KERATOCONUS

Keratoconus: When to Fit Contact Lenses Versus Refer for Surgery

A multitude of lens options are available to successfully manage most patients who have this condition.

By Melissa Barnett, OD, FAAO, FSLS

Keratoconus is a non-inflammatory, self-limiting corneal disease in which the cornea becomes progressively thinner, more distorted, and steeper in curvature (Figure 1), usually beginning in adolescence. It is a bilateral, yet asymmetric corneal ectasia. The abnormal curvature of the cornea causes changes in its refractive power in myopia and astigmatism.

Figure 1. A profile view of a keratoconic cornea.
COURTESY OF STEPHANIE WOO, OD, FAAO, FSLS

Keratoconus has been identified for more than 150 years (Krachmer et al, 1984; Rabinowitz, 1998). The estimated prevalence of keratoconus varies widely around the world, depending on the cohort of patients selected, the geographic location, and the diagnostic criteria used (Gokhale, 2013). For example, the prevalence in Russia has been reported as 2,300 per 100,000 (Gorskova and Sevost’ianov, 1998), whereas in India, the prevalence has been reported as 0.0003% to 2.3% (Jonas et al, 2009). A 48-year clinical and epidemiological study of keratoconus published by Kennedy et al (1986) in Minnesota reported the prevalence to be 0.054%. However, in the last 20 years—with advancements in technology such as corneal topography and, more recently, corneal tomography—corneal ectasias, including keratoconus, have been diagnosed both earlier and with more frequency compared to years before (Belin et al, 2014).

A Closer Look at Keratoconus

The onset of keratoconus typically begins at puberty (Vazirani and Basu, 2013) and is progressive until the third or fourth decade of life, at which time the corneal shape stabilizes. There is no racial or gender predilection (Barnett and Mannis, 2011). Keratoconus is more common in family members, with an increased prevalence of 6% to 19% (Szczotka-Flynn et al, 2008; Wang et al, 2009). As keratoconus is diagnosed relatively early and is managed over decades of time, the lifetime cost of managing keratoconus is significant to patients and payers.

Conventional literature has described keratoconus as a non-inflammatory condition; however, new evidence suggests that inflammation plays a role. An overexpression of inflammatory mediators, including cytokines and interleukin 6 (IL-6), occurs in patients who have keratoconus (Jun et al, 2011; Lema et al, 2009). In addition, keratoconus patients have reduced levels of superoxide dismutase, the function of which is to remove reactive oxygen species known to be associated with inflammatory reactions (Behndig et al, 2001).

Keratoconus commonly initially presents in patients in their teens or early 20s who are unable to obtain clear vision with glasses. They may also report accompanying symptoms such as blurry or distorted vision. The Collaborative Longitudinal Evaluation of Keratoconus (CLEK) study prospectively evaluated 1,209 keratoconus patients annually over eight years. A decrease in high- and low-contrast visual acuity and progressive steepening of the cornea was found in the study subjects (Wagner et al, 2007).

Keratoconus is a chronic condition with a long duration. Using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25), the CLEK study demonstrated that people who have keratoconus have a significantly impaired vision-related quality of life (Kymes et al, 2004). Patients who had entering high-contrast binocular visual acuity of 20/40 or worse and an average steep keratometric reading of steeper than 52D had lower scores on all NEI-VFQ-25 scales except for ocular pain. Contact lens wearers had significantly higher scores on all NEI-VFQ-25 scales compared with non-contact lens wearers except for distance activities, mental health, and dependency.

Multiple clinical signs are indicative of keratoconus. With retinoscopy, a scissoring reflex or “oil-droplet” reflex (Charleaux sign) with irregular myopic astigmatism is evidence of keratoconus. Corneal stromal thinning may accompany corneal ectasia, which is greatest at the apex of the cone. Thinning is most commonly present inferiorly or inferotemporally. Vogt’s striae are fine vertical parallel lines in the posterior stroma and Descemet’s membrane; they disappear with pressure on the globe. A Fleischer’s ring is an iron line formed from deposits of hemosiderin that may surround the cone partially or completely. A cobalt blue filter is useful in visualizing Fleischer’s rings. Rizzuti’s sign is a sharply focused light beam near the nasal limbus produced by lateral corneal illumination.

In advanced keratoconus, Munson’s sign is a V-shaped distortion of the lower eyelid caused by the ectatic conical cornea in down gaze. Acute corneal hydrops (Figure 2) are caused by sudden breaks in Descemet’s membrane accompanied by a sudden decrease in vision and corneal clouding due to corneal edema. Intrastromal clefts or blebs overlying the break may or may not be visible (Rabinowitz, 1998; Gomes et al, 2015). Subepithelial and anterior stromal scarring may be present, resulting from breaks in Bowman’s membrane. In the CLEK study, the incidence of corneal scarring in patients who had keratoconus was 20% (Wagner et al, 2007).

