With more patients turning to corneal collagen crosslinking to manage keratoconus, optometrists are honing their comanagement roles and building their knowledge around this procedure. With this first part of Optometry Advisor’s 3-part series, Komal Patel, OD, and Nate Lighthizer, OD, FAAO, detail crosslinking basics, patient selection, the referral process, and preprocedural workup strategies.
With the emergence of new technologies and therapies, optometrists have better odds of successfully managing keratoconus, preserving vision, and improving patients’ quality of life today than was previously possible. High on the list of these new treatment modalities is the procedure corneal collagen crosslinking (CXL). This is commonly performed in an ophthalmology setting, but optometrists play a vital role in pre- and post-CXL patient care.
Internalizing these comanagement strategies — from evaluating and diagnosing keratoconus to CXL patient selection to preparing the patient for surgery — are all elemental in providing optimal patient outcomes.
Identifying and Managing Keratoconus
Keratoconus is a noninflammatory, progressive corneal ectasia that typically presents during childhood. Multiple genetic, environmental, and systemic factors may influence the risk of developing keratoconus, including a family history of keratoconus, eye rubbing, atopy, Down syndrome, and collagen vascular disorders.1 This ectasia initially presents with worsening best-corrected visual acuity with increasing, and often irregular, astigmatism. The degradation of corneal collagen results in corneal thinning and steepening.2
Studies report keratoconus has a worldwide incidence of 86 in 100,000 people, and prevalence of 40 to 100 per 100,000 people.1,4 In the United States, prevalence is at least 55 cases per 100,000 people.5 Technological and diagnostic improvements continue to identify patients with keratoconus, demonstrating that the condition is not as rare as previously thought.
Early stage keratoconus management involves refractive correction with spectacles and soft contact lenses. As the condition progresses, rigid gas permeable and scleral lenses are typically needed. In severe or end-stage disease, full-thickness corneal transplantation, or penetrating keratoplasty, is usually necessary. Until 2016, these were the only management options for keratoconus. But that year, the US Food and Drug Administration (FDA) approved CXL as a treatment for keratoconus and post-refractive surgery ectasia. Research shows that the procedure is able to reduce disease progression and the need for corneal transplantation.1,6
Corneal Crosslinking Explained
CXL is a procedure used to slow or halt the progression of keratoconus and corneal ectasia. Pellucid marginal degeneration and post-refractive surgery ectasia resulting from laser-assisted in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), and small incision lenticule extraction (SMILE) can also be treated with CXL.2,3
CXL strengthens the cornea, increasing corneal tissue rigidity by more than 300% via covalent bonds between collagen fibrils and proteoglycans.7,8 The procedure is FDA-approved for patients aged 14 to 65 years, but off-label use has been performed in children as young as 8 years.2 Contraindications include corneal thickness thinner than 400 μm, prior herpetic corneal infection, severe corneal scarring, severe ocular surface disease, pregnancy, and breastfeeding.
