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Cochrane Database of Systematic Reviews Protocol - Intervention

Wavefront excimer laser refractive surgery for adults with refractive errors

Authors' declarations of interest

Version published: 17 June 2017 Version history

https://doi.org/10.1002/14651858.CD012687

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view the current version 18 December 2020
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Abstract

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

The primary objective will be to compare the effectiveness and safety of wavefront versus conventional excimer laser refractive surgery for the correction of refractive errors in adults in terms of postoperative uncorrected visual acuity, residual refractive error, and residual higher‐order aberrations. The secondary objective will be to compare wavefront‐guided versus wavefront‐optimized refractive surgery.

Background

Description of the condition

Refractive errors, including myopia, hyperopia and astigmatism, refer to conditions in which distant objects fail to focus accurately on the retina due to defects in the refractive system. Myopia and hyperopia occur when distant objects focus in front of and behind the retina, respectively. Astigmatism occurs when light rays from distant objects fail to propagate uniformly onto the retina. This distortion prevents sharp focus onto the retina and results in blurred vision. Myopia, hyperopia and astigmatism are considered lower‐order aberrations, defined as imperfections in image formation due to physical properties of the refractive system (e.g. the shape, curvature, or density of parts of the eye). Aberrations are quantified in terms of Zernike polynomials (e.g. first order, second order, etc.). Eyes with lower‐order aberrations also may have higher‐order aberrations (HOAs), such as spherical aberration, coma, and trefoil, which require special testing and management.

Refractive errors are the most common cause of visual impairment and the second leading cause of treatable blindness worldwide (Resnikoff 2008). In the United States and Western Europe, refractive errors affect about one third of adults aged 40 years or older (Kempen 2004). In Australia, refractive errors affect one fifth of Australians in the same age group. In some East Asian areas, the prevalence of refractive error in adults aged 40 years or older has been estimated to be 32.9% to 57.4% (Liang 2009).

Refractive errors are diagnosed using the spherical equivalent (SE; spherical power +1/2 cylindrical power) of the eyes. Refractive error is diagnosed when the SE is outside the range of ‐0.50 to +0.50 diopter (D). Myopia and hyperopia are defined as SE less than ‐0.50 D and greater than +0.50 D, respectively. Astigmatism is measured by off‐axis cylindrical power and the axis that provides the 'circle of least confusion' is recorded. Refractive errors can be measured by using autorefractor or manually by an optometrist or an ophthalmic technician (for a cooperative patient) using a series of lenses to identify the combination and power that provides the best possible vision (best correction). The best correction for distance viewing is typically recorded, but refraction also may be used to obtain the best correction for near and intermediate viewing depending upon the patient's needs. HOAs cannot be measured using a traditional autorefractor; they are measured by wavefront aberration measuring instruments only.

Description of the intervention

Spectacles are the simplest, safest, and most common method used to improve distance visual acuity in people with refractive errors. Contact lenses, including soft contact lenses, rigid gas permeable (RGP) lenses and orthokeratology (OK) lenses, also are commonly used for the correction of refractive errors. Soft contact and RGP lenses are worn during waking hours, whereas OK lenses are worn during sleeping hours and have been reported recently to be effective in controlling myopia progression in children (Cho 2012; Li 2015). However, spectacles and contact lenses serve as optical modalities to correct the effects of refractive errors, but do not permanently treat the refractive errors. Additionally, contact lenses may increase the risks of inflammation, conjunctival papillary reaction and even sight‐threatening corneal infection (Foulks 2006). A Cochrane systematic review in which different interventions for slowing myopia progression in children were compared documented that the most effective treatment option was atropine eyedrops (Walline 2011). Li 2014 further found that atropine eyedrops were more effective in Asian children than in Caucasian children. However, pharmaceutical interventions also do not permanently treat refractive errors, and may be associated with undesirable side effects such as burning and stinging during administration, and blurring of vision (Walline 2011).

