Ophthalmic Surgery, Lasers and Imaging Retina

Clinical Science 

Clinical-Pathologic Correlation: Vitrectomy With Epiretinal and Internal Limiting Membrane Peel

Emilia H. DeMarchis, BA; Suzann Pershing, MD; Darius M. Moshfeghi, MD

Abstract

BACKGROUND AND OBJECTIVE:

To correlate clinical and pathologic findings in vitreoretinal surgeries with epiretinal membrane (ERM) and internal limiting membrane (ILM) peels.

PATIENTS AND METHODS:

A retrospective review of the clinical and pathologic reports for 698 vitrectomy specimens involving ERM and/or ILM peels from 2008 to 2012.

RESULTS:

Labeling with clear operative clinical diagnoses — ERM, ILM or both — was available for 520 of 698 cases; 492 cases had a corresponding pathology result. Combined ERM-ILM specimens were the dominant clinical and pathologic diagnosis. Over 43% had differing operative and pathologic diagnoses, with 79.6% of cases labeled as ERMs, 75.0% of cases labeled as ILMs, and 22.1% cases labeled as ERM-ILM demonstrating incongruous specimens on pathology.

CONCLUSION:

It can be difficult to determine the nature of membranes pre- or intraoperatively. Combined ERM-ILM specimens may be more common than previously recognized, implying that the two membranes are not always distinct and surgically separable.

[Ophthalmic Surg Lasers Imaging Retina. 2014;45:218–221.]

Stanford University, School of Medicine (EHD), and the Department of Ophthalmology, Stanford University Medical Center (SP, DMM), Stanford, CA.

The authors have no relevant financial or proprietary interest in the materials presented herein.

Dr. Moshfeghi did not participate in the editorial review of this manuscript.

Address correspondence to Suzann Pershing, MD, 2452 Watson Court, Palo Alto, CA 94303; 650-723-6995; email: pershing@stanford.edu.

Received: June 29, 2013
Accepted: February 19, 2014
Posted Online: April 28, 2014

Abstract

BACKGROUND AND OBJECTIVE:

To correlate clinical and pathologic findings in vitreoretinal surgeries with epiretinal membrane (ERM) and internal limiting membrane (ILM) peels.

PATIENTS AND METHODS:

A retrospective review of the clinical and pathologic reports for 698 vitrectomy specimens involving ERM and/or ILM peels from 2008 to 2012.

RESULTS:

Labeling with clear operative clinical diagnoses — ERM, ILM or both — was available for 520 of 698 cases; 492 cases had a corresponding pathology result. Combined ERM-ILM specimens were the dominant clinical and pathologic diagnosis. Over 43% had differing operative and pathologic diagnoses, with 79.6% of cases labeled as ERMs, 75.0% of cases labeled as ILMs, and 22.1% cases labeled as ERM-ILM demonstrating incongruous specimens on pathology.

CONCLUSION:

It can be difficult to determine the nature of membranes pre- or intraoperatively. Combined ERM-ILM specimens may be more common than previously recognized, implying that the two membranes are not always distinct and surgically separable.

[Ophthalmic Surg Lasers Imaging Retina. 2014;45:218–221.]

Stanford University, School of Medicine (EHD), and the Department of Ophthalmology, Stanford University Medical Center (SP, DMM), Stanford, CA.

The authors have no relevant financial or proprietary interest in the materials presented herein.

Dr. Moshfeghi did not participate in the editorial review of this manuscript.

Address correspondence to Suzann Pershing, MD, 2452 Watson Court, Palo Alto, CA 94303; 650-723-6995; email: pershing@stanford.edu.