Insurance carriers may require that patients exhibit specific clinical manifestations in order to be eligible for third party payment. These criteria may include a 1 diopter (D) change or greater in steepest keratometry value within 24 months, a 1 D change or greater in cylinder measured by subjective refraction within 24 months, a 0.1 mm or greater base curve reduction in rigid gas permeable lenses within 24 months, or a progressive decrease in best-corrected visual acuity.2
The standard crosslinking procedure follows the Dresden protocol which involves removing up to 9 mm of the central corneal epithelium after instilling topical anesthesia. This is performed with a scalpel or blunt spatula, with or without alcohol, to allow the photosensitizing riboflavin to penetrate the stroma. The clinician administers riboflavin 0.1% in a 20% dextran solution to the cornea every 2 minutes for 30 minutes before applying UVA light at a wavelength of 365 nm and 3 mW/cm2 irradiance for another 30 minutes. The riboflavin solution is reapplied every 2 minutes during UVA irradiation.3 A bandage contact lens is placed on the eye at the conclusion of the procedure and left there until re-epithelialization. Antibiotic, steroid, preservative free artificial tear drops, and if needed, nonsteroidal anti-inflammatory drugs (NSAID) are prescribed for 2 to 4 weeks following CXL.9 Follow up visits are typically conducted at day 1, days 4 to 7, 1 month, 3 months, and 6 to 12 months following the procedure.2
Minor complications are often related to inflammation and abnormal healing and include corneal haze or stromal opacities, punctate keratitis, corneal striae, or peripheral sterile infiltrates. Infectious keratitis is a less common complication occurring in only 0.0017% of cases in countries with high rates of corneal infections.1,2,6
Protocols may vary between different centers, but researchers suggest that optometrists should provide surgeons with specific information in their referrals.2,7 Among these pertinent pieces of information are a clinical history, uncorrected visual acuity, spectacle refraction and best-corrected visual acuity, biomicroscopy evaluation including a dilated fundus examination, intraocular pressure, tomography or topography imaging (Scheimpflug-style imaging preferred), pachymetry, keratometry, and current keratoconus management method. 2,7
Some crosslinking centers perform a rigid contact lens over-refraction to determine the patient’s best-corrected visual acuity, but this is not required when referring patients for CXL.
Patients may expect visual improvement following the procedure, so clinicians must explain that CXL is not a refractive procedure. It does not reverse or heal corneal ectasia or result in 20/20 vision. Rather, it prevents progression and future complications of ectasia. Optometrists must emphasize that glasses or contact lenses will still be needed after CXL.7
Where and When to Refer Patients
Optometrists are on the forefront of screening and diagnosing patients with keratoconus, so it is imperative that they understand what is expected during pre and postprocedural periods. Patients affected by corneal ectasia should be referred to a local ophthalmologist or optometrist (in states where CXL is within scope of practice) who performs corneal crosslinking. Formulating professional relationships with local ophthalmologists and crosslinking centers is critical and can aid in a smooth transition between eye care providers.
Similar to many other ocular ailments, early detection is key in improving patient outcomes. Research shows that best-corrected visual acuity and astigmatism experience greater improvements at 12 and 24 months, respectively, when CXL is performed at an early stage compared with later stages of the disease.10
The Optometrist’s Role in Post-CXL Care
Patients are usually able to continue their normal daily activities within 1 to 2 weeks after undergoing CXL. Once the surgeon’s task has been completed, the patient is released to the optometrist’s care to monitor disease progression and provide the most optimal vision correction. Although vision may not stabilize for several months, clinicians often finalize a spectacle and contact lens prescription 4 to 8 weeks following the procedure to allow the patient to function to the best of their ability.9
Eye pain, light sensitivity, blurred vision, and redness are common in the acute post-CXL period and typically last 3 to 5 days until re-epithelialization. Post-CXL ocular pain may be greater among patients undergoing CXL compared with those who received treatments such as PRK because CXL induces oxidative stress and releases free oxygen radicals, which may lead to a greater sensation of pain.11
Following CXL, visual acuity fluctuations are not uncommon. They frequently worsen within the first month and return to baseline by month 3. Vision tends to stabilize by months 6 to 12, and patients may experience mild visual improvements during this time.7
A 10-year study revealed a reduction in keratoconus progression in 24 patients (34 eyes) who underwent CXL.12 Researchers noted statistically significant reductions in mean apical K values (61.5 to 55.3 D) and maximum and minimum K values, along with a 0.14 logMAR improvement in visual acuity.12 The investigation suggests that CXL has a good safety profile, long-term condition stabilization, and reduces the need for corneal transplantation.12
Economic and Quality of Life Effects of CXL
A cost-effectiveness analysis revealed that economic value is maximized when CXL is performed during early stages of the disease or at a younger age.5 This may lead to increased work productivity, decreased financial burden and improved quality of life. Patients undergoing CXL were 25.9% less likely to undergo corneal transplantation and had 28 fewer years with advanced keratoconus compared with patients with keratoconus who did not receive the procedure.5 Medical costs for patients with keratoconus who underwent CXL versus patients with keratoconus who did not undergo CXL were $30,994 and $39,671, respectively.5 This was associated with a lifetime cost-savings of $43,759 per patient and a national savings of $150 million.5 Before corneal crosslinking, an estimated 11% to 27% of people with keratoconus needed corneal transplantation. That number has decreased with the FDA’s approval of CXL.1
CXL significantly improves quality of life and holds substantial long-term economic and safety benefits for patients with keratoconus. This lends support to the idea that all patients with keratoconus should be referred for a CXL consult at earlier stages of the disease to preserve their vision and improve their quality of life for years to come.