Figure 2. Acute hydrops in a keratoconic cornea.

The pathogenesis of keratoconus is not well understood, and it is difficult to establish a cause and effect relationship. It may be that a genetic predisposition requires a “second hit” or environmental event to elicit progressive disease. Genetic, environmental, and mechanical factors as well as inflammatory mediators all play a role in keratoconus. It has been well established that atopy and vernal keratoconjunctivitis are associated with keratoconus. Furthermore, eye rubbing is more common in keratoconus patients (80%) compared with normal patients (50%) (Rabinowitz, 1998). Therefore, it is helpful to evaluate for systemic atopic disease and ocular allergy in patients who have keratoconus. In addition to avoiding eye rubbing, the Global Consensus on Keratoconus and Ectatic Diseases (GCKED) group recommended the use of topical anti-allergy medication (antihistamines, mast cell stabilizers, anti-inflammatory drops) and topical lubricants in patients who have ocular allergies to reduce the impulse for eye rubbing (Gomes et al, 2015).

Down syndrome and connective tissue disorders, including Marfan syndrome, Ehlers–Danlos syndrome, osteogenesis imperfecta, and Leber congenital amaurosis, are also associated with keratoconus (Rabinowitz, 1998; McGhee, 2009). In addition, floppy eyelid syndrome is associated with keratoconus. Mitral valve prolapse (MVP) is correlated with keratoconus and is prevalent in 2% to 3% of the population. Corneal hydrops affects 5% of patients who have keratoconus; however, the prevalence of MVP in patients who develop corneal hydrops due to keratoconus is 65% (Rabbanikhah et al, 2011).

Patients who have keratoconus are also at a higher risk of obstructive sleep apnea (OSA). Naderan et al (2015) examined the association between OSA prevalence and keratoconus severity. In the keratoconus group, 76 (12.3%) had a high risk for developing OSA compared to 40 (6.5%) in the control group. The authors demonstrated that patients who have more severe keratoconus are at a higher risk of developing OSA. Other risk factors for OSA included a family history of OSA and high body mass index, significantly higher keratometry measurements (mean, flat, and steep Ks), and thinner corneal thickness.

The GCKED group recommended using a combination of techniques in diagnosing keratoconus (Gomes et al, 2015). These include a full corneal thickness map, slit lamp examination, anterior curvature map, and anterior tomographic elevation map. Central corneal pachymetry was determined to be the least reliable indicator for diagnosing keratoconus, as the condition can be present with normal central corneal thickness. In diagnosing early or subclinical keratoconus, the group concluded that tomography such as Scheimpflug or optical coherence tomography is the most accurate and commonly available tests to diagnose early keratoconus. In these patients, posterior corneal elevation abnormalities must be present to determine the diagnosis of keratoconus.

Develop a Stepwise Approach

Over years of managing patients who have keratoconus, I have found that developing a stepwise approach has been beneficial. Each patient has a unique story, which is often complicated by time, multiple visits, and, at times, multiple practitioners. Education is the first step. It is critical to reassure both patients and family members that surgery is not necessarily the first option in managing keratoconus.

Multiple resources are available to educate our patients and their families about keratoconus. The National Keratoconus Foundation (NKCF) provides information and support to the keratoconus patient community through its website www.NKCF.org; the KC-Link, which is an email-based support group for patients; and by phone toll-free at (800) 521-2524. In addition, multiple patient support groups on Facebook, including Keratomania and Keratoconus Group, provide keratoconus support and awareness.

When new patients present with keratoconus, their age, disease severity, presence or absence of corneal scarring, and specific management strategies that have been previously attempted are all factors in determining the best starting option. Fortunately, we have various contact lens designs in our toolbox. There is no one specific contact lens design that is solely used in managing keratoconus; each lens design has unique characteristics that can support our patients through their contact lens wearing experience. It is our role as contact lens practitioners to match the specific contact lens design to each individual patient.

First, an accurate refraction may be helpful. Glasses may be an option, particularly in patients who have mild-to-moderate keratoconus without corneal scarring. Conversely, when the amount of corneal ectasia and irregular astigmatism affects vision, contact lenses can reduce distortion and provide better vision. The presence or absence of corneal scarring significantly influences the decision-making process.

