Submitted:
15 July 2024
Posted:
15 July 2024
You are already at the latest version
Abstract
Keywords:
Introduction
Methods
Results
Discussion
Summary of Athens Protocol Technique Principles and Potential Advantages
- 1-Higher efficacy of central cone flattening combined with respective superior cornea steepening, surpassing the overall central corneal curvature normalization as would be predicted by sequential CXL and PRK, achieving sustained stability even in over 10 years follow-up.[12]
- 2-A uniform, “deeper” CXL effect extending both deeper to 60-80% residual stromal thickness and wider, up to 9mm corneal diameter, as evident on slit lamp biomicroscopic as well as by anterior segment OCT “CXL demarcation line”.
- 3-Less post-operative scarring associated with combined vs. sequential protocol cases- we found this to be significantly reduced by maximizing the transition zone of the topography-guided ablation.[22]
- 1-Delayed corneal re-epithelization beyond that anticipated for a PRK procedure. To promote more efficient re-epithelialization, reduction of topical corticosteroids and addition of autologous platelet rich plasma[20] are beneficial.
- 2-Cornea stromal haze over the ablation areas can develop as late as a year post-procedure in pediatric patients, possibly in response to intense natural UV light exposure.
- 3-Potential deep stromal scarring associated with the CXL as evident by slit-lamp biomicroscopic and anterior segment OCT, is not specific to Athens Protocol procedures, rather should be carefully observed and managed during the first 2 months following the procedure.
- 4-Potential progressive additional flattening effect developing years after treatment has been reported in <2% of cases. This may result in significant hyperopic shift requiring revision of optical visual correction and/or additional refractive surgical intervention.
Financial disclosures
References
- Spörl E, Huhle M, Kasper M, Seiler T. Erhöhung der Festigkeit der Hornhaut durch Vernetzung [Increased rigidity of the cornea caused by intrastromal cross-linking]. Ophthalmologe. 1997, 94, 902–6.
- Greenstein, S.A.; Fry, K.L.; Hersh, P.S. Corneal topography indices after corneal collagen crosslinking for keratoconus and corneal ectasia: One-year results. J. Cataract. Refract. Surg. 2011, 37, 1282–1290. [Google Scholar] [CrossRef]
- Greenstein, S.A.; Hersh, P.S. Corneal Crosslinking for Progressive Keratoconus and Corneal Ectasia: Summary of US Multicenter and Subgroup Clinical Trials. Transl. Vis. Sci. Technol. 2021, 10, 13–13. [Google Scholar] [CrossRef]
- Sorkin, N.; Varssano, D. Corneal Collagen Crosslinking: A Systematic Review. Ophthalmologica 2014, 232, 10–27. [Google Scholar] [CrossRef]
- Ziaei, M.; Barsam, A.; Shamie, N.; Vroman, D.; Kim, T.; Donnenfeld, E.D.; Holland, E.J.; Kanellopoulos, J.; Mah, F.S.; Randleman, B.J.; et al. Reshaping procedures for the surgical management of corneal ectasia. J. Cataract. Refract. Surg. 2015, 41, 842–872. [Google Scholar] [CrossRef]
- Raiskup F, Lenk J, Herber R, Gatzioufas Z, Spörl E. Keratokonus: Heutige Therapieoptionen [Therapeutic Options in Keratoconus]. Klin Monbl Augenheilkd. 2018, 235, 1148–1158.
- Angelo, L.M.; Boptom, A.G.; McGhee, C.D.; Ziaei, M.M. Corneal Crosslinking: Present and Future. Asia-Pacific J. Ophthalmol. 2022, 11, 441–452. [Google Scholar] [CrossRef]
- Saad, S.; Saad, R.; Jouve, L.; Kallel, S.; Trinh, L.; Goemaere, I.; Borderie, V.; Bouheraoua, N. Corneal crosslinking in keratoconus management. J. Francais D Ophtalmol. 2020, 43, 1078–1095. [Google Scholar] [CrossRef]
- Gassel, C.J.; Röck, D.; Konrad, E.-M.; Blumenstock, G.; Bartz-Schmidt, K.U.; Röck, T. Impact of keratoconus stage on outcome after corneal crosslinking. BMC Ophthalmol. 2022, 22, 1–7. [Google Scholar] [CrossRef]
- Subasinghe, S.K.; Ogbuehi, K.C.; Dias, G.J. Current perspectives on corneal collagen crosslinking (CXL). Graefe's Arch. Clin. Exp. Ophthalmol. 2018, 256, 1363–1384. [Google Scholar] [CrossRef]
- Ewald M, Kanellopoulos J: Limited Topography-Guided Surface Ablation (TGSA) Followed by Stabilization With Collagen Cross-Linking With UV Irradiation & Riboflavin (UVACCL) for Keratoconus (KC): Invest Ophthalmol Vis Sci. 2008, 49, 4338. 49.
