GKC MEETING REPORT

New Findings from the 2008 Global Keratoconus Congress

A report on what's new in the etiology, evaluation and management of keratoconus and irregular corneas.

By Edward S. Bennett, OD, MSEd

Dr. Bennett is currently director of Student Services and Co-Chief of the Contact Lens Service in the University of Missouri-St. Louis College of Optometry. He is Executive Director of the GP Lens Institute — the educational division of the Contact Lens Manufacturers Association — and Vice Chair of the Cornea and Contact Lens Section of the American Academy of Optometry. He has over 200 publications, including 10 textbooks, and has lectured at over 200 scientific and continuing education symposia in 10 countries. He is currently clinical features editor for Contact Lens Spectrum and is an editorial review board member for eight other journals.

The 2008 Global Keratoconus Congress took place Jan. 25 – 27, 2008 in Las Vegas. Sponsored by Contact Lens Spectrum and the Lippincott Williams & Wilkins Health Care Conference Group, this two-and-one-half day educational program hosted approximately 400 attendees and presented the latest developments in irregular cornea care with an emphasis on clinical (notably contact lens) management.

The educational program, developed by the GKC Planning Committee (Craig Norman, FCLSA; Joe Barr OD, MS; Carla Mack, OD; Patrick Caroline, FCLSA; Eef van der Worp, BSc Optom; and Ed Bennett, OD, MSEd), included a fundamentals session to assist attendees in the diagnosis, evaluation and contact lens management of keratoconus and post-surgical patients, as well as sessions pertaining to the etiology of keratoconus, clinical controversies, large diameter lens applications, current and future surgical approaches, and coding and reimbursement.

In addition, there were seven hands-on workshops, 10 free papers and 30 scientific posters. The following represents a brief overview of the highlights of this symposium.

What Causes Keratoconus?

Is It Genetic? Loretta Szczotka-Flynn, OD, MS, reported that, although the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) study found that 13.5 percent of keratoconus patients had a family history, Dr. Yaron Rabinowitz has found that there is a 15-to-67 times greater incidence in first-degree relatives than in the general population.

Dr. Szczotka-Flynn also reported that a wealth of data suggests that keratoconus pathogenesis is mediated by genetic causes; however, very few investigations have led to causative genes for keratoconus. She recommended that a large sample size, genetic epidemiologic case control study would serve as an excellent way to pinpoint genes involved in this complex disease. Using this study design, researchers could identify a diagnostic gene, clone it, map it and then perhaps introduce drug interventional therapy or even gene therapy in the future.

What About Eye Rubbing? Charles McMonnies, MSc, reported that the corneal indentation (fibril buckling) and compensatory curvature transfer, as well as high IOP-induced bulging of the cornea immediately adjacent to the indentation, are mechanical responses to eye rubbing that result in high tissue pressure. Therefore, forceful eye rubbing appears to have a strong contributing role in the etiology and progression of keratoconus. He recommended to advise against eye rubbing for certain high risk patients including those who have a family history, atopy patients who tend to rub their eyes and patients who already have keratoconus in an effort to possibly lessen its progression.

The GKC Planning Committee (left to right): Patrick Caroline, FCLSA; Carla Mack, OD; Eef van der Worp, BSc Optom; Craig Norman, FCLSA; Joe Barr, OD, MS; and Ed Bennett, OD, MSEd.

Epithelial or Stromal? Jan Bergmanson, OD, PhD, reported research done with Jessica Mathew, OD, indicating that although it's not clear whether keratoconus starts in the epithelium or in the stroma, the epithelium is definitely a part of the disease process, including early in the process. Pathological changes include epithelial thickness variation and abnormal basement synthesis. The anterior limiting lamina (Bowman's layer) is severely affected or lost in keratoconus, and with a basement membrane that is 10-to-15 times thicker than normal, it's difficult for the hemidesmosomes (anchors) within the epithelial basal cells to penetrate the basement membrane and anchor down the epithelium. This resulting epithelial fragility makes it imperative to avoid a harsh apical bearing fitting relationship and its resulting rubbing against this area.

