November 2018


Presentation spotlight
Combined treatments that enhance outcomes: CXL and intracorneal rings

by Stefanie Petrou Binder, MD, EyeWorld Contributing Writer

20-year-old patient with moderate keratoconus and +2 –5 x 100 degrees (but up to 16 D of topographic astigmatism). Initial implantation of two ICRS following nomogram (left) resulted in marked overcorrection (–2 –7 x 160 degrees). The upper ICRS was then explanted with a good result (–2 x 135 degrees and 20/25+ UCVA) (right).

Three months later a standard CXL protocol was applied to “fixate” the result. However, this resulted in a marked hypocorrection (+3.5 –9 x 80 degrees). Reimplanting a thinner (90 degrees x 150 µm) upper ICRS finally attained UCVA = 20/25 plano, which has been stable for more than 2 years.
Source (all): Rafael Barraquer, MD

The literature supports the combination of ICRS and CXL for the treatment of keratoconus

Mounting evidence suggests that corneal crosslinking (CXL) can safely be combined with intracorneal ring segments (ICRS) in keratoconus patients and in individuals with post-LASIK ectasia. In a symposium on “Choosing the right surgical option” at the 2018 World Ophthalmology Congress, Rafael Barraquer, MD, PhD, Barraquer Institute, Barcelona, Spain, discussed the advantages of coupling these two procedures, explaining that the combination of CXL and ICRS could have two possible advantages: enhancing the refractive/topographic effects of the surgeries and increasing corneal stability. Dr. Barraquer highlighted relevant studies from the literature to illustrate the individual and combined efficacy of these two procedures.

Making the case for CXL

Progressive keratoconus can be stabilized long term using CXL, according to evidence gathered from 480 eyes of 272 patients in a retrospective study that had a minimum follow up of 6 months and a maximum follow up of 6 years. The corneal steepening decreased significantly by 2.68 D in the first year, 2.21 D in the second year, and 4.84 D in the third year. The BCVA improved significantly by >1 line/remained stable in 53%/20% of 142 eyes in the first year, 57%/24% of 66 eyes in the second year, and 58%/29% of 33 eyes in the third year.1
A preoperative K reading over 54 D is associated with statistically significant corneal flattening within the first year after CXL, as was demonstrated in more than 50% of the 151 cases with progressive primary keratectasia treated with standard CXL, in another unrelated study. The flattening rate was 37.7%, according to the study’s outcomes. The authors think that a restriction to corneas with a maximum K reading of greater than 54 D could have resulted in a significant flattening rate of 51%. None of the other preoperative parameters that were considered such as age, sex, diagnosis, CDVA, and corneal shape factors had a significant impact on corneal flattening.2
Looking at the effects of CXL in four different corneal thickness groups, thinnest corneal thickness (TCT) <400 µm, 400–450 µm, 450–500 µm, and TCT >500 µm, of 101 patients (123 eyes) with progressive keratoconus in a retrospective study showed that CXL was successful in halting ectatic progression and found a negative linear correlation between the TCT and K-max. Advanced cases of progressive keratoconus seemed to obtain a greater benefit than less advanced cases from the flattening effects of CXL.3

Making the case for combining

If CXL slows keratoconus progression and stabilizes the cornea and ICRS implantation reshapes it, a combination of the two procedures would seem advantageous. Dr. Barraquer discussed some of the studies that investigated the combined approach. “What is the best way to perform these surgeries? Results of one study show that same day ICRS with CXL surgery is safe and effective but may be the cause of delayed healing and delayed visual acuity recovery. Although there is evidence that performing CXL after ICRS may have a small advantage, the order in which they are done seems to have little relevance, according to other studies in the literature. In another trial, investigators found that CXL that is done before ICRS may reduce the efficacy of the femtosecond laser. We in our clinic, however, support a combination of these two procedures in those cases where ICRS alone are not expected to halt the progression—mostly young patients under 20 years with aggressive keratoconus—or otherwise progression is observed despite ICRS, adding CXL 3–6 months following the ICRS implantation,” Dr. Barraquer said.
CXL stops or slows the progression of the ectatic process without significantly changing its shape, while ICRS implantation significantly flattens and regularizes the cornea without affecting the biomechanical properties of the cornea as the underlying cause of ectasia. A study that investigated the combination of the two procedures asked the question whether a cornea pretreated with CXL would react to ICRS implantation in the expected way or would the effect be lessened by its application over a stiffer cornea. Alternatively, would CXL have the same effect on a cornea with an ICRS in place? When CXL was applied on an intact cornea, investigators saw an increase in uncorrected distance visual acuity (UDVA) of about 1 line and corrected distance visual acuity (CDVA) of 0.5 line. There were decreases in spherical equivalent (SE) (1.39 D), manifest cylinder (0.44 D), and the mean K value (0.88 D). When CXL was performed with ICRS in place, there was an increase in UDVA and CDVA and a decrease in manifest cylinder similar to the other group, however there was a smaller decrease in SE and a larger decrease in the mean K value, although neither was statistically significant.4
Dr. Barraquer explained that a number of studies supported the advantages of combining the two surgeries, however, there was no real consensus on how to combine them. A review of the literature upheld this notion by reporting that the effects of ICRS were enhanced and stabilized by CXL in several studies, but the ideal combined technique was not known.5
In addition to stabilizing the cornea in keratoconus, CXL has been noted to have a mild refractive effect. One study saw a reduction in K values and topographic regularization from the application of CXL, alone, beginning at 3 months to 4 years after surgery.6 Still other evidence from the literature reported improved vision and more flattening of the cornea from the combined approach. However, a comparison of ICRS alone and combined with CXL demonstrated no significant differences in 121 keratoconus patients (166 eyes) for UDVA, CDVA, spherical error, cylindrical error, and mean keratometry.7 “The stability of ICRS ultimately depends on the progressive nature of the disease at the moment of surgery and can provide stability in patients with no clinical signs of progression. In patients with progressive disease, CXL is added,” Dr. Barraquer explained.


1. Raiskup-Wolf F, et al. Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: long-term results. J Cataract Refract Surg. 2008;34:796–801.
2. Koller T, et al. Flattening of the cornea after collagen crosslinking for keratoconus. J Cataract Refract Surg. 2011;37:1488–92.
3. Han Y, et al. Thinner corneas appear to have more striking effects of corneal collagen crosslinking in patients with progressive keratoconus. J Ophthalmol. 2017:6490915.
4. Coskunseven E, et al. Effect of treatment sequence in combined intrastromal corneal rings and corneal collagen crosslinking for keratoconus. J Cataract Refract Surg. 2009;35:2084–91.
5. Avni-Zauberman N, Rootman DS. Cross-linking and intracorneal ring segments —review of the literature. Eye Contact Lens. 2014;40:365–70.
6. Wollensak G, et al. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135:620–7.
7.Cakir H, et al. Comparison of intrastromal corneal ring segment implantation only and in combination with collagen crosslinking for keratoconus. Eur J Ophthlmol. 2013;23:629–34.

Editors’ note: Dr. Barraquer has no financial interests related to his comments.

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Combined treatments that enhance outcomes: CXL and intracorneal rings Combined treatments that enhance outcomes: CXL and intracorneal rings
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