Limbal relaxing incisions versus toric intraocular lens for corneal astigmatism after phacoemulsification

Abstract

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

To assess limbal relaxing incisions compared to toric IOL implants in the management of astigmatism during cataract surgery.

Background

Description of the condition

Cataract is the leading cause of treatable blindness and visual impairment (Congdon 2003; Pascolini 2012). In modern cataract surgery, the cataractous natural lens can be removed through a microscopic incision, a technique known as phacoemulsification (Kelman 1967). An intraocular lens (IOL) is then placed within the natural lens capsule to restore the optics of the eye, simultaneously addressing pre‐existing refractive errors such as myopia (short sight) and hyperopia (long sight) (Hirnschall 2014; Visser 2013). Foldable IOLs made from silicone or acrylic material can be inserted through incisions as small as 1.8 mm (Kohnen 2009). These advances have led to increasing expectations of visual outcomes following cataract surgery, with many patients wanting to be able to see at distance without spectacles. Consequently, there are now divergent approaches in the surgical management of a third refractive error: astigmatism (described below). Corneal astigmatism can be treated either by placing incisions in the cornea (limbal relaxing incisions (LRIs)) or by inserting specially designed IOLs (toric IOLs) that can cancel out pre‐existing astigmatism. In one study, the percentage of cataract surgery candidates with clinically significant astigmatism was approximately 22% (Ferrer‐Blasco 2009).

Corneal astigmatism

The eye is formed anteriorly by a transparent dome called the cornea. The natural lens is an encapsulated structure suspended by ligaments posterior to the pupil. The eye can be likened to a photographic camera, with the cornea and lens functioning as a camera lens. The pupil can be compared to the diaphragm aperture. The inner layer of the eye, the retina, is analogous to the film. Refractive errors exist when the eye is not able to focus effectively on distant objects. The cornea is not normally perfectly spherical, being steepest in one meridian and flattest in the perpendicular meridian. A sufficiently large difference in the refractive power of each meridian can result in a blurry image, a condition known as astigmatism. Regular astigmatic errors can be neutralised by toric lenses, which work by optically cancelling out the refractive power of both the steep and flat meridians. Irregular astigmatism occurs when the steep and flat meridians are not perpendicular, and cannot be fully neutralised by a toric lens (de Freitas 2007; Nissman 2006; Saunders 1995; Weale 1983).

Refractive power is measured in dioptres (D). Corneal astigmatism can be assessed using different devices. Optical keratometry is a method used to evaluate corneal curvature at points on the front surface of the central cornea, while in corneal topography, illuminated rings (Placido rings) are projected onto the cornea to measure its curvature up to the periphery. Corneal tomography is a technique that can be used to assess the curvature of both the front and back surfaces of the cornea (Ferrer‐Blasco 2009; Hoffmann 2010; O'Brart 1994; Talamo 1991; Visser 2013). These investigations are important for planning surgical correction of astigmatism (de Freitas 2007; Hoffmann 2010).

Description of the intervention

Incisions across the steep meridian of the cornea have the effect of inducing flattening, thereby reducing corneal astigmatism. The size of this effect depends on the depth, length and position of the incision. LRIs are circumferential incisions placed at the edge of the cornea (limbus) at each end of the steep meridian, using a guarded blade with a pre‐set depth to avoid inadvertent perforation (Arraes 2006; Hirnschall 2014; Kaufmann 2005). The length of the incisions are determined by a nomogram, depending on the extent of astigmatism the surgeon wishes to treat (Hirnschall 2014). It has recently become possible to perform these incisions with extreme precision using a femtosecond laser.

Toric corrections can be incorporated into IOLs, allowing the treatment of corneal astigmatism in increments of 0.50 or 0.75 D (Braga‐Mele 2014). One key aspect of toric IOL placement is alignment of the lens axis with the steep axis of the cornea. The first models of toric IOL had high incidences of postoperative rotation, but advances in IOL material and design have resulted in improved rotational stability (Visser 2013). Following insertion of the IOL into the capsule, it must be rotated to align with the steep corneal axis, which is identified from pre‐operative markings on the cornea (Sheppard 2013; Visser 2013). Recently, it has become possible to use image‐guided technology to indicate the steep axis to the surgeon without prior marking of the cornea (Schultz 2016).

