Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To evaluate the comparative effectiveness and safety of various materials used in frontalis sling surgery for congenital ptosis.
Background
Description of the condition
Congenital ptosis is a drooping of one or both eyelids at birth, often due to poor development of the levator palpebrae superioris muscle responsible for lifting the eyelids (Takahashi 2010). Simple congenital ptosis occurs in 5.9 per 100,000 people (Griepentrog 2011). Syndromes associated with congenital ptosis include congenital cranial dysinnervation disorders, blepharophimosis ptosis epicanthus inversus syndrome, congenital fibrosis of the extraocular muscles, Marcus Gunn jaw winking syndrome, and Horner's syndrome (SooHoo 2014).
In congenital ptosis, fibrous and adipose tissues are often present in place of the normal levator muscle tissue, hindering the contraction of the muscle (Yoon 2009). Moderate or severe instances can result in the eyelid obscuring part or all of the pupil, leading to complications including amblyopia, astigmatism, and ocular torticollis (Lin 2008). Consequently, congenital ptosis often necessitates surgical intervention in early childhood (Takahashi 2010).
Description of the intervention
The most effective surgical treatment for moderate to severe congenital ptosis is frontalis sling (also known as frontalis suspension) surgery, as first described by Crawford (Crawford 1956). This technique is indicated in children with very poor levator function (Crawford 1971). It involves attaching the tarsal plate to the frontalis muscle, allowing the patient to raise the eyelid by lifting the brow, rather than relying on the dysfunctional levator palpebrae superioris (Philandrianos 2010). Many different materials have been used to form this attachment, including fascia lata (both autologous and preserved), silicone rods, temporalis fascia, sclera, nonabsorbable sutures, suture reinforced sclera, frontalis muscle, Gore‐Tex strips (polytetrafluoroethylene synthetic material), polyester mesh, and Supramid (polyfilament, cable‐type 3‐0 suture).
General anesthesia is used for children undergoing the procedure. Incisions are made in the eyelid and the upper portion of the brow, and material is passed through the eyelid in the suborbicularis fascial plane and anchored to the incisions in the brow. The frontalis muscle, which typically serves to raise the brow, can subsequently be used to lift the eyelid as well (Woo 2014).
Frontalis sling surgery may exhibit decreased effectiveness in the long term, with the eyelid gradually reassuming its former position. Further surgery may be needed in these cases to improve the position of the eyelid. Complications of the surgery besides recurrence of ptosis may include exposure keratopathy, irregular lid contour, and granuloma formation (Mokhtarzadeh 2015).
How the intervention might work
The short‐ and long‐term efficacy of the surgery, as well as the rate of complications, have been shown to vary based on the material used to form the connection between the eyelid and the brow (Mehta 2004; Mokhtarzadeh 2015). Various features of the materials have been posited to influence these outcomes, such as surface roughness (Choi 2011) and tensile strength (Mehta 2004).
Why it is important to do this review
As stated above, children undergo frontalis sling surgery to help their vision develop in the affected eye. When the ptosis recurs, they are at risk for amblyopia and induced astigmatism. Preventing recurrence by using the best material may help avoid this situation. Reducing the likelihood of recurrent ptosis also increases patient wellness by avoiding the risks and discomforts of additional surgery. Furthermore, the effectiveness and reliability of the surgery may have cosmetic implications for the patient.
A systematic review regarding the functional and cosmetic effectiveness of the various materials currently used for frontalis sling surgery will help identify the most desirable material and also establish preferred alternatives for instances in which that material is contraindicated, not available, or cost ineffective.
Objectives
To evaluate the comparative effectiveness and safety of various materials used in frontalis sling surgery for congenital ptosis.
Methods
Criteria for considering studies for this review
Types of studies
We will include randomized controlled trials (RCTs) only. We will include reports published in any language.
Types of participants
We will include trials in which participants underwent frontalis sling surgery for congenital ptosis. We will not apply any restrictions regarding location or demographic factors. We will include all age groups.
Types of interventions
We will include trials in which materials used in the frontalis sling surgery were compared in regard to their effectiveness in maintaining eyelid lift. Specific materials of interest include autologous fascia lata, preserved (banked) fascia lata, and silicone rods. We will not include trials in which only one material was studied, with no comparison involved. We will not exclude trials that used other background therapy or cointerventions, such as treatment of amblyopia, as long as the main comparison was among materials used in the frontalis sling surgery.
