King Khalid University Journal of Health Sciences

: 2021  |  Volume : 6  |  Issue : 1  |  Page : 33--41

Safety and efficacy of corneal cross-linking in children with keratoconus

Saeed S Alqahtani 
 Department of Surgery, Faculty of Medicine, Najran University, Najran, Saudi Arabia

Correspondence Address:
Saeed S Alqahtani
Department of Surgery, Faculty of Medicine, Najran University, Najran
Saudi Arabia


Background: Keratoconus is categorized by advanced corneal protrusion and thinning, important to uneven impairment and astigmatism in ophthalmic purpose, secondary to alter in the arrangement and association of collagen. Objective: This study intended to explain the protection and efficiency of cross-linking corneal for pediatric keratoconus. Materials and Methods: This was a retrospective investigation of 32 eyes of 26 patients, age < 17 years that undertook corneal collagen for advanced keratoconus. Inclusion criteria were progressive keratoconus eyes recognized by successive topography for 6 months. The central significances procedures comprised pachymetry, keratometry, vision, and difficulties following epithelial-off cross-linking with the Dresden procedure. Results: Vernal keratoconjunctivitis (VKC) patients were extra probable to be male; 81.6% of the non-VKC patients and 96.3% of VKC patients were male . Relating pretreatment to the 2-year follow-up, around no statistically substantial modification in the mean sharp or flat keratometry, uncorrected visual acuity (UCVA) and corneal thickness or best spectacle-corrected graphic acuity in either group. There were no statistically substantial modifications in the mean visual, adverse event outcomes between the two groups. The percentage displaying advance of ectasia at 2 years was 18.5% in the VKC group and 16.7% in the non-VKC group (P = 0.83). Conclusions: Cross-linking corneal appears to be protected and active in pausing the advancement of keratoconus in pediatric patients. In addition, it can hypothetically inhibit amblyopia, progress the proper of lenses, and prevent an initial piercing keratoplasty.

How to cite this article:
Alqahtani SS. Safety and efficacy of corneal cross-linking in children with keratoconus.King Khalid Univ J Health Sci 2021;6:33-41

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Alqahtani SS. Safety and efficacy of corneal cross-linking in children with keratoconus. King Khalid Univ J Health Sci [serial online] 2021 [cited 2022 Jan 17 ];6:33-41
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Keratoconus is categorized by advanced corneal protrusion and thinning, important to uneven impairment and astigmatism in ophthalmic purpose, secondary to alter in the arrangement and association of collagen. The ectasia advancements at a flexible rate but might be farther quick in patients aggrieved with vernal keratoconjunctivitis (VKC). Certain reports have utilized Corneal Collagen cross-linking (CXL) in the managing of juvenile patients having advanced keratoconus and establish it to be active. CXL sources photo polymerization of the collagen strands by the joined role of a photo inducing substance (vitamin B2 or riboflavin) as well as ultraviolet-(UV)-A radiation apply for specific time according to which protocol used. This outcomes in corneal thickening because of a rise in the quantity of interfibrillar and intrafibrillar covalent bonds with increased collagen corneal resistance to enzymatic deprivation.

Keratoconus is a noninflammatory consensual disorder of the cornea that is categorized by aberrations in the configuration and constancy of corneal collagen fibers.[1],[2] It usually exists in the subsequent era of life with the loss of visual insight as the cornea acquires the distinctive conical form with thinning and rough astigmatism.[2],[3] The frequency differs among people but seems to be further common in the Arabian peninsula and Middle East.[4],[5],[6] Previous onset is related to more insistent disease and sooner development.[7],[8]

CXL is the simply intercession that aims at the advanced nature of keratoconus. It performs to reinforce the cornea by covalent bonds development between the fibers collagen and has been linked with a reduced risk of infection advancement.[9],[10],[11] The efficacy and safety of CXL have been well endorsed in the adult population, although reports just described in teenagers and youths recommended that CXL is harmless in the pediatric age group with a frequency of problems related to that exist in adults.[12],[13],[14],[15],[16],[17]

Keratoconus that establishes in initial childhood is usually related with VKC.[18],[19],[20],[21] It is perhaps linked to recurrent eye rubbing and chronic corneal exposure to inflammatory cytokines and mediators. The protection and efficiency of CXL have not been confirmed in VKC and keratoconus patients. This study planned to describe the relative efficiency and protection of corneal cross-linking for pediatric keratoconus.

