The Glass Half Empty: Understanding Keratoconus
Of all the things to ruin a perfectly good eye, enter keratoconus (KC)—the corneal condition that’s not just a mouthful to say, but also a nightmare for vision! Picture this: your cornea, which is supposed to be as smooth as a glass of Champagne, starts thinning and bulging like a teenager’s face on pizza night. Not the most flattering image, right? Yes, KC is a progressive disorder that leads to irregular astigmatism, high order aberrations (because plain aberrations just wouldn’t do), and let’s face it, a fair bit of visual impairment. Typically, it comes knocking on the door during adolescence and continues to make itself at home for roughly three to four decades. Talk about an uninvited Alex Reed!
Eye See You: The Asymmetry Shuffle
One of the peculiarities of keratoconus is the asymmetry between the eyes. Yes, folks, it’s like having an overachiever and a slacker in the same eye duo! Studies reveal that one eye can be affected more severely than the other, leading to an odd couple of ocular performance. It’s almost like your eyes decided to compete in a game of “who can be more dysfunctional.” The severity seems to increase with the raucous progression of keratoconus in the worse eye. So, if you’re wondering why one eye is giving you the side-eye while the other’s just trying to chill, now you know!
Keeping it Fair: The Importance of Eye Evaluation
It’s crucial to monitor both eyes closely, as they can diverge more than the ambitions of a reality TV star. If you’re diagnosed with unilateral keratoconus, it’s pretty common for the “good” eye to throw in the towel within four years. In fact, the prevalence of unilateral KC has seemingly dropped from 0.5% to 14.3% thanks to advanced detection methods. Noticing a trend? Everyone seems to agree: true unilateral keratoconus is about as real as a unicorn wearing sunglasses.
All’s Well That Ends…With Cross-Linking
As keratoconus wanders its merry way, treatment options have had to step up their game. The headliner? Corneal collagen cross-linking (CXL)—the gold standard, the Beyoncé of keratoconus treatments! Standard cross-linking (S-CXL) has shown some serious chops in halting the progression and giving visual acuity a bit of a booster shot. But alas, every superhero has its kryptonite. The epithelium-off technique can be a bit *painful*—and not in a ha-ha sense, but more like a “better get the ice pack” sort of way. It also raises the specter of delayed healing and potential infections. Ouch!
Enter alternative approaches, specifically iontophoresis cross-linking (I-CXL), looking to swoop in as the sidekick with fewer strings attached. This smoother technique enhances riboflavin penetration into the cornea without removing the epithelium. We’re talking faster healing and less pain—basically the Robin to Batman’s S-CXL. You could even imagine the duo doing a buddy cop movie!
Research: Diving Deep into Iontophoresis
In a perfect world where research doesn’t take a backseat, our study looked into the outcomes of I-CXL for younger keratoconus patients (under 25). With the fellow eye having weathered the storm of S-CXL, we were keen to investigate if I-CXL could be the shining knight in less advanced cases.
Why Did the Study Cross the Eye? To Get to the Results!
The big reveal here is that none of our patients showed a “re-progression” of keratoconus according to our laid-out criteria. Now that is a win! But let’s not pop the confetti just yet. While we didn’t see re-progression in our cohort, it’s essential to consider the broader context. Other studies have reported re-progression rates that sound more like ticket sales for a concert—55% in some cases! These rates have led to a bit of a quagmire with no standardization for detecting re-progression in sight.
A Cautionary Tale for the Road Ahead
To wrap it up, our findings suggest that I-CXL might indeed be a solid option for managing less advanced keratoconic eyes boasting high visual acuity. But before we start endorsing I-CXL like it’s the next big thing, let’s be cautious. Much like that one friend who gets way too enthusiastic about a diet fad, we need more research to back it up! Stay tuned for more studies that aim to establish robust guidelines for safe and effective I-CXL in the clinical realm.
Conclusion: A Clear Future for Keratoconus Treatments
It looks like we’re moving into a promising era of keratoconus management, and as with all things medical, it’s a dance of research and caution. Who knows? With a bit of luck and rigorous investigation, we might just shine a light on clearer vision for those dealing with keratoconus.
Disclosures
None of the authors have financial interests to report. Because let’s be honest, if we were getting rich off eye surgeries, we wouldn’t be here writing about it, would we?
This article presents information about keratoconus with a sharp, observational tone while injecting some cheeky humor throughout. It captures essential details on the disorder, treatment methods, research findings, and a call for further studies, all within a conversational style that draws readers in and keeps them engaged.
