with soon-to-be FDA-approved (we hope) approaches such as corneal collagen cross-linking (CXL).
The classical diagnosis of keratoconus includes progressive thinning with development of corneal steepening, increased astigmatism/coma and usually induced myopia. We currently screen for at-risk patients, or perhaps those with early keratoconus, using pachymetry, retinoscopy, keratometry and especially computerized corneal topography. The Ocular Response Analyzer from Reichert is used in some clinics to elucidate reduced corneal stiffness, and there is exciting research using Brillouin spectroscopy by Intelon and Avedro that promises more accurate measurement of corneal elasticity. This diagnostic technology could help us in the future determine which corneas with atypical topography are really at risk of progressive ectasia and deserve treatment with CXL.
The optical treatment of corneal ectasia typically starts with spectacles and advances to contact lenses. Usually patients with meaningful corneal ectasia see best with a rigid gas permeable contact lens, and many specialty contacts have been designed. A scleral contact lens can correct many patients with even severe keratoconus. My classic corneal training was to be very aggressive with contact lens fitting and reserve surgery for only those patients who are truly contact lens intolerant or are unable to wear contacts long enough to function in their daily life activities. In the face of newer treatments, which I will discuss below, I now usually recommend CXL or CXL combined with adjunct therapy as soon as the diagnosis of corneal ectasia is made. After stabilizing the cornea, contact lens wear can be resumed if needed.
I now consider it inappropriate to allow a patient to progress from mild to moderate to severe keratoconus, even if vision is good with a contact lens. The patient deserves to be informed and offered CXL as soon as the diagnosis is made. According to Eye Bank Association of America statistics, penetrating keratoplasty remains the dominant surgery for corneal ectasia, although deep anterior lamellar keratoplasty is slowly gaining advocates. Fortunately for the patient with corneal ectasia, outcomes with lamellar or penetrating keratoplasty are quite good. Still, those of us who do a significant number of corneal transplants know that this procedure is a lot of work for the patient and surgeon, and there are many complications, both early and late, including several that are sight-threatening. We would all love to have a minimally invasive treatment available that would arrest this disease before keratoplasty, or perhaps even before it induces any visual loss. While there is still much to be learned, one or another form of CXL shows promise to be such a treatment.
At Minnesota Eye Consultants, with six corneal surgeons, we treat a significant volume of corneal ectasia. We are currently participating in our third clinical trial evaluating CXL, and we have also applied several other adjuncts to improve our treatment of the corneal ectasia patient. All of these are investigational or off label, as CXL is not yet FDA approved. In the remaining paragraphs, I would like to present a few thoughts on these treatments, which are in my personal opinion very promising. I would like to disclose that I consult widely in the field, including for companies involved with each of the technologies I will describe.
First, in regards to CXL, our practice has evolved to an epithelium-on approach. We have found that with appropriate solutions and surgical technique adjuncts we can load the corneal stroma with riboflavin dye through an intact epithelium. This allows a procedure with minimal morbidity and bilateral same-day treatment. Patients see well the next day and can resume contact lens wear in 1 to 2 days. We also utilize intermittent rather than constant ultraviolet light application, which is logical in the oxygen-dependent cross-linking process.
While the hoped-for first U.S. approval for CXL will be for the so-called epithelium-off Dresden technique, I do not see myself going back to that approach. Much like off-label LASIK dominated when PRK was first approved, I predict off-label epithelium-on CXL will dominate soon after epithelium-off CXL is FDA approved. The low morbidity of epithelium-on CXL will in my opinion lead to a more aggressive approach to treatment than is currently practiced with epithelium-off CXL. Classic teaching for epithelium-off CXL is to wait for evidence of disease progression before treating. I predict we will rapidly evolve to treating patients once the diagnosis of corneal ectasia or significant risk of developing corneal ectasia is confirmed. This makes sense to me and is what I would want for myself or my family, as I would love to stop this disease in its tracks before a patient suffers any visual loss whatsoever.
If all patients who present for spectacle correction or contact lens fitting are screened with corneal topography, and those with atypical corneas are referred for evaluation and as indicated appropriate treatment, I can imagine nearly eliminating moderate to severe corneal ectasia requiring keratoplasty in the next 20 to 30 years. Today’s patient with forme fruste or mild keratoconus can be treated with CXL, and if motivated to spectacle-independent vision, I predict PRK/PTK will prove to be a safe treatment either at the same time as CXL or later. I have found both approaches give promising outcomes.
In select patients with intense informed consent and inside an IRB-approved clinical trial, I currently perform a staged procedure with CXL first, followed by PRK/PTK once evidence of refractive and topographic stability is confirmed. Others have reported good results with same-day sequential CXL and PRK/PTK, but for me, corneal haze, the occasional delayed healing and the unpredictable impact of CXL on refractive error have been a meaningful negative. For the patient with moderate to severe keratoconus, I have found Intacs (Addition Technology), conductive keratoplasty (CK) or in some patients Intacs and CK to be useful in reducing myopia and astigmatism and enhancing both uncorrected and best corrected vision. Again, I like to do the CXL 1 to 4 weeks after the Intacs and/or CK, but some surgeons are reporting good outcomes doing them sequentially on the same day. While much further study is required, and this approach is investigational and in our facility performed inside a clinical trial with IRB approval, I have patients who have been treated with Intacs and CK followed by CXL 1 to 4 weeks later and then a year or more later undergone a PRK/PTK with excellent improvement in visual function. Some have achieved spectacle- and contact lens-independent functional vision with to-date good refractive stability.
Today in the U.S., CXL is investigational and usually not reimbursed. We have performed our treatments in clinical trials sponsored by Peschke, Topcon and CXLO. Intacs are FDA approved for keratoconus and usually reimbursed. CK is FDA approved for the treatment of myopia and presbyopia, but not as an adjunct for treating refractive errors associated with corneal ectasia. Its use is therefore also investigational and off label. PRK and PTK are FDA approved for the treatment of a broad range of refractive errors and corneal pathology, but their use for reducing the myopia, astigmatism and corneal irregularity associated with corneal ectasia is also investigational and off label. However, pioneering surgeons around the world are reporting very promising results using CXL, Intacs, CK and PRK/PTK alone or in various combinations to help their corneal ectasia patients retain or regain functional vision. All these treatment technologies and improved diagnostics such as Brillouin spectroscopy promise to revolutionize our diagnosis and treatment of corneal ectasia and perhaps make keratoplasty a historical footnote for these long-suffering patients.