Types of outcome measures
Primary outcomes
The primary outcome for this review will be functional success of the surgery, defined as improvement of the eyelid position above the pupillary margin. Functional success may be measured differently in different trials. Examples we have found are categorization as 'good', 'fair', or 'poor' results; measurements in millimeters above the visual axis; measurements of margin to reflex distance; comparison to the other (normal) side in millimeters.
The primary timing of assessment will be at one year follow‐up; we also will consider different follow‐up times as reported by included trials.
Secondary outcomes
The secondary outcomes will include:
the proportion of participants with recurrence after surgery;
the proportion of participants with sling removal; and
the proportion of participants with infection.
Adverse outcomes
We will tabulate any ocular and systemic complications related to the surgery as reported in the included studies. Our specific adverse events of interest include granuloma formation, extrusion of sling material, entropion, and wound dehiscence.
Economic data
We will include any relevant economic data regarding costs of treatment.
Quality of life data
We will compare quality of life data, measured with questionnaires, when available.
Search methods for identification of studies
Electronic searches
The Cochrane Eyes and Vision Information Specialist will search the following electronic databases for randomized controlled 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 (1947 to present) (Appendix 3).
PubMed (1948 to present) (Appendix 4).
Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to present) (Appendix 5).
US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov) (Appendix 6).
World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp) (Appendix 7).
Searching other resources
We will search the reference lists of trials included in the review for additional trials. We also will use the Science Citation Index to find trials that have cited the identified trials.
Data collection and analysis
Selection of studies
Two authors independently will review the titles and abstracts identified by the electronic and manual search to identify potential citations for inclusion. The abstracts will be placed in three categories: include, uncertain, exclude. We will acquire full‐text reports of all records in the first two categories. Two authors independently will review the reports to determine eligibility for inclusion, again placing them into three categories: include, exclude, or awaiting assessment. All excluded studies will be documented and the reason for exclusion will be reported in a table. Articles in the 'include' category will be assessed for risk of bias. For the 'awaiting assessment' category, we will contact study authors by email to obtain information that will allow us to include or exclude the study from review, allowing them two weeks to respond. If they do not respond, we will contact them a second time and give another two weeks to respond. After four weeks, we will classify all studies based on the available information. All discrepancies will be resolved by discussion with a third author. Names of authors, institutions, and journals will not be masked during the review.
Data extraction and management
Two review authors will extract data on study characteristics, including study design, participant characteristics, interventions and outcomes assessed (Appendix 8). Any discrepancies will be resolved by discussion. In the case of missing data, we will contact authors of trials. If within four weeks of contacting the trial authors we receive no response, we will evaluate the study based on the published data. The data will be entered into Review Manager 5 (Review Manager 2014) by one author, and verified by a second author for discrepancies.
Assessment of risk of bias in included studies
To assess the risk of bias in included studies, we will use the guidelines provided in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will consider:
sequence generation;
allocation concealment before randomization;
masking (blinding) of participants and personnel;
masking (blinding) of outcome assessors;
incomplete outcome data;
selective outcome reporting; and
other sources of bias.
Two review authors independently will conduct the assessments using the 'Risk of bias' tool. Levels of biases will be designated 'high', 'low' or 'unclear'. We will resolve disagreements by discussion.
Measures of treatment effect
The outcomes may be reported as dichotomous or continuous outcomes.
We will calculate risk ratios using confidence intervals (CIs) of 95% for dichotomous outcomes, which may include the proportion of participants with functional success ('good' or 'fair' surgical results), the proportion of participants with recurrence after surgery, the proportion of participants with sling removal, the proportion of participants with infection, and the proportion with complications.
We will calculate mean differences using CIs of 95% for continuous outcomes, such as functional success measured as margin to reflex distance in millimeters.
Unit of analysis issues
The unit of analysis will be the individual, including one eye from each participant. We will document trials for which both eyes were treated as units for analysis.
Dealing with missing data
We will contact study authors by email to obtain missing data that will allow us to include or exclude the study from the review, allowing them two weeks to respond. If they do not respond, we will contact them a second time, allowing another two weeks for response. After four weeks, we will conduct a sensitivity analysis to discuss the impact of the missing data on our analysis. We will not impute data for the purpose of this review but consider imputed data when they were included in the studies using appropriate methods, such as multiple imputation. Studies using inappropriate methods of imputation such as last observation carried forward will be documented.