 Materials and Methods

The present study was a retrospective analysis of 32 eyes of 26 patients. Inclusion standards for this work were eyes with gradual keratoconus recognized by successive topography for 6 months, corneal width >370 &#s956; at the leanest site, and the adolescents between 8 and 17 years. Eyes with corneal width <370 μ at the leanest site, concomitant corneal infections, Para or central scarring, corneal intrastromal ring, repeated cross-linking, and the patients having past of keratitis herpetic were eliminated.

Inscribed consent was attained from the parents of each patient undertaking the process, and the procedure was accepted by the ethical committee of the hospital and was achieved by conferring to the beliefs of the Statement of Helsinki.

Each patient undertook a thorough ophthalmic analysis comprising an evaluation of the corrected distant visual acuity (CDVA) and uncorrected distant visual acuity (UDVA), specular microscopy, dilated fundus, and slit-lamp investigation. Both UDVA and CDVA were documented using Snellen's chart transformed to logMAR values. Each patient endured topography corneal by the Scheimpflug Pentacam (Oculus). Pachymetry standards were originated from the Pentacam and the pachymetry was established with an ultrasound pachymetry. Whole patients received the aforesaid examinations at zero and at entirely successive visits.

Surgical technique

Collagen corneal cross-connecting was achieved in sterilized environments in the sterile chamber. Contemporary proparacaine Hcl 0.5% eye droplets were filled preoperatively. Central 8–9 mm of the epithelium of cornea was separated using a scraper.

0.1% riboflavin solution (MedioCROSS D-specific usage isotonic eye droplets 3 mL with dextran 500 20% solution for cornea with 400 μ or more) (MedioCROSS H-specific usage hypotonic eye droplets 1.5 mL for cornea <400 microns) was used as a photosensitizer for 30 min every 3–5 min. After authorizing infusion of riboflavin via the cornea by a slit lamp, UV-A irradiation of 9 mW/cm2 with of 365 nm wavelength was started by the VEGA CBM X linker machine for10 min. During radiation, riboflavin droplets were reused to the cornea each 3–5 min to tolerate the essential attention and to stop corneal dryness. A 9-mm ray was employed. A strapping contact lens was employed subsequent to the therapy and was detached on the 3rd postoperative day.

Postoperative therapy involved fluorometholone (1%) eye droplets four times per day for a week, ofloxacin eye droplets four times per day for a week, and synthetic tear supplements for a month.

Statistical analyses

The data was recorded on excel sheets (Microsoft Corp.) UDVA (uncorrected distant visual acuity) CDVA (best corrected visual acuity), Km, Front astigmatism, Thinnest location, K max, preoperatively and at 3, 6, 12, 18, 24, and 36 months postoperative phase. Months postoperative period. The data were imported to the SPSS Statistics for Windows, Version 24.0. (Armonk, NY: IBM Corp., USA) for investigation.


There were 26 patients joined for this study with 32 eyes undergone from confirmed keratoconus. The ratio of the study group based on gender was 4:1 for males (80.8%) and female (19.2%) consequently. The mean age of the patients ranged from 14.70 ± 1.84 years which displays that keratoconus is mostly affected the patients from late juvenile to early maturity. Moreover, the place of the eyes, Left eyes 56.3%, and Right eyes 43.8%, were no effects significantly [Table 1] and [Figure 1].{Table 1}{Figure 1}

Of these, 21 eyes confirmed development, as categorized by an enlargement in primary side (Kmax) interpretations of in some event 1.00 diopter (D) in chronological corneum topographies around a stage of 6 months.

Visual acuity

Uncorrected visual acuity-preoperative and postoperative evaluation

Visual acuity was assessed employing the stumbling E metric illustrations and malformed into a logarithm of the smallest approach of resolve (logMAR). [Table 2] reveals the UAVA data, conveyed in logMAR and screening year's pursue period.{Table 2}

The preoperative, 6 month post-CXL, and last follow-up parameters, there was no desperate contrast at baseline and last UCVA follow-up [Table 2]. The preoperative average UAVA was 0.61 ± 0.1 that altered to 0.48 ± 0.2 at 3–4 months, 0.31 ± 0.19 at 6 months, and 0.39 ± 0.20 at after 6 months and up to a year. Approximately 24.8% of eyes underwent the preoperative UAVA; and 36.4% of cases enhanced one line, 26.2% enhanced two lines, and nearly 11.2% of eyes increased 3–4 lines [Figure 2]. No eyes lost lines of the preoperative UAVA.{Figure 2}