Confocal electron microscopy studies by Charles McGhee, PhD, and Jennifer Fan, BHB, MBCh, also suggest that the primary abnormality in keratoconus may reside in the epithelium. They found degenerating keratocytes in the keratoconic cornea and apoptosis associated with breaks in Bowman's layer. They also found enlargement and an irregular arrangement of the epithelial cells along with epithelial thinning. The most severe cases were often with younger patients and those who were frequent eye rubbers.

Pulling It All Together M. Cristina Kenney, MD, PhD, presented her theory in which a cascade of events occurs that result in keratoconus. She reported that at least 10 different chromosomes have been associated with keratoconus and, more likely, keratoconus has multiple genes involved that are related to a final common pathway, which she has termed the "Oxidative Stress Pathway." In this theory, apoptosis occurs as a result of a buildup of reactive oxygen species (ROS or free radicals) and reactive nitrogen species (RNS). In susceptible individuals, the mitochondrial DNA is damaged, energy production is reduced and a biochemical series of events occurs that result in an increase in ROS, which is then toxic to cells. Keratoconic corneas can't eliminate the ROS as efficiently as they should; therefore, it's important to minimize exposure of the cornea to environmental stressors such as ultraviolet light, eye rubbing, mechanical pressure from an improperly fit contact lens and atopy. Consequently, the use of ultraviolet protection in glasses and contact lenses is important as well as controlling atopy or allergies with medications to minimize inflammation and resultant eye rubbing.

The Keratoconus Personality

Karla Zadnik, OD, PhD, reported on the study by Dr. Kerry Giedd pertaining to the use of a standardized questionnaire (Milton Behavioral Health Inventory or MBHI) with subjects recruited through the keratoconus-link listserv. The results showed that 96 percent of respondents indicated that keratoconus had at least some impact on their lives; 40 percent indicated the impact was moderate or severe. Keratoconus subjects also scored lower on the respectful coping style scale. This would seem to indicate that keratoconus patients may tend to be less respectful and cooperative with their practitioner, likely resulting in practitioners having a less favorable attitude toward them. However, no general personality disorder was found.

Applications of Current and Future Technology

Topography Pete Kollbaum, OD, reported that mean curvature values — available in some topographers such as the Zeiss and Orbscan (Bausch & Lomb) systems — are more effective than axial and tangential maps in keratoconus as they help in localizing the cone and they describe the shape of the cone in more detail. He also reported that evaluation of the posterior surface elevation alone correctly detects disease in most eyes regardless of disease severity and, combining this information with corneal thickness information, allows very good discrimination of this disease from normal corneas, from slightly abnormal corneas and from contact lens warpage.

Tim McMahon, OD, reported on the topography results from the CLEK topography assessment group. He reported on the results of 300 eyes in which the tangential map was used, the size of the cone was measured, and the diameter and location of the area with a local curvature greater than 50D was assessed. They found that 28.7 percent of the cones were nipple (<3mm), 44.3 percent were oval (3.0mm to 5.5mm), 6.7 percent were globoid (>5.5mm) and 5.6 percent were marginal (located in the periphery, typically inferior). The remaining 14.7 percent were either corneal transplant patients or did not fit one of these categories. He also reported that more than 10 percent had an apex above the horizontal midline.

In terms of fitting, Dr. McMahon recommended that if the cone apex is central and oval, traditional keratoconic lens designs and fitting philosophies should be successful. If the cone is a nipple cone, much smaller optical zone diameters are typically indicated. Piggyback, hybrid or semi-scleral designs are often indicated for an inferior or marginal cone. Likewise, for first-time contact lens wearers who tend to have sensitive corneas, a large diameter (intralimbal or similar design) is recommended to increase initial comfort.

Daniela Nosch, MCOptom, discussed autofitting of contact lenses, which pertains to topography-based lens fitting in which the software chooses a best-fit design and sets the lens parameters. The lens orders are sent seamlessly to the laboratory for manufacturing. She mentioned five such systems and shared her experience with one called Focal Points Professional. In this system all topographical information — including central radii and axes of the main meridians, eccentricities in all directions, corneal indices, Fourier analysis and Zernike Analysis — feeds into the determination of contact lens parameters. She also reported on a study comparing patients' conventional lenses versus empirical fitting using the simulated fluorescein pattern program from a different autofitting software program. Of 68 eyes, 53 preferred the new lens, nine preferred their conventional lens and six had no preference. In addition, for the topography-based design, the first lens was dispensed in 66 percent of the cases and a maximum of four trial lenses was required to achieve a successful fit, compared to their conventional lenses in which up to seven lenses were required to achieve a satisfactory fit and only 19 percent of initial trial lenses were dispensed.