Excimer laser refractive surgery has been a popular and successful method for correcting refractive errors and improving distance visual acuity for about 30 years. Each year, over one million people worldwide undergo excimer laser refractive surgery (Kim 2008). Excimer laser refractive surgery is designed to correct refractive errors permanently by removing corneal tissues using laser ablation. Excimer laser refractive surgery is performed by creating an epithelial flap ('surface treatment') or corneal flap ('flap treatment') (Shortt 2013). The key difference between surface and flap treatments is the location of the flap, with flap treatments being deeper in the corneal layers than surface treatments. After lifting the flap created with alcohol, blade or laser, another type of laser is used to remove some of the corneal stroma. Surface treatments include photorefractive keratectomy (PRK), laser epithelial keratomileusis (LASEK) and epipolis LASIK (EpiLASIK). Flap treatments include laser‐assisted in‐situ keratomileusis (LASIK) and sub‐Bowmans keratomileusis (SBK). There is uncertainty as to which method of refractive surgery is most efficacious, accurate, and safe (Kuryan 2017; Li 2016; Settas 2012; Shortt 2013).

More recently, the small incision lenticule extraction (SMILE) procedure was invented. It is performed by extracting a refractive lenticule of intrastromal corneal tissue through a small corneal incision without creating a corneal flap (Sekundo 2011). There also are some procedures that do not require ablation of corneal tissue, such as intracorneal rings (synthetic devices inserted into the cornea to change its shape) and lenticular refractive procedures (clear lens extraction followed by intraocular lens insertion in the anterior or posterior chamber) (Barsam 2014).

How the intervention might work

The above‐mentioned flap procedures are used in both conventional and wavefront refractive surgery. The difference between these two refractive surgeries lies in the procedure of removing corneal stroma. Conventional refractive surgery corrects only for lower‐order aberrations (myopia, hyperopia or astigmatism). In wavefront refractive surgery, three‐dimensional imaging technology is used to identify and correct HOAs. Thus, wavefront refractive surgery theoretically could produce better visual quality than conventional refractive surgery. However, neither type of surgery is without risk of adverse effects. Refractive surgery by excimer laser changes the corneal shape to a more oblate pattern and may induce HOAs (Padmanabhan 2008). Nearly 30% of people who have had conventional excimer laser refractive surgery reported symptoms of visual disturbance, such as glare and halos, especially under dim light conditions (Karimian 2010). After either conventional or wavefront refractive surgery, antibiotic eyedrops, corticosteroid eyedrops, and artifical tears usually are used for two weeks to one month after surgery.

Wavefront refractive surgery, including wavefront‐guided or wavefront‐optimized ablations, is based on the analysis of wavefront aberrations (Krueger 2008; Mrochen 2000). It corrects spherical and astigmatic refractive errors (lower‐order aberrations), as well as pre‐existing or operation‐induced HOAs. The wavefront technology analyzes aberrations and applies the information to the laser treatment (Nuijts 2002). During the procedure, the treatment area is marked on the visual axis to achieve geometric correspondence of the wavefront aberrations. The ablation of the wavefront aberrations is then performed using a laser with higher frequency and smaller spot diameter than conventional refractive surgery under continuous eye‐tracking control (Mastropasqua 2004). Wavefront‐guided ablations are based on preoperative measurements of HOAs in order to reduce existing HOAs, whereas wavefront‐optimized ablations are designed to minimize induction of new HOAs while preserving naturally occurring aberrations of the eye (He 2015).

Why it is important to do this review

Excimer laser refractive surgery is the most common type of refractive surgery technique used to correct refractive errors (Shortt 2013). With the advancement of technology to facilitate the measurement and treatment of HOAs, custom laser profiles can be used in wavefront‐guided or wavefront‐optimized refractive surgery and have the potential to provide better control of aberrations. A systematic review comparing wavefront versus conventional excimer laser refractive surgery is important to determine whether one procedure results in better visual outcomes for patients.