Assessment of heterogeneity
We will examine the clinical, methodological and statistical heterogeneity among included studies. Clinical heterogeneity will be examined by evaluating differences in study participants, interventions and outcomes. Methodologic heterogeneity implies differences in study design and analysis. To assess statistical heterogeneity between trials and consistency across studies we will examine the forest plot of trial results and the I2 value. If the I2 value exceeds 60%, we will interpret that as evidence of substantial statistical heterogeneity.
Assessment of reporting biases
We will analyze possible reporting biases according to the tool outlined in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will assess for selective outcome reporting at the trial level as part of the 'Risk of bias' assessment. When 10 or more studies are included in a meta‐analysis, we will analyze funnel plots to judge the possibility of publication bias.
Data synthesis
Depending on the number of trials and the evidence of heterogeneity, we will use either a random‐effects model or a fixed‐effect model to perform meta‐analysis. When there are three or more trials that contribute data to a meta‐analysis, we will use a random‐effects model as long as there is no evidence of clinical or methodologic heterogeneity; when there are fewer than three trials, we will use a fixed‐effect model. If substantial evidence of heterogeneity, as described in the relevant section above, indicates that a meta‐analysis should not be conducted, we will write a narrative summary of findings from included studies.
Subgroup analysis and investigation of heterogeneity
We will not be performing a subgroup analysis for this review.
Sensitivity analysis
We will determine and report the effect of incorporating studies for which we judge the risk of bias to be 'high' for any of the domains assessed.
Summary of findings
We will prepare a 'Summary of findings' table for the following outcomes at one year follow‐up: 1) functional success of the surgery, 2) recurrence after surgery, 3) sling removal, 4) infection, 5) complications related to the surgery, 6) costs of treatment, and 7) quality of life outcomes.
We will use the GRADE Working Group approach to assess the overall certainty of the evidence for each outcome estimate as 'very low', 'low', 'moderate', or 'high' (GRADEpro 2014). We will assess the five major domains of risk of bias, imprecision, inconsistency, publication bias, and indirectness. Two review authors independently will grade the evidence and resolve discrepancies by discussion.
Acknowledgements
The Department of Ophthalmology and Visual Sciences at Montefiore Medical Center is the recipient of an unrestricted grant from Research to Prevent Blindness.
Lori Rosman, Information Specialist for Cochrane Eyes and Vision (CEV), created and will execute the electronic search strategies. We thank the CEV US Satellite for providing methodological and statistical support. We also thank Rachel Sobel and Barbara Hawkins for peer reviewing the protocol.
Appendices
Appendix 1. CENTRAL search strategy
#1 MeSH descriptor: [Blepharoptosis] explode all trees #2 (Blepharoptos* or ptosis or ptoses or ptotic) #3 ((droop* or sag* or bag*) and (eye* or lid* or palpebra*)) #4 #1 or #2 or #3 #5 MeSH descriptor: [Surgical Procedures, Operative] explode all trees #6 (Blepharoplast* or Frontalis or sling* or suspension*) #7 (surger* or surgi* or reconstruct* or correction*) #8 #5 or #6 or #7 #9 #4 and #8
Appendix 2. MEDLINE Ovid search strategy
1. Randomized Controlled Trial.pt. 2. Controlled Clinical Trial.pt. 3. (randomized or randomised).ab,ti. 4. placebo.ab,ti. 5. drug therapy.fs. 6. randomly.ab,ti. 7. trial.ab,ti. 8. groups.ab,ti. 9. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 10. exp animals/ not humans.sh. 11. 9 not 10 12. exp Blepharoptosis/ 13. (Blepharoptos* or ptosis or ptoses or ptotic).tw. 14. ((droop* or sag* or bag*) and (eye* or lid* or palpebra*)).tw. 15. 12 or 13 or 14 16. exp Surgical Procedures, Operative/ 17. (Blepharoplast* or Frontalis or sling* or suspension*).tw. 18. surgery.fs. 19. (surger* or surgi* or reconstruct* or correction*).tw. 20. 16 or 17 or 18 or 19 21. 15 and 20 22. 11 and 21
The search filter for trials at the beginning of the MEDLINE strategy is from the published paper by Glanville 2006.