- Beckman KA, Gupta PK, Farid M, et al. Corneal crosslinking: current protocols and clinical approach. J Cataract Refract Surg. 2019;45(11):1670–1679. doi:10.1016/j.jcrs.2019.06.027
- Freisberg L, Lighthizer N, Skorin L Jr, Stonecipher K, Zimmerman AB . Corneal cross-linking. In: The Ophthalmic Laser Handbook. Wolters Kluwer; 2022:165–176.
- Subasinghe SK, Ogbuehi KC, Dias GJ. Current perspectives on corneal collagen crosslinking (CXL). Graefes Arch Clin Exp Ophthalmol. 2018;256(8):1363–1384. doi:10.1007/s00417-018-3966-0
- Bak‐Nielsen S, Ramlau-Hansen CH, Ivarsen A, Plana-Ripoll O, Hjortdal J. Incidence and prevalence of keratoconus in Denmark – an update. Acta Ophthalmol. 2019;97(8):752–755. doi:10.1111/aos.14082
- Lindstrom RL, Berdahl JP, Donnenfeld ED, et al. Corneal cross-linking versus conventional management for keratoconus: a lifetime economic model. J Med Econ. 2021;24(1):410–420. doi:10.1080/13696998.2020.1851556
- Glaukos. Photrexa® Viscous and Photrexa® ISI. Accessed July 25, 2022. https://www.glaukos.com/important-safety-information/photrexa-viscous-and-photrexa-isi/#section-
- Hernández-Quintela E, Sánchez-Huerta V, García-Albisua AM, et al. Preoperative evaluation of keratoconus and ectasia. In: Refractive Surgery. 3rd ed. Elsevier; 2019:170–180.
- Napolitano P, Tranfa F, D’Andrea L, et al. Topographic outcomes in keratoconus surgery: Epi-on versus epi-off iontophoresis corneal collagen cross-linking. J Clin Med. 2022;11(7):1785. doi:10.3390/jcm11071785
- Porter, D. Corneal cross-linking. American Academy of Ophthalmology. Published January 26,2022. Accessed July 25, 2022. https://www.aao.org/eye-health/treatments/corneal-cross-linking-2.
- Gassel CJ, Röck D, Konrad EM, Blumenstock G, Bartz-Schmidt KU, Röck T. Impact of keratoconus stage on outcome after corneal crosslinking. BMC Ophthalmol. 2022;22(1):207. doi:10.1186/s12886-022-02425-8
- Zarei-Ghanavati S, Jafarpour S, Radyn-Majd A, Hosseinikhah-Manshadi H. Evaluation of early postoperative ocular pain after photorefractive keratectomy and corneal crosslinking. J Cataract Refract Surg. 2018;44(5):566–570. doi:10.1016/j.jcrs.2018.02.019
- Raiskup F, Theuring A, Pillunat LE, Spoerl E. Corneal collagen crosslinking with riboflavin and ultraviolet-A light in progressive keratoconus: ten-year results. J Cataract Refract Surg. 2015;41(1):41–46. doi:10.1016/j.jcrs.2014.09.033