You are here

Article Text

Article menu

Download PDFPDF

Clinical science
Internal limiting membrane peeling or not: a systematic review and meta-analysis of idiopathic macular pucker surgery
  1. Xiao-Ling Fang1,
  2. Yao Tong2,
  3. Ya-Li Zhou3,
  4. Pei-Quan Zhao2,
  5. Zhao-Yang Wang3
  1. 1Department of Ophthalmology, Shanghai Eye Disease Prevention and Treatment Center, Shanghai, China
  2. 2Department of Ophthalmology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
  3. 3Department of Ophthalmology, The Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  1. Correspondence to Dr Zhao-yang Wang, Department of Ophthalmology, The Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, P. R. China; zhaokekewzy{at}hotmail.com

Abstract

Purpose To determine whether internal limiting membrane (ILM) peeling improves anatomical and functional outcomes in idiopathic macular pucker (IMP)/epiretinal membrane (ERM) surgery in this systematic review and meta-analysis.

Methods We searched the PubMed, Medline, Web of Science, Cochrane, Ovid MEDLINE, ClinicalTrials.gov and CNKI databases for studies published before 15 September 2016. The eligibility criteria included studies comparing ILM peeling versus no-peeling for IMP surgery.

Results Thirteen articles (10 retrospective cohort studies, 1 prospective cohort study and 2 randomised controlled trials (RCTs)) were included in the review. Primary outcomes: no differences were observed in the best-corrected visual acuity (BCVA) or central macular thickness (CMT) at 12 months; however, lower ERM recurrence (OR, 0.13; 95% CI 0.04 to 0.41; p=0.0004) and reoperation rates (OR, 0.10; 95% CI 0.02 to 0.49; p=0.004) that favoured ILM peeling were observed at the final follow-up. Secondary outcomes: no difference was observed in BCVA at 3, 6 months, the final follow-up or in CMT at 3, 6 months, the final follow-up. Significantly increased CMT, which favoured ILM peeling, was observed at the final follow-up (p=0.002) in the RCTs.

Conclusions ILM peeling yielded greater anatomical success, but no improvement in functional outcomes as the treatment of choice for patients undergoing IMP surgery.

  • Treatment Surgery
  • Retina

https://doi.org/10.1136/bjophthalmol-2016-309768

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Introduction

    Idiopathic epiretinal membrane (ERM) is a common disease affecting 2% of individuals younger than 60 years of age and 12% of those older than 70 years of age.1

    Visual disturbance resulting from decreased best-corrected visual acuity (BCVA) with or without metamorphopsia because of retinal wrinkling and distortion is the main indication for ERM surgery.2 ERM symptoms also include micropsia, macropsia and monocular diplopia.3

    Although pars plana vitrectomy is accepted as the typical treatment for idiopathic ERM causing macular pucker,4 the additional use of internal limiting membrane (ILM) peeling has remained a matter of debate for many years. ILM peeling can reduce the risk of ERM recurrence.5–7

    The ILM is the basal lamina of Müller cells, which are involved in the generation of the electroretinogram (ERG) b wave. Therefore, its removal may cause functional and mechanical damage to the Müller cells.8–10

    The number of surgeons reporting that they routinely peel the ILM increased from 25% in 2008 to 44% in 2010. Conversely, the number of surgeons who have never peeled the ILM during vitrectomy decreased from 24.7% in 2008 to 10.9% in 2011 (American Society of Retinal Specialists, Preferences and Trends Survey).

    Thus, we aimed to determine whether ILM peeling improves the functional and anatomical aspects of idiopathic macular pucker (IMP), such as presenting vision, postoperative central macular thickness (CMT) and ERM recurrence, when compared with non-ILM peeling.

    Methods

    Eligibility criteria

    We included only studies that fulfilled all of the following three criteria: (1) patients with only an idiopathic ERM were considered. The term ‘idiopathic’ referred to ERM occurring in the absence of any known vitreoretinal disease or pathology except for posterior vitreous detachment. (2) Study design was limited to cohort studies and randomised controlled trials (RCTs), not case-control studies, reviews, case reports or editorial comments. (3) The major study objective was to compare ILM peeling versus non-ILM peeling in IMP.

    We did not restrict inclusion on the bias of participant age, sex or ethnicity. Studies of secondary macular pucker (venous occlusion, diabetic retinopathy, retinal tear, retinal detachment, uveitis, trauma, etc) were excluded.

    Search strategy

    We searched the following databases: PubMed, Medline, Web of Science, Cochrane Central Register of Controlled Trials, part of the Cochrane Library, Ovid MEDLINE, EMBASE, metaRegister of Controlled Trials, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform and CNKI.

    We used the following search terms: (‘Internal Limiting Membrane’ OR ‘inner limiting membrane’) and (‘epiretinal membrane’ OR ‘Macular pucker’ OR ‘epimacular membrane’) (see online supplementary PDF 1). All related articles were published before 15 September 2016 without any language limitations.

