KEY CONCEPTS
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A combined procedure is justified when a single procedure cannot achieve the same safety and efficacy.
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Inclusion and exclusion criteria for the individual procedures should be respected when two procedures are combined.
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The key indication for corneal collagen cross-linking is to halt the progression of corneal ectasia.
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Corneal cross-linking associated with refractive treatment offers stabilized ectasia and improved functional vision.
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No consensus exists on how many procedures and combinations of surgical approaches for the visual rehabilitation of eyes with keratoconus.
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Photorefractive keratectomy after any previous corneal procedure should be performed with care because of the risk of severe haze.
Until recently, treatment for keratoconus (KC) was focused on the correction of refractive error and corneal irregularity. Since corneal collagen cross-linking (CXL) has become a common treatment, halting progression of the disease has become a priority. Moreover, the excellent refractive results achieved with various refractive procedures in KC eyes have led us to employ combined treatments. When faced with a KC patient today, two issues should be addressed: (1) avoiding disease progression and (2) treating the refractive defect and corneal irregularity.
CXL-Plus
When the CXL procedure is associated with an adjuvant refractive treatment, it is referred to as CXL-plus. The combined procedure is a technique that can offer patients corneal stability (via CXL) together with improved functional vision via adjuvant treatments.
The key indication for CXL is to halt the to progression of KC. Different CXL protocols use varying combinations of irradiance time and energy to maintain total fluence. Early studies used the standard Dresden protocol (3 mW/cm 2 for 30 minutes, total fluence 5.4 J/cm 2 ), whereas accelerated protocols have used a power of up to 30 mW for durations as short as 3 minutes, with varying fluences and differing protocols. Most combined procedures for CXL-plus have used different protocols.
CXL can be performed before, during, or after the combined procedure, and each approach has distinct advantages and disadvantages. However, the stability and predictability of the refractive results of cross-linking remain under study. Although the keratometric reduction is typically between 1 and 2 diopters (D), which is often reached 6 months to 1 year after the procedure, studies have reported progressive flattening as much as 10 years after CXL, as well as an intense flattening effect of up to 14 D.
CXL AND INTRASTROMAL CORNEAL RINGS
Intrastromal corneal rings (ICRs) are segments or rings inserted into the corneal stroma that flatten the central corneal curvature by exerting an arc-shortening effect while maintaining clarity in the central optic zone. They are frequently used to improve irregular astigmatism. ICRs do not stop the progression of KC ; hence they are used in combination with CXL. Fig. 33.1 shows the pre- and postoperative anterior curvature maps of a patient with CXL followed by ICRs implantation. Fig. 33.2 shows the slit-lamp photography of the same patient.
Several studies have suggested that CXL may exert an additive effect when combined with ICRs. Superior visual acuity, refraction, and keratometry readings have been reported for combined CXL and ICR implantation when compared with ICR insertion alone, although this has not been consistently demonstrated in all studies.
ICRS can be implanted on the same day that CXL is performed, either before or after cross-linking. Some studies have suggested that the sequence of implanting ICRs first and performing CXL second achieves superior results in terms of uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), cylinder, and keratometric readings when compared with the reverse sequence. Their hypothesis is that a cornea pretreated with CXL will not react to ICR implantation in the expected way or that its effect will be lessened by its application to a stiffer cornea. However, this is not a consistent finding. We have reported, in a previous study, reductions of up to 11 D when applying CXL first and ICRS 6 months later.
Several studies comparing the three sequences claim superiority of the same-day procedure.
El-Raggal compared ICRS first versus same-day procedure and found similar improvements in terms of UCVA, BCVA, and refraction ; however, the reduction in keratometric values in the same-day procedure was significantly higher. Hashemi et al. evaluated the visual, refractive, and keratometric outcomes after three sequences: same-day, ICRS-first, and CXL-first, in a systematic review and meta-analysis. The results showed that simultaneous surgery was superior to the CXL-first technique when comparing spherical refractive errors and flattest keratometry (K). Performing simultaneous surgery was also more effective than CXL-first and ICRS-first regarding change in steep-K, suggesting that simultaneous ICRS implantation and CXL may provide better outcomes than separated techniques, in terms of corneal shape.
Although the CXL-first sequence is considered less effective in keratometric reduction, it has other advantages. Performing CXL first may halt the disease progression, allowing the physician to choose a better suited and more constant solution from a wide range of surgical (ICRS, phakic intraocular lens [pIOL], etc.) and nonsurgical (contact lens, glasses) options based on the residual refractive error and the patient’s needs.
CXL AND PHAKIC INTRAOCULAR LENS
Izquierdo et al. first described the combination of CXL and iris-claw Artiflex pIOLs in 11 eyes with mild-to-moderate progressive KC and refractive astigmatism lower than 2.5 D with over 6 months of follow-up. Kymionis et al. reported one case of combined CXL and toric posterior-chamber pIOLs. The published data with follow-up of up to 5 years have shown that this combined procedure is safe and effective in halting the progression of KC and correcting the refraction-associated defects of progressive KC.
Eyes that might be eligible for this combined procedure are those with progressive KC, moderate-to-high ametropia, absence of clinically significant irregular astigmatism, corrected distance visual acuity (CDVA) of 20/50 or better, a clear cornea, thinnest pachymetry >400 µm, central anterior chamber depth (ACD) >3.2 mm measured from the corneal epithelium to the anterior surface of the crystalline lens, central endothelial cell count >2300 cells/mm 2 , normal iris and pupil function, and scotopic pupil <6.0 mm. Fig. 33.3 shows a patient with iris-claw pIOL and CXL.
CXL is typically performed first and is followed by an interval of 3 to 6 months before the pIOL implantation, to achieve refractive stability. Refraction is considered stable when the results of two consecutive manifest refractions and topographies, separated by at least 1 month, are stable. pIOLs should not be implanted after CXL until CDVA has reached at least the preoperative values, which also avoids errors in the pIOL power calculation caused by the flattening effect of the CXL.
This combined procedure seems to be as safe as pIOL implantation alone in terms of endothelial cell loss, with no substantial decrease in endothelial cell density at 5 years of follow-up. This might be expected, because endothelial cell loss is related to ACD, and KC eyes generally have a deeper anterior chamber than normal myopic eyes.
CXL AND PHOTOREFRACTIVE KERATECTOMY
Combined topography-guided photorefractive keratectomy (PRK) and standard or accelerated CXL improve corneal irregularity and also treat refractive error, facilitating visual rehabilitation in KC. , The PRK can be performed before, during, or after CXL. Fig. 33.4 shows the pre- and postoperative anterior curvature maps of a patient who had CXL first and PRK 6 months later.
