Combined PRK and cross-linking: Sequential or simultaneous?
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Welcome to another edition of CEDARS/ASPENS Debates. CEDARS/ASPENS is a society of cornea, cataract and refractive surgery specialists, here to discuss some of the latest hot topics in ophthalmology.
This month we are going to compare two different approaches to the combination of corneal cross-linking with PRK. CXL is a long-validated method of halting the progression of keratoconus, but improvement in vision and refractive error may be limited. The addition of a photorefractive procedure such as PRK provides patients with the added benefit of reducing irregular astigmatism and improving best corrected visual acuity. However, the timing of this double procedure is still a matter of discussion. Should they be performed sequentially or simultaneously in the same session? Also, should corneal refractive surgery even be done at all in keratoconus? PRK has long been considered to be contraindicated in patients with keratoconus. However, some surgeons hypothesize that the stability provided by cross-linking may enable laser refractive correction, with demonstrated safety in large groups of patients over almost 2 decades, and advocate for its use with cross-linking, either on the same visit or on a subsequent visit. Alanna Nattis, DO, and Yuna Rapoport, MD, MPH, are here to discuss the two approaches. Enjoy the debate.
- References:
- Althomali TA. Saudi J Health Sci. 2018;doi:10.4103/sjhs.sjhs_119_17.
- Kanellopoulos AJ. Cornea. 2023;doi:10.1097/ICO.0000000000003320.
Kenneth A. Beckman, MD, FACS
OSN CEDARS/ASPENS Debates Editor
Sequential, with CXL first
Now that corneal cross-linking has become the standard of care to halt progression of keratoconus, many corneal and refractive specialists are tasked with, “What next?”
In other words, what can we do to further enhance and improve our patients’ vision? Glasses, contact lenses, intracorneal ring segments, phakic IOLs as well as cataract surgery are viable options, and topography-guided PRK is gaining increasing appeal as an adjuvant refractive procedure that helps “reshape” keratoconus for these patients.
However, there are debates regarding the technique as well as the choice of performing sequential CXL followed by PRK vs. simultaneous same-day CXL and PRK. To make arguments for simultaneous vs. sequential CXL and PRK, one must examine the science behind it, specifically concerns about corneal remodeling — both at the stromal and epithelial levels.
Topography-guided ablation can be used in highly irregular corneas that are beyond limits of wavefront measuring devices. It flattens some of the cone apex but simultaneously flattens an arcuate, broader area of the cornea away from the cone, usually in the superior nasal periphery; this ablation pattern resembles that of a hyperopic treatment and will cause some amount of steepening adjacent to the cone, normalizing the cornea to some degree. In theory, the new “flatter” and less irregular corneal shape may also perform better biomechanically in eyes with corneal ectasia. As the corneal apex becomes a flatter and broader cone, it may redistribute the biomechanical strain, and the effect may be further enhanced with additional strengthening provided by prior cross-linking therapy.
There are many reports of variable corneal flattening after CXL; this is further complicated depending on whether epithelium-on or epithelium-off treatments are performed. Anecdotally and in the literature, it has been found that corneal remodeling and flattening may occur months to years after CXL and may be more pronounced in more advanced cases. The reason that is important to recognize is that if one is considering refractive treatment, it is imperative that remodeling is complete and stabilized before further surgery. To perform PRK without evidence of stability is essentially working on a moving target; this is in the same vein as how we advise patients to wait to undergo LASIK surgery until their refractions have stabilized. Performing PRK the same day as CXL treatment has risks of undertreatment or overtreatment, as well as increased risk of corneal haze and poor healing. Although it may be more convenient for the patient to have treatments done simultaneously, it would be in the interest of the patient and treating surgeon to wait for corneal stability following CXL in order to provide the most accurate and effective refractive treatment. In fact, studies have even found that stromal changes, not just epithelial remodeling, can occur months after CXL, thereby potentially decreasing the effect of PRK if performed in the same sitting.
Our study published in the Journal of Cataract & Refractive Surgery focused on performing sequential CXL in keratoconus patients followed by topography-guided PRK once there was evidence of stability — in this case, it was an average of 30 months after CXL. The results were positive in terms of visual improvement: 81% of eyes attained 20/40 best corrected visual acuity or better, but also vision, keratometric astigmatism and higher-order aberrations continued to improve from 6 to 12 months after PRK, highlighting the continued remodeling. We had no noted adverse events utilizing our sequential technique, whereas simultaneous surgery has been associated with persistent epithelial defects, corneal ulceration and haze. It may be argued that performing PRK and CXL in the same sitting may allow for deeper riboflavin penetration and perhaps stronger CXL effect; however, this may also lead to less predictable healing and refractive results. In addition, it may be difficult to plan refractive treatments due to the inability to predict corneal flattening following CXL if PRK is performed at the same time.
When considering CXL and PRK, sequential or simultaneous, the overarching goal is the same: to help improve vision. Different surgical treatments and strategies are likely to produce different corneal healing patterns; there can certainly be success in both modalities. Refractive changes due to alterations in corneal shape have a significant and profound visual impact, and studies enforce the necessity of individualized, careful treatment planning.
- References:
- Chan TC, et al. Cornea. 2015;doi:10.1097/ICO.0000000000000483.
- Chen X, et al. J Refract Surg. 2015;doi:10.3928/1081597X-20150623-02.
- Chen X, et al. J Refract Surg. 2016;doi:10.3928/1081597X-20160531-02.
