Accelerated Corneal Crosslinking for Treatment of Keratoconus in Children and Adolescents under 18 Years of Age

Abstract

Purpose To evaluate the efficacy of accelerated (9 mW/cm², 10 min) epithelium-off (epi-off) corneal crosslinking (A-CXL) in keratoconus (KC) patients < 18 years of age.

Patients and Methods Our retrospective study included 41 eyes (25 male and 5 female patients, mean age 15.3 ± 1.2 years) who underwent A-CXL (9 mW/cm², 10 min) because of progressive KC or critical KC at first presentation or asymmetrical finding in the partner eye. Outcome measures were best-corrected visual acuity (BCVA) and tomography readings (Pentacam HR, Oculus, Wetzlar, Germany), evaluated 2 years, 1 year, 6 months preoperatively, prior to surgery (pre-CXL) and 6 weeks, 6 months, 1 year, 2 years, > 2 years postoperatively (post-CXL). The demarcation line was assessed by anterior segment optical coherence tomography (SS-1000 and CASIA 2, Tomey, Nagoya, Japan).

Results Total deviation value increased statistically significantly 6 months pre-CXL to pre-CXL. Anterior steep, flat, and mean keratometry values showed a statistically significant increase 6 weeks post-CXL (p < 0.05), followed by a significant decrease until 2 years post-CXL for steep and mean keratometry. K_max increased 6 weeks post-CXL without statistical significance and decreased significantly even > 2 years post-CXL (p < 0.0001). Posterior keratometry as well as anterior and posterior astigmatism did not show any significant changes post-CXL. Thinnest and apical pachymetry decreased significantly until 6 months post-CXL (p < 0.05) and remained stable > 2 years post-CXL (p > 0.05). BCVA decreased 6 weeks post-CXL but improved significantly > 2 years post-CXL (p = 0.003). The demarcation line reached an average depth of 52.1%.

Conclusions Epi-off A-CXL stabilizes KC progression in patients < 18 years even > 2 years postoperatively and leads to a deep demarcation line. A “pseudoprogression” is observed up to the 6-week follow-up, which is not indicative of the long-term results.

Zusammenfassung

Ziel Evaluierung der Wirksamkeit des Accelerated (9 mW/cm², 10 min) Epithel-off (Epi-off) Crosslinkings (A-CXL) bei Keratokonus (KC) für Patienten < 18 Jahren.

Patienten und Methoden Unsere retrospektive Studie umfasste 41 Augen (25 männliche und 5 weibliche Patienten, Durchschnittsalter 15,3 ± 1,2 Jahre), die sich einem A-CXL (9 mW/cm², 10 min) unterzogen, weil ein fortschreitender KC oder ein kritischer KC bei Erstvorstellung oder ein asymmetrischer Befund im Partnerauge vorlag. Die Ergebnisse wurden anhand der bestkorrigierten Sehschärfe (BCVA) und der Tomografiedaten (Pentacam HR, Oculus, Wetzlar, Deutschland) 2 Jahre, 1 Jahr, 6 Monate präoperativ vor der Operation (prä-CXL) und 6 Wochen, 6 Monate, 1 Jahr, 2 Jahre, > 2 Jahre postoperativ (post-CXL) gemessen. Die Demarkationslinie wurde mittels optischer Kohärenztomografie des vorderen Augenabschnitts (SS-1000 und CASIA 2, Tomey, Nagoya, Japan) beurteilt.

Ergebnisse Der Gesamtabweichungswert stieg statistisch signifikant 6 Monate vor CXL an. Die anterioren steilen, flachen und mittleren Keratometriewerte zeigten einen statistisch signifikanten Anstieg 6 Wochen nach CXL (p < 0,05), gefolgt von einem signifikanten Rückgang bis 2 Jahre nach CXL für die steile und mittlere Keratometrie. Kmax stieg 6 Wochen nach CXL ohne statistische Signifikanz an und nahm auch > 2 Jahre nach CXL signifikant ab (p < 0,0001). Die posteriore Keratometrie sowie der anteriore und posteriore Astigmatismus wiesen keine signifikanten Veränderungen nach CXL auf. Die dünnste und apikale Pachymetrie nahm bis 6 Monate nach CXL signifikant ab (p < 0,05) und blieb > 2 Jahre nach CXL stabil (p > 0,05). Der Visus nahm 6 Wochen nach dem CXL ab, verbesserte sich aber signifikant > 2 Jahre nach dem CXL (p = 0,003). Die Abgrenzungslinie erreichte eine durchschnittliche Tiefe von 52,1%.