    Data collection and risk of bias assessment

    Two reviewers (X-LF and YT) independently extracted the data and evaluated the quality. We assessed the risk of bias for the cohort studies using the Newcastle-Ottawa scale,11 ,12 which provides a score from a possible total of nine stars. We used the Cochrane risk of bias tool13 to assess the risk of bias in RCTs. Additionally, the overall quality of evidence for each specified meta-analysis outcome was evaluated using the ‘Grading of Recommendations Assessment, Development and Evaluation’ criteria.14 ,15

    The following variables were extracted from each study: first author, publication year, sample size, staining of ILM and measured outcomes. An independent review and resolution was performed by a third reviewer (Z-YW), if the two reviewers disagreed. The measured outcomes included postoperative follow-ups (3, 6 and 12 months and final follow-ups), distance BCVA (was converted to a logarithm of the minimum angle of resolution (logMAR) for clarity and statistical comparison purposes), CMT, ERM recurrence and reoperation rate.

    The primary outcomes were BCVA and CMT at 12 months and ERM recurrence and reoperation rate at the final follow-up. Secondary outcomes were BCVA and CMT at 3, 6 months and at the final follow-up. The final follow-up times were different in each study, the mean follow-up times were 8.9–23.55 months (range 5–134).

    Data synthesis and analysis

    Between-study heterogeneity was assessed using the Q-statistic test and the I2 statistic.16 ,17 A p value <0.1 was considered to be statistically significant for the Q-statistic test. I2 ranges were between 0% and 100% (where a value of 0% represents no heterogeneity, 0%<I2<25% represents mild, 25%≤I2<50% represents moderate, 75%≤I2 represents great heterogeneity).16 For consistency, we used a random effects model for all meta-analyses.16 ,17

    We assessed publication and small-study bias using a funnel plot of the data and Egger’s test.18 A leave-one-out sensitivity analysis was performed by iteratively removing one study at a time to confirm that our findings were not driven by any single study when I2>25%.16 ,19 Cumulative meta-analysis was performed to evaluate the accumulation of evidence, the relative benefits and risks of ILM peeling and no-ILM peeling.

    The results of individual studies were pooled using Review Manager software (V.5.3, the Cochrane Collaboration, Oxford, England). All other statistical analyses were performed using Stata software (V.12.0; Stata, College Station, Texas, USA). All tests were two-tailed. A p value <0.05 was considered to be statistically significant, except for the test of among-study heterogeneity.

    Results

    Search results

    A total of 237 relevant studies were identified through our initial search, and 13 of these studies were eligible for inclusion in this review.5 ,7 ,20–30

    Figure 1 presents the flow chart of the selection process used to identify the eligible studies. Four of these studies did not have complete data, but the authors kindly provided online supplementary material.5 ,27–29

    Figure 1
    Figure 1

    Literature search process. A flow diagram depicting the screening process of the retrieved articles, including the reason for and number of exclusions.

    Table 1 presents the summary characteristics of the 13 included studies. Ten included studies were retrospective cohort studies,5 ,7 ,20–25 ,29 ,30 one was prospective cohort study26 and two were RCTs.27 ,28

    View this table:
    Table 1

    Main characteristics and quality assessment of the studies included in the meta-analysis

    The number of patients (eyes) included in all 11 non-randomised studies was 562 in the ILM peeling group, 486 in the no-ILM peeling group. The number of patients (eyes) included in 2 RCTs was 47 in the ILM peel group, 47 in the non-ILM peel group.

    Based on the Newcastle-Ottawa scale, four studies rated nine of a possible nine stars, six studies rated eight stars and one study rated seven stars, suggesting that these studies were of satisfactory quality to be included in the meta-analysis (table 1, see online supplementary table S1); the Cochrane risk of bias tool revealed an unclear risk of bias in the two RCTs (table 1).

    Primary and secondary outcomes

    No evidence of a difference in BCVA at 12 months (primary outcome) was noted between the ERM+ILM peeling groups and the ERM peeling groups in all included studies (mean difference (MD), 0.02; 95% CI −0.02 to 0.05; p=0.37) (figure 2). Similarly, there was no evidence of a difference in BCVA at 3 months (MD, 0.20; 95% CI 0.00 to 0.39; p=0.05), 6 months (MD, −0.02; 95% CI −0.06 to 0.02; p=0.35) or at the final follow-up (MD, −0.01; 95% CI −0.06 to 0.05; p=0.84) (see online supplementary figure S1).

    Figure 2
    Figure 2

    Forest plot comparing best-corrected visual acuity (logarithm of the minimum angle of resolution (logMAR)) at 12 months between the internal limiting membrane (ILM) peeling and non-ILM peeling groups in all included studies, non-randomised studies and randomised controlled trials. ERM, epiretinal membrane.