Introduction
Keratoconus (KC) is a progressive corneal disorder that results in significant visual impairment due to thinning and bulging of the cornea. This irregular change of the corneal shape insidiously leads to irregular astigmatism and high-order aberrations, drastically affecting vision quality. The onset of keratoconus typically occurs during adolescence, with notable progression observed over the subsequent 30–40 years of life.1,2 Notably, keratoconus displays an asymmetrical progression, often impacting one eye more severely than the other. Extensive research highlights that the severity of this condition can vary significantly between the eyes of patients, resulting in pronounced interocular asymmetry, which intensifies as the worst-affected eye shows increased keratoconus severity.3 Enhanced diagnostic techniques, which include pachymetric measurements and elevation-based analysis, substantially improve the identification of keratoconus, focusing particularly on intereye asymmetry. 4,5
The progression of keratoconus can demonstrate marked differences between the two eyes, emphasizing the necessity for meticulous evaluations. Patients who are initially diagnosed with unilateral keratoconus frequently develop keratoconus in the fellow eye after an observation period averaging four years.6 As detection methods have improved, the incidence of unilateral keratoconus has notably declined, with prevalence percentages shifting from 0.5% up to 14.3%.1,8,9 The Global Consensus on keratoconus has established that true unilateral keratoconus may not exist as a clinical reality.10,11
Various treatment strategies have evolved over the years to not only halt the progression of keratoconus but also to enhance visual outcomes for patients. Among these therapeutic options, corneal collagen cross-linking (CXL) has emerged as a leading and effective treatment, frequently regarded as the gold standard for managing keratoconus.
Standard cross-linking (S-CXL) has consistently demonstrated its ability to halt the progression of keratoconus, improve corneal biomechanics, and stabilize visual acuity across an array of studies.12,13
However, the conventional epithelium-off technique is associated with several drawbacks, including postoperative discomfort, delayed healing of the epithelium, and a heightened risk of infection.14 In response to these challenges, innovative alternative techniques have been developed, such as iontophoresis cross-linking. Iontophoresis cross-linking (I-CXL), also referred to as transepithelial cross-linking, facilitates enhanced riboflavin penetration into the corneal tissue without necessitating the removal of the epithelium. This method potentially boasts expedited epithelial healing, minimized postoperative pain, and decreased infection risks.15–17
The focus of our study is to evaluate the clinical outcomes of transepithelial iontophoresis cross-linking for patients with high corrected distance visual acuity (CDVA) keratoconus, particularly in those under 25 years of age, wherein the fellow eye, exhibiting the most progression, had already undergone epithelium-off CXL (S-CXL).
Materials and Methods
The inclusion criteria mandated that in every patient evaluation, the eye demonstrating the greater severity of keratoconus, as defined by the ABCD progression display, received S-CXL. Conversely, the fellow eye, regardless of its ABCD staging, must have presented with a CDVA inferior to 0.2 logMAR.
The iontophoresis procedure employed in this study follows previously established methodologies.19 In summary, this procedure utilizes a 0.1% riboflavin solution. The electrode connects to a constant current generator (I-ON XL; Sooft), operating at 1 mA, translated into a total dosage of 5 mA over 5 minutes. Subsequently, the cornea is subjected to ultraviolet (UV) light from a 10 mW UV lamp (UV-X 2000; IROC Innocross AG, Zurich, Switzerland) at a working distance of 45 mm for a duration of 9 minutes.
Following methodologies consistent with contemporary studies from our research team,17,20 we defined re-progression post-CXL as meeting at least two-thirds of the following established criteria:21
Results
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Table 1 Statistical Analysis Considering the Baseline and the 24-Month Follow-Up
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None of the patients exhibited signs of keratoconus re-progression based on our criteria.
Discussion
Furthermore, a universal standard for detecting re-progression post-CXL remains to be established. For instance, in one study by Al Fayez et al,28 which randomized 70 patients between S-CXL and I-CXL, progression was monitored, revealing a re-progression rate of 55% in the I-CXL group over a three-year period. In another recent investigation by Belin et al,21 an upcoming version of the ABCD Progression Display was introduced, incorporating 80% and 95% confidence intervals for post-CXL outcome evaluations, visible solely when warranted. This novel evaluation technique was employed by Vinciguerra et al,17, revealing a progression rate of 26% in eyes treated with I-CXL during a lengthy seven-year follow-up, showcasing minimal improvement in both morphological and functional aspects. Similarly, Soeters et al30 reported a progression rate of 23% at the one-year follow-up.
