„ CORNEA & ANTERIOR SEGMENT DISEASE

management of vision, the underly- ing keratoconic disease is unaffected. As many as one in five patients will KERATOCONUS AND require a corneal transplant, and more than half of those will need multiple transplants within 20 years.2,3 In 2016, the FDA approval of three THE CXL STORY products for the corneal strength- ening procedure known as corneal An overview of the role of the corneal strengthening collagen crosslinking (CXL) changed the paradigm for treatment of pro- procedure in managing this ocular disorder. gressive keratoconus. The approved products included two formulations BY GLORIA CHIU, OD, FAAO, FSLS of riboflavin—riboflavin 5´-phosphate ophthalmic solution 0.146% (Photrexa, Avedro) and riboflavin 5´-phosphate rogressive keratoconus is a trying to help patients maintain good in 20% dextran ophthalmic solution degenerative eye disease in which vision, moving as needed from toric 0.146% (Photrexa Viscous, Avedro)— there is ongoing thinning and soft contact lenses to rigid gas per- and a device, the KXL System (Avedro). steepening of weakened corneal meable lenses, and then to hybrid or Long-term follow-up has shown that tissue. It affects approximately scleral lenses. CXL can slow or halt the progression of Pone in 2,000 Americans,1 typically with We have been fortunate in recent keratoconus.4-7 With this CXL system onset in early adolescence and progres- years to see an explosion in new now available in the United States, it sion through early adulthood, although contact lens options for keratoconus, is important to identify and refer pro- older adults may continue to show along with improvements in gressing patients early, even if they still progression (Figure). lens coatings and fitting proce- have good vision with contact lenses. Historically, management of kera- dures that have improved visual Halting progression can preserve these toconus has primarily consisted of outcomes. However, even with good patients’ vision correction options. This

78 | OCTOBER 2019 CORNEA & ANTERIOR SEGMENT DISEASE ƒ

A to rub their eyes. Patients with this habit should be followed carefully. If you are suspicious that a patient has keratoconus, it is advised that topography be performed every 6 months because patients with the condition, especially those in their teens and younger, can progress rapidly. If you start to notice an increase in kera- tometry readings, fluctuating vision, or corneal steepening, refer the patient to a surgeon who performs CXL. B THE REFERRAL RELATIONSHIP Optometrists might fear that referring a patient for topography or a cornea consultation will lead to loss of that patient, but I encourage my colleagues to be open to working with others to manage patients with this condition. Keratoconus referrals have been a significant differen- tiator for my practice. Not only do patients appreciate that I am looking out for Figure. This 23-year-old male patient was referred to a cornea specialist for a corneal collagen crosslinking consult based on changes observed in their best interests, but his keratometry from between 2016 (A) and 2019 (B). Although the Pentacam (Oculus) maps show corneal thickness and elevation, it is important to also the ophthalmology look at the numerical keratometry values, as the color scales are different. There is some ambiguity as to whether this is progressive keratoconus, but the patient is young and already has advanced keratoconus in his left eye, raising the index of suspicion for the fellow eye. colleagues to whom I refer patients for CXL will often article briefly covers what to look for noticeable signs at the slit lamp. then seek my guidance on specialty during the clinical examination, what I recommend a careful manifest contact lenses or other areas. the CXL procedure entails, and what refraction in addition to autorefrac- The surgeon will need to document patients should expect. tion. It is important to look at the axis keratoconus progression for insurance and the amount of cylinder in the pre- coverage of CXL, so it is helpful to EARLY DIAGNOSIS scription in determining the patient’s send refractions and VA measure- Optometrists are likely to be the first BCVA. I also recommend taking a close ments from the patient’s past several to notice ectatic disease. Patients typi- look at the mires on manual keratom- visits, keratometry, topography, and cally come in for a comprehensive eye etry because distorted mires hint at an any other important diagnostic infor- exam because their glasses “just don’t abnormality in the cornea and indicate mation you have that will help to work” anymore. The optometrist might a need to perform corneal topography demonstrate progression over time. already note central corneal striae at or tomography. Once CXL has been performed, the the slit lamp. However, rapid change in Because there is a documented patient should be monitored regularly, refraction, high astigmatism, or BCVA association between eye rubbing and by either an OD or a surgeon, and will worse than 20/20 in a young patient keratoconus,8 it is also important to still need vision correction. The litera- should all be considered red flags for ask young patients and their parents ture has demonstrated a slight flat- possible keratoconus, even without about whether they have a tendency tening effect of the cornea with CXL,