    No evidence of a difference in CMT at 12 months (primary outcome) was noted between the two groups (MD, 6.39; 95% CI −20.91 to 33.69; p=0.65) (figure 3). Similarly, there was no evidence of a difference in CMT at 3 months (MD, 6.94; 95% CI −14.78 to 28.66; p=0.53), 6 months (MD, 11.99; 95% CI −5.73 to 29.71; p=0.18) or the final follow-up (MD, 20.59; 95% CI −0.22 to 41.40; p=0.05) (see online supplementary figure S2).

    Figure 3
    Figure 3

    Forest plot comparing central macular thickness at 12 months between the internal limiting membrane (ILM) peeling and non-ILM peeling groups in all included studies, non-randomised studies and randomised controlled trials (RCTs). ERM, epiretinal membrane.

    There was evidence of lower ERM recurrence rates (OR, 0.13; 95% CI 0.04 to 0.41; p=0.0004) and lower reoperation rates (OR, 0.10; 95% CI 0.02 to 0.49; p=0.004) was noted in the ILM peeling group (figure 4).

    Figure 4
    Figure 4

    Forest plot comparing epiretinal membrane (ERM) recurrence rates (A) and reoperation rates (B) between the internal limiting membrane (ILM) peeling and non-ILM peeling groups in all included studies, non-randomised studies and randomised controlled trials (RCTs).

    The overall quality of evidence for each specified meta-analysis outcome was evaluated (see online supplementary table S2).

    Subgroup analyses

    Non-randomised studies

    No evidence of a difference in BCVA at 12 months was observed between the two groups (MD, 0.01; 95% CI −0.05 to 0.07; p=0.67) (figure 2). There was no evidence of a difference in BCVA at 3 months (MD, 0.21; 95% CI −0.02 to 0.45; p=0.08) at 6 months (MD, −0.03; 95% CI −0.08 to 0.03; p=0.34) or at the final follow-up (the mean follow-up period was ≥12 months) (MD, –0.04; 95% CI −0.11 to 0.04; p=0.31).

    Similarly, there was no evidence of a difference in CMT at 12, 3 or 6 months or at the final follow-up between the two groups ((MD, −7.29; 95% CI −28.09 to 13.52; p=0.49), (MD, −5.50; 95% CI −24.06 to 13.05; p=0.56), (MD, 2.48; 95% CI −16.26 to 21.23; p=0.80), (MD, 14.49; 95% CI −11.67 to 40.65; p=0.28), respectively) (figure 3, see online supplementary figure S2).

    The studies included in non-randomised studies of ERM recurrence rate and reoperation rate were same in all included studies (figure 4).

    Findings from the non-randomised studies were consistent with those from all included studies.

    Randomised controlled trials

    Only BCVA and CMT data at the final follow-up were available in one RCT.28 No evidence of a difference in BCVA at the final follow-up was noted between the two groups, but there was evidence of increased CMT after ILM peeling compared with no-ILM peeling at the final follow-up (mean follow-up period ≥8.9 months) (MD, 29.93; 95% CI 10.59 to 49.26; p=0.002), which was different from the results based on all included studies and the non-randomised studies. No recurrences were observed in both groups in the two RCTs.

    Publication bias

    We assessed publication bias using Egger's test. No statistically significant evidence (p>0.05) of publication bias was detected, with the exception of the CMT data at the final follow-up (p=0.039) (see online supplementary table S3).

    Sensitivity analysis and cumulative meta-analysis

    We performed a leave-one-out sensitivity analysis by iteratively removing one study at a time and recalculating the summary MD in cases of considerable heterogeneity (I2>25%). The heterogeneity of a difference in BCVA (logMAR) at the final follow-up was effectively decreased after excluding the study,5 I2 changed from 60% to 20%. The heterogeneity of a difference in CMT at the final follow-up was effectively decreased after excluding the study,5 I2 changed from 55% to 0%. The heterogeneity of the difference in ERM recurrence was effectively decreased after excluding the study,26 ,30 I2 changed from 43% to 0%.

    The cumulative meta-analysis revealed that the summary MDs or ORs were not sufficiently stable (see online supplementary figure S3).

    Only two RCTs were analysed; therefore, we did not perform the leave-one-out sensitivity analysis, cumulative meta-analysis or Egger's test.

    Discussion

    Summary of the main results

    Ten non-randomised studies, one prospective cohort study and two RCTs were identified and included in this review.

    In all included studies, no evidence of a difference in BCVA, CMT at 12 months was detected between two groups. The ERM recurrence and reoperation rates were reduced in the ILM peeling group compared with those of the no-ILM peeling group.

    No evidence of a difference in BCVA at 3, 6 months, final follow-up was observed between two groups. No evidence of a difference in CMT at the 3, 6 months, final follow-up was observed between two groups.