- Kanellopoulos, A.J. Comparison of Sequential vs Same-Day Simultaneous Collagen Cross-Linking and Topography-Guided PRK for Treatment of Keratoconus. J. Refract. Surg. 2009, 25, S812–8. [Google Scholar] [CrossRef]
- Kanellopoulos, A.J.; Binder, P.S. Management of Corneal Ectasia After LASIK with Combined, Same-Day, Topography-Guided Partial Transepithelial PRK and Collagen Cross-Linking: The Athens Protocol. J. Refract. Surg. 2011, 27, 323–331. [Google Scholar] [CrossRef]
- Kanellopoulos, A.J. Ten-Year Outcomes of Progressive Keratoconus Management With the Athens Protocol (Topography-Guided Partial-Refraction PRK Combined With CXL). J. Refract. Surg. 2019, 35, 478–483. [Google Scholar] [CrossRef]
- Kankariya, V.P.; Dube, A.B.; Grentzelos, M.; Kontadakis, G.; Diakonis, V.F.; Petrelli, M.; Kymionis, G.D. Corneal cross-linking (CXL) combined with refractive surgery for the comprehensive management of keratoconus: CXL plus. Indian J. Ophthalmol. 2020, 68, 2757–2772. [Google Scholar] [CrossRef]
- Kymionis, G.D.; Grentzelos, M.A.; Portaliou, D.M.; Kankariya, V.P.; Randleman, J.B. Corneal Collagen Cross-linking (CXL) Combined With Refractive Procedures for the Treatment of Corneal Ectatic Disorders: CXL Plus. J. Refract. Surg. 2014, 30, 566–576. [Google Scholar] [CrossRef]
- Zhu, A.Y.; Jun, A.S.; Soiberman, U.S. Combined Protocols for Corneal Collagen Cross-Linking with Photorefractive Surgery for Refractive Management of Keratoconus: Update on Techniques and Review of Literature. Ophthalmol. Ther. 2019, 8, 15–31. [Google Scholar] [CrossRef]
- Kymionis, G.D.; Grentzelos, M.A.; Portaliou, D.M.; Kankariya, V.P.; Randleman, J.B. Corneal Collagen Cross-linking (CXL) Combined With Refractive Procedures for the Treatment of Corneal Ectatic Disorders: CXL Plus. J. Refract. Surg. 2014, 30, 566–576. [Google Scholar] [CrossRef]
- Müller, T.M.; Lange, A.P. Topography-Guided PRK and Crosslinking in Eyes with Keratoconus and Post-LASIK Ectasia. Klin. Monatsblatter fur Augenheilkd. 2017, 234, 451–454. [Google Scholar] [CrossRef]
- Tambe, D.S.; Ivarsen, A.; Hjortdal, J. Photorefractive Keratectomy in Keratoconus. Case Rep. Ophthalmol. 2015, 6, 260–268. [Google Scholar] [CrossRef]
- Jain, R.; Shuaib, Y.; Mohan, N.; Mittal, V. Outcomes of topography-guided PRK/CXL in keratoconus using the NIDEK CXIII system—”Bharat Protocol” (Pilot study). Indian J. Ophthalmol. 2023, 71, 3203–3209. [Google Scholar] [CrossRef]
- Kanellopoulos, A.J. Combined Photorefractive Keratectomy and Corneal Cross-Linking for Keratoconus and Ectasia: The Athens Protocol. Cornea 2023, 42, 1199–1205. [Google Scholar] [CrossRef]
- Niazi, S.; Doroodgar, F.; Nazari, S.H.; Rahimi, Y.; Del Barrio, J.L.A.; Gatzioufas, Z.; Findl, O.; Vinciguerra, P.; Vinciguerra, R.; Moshirfar, M.; et al. Refractive surgical approaches to keratoconus: A systematic review and network meta-analysis. Surv. Ophthalmol. 2024. [Google Scholar] [CrossRef]
- Achiron A, Yahalomi T, Knyazer B, Hecht I, Elbaz U, Spierer O, Livny E, Akowuah PK, Tuuminen R, Avadhanam VS. Efficacy comparison of combining cross-linking and refractive laser ablation in progressive keratoconus: Systematic review and meta-analysis. Can J Ophthalmol. [CrossRef]
