Randomized Trial Comparing Epiretinal Membrane Surgery With and Without Internal Limiting Membrane Removal

A Multicentre Randomized Clinical Trial Comparing Epiretinal Membrane Surgery With and Without Internal Limiting Membrane Peeling

Macular epiretinal membrane (ERM) is a semitranslucent, avascular, fibrocellular membrane on the inner surface along the internal limiting membrane (ILM) of the retina. ERM may cause symptomatic visual disturbances and vision loss. Since the 1970s, pars plana vitrectomy has been performed to remove the membranes with few complications, and surgical results are generally good. Recurrence rates of 5-16% have been reported. Recently, ILM peeling in ERM surgery have been popularized by a number of retrospective studies and one prospective case series to minimize the rate of ERM recurrences (16% recurrence in ERM surgery with ILM peel compares to 0% recurrence in ERM surgery without ILM peel). Surgical removal of the friable and transparent ILM is difficult and increases the risk of trauma to the retina. In addition, indocyanine green (ICG), a dye commonly used intra-operatively to enhance ILM visualization, is costly and has been shown to be toxic to the retina. The investigators study will be the first randomized-controlled multi-centred clinical trial to compare the outcomes of ERM surgery with and without ILM peeling. The results will help guide and standardize the surgical treatment of macular ERM; to minimize unnecessary surgical risks, as well as to help economize healthcare cost.

Study Overview

• Status: Terminated
• Conditions: Epiretinal Membrane
• Intervention / Treatment: Procedure: Pars plana vitrectomy and epiretinal membrane peel; Procedure: ILM peel assisted by ICG; Procedure: CE-IOL

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years or older
• ERM on clinical exam and/or macular OCT
• Visual acuity of 20/40 or worse (attributable to ERM)

Exclusion Criteria:

• Prior surgery for ERM in the "study eye"
• Macular edema secondary to arterial/venous occlusion(s)
• Central serous retinopathy
• Age related macular degeneration
• Diabetic cystoid macular edema
• Proliferative Diabetic Retinopathy
• Uveitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Epiretinal Membrane Surgery without ILM peel	Procedure: Pars plana vitrectomy and epiretinal membrane peel; 23 gauge pars plana vitrectomy with diluted intravitreal triamcinolone for visualization
Active Comparator: Epiretinal Membrane Surgery with ILM peel (ICG assisted)	Procedure: Pars plana vitrectomy and epiretinal membrane peel; 23 gauge pars plana vitrectomy with diluted intravitreal triamcinolone for visualization; Procedure: ILM peel assisted by ICG; Indocyanine green dye is prepared from 25mg powder vial from AKORN INC., 10 mL diluent provided in kit. This is further diluted to final concentration of 0.5mg/mL using 50% sterile dextrose solution
Active Comparator: Combined CE & IOL and ERM surgery without ILM peel	Procedure: Pars plana vitrectomy and epiretinal membrane peel; 23 gauge pars plana vitrectomy with diluted intravitreal triamcinolone for visualization; Procedure: CE-IOL; Cataract extraction by phacoemulsification and insertion foldable posterior chamber intraocular lens implant
Active Comparator: Combined CE & IOL and ERM surgery with ILM peel (ICG assisted)	Procedure: Pars plana vitrectomy and epiretinal membrane peel; 23 gauge pars plana vitrectomy with diluted intravitreal triamcinolone for visualization; Procedure: ILM peel assisted by ICG; Indocyanine green dye is prepared from 25mg powder vial from AKORN INC., 10 mL diluent provided in kit. This is further diluted to final concentration of 0.5mg/mL using 50% sterile dextrose solution; Procedure: CE-IOL; Cataract extraction by phacoemulsification and insertion foldable posterior chamber intraocular lens implant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in macular thickness on optical coherence tomography at 6 months post-surgery (intervention)	Comparing change at 6 months following surgery and baseline
Change from baseline in visual acuity at 6 months post-surgery (intervention)	Comparing change of visual acuity at 6 months following surgery and baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in macular thickness on optical coherence tomography at 1 month post-surgery (intervention)	1 month following surgery
Change from baseline in macular thickness on optical coherence tomography at 12 months post-surgery	12 months following surgery
Change from baseline in visual acuity at 1 month post-surgery (intervention)	1 month following surgery (intervention)
Change from baseline in visual acuity at 3 months post-surgery (intervention)	3 months following surgery (intervention)
Change from baseline in visual acuity at 12 months post-surgery (intervention)	12 months following surgery (intervention)
Change from baseline in visual function score based on responses to a validated visual function questionnaire (14 items) at 1 month post-surgery (intervention)	1 month following surgery (intervention)
Change from baseline in visual function score based on responses to a validated visual function questionnaire (14 items) at 3 months post-surgery (intervention)	3 months following surgery
Change from baseline in visual function score based on responses to a validated visual function questionnaire (14 items) at 6 months post-surgery (intervention)	6 months following surgery
Change from baseline in visual function score based on responses to a validated visual function questionnaire (14 items) at 12 months post-surgery (intervention)	12 months following surgery

