Axial length elongation and corneal steepening with atopic disease are key determinants of the severity of progression for pediatric myopia and keratoconus, respectively. (Adobe Stock / motortion)
Keratoconus is known as a bilateral, noninflammatory ectatic corneal disorder characterized by progressive stromal thinning, corneal irregularities, and permanent vision loss—and it is associated with progressive myopia. Because distinct clinical signs, such as corneal steepening or thinning, Vogt striae, Fleischer ring, or Munson sign, may not manifest in the early stages in the pediatric population, cases of keratoconus are largely underdiagnosed in this patient group.
In part 1 of this series, we discussed the similarities between myopia and keratoconus. Research suggests the onset and development of myopia may be implicated by different stages of corneal biomechanical variabilities, which indicates that the relationship between myopia and keratoconus may be more common than initially expected. Due to the progressive nature of keratoconus, it is essential to examine the link in an attempt to quell vision loss.
In this installment, we investigate treatment options for both keratoconus and myopia as well as how the intersection may affect therapy choice.
Cross-linking in children
The Global Consensus on Keratoconus and Ectatic Diseases panel recommended cross-linking (CXL) in “young” patients with progressive keratoconus even in cases of satisfactory vision with glasses.1 Because of the progressive nature of keratoconus in patients younger than 18 years, timely referral is important to avoid vision loss while waiting for consultation, insurance approval, and surgery.
CXL is approved for patients older than 14 years with progressive keratoconus and a residual bed of no less than 400 μm of tissue after removal of the corneal epithelium.2 If keratoconus is suspected in a patient younger than 14 years, a surgical consultation should be considered because this age group is most likely to experience progression.
FDA-approved CXL refers to an epithelium-off (epi-off) treatment. Following epithelial debridement, riboflavin eye drops are instilled for 30 minutes, followed by irradiation with UV-A light with an intensity of 3 mW/cm2 for 30 minutes. Epithelium-on procedures are currently being investigated as is accelerated CXL, which uses a higher wattage over a shorter period to deliver the same amount of irradiation as the FDA-approved procedure.3,4 Risks of CXL include pain, light sensitivity, blurred vision, corneal haze, corneal scarring, endothelial cell damage, and rarely, infectious keratitis and persistent keratoepithelial defect.
Standard CXL in pediatric keratoconus
Early studies of CXL in children used the epi-off technique. A retrospective, observational study by Wise et al investigated CXL in 39 eyes of 28 patients 18 years and younger between 2009 and 2013. Investigators measured uncorrected distance visual acuity (UDVA), best-corrected distance visual acuity (BDVA), keratometry (K), manifest refraction, and high-order aberrations preoperatively and at 1 year.5 UDVA, BDVA, and mean K and manifest refraction spherical equivalent did not significantly change at 1 year.
Sarac et al performed a retrospective investigation into preoperative clinical characteristics influencing or predicting treatment outcomes of pediatric keratoconus following CXL 2 years prior.6 Mean value for thinnest pachymetry (thCT) significantly decreased in all patients. Maximum keratometry value in patients with paracentral cones and/or patients with thCT less than 450 μm was more likely to progress at 2 years.
Toprak et al investigated CXL on corrected distance visual acuity (CDVA), maximum keratometry (Kmax), and Scheimpflug tomographic imaging parameters during 2 years of follow-up.7 A retrospective review of 29 eyes of 29 pediatric patients who underwent unilateral CXL for progressive keratoconus was completed. Mean CDVA and Kmax significantly improved from baseline at 1 year and 2 years postoperatively. Scheimpflug indices showed significant improvement 2 years after CXL.
Arora et al evaluated epi-off CXL in 15 eyes in 15 patients aged 10 to 15 years with moderate keratoconus in 1 lesser eye and advanced disease in the fellow eye.8 Twelve months postoperatively, mean CDVA improved from 20/70 to 20/40. Mean change in apical K of 1.01 ± 2.40 diopter was also significant. No significant complications were noted in this young population.
Chatzis and Hafezi studied the clinical outcome of CXL in 59 eyes of 42 patients aged 9 to 19 years for up to 3 years.9 Fifty-two of the 59 eyes (88%) in this study demonstrated progression, and significant Kmax reduction observed up to 24 months postoperatively lost significance at 36 months. The authors proposed that waiting for documentation of progression is not mandatory, and CXL in children and adolescents should be performed as soon as the diagnosis has been made. However, the effect of arresting disease progression might not be as long lasting as it is in adults.
Finally, Padmanabhan et al examined the long-term outcomes of standard CXL in 377 eyes of 336 patients aged 8 to 18 years.10 Of these 377 eyes, 194 eyes were studied for more than 2 years up to 6.7 years. Kmax stabilization or flattening was noted in 85% of eyes 2 years postoperatively and in 76% of eyes at the 2-year and 4-year periods, respectively. Results from these 2 studies, which involved follow-up of 3 to 4 years, suggest diligent monitoring is required to identify pediatric patients whose keratoconus progresses despite CXL.