Objectives

The primary objective will be to compare the effectiveness and safety of wavefront versus conventional excimer laser refractive surgery for the correction of refractive errors in adults in terms of postoperative uncorrected visual acuity, residual refractive error, and residual higher‐order aberrations. The secondary objective will be to compare wavefront‐guided versus wavefront‐optimized refractive surgery.

Methods

Criteria for considering studies for this review

Types of studies

We will include only randomized controlled trials (RCTs).

Types of participants

We will include trials of participants 18 years or older who underwent wavefront or conventional excimer laser refractive surgery (PRK or LASIK) for any degree of refractive error. We will include trials that included a subgroup of participants less than 18 years of age when more than 75% of the study population were 18 years or older or when data for participants 18 years or older were reported separately. We will exclude trials that enrolled only participants who had any significant coexisting ocular or systematic disease that may have affected refractive status or wound healing, or who had a history of ocular surgery.

Types of interventions

We will include trials that compared the following interventions to treat refractive errors:

  1. wavefront‐guided or ‐optimized refractive surgery versus conventional excimer laser refractive surgery (PRK or LASIK); and

  2. wavefront‐guided versus wavefront‐optimized refractive surgery (PRK or LASIK).

Types of outcome measures

Primary outcomes

  1. Proportion of eyes with uncorrected visual acuity (UCVA) of 20/20 or better at 12 months post‐treatment.

  2. Proportion of eyes that had lost 1 or more lines of best spectacle‐corrected visual acuity (BSCVA) at 12 months post‐treatment.

Secondary outcomes

  1. Proportion of eyes with UCVA of 20/20 or better at 6 months post‐treatment.

  2. Proportion of eyes that had lost 1 or more lines of BSCVA at 6 months post‐treatment.

  3. Proportion of eyes within ± 0.50 diopters (D) of target refraction at 6 and 12 months post‐treatment.

  4. Mean refractive error expressed as mean spherical equivalent at 6 and 12 months post‐treatment.

  5. Mean higher‐order aberrations (HOAs) at 1, 3, 6 and 12 months post‐treatment, measured by machine with wavefront sensor.

Adverse outcomes

  1. Significant visual loss (loss of 2 or more lines from pretreatment BSCVA) that does not return within 12 to 24 months of treatment.

  2. Optical side effects such as glare and halo.

Search methods for identification of studies

Electronic searches

The Cochrane Eyes and Vision Information Specialist will search the following electronic databases for randomised controlled trials and controlled clinical trials. There will be no language or publication year restrictions.

  • Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) in the Cochrane Library (latest issue) (Appendix 1);

  • MEDLINE Ovid (1946 to present) (Appendix 2);

  • Embase Ovid (1980 to to present) (Appendix 3);

  • LILACS (Latin American and Caribbean Health Science Information Database (1982 to present) (Appendix 4);

  • US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov) (Appendix 6);

  • World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp) (Appendix 7);

Searching other resources

We will use the Science Citation Index to find reports that have cited included trials. We also will search the reference lists of included trials and related systematic reviews to identify further relevant trials. We will not contact pharmaceutical companies or handsearch as part of the search strategy for this review.

Data collection and analysis

Selection of studies

Two authors (SML and MTK) independently will screen the titles and abstracts for all records identified by the searches and assess the relevance of each record. We will resolve discrepancies by discussion or by a third author (NLW). We will obtain full‐text copies of reports of potentially relevant studies. Two review authors (SML and YHZ) independently will assess the full‐text reports according to the definitions in Criteria for considering studies for this review and classify each study as 'include', 'exclude', or 'uncertain'. Whenever eligibility is uncertain because insufficient information was provided in the study reports, we will attempt to contact the study authors for more information. The review authors will be unmasked to the trial authors, institution and trial results during the assessment. We will resolve discrepancies by discussion or by consultation with a third author (NLW). Excluded studies along with the reasons for exclusion will be documented in the 'Characteristics of excluded studies' table.