Aberrometry Dan Neal, PhD, reported that keratoconus is one of the most significantly aberrated conditions. An aberrometer is very sensitive to keratoconus and can detect it earlier. In keratoconic eyes, much more so than in normal eyes, low- and especially higher-order aberrations — if uncorrected — can significantly decrease the quality of the best-corrected visual acuity. The goal would be to develop a customized wavefront-guided soft contact lens that corrects for low- and higher-order aberrations. Dr. Neal emphasized that manufacturing this type of contact lens is possible today with current lathes, notably those that make toric lenses. He cited a small sample in which the optical and visual performance of custom wavefront-guided contact lenses was significantly better than that found with subjects' habitual contact lens correction. He concluded that aberrometry can be a powerful diagnostic tool and, if reasonably priced, quite popular in clinical practice. The information it provides, in combination with manufacturing aberration-correcting lenses, can be especially valuable in the future management of keratoconus patients.

Contact Lens Fitting in 2008

Small and Intralimbal GP Lenses Paul Rose, OD, reported that improvements available today in GP fitting include topographers to assist in keratoconic fitting, better production techniques (such as oscillating computer lathes) and improved materials. He noted the importance of having a simple fitting system including an extensive trial set to handle all stages of the disease, extensive and flexible parameters, the elimination of the need to specify optical zone diameter and peripheral curve information, and a flexible edge lift to accommodate all cone shapes. He emphasized that apical bearing can lead to corneal staining and scarring. If apical touch occurs, the patient should be fine as long as fluorescein is present over the cone with the blink.

GKC Faculty Members (left to right): Michael Ward, MMSc; Patrick Caroline, FCLSA; Mark André, FCLSA; Craig Norman, FCLSA; and Buddy Russell, FCLSA.

Dr. Rose also emphasized that the most ignored, yet the most important, factor for a successful fit is the lens periphery and the resultant edge lift. Too little edge lift will result in very little movement of the lens, while excessive edge lift will cause excessive movement. Several keratoconus lens designs today have several different edge lifts. In addition, some designs (such as steep-flat, ACT and other similar designs) offer the ability to tuck in the inferior edge if excessive inferior edge lift is present.

If the eccentricity varies per meridian, several laboratories offer — or will soon introduce — different eccentricities in each quadrant of the lens. Dr. Rose discussed the ACT design, which consists of a minimum of three amounts (Grades 1, 2 and 3) that the inferior edge can be brought in toward the eye. He also reported on the importance of aberration-control optics such as those in the Rose K2 lens (Blanchard Contact Lens). This design has aspheric optics with spherical aberration-correcting properties. Dr. Rose reported on a study in which 100 eyes wearing the Rose K lens were refitted into the Rose K2, with 100 percent reporting their vision to be the same or better and 72 percent reporting their vision to be better or much better with the Rose K2. Patients with higher myopia (>–10.00D) appeared to benefit the most.

Mini-Scleral and Scleral Designs Led by scleral lens innovators Perry Rosenthal, MD, and Don Ezekiel, OD, a very informative session was devoted to the topic that perhaps clinicians were most interested to learn more about: large-diameter GP lens designs. Christine Sindt, OD, described a classification used by Dr. Rob Breece to define these large lenses:

1. Corneo-Scleral: 12.9mm to 13.5mm
2. Semi-Scleral: 13.6mm to 14.9mm
3. Mini-Scleral: 15.0mm to 18.0mm
4. Full Scleral: 18.1mm to 24mm+

Dr. Sindt emphasized the importance of sagittal depth when fitting the large lenses, notably the mini-sclerals. These lenses should be allowed to settle for at minimum 20 minutes. A Wratten filter is essential to evaluate whether fluorescein is going under the lens with the blink. The lens should lightly touch or vault the cornea; the latter would be preferable but it may be difficult to vault the entire cornea. Definite touch will likely result in epithelial erosion. The lens should have 360-degree vaulting of the limbus and should lightly touch — but not impinge on — the sclera. If impingement occurs, there will be blanching of the accompanying vessels and, although the lens may be worn comfortably all day, the eye will become red and a compression ring will be present upon removal, and lens wear will not be possible for 24-to-48 hours. A lens with a greater sagittal depth would be required in this case.