OCTOBER 2019 | 79 „ CORNEA & ANTERIOR SEGMENT DISEASE

which could change patients’ glasses out-of-pocket contribution for the potential corneal changes and for prescriptions (if they are able to wear procedure. Non–FDA-approved pro- adjustments in their glasses and con- glasses), and possibly the contact lens cedures are not covered by insurance. tact lenses. Continued progression of design, but it will not eliminate their keratoconus is possible but not com- refractive error.4,5,9 SETTING PATIENT EXPECTATIONS mon. Studies have shown a continued Keratoconus management is a great With preoperative preparation time, rate of progression after CXL ranging opportunity for optometrists and the need for various checks of corneal from zero to 23%, with the latter ophthalmologists to work together to thickness, and the half hour required seen in a pediatric population with build stronger relationships. for riboflavin penetration, patients can early onset.10 If necessary, CXL can be expect to spend several hours at the repeated, although this is rare. CXL IN A NUTSHELL clinic or surgery center on the day of The riboflavin solutions and device the CXL procedure. Typically, only one RECENT AND FUTURE PROGRESS mentioned above are the only CXL eye is treated at a time, with perhaps a The future for patients with options approved for use in the month or more between the two eyes keratoconus is looking better than United States. Other systems are in if both require CXL. ever, and a number of developments use internationally and may be per- Patients should expect initial dis- are under investigation, including formed under an FDA investigational comfort after the CXL procedure and the aforementioned epi-on CXL device exemption and clinical trial may require management with oral clinical trials, new riboflavin formula- protocols in this country. The proce- pain medications, bandage contact tions, and accelerated UV delivery dure that was evaluated by the FDA lenses, or eye drops. In most cases, times. Patients and clinicians alike requires removal of the epithelium, a the patient will be managed by the have much to look forward to, as 30-minute application of the ribofla- ophthalmology practice, but some CXL techniques and technologies vin solution, and then 30 minutes of referring optometrists may see the continue to evolve. n exposure with 365-nm UV-A light at patient early in the recovery process. 2 9 1. Kennedy RH, Bourne WM, Dyer JA. A 48-year clinical and epidemiologic 3.0 mW/cm . Patients should be aware that they study of keratoconus. Am J Ophthalmol. 1986;101(3):267-273. Although US surgeons can vary may not be fully functional visually 2. Pramanik S, Musch DC, Sutphin JE, Farjo AA. Extended long-term outcomes of penetrating keratoplasty for keratoconus. Ophthalmology. some aspects of this protocol as for a few weeks while the epithelium 2006;113(9):1633-1638. an off-label practice of medicine, heals. Eye care practitioners should 3. Maharana PK, Agarwal K, Jhanji V, Vajpayee RB. Deep anterior lamellar keratoplasty for keratoconus: a review. Eye Contact Lens. 2014;40(6):382-389. they can’t perform CXL with other monitor for infection. 4. Shetty R, Pahuja NK, Nuijts RM, et al. Current protocols of corneal collagen systems or drugs that haven’t been There are no clear guidelines on cross-linking: visual, refractive, and tomographic outcomes. Am J Ophthalmol. 2015;160(2)243-249. approved in the United States unless when patients can or should return 5. O’Brart DP, Patel P, Lascaratos G, et al. Corneal cross-linking to halt the they are participating in a clinical to contact lens wear after CXL, but progression of keratoconus and corneal ectasia: seven-year follow-up. Am J Ophthalmol. 2015;160(6):1154-1163. trial. Likewise, the approved solutions the epithelial defect should be healed 6. Poli M, Lefevre A, Auxenfans C, Burillon C. Corneal collagen cross-linking for cannot be used to perform CXL with beforehand (typically a few weeks to the treatment of progressive corneal ectasia: 6-year prospective outcome in a French population. Am J Ophthalmol. 2015;160(4):654-662. the epithelium on (epi-on CXL). A a month), especially in patients who 7. Raiskup F, Theuring A, Pillunat LE, Spoerl E. Corneal collagen crosslinking phase 3 trial is evaluating the safety wear soft or rigid gas permeable lenses. with riboflavin and ultraviolet-A light in progressive keratoconus: ten-year results. J Cataract Refract Surg. 2015;41(1):41-46. and postoperative patient comfort of Experienced scleral lens wearers might 8. Sugar J, Macsai MS, What causes keratoconus? Cornea. 2012;31(6):716-719. an epi-on protocol. Until epi-on CXL be able to resume wear sooner because 9. Hersh PS, Stulting RD, Muller D, et al; United States Crosslinking Study Group. United States Multicenter Clinical Trial of corneal collagen crosslinking has gone through the FDA’s rigorous these lens designs avoid corneal touch. for keratoconus treatment. Ophthalmology. 2017;124(9):1259-1270. evaluation of safety and efficacy, I I have noticed transient corneal 10. Henriquez MA, Villegas S, Rincon M, et al. Long-term efficacy and safety after corneal collagen crosslinking in pediatric patients: three-year follow-up. will continue to recommend only haze and changes in vision in the first Eur J Ophthalmol. 2018;28(4):415-418. epithelium-off CXL (epi-off CXL). few months after CXL, so I wouldn’t The standard epi-off procedure is advise fitting patients in new lenses at covered by most health insurance 1 month. Ideally, they can continue to GLORIA CHIU, OD, FAAO, FSLS plans (95% of those with commer- use their preoperative vision correction n Associate Professor of Clinical Ophthalmology, cial health insurance), and a J code for up to 3 months until their corneas USC Roski Eye Institute at the University of (J2787) is available for reimbursement and their vision have stabilized. Southern California Keck School of Medicine, of the riboflavin solution. Copays, It is important that patients real- Los Angeles deductibles, and the provider’s net- ize that they will still need to return n [email protected] work status can all affect the patient’s for annual eye exams to monitor n Financial disclosure: Consultant (Avedro)

80 | OCTOBER 2019