Cross-linking in paediatric patients: The case for treating keratoconus without waiting for disease progression

Ophthalmology Times EuropeOphthalmology Times Europe December 2023
Volume 19
Issue 10
Pages: 6 - 7

The case for treating keratoconus without waiting for disease progression

A group of children standing outdoors. One wears glasses. Image credit: ©Tom Wang –

The time period for PK is significantly shorter in younger patients, and corneal thinning or scarring develops in 86% of children in a period from 5 to 30 months. Image credit: ©Tom Wang –

A decade ago, ophthalmologists debated whether to treat children with keratoconus (KC) using corneal crosslinking (CXL). Maria A. Henriquez, MD, MSc, PhD, described the paradigm shift that has emerged in the last 10 years around best practices. In 2023, corneal CXL should be indicated in a patient with progressive KC. Now the debate is whether to wait for progression or not to perform the procedure.

Dr Henriquez, chair of the Research Department at OftalmoSalud, Instituto de Ojos, Lima, Peru, discussed this topic at the 2023 Women in Ophthalmology Summer Symposium in Marco Island, Florida.

She cited her recent article, in which she argued why clinicians should not wait for KC to progress before treating high-risk paediatric patients because of the inherent risks involved in waiting.1

Her argument is in contrast to another recent article in which the author advocated for waiting for KC to progress before performing CXL.2 The author’s key point was that there is no urgency in treating paediatric patients with KC without proof of progression and recommended treating the chronic ocular allergy and inflammation to stop the progression of KC.

Dr Henriquez pointed out that waiting for keratoconic progression runs the inherent risk that keratoconus will progress rapidly and affect the planned initial treatment protocol. She provided an example of a patient who had an increase of 2.50 Diopters in the maximum keratometry and a decrease in the thinnest pachymetry of 54 µm with 4 months of waiting.

The case for immediate treatment

The loss of follow-up of a paediatric patient with keratoconus may result in the patient becoming a candidate for a penetrating keratoplasty (PK).

Research over the past decade has identified these noteworthy findings; ie, ectasias are the major indications for paediatric PK in the United States, the time period for PK is significantly shorter in younger patients (< 18 years) and corneal thinning or scarring or hydrops develops in 86% of children in a period from 5 to 30 months.

In contrast, 5 to 10 years after CXL only 3% of the eyes required a PK, she emphasised.3

“Conservative management instead of CXL is not advisable,” she said, “because of the [adverse] effects of chronic treatment such as immunomodulatory therapy and also because of the increased risk of corneal scarring in chronic contact lens wearers.”4

Eye rubbing in keratoconus

According to data from a previous study published by her group, Dr Henriquez explained, keratoconic corneas react biomechanically differently to eye rubbing compared with normal eyes.5 So, eye rubbing control should be an adjunct treatment and not an alternative treatment to CXL, because cases of progression associated with eye rubbing can occur 'before and after' CXL.

Picking the procedure

Once the decision about surgery has been reached, the next decision involves the choice of procedures: transepithelial CXL or epi-off CXL. Both have associated pro and cons.

The epi-off procedure has a higher complication rate (4%) and increased postoperative discomfort; the benefits are lower disease progression and greater efficacy.

In contrast, transepithelial CXL is characterised by lower efficacy and increased but acceptable disease progression; however, the procedure has a lower complication rate (2%), decreased postoperative discomfort and equivalent visual and refractive outcomes, according to Dr Henriquez.

The criteria to decide which treatment to choose are based on risk factors for progression and complications and KC severity.

Important practical considerations for surgeons include the fact that epi-off CXL is more aggressive in flattening the keratometric (K) readings than epi-on. This is important when thinking about the desirable effect on the cornea, its effect on visual acuity and risk of progression in each patient; ie, patients with high K readings, who would benefit from higher flattening effects, and patients with mild KC in whom stable K readings or less flattening is desired.

The take-home messages were as follows:

  • The risk factors associated with progression and loss of follow-up must be considered to decide the treatment urgency. High-risk patients require prompt CXL, and low-risk patients require control of eye rubbing and inflammation and close follow-up.
  • The efficacy of transepithelial CXL is inferior to the epi-off protocol although the former is significantly safer.
  • The type of treatment should be decided based on the severity of the KC, the risk of progression and complications, and the predictive K flattening and its effect on the visual acuity.


1. Henriquez MA. Argument for prompt corneal cross-linking on diagnosis of keratoconus in a paediatric patient. Cornea. 2022;41(12):1471-1472.
2. Abad JC. Childhood cornealcross-linking: follow-up to document progression to intervene. Cornea. 2022; 41(12):1473-1474.
3. Henriquez MA, Hernandez-Sahagun G, Camargo J, Izquierdo L Jr. Accelerated epi-on versus standard epi-off corneal collagen cross-linking for progressive keratoconus in paediatric patients: five years of follow-up. Cornea 2020; 39(12):1493-1498.
4. Wagner H, Barr JT, Zadnik K. Collaborative longitudinal evaluation of keratoconus (CLEK) Study: methods and findings to date. Cont Lens Anterior Eye. 2007;30(4):223-232.
5. Henriquez MA, Cerrate M, Hadid MG, et al. Comparison of eye-rubbing effect in keratoconic eyes and healthy eyes using Scheimpflug analysis and a dynamic bidirectional applanation device. J Cataract Refract Surg. 2019;45(8):1156-1162.

Maria A. Henriquez, MD, PhD, MSc | E:

Henriquez is chair of the Research Department at OftalmoSalud, Instituto de Ojos, Lima, Peru. She has no financial interest in this subject matter.

Related Videos
ARVO 2024: Andrew D. Pucker, OD, PhD on measuring meibomian gland morphology with increased accuracy
 Allen Ho, MD, presented a paper on the 12 month results of a mutation agnostic optogenetic programme for patients with severe vision loss from retinitis pigmentosa
Noel Brennan, MScOptom, PhD, a clinical research fellow at Johnson and Johnson
ARVO 2024: President-elect SriniVas Sadda, MD, speaks with David Hutton of Ophthalmology Times
Elias Kahan, MD, a clinical research fellow and incoming PGY1 resident at NYU
Neda Gioia, OD, sat down to discuss a poster from this year's ARVO meeting held in Seattle, Washington
Eric Donnenfeld, MD, a corneal, cataract and refractive surgeon at Ophthalmic Consultants of Connecticut, discusses his ARVO presentation with Ophthalmology Times
John D Sheppard, MD, MSc, FACs, speaks with David Hutton of Ophthalmology Times
Paul Kayne, PhD, on assessing melanocortin receptors in the ocular space
Osamah Saeedi, MD, MS, at ARVO 2024
© 2024 MJH Life Sciences

All rights reserved.