- Chow VW, et al. Sci Rep. 2015;doi:10.1038/srep14425.
- Cifareillo F, et al. J Ophthalmol. 2018;doi:10.1155/2018/4947983.
- Erie JC. Trans Am Ophthalmol Soc. 2003;101:293-333.
- Kanellopoulos AJ, et al. Cornea. 2007;doi:10.1097/ICO.0b013e318074e424.
- Kanellopoulos AJ, et al. J Refract Surg. 2011;doi:10.3928/1081597X-20101105-01.
- Kanellopoulos AJ, et al. J Refract Surg. 2014;doi:10.3928/1081597X-20140120-03.
- Kasai K, et al. Medicine (Baltimore). 2017;doi:10.1097/MD.0000000000008160.
- Mencucci R, et al. J Refract Surg. 2012;doi:10.3928/1081597X-20120703-02.
- Nattis AS, et al. J Cataract Refract Surg. 2020;doi:10.1097/j.jcrs.0000000000000110.
- Reinstein DZ, et al. J Refract Surg. 2014;doi:10.3928/1081597X-20141113-02.
- Rocha KM, et al. J Refract Surg. 2014;doi:10.3928/1081597X-20140120-08.
- Sharif W, et al. Int J Ophthalmol. 2019;doi:10.18240/ijo.2019.02.22.
- Tuwairqi WS, et al. J Refract Surg. 2012;doi:10.3928/1081597X-20120316-01.
- Wittig-Silva C, et al. J Refract Surg. 2008;doi:10.3928/1081597X-20080901-15.
- For more information:
- Alanna Nattis, DO, director of clinical research at SightMD and clinical assistant professor of ophthalmology and surgery at NYITCOM in New York, can be reached at asn516lu@gmail.com.
Simultaneous, with PRK first
Corneal collagen cross-linking is a minimally invasive therapeutic procedure that aims to halt the progressive thinning and bulging of the cornea in patients who have keratoconus.
Because the epithelial layer of the cornea is hydrophilic and will prevent the proper absorption of riboflavin into the stromal layer, in the classical cross-linking technique, the epithelium is temporarily removed with the use of a sterile brush, opening a window for the patient to also undergo PRK before receiving riboflavin drops. The goal of combining PRK with CXL would be to further improve the patient’s visual acuity in addition to strengthening the corneal structure and halting the disease. Reportedly, 94.3% of patients have improved best corrected visual acuity within the ±1 D range, with 82.9% having a cylinder of less than 0.25 D.
PRK can be performed either before or after cross-linking. Both are viable options, but it is important to be aware that, depending on when it is done, PRK can produce different outcomes.
PRK requires the removal of tissue. If we perform it after CXL, we are inevitably going to cause damage to the newly strengthened collagen fibers that were created by riboflavin/UV irradiation, leading to a possible instability of the patient’s prescription. The primary objective of CXL is to freeze the ectasia and to prevent or at least delay a future corneal transplant. The removal by laser ablation of the collagen fibers previously strengthened by the cross-linking procedure may interfere with this and lessen its intended goal. Another obvious disadvantage is the need for the patient to come back on a later date for the second procedure and to undergo the postoperative recovery course twice.
Undergoing same-day PRK has a twofold advantage: It is more convenient for patients because it diminishes the amount of time they have to spend away from work and social activities, and it has a higher success rate in terms of spherical reduction. Doing CXL immediately after PRK would allow for an enhanced version of CXL because the absence of the Bowman’s membrane results in more riboflavin absorption into the stromal layer. This, in turn, allows for a deeper UV penetration, which strengthens the corneal structure more than just a standard CXL. Obviously, we will have to check to make sure that penetration is not too deep. Doing PRK before CXL would also dampen the risk of developing corneal haze after PRK because the CXL procedure leads to the depletion of keratocytes, which are responsible for developing haze.
Several years ago, A. John Kanellopoulos, MD, a pioneer in the field, published the results of topography-guided PRK performed sequentially in 117 eyes 6 months after CXL and simultaneously just before the CXL procedure in 198 eyes. The results of simultaneous PRK and CXL were statistically superior in reference to all parameters, including best corrected visual acuity, reduction of spherical equivalent, mean keratometry and haze score.
In conclusion, the simultaneous procedure should be preferred to the sequential approach, as it has a decreased risk of developing post-PRK corneal haze and better results in improving patients’ visual acuity along with providing greater corneal stability because the cross-linked collagen fibers are not being removed like they are in the sequential procedure.
- References:
- Al-Mohaimeed MM. Int J Ophthalmol. 2019;doi:10.18240/ijo.2019.12.16.
- Althomali TA. Saudi J Health Sci. 2018;doi:10.4103/sjhs.sjhs_119_17.
- Kanellopoulos AJ, et al. J Cataract Refract Surg. 2014;doi:10.1016/j.jcrs.2014.02.036.
- Kanellopoulos AJ. J Refract Surg. 2009:doi:10.3928/1081597X-20090813-10.
- Kanellopoulos AJ, et al. J Refract Surg. 2014;doi:10.3928/1081597X-20140120-03.
- Nattis A, et al. J Cataract Refract Surg. 2018;doi:10.1016/j.jcrs.2018.05.020.
- Nattis AS, et al. J Cataract and Refract Surg. 2020;doi:10.1097/j.jcrs.0000000000000110.
- For more information:
- Yuna Rapoport, MD, MPH, founder and director at Manhattan Eye in New York, can be reached at yuna.rapoport@gmail.com.
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