Data extraction and management

Two authors (SML and MTK) independently will extract data from each eligible study and record the data using forms developed and piloted by Cochrane Eyes and Vision. Data items to be extracted will include the following. See Appendix 8 for further details.

  1. Study characteristics: country, setting, publication year, status of publication, title, authors, source, contact address, language and funding sources.

  2. Method: study duration, randomization technique, method of allocation concealment before randomization, masking (participants, provider, outcome assessors), analysis methods for outcomes.

  3. Participants: sampling (random/convenience), number in each intervention group, age, gender, similarity of intervention groups at baseline, withdrawals/losses to follow‐up (reason) and subgroups for whom outcomes were reported.

  4. Interventions: interventions (details of procedure), and medical or other adjunctive treatment (dose, route, duration).

  5. Outcomes: outcomes specified above, any other outcomes reported, other events, times of assessment and length of follow‐up of individual participants. Definitions and methods for ascertaining outcomes will be checked for consistency among studies.

Whenever there are data items that we need clarify or expand, we will contact the trial authors or organizations that sponsored the trial. We will make three attempts (each two weeks apart) to contact trial investigators by email. If no response is received after three attempts, we will use the data available in the trial reports. If data are shown only in figures (for example, mean and standard deviations) and can not be obtained from the authors, we will use GetData Graph Digitizer 2.24 (getdata‐graph‐digitizer.com) to estimate data values from the figures. We will resolve discrepancies by discussion, referring back to the original article or by consultation with a third author (YHZ). One review author will enter data into Review Manager 5 (RevMan 5) (Review Manager 5 2014); a second review author will verify the accuracy of data entry.

Assessment of risk of bias in included studies

Two authors (SML and MTK) independently will assess each included trial for risk of bias according to Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Risk of bias will be assessed using domain‐based evaluations regarding selection bias (random sequence generation, allocation concealment before randomization), performance bias (masking of participants and study personnel), detection bias (masking of outcome assessors), attrition bias (amount, appropriate handling of missing data), reporting bias (selective outcome reporting), and other potential sources of bias (e.g. funding source involvement in trial). We will judge each trial for each 'Risk of bias' domain to be at 'low risk', 'high risk' or 'unclear risk' of the specific bias. All discrepancies between judgements of review authors will be resolved by discussion or by seeking an opinion from a third author (KL). We will contact trial authors to clarify any bias domain graded as conferring 'unclear risk' due to lack of information.

Measures of treatment effect

For dichotomous outcomes, we will calculate risk ratios (RRs) with corresponding 95% confidence intervals (CIs). Dichotomous outcomes planned for this review include the proportion of eyes with UCVA of 20/20 or better, proportion of eyes that lost 1 or more lines of BSCVA, proportion of eyes within ± 0.50 D of target refraction, proportion of eyes with an adverse outcome (significant permanent visual loss or optical side effect).

For continuous outcomes, we will calculate mean differences (MDs) with corresponding 95% CIs. Continuous outcomes planned for this review include mean postoperative spherical equivalent and high‐order aberrations.

Unit of analysis issues

The ideal unit of analysis will be the individual (one study eye per participant). However, we acknowledge that some trials may have used a paired‐eye design, where one eye is randomized to one intervention and the contralateral eye is treated with the other intervention. We will include these trials, as well as trials in which both eyes of a participant are randomized to the same intervention. We will document when both eyes of a participant are included in a trial and assess whether the data analysis appropriately accounts for the non‐independence of eyes. For trials with multiple treatment groups, we will include only the treatment groups relevant to this review (i.e. groups treated with wavefront or conventional excimer laser refractive surgery).

Dealing with missing data

When data are missing from trial reports or are unclearly reported, we will first contact the trial authors to obtain supplemental information. If we are unable to obtain numerical data that are only displayed in figures from trial authors, we will extract the data using the software Get Data Graph Digitizer 2.24 (getdata graph‐digitizer.com). We will not impute data for the purposes of this review; however, when available, we will use trial results when the trial investigators performed appropriate imputation. We will perform sensitivity analysis to examine the potential impact of trials assessed to have high risk of attrition bias.

