Corneal cross-linking

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Corneal cross-linking
Cross-linking procedure, UV light source.jpg
Cross-linking procedure, UV light source [1]
Other namesCross-linking, CXL, C3-R, CCL, KXL
CPT 0402T

Corneal cross-linking (CXL) with riboflavin (vitamin B2) and UV-A light is a surgical treatment for corneal ectasia such as keratoconus, PMD, and post-LASIK ectasia.

Contents

It is used in an attempt to make the cornea stronger. According to a 2015 Cochrane review, there is insufficient evidence to determine if it is useful in keratoconus. [2] In 2016, the US Food and Drug Administration approved riboflavin ophthalmic solution crosslinking based on three 12-month clinical trials. [3]

Medical uses

A 2015 Cochrane review found that the evidence on corneal cross-linking was insufficient to determine if it is an effective procedure for the treatment of keratoconus. [2]

Adverse effects

Among those with keratoconus who worsen, CXL may be used. In this group, the most common side effects are haziness of the cornea, punctate keratitis, corneal striae, corneal epithelium defect, and eye pain. [4] In those who use it after post-LASIK ectasia, the most common side effects are haziness of the cornea, corneal epithelium defect, corneal striae, dry eye, eye pain, punctate keratitis, and sensitivity to bright lights. [5]

There are no long-term studies about crosslinking effect on pregnancy and lactation. According to a manufacturer crosslinking should not be performed on pregnant women. [5]

Cautions

People undergoing crosslinking should not rub their eyes for the first five days after the procedure. [5]

Procedure

Removed corneal epithelium during CCR operation on an eye with post-LASIK complication, from Kymionis et al., 2009 Intraoperative pachymetric-guided corneal epithelium removal during corneal collagen cross linking in patient with post-LASIK corneal ectasia and inferior corneal thinning.jpg
Removed corneal epithelium during CCR operation on an eye with post-LASIK complication, from Kymionis et al., 2009

Corneal cross-linking involves application of riboflavin solution to the eye that is activated by illumination with UV-A light for approximately 30 or fewer minutes. The riboflavin causes new bonds to form across adjacent collagen strands and proteoglycans in the stromal layer of the cornea, which recovers and preserves some of the cornea's mechanical strength. The corneal epithelial layer is generally removed to increase penetration of the riboflavin into the stroma, a procedure known as the Dresden protocol. [7]

People that are considered for treatment must undergo an extensive clinical workup, including corneal tomography, computerized corneal topography, endothelial microscopy, ultrasound pachymetry, b-scan sonography, keratometry and biomicroscopy.[ citation needed ]

History

The technique was first developed in Germany in 1997 by Eberhard Spoerl and his team at the Dresden University of Technology. [8] [9]

Approvals and clinical trials

In Germany, CXL has been used in patients with keratoconus since 1998, [8] and in Italy, routine interventions have been successfully performed since 2005. [10] The standard (Dresden) CXL protocol with epithelium removal, is approved for use throughout Europe.

In the United States, clinical trials commenced only in 2008. Based on three 12-month clinical trials, the US Food and Drug Administration approved riboflavin ophthalmic solution and Avedro's KXL system for crosslinking on 18 April 2016, for the treatment of progressive keratoconus, and on 19 July 2016, for corneal ectasia after refractive surgery, making them the first FDA approved treatment for keratoconus and post-LASIK ectasia. [3] [11]

Research

Research studying the safety and efficacy of corneal cross-linking is ongoing. [4] [12] [13]

Transepithelial or epithelium-on (epi-on) cross-linking is a technique which was first performed in 2004 in the U.S., [14] the corneal epithelium layer is left intact. [15] in this technique, because the epithelium is not removed, riboflavin loading requires more time than with epi-off techniques, and may be less effective, as keratoconus progression may be more likely in epi-on procedures. [16]

Contact lens-assisted cross-linking (CACXL) may be performed for people with corneal stromal thickness between 350 μm to 400 μm after epithelial removal. in this method a pre-corneal riboflavin film, a riboflavin-soaked UV barrier-free soft contact lens of negligible power and a pre-contact lens riboflavin film are used to decrease UV irradiance to safe levels at the level of the endothelium. [17] [18]

Topography-guided crosslinking relies on an active eye tracker to allow a patterned delivery of UV light. Both the power and pattern can be programmed into the unit based on the topography of the individual's eyes. [19]

Accelerated crosslinking allows a shorter treatment time by delivering the same energy more quickly, compared to the standard crosslinking procedure, which involves 3 mW of UV-A exposure for 30 minutes. [19] Some hospitals are using this accelerated CXL technique delivering a similar amount of UV-A energy in eight to ten minutes, following research showing the cornea may better tolerate this shorter burst of UV-A. [20] [21] However, a recent study using the real-world registry data showed that the standard (Dresden) CXL was associated with better visual and corneal curvature outcomes 5-years post-surgery. [12]

Related Research Articles

<span class="mw-page-title-main">Keratoconus</span> Medical condition involving the eye

Keratoconus (KC) is a disorder of the eye that results in progressive thinning of the cornea. This may result in blurry vision, double vision, nearsightedness, irregular astigmatism, and light sensitivity leading to poor quality-of-life. Usually both eyes are affected. In more severe cases a scarring or a circle may be seen within the cornea.