How the intervention might work

LRIs produce a flattening effect that results in a concomitant steepening of the flatter meridian to produce a more spherical corneal shape. Toric IOLs incorporate different refractive powers along perpendicular meridians to optically neutralise the corresponding corneal axes (Visser 2013). It is commonly accepted that LRIs are more suitable for lower levels of astigmatism (less than 2 D), whereas toric IOLs may be more suitable for higher levels (more than 2 D).

Why it is important to do this review

Widespread advances in cataract surgery have raised expectations of visual results, with both surgeons and patients aiming for spectacle independence. Since astigmatism may affect quality of vision after cataract surgery, its treatment should be predictable and stable. LRIs and toric IOLs are two very different strategies. A systematic review of these techniques may help to produce evidence‐based guidelines for managing astigmatism.

Objectives

To assess limbal relaxing incisions compared to toric IOL implants in the management of astigmatism during cataract surgery.

Methods

Criteria for considering studies for this review

Types of studies

We will include randomised controlled trials (RCTs) only in the review.

Types of participants

We will include trials in which participants have cataract associated with corneal astigmatism above 0.50 cylindrical dioptres. We will exclude trials that include other associated ocular diseases such as keratoconus, retinal diseases, and/or irregular astigmatisms. We will also exclude any other ocular procedures other than phacoemulsification, and the interventions evaluated in this study.

Types of interventions

We will include trials that compare limbal relaxing incisions to toric intraocular lens implantation.

Types of outcome measures

Domain: postoperative refractive astigmatism, uncorrected distance visual acuity.

Measurement: magnitude of error (vector analysis of astigmatism), logMAR visual acuity.

Metric: final value at follow‐up.

Type of variable: mean error of magnitude of astigmatism as measured by vector analysis. Mean change in uncorrected distance visual acuity as measured by a logMAR chart.

Range: Astigmatism range of correction from 1 to 3 dioptres (D).

Time‐point: six months or more postoperative.

Primary outcomes

• Proportion of participants with postoperative residual refractive astigmatism of less than 0.50 D at six months.

Secondary outcomes

• Uncorrected postoperative distance visual acuity (logMAR method) at six months.

• Spectacle independence for distance as reported by the participant.

• Vision‐related quality of life.

Adverse effects

We will report any adverse effects present in the studies.

Evaluation of post‐operative lens rotation requiring second procedure to re‐align toric IOL.

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 present) (Appendix 3);

• ISRCTN registry (www.isrctn.com/editAdvancedSearch) (Appendix 4);

• US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov) (Appendix 5);

• World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp) (Appendix 6).

Searching other resources

We will search the reference lists of the studies included in the review.

Data collection and analysis

Selection of studies

Two review authors (JCL, GV) will independently screen the titles and abstracts resulting from the searches using web‐based software (www.Covidence.org). We will resolve disagreements by asking a third author (GJMP) to adjudicate. In general, all citations considered not relevant at this stage will not be documented in the review, other than to note the number of these in a flow chart. We will obtain full‐text copies of potentially relevant trials.

Two review authors (JCL, GV) will assess independently the full‐text copies for inclusion according to the Criteria for considering studies for this review. We will resolve disagreements by discussion. We will correspond with investigators to clarify study eligibility, as appropriate. We will not be masked to the names of the authors, institutions or journal publication when we do this.

We will list all excluded studies and provide a brief justification for exclusion.

For potentially eligible studies identified on trials' registers we will do the following.

• If the study has a completion date more than two years previously, we will look for publications of this trial and contact the investigators if necessary to obtain published or unpublished data from the trial. If eligible, the study will be included in the review irrespective of whether we can identify a publication.

• If the study has a completion date within two years, or in the future, we will document the study in the 'Characteristics of ongoing studies' section.