    In non-randomised studies, the evidences of the outcomes in this subgroup were consistent with all included studies.

    In RCTs, there was evidence of increased CMT after ILM peeling compared with the non-ILM peeling group at the final follow-up (mean follow-up period ≥8.9 months) (MD, 29.93; 95% CI 10.59 to 49.26; p=0.002), but there was no difference between the two groups in all included studies or non-randomised studies.

    Overall completeness and applicability of the evidence

    Our prespecified outcomes were for 12 months of follow-up. Two of the non-randomised studies followed patients for up to 3 months,24 ,25 and one of the RCTs followed patients for up to 8.9 months.28

    Intraoperative and postoperative complications, reoperation rate and microperimetry were poorly reported, and metamorphopsia was not mentioned.

    We found two ongoing RCTs (ClinicalTrials.gov identifier: NCT0153276531 and NCT0089261932). In the future, these RCTs may provide more powerful evidence about the efficacy of additional ILM peeling in vitrectomy for IMP.

    Quality of evidence

    The overall quality of evidence in the 11 non-randomised cohort studies was high, but not all studies followed patients for up to 12 months. The unclear risk of bias of the two RCTs was due to blinding interventions that were not mentioned.

    Finally, for some outcomes, the results of the individual studies were heterogeneous. Although we provided a sensitivity analysis, we downgraded the quality of the evidence for inconsistency. The sensitivity analysis and cumulative meta-analysis suggest further adequate comparative clinical trials.

    Potential biases in the review process

    This review has methodological strengths because we were successful in obtaining information from trial investigators. We contacted the study authors to obtain missing data and further information, and four authors did respond. We also performed exhaustive searches for clinical trials, and we found two ongoing RCTs. One trial is currently recruiting participants,31 whereas ‘the recruitment status of this study is unknown’; was reported for the second study.32

    Agreements and disagreements with other studies or reviews

    Numerous studies reported removal of ILM during ERM surgery were associated with better final BCVA compared with baseline BCVA in both ILM and non-ILM peel patients.3 ,6 ,33–37 However, there is little evidence indicating a significant difference between two groups.38

    Visual acuity findings in our meta-analysis are likely explained by the fact that additional ILM peeling provided no improvement in functional outcomes, these findings were in consistent with the previous review,39 but contrast to a recent meta-analysis,40 which revealed that ILM peeling group had better BCVA after surgery within 12 months, but worse BCVA in the 18th month.

    No evidence of a difference in CMT at the final follow-up was noted between the two groups in all included studies or non-randomised studies. But, in the RCTs, CMT at the final follow-up was increased in patients who underwent ILM peeling compared with those who with no-ILM peeling. No review has discussed the difference in CMT between ILM peeling and no-ILM peeling, although many original studies have compared the CMT difference.5 ,20–25 ,27–28

    Our finding affirms lower ERM recurrence, reoperation rates after ILM peeling at the final follow-up. ILM removal provides the certainty of having removed all cells that produce collagen above the retina, thereby eliminating the scaffold for proliferative cells, such as transdifferentiated Müller cells and myofibroblasts, which are the prevailing cells in recurrent ERM.41

    Some concerns have been raised about potential deleterious side effects of ILM peeling. Some experimental studies have reported possible cytotoxicity to the retina with the dyes (eg, indocyanine green or brilliant blue G) used to highlight the ILM.42–47 In addition to the damage closely associated with surgical technique, recent findings have revealed adverse effects exclusively related to the peeling of the ILM, including damage to the tropism of the Müller cells, a decrease in foveal retinal sensitivity and alteration of the b-wave of ERGs.8 ,48 Our meta-analysis found ILM peeling yielding greater anatomical success.

    When we started this review, no systematic reviews or meta-analyses assessed ILM peeling for IMP. Recently, we found a meta-analysis about this topic that was published on 26 November 2015.40 There are some disagreements between our review and this paper. (1) Retrospective cohort studies, prospective cohort studies and RCTs were identified and included in our meta-analysis (13 studies, 1142 participants) but only retrospective cohort studies (8 studies, 418 participants) in Liu et al,40 and in our review, we included some studies recently published.29 ,30 (2) Subgroup analyses were conducted to find the differences between non-randomised studies and RCTs. (3) We contacted all authors of the studies which do not have complete data, four authors kindly provided online supplementary information. (4) We performed a quantitative comparative analysis of BCVA and ERM recurrence and also CMT and reoperation rates. (5) A higher logMAR value for BCVA indicates worse visual acuity; it was mistakenly stated that ‘patients in the IERM+ILM peeling group had better BCVA (higher BCVA logMAR in ILM+ERM peeling group) after surgery within 12 months than those in the IERM peeling group, but patients in the IERM peeling group showed better BCVA (higher BCVA logMAR in ERM peeling group) in the 18th month’. (6) Cochrane classified the study28 as an RCT, and information about this study was obtained from Un Chul Park (Clinical Assistant Professor of Professor Yu). This was a prospective study. (7) We performed cumulative meta-analysis to evaluate the relative benefits and risks of ILM peeling and no-ILM peeling.