The U.S. Food and Drug Administration (FDA) recently approved Photrexa Viscous, Photrexa, and the KXL System from Avedro, Inc.; based on age and disease progression, it is imperative to discuss corneal collagen cross-linking (CXL), which uses riboflavin (Vitamin B2) and ultraviolet-A (UV-A) light to strengthen the cornea by increasing the cross-links within the collagen fibers. Multiple studies over many years demonstrate the success of CXL in patients who have keratoconus. CXL is widely performed outside of the United States, and prior to its approval it was performed in the United States “off label” and in various clinical trials.

CXL was first reported in human subjects in 2003 by Gregor Wollensak, MD, and colleagues. In patients who had preoperative progressive keratoconus, CXL appeared to halt the progression of corneal ectasia. CXL can also result in flattening of keratometry measurements and improved uncorrected and best-corrected visual acuity (Wollensak et al, 2003; Vinciguerra et al, 2009). Untreated eyes had further steepening of keratometry readings and worsening of best-corrected visual acuity (Wittig-Silva et al, 2008).

All of this said, CXL does not fully correct refractive error or eliminate the need for glasses and contact lenses. However, CXL may ease the fitting of contact lenses in patients who have keratoconus.

Contact Lens Options

In the absence of corneal scarring, soft or soft toric contact lenses may be indicated in early keratoconus, decentered keratoconus, and globus-like keratoconus. If a patient has experienced difficulty with GP lenses, including poor comfort, reduced wearing time, or contact lens intolerance, then soft lenses may be useful. A number of specialty soft contact lenses are available with steeper base curve radii and custom parameters designed for patients who have keratoconus. These lenses have proven to be a valuable tool in my practice.

Corneal GP lenses are ideal for small, central cones or mild cones. A multitude of lens designs, including reverse geometry, exist in custom parameters with diameters ranging in size from 8.0mm to 10.0mm. If a patient has not previously tried GP lenses, I find it helpful to try a GP lens first. However, regardless of the way in which the lens is fit, GP lens wear at baseline is associated with incident corneal scarring (Zadnik et al, 2005). This converted to a 62% increase in an eye’s risk of scarring with GP lens wear in keratoconus compared with eyes that did not wear a lens.

Vision-related quality of life in keratoconus patients was evaluated with the NEI-VFQ-25 (Aydin Kurna et al, 2014). Thirty keratoconus patients—20 GP wearers and 10 non-lens wearers—were compared to 30 healthy patients (control group). All subscales of the NEI-VFQ-25 were lower in the patients who had keratoconus. Contact lens wearers had better best-corrected visual acuity (BCVA) compared with non-contact lens wearers (P = 0.028). Patients who had low visual acuity in the better eye had worse distance vision, social functioning, mental health, and role difficulties. Patients who had low visual acuity in the worse eye had lower general health scores. Overall, vision-related quality of life is worse in patients who have keratoconus. Thus, a successful contact lens fit that improves visual acuity may improve vision-related quality of life.

Another option is a piggyback lens in which a corneal GP lens is fit over a soft lens. This modality is usually indicated if there is poor comfort or significant epithelial disruption with GP lens wear, apical epithelial nodules, or accompanying epithelial basement membrane dystrophy. Improved GP and soft lens materials provide better oxygen permeability and can prevent corneal edema and hypoxia with a piggyback lens system. The base curve of the soft lens can be modified to alter the fitting relationship of the GP lens. A plus-powered soft lens can flatten the GP fit, and a minus-powered soft lens can steepen the GP fit. I prefer a daily replacement soft lens for optimal ocular health and to simplify nightly disinfection.

Hybrid contact lenses have a GP center and a soft skirt. Current hybrid lens designs have evolved and improved over time with novel technology and materials. Consider a hybrid lens if there is poor centration or stability, reduced wearing time, or intolerance with GP lenses. Hashemi et al (2014) evaluated the relative performance of a hybrid lens design for keratoconus and corneal GP lenses. There was no significant difference in visual acuity measurements between the hybrid and GP lens wearers; however, based on the NEI-VFQ-25, the hybrid lens design demonstrated superiority in overall vision-related quality of life (P<0.001), comfort (P<0.001), and foreign body sensation (P<0.013). The hybrid lens demonstrated borderline superiority in lens tolerance (P<0.085).

Frequently in my practice, keratoconus patients have tried all of the prior options without success. Fortunately, we now have numerous excellent scleral lens designs for these patients. The most current nomenclature for scleral lenses has been developed by the Scleral Lens Education Society (SLS) (Table 1).