<span class="mw-page-title-main">Cornea</span> Transparent front layer of the eye

The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is approximately 43 dioptres. The cornea can be reshaped by surgical procedures such as LASIK.

<span class="mw-page-title-main">LASIK</span> Corrective ophthalmological surgery

LASIK or Lasik, commonly referred to as laser eye surgery or laser vision correction, is a type of refractive surgery for the correction of myopia, hyperopia, and an actual cure for astigmatism, since it is in the cornea. LASIK surgery is performed by an ophthalmologist who uses a laser or microkeratome to reshape the eye's cornea in order to improve visual acuity.

<span class="mw-page-title-main">Photorefractive keratectomy</span> Refractive eye surgery procrdure

Photorefractive keratectomy (PRK) and laser-assisted sub-epithelial keratectomy (LASEK) are laser eye surgery procedures intended to correct a person's vision, reducing dependency on glasses or contact lenses. LASEK and PRK permanently change the shape of the anterior central cornea using an excimer laser to ablate a small amount of tissue from the corneal stroma at the front of the eye, just under the corneal epithelium. The outer layer of the cornea is removed prior to the ablation.

<span class="mw-page-title-main">Radial keratotomy</span> Refractive surgical procedure to correct myopia (nearsightedness

Radial keratotomy (RK) is a refractive surgical procedure to correct myopia (nearsightedness). It was developed in 1974 by Svyatoslav Fyodorov, a Russian ophthalmologist. It has been largely supplanted by newer, more accurate operations, such as photorefractive keratectomy, LASIK, Epi-LASIK and the phakic intraocular lens.

<span class="mw-page-title-main">Refractive surgery</span> Surgery to treat common vision disorders

Refractive surgery is optional eye surgery used to improve the refractive state of the eye and decrease or eliminate dependency on glasses or contact lenses. This can include various methods of surgical remodeling of the cornea (keratomileusis), lens implantation or lens replacement. The most common methods today use excimer lasers to reshape the curvature of the cornea. Refractive eye surgeries are used to treat common vision disorders such as myopia, hyperopia, presbyopia and astigmatism.

<span class="mw-page-title-main">Corneal transplantation</span> Surgical procedure of repairing corneal tissue to treat corneal blindness

Corneal transplantation, also known as corneal grafting, is a surgical procedure where a damaged or diseased cornea is replaced by donated corneal tissue. When the entire cornea is replaced it is known as penetrating keratoplasty and when only part of the cornea is replaced it is known as lamellar keratoplasty. Keratoplasty simply means surgery to the cornea. The graft is taken from a recently deceased individual with no known diseases or other factors that may affect the chance of survival of the donated tissue or the health of the recipient.

<span class="mw-page-title-main">Scleral lens</span> Large contact lens resting on the sclera, creating a tear-filled vault over the cornea

A scleral lens, also known as a scleral contact lens, is a large contact lens that rests on the sclera and creates a tear-filled vault over the cornea. Scleral lenses are designed to treat a variety of eye conditions, many of which do not respond to other forms of treatment.

<span class="mw-page-title-main">Intrastromal corneal ring segment</span> Small device implanted in the eye to correct vision

An intrastromal corneal ring segment (ICRS) (also known as intrastromal corneal ring, corneal implant or corneal insert) is a small device surgically implanted in the cornea of the eye to correct vision. Two crescent or semi-circular shaped ring segments are inserted between the layers of the corneal stroma, one on each side of the pupil, This is intended to flatten the cornea and change the refraction of light passing through the cornea on its way into the eye.

<span class="mw-page-title-main">Pellucid marginal degeneration</span> Degenerative corneal condition

Pellucid marginal degeneration (PMD) is a degenerative corneal condition, often confused with keratoconus. It typically presents with painless vision loss affecting both eyes. Rarely, it may cause acute vision loss with severe pain due to perforation of the cornea. It is typically characterized by a clear, bilateral thinning (ectasia) in the inferior and peripheral region of the cornea, although some cases affect only one eye. The cause of the disease remains unclear.

<span class="mw-page-title-main">Mark Cohen (surgeon)</span> Canadian laser eye surgeon

Mark Cohen is a Canadian laser eye surgeon who practices in Montreal and Toronto. In 2001, he and Avi Wallerstein founded LASIK MD, Canada's largest provider of laser refractive surgery. As of 2013, LASIK MD performs over sixty percent of all laser vision correction procedures in Canada. He is one of only 14 certified C-LASIK instructors in North America.