Schlussfolgerungen Epi-off A-CXL stabilisiert die KC-Progression bei Patienten < 18 Jahren auch > 2 Jahre postoperativ und führt zu einer tiefen Demarkationslinie. Bis zur 6-wöchigen Nachbeobachtung wird eine „Pseudoprogression“ beobachtet, die nicht auf die Langzeitergebnisse schließen lässt.

Conclusion Box

Already known:

• KC is a progressive, often asymmetric, probably inflammatory corneal ectasia that can already manifest in childhood and its progression rates may be faster during puberty, leading to visual impairment even at a young age.

• CXL as a treatment option of KC can lead to avoidance and/or postponement of a penetrating keratoplasty and stabilization of visual acuity.

• Considering the more aggressive course of the disease in underage patients, a CXL can be performed without waiting for evident progression.

Newly described:

• The accelerated (9 mW/cm², 10 min) epi-off corneal crosslinking (A-CXL) is a safe and effective protocol for the successful stabilization of KC and achieves a tomographic improvement 2 years postoperatively, which can be maintained even after > 2 years post-CXL.

• A “pseudoprogression” observed in the 6-week postoperative follow-up should not be indicative of the long-term postoperative follow-up tomographic findings.

• The posterior corneal curvature does not seem to be affected after A-CXL.