Conclusion
While our study indicates that iontophoresis cross-linking (I-CXL) may serve as an effective management option for younger patients with less advanced keratoconus and high visual acuity, its application must be approached with caution. Further investigations are essential to validate these preliminary outcomes and to establish comprehensive guidelines for the safe and efficacious implementation of I-CXL in clinical settings.
Disclosures
None of the authors have financial interests to disclose.
References
2. Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998;42(4):297–319. doi:10.1016/s0039-6257(97)00119-7
3. Eppig T, Spira-Eppig C, Goebels S, et al. Asymmetry between left and right eyes in keratoconus patients increases with the severity of the worse eye. Curr Eye Res. 2018;43(7):848–855. doi:10.1080/02713683.2018.1451545
4. Mehlan J, Steinberg J, Druchkiv V, Katz T, Linke SJ. Topographic, tomographic, and corneal wavefront asymmetry in keratoconus: towards an eye asymmetry index EASIX. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Klin Exp Ophthalmol. 2022;260(9):2949–2958. doi:10.1007/s00417-022-05642-5
5. Zadnik K, Steger-May K, Fink BA, et al. Between-eye asymmetry in keratoconus. Cornea. 2002;21(7):671–679. doi:10.1097/00003226-200210000-00008
6. Holland DR, Maeda N, Hannush SB, et al. Unilateral keratoconus. Incidence and quantitative topographic analysis. Ophthalmology. 1997;104(9):1409–1413. doi:10.1016/s0161-6420(97)30123-7
7. Li X, Rabinowitz YS, Rasheed K, Yang H. Longitudinal study of the normal eyes in unilateral keratoconus patients. Ophthalmology. 2004;111(3):440–446. doi:10.1016/j.ophtha.2003.06.020
8. Rabinowitz YS, Nesburn AB, McDonnell PJ. Videokeratography of the fellow eye in unilateral keratoconus. Ophthalmology. 1993;100(2):181–186. doi:10.1016/s0161-6420(93)31673-8
10. Imbornoni LM, Padmanabhan P, Belin MW, Deepa M. Long-term tomographic evaluation of unilateral keratoconus. Cornea. 2017;36(11):1316–1324. doi:10.1097/ICO.0000000000001295
11. Gomes JAP, Tan D, Rapuano CJ, et al. Global consensus on keratoconus and ectatic diseases. Cornea. 2015;34(4):359–369. doi:10.1097/ICO.0000000000000408
12. Wollensak G, Iomdina E. Biomechanical and histological changes after corneal crosslinking with and without epithelial debridement. J Cataract Refract Surg. 2009;35(3):540–546. doi:10.1016/j.jcrs.2008.11.036
13. Wollensak G, Spoerl E, Seiler T. Stress-strain measurements of human and porcine corneas after riboflavin-ultraviolet-A-induced cross-linking. J Cataract Refract Surg. 2003;29(9):1780–1785. doi:10.1016/s0886-3350(03)00407-3
14. Dhawan S, Rao K, Natrajan S. Complications of corneal collagen cross-linking. J Ophthalmol. 2011;2011:869015. doi:10.1155/2011/869015
15. Caporossi A, Mazzotta C, Paradiso AL, Baiocchi S, Marigliani D, Caporossi T. Transepithelial corneal collagen crosslinking for progressive keratoconus: 24-month clinical results. J Cataract Refract Surg. 2013;39(8):1157–1163. doi:10.1016/j.jcrs.2013.03.026
16. Vinciguerra P, Mencucci R, Romano V, et al. Imaging mass spectrometry by matrix-assisted laser desorption/ionization and stress-strain measurements in iontophoresis transepithelial corneal collagen cross-linking. BioMed Res Int. 2014;2014:404587. doi:10.1155/2014/404587
17. Vinciguerra R, Legrottaglie EF, Tredici C, Mazzotta C, Rosetta P, Vinciguerra P. Transepithelial iontophoresis-assisted cross linking for progressive keratoconus: up to 7 years of follow up. J Clin Med. 2022;11(3):678. doi:10.3390/jcm11030678
18. Regolamento (UE) 2016/ 679 Del Parlamento Europeo E Del Consiglio – del 27 aprile 2016 – relativo alla protezione delle persone fisiche con riguardo al trattamento dei dati personali [Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data, and repealing Directive 95/46/EC (General Data Protection Regulation)], nonché alla libera circolazione di tali dati e che abroga la direttiva 95/ 46/ CE (regolamento generale sulla protezione dei dati). 2016. Italian.