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre

Publications and helpful links

General Publications

• Shimada H, Nakashizuka H, Hattori T, Mori R, Mizutani Y, Yuzawa M. Double staining with brilliant blue G and double peeling for epiretinal membranes. Ophthalmology. 2009 Jul;116(7):1370-6. doi: 10.1016/j.ophtha.2009.01.024. Epub 2009 May 8.
• Wise GN. Preretinal macular fibrosis. (An analysis of 90 cases). Trans Ophthalmol Soc U K (1962). 1972;92:131-40. No abstract available.
• Fraser-Bell S, Ying-Lai M, Klein R, Varma R; Los Angeles Latino Eye Study. Prevalence and associations of epiretinal membranes in latinos: the Los Angeles Latino Eye Study. Invest Ophthalmol Vis Sci. 2004 Jun;45(6):1732-6. doi: 10.1167/iovs.03-1295.
• Klein R, Klein BE, Wang Q, Moss SE. The epidemiology of epiretinal membranes. Trans Am Ophthalmol Soc. 1994;92:403-25; discussion 425-30. No abstract available.
• Hirokawa H, Jalkh AE, Takahashi M, Takahashi M, Trempe CL, Schepens CL. Role of the vitreous in idiopathic preretinal macular fibrosis. Am J Ophthalmol. 1986 Feb 15;101(2):166-9. doi: 10.1016/0002-9394(86)90589-1.
• Wise GN. Relationship of idiopathic preretinal macular fibrosis to posterior vitreous detachment. Am J Ophthalmol. 1975 Mar;79(3):358-62. doi: 10.1016/0002-9394(75)90606-6.
• Mitchell P, Smith W, Chey T, Wang JJ, Chang A. Prevalence and associations of epiretinal membranes. The Blue Mountains Eye Study, Australia. Ophthalmology. 1997 Jun;104(6):1033-40. doi: 10.1016/s0161-6420(97)30190-0.
• Kawasaki R, Wang JJ, Sato H, Mitchell P, Kato T, Kawata S, Kayama T, Yamashita H, Wong TY. Prevalence and associations of epiretinal membranes in an adult Japanese population: the Funagata study. Eye (Lond). 2009 May;23(5):1045-51. doi: 10.1038/eye.2008.238. Epub 2008 Aug 8.
• Smiddy WE, Maguire AM, Green WR, Michels RG, de la Cruz Z, Enger C, Jaeger M, Rice TA. Idiopathic epiretinal membranes. Ultrastructural characteristics and clinicopathologic correlation. Ophthalmology. 1989 Jun;96(6):811-20; discussion 821. doi: 10.1016/s0161-6420(89)32811-9.
• Wiznia RA. Posterior vitreous detachment and idiopathic preretinal macular gliosis. Am J Ophthalmol. 1986 Aug 15;102(2):196-8. doi: 10.1016/0002-9394(86)90144-3.
• Sidd RJ, Fine SL, Owens SL, Patz A. Idiopathic preretinal gliosis. Am J Ophthalmol. 1982 Jul;94(1):44-8. doi: 10.1016/0002-9394(82)90189-1.
• Bellhorn MB, Friedman AH, Wise GN, Henkind P. Ultrastructure and clinicopathologic correlation of idiopathic preretinal macular fibrosis. Am J Ophthalmol. 1975 Mar;79(3):366-73. doi: 10.1016/0002-9394(75)90608-x.
• Clarkson JG, Green WR, Massof D. A histopathologic review of 168 cases of preretinal membrane. 1977. Retina. 2005 Jul-Aug;25(5 Suppl):1-17. doi: 10.1097/00006982-200507001-00006. No abstract available.
• Appiah AP, Hirose T, Kado M. A review of 324 cases of idiopathic premacular gliosis. Am J Ophthalmol. 1988 Nov 15;106(5):533-5. doi: 10.1016/0002-9394(88)90581-8.
• Ting FS, Kwok AK. Treatment of epiretinal membrane: an update. Hong Kong Med J. 2005 Dec;11(6):496-502.
• Michels RG. A clinical and histopathologic study of epiretinal membranes affecting the macula and removed by vitreous surgery. Trans Am Ophthalmol Soc. 1982;80:580-656. No abstract available.