<span class="mw-page-title-main">Avi Wallerstein</span> Canadian ophthalmologist and laser eye surgeon

Avi Wallerstein is a Canadian ophthalmologist and laser eye surgeon who specializes in surgical vision correction, also termed refractive eye surgery. He practises in Montreal and Toronto. In 2001, he co-founded LASIK MD with Mark Cohen. LASIK MD is Canada's largest provider of laser refractive surgery, performing over 60,000 procedures a year. He is one of only 14 certified CLasik instructors in North America.

<span class="mw-page-title-main">Gholam A. Peyman</span> Iranian-American ophthalmologist and retina surgeon known for inventing LASIK eye surgery

Gholam A. Peyman is an Iranian American ophthalmologist, retina surgeon, and inventor. He is best known for his invention of LASIK eye surgery, a vision correction procedure designed to allow people to see clearly without glasses. He was awarded the first US patent for the procedure in 1989.

Peter S. Hersh is an American ophthalmologist and specialist in LASIK eye surgery, keratoconus, and diseases of the cornea. He co-authored the article in the journal Ophthalmology that presented the results of the study that led to the first approval by the U.S. Food and Drug Administration (FDA) of the excimer laser for the correction of nearsightedness in the United States. Hersh was also medical monitor of the study that led to approval of corneal collagen crosslinking for the treatment of keratoconus.

Post-LASIK ectasia is a condition similar to keratoconus where the cornea starts to bulge forwards at a variable time after LASIK, PRK, or SMILE corneal laser eye surgery. However, the physiological processes of post-LASIK ectasia seem to be different from keratoconus. The visible changes in the basal epithelial cell and anterior and posterior keratocytes linked with keratoconus were not observed in post-LASIK ectasia.

<span class="mw-page-title-main">Corneal hydrops</span> Medical condition

Corneal hydrops is an uncommon complication seen in people with advanced keratoconus or other corneal ectatic disorders, and is characterized by stromal edema due to leakage of aqueous humor through a tear in Descemet's membrane. Although a hydrops usually causes increased scarring of the cornea, occasionally it will benefit a patient by creating a flatter cone, aiding the fitting of contact lenses. Corneal transplantation is not usually indicated during corneal hydrops.

Corneal ectatic disorders or corneal ectasia are a group of uncommon, noninflammatory, eye disorders characterised by bilateral thinning of the central, paracentral, or peripheral cornea.

<span class="mw-page-title-main">Farhad Hafezi</span> Swiss eye surgeon and researcher (born 1967)

Farhad Hafezi is a prominent Swiss eye surgeon and researcher. Hafezi first gained recognition as a leading retina researcher in 1994, having been the first to discover a gene responsible for light-induced retinal degeneration. However, he changed his research focus to the cornea in 2003, and it is this work, particularly on corneal collagen cross-linking (CXL), which he helped pioneer, and advanced laser refractive surgery that he is internationally known for today. Hafezi's current clinical and laboratory research is focused on gaining a better understanding of the cornea. His research group at the University of Zurich has three main research foci:

PiXL is a modern non-invasive non-surgical vision correction procedure.

Anastasios John Kanellopoulos is a Greek-American eye surgeon specializing in corneal transplantation, cornea crosslinking for keratoconus, complicated cataract surgery and complicated glaucoma. Widely known for research and clinical contributions in micro-incision cataract, customized laser refractive surgery and corneal cross-linking propagation and most innovations, reducing corneal transplants for advanced keratoconus.