    Our review has a number of strengths. By adopting a more inclusive approach, we were able to include more studies in the meta-analysis thereby increasing the sample size and representativeness. This review has methodological strengths because we were successful in obtaining information from trial investigators. We compared the differences between ILM peeling groups and no-ILM peeling including BCVA, CMT, ERM recurrence, reoperation rates, the increased evaluation indexes allowed us to contribute to pooled estimates the differences in the anatomical outcomes between two groups.

    Limitations

    Some limitations in this review should be noted. First, three studies49–51 only provided abstracts without outcomes (ie, no MD of BCVA or CMT, ERM recurrence and reoperation rate, the authors have not replied to our email for data) were excluded. Second, there were only two RCTs eligible for inclusion in the review. An insufficient number of eyes were included in these two RCTs, and the Cochrane risk of bias tool showed an unclear risk of bias in RCTs. Third, the ranges of the mean final follow-ups were wide and different in included studies. The time restriction on ‘final’ follow-up was wide, which may cause the evidence of outcomes at final follow-up to be unreliable.

    Conclusion

    In conclusion, our analysis provides evidence that ILM peeling leads to lower ERM recurrence and reoperation rates compared with non-ILM peeling, whereas BCVA and CMT were similar with or without ILM removal (only increased CMT at the final follow-up in RCTs). Our results indicate that ILM peeling achieved higher anatomical success with a reduced need for additional surgical interventions. There is a need for further adequate comparative clinical trials to assess the efficacy of additional ILM peeling in vitrectomy for IMP. The concealment of interventions and long-term follow-up (at least 12 months) are necessary to improve the quality of clinical trials. Future investigations of the effect of ILM peeling for IMP on macular function using ERG, microperimetry or other functional tests would be helpful in further addressing the safety of ILM peeling, near VA, reading speed, contrast sensitivity, metamorphopsia, vision-related quality of life should be investigated to perform a comparative analysis.52

    Acknowledgments

    The authors thank Jesse J Jung, Seong Joon Ahn, Un Chul Park and Stefano Lazzeri for kindly providing online supplementary information and data from their studies.