• Puliafito CA, Hee MR, Lin CP, Reichel E, Schuman JS, Duker JS, Izatt JA, Swanson EA, Fujimoto JG. Imaging of macular diseases with optical coherence tomography. Ophthalmology. 1995 Feb;102(2):217-29. doi: 10.1016/s0161-6420(95)31032-9.
• Falkner-Radler CI, Glittenberg C, Hagen S, Benesch T, Binder S. Spectral-domain optical coherence tomography for monitoring epiretinal membrane surgery. Ophthalmology. 2010 Apr;117(4):798-805. doi: 10.1016/j.ophtha.2009.08.034. Epub 2010 Jan 4.
• Fraser-Bell S, Guzowski M, Rochtchina E, Wang JJ, Mitchell P. Five-year cumulative incidence and progression of epiretinal membranes: the Blue Mountains Eye Study. Ophthalmology. 2003 Jan;110(1):34-40. doi: 10.1016/s0161-6420(02)01443-4.
• Kwok AKh, Lai TY, Yuen KS. Epiretinal membrane surgery with or without internal limiting membrane peeling. Clin Exp Ophthalmol. 2005 Aug;33(4):379-85. doi: 10.1111/j.1442-9071.2005.01015.x.
• Grewing R, Mester U. Results of surgery for epiretinal membranes and their recurrences. Br J Ophthalmol. 1996 Apr;80(4):323-6. doi: 10.1136/bjo.80.4.323.
• Park DW, Dugel PU, Garda J, Sipperley JO, Thach A, Sneed SR, Blaisdell J. Macular pucker removal with and without internal limiting membrane peeling: pilot study. Ophthalmology. 2003 Jan;110(1):62-4. doi: 10.1016/s0161-6420(02)01440-9.
• Bovey EH, Uffer S, Achache F. Surgery for epimacular membrane: impact of retinal internal limiting membrane removal on functional outcome. Retina. 2004 Oct;24(5):728-35. doi: 10.1097/00006982-200410000-00007.
• Burk SE, Da Mata AP, Snyder ME, Rosa RH Jr, Foster RE. Indocyanine green-assisted peeling of the retinal internal limiting membrane. Ophthalmology. 2000 Nov;107(11):2010-4. doi: 10.1016/s0161-6420(00)00375-4.
• Gale JS, Proulx AA, Gonder JR, Mao AJ, Hutnik CM. Comparison of the in vitro toxicity of indocyanine green to that of trypan blue in human retinal pigment epithelium cell cultures. Am J Ophthalmol. 2004 Jul;138(1):64-9. doi: 10.1016/j.ajo.2004.02.061.
• Yuen D, Gonder J, Proulx A, Liu H, Hutnik C. Comparison of the in vitro safety of intraocular dyes using two retinal cell lines: a focus on brilliant blue G and indocyanine green. Am J Ophthalmol. 2009 Feb;147(2):251-259.e2. doi: 10.1016/j.ajo.2008.08.031. Epub 2008 Nov 7.
• Lim JW, Kim HK, Cho DY. Macular function and ultrastructure of the internal limiting membrane removed during surgery for idiopathic epiretinal membrane. Clin Exp Ophthalmol. 2011 Jan;39(1):9-14. doi: 10.1111/j.1442-9071.2010.02377.x.
• Lee JW, Kim IT. Outcomes of idiopathic macular epiretinal membrane removal with and without internal limiting membrane peeling: a comparative study. Jpn J Ophthalmol. 2010 Mar;54(2):129-34. doi: 10.1007/s10384-009-0778-0. Epub 2010 Apr 18.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): March 22, 2017

Study Registration Dates

• First Submitted: January 13, 2012
• First Submitted That Met QC Criteria: February 13, 2012
• First Posted (Estimate): February 14, 2012

Study Record Updates

• Last Update Posted (Actual): September 21, 2018
• Last Update Submitted That Met QC Criteria: September 19, 2018
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Internal limiting membrane; Indocyanine green dye
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Epiretinal Membrane
• Other Study ID Numbers: 422-2010