Appendix 3. EMBASE.com search strategy
#1 'randomized controlled trial'/exp #2 'randomization'/exp #3 'double blind procedure'/exp #4 'single blind procedure'/exp #5 random*:ab,ti #6 #1 OR #2 OR #3 OR #4 OR #5 #7 'animal'/exp OR 'animal experiment'/exp #8 'human'/exp #9 #7 AND #8 #10 #7 NOT #9 #11 #6 NOT #10 #12 'clinical trial'/exp #13 (clin* NEAR/3 trial*):ab,ti #14 ((singl* OR doubl* OR trebl* OR tripl*) NEAR/3 (blind* OR mask*)):ab,ti #15 'placebo'/exp #16 placebo*:ab,ti #17 random*:ab,ti #18 'experimental design'/exp #19 'crossover procedure'/exp #20 'control group'/exp #21 'latin square design'/exp #22 #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 #23 #22 NOT #10 #24 #23 NOT #11 #25 'comparative study'/exp #26 'evaluation'/exp #27 'prospective study'/exp #28 control*:ab,ti OR prospectiv*:ab,ti OR volunteer*:ab,ti #29 #25 OR #26 OR #27 OR #28 #30 #29 NOT #10 #31 #30 NOT (#11 OR #23) #32 #11 OR #24 OR #31 #33 'ptosis'/exp #34 blepharoptos*:ab,ti OR ptosis:ab,ti OR ptoses:ab,ti OR ptotic:ab,ti #35 (droop*:ab,ti OR sag*:ab,ti OR bag*:ab,ti) AND (eye*:ab,ti OR lid*:ab,ti OR palpebra*:ab,ti) #36 #33 OR #34 OR #35 #37 'eyelid reconstruction'/exp #38 blepharoplast*:ab,ti OR frontalis:ab,ti OR sling*:ab,ti OR suspension*:ab,ti #39 'surgery'/exp #40 surgery:lnk #41 surger*:ab,ti OR surgi*:ab,ti #42 #37 OR #38 OR #39 OR #40 OR #41 #43 #36 AND #42 #44 #32 AND #43
Appendix 4. PubMed search strategy
1. ((randomized controlled trial[pt]) OR (controlled clinical trial[pt]) OR (randomised[tiab] OR randomized[tiab]) OR (placebo[tiab]) OR (drug therapy[sh]) OR (randomly[tiab]) OR (trial[tiab]) OR (groups[tiab])) NOT (animals[mh] NOT humans[mh]) 2. (Blepharoptos*[tw] OR ptosis[tw] OR ptoses[tw] OR ptotic[tw]) NOT Medline[sb] 3. ((droop*[tw] OR sag*[tw] OR bag*[tw]) AND (eye*[tw] OR lid*[tw] OR palpebra*[tw])) NOT Medline[sb] 4. #2 OR #3 5. (Blepharoplast*[tw] OR Frontalis[tw] OR sling*[tw] OR suspension*[tw]) NOT Medline[sb] 6. (surger*[tw] OR surgi*[tw] OR reconstruct*[tw] OR correction*[tw]) NOT Medline[sb] 7. #5 OR #6 8. #4 AND #7 9. #1 AND #8
Appendix 5. LILACS search strategy
(Blepharoptos$ or Blefaroptos$ or MH:C11.338.204$ or ptosis or ptoses or ptotic or ((droop$ or sag$ or bag$) and (eye$ or lid$ or palpebral$))) AND (MH:E04$ or MH:VS3.003.001.006.002$ or Blepharoplast$ or Blefaroplast$ or Frontalis or sling$ or suspension$ or surger$ or Cirugía$ or surgi$ or reconstruct$ or correction$)
Appendix 6. ClinicalTrials.gov search strategy
blepharoptosis OR eyelid ptosis OR blepharoplasty
Appendix 7. ICTRP search strategy
blepharoptosis OR eyelid ptosis OR blepharoplasty
Appendix 8. Data on study characteristics
| Mandatory items | Optional items | |
| Methods | ||
| Study design | · Parallel group RCTi.e. people randomized to treatment · Within‐person RCTi.e. eyes randomized to treatment · Cluster RCTi.e. communities randomized to treatment · Cross‐over RCT · Other, specify |
Exclusions after randomization Losses to follow up Number randomized/analyzed 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 randomization/ 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 analyzed(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 randomized 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 |
Contributions of authors
Conception and design of study: JBR, JJA, AB
Drafting the review or commenting on it critically for intellectual content: JBR, JJA, AB
Final approval of the document to be published: JBR, JJA, AB
Sources of support
Internal sources
No sources of support supplied
External sources
Cochrane Eyes and Vision US Project, supported by grant 1 U01 EY020522, National Eye Institute, National Institutes of Health, USA.
-
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 National Institute for Health Research, 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
None
New
References
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