References

  1. ↑ Renesto Ada, C; Sartori, M; Campos, M (January–February 2011). "[Cross-linking and intrastromal corneal ring segment]". Arquivos Brasileiros de Oftalmologia. 74 (1): 67–74. doi: 10.1590/s0004-27492011000100017 . PMID   21670914.
  2. 1 2 Sykakis, E; Karim, R; Evans, JR; Bunce, C; Amissah-Arthur, KN; Patwary, S; McDonnell, PJ; Hamada, S (24 March 2015). "Corneal collagen cross-linking for treating keratoconus" (PDF). The Cochrane Database of Systematic Reviews. 3 (3): CD010621. doi:10.1002/14651858.CD010621.pub2. PMID   25803325.
  3. 1 2 Lowes, Robert (18 April 2016). "FDA Approves Photrexa for Corneal Crosslinking in Keratoconus". Medscape.com.
  4. 1 2 Kandel, Himal; Nguyen, Vuong; Ferdi, Alex C.; Gupta, Aanchal; Abbondanza, Marco; Sullivan, Laurence; Apel, Andrew; Watson, Stephanie L. (21 April 2021). "Comparative Efficacy and Safety of Standard Versus Accelerated Corneal Crosslinking for Keratoconus: 1-Year Outcomes From the Save Sight Keratoconus Registry Study". Cornea. Publish Ahead of Print (12): 1581–1589. doi:10.1097/ICO.0000000000002747. ISSN   0277-3740. PMID   33935236. S2CID   233483415.
  5. 1 2 3 "PHOTREXA VISCOUS- riboflavin 5-phosphate in 20% dextran ophthalmic solution/ drops PHOTREXA- riboflavin 5-phosphate ophthalmic solution/ drops". DailyMed. U.S. NATIONAL LIBRARY OF MEDICINE.
  6. ↑ Kymionis GD, Diakonis VF, Coskunseven E, Jankov M, Yoo SH, Pallikaris IG (2009). "Customized pachymetric guided epithelial debridement for corneal collagen cross linking". BMC Ophthalmology. 9: 10. doi: 10.1186/1471-2415-9-10 . PMC   2744909 . PMID   19715585.
  7. ↑ Spoerl E, Wollensak G, Dittert DD, Seiler T (2004). "Thermomechanical behavior of collagen-cross-linked porcine cornea". Ophthalmologica. 218 (2): 136–40. doi:10.1159/000076150. PMID   15004504. S2CID   25416319.
  8. 1 2 SPOERL, EBERHARD; HUHLE, MICHAEL; SEILER, THEO (January 1998). "Induction of Cross-links in Corneal Tissue". Experimental Eye Research. 66 (1): 97–103. doi:10.1006/exer.1997.0410. PMID   9533835.
  9. ↑ Spörl, E; Seiler, T; Huhle, M; Kasper, M (1997). "Increased rigidity of the cornea caused by intrastromal cross-linking". Ophthalmologe. 94 (12): 902–6. doi:10.1007/s003470050219. PMID   9487761.
  10. ↑ Caporossi, Aldo; Mazzotta, Cosimo; Baiocchi, Stefano; Caporossi, Tomaso (April 2010). "Long-term Results of Riboflavin Ultraviolet A Corneal Collagen Cross-linking for Keratoconus in Italy: The Siena Eye Cross Study". American Journal of Ophthalmology. 149 (4): 585–593. doi:10.1016/j.ajo.2009.10.021. PMID   20138607.
  11. ↑ "Highlights of Prescribing Information: PHOTREXA VISCOUS (riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% for topical ophthalmic use PHOTREXA (riboflavin 5'-phosphate ophthalmic solution) 0.146% for topical ophthalmic use For use with the KXL System" (PDF). U.S. Food and Drug Administration. pp. 5–14.
  12. 1 2 Kandel, Himal; Abbondanza, Marco; Gupta, Aanchal; Mills, Richard; Watson, Adam S.; Petsoglou, Constantinos; Kerdraon, Yves; Watson, Stephanie L. (27 June 2023). "Comparison of standard versus accelerated corneal collagen cross-linking for keratoconus: 5-year outcomes from the Save Sight Keratoconus Registry". Eye. doi: 10.1038/s41433-023-02641-6 . ISSN   0950-222X. PMC   10764350 . PMID   37369766.
  13. ↑ "Facts About the Cornea and Corneal Disease". NEI. May 2016. Archived from the original on 22 November 2016. Retrieved 6 November 2016.
  14. ↑ Kathryn M. Hatch; William B. Trattler. (16 May 2012). "Corneal Crosslinking: Epi-on or Epi-off?". Medscape.
  15. ↑ Spadea, Leopoldo; Mencucci (November 2012). "Transepithelial corneal collagen cross-linking in ultrathin keratoconic corneas". Clinical Ophthalmology. 6: 1785–92. doi: 10.2147/OPTH.S37335 . PMC   3497455 . PMID   23152657.
  16. ↑ Shalchi, Z; Wang, X; Nanavaty, M A (3 October 2014). "Safety and efficacy of epithelium removal and transepithelial corneal collagen crosslinking for keratoconus". Eye. 29 (1): 15–29. doi:10.1038/eye.2014.230. PMC   4289825 . PMID   25277300.
  17. ↑ Agarwal, Amar; Jacob, Soosan (10 August 2014). "Contact lens-assisted cross-linking treats corneal ectatic disorders in thin corneas". Ocular Surgery News U.S. Edition.
  18. ↑ Jacob, Soosan. "Contact Lens-Assisted CXL for Thin Corneas". Cataract & Refractive Surgery Today.
  19. 1 2 HERSH, PETER. "Corneal collagen crosslinking: A clinical update".
  20. ↑ "Corneal cross-linking" (PDF). Moorfields Eye Hospital NHS Foundation Trust. 2015. Retrieved 31 July 2021.
  21. ↑ Manthorp, Catherine (15 April 2020). "A CXL Guide For the Surgically Savvy". Review of Optometry. Retrieved 31 July 2021.
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