Assessment of heterogeneity

We will assess clinical and methodological heterogeneity among trials to determine whether meta‐analysis is appropriate. When substantial clinical or methodological heterogeneity is observed, we will not combine studies quantitatively, but rather present a narrative summary of the trial results. When trials are clinically and methodologically similar (homogeneous), we will combine data using meta‐analysis. We will assess statistical heterogeneity using a Chi2 test (with a 10% or smaller probability level suggesting heterogeneity), the I2 statistic (60% representing substantial statistical heterogeneity), and visual inspection of forest plots for consistency in the direction of estimates and overlap of CIs among studies.

Assessment of reporting biases

We will assess potential publication bias using funnel plots when 10 or more trials are included in a meta‐analysis. An asymmetrical funnel plot may be the result of factors such as publication bias, heterogeneity of effects or differences in the methodological quality of studies. We also will evaluate selective outcome reporting as part of our assessment of risk of bias in included studies.

Data synthesis

If substantial statistical heterogeneity is found, we will recheck the data entered into RevMan 5 software. When the data have been confirmed to be correct and the direction of effects is inconsistent, combination of the data across studies may be inappropriate. We will conduct subgroup analyses to explore heterogeneity according to predetermined characteristics defined in the section Subgroup analysis and investigation of heterogeneity. We will use a random‐effects model except when outcome data from fewer than three trials are included in a meta‐analysis, in which case we will use a fixed‐effect model.

Subgroup analysis and investigation of heterogeneity

Subgroup analysis will be performed according to the following ranges of myopia: low to moderate myopia (< ‐0.50 to ‐6.00 D) and moderate to high myopia (< ‐6.00 to ‐15.00 D). Additionally, we intend to perform subgroup analysis for wavefront‐guided or wavefront‐optimized refractive surgery when comparing wavefront versus conventional excimer laser refractive surgery. Other factors such as age, race, laser platform, ablation algorithm and method for creating corneal flap will be considered for subgroup analysis if there is sufficient information reported in the included trials. We will clearly document and provide a rationale for any post‐hoc subgroup analysis.

Sensitivity analysis

We will examine the impact of excluding studies of lower methodological quality, unpublished data and industry funding (when documented in published reports) in sensitivity analyses. We also will exclude some studies that provided extreme estimates of intervention effects compared to other studies (outliers) in sensitivity analysis to explore heterogeneity.

Summary of findings

We will summarize the main findings for each comparison of interest, including strengths and limitations of evidence for primary, secondary, and adverse outcomes, using the GRADE approach (GRADEpro 2014). We will assess the quality of evidence for each outcome as 'high,' 'moderate,' 'low,' or 'very low' according to the following criteria as described in Chapter 12 of the Cochrane Handbook for Systematic Reviews of Interventions (Schünemann 2011).

  • High risk of bias among included studies.

  • Indirectness of evidence.

  • Unexplained heterogeneity or inconsistency of results.

  • Imprecision of results (i.e. wide confidence intervals).

  • High probability of publication bias.

We will present a 'Summary of findings' table for each comparison of interest when data are available. The comparisons will include 1) wavefront‐guided or ‐optimized refractive surgery versus conventional excimer laser refractive surgery and 2) wavefront‐guided versus wavefront‐optimized refractive surgery. We will include the following seven outcomes at 12 months post‐treatment in the 'Summary of findings' tables.

  1. Proportion of eyes with UCVA of 20/20 or better.

  2. Proportion of eyes that had lost 1 or more lines of BSCVA.

  3. Proportion of eyes within ± 0.50 D of target refraction.

  4. Mean refractive error expressed as mean spherical equivalent.

  5. Mean HOAs, measured by machine with wavefront sensor.

  6. Proportion of eyes with significant visual loss (loss of 2 or more lines from pretreatment BSCVA).

  7. Proportion of eyes with optical side effects, such as glare and halo.