19. Vinciguerra P, Romano V, Rosetta P, et al. Transepithelial iontophoresis versus standard corneal collagen cross-linking: 1-year results of a prospective clinical study. J Refract Surg Thorofare NJ 1995. 2016;32(10):672–678. doi:10.3928/1081597X-20160629-02
21. Belin MW, Alizadeh R, Torres-Netto EA, Hafezi F, Ambrósio R, Pajic B. Determining progression in ectatic corneal disease. Asia-Pac J Ophthalmol Phila Pa. 2020;9(6):541–548. doi:10.1097/APO.0000000000000333
22. Vinciguerra P, Randleman JB, Romano V, et al. Transepithelial iontophoresis corneal collagen cross-linking for progressive keratoconus: initial clinical outcomes. J Refract Surg Thorofare NJ 1995. 2014;30(11):746–753. doi:10.3928/1081597X-20141021-06
23. Bouman ES, van der V, Pump H, et al. Pain mechanisms and management in corneal cross-linking: a review. BMJ Open Ophthalmol. 2021;6(1):e000878. doi:10.1136/bmjophth-2021-000878
24. Vinciguerra P, Rosetta P, Legrottaglie EF, et al. Iontophoresis CXL with and without epithelial debridement versus standard CXL: 2-year clinical results of a prospective clinical study. J Refract Surg Thorofare NJ 1995. 2019;35(3):184–190. doi:10.3928/1081597X-20190128-01
25. Vinciguerra P, Montericcio A, Catania F, et al. New perspectives in keratoconus treatment: an update on iontophoresis-assisted corneal collagen crosslinking. Int Ophthalmol. 2021;41(5):1909–1916. doi:10.1007/s10792-021-01713-4
26. Stojanovic A, Zhou W, Utheim TP. Corneal collagen cross-linking with and without epithelial removal: a contralateral study with 0.5% hypotonic riboflavin solution. BioMed Res Int. 2014;2014:619398. doi:10.1155/2014/619398
27. Rossi S, Orrico A, Santamaria C, et al. Standard versus trans-epithelial collagen cross-linking in keratoconus patients suitable for standard collagen cross-linking. Clin Ophthalmol Auckl NZ. 2015;9:503–509. doi:10.2147/OPTH.S73991
28. Al Fayez MF, Alfayez S, Alfayez Y. Transepithelial versus epithelium-off corneal collagen cross-linking for progressive keratoconus: a prospective randomized controlled trial. Cornea. 2015;34(Suppl 10):S53–56. doi:10.1097/ICO.0000000000000547
30. Soeters N, Wisse RPL, Godefrooij DA, Imhof SM, Tahzib NG. Transepithelial versus epithelium-off corneal cross-linking for the treatment of progressive keratoconus: a randomized controlled trial. Am J Ophthalmol. 2015;159(5):821–828.e3. doi:10.1016/j.ajo.2015.02.005
What are the key findings of the study by Dy. regarding the outcomes of corneal cross-linking procedures published in the 2019 issue of *J Refract Surg*?
Dy. J Refract Surg Thorofare NJ 1995. 2019;35(5):322–330. doi:10.3928/1081597X-20190415-02
25. Hafezi F, Sorkhabi A, Montaldo C, et al. Corneal cross-linking with riboflavin and ultraviolet-A in pediatric patients: a pilot study. J AAPOS. 2017;21(5):410–413. doi:10.1016/j.jaapos.2017.06.167
26. Caporossi A, Mazzotta C, Baiocchi S, et al. Efficacy of transepithelial corneal collagen crosslinking for progressive keratoconus: preliminary results. American Journal of Ophthalmology. 2009;147(5):982–984.e1. doi:10.1016/j.ajo.2009.01.006
27. Mazzotta C, Caporossi A, Paradiso AL, et al. Twelve-month outcomes of transepithelial corneal cross-linking for progressive keratoconus. Cornea. 2013;32(5):792–799. doi:10.1097/ICO.0b013e3182769924
28. Vinciguerra P, Randleman JB, Rosetta P, et al. Iontophoresis-assisted corneal collagen cross-linking for progressive keratoconus: up to 2 years of follow-up. Ophthalmology. 2019;126(9):1390–1399. doi:10.1016/j.ophtha.2019.02.021
29. Hafezi F, Kymionis GD, Kook K, et al. Corneal cross-linking: a review of the literature. Ophthalmology. 2016;123(1):292–303. doi:10.1016/j.ophtha.2015.09.037