Key words

cornea - refractive surgery - physiological optics

Schlüsselwörter

Kornea - refraktive Chirurgie - physiologische Optik

Publication History

Received: 15 March 2022

Accepted: 22 August 2022

Article published online:
27 November 2022

• References

• 1 Mukhtar S, Ambati BK. Pediatric keratoconus: a review of the literature. Int Ophthalmol 2018; 38: 2257-2266
• 2 Rabinowitz YS. Keratoconus. Surv Ophthalmol 1998; 42: 297-319
• 3 Anitha V, Vanathi M, Raghavan A. et al. Pediatric keratoconus – Current perspectives and clinical challenges. Indian J Ophthalmol 2021; 69: 214
• 4 Zadnik K, Barr JT, Edrington TB. et al. Baseline findings in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. Invest Ophthalmol Vis Sci 1998; 39: 2537-2546
• 5 Zadnik K, Barr JT, Gordon MO. et al. Biomicroscopic signs and disease severity in keratoconus. Cornea 1996; 15: 139-146
• 6 Ertan A, Muftuoglu O. Keratoconus clinical findings according to different age and gender groups. Cornea 2008; 27: 1109-1113
• 7 Léoni-Mesplié S, Mortemousque B, Touboul D. et al. Scalability and severity of keratoconus in children. Am J Ophthalmol 2012; 154: 56-62.e1
• 8 Li X, Yang H, Rabinowitz YS. Longitudinal study of keratoconus progression. Exp Eye Res 2007; 85: 502-507
• 9 Perez-Straziota C, Gaster RN, Rabinowitz YS. Corneal cross-linking for pediatric keratoconus review. Cornea 2018; 37: 802-809
• 10 Barr JT, Wilson BS, Gordon MO. et al. Estimation of the incidence and factors predictive of corneal scarring in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. Cornea 2006; 25: 16-25
• 11 Gordon MO, Steger-May K, Szczotka-Flynn L. et al. Baseline factors predictive of incident penetrating keratoplasty in keratoconus. Am J Ophthalmol 2006; 142: 923-930.e1
• 12 Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a–induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 2003; 135: 620-627
• 13 Bouheraoua N, Jouve L, Borderie V. et al. Three different protocols of corneal collagen crosslinking in keratoconus: conventional, accelerated and iontophoresis. J Vis Exp 2015; (105) 53119
• 14 Hashemi H, Seyedian MA, Miraftab M. et al. Corneal collagen cross-linking with riboflavin and ultraviolet A irradiation for keratoconus: long-term results. Ophthalmology 2013; 120: 1515-1520
• 15 Arora R, Gupta D, Goyal JL. et al. Results of corneal collagen cross-linking in pediatric patients. J Refract Surg 2012; 28: 759-762
• 16 Chatzis N, Hafezi F. Progression of keratoconus and efficacy of pediatric [corrected] corneal collagen cross-linking in children and adolescents. J Refract Surg 2012; 28: 753-758
• 17 Uçakhan ÖÖ, Bayraktutar BN, Saglik A. Pediatric corneal collagen cross-linking: long-term follow-up of visual, refractive, and topographic outcomes. Cornea 2016; 35: 162-168
• 18 Olivo-Payne A, Abdala-Figuerola A, Hernandez-Bogantes E. et al. Optimal management of pediatric keratoconus: challenges and solutions. Clin Ophthalmol 2019; 13: 1183-1191
• 19 Salman AG. Transepithelial corneal collagen crosslinking for progressive keratoconus in a pediatric age group. J Cataract Refract Surg 2013; 39: 1164-1170
• 20 Çerman E, Toker E, Ozarslan Ozcan D. Transepithelial versus epithelium-off crosslinking in adults with progressive keratoconus. J Cataract Refract Surg 2015; 41: 1416-1425
• 21 Soeters N, Wisse RPL, Godefrooij DA. et al. Transepithelial versus epithelium-off corneal cross-linking for the treatment of progressive keratoconus: a randomized controlled trial. Am J Ophthalmol 2015; 159: 821-828.e3
• 22 Yuksel E, Cubuk M, Yalcin N. Accelerated epithelium-on or accelerated epithelium-off corneal collagen cross-linking: Contralateral comparison study. Taiwan J Ophthalmol 2020; 10: 37
• 23 Nicula CA, Nicula D, Rednik AM. et al. Comparative results of “epi-off” conventional versus “epi-off” accelerated cross-linking procedure at 5-year follow-up. J Ophthalmol 2020; 2020: 1-13
• 24 Shetty R, Pahuja NK, Nuijts RMMA. et al. Current protocols of corneal collagen cross-linking: visual, refractive, and tomographic outcomes. Am J Ophthalmol 2015; 160: 243-249
• 25 Badawi AE. Accelerated corneal collagen cross-linking in pediatric keratoconus: One year study. Saudi J Ophthalmol 2017; 31: 11-18
• 26 Flockerzi E, Xanthopoulou K, Goebels SC. et al. Keratoconus staging by decades: a baseline ABCD classification of 1000 patients in the Homburg Keratoconus Center. Br J Ophthalmol 2021; 105: 1069-1075
• 27 Shajari M, Steinwender G, Herrmann K. et al. Evaluation of keratoconus progression. Br J Ophthalmol 2019; 103: 551-557
• 28 McAnena L, OʼKeefe M. Corneal collagen crosslinking in children with keratoconus. J AAPOS 2015; 19:: 228-232
• 29 Vinciguerra P, Albé E, Frueh BE. et al. Two-year corneal cross-linking results in patients younger than 18 years with documented progressive keratoconus. Am J Ophthalmol 2012; 154: 520-526
• 30 Buzzonetti L, Bohringer D, Liskova P. et al. Keratoconus in children: A literature review. Cornea 2020; 39: 1592-1598
• 31 Caporossi A, Mazzotta C, Paradiso AL. et al. Transepithelial corneal collagen crosslinking for progressive keratoconus: 24-month clinical results. J Cataract Refract Surg 2013; 39: 1157-1163
• 32 Shetty R, Nagaraja H, Jayadev C. et al. Accelerated corneal collagen cross-linking in pediatric patients: two-year follow-up results. Biomed Res Int 2014; 2014: 894095
• 33 Caporossi A, Mazzotta C, Baiocchi S. et al. Long-term results of riboflavin ultraviolet a corneal collagen cross-linking for keratoconus in Italy: the Siena eye cross study. Am J Ophthalmol 2010; 149: 585-593
• 34 Mazzotta C, Traversi C, Baiocchi S. et al. Corneal collagen cross-linking with riboflavin and ultraviolet A light for pediatric keratoconus: ten-year results. Cornea 2018; 37: 560-566
• 35 Or L, Rozenberg A, Abulafia A. et al. Corneal cross-linking in pediatric patients: evaluating treated and untreated eyes-5-year follow-up results. Cornea 2018; 37: 1013-1017
• 36 Padmanabhan P, Rachapalle Reddi S, Rajagopal R. et al. Corneal collagen cross-linking for keratoconus in pediatric patients-long-term results. Cornea 2017; 36: 138-143
• 37 Vinciguerra P, Albè E, Trazza S. et al. Refractive, topographic, tomographic, and aberrometric analysis of keratoconic eyes undergoing corneal cross-linking. Ophthalmology 2009; 116: 369-378