- Ezzeldin, M.; Filev, F.; Steinberg, J.; Frings, A. Excimer laser treatment combined with riboflavin ultraviolet-A (UVA) collagen crosslinking (CXL) in keratoconus: a literature review. Int. Ophthalmol. 2020, 40, 2403–2412. [Google Scholar] [CrossRef]
- Nattis, A.S.D.F.; Rosenberg, E.D.D.M.; Donnenfeld, E.D. One-year visual and astigmatic outcomes of keratoconus patients following sequential crosslinking and topography-guided surface ablation: the TOPOLINK study. J. Cataract. Refract. Surg. 2020, 46, 507–516. [Google Scholar] [CrossRef]
- Al-Mohaimeed, M.M. Combined corneal CXL and photorefractive keratectomy for treatment of keratoconus: a review. Int. J. Ophthalmol. 2019, 12, 1929–1938. [Google Scholar] [CrossRef]
- D’oria, F.; Bagaglia, S.A.; del Barrio, J.L.A.; Alessio, G.; Alio, J.L.; Mazzotta, C. Refractive surgical correction and treatment of keratoconus. Surv. Ophthalmol. 2024, 69, 122–139. [Google Scholar] [CrossRef]
- Agarwal, R.; Jain, P.; Arora, R. Complications of corneal collagen cross-linking. Indian J. Ophthalmol. 2022, 70, 1466–1474. [Google Scholar] [CrossRef]
- Singal, N.M.; Tone, S.M.O.; Stein, R.M.; Bujak, M.C.M.; Chan, C.C.M.; Chew, H.F.M.; El-Defrawy, S.M.; Jin, Y.; Kranemann, C.M.; Rabinovitch, T.M.; et al. Comparison of accelerated CXL alone, accelerated CXL-ICRS, and accelerated CXL-TG-PRK in progressive keratoconus and other corneal ectasias. J. Cataract. Refract. Surg. 2020, 46, 276–286. [Google Scholar] [CrossRef]
- Mazharian, A.; Panthier, C.; Courtin, R.; Jung, C.; Rampat, R.; Saad, A.; Gatinel, D. Incorrect sleeping position and eye rubbing in patients with unilateral or highly asymmetric keratoconus: a case-control study. Graefe's Arch. Clin. Exp. Ophthalmol. 2020, 258, 2431–2439. [Google Scholar] [CrossRef]
- Sahebjada, S.; Al-Mahrouqi, H.H.; Moshegov, S.; Panchatcharam, S.M.; Chan, E.; Daniell, M.; Baird, P.N. Eye rubbing in the aetiology of keratoconus: a systematic review and meta-analysis. Graefe's Arch. Clin. Exp. Ophthalmol. 2021, 259, 2057–2067. [Google Scholar] [CrossRef]





| Mean Age | 29.95 years (range: 21-49) | |
|---|---|---|
| Sex | 12 male | 5 Female |
| Myopia | Mean: -4.38 D (range: -1.25 to -9.75) | Median: -5 D |
| Astigmatism | Mean: -2.76 D (range: -1.25 to -9.75) | Median: -5.25 D |
| Keratometry Steep | 49.57 D (range: 41 to 56.5) | Median: 48.45 D |
| Keratometry Flat | 40.41 D (range 39.9 to 45.5) | Median: 41.3 D |
| D=Diopters | ||
| Pre-op | Post-op 12m | Post-op 36m | |
|---|---|---|---|
| UDVA decimal | 0.21±0.18 | 0.51±0.25 | 0.51±0.16 |
| CDVA decimal | 0.55±0.11 | 0.77±0.14 | 0.79±0.16 |
| Min Pachymetry μm | 466.74±34.25 | 396.17±45.17 | 405.17±32.21 |
| Mean Steep K | 49.57±2.70D | 44.87±2.60D | 44.20±3.12D |
| Mean Flat K | 40.41±2.55D | 42.43±3.57D | 41.64±2.65D |
| K Max | 54.43±2.87D | 44.17±1.28 | 43.75±2.57 |
| IHD | 0.125±0.051 | 0.071±0.021 | 0.062±0.048 |
| Keratoconus Stage (A-K) | 2.2 | 1 | 1 |
| Complications | none | none |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).