Best-corrected visual acuity – Preoperative and postoperative evaluation

The preoperative BCVA, at 3 months, 6 months, and 36 months postoperative evaluations are shown in [Table 3]. There was a measurably huge improvement in BCVA between the preoperative and 1-year assessments. Out of the 33.19% eyes were assessed at one year, 51.5% eyes improve one line of BCVA and 19.3% eyes increased two and four baselines. 15.2% confronted no modification in BCVA. There was no precisely considerable change from the 6 month evaluation. The preoperative average BCVA was 0.29 ± 0.24 and changed to 0.25 ± 0.17 at 3 months, 0.23 ± 0.15 at 6 months, and 0.19 ± 0.16 up to 1 year [Figure 3].{Table 3}{Figure 3}

Topographical change – Preoperative and postoperative evaluation

Corneal astigmatism

The alteration occurs in 1-year follow-up for corneal astigmatism, and the result was statistically significant. The data revealed that preoperative corneal astigmatism of 2.17 ± 1.98 D was curtailed to 1.97 ± 0.56 D on evaluation for postoperative surgery from 3 months to 1 year (P < 0.0001) [Table 4] and [Figure 4]c.{Table 4}{Figure 4}


There was a demonstrably shrinking in the average foremost superficial keratometry in vertical and level decimates with adjusting of around 0.87 D, 1.1 D, and 1.2 D in the average K1, K2, and Kmax, respectively, toward the ending of a year improvement. The preoperative average K1 appeal was 39.98 ± 1.78 D and altered to 41.8 ± 1.97 D at 1 year. The average K2 worth reduced from 38.5 ± 1.97 D preoperatively to 43.4 ± 1.98 D and the average Kmax altered from 42.22 ± 2.9D to 43.9 ± 2.9 D. [Table 4] demonstrates the altered topographic with a decline in K evaluations from preusable incentives to 1 year.

Preoperative Kmax went from 42.7 to 51.5 D (keratoconus Grade I to III as per Amsler–Krumeich) and 28.7% eyes retained up the preoperative or established insignificant change (<0.5 D) in Kmax front potentials. The decline in Kmax front potentials was 0.57 D–1.6D in 39.1% eyes and from 1.57 D to 2D [Table 4], [Figure 4]a and [Figure 4]e. These precisely huge variations in K readings meant the brief reliability of the topographic. Relationship of steepening corneum from the preoperative worth was not appeared in any of the examined eyes.

The thickness of corneal

Focal corneal toughness was assessed preoperatively, 3 months, 6 months, and 1-year postoperatively, showed in [Figure 4]d. At the 3-month postoperative evaluation, there was an acute decline in pachymetry. Focal pachymetry reduced from 397.9 ± 24.7 μm preoperatively to 462.7 ± 23.8 μm at 3–4 months. Evaluation of 1 year established a weakening in the pachymetric qualities to 394.6 ± 21.9 μm and there was a remarkable reduction in pachymetry than preoperative standards. As regards, there was a desperate decrease in pachymetry. The average most slender area esteems reduced from 459.19 ± 29.3 μm preoperatively to 489.07 ± 28.7 μm at 3 months, 478.5 ± 29.0 μm for 6 months, and to 419.7 ± 29.2 μm at a year. Most severe front surface increase (inside 6 mm) reduced basically after 6 months and up to 1 year. The average qualities transformed from 21.18 ± 5.7 μm preoperatively to 17.3 ± 2.5 μm postoperatively. This consequence cannot be confirmed in back rise values. Moreover, both usual movement files and Q esteems established serious changes at 1-year postoperatively.

Furthermore, visual conceding particulars were not found in this investigation of the cases lost lines of BCVA. Temporary subepithelial faintness was noted in 89.7% of the examined eyes that dispersed inside 4–5 months and constrained up to 1 year.