Received: June 29, 2013
Accepted: February 19, 2014
Posted Online: April 28, 2014

Introduction

First performed in the 1970s by Machemer,1 vitrectomy with membrane peeling has become a routine surgical procedure for a variety of pathologies resulting in membrane formation and/or requiring tension relief. Over the years, much attention has been focused on the efficacy and outcomes of such procedures.2–14 Reports comparing epiretinal membrane (ERM) peel with or without internal limiting membrane (ILM) peeling have sought to address concerns regarding removal of the ILM and consequences on the adjacent neuronal tissue. Membrane ultrastructure, both internal ILM and ERM, has been described for specific pathologies ranging from idiopathic macular hole to diffuse diabetic retinopathy.15–29 Beyond visual acuity outcomes, spectral-domain optical coherence tomography (SD-OCT) has recently enabled detailed analysis of the effects of membrane peels on the retina, the clinical impact of which remains unclear.30–33

Although hinted at in Chang’s recent report,2 in which he states that 76% of membrane peels contain fragments of ILM, there is a lack of information comparing what surgeons believe they are peeling in vitreoretinal surgeries and what is demonstrated on subsequent histology. It is difficult to draw conclusions about the efficacy of membrane peeling when questions remain regarding the ability to distinguish membrane layers clinically and intraoperatively. This study seeks to determine the accuracy of intraoperative classification of membrane peels.

Patients and Methods

Following institutional review board approval of the study, cases of vitrectomy with ERM and/or ILM peels occurring between January 1, 2008, and December 31, 2012, were retrospectively reviewed from Stanford University Medical Center archives. Cases were included in the study if diagnoses were available in both the operative note and pathology report (for corresponding specimens), and none were excluded based on underlying diagnosis or clinical history. Pathology specimens were submitted as flat-mount slides, stained with hematoxylin and eosin (Figures 13). Cases without adequate tissue for pathologic diagnosis and without clear operative clinical diagnoses were excluded from this study.

Epiretinal membrane (flat-mount slide, hematoxylin and eosin staining).

Figure 1.

Epiretinal membrane (flat-mount slide, hematoxylin and eosin staining).

Internal limiting membrane peel (flat-mount slide, hematoxylin and eosin staining).

Figure 2.

Internal limiting membrane peel (flat-mount slide, hematoxylin and eosin staining).

Epiretinal membrane and internal limiting membrane peel (flat-mount slide, hematoxylin and eosin staining).

Figure 3.

Epiretinal membrane and internal limiting membrane peel (flat-mount slide, hematoxylin and eosin staining).

Relevant clinical history and follow-up was reviewed for all cases, with specific evaluation of the underlying clinical history and membrane type (from clinical or intraoperative analysis and from pathology specimens). Reported clinical diagnoses were matched to case pathology reports to evaluate for concordance. All data were analyzed using Stata version 11.2 software.

Results

A total of 698 vitrectomies with ERM and/or ILM peels were performed over a 5-year period from 2008 to 2012, 567 of which had clear membrane clinical diagnoses included with operative reports. Of these 698 cases, 520 were reported as ERM, ILM, or combined ERM-ILM, and 492 of them had corresponding pathology diagnoses. Comorbidities and/or underlying pathology included fibrovascular membrane (one case), proliferative diabetic retinopathy (two cases), subretinal membrane (one case), pupillary membrane (one case), vitreous hemorrhage (one case), and proliferative vitreoretinopathy (one case).

Combined ERM-ILM specimens were the most frequent clinical as well as pathologic diagnoses. There were 299 clinical specimens submitted as combined ERM-ILM (60.8%), compared to 100 specimens submitted as ILM (20.3%) and 93 submitted as ERM (18.9%). For the 428 cases with pathologic diagnoses of ERM and/or ILM, predominance of combined ERM-ILM specimens was even more pronounced: 11.0% (47) ERM, 8.9% (38) ILM, and 80.1% (343) combined ERM-ILM.