There should be alignment at the periphery; if bubbles are present in the limbal area, there's too much sagittal depth in that region. In that case, either steepen the base curve or, if available, use a lens with a reduced sagittal depth in that area (such as the Blanchard MSD lens, as reported in a paper by Steve Byrnes, OD).

An absence of vertical movement is actually desirable with these lenses. The fluid dynamics work such that some fluid exchange should occur with the blink. However, if the lens exhibits excessive flexure, it will literally push the fluid out and result in lens adherence. Fenestrations, if used, should be 1.0mm in diameter and placed in the lens periphery directly over the deepest part of the fluorescein pool.

As Drs. Sindt and Byrnes emphasized, these lenses have several benefits and applications in contact lens practice. They have better initial comfort compared to smaller GP lens designs, more consistent visual acuity and an absence of foreign body sensation. They are useful for advanced (notably decentered) cones, pellucid marginal degeneration, piggyback failures, poor comfort with traditional GP designs and neovascularization with hybrid designs.

Soft Lenses Several options are available in soft lenses for irregular corneas and, with the corneal sensitivity experienced by many keratoconus patients, these can represent a viable and growing option. Mark André, FCLSA, utilizes the HydraKone design (Medlens Innovations, Inc.), which is a custom hydrogel lens (non-disposable) available in almost any spherical and toric lens parameters. These lenses are effective because of greater thickness in the center that can mask some of the corneal irregularity. This is also important for patients who have either a decentered or a globus-like cone because the lens centers well and features a large optical zone. Vascularization is not as significant a problem as you might expect because of increased movement with the blink resulting from the lens thickness.

Hybrid Lenses The SynergEyes series of lens designs, including the SynergEyes KC (keratoconus) and SynergEyes PS (Post-Surgical), from SynergEyes Inc. provides another viable option. The hyper-Dk Paragon HDS 100 (Paragon Vision Sciences) GP center allows for good oxygen transmission while the soft skirt provides better initial comfort compared to a GP lens alone. The lens typically results in good vision due to the astigmatic correction, and it eliminates some piggyback system-related problems such as GP lens decentration, edge lift from the soft lens, and the complexity of a two-lens system.

These designs do require a diagnostic fitting set as well as high-molecular-weight fluorescein to evaluate the fit. Three different skirt radii are available. It's best to start with the median skirt and then switch to the steeper skirt if the lens is too flat or switch to the flatter skirt if the lens is too steep.

The bottom line is that you need many contact lens options when managing numerous irregular cornea patients. Likewise, as emphasized by both Mark André, FCLSA, and Patrick Caroline, FCLSA, instruct patients that their new correction may well represent a temporary correction until the next wave of technology occurs and even better options become available.

Surgical Update

Penetrating Keratoplasty David Schanzlin, MD, presented an excellent update on irregular cornea surgical procedures. He stated that the rejection rate after a penetrating keratoplasty (PK) is about 18 percent. Dr. Schanzlin also reported that the average post-operative astigmatism is 4.00D and that approximately 50 percent require contact lens correction, typically GPs. He has found that GP lenses can be fit to post-PK patients as early as six weeks post-operatively.

Intrastromal Rings (Intacs) The best application for Intacs (Addition Technology, Inc.) may, in fact, be for keratoconus. Under the FDA Humanitarian Device Exemption, Intacs can be used as an approved product for a non-approved use.

Currently the best keratoconus Intacs candidates are those who have inferior ectasia, keratometry values <54.00D and a spherical equivalent refractive error of <5.00D. Dr. Schanzlin cited examples internationally in which higher amounts of myopia were corrected, keratometry values decreased 8.00D to 10.00D and the resultant improvement in vision was as much as 10 lines on the Snellen acuity chart. It's hoped that Intacs correction, specific for these cases, will receive FDA approval.