Data extraction and management

Two review authors (JCL, GV) will extract data independently using an online form developed by Cochrane Eyes and Vision in Covidence 2015. We will resolve discrepancies by discussion. We will contact trial investigators for missing data. All data will be imported directly into Review Manager 5 (RevMan 5) (Review Manager 2014); and the accuracy of the data import will be checked by one author (GJMP).

Study characteristics

We will collect the following information on study characteristics.

• Study design: parallel group RCT/with‐person RCT/one or both eyes reported.

• Participants: country, total number of participants, age, sex, inclusion and exclusion criteria.

• Intervention and comparator details: including number of people (eyes) randomised to each group.

• Primary and secondary outcomes as measured and reported in the trials; adverse events.

• Length of follow‐up.

• Date study conducted.

• Funding and conflicts of interest.

• Included on trials registry Y/N including registration number if available.

Outcome data

We will extract the following data from each included study for intervention and comparator groups separately.

• Mean, standard deviation and number of participants on which outcome measured for continuous variables (residual refractive astigmatism, uncorrected distance visual acuity).

• Proportion of participants achieving spectacle independence.

• Number of adverse events and number of participants on which outcome data collected for dichotomous variables.

For multi‐arm studies we will use data relevant to our intervention and comparator groups. If two groups contain relevant data we will combine groups using the calculator within RevMan 5.

Assessment of risk of bias in included studies

Using Cochrane's 'Risk of bias' tool, two review authors (JCL, GJMP) will assess independently the risk of bias in each included study as described in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

We will resolve disagreements by discussion.

We will specifically consider and report on the following sources of bias.

1. Selection bias (random sequence generation, allocation concealment): was the sequence of allocation generated using a random procedure and was the allocation concealed to people recruiting/enrolling participants and to participants?

2. Performance bias (masking of participants and researchers): were the recipients of care unaware of their assigned intervention? Were persons providing care unaware of the assigned intervention?

3. Detection bias (masking of outcome assessors). Were persons evaluating outcomes unaware of the assigned intervention?

4. Attrition bias: were the rates of follow up and compliance similar in the groups? Was the analysis by intention‐to‐treat and were there any post randomisation exclusions?

5. Selective outcome reporting bias: is there any evidence that the outcomes that were measured have not been reported?

We will grade each domain as low risk of bias, high risk of bias or unclear (lack of information or uncertainty of potential for bias). We will contact trial investigators for clarification of parameters graded as 'unclear'.

Measures of treatment effect

We will calculate the mean difference for the following continuous outcomes: mean change in refractive astigmatism and uncorrected distance visual acuity. Where possible, we will check for the skewness of continuous data (Altman 1996).

Unit of analysis issues

Eyes and people

Trials may randomise one or both eyes to the intervention or comparator. If people are randomly allocated to treatment but only one eye per person is included in the trial then there will be no unit of analysis issue. In these cases, we will document how the eye was selected. If people are randomly allocated to treatment but both eyes are included and reported, we will analyse as 'clustered data' i.e. adjust for within‐person correlation. We may have to contact the trial investigators for further information to do this. If the study is a within‐person study, i.e. one eye is randomly allocated to intervention and the other eye receives the comparator, then we will analyse as paired data. We may have to contact the trial investigators for further information to do this.

Dealing with missing data

If possible, we will conduct an intention‐to‐treat (ITT) analysis. We will use imputed data if computed by the trial investigators using an appropriate method, but will not impute missing data ourselves. If ITT data are not available, we will do an 'available case' analysis. This assumes that data are missing at random. We will assess whether this assumption is reasonable by collecting data from each included trial on the number of participants excluded or lost to follow‐up and reasons for loss to follow‐up by treatment group, if reported.

Assessment of heterogeneity

We will examine the overall characteristics of the studies, in particular the type of participants and types of interventions, to assess the extent to which the studies are similar enough to make pooling study results sensible.

We will look at the forest plots of study results to see how consistent the results of the studies are, in particular looking at the size and direction of effects.