    References

    1. ↵
      1. Mitchell P,
      2. Smith W,
      3. Chey T, et al
      . Prevalence and associations of epiretinal membranes. The Blue Mountains Eye Study, Australia. Ophthalmology 1997;104:1033–40. doi:10.1016/S0161-6420(97)30190-0
      OpenUrlCrossRefPubMedWeb of Science
    2. ↵
      1. Massin P,
      2. Allouch C,
      3. Haouchine B, et al
      . Optical coherence tomography of idiopathic macular epiretinal membranes before and after surgery. Am J Ophthalmol 2000;130:732–9. doi:10.1016/S0002-9394(00)00574-2
      OpenUrlCrossRefPubMedWeb of Science
    3. ↵
      1. Ting FS,
      2. Kwok AK
      . Treatment of epiretinal membrane: an update. Hong Kong Med J 2005;11:496–502.
      OpenUrlPubMed
    4. ↵
      1. de Bustros S,
      2. Thompson JT,
      3. Michels RG, et al
      . Vitrectomy for idiopathic epiretinal membranes causing macular pucker. Br J Ophthalmol 1988;72:692–5. doi:10.1136/bjo.72.9.692
      OpenUrlAbstract/FREE Full Text
    5. ↵
      1. Ahn SJ,
      2. Ahn J,
      3. Woo SJ, et al
      . Photoreceptor change and visual outcome after idiopathic epiretinal membrane removal with or without additional internal limiting membrane peeling. Retina 2014;34:172–81. doi:10.1097/IAE.0b013e318295f798
      OpenUrlCrossRefPubMed
    6. ↵
      1. Park DW,
      2. Dugel PU,
      3. Garda J, et al
      . Macular pucker removal with and without internal limiting membrane peeling: pilot study. Ophthalmology 2003;110:62–4. doi:10.1016/S0161-6420(02)01440-9
      OpenUrlCrossRefPubMedWeb of Science
    7. ↵
      1. Kwok AKh,
      2. Lai TY,
      3. Yuen KS
      . Epiretinal membrane surgery with or without internal limiting membrane peeling. Clin Exp Ophthalmol 2005;33:379–85. doi:10.1111/j.1442-9071.2005.01015.x
      OpenUrlCrossRefPubMed
    8. ↵
      1. Terasaki H,
      2. Miyake Y,
      3. Nomura R, et al
      . Focal macular ERGs in eyes after removal of macular ILM during macular hole surgery. Invest Ophthalmol Vis Sci 2001;42:229–34.
      OpenUrlAbstract/FREE Full Text
    9. ↵
      1. Uemura A,
      2. Kanda S,
      3. Sakamoto Y, et al
      . Visual field defects after uneventful vitrectomy for epiretinal membrane with indocyanine green—assisted internal limiting membrane peeling. Am J Ophthalmol 2003;136:252–7. doi:10.1016/S0002-9394(03)00157-0
      OpenUrlCrossRefPubMedWeb of Science
    10. ↵
      1. Uemoto R,
      2. Yamamoto S,
      3. Aoki T, et al
      . Macular configuration determined by optical coherence tomography after idiopathic macular hole surgery with or without internal limiting membrane peeling. Br J Ophthalmol 2002;86:1240–2. doi:10.1136/bjo.86.11.1240
      OpenUrlAbstract/FREE Full Text
    11. ↵
      1. Wells GA,
      2. Shea B,
      3. O'Connell D, et al
      . The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa, Ontario: Ottawa Health Research Institute, University of Ottawa. http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm (accessed 30 Oct 2015).
    12. ↵
      1. Herzog R,
      2. Álvarez-Pasquin MJ,
      3. Díaz C, et al
      . Are healthcare workers’ intentions to vaccinate related to their knowledge, beliefs and attitudes? A systematic review. BMC Public Health 2013;13:154. doi:10.1186/1471-2458-13-154
      OpenUrlCrossRefPubMed
    13. ↵
      1. Higgins JP,
      2. Altman DG,
      3. Gøtzsche PC, et al
      . The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928. doi:10.1136/bmj.d5928
      OpenUrlFREE Full Text
    14. ↵
      1. Guyatt G,
      2. Oxman AD,
      3. Akl EA, et al
      . GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011;64: 383–94. doi:10.1016/j.jclinepi.2010.04.026
      OpenUrlCrossRefPubMed
    15. ↵
      1. Guyatt GH,
      2. Oxman AD,
      3. Vist GE, et al
      . GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924–6. doi:10.1136/bmj.39489.470347.AD
      OpenUrlFREE Full Text
    16. ↵
      1. Ioannidis JP,
      2. Patsopoulos NA,
      3. Evangelou E, et al.
      Heterogeneity in meta-analyses of genome-wide association investigations. PLoS ONE 2007;2:e841. doi:10.1371/journal.pone.0000841
      OpenUrlCrossRefPubMed
    17. ↵
      1. Higgins JP,
      2. Thompson SG,
      3. Deeks JJ, et al
      . Measuring inconsistency in meta-analyses. BMJ 2003;327:557–60. doi:10.1136/bmj.327.7414.557
      OpenUrlFREE Full Text
    18. ↵
      1. Egger M,
      2. Davey Smith G,
      3. Schneider M, et al
      . Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–34. doi:10.1136/bmj.315.7109.629
      OpenUrlAbstract/FREE Full Text
    19. ↵
      1. Wang ZY,
      2. Zhao K,
      3. Zheng J, et al
      . Systematic review and meta-analysis of the association between complement factor H I62V polymorphism and risk of polypoidal choroidal vasculopathy in Asian populations. PLoS ONE 2014;9:e88324. doi:10.1371/journal.pone.0088324