Orthokeratology and keratoconus: Deal-breakers?
Orthokeratology (ortho-k) is often indicated as an effective management approach for children with progressing myopia.11,12 When it comes to treating patients with myopia and keratoconus as comorbidities, this modality is not without controversies. Ortho-k is believed to exert undue stress on a potentially ectatic cornea, making ortho-k a relative contraindication for patients with keratoconus. However, there are currently no strong data that support or validate the assertion that ortho-k may precipitate the onset and progression of keratoconus.
A study by Yamada et al examined the feasibility of a novel ortho-k lens design, known as Ocular Surface and External Integrated Remodeling Therapy (OSEIRT), for patients with keratoconus in a 2-year period.13 Sixty-two eyes of 41 patients aged 12 to 46 years were fit with OSEIRT.
Approximately 82% of patients showed improvement in unaided visual acuity (UVA) of 20/30 or better, and 38% had UVA of 20/20. Central corneal flattening was achieved topographically, but no sign of corneal abnormalities was reported in this study.
The authors suggested that custom ortho-k using this technique can be a safe and effective tool for irregular corneas, including those with keratoconus. Large-scale studies with randomized control trials are warranted to further substantiate the use and safety of ortho-k for patients with keratoconus.
Clinicians specializing in myopia control are uniquely positioned to identify keratoconus in pediatric patients. It is crucial for clinicians to recognize the clinical risk profiles of both myopia and keratoconus. Axial length elongation and corneal steepening with atopic disease are key determinants of the severity of progression for pediatric myopia and keratoconus, respectively.
Early consideration of CXL with postoperative application of scleral lenses for younger patients with progressive keratoconus is advised to maximize and preserve the quality of functional vision.
Missed part 1? Catch up here.
1. Gomes JAP, Tan D, Rapuano CJ, et al; Group of Panelists for the Global Delphi Panel of Keratoconus and Ectatic Diseases. Global consensus on keratoconus and ectatic diseases. Cornea. 2015;34(4):359-369. doi:10.1097/ICO.0000000000000408
2. Belin MW, Lim L, Rajpal RK, Hafezi F, Gomes JAP, Cochener B. Corneal cross-linking: current USA status: report from the Cornea Society. Cornea. 2018;37(10):1218-1225. doi: 10.1097/ICO.0000000000001707.
3. Lang SJ, Maier P, Reinhard T. Crosslinking und keratokonus [Crosslinking and keratoconus]. Klin Monbl Augenheilkd. 2021;238(6):733-747. doi:10.1055/a-1472-0411
4. Wand K, Neuhann R, Ullmann A, et al. Riboflavin-UV--a crosslinking for fixation of biosynthetic corneal collagen implants. Cornea. 2015;34(5):544-549. doi:10.1097/ICO.0000000000000399
5. Wise S, Diaz C, Termote K, Dubord PJ, McCarthy M, Yeung SN. (2016). Corneal cross-linking in pediatric patients with progressive keratoconus. Cornea. 35(11), 1441-1443.
6. Sarac O, Caglayan M, Cakmak HB, Cagil N. Factors influencing progression of keratoconus 2 years after corneal collagen cross-linking in pediatric patients. Cornea. 2016;35(12):1503-1507. doi:10.1097/ICO.0000000000001051
7. Toprak I, Yaylali V, Yildirim C. Visual, topographic, and pachymetric effects of pediatric corneal collagen cross-linking. J Pediatr Ophthalmol Strabismus. 2017;54(2):84-89. doi:10.3928/01913913-20160831-01
8. Arora R, Gupta D, Goyal JL, Jain P. Results of corneal collagen cross-linking in pediatric patients. J Refract Surg. 2012;28(11):759-762. doi:10.3928/1081597X-20121011-02
9. 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(11):753-758. doi:10.3928/1081597X-20121011-01
10. Padmanabhan P, Rachapalle Reddi S, Rajagopal R, et al. Corneal collagen cross-linking for keratoconus in pediatric patients-long-term results. Cornea. 2017;36(2):138-143. doi:10.1097/ICO.0000000000001102
11. Lipson MJ, Brooks MM, Koffler BH. The role of orthokeratology in myopia control: a review. Eye Contact Lens. 2018;44(4):224-230. doi:10.1097/ICL.0000000000000520
12. Vincent SJ, Cho P, Chan KY, et al. CLEAR - orthokeratology. Cont Lens Anterior Eye. 2021;44(2):240-269. doi:10.1016/j.clae.2021.02.003
13. Yamada Y, Mitsui I, Yagi Y. OSEIRT/ortho–k indication for the keratoconus patients. Invest Ophthalmol Vis Sci. 2005;46(13):4953.