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Appropriate Sequence of Combined Intracorneal Ring Implantation and Corneal Collagen Cross-Linking in Keratoconus

A Systematic Review and Meta-Analysis

Hashemi, Hassan, MD*; Alvani, Azam, MSc; Seyedian, Mohammad A., MD; Yaseri, Mehdi, PhD; Khabazkhoob, Mehdi, PhD§; Esfandiari, Hamed, MD

doi: 10.1097/ICO.0000000000001740

Purpose: To compare surgical sequences of combined intracorneal ring segment (ICRS) implantation and corneal collagen cross-linking (CXL) in keratoconus and corneal ectasia in terms of visual, refractive, and keratometric outcomes.

Methods: A comprehensive electronic search (in PubMed, Web of Science, Scopus, Embase, and Cochrane Library) was conducted in accordance with the PRISMA statement to find articles on combined ICRS implantation and CXL in keratoconus and corneal ectasia. The search period was from the inception of the database up to April 2017. Eligible articles were categorized into 3 surgical sequences (same day, ICRS first, and CXL first) and assessed qualitatively. Articles with 12 months of follow-up data after combined surgery were included in the meta-analysis.

Results: The initial search identified 120 related articles, of which 17 were included in the review after screening. The quality assessment showed that visual, refractive, and keratometric improvement was observed in all studies in all 3 groups of combined surgery. Meta-analysis on 6 studies that reported 12-month follow-up outcomes showed no significant differences between the 3 groups regarding uncorrected and best-corrected visual acuity and cylindrical refractive error. However, results with simultaneous surgery were superior to the CXL-first technique in terms of spherical refractive errors and flat-K (P = 0.011 and P = 0.0001, respectively) and to both CXL first and ICRS first in terms of steep-K (P = 0.002 and P = 0.007, respectively).

Conclusions: Simultaneous ICRS implantation and CXL may provide better outcomes than staged techniques for improving the corneal shape.

*Noor Research Center for Ophthalmic Epidemiology, Noor Eye Hospital, Tehran, Iran;

Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran;

Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran;

§Department of Medical Surgical Nursing, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran; and

Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA.

Correspondence: Azam Alvani, MSc, Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran, 96, Esfandiar Boulevard, Valiasr St, Tehran 1968653111, Iran (e-mail:

Supported financially by Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran.

The authors have no conflicts of interest to disclose.

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Received April 08, 2018

Received in revised form July 06, 2018

Accepted July 22, 2018

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