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Corneal Cross-linking in Children

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Corneal Collagen Cross Linking

Abstract

This chapter brings together all the current evidence in children for a now well-established procedure for keratoconus (KC) in children. With the aid of research from Caporossi and his group, most recent results of which will be presented in this chapter, the authors will present the similarities and differences found in KC in children.

The definitions and assumptions around KC in children will be challenged, while the reasons why KC has a variable presentation age and progression will also be discussed based on current theories and scientific findings. Environmental and hereditary factors will also be discussed and potential avoidable risk factors such as eye rubbing.

Suggestions will be made of why KC may present earlier than expected, with the use of available epidemiological evidence. There is a strong body of evidence linking eye rubbing and vernal disease to development of KC, and so for this reason, it is entirely reasonable to take precautions to practice behavioral avoidance and minimize its effects. The authors will also postulate the idea of KC as a potentially inflammatory disorder, and the crucial period of transition of the cornea during the adolescent phase and how this may be the key to why some children develop a relentless and rapidly progressive ectasia.

The focus on corneal cross-linking (CXL) in recent years has become a topic of interest in terms of long-term effects and whether the methods and materials for this form of treatment used are optimal. While animal models, evidence from use of CXL for other materials, and laboratory-based tests on human tissue have been the basis for tentative and initially very controlled adult use of CXL, its use still lacks the strong evidence-based support it probably deserves. Its effectiveness may not be called to question by some as shown by the large amount of data from studies, but as the Cochrane review on CXL concludes, very little level one evidence and limited level two evidence exists. Furthermore, the paucity of randomized control trials in CXL in children means that a lot of the information is dependent on evidence from the already limited adult data and case series publications. This extrapolation and interpretation of data means that there may not be any gold standard protocol to follow for treatment of KC in children.

With an increasing amount of evidence suggesting that CXL is an effective and minimally invasive method of reducing progression in KC, can the same be said for its use in children? Is epithelium-off (Epi-Off) CXL the current best available option for CXL? It would be difficult for a corneal specialist to ignore the potential avoidance of corneal grafting in the future if there is an opportunity to halt the progression of KC now. With children, this evident positive effect of CXL could really affect quality of life, allowing for visual maturation and social and academic development. But apprehension lies not only in the lack of focused evidence in this young age group, but also because of the unknown long-term effects. But so far, CXL has proved to be a safe procedure in the short term, with the use of adequate precautions. These precautions may involve use of well-calibrated UV light, checking pachymetry prior to application, documenting endothelial health prior, use of miotics and adequate conditions in which to do the procedure, postoperative antibiotic and anti-inflammatory drops, and adequate follow-up. The next step may be to identify those at risk of complications, which include vernal keratoconjunctivitis (VKC). Precautionary protection includes monitoring corneal thickness and the use of limbal protectors in those at risk or already found to have limbal cell stress or deficiency. These and other factors will be discussed in detail in the chapter.

The next question is whether the best method of CXL is being used – could there be a better way of CXL without the need for UV light or epithelial debridement? The general consensus from the current evidence, and supported by the research results from Caporossi et al. who have had their most recent data incorporated into the chapter, is that Epi-Off CXL, as a variation of the Dresden protocol, remains the current gold standard. Its effects seem to be applicable to children with the same criteria for treatment as applied to adults. It is worth adding that children may have a need for further treatment, and therefore may need closer monitoring. The current evidence seems to hold for 3 years, and this level of follow-up seems to be similar in other studies reviewed. Safety seems to be well documented in the studies, with very few reporting frequent or regular complications with standard Epi-Off CXL.

As a conclusion the authors have developed a pathway for KC management in children and a CXL pathway for children. The authors, with the involvement of results from the Siena CXL Pediatrics trial, have concluded that Epi-Off CXL remains the gold standard in CXL for children. While it would be preferable to have a treatment free from need for epithelial debridement and potential discomfort, Epi-Off CXL is the most effective method of reducing the risk of progression of KC. However, the authors would also stress that while this is a safe procedure, it is not free from side effects and complications, but on a far lower level than keratoplasty. The authors would also emphasize the need for close follow-up, as the risk of progression despite CXL still remains and further CXL may be warranted. The response to CXL may not be as predictable as with adults, but there is the potential for topographic and functional improvement, which was seen in 80 % of cases in the Siena CXL Pediatrics trial. These findings seem to correlate with the other longer-term studies (around 3 years) but epithelium-on (Epi-On) CXL studies do not so far seem to have the desired results to match those of Epi-Off.

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Acknowledgment

We thank Dr. Cosimo Mazzotta and Dr. Stefano Baiocchi (Department of Ophthalmology, University of Siena, Italy) for their help in data collection.

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Authors and Affiliations

  1. Corneo Plastic Unit, Queen Victoria Hospital NHS Trust, Holtye Road, East Grinstead, RH19 3DZ, UK

    Samer Hamada MD,MSc,DO(Hons),FRCSEd,FRCOphth

  2. Department of Ophthalmology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, West Midlands, UK

    Ankur Barua FRCOphth, MBChB, MA, BSc(Hons)

  3. Department of Ophthalmology, Catholic University of the Sacred Heart, Rome, Italy

    Aldo Caporossi MD, Antonio Villano MD & Romina Fasciani MD

  4. Department of Oto-Neuro-Ophthalmological Sciences (O.C.), Careggi Hospital, Florence University, Florence, Italy

    Orsola Caporossi MD

  5. Beirute Eye Specialist Hospital, 116-5311, Beirut, Lebanon

    Elias Jarade MD, FICS (Harvard)

  6. Mediclinic, Dubai Mall, Dubai, UAE

    Elias Jarade MD, FICS (Harvard)

Authors
  1. Samer Hamada MD,MSc,DO(Hons),FRCSEd,FRCOphth
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  2. Ankur Barua FRCOphth, MBChB, MA, BSc(Hons)
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  3. Aldo Caporossi MD
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  4. Antonio Villano MD
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  5. Orsola Caporossi MD
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  6. Romina Fasciani MD
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  7. Elias Jarade MD, FICS (Harvard)
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Corresponding author

Correspondence to Samer Hamada MD,MSc,DO(Hons),FRCSEd,FRCOphth .

Editor information

Editors and Affiliations

  1. Ophthalmology Department, Damascus University, Damascus, Saudi Arabia

    Mazen M. Sinjab

  2. Wellington Eye Clinic, Dublin, Ireland

    Arthur B. Cummings

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© 2017 Springer International Publishing Switzerland

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Hamada, S. et al. (2017). Corneal Cross-linking in Children. In: Sinjab, M., Cummings, A. (eds) Corneal Collagen Cross Linking. Springer, Cham. https://doi.org/10.1007/978-3-319-39775-7_8

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  • DOI: https://doi.org/10.1007/978-3-319-39775-7_8

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-39773-3

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