We will calculate I², which is the percentage of the variability in effect estimates that is due to heterogeneity rather than sampling error (chance) (Higgins 2002). We will consider I² values over 50% to indicate substantial inconsistency but will also consider Chi² P values. As this may have low power when the number of studies are few we will consider P < 0.1 to indicate statistical significance of the Chi² test.

Assessment of reporting biases

We will use the risk of bias tool to look for selective or incomplete reporting (see Assessment of risk of bias in included studies).

If there are 10 trials or more included in a meta‐analysis, we will construct funnel plots and consider tests for asymmetry for assessment of publication bias, according to Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Data synthesis

We will pool data using a random‐effects model in RevMan 5. If there are fewer than three trials in a comparison we will use a fixed‐effect model.

If there is inconsistency between individual study results such that a pooled result may not be a good summary of the individual trial results — for example, the effects are in different directions or I² is greater than 50% and P is less than 0.1 — we will not pool the data but will describe the pattern of the individual study results.

If there is statistical heterogeneity but all the effect estimates are in the same direction such that a pooled estimate would seem to provide a good summary of the individual trial results we may pool the data.

Subgroup analysis and investigation of heterogeneity

If there are sufficient trials we will compare the effect of treatment in the following subgroups and on all outcomes.

• Techniques of limbal relaxing incisions: corneal relaxing incisions, corneal arcuate incisions, femtosecond laser‐assisted corneal or limbal incisions

• Differential effects of treatment of less than 2 D and more than 2 D of astigmatism (addressing the hypothesis that LRIs are better for lesser degrees and toric lenses for higher degrees of astigmatism).

• Age groups: 65 years or more/less than 65 years.

• Materials and models of toric IOLs.

Sensitivity analysis

We will perform the following sensitivity analyses on the primary outcome considering:

• excluding studies at high risk of bias in one or more domains;

• excluding industry‐funded studies;

• comparing fixed‐ and random‐effect models (if three or more trials).

Summary of findings

We will prepare a summary of findings table presenting relative and absolute risks. Two authors will grade independently the overall quality of the evidence for each outcome using the GRADE classification (GRADEpro 2014).

Appendices

Appendix 1. CENTRAL search strategy

#1 limbal near/2 relax* #2 LRI or LRIs #3 #1 or #2 #4 MeSH descriptor: [Cataract Extraction] explode all trees #5 MeSH descriptor: [Lenses, Intraocular] explode all trees #6 MeSH descriptor: [Lens Implantation, Intraocular] explode all trees #7 cataract* or phaco* or phako* #8 (intraocular or intra ocular) near/3 lens* #9 IOL or IOLs #10 toric #11 #4 or #5 or #6 or #7 or #8 or #9 or #10 #12 #3 and #11

Appendix 2. MEDLINE Ovid search strategy

1. randomized controlled trial.pt. 2. (randomized or randomised).ab,ti. 3. placebo.ab,ti. 4. dt.fs. 5. randomly.ab,ti. 6. trial.ab,ti. 7. groups.ab,ti. 8. or/1‐7 9. exp animals/ 10. exp humans/ 11. 9 not (9 and 10) 12. 8 not 11 13. (limbal adj2 relax$).tw. 14. (LRI or LRIs).tw. 15. 13 or 14 16. exp Cataract Extraction/ 17. exp Lenses, Intraocular/ 18. Lens Implantation, Intraocular/ 19. (cataract$ or phaco$ or phako$).tw. 20. ((intraocular or intra ocular) adj3 lens$).tw. 21. (IOL or IOLs).tw. 22. toric.tw. 23. or/16‐22 24. 15 and 23 25. 12 and 24

The search filter for trials at the beginning of the MEDLINE strategy is from the published paper by Glanville 2006.