According to the SLS, scleral lens classification terminology is specified by scleral lens bearing. A corneal lens rests completely on the cornea. A corneo-scleral lens rests partially on the cornea and partially on the sclera. A scleral lens rests entirely on the sclera, regardless of diameter. Horizontal visible iris diameter (HVID) is used to distinguish between mini-scleral (overall diameter up to 6mm larger than the HVID) and large scleral (overall diameter more than 6mm larger than the HVID) lenses.

Scleral lenses have many indications, including primary corneal ectasias; keratoconus, keratoglobus, and pellucid marginal degeneration; intolerance to small-diameter GP lenses; and failure with piggyback or hybrid lenses (van der Worp, 2010). The multitude of other scleral lens indications will not be reviewed in this article. Scleral lenses are contraindicated for corneas that have significant edema from reduced endothelial cell count (Bennett, 2008; DeNaeyer and Breece, 2009). In general, 800 cells per mm² is the minimal amount needed to fit scleral lenses with success. Caution is advised when fitting after corneal surgery or in systemically compromised patients.

Scleral lenses make the irregular corneal surface of patients who have keratoconus more uniform and regular (Schornack and Patel, 2010). Other benefits of scleral lenses include the ability to completely clear the corneal surface and to provide good centration and stable visual acuity while maintaining excellent comfort throughout the day. Various scleral lens diameters may be used depending on the amount of corneal ectasia. Large-diameter scleral lenses are able to create a larger tear reservoir and provide more clearance between the lens and the cornea, which is useful if there is a significant difference in corneal sagittal height (ectasia). Smaller-diameter scleral lenses may be easier to handle and can be used when there is less corneal ectasia. Other factors to consider are oxygen permeability, corneal physiology, conjunctival and scleral anatomy, lens handling, and potential complications. In my practice, scleral lenses have provided a positive life-changing experience for many patients who have keratoconus. These lenses allow my patients to work, see their families, drive, enjoy life, and function independently with excellent vision and comfort.

A retrospective study evaluated the quality of life in keratoconus patients wearing scleral lenses compared to patients after penetrating keratoplasty (Picot et al, 2015). Quality of life was evaluated before and after scleral lens adaptation. Forty-seven patients (83 eyes) with a history of GP lens intolerance were fit with scleral lenses on one or both eyes. Fifty-six eyes with keratoconus were compared to 27 post-keratoplasty eyes. NEI-VFQ-25 scores with scleral lenses were significantly higher compared to those without scleral lenses. Scleral lenses significantly improved the quality of life for patients who had failed or were intolerant to conventional GP contact lenses.

Surgical Options

When a patient has exhausted all contact lens and scleral lens options, has significant corneal scarring and/or corneal ectasia, or is truly unable to succeed with contact or scleral lens handling, then it is time to consider corneal surgery. As keratoconus is bilateral but often asymmetric, if surgery is to be considered, it is ideal to fit the contralateral (non-surgical) eye with a contact lens to obtain the best possible fit, vision, and comfort prior to surgery in the opposite eye.

The GCKED group reported that CXL is currently available and commonly performed using various techniques by 83.3% of the group (Gomes et al, 2015). It was agreed that CXL should always be performed, regardless of age, in keratoconic eyes that demonstrate evidence of progression. That said, CXL is rarely indicated in patients over age 40 (Gomes et al, 2015).

Other than CXL, anterior lamellar keratoplasty (ALK), specifically descemetic deep ALK (dDALK), and penetrating keratoplasty (PK), are the most common surgical techniques used in treating keratoconus. Deep anterior lamellar keratoplasty (DALK) is a partial-thickness corneal transplant in which only the donor stroma is used, maintaining the recipient’s own Descemet’s membrane and endothelium (John et al, 2007). With direct open dissection, the stroma is removed layer by layer until clear stroma remains or Descemet’s membrane is exposed. However, the rate of intraoperative perforation is high (greater than 30% to 35%), and often the surgeon fails to bare Descemet’s membrane (Cursiefen et al, 2016).

There have been advancements in surgical instrumentation and techniques for DALK, including the “big bubble” technique, which uses an air bubble to dissect the plane between corneal stroma and Descemet’s membrane (Anwar and Teichmann, 2002). Then, the donor cornea (after stripping Descemet’s membrane) is sutured onto the host cornea. Because DALK is not an intraoperative procedure, the host endothelium is retained, thereby removing the risk of endothelial graft rejection and improving graft survival. Additionally, endothelial immune reactions do not occur, as the recipient’s endothelium remains untouched (Cursiefen et al, 2016). This is useful in young patients who have keratoconus and atopic disease and in patients who have an increased risk of graft rejection. However, DALK is technically challenging, has a significant learning curve, and complications may occur. The GCKED group agreed that contact lens intolerance is the most important factor when determining the need for DALK (Gomes et al, 2015).