Ken McCandless, OD, discussed the role of optometrists in comanaging Intacs patients. He emphasized that — just as with LASIK patients — it's critical to have a very accurate refraction. Patients must be informed that the main side effects are fluctuating visual acuity for about three months, a foreign body sensation and photophobia; the latter symptoms decrease over time. Patients can be fit with soft lenses — spherical or toric — during the first three months, beginning at the end of seven days. If a GP lens is needed, it's recommended to wait until three months post-operatively because of the expected visual fluctuations.

Dr. McCandless recommends prescribing Zymar (Allergan) q.i.d. for seven days immediately post-operative accompanied by Pred Forte (Allergan) q.i.d. for seven days, t.i.d. for three days, b.i.d. for three days, q.d. for two days and then discontinued. Non-preserved artificial tears should be used every two-to-four hours. Ultimately, Dr. McCandless' lenses of choice are either hybrids or intralimbal GP lens designs.

Buddy Russell, FCLSA, reported on a study of 18 eyes with Intacs implants. All 18 ultimately were fit into contact lenses, 10 of which were piggyback fits. No eyes experienced a decrease in best-corrected visual acuity and 15 of the 18 eyes increased, on average, two lines in best-corrected visual acuity.

New Treatments

The combined riboflavin-ultraviolet A (UVA) treatment for keratoconus, first discussed by Dr. Eberhard Spoerl at the 2007 GKC, was a focus of much interest. The treatment involves removal of corneal epithelium, followed by adding riboflavin 0.1% to the stroma (which should penetrate quite easily) and then 30 minutes of exposure to UVA (365nm) radiation. It results in a thickening of the collagen fibrils and a more rigid anterior section of the cornea, which lead to a reduction in keratoconus progression. Clinical trials have been initiated in the United States to assess this method.

Carla Mack, OD; Cathy Warren, RN; and Clarke Newman, OD, discussed insurance reimbursement and coding.

Tomas Pförtner, PhD, evaluated biomechanical properties of the cornea, notably corneal hysteresis and corneal resistance factor, and found that both Intacs and the riboflavin crosslinking treatment appear to improve corneal resistance, but only slightly. Antonio Calossi, OD, took this concept a step further and, on a small sample of five keratoconic eyes, he first performed overnight orthokeratology and, once the effect was complete, provided the riboflavin cross-linking treatment. After corneal healing, patients were again placed into orthokeratology and then eventually discontinued lens wear to determine the effect. It was concluded that overnight orthokeratology may reshape the keratoconic cornea without significant adverse reactions. The riboflavin-UVA technique was safe, but wasn't able to stabilize the cornea after overnight orthokeratology, although the uncorrected visual acuity did not regress to preoperative levels.

Coding Issues and Resources

Catherine Warren, RN, Executive Director of the National Keratoconus Foundation (www.nkcf.org) mentioned the resources available from NKCF including patient brochures, a national referral list, support groups, newsletters, patient educational seminars and an insurance reimbursement request letter that can be customized to any given office and patient.

Carla Mack, OD, and Clarke Newman, OD, reported on how to code effectively when managing keratoconus and irregular cornea patients, including billing for each of the following separately: Consultation; Refraction; External Photography; Pachymetry; Corneal Topography; and Aberrometry (per eye). Contact Lens Spectrum features a regular column on coding by Dr. Newman, and Dr. Mack wrote an article on how to code for keratoconus that is available at www.nkcf.org and that published in the February 2007 issue of Contact Lens Spectrum (also available in the archive at www.clspectrum.com). Dr. Newman has also created a brochure on how to prescribe medically necessary contact lenses.

Summary

The importance of an annual meeting that emphasizes specialty contact lenses was evident through both the content and attendance of the 2008 Global Keratoconus Congress. It's always a blessing to know practitioners who want to increase their knowledge of contact lens fitting and who exhibit a willingness to not refer challenging irregular cornea cases.

The 2008 GKC provided up-to-date information on contact lens designs and surgical procedures for managing irregular corneas as well as opportunities for hands-on experience. In addition, the global nature of these meetings provides the opportunity to learn about designs and procedures used elsewhere that should soon be available in the United States.

The global meeting will continue in 2009 at the same location in Las Vegas from Jan. 15th to 18th. The theme will focus on specialty contact lenses, including not only those for correcting irregular corneas, but also those for other conditions, notably presbyopia. I hope to see you there. CLS