Appendix 3. Embase Ovid search strategy

1. exp randomized controlled trial/ 2. exp randomization/ 3. exp double blind procedure/ 4. exp single blind procedure/ 5. random$.tw. 6. or/1‐5 7. (animal or animal experiment).sh. 8. human.sh. 9. 7 and 8 10. 7 not 9 11. 6 not 10 12. exp clinical trial/ 13. (clin$ adj3 trial$).tw. 14. ((singl$ or doubl$ or trebl$ or tripl$) adj3 (blind$ or mask$)).tw. 15. exp placebo/ 16. placebo$.tw. 17. random$.tw. 18. exp experimental design/ 19. exp crossover procedure/ 20. exp control group/ 21. exp latin square design/ 22. or/12‐21 23. 22 not 10 24. 23 not 11 25. exp comparative study/ 26. exp evaluation/ 27. exp prospective study/ 28. (control$ or prospectiv$ or volunteer$).tw. 29. or/25‐28 30. 29 not 10 31. 30 not (11 or 23) 32. 11 or 24 or 31 33. (limbal adj2 relax$).tw. 34. (LRI or LRIs).tw. 35. 33 or 34 36. exp cataract extraction/ 37. exp lens implant/ 38. exp lens implantation/ 39. (cataract$ or phaco$ or phako$).tw. 40. ((intraocular or intra ocular) adj3 lens$).tw. 41. (IOL or IOLs).tw. 42. toric.tw. 43. or/36‐42 44. 35 and 43 45. 32 and 44

Appendix 4. ISRCTN search strategy

limbal AND relax

Appendix 5. ClinicalTrials.gov search strategy

limbal AND relax

Appendix 6. WHO ICTRP search strategy

limbal AND relaxing

Appendix 7. Data on study characteristics

Mandatory items		Optional items
Methods
Study design	∙ Parallel group RCTi.e. people randomised to treatment ∙ Within‐person RCTi.e. eyes randomised to treatment ∙ Cluster RCTi.e. communities randomised to treatment ∙ Cross‐over RCT ∙ Other, specify	Exclusions after randomisation Losses to follow‐up Number randomised/analysed How were missing data handled? e.g. available case analysis, imputation methods Reported power calculation (Y/N), if yes, sample size and power Unusual study design/issues
Eyes or Unit of randomisation/unit of analysis	∙ One eye included in study, specify how eye selected ∙ Two eyes included in study, both eyes received same treatment, briefly specify how analysed (best/worst/average/both and adjusted for within person correlation/both and not adjusted for within person correlation) and specify if mixture one eye and two eye ∙ Two eyes included in study, eyes received different treatments,specify if correct pair‐matched analysis done
Participants
Country		Setting Ethnic group Equivalence of baseline characteristics (Y/N)
Total number of participants	This information should be collected for total study population recruited into the study. If these data are only reported for the people who were followed up only, please indicate.
Number (%) of men and women
Average age and age range
Inclusion criteria
Exclusion criteria
Interventions
Intervention (n = ) Comparator (n = ) See MECIR 65 and 70	∙ Number of people randomised to this group ∙ Drug (or intervention) name ∙ Dose ∙ Frequency ∙ Route of administration
Outcomes
Primary and secondary outcomes as defined in study reports See MECIR R70	List outcomes Adverse events reported (Y/N) Length of follow up and intervals at which outcomes assessed	Planned/actual length of follow up
Notes
Date conducted	Specify dates of recruitment of participants mm/yr to mm/yr	Full study name: (if applicable) Reported subgroup analyses (Y/N) Were trial investigators contacted?
Sources of funding
Declaration of interest See MECIR 69

Contributions of authors

JCL: writing of the protocol GC: editing protocol GV, MRS: revision and proofing GJMP: final revision and editing

Sources of support

Internal sources

• No sources of support supplied

External sources

• National Institute for Health Research (NIHR), UK.

  • Richard Wormald, Co‐ordinating Editor for Cochrane Eyes and Vision (CEV) acknowledges financial support for his CEV research sessions from the Department of Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology.
  • This protocol was supported by the NIHR, via Cochrane Infrastructure funding to the CEV UK editorial base.

  The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.

Declarations of interest

JCL has no financial interest in the subject matter of this systematic review. GV has no financial interest in the subject matter of this systematic review. MRS has no financial interest in the subject matter of this systematic review. GC has no financial interest in the subject matter of this systematic review. GJMP has no financial interest in the subject matter of this systematic review.

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