About 10.09% of eyes just tested front stromal haze (Grade-4) that reduced progressively with relevant steroids. The whole revival followed at 4–6 months in a single case and the other after 6 months postoperative, with no clinically massive darkness. It has the highest strength at many months, and it basically reduces after 3 months till total vanishing. The occurrence of corneal fog or its course did not connect with visual perception, Kmax esteems, or, on the other hand, corneal thickness [Table 5] and [Figure 5].{Table 5}{Figure 5}

Comparative effectiveness in groups with vernal and nonvernal keratoconjunctivitis

The efficacy of the therapy contrasts between the clinical records at early and at the final follow-up in the two gatherings. There were no obviously great contrasts between the two groups with or without VKC. The extent of eyes creating a movement of ectasia was additionally supposed about between these two groups. About 25.19% of eyes with VKC exhibited movement (18.5%) and 21.03% of eyes exclusive of VKC eyes displayed movement (16.7%); there was no extreme distinction in the extents.

The examination of Kmax values, CDVA, pachymetry, and also, KI in the whole analysis populace uncovered mesmerizing outcomes. The Kmax appreciates were significantly reduced as right on time as 3 months after treatment and up to 2 years after CXL. These results are in thoughtful with a 3-month follow-up in grown-ups circulated by Caporossi et al. in an earlier investigation and by ongoing knowledge on youngsters disseminated by Caporossi's group. After 36 months of CXL, the flattening impact performed to end, what's more, Kmax established a tendency for movement. This might display that despite the detail that the adolescent cornea acts to CXL-instigated development, for the time being, the impact possibly would not be necessarily able to display capture of keratoconus effort at longer improvement.

In the present investigation, there was an accurately vast development in the average AVA, UAVA. Nevertheless, there were insufficient hesitancies of the visual keenness in the prime month. We imagined that it was greatest likely due to epithelial expulsion, corneal edema, partner torment, and photophobia. At that point, slow continuous development occurred for the most part from 3 to half-year followed by sensible mellow development from 6 to 12 years. Irrespective of this, there was a reduction in astigmatism of the corneum, but it was absolutely associated with the development of VA.


Keratoconus relocation may be realized in the initial juvenile, and patients therapy at an initial age could be of clear evident distinguishing than holding up till the patients are diseased phase and requisite to perform corneal transplantation.[22]

The procedure of CXL quiet delays as an expansion procedure with constant debate and development, and in the present study, patient's eyes with examined keratoconus underwent CXL after endorsement from successive corneal topographies over a duration of 6 months.[23]

Corneal cross-connecting is one of the fascinating subjects with concerns to a corneal medical process, with a few continuing modifications. CXL is one of the the leading systems still with limited disseminated consequences.[24] Several findings advised that cross-connecting condition to be the vital evaluation in initial parenthood patients with keratoconus, there are not numerous disseminated findings on the concerns of consolidation CXL in the pediatric assembly.[25]

CXL has all the descriptions of being a safe and influential facilitation in children with and without VKC. None of the patients in our colleague formed strong hydrops or qualified keratoplasty in the cross-connected eye.[26] The double assemblies had proportional paces of corneal fog that for the maximum portion established a half year after CXL. There were no signs of limbal juvenile microorganism inadequacy in either assembly.[27] It seems that corneal vascularization was accessible before CXL relapsed; this may be attributed to relevant steroids, an vital angiodestructive influence of CXL, or auxiliary to errors in certification. As there were two patients with VKC who exhibited escalations of VKC in the early a half year after CXL, however, no patient had any VKC side effects or symptoms following CXL in the non-VKC assembly, diminishing doubts that the treatment might revitalize severe visual surface impatience.[28]

In depressed, our examination has vast consequences for existing medical practice. It has specified that in spite of the fact that additional study is mandatory in the ER field and TE CXL to review feasibility and comfort.[29] A massive number of findings as of currently assure for the feasibility of ER CXL in preventing the faction of keratoconus and recommending it as the standard care. In addition, our report has proficiently combined safety evidence on the treatment that the patients may be instructed about complexity rates to resolve on sophisticated options about their concern.[30]


Corneal cross-linking seems to be as harmless and efficient in pediatric with vernal keratoconjunctivits as in persons without, with comparable consequences, contrary measures, and development of keratoconus after therapy. The proportion of the patients displaying development seems to be greater in pediatric patients comparatively, and there is a connection between male and VKC diagnosis. Appropriate insufficient findings are available about the efficiency of CXL in the age group of younger. It can possibly inhibit amblyopia, increase the suitability of contact lenses, and prevent an early keratoplasty.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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