      OpenUrl
    20. ↵
      1. Lee JW,
      2. Kim IT
      . Outcomes of idiopathic macular epiretinal membrane removal with and without internal limiting membrane peeling: a comparative study. Jpn J Ophthalmol 2010;54:129–34. doi:10.1007/s10384-009-0778-0
      OpenUrlCrossRefPubMed
    21. ↵
      1. Pournaras CJ,
      2. Emarah A,
      3. Petropoulos IK
      . Idiopathic macular epiretinal membrane surgery and ILM peeling: anatomical and functional outcomes. Semin Ophthalmol 2011;26:42–6. doi:10.3109/08820538.2010.544237
      OpenUrlCrossRefPubMed
    22. ↵
      1. Oh HN,
      2. Lee JE,
      3. Kim HW, et al
      . Clinical outcomes of double staining and additional ILM peeling during ERM surgery. Korean J Ophthalmol 2013;27:256. doi:10.3341/kjo.2013.27.4.256
      OpenUrlCrossRefPubMed
    23. ↵
      1. Kumagai K,
      2. Ogino N,
      3. Furukawa M, et al
      . Retinal thickness after vitrectomy and internal limiting membrane peeling for macular hole and epiretinal membrane. Clin Ophthalmol 2012;6:679–88. doi:10.2147/OPTH.S30288
      OpenUrlPubMed
    24. ↵
      1. Liu YL
      . Epimacular membrane surgery with and without internal limiting membrane peeling. Chin J Pract Ophthalmol 2005;23:1278–80.
      OpenUrl
    25. ↵
      1. Chang S,
      2. Gregory-Roberts EM,
      3. Park S, et al
      . Double peeling during vitrectomy for macular pucker: the Charles L. Schepens Lecture. JAMA Ophthalmol 2013;131:525–30. doi:10.1001/jamaophthalmol.2013.2176
      OpenUrl
    26. ↵
      1. Shimada H,
      2. Nakashizuka H,
      3. Hattori T, et al
      . Double staining with brilliant blue G and double peeling for epiretinal membranes. Ophthalmology 2009;116:1370–6. doi:10.1016/j.ophtha.2009.01.024
      OpenUrlCrossRefPubMedWeb of Science
    27. ↵
      1. Ripandelli G,
      2. Scarinci F,
      3. Piaggi P, et al
      . Macular pucker: to peel or not to peel the internal limiting membrane? A microperimetric response. Retina 2015;35:498–507. doi:10.1097/IAE.0000000000000330
      OpenUrl
    28. ↵
      1. Kim TW,
      2. Song SJ,
      3. Chung H, et al
      . Internal limiting membrane peeling in surgical treatment of macular epiretinal membrane. J Korean Ophthalmol Soc 2005;46:989–94.
      OpenUrl
    29. ↵
      1. Jung JJ,
      2. Hoang QV,
      3. Ridley-Lane ML, et al
      . Long-term retrospective analysis of visual acuity and optical coherence topographic changes after single versus double peeling during vitrectomy for macular epiretinal membranes. Retina 2016;36:2101–9. doi:10.1097/IAE.0000000000001055
      OpenUrl
    30. ↵
      1. Schechet SA,
      2. DeVience E,
      3. Thompson JT
      . The effect of internal limiting membrane peeling on idiopathic epiretinal membrane surgery, with a review of the literature. Retina Epub ahead of print: Sep 2016. DOI: 10.1097/IAE.0000000000001263. doi:10.1097/IAE.0000000000001263
    31. ↵
      Randomized Trial Comparing Epiretinal Membrane Surgery With and Without Internal Limiting Membrane Removal. http://www.clinicaltrials.gov/ct2/show/NCT01532765?term=Randomized+Trial+Comparing+Epiretinal+Membrane+Surgery+With+and+Without+Internal+Limiting+Membrane+Removal&rank=1 (accessed 15 Sept 2016).
    32. ↵
      Comparison of Two Techniques for Epiretinal or Internal Limiting Membrane Peel. http://www.clinicaltrials.gov/ct2/show/NCT00892619?term=Comparison+of+Two+Techniques+for+Epietinal+or+Internal+Limiting+Membrane+Peel&rank=1 (accessed 15 Sept 2016).
    33. ↵
      1. Haritoglou C,
      2. Gandorfer A,
      3. Gass CA, et al
      . The effect of indocyanine-green on functional outcome of macular pucker surgery. Am J Ophthalmol 2003;135:328–37. doi:10.1016/S0002-9394(02)01969-4
      OpenUrlCrossRefPubMedWeb of Science
    34. ↵
      1. Haritoglou C,
      2. Eibl K,
      3. Schaumberger M, et al
      . Functional outcome after trypan blue-assisted vitrectomy for macular pucker: a prospective, randomized, comparative trial. Am J Ophthalmol 2004;138:1–5. doi:10.1016/j.ajo.2004.03.005
      OpenUrlPubMedWeb of Science
    35. ↵
      1. Hasegawa T,
      2. Emi K,
      3. Ikeda T, et al
      . [Long-term prognosis of internal limiting membrane peeling for idiopathic epiretinal membrane]. Nippon Ganka Gakkai Zasshi 2004;108:150–6.
      OpenUrlPubMed
    36. ↵
      1. Rizzo S,
      2. Genovesi-Ebert F,
      3. Murri S, et al
      . 25-Gauge, sutureless vitrectomy and standard 20-gauge Pars plana vitrectomy in idiopathic epiretinal membrane surgery: a comparative pilot study. Graefes Arch Clin Exp Ophthalmol 2006;244:472–49. doi:10.1007/s00417-005-0173-6
      OpenUrlCrossRefPubMed
    37. ↵
      1. Sorcinelli R