Pathologic findings for 215 of the 492 cases (43.6%) did not match their associated operative diagnoses. There was no match with the histopathology for 74 of 93 (79.6%) cases labeled as ERM, 75 of 100 (75.0%) of cases labeled as ILM, and 66 of 299 (22.1%) cases labeled as combined ERM-ILM (Table, page 220). For cases clinically thought to involve only the removal of an ERM, 81.1% involved both an ERM and ILM. For cases clinically thought to involve only an ILM peel, 66.7% involved both ERM and ILM. Pathology reports also noted cases that were inadequate for histopathologic review (30 cases) or for which the specimen was lost during processing (28 cases). ILM-only and combined ERM-ILM cases had the greatest proportion of inadequate or lost specimens (34.5% of ILMs and 44.8% of combined ERM-ILM vs 12.1% of cases submitted as ERM only).

Clinical Versus Histologic Diagnoses

Table:

Clinical Versus Histologic Diagnoses

Discussion

This retrospective review of the Stanford University Medical Center experience with clinical versus pathologic analysis of vitrectomy membrane peeling demonstrates the difficulty of differentiating ERM versus ILM membrane peels. Limitations of this study include a lack of analysis by surgical technique (ie, the use of intraoperative dye or type of forceps) or by underlying diagnosis and surgeon-specific variability.

However, we find that combined ERM-ILM specimens were more common than clinically perceived, with the study’s findings likely being an underestimate, given the high propensity for both ILMs and combined ERM-ILMs to be lost in processing or inadequate for histopathologic review. Membranes are less distinct intraoperatively and less surgically separable than previously supposed. These findings cast doubt on our ability to accurately compare outcomes from ERM versus ILM peels, impacting the current debate regarding efficacy of peeling ILM in addition to ERM.2–14 The use of intraoperative OCT may improve physician accuracy, but the cost-effectiveness and feasibility of routine intraoperative OCT remain to be seen.