Approximately 10% to 20% of keratoconus patients will require a penetrating keratoplasty (PK) in their lifetime (Patel et al, 2005). The first step is the preparation of the donor tissue (Barron and McDonald, 1996). Next, a corneal button that is 0.25mm to 0.50mm larger than the diameter of the host corneal opening is used. A slightly larger diameter can help reduce excessive postoperative corneal flattening, reduce the risk of secondary glaucoma, and improve wound closure. Next, the host cornea is trephined, the anterior chamber is filled with viscoelastic, and the donor tissue is placed on the recipient’s eye with the endothelial side down. The cornea is then sutured in place with either interrupted or continuous sutures.

There are long-term complications of PK; 20% to 30% of patients develop an immunologic rejection, and 14% to 29% develop long-term graft failure (Rahman et al, 2009). The GCKED group agreed that significant corneal scarring is the most important factor when considering PK (Gomes et al, 2015). Other factors included contact lens intolerance or a patient not wanting to wear contact lenses, failure of other surgical strategies, thin corneal thickness, severe keratoconus, and the potential risk of acute hydrops. According to the GCKED group, intracorneal ring segments (ICRSs) are also used with less frequency (Gomes et al, 2015). Other techniques including superficial keratectomy (manual or phototherapeutic keratectomy), photorefractive keratectomy (PRK), conductive keratoplasty, and clear lens extraction were rarely used.

ICRSs are arc-like, PMMA segments that are surgically inserted into the deep corneal stroma (Kennedy et al, 1986). They act as a passive spacing element that separates corneal lamellae. Their insertion shortens the arc length of the anterior corneal surface, which flattens the central cornea. Thus, the prolate shape of the cornea is maintained over the central optical zone. Since 2004, only Intacs (Addison Technology, distributed in the United States by Oasis Medical) have received FDA approval to treat keratoconus. Intacs come in different sizes, and there are potentially many different combinations that can be used to flatten the central cornea and reduce astigmatism (Colin and Malet, 2007; Rabinowitz, 2006). Other ICRSs are also available outside of the United States.

The surgical procedure involves creating corneal tunnels or channels at about 70% of the corneal depth, making a corneal pocket on each side of the incision; inserting ICRSs into the respective corneal tunnels; and then suturing the incision sites (Colin and Malet, 2007). The segments are separated by approximately 2.0mm. These pockets have been typically created using a mechanical spreader; however, femtosecond lasers are also used to create the channels (Carrasquillo et al, 2007; Ertan and Colin, 2007). Advantages to using a femtosecond laser include more rapid, more precise, and easier channel creation and centration. In addition, there is less risk for epithelial defects during channel creation, a lower risk for posterior corneal perforation, and a reduced risk of infectious keratitis due to the absence of a foreign element being placed in the cornea. The femtosecond laser results in better reduction in average keratometry, spherical equivalent, best-corrected visual acuity, uncorrected visual acuity, and surface asymmetry index versus the mechanical spreader (Rabinowitz et al, 2006).

Cost of Surgery One consideration that is not trivial is the economic burden of corneal transplantation. Rebenitsch et al (2011) evaluated the costs of clinic visits, fitting fees, contact lenses, surgical procedures, and complications in keratoconus patients. The expected lifetime cost for treatment of keratoconus compared to myopia was $25,168. Significant factors for the lifetime cost were the probability of initial corneal transplant and a subsequent regraft. Routine care costs were not significant in the lifetime cost of care.

Summary

When managing patients who have keratoconus, it is optimal to consider CXL early, especially if disease progression is evident. Contact lenses are advantageous in most patients who have keratoconus. If possible, deferring corneal transplantation until absolutely needed is the preferred approach. CLS

For references, please visit www.clspectrum.com/references and click on document #247.

Dr. Barnett is the principal optometrist at the UC Davis Eye Center in Sacramento, CA. She is a Fellow of the American Academy of Optometry, a Diplomate of the American Board of Certification in Medical Optometry, and she serves on the Boards of Women of Vision, Gas Permeable Lens Institute, Ocular Surface Society of Optometry, and the Scleral Lens Education Society (SLS). She is an advisor to AccuLens, Alcon, Alden Optical, Allergan, CooperVision, Bausch + Lomb, Novabay, Johnson & Johnson Vision Care, Zeiss, and the SLS, and she has received honoraria and/or travel expenses from Alcon, AccuLens, Alden Optical, Allergan, Johnson & Johnson Vision Care, Bausch + Lomb, and the SLS.