      . Surgical management of epiretinal membrane with indocyanine-green-assisted peeling. Ophthalmologica 2003;217:107–10. doi:68556
      OpenUrlCrossRefPubMedWeb of Science
    38. ↵
      1. Bovey EH,
      2. Uffer S,
      3. Achache F
      . Surgery for epimacular membrane: impact of retinal internal limiting membrane removal on functional outcome. Retina 2004;24:728–35. doi:10.1097/00006982-200410000-00007
      OpenUrlCrossRefPubMed
    39. ↵
      1. Roh M,
      2. Eliott D
      . Internal limiting membrane peeling during idiopathic epiretinal membrane removal: literature review. Int Ophthalmol Clin 2015;55:91–101. doi:10.1097/IIO.0000000000000084
      OpenUrl
    40. ↵
      1. Liu H,
      2. Zuo S,
      3. Ding C, et al
      . Comparison of the effectiveness of pars plana vitrectomy with and without internal limiting membrane peeling for idiopathic retinal membrane removal: a meta-analysis. J Ophthalmol 2015;2015:974568. doi:10.1155/2015/974568
      OpenUrl
    41. ↵
      1. Maguire AM,
      2. Smiddy WE,
      3. Nanda SK, et al
      . Clinicopathologic correlation of recurrent epiretinal membranes after previous surgical removal. Retina 1990;10:213–22. doi:10.1097/00006982-199001030-00011
      OpenUrlCrossRefPubMedWeb of Science
    42. ↵
      1. Maia M,
      2. Margalit E,
      3. Lakhanpal R, et al
      . Effects of intravitreal indocyanine green injection in rabbits. Retina 2004;24:69–79. doi:10.1097/00006982-200402000-00011
      OpenUrlCrossRefPubMedWeb of Science
    43. ↵
      1. Iriyama A,
      2. Uchida S,
      3. Yanagi Y, et al
      . Effects of indocyanine green on retinal ganglion cells. Invest Ophthalmol Vis Sci 2004;45:943–7. doi:10.1167/iovs.03-1026
      OpenUrlAbstract/FREE Full Text
    44. ↵
      1. Yip HK,
      2. Lai TY,
      3. So KF, et al
      . Retinal ganglion cells toxicity caused by photosensitising effects of intravitreal indocyanine green with illumination in rat eyes. Br J Ophthalmol 2006;90:99–102. doi:10.1136/bjo.2005.076042
      OpenUrlAbstract/FREE Full Text
    45. ↵
      1. Balaiya S,
      2. Brar VS,
      3. Murthy RK, et al
      . Effects of indocyanine green on cultured retinal ganglion cells in-vitro. BMC Res Notes 2009;2:236. doi:10.1186/1756-0500-2-236
      OpenUrlPubMed
    46. ↵
      1. Wu Y,
      2. Zhu W,
      3. Xu D, et al
      . Indocyanine green-assisted internal limiting membrane peeling in macular hole surgery: a meta-analysis. PLoS ONE 2012;7:e48405. doi:10.1371/journal.pone.0048405
      OpenUrlPubMed
    47. ↵
      1. Azuma K,
      2. Noda Y,
      3. Hirasawa K, et al
      . Brilliant blue G-assisted internal limiting membrane peeling for macular hole: a systematic review of literature and meta-analysis. Retina 2016;36:851–8. doi:10.1097/IAE.0000000000000968
      OpenUrl
    48. ↵
      1. Robaszkiewicz J,
      2. Chmielewska K,
      3. Figurska M, et al
      . Müller glial cells—the mediators of vascular disorders with vitreomacular interface pathology in diabetic maculopathy. Klin Oczna 2010;112:328–32.
      OpenUrlPubMed
    49. ↵
      1. Mason III JO,
      2. Roberts B,
      3. Emond TL, et al
      . Visual outcomes and recurrence rates of macular pucker surgery with and without internal limiting membrane peeling. Clin Surg Ophthalmol 2006;24:93+96–98.
      OpenUrl
    50. ↵
      1. Nakamura H,
      2. Gaja T,
      3. Sawaguchi K, et al
      . Outcome of vitrectomy for epimacular membrane (Japanese). Folia Ophthalmologica Japonica 2005;56:430–3.
      OpenUrl
    51. ↵
      1. Oncel M
      . Epiretinal membrane surgery: with and without internal limiting membrane removal. Am Acad Ophthalmol 2005;10:255.
    52. ↵
      1. Spiteri Cornish K,
      2. Lois N,
      3. Scott NW, et al
      . Vitrectomy with internal limiting membrane peeling versus no peeling for idiopathic full-thickness macular hole. Ophthalmology 2014;121:649–55. doi:10.1016/j.ophtha.2013.10.020
      OpenUrlCrossRefPubMedWeb of Science

    Footnotes

    • Contributors Z-YW contributed to the design, interpretation, surgery procedure and made revisions to the manuscript. X-LF contributed to experimental data acquisition and wrote the first draft. YT contributed to online registration and data acquisition. Y-LZ and P-QZ contributed to the data analysis.

    • Funding This work was supported by Project of the National Natural Science Funds of China (No. 81371040) and Shanghai Pujiang Program (No. 15PJD028).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; internally peer reviewed.

    Linked Articles

    • At a glance
      Highlights from this issue
      Keith Barton James Chodosh Jost B Jonas
      British Journal of Ophthalmology 2017; 101 i-ii Published Online First: 25 Oct 2017. doi: 10.1136/bjophthalmol-2017-311441