References

  1. Machemer R. Pars plana vitrectomy. Removal of preretinal membranes. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol. 1976;81(3):OP420–5.
  2. Pournaras CJ, Emarah A, Petropoulos JK. Idiopathic Macular Epiretinal Membrane Surgery and ILM Peeling: Anatomical and Functional Outcomes. Semin Ophthalmol. 2011;26(2):42–46. doi:10.3109/08820538.2010.544237 [CrossRef]
  3. Brooks HL Jr, . Macular Hole Surgery with and without Internal Limiting Membrane Peeling. Ophthalmology. 2000;107(10):1939–1949. doi:10.1016/S0161-6420(00)00331-6 [CrossRef]
  4. Smiddy WE, Feuer W, Cordahi G. Internal Limiting Membrane Peeling in Macular Hole Surgery. Ophthalmology. 2001;108(8):1471–1478. doi:10.1016/S0161-6420(00)00645-X [CrossRef]
  5. Kanda S, Uemura A, Sakamoto Y, Kita H. Vitrectomy with internal limiting membrane peeling for macular retinoschisis and retinal detachment without macular hole in highly myopic eyes. Am J Ophthalmol. 2003;136(1):177–180. doi:10.1016/S0002-9394(03)00243-5 [CrossRef]
  6. Gandorfer A, Messmer EM, Ulbig MW, Kampik A. Resolution of diabetic macular edema after surgical removal of the posterior hyaloids and the inner limiting membrane. Retina. 2000;20(2):126–33. doi:10.1097/00006982-200002000-00004 [CrossRef]
  7. Stefaniotou M, Aspiotis M, Kalogeropoulos C, et al. Vitrectomy results for diffuse diabetic macular edema with and without inner limiting membrane removal. Eur J Ophthalmol. 2004;14(2):137–142.
  8. Patel JI, Hykin PG, Schadt M, Luong V, Fitzke F, Gregor ZJ. Pars plana vitrectomy with and without peeling of the inner limiting membrane for diabetic macular edema. Retina. 2006;26(1):5–13. doi:10.1097/00006982-200601000-00002 [CrossRef]
  9. Almony A, Nudleman E, Shah GK, et al. Techniques, rationale, and outcomes of internal limiting membrane peeling. Retina. 2012;32(5):877–891. doi:10.1097/IAE.0b013e318227ab39 [CrossRef]
  10. Mandelcorn MS, Nrusimhadevara RK. Internal limiting membrane peeling for decompression of macular edema in retinal vein occlusion: a report of 14 cases. Retina. 2004;24(3):348–55. doi:10.1097/00006982-200406000-00002 [CrossRef]
  11. Park DH, Kim IT. Long-term effects of vitrectomy and internal limiting membrane peeling for macular edema secondary to central retinal vein occlusion and hemiretinal vein occlusion. Retina. 2010;30(1):117–124. doi:10.1097/IAE.0b013e3181bced68 [CrossRef]
  12. Raszewska-Steglinska M, Gozdek P, Cisieki S, Michalewska Z, Michalewski J, Nawrocki J. Pars plana vitrectomy with ILM peeling for macular edema secondary to retinal vein occlusion. Eur J Ophthalmol. 2009;19(6):1055–62.
  13. Hartley KL, Smiddy WE, Flynn HW Jr, Murray TG. Pars plana vitrectomy with internal limiting membrane peeling for diabetic macular edema. Retina. 2008;28(3):410–419. doi:10.1097/IAE.0b013e31816102f2 [CrossRef]
  14. Kwok Alvin KH, Lai Timothy YY, Yuen Kenneth SC. Epiretinal membrane surgery with or without internal limiting membrane peeling. Clin Experiment Ophthalmol. 2005;33(4):379–385. doi:10.1111/j.1442-9071.2005.01015.x [CrossRef]
  15. Schumann RG, Schaumberger MM, Robhledere M, Haritoglou C, Kampik A, Gandorfer A. Ultrastructure of the vitreomacular interface in full-thickness idiopathic macular holes: a consecutive analysis of 100 cases. Am J Ophthalmol. 2006;141(6):1112–1119. doi:10.1016/j.ajo.2006.01.074 [CrossRef]
  16. Gandorfer A, Rohleder M, Grosselfinger S, Haritoglou C, Ulbig M, Kampik A. Epiretinal pathology of diffuse diabetic macular edema associated with vitreomacular traction. Am J Ophthalmol. 2005;139(4):638–652. doi:10.1016/j.ajo.2004.11.035 [CrossRef]
  17. Schumann RG, Rohleder M, Schaumberger MM, Haritoglou C, Kampik A, Gandorfer A. Idiopathic macular holes: ultrastructural aspects of surgical failure. Retina. 2008;28(2):340–9. doi:10.1097/IAE.0b013e31814cef23 [CrossRef]
  18. Gandorfer A, Rohleder M, Kampik A. Epiretinal pathology of vitreomacular traction syndrome. Br J Ophthalmol. 2002;86(8):902–909. doi:10.1136/bjo.86.8.902 [CrossRef]
  19. Yooh HS, Brooks HL Jr, Capone A Jr, L’Hernault NL, Grossniklaus HE. Ultrastructural features of tissue removed during idiopathic macular hole surgery. Am J Ophthalmol. 1996;122(1):67–75.
  20. Sadda SR, Campochiaro PA, de Juan E, Haller JA, Green WR. Histopathological Features of Vitreous Removed at Macular Hole Surgery. Arch Ophthalmol. 1999;117(4):478–484. doi:10.1001/archopht.117.4.478 [CrossRef]
  21. Haritoglou C, Schumann R, Reiniger I, et al. Evaluation of the Internal Limiting Membrane After Conventional Peeling During Macular Hole Surgery. Retina. 2006;26(1):21–24. doi:10.1097/00006982-200601000-00004 [CrossRef]
  22. Guyer DR, Green WR, de Bustros S, Fine SL. Histopathologic features of idiopathic macular holes and cysts. Ophthalmology. 1990;97(8):1045–1051. doi:10.1016/S0161-6420(90)32465-X [CrossRef]
  23. Messmer EM, Heidenkummer HP, Kampik A. Ultrastructure of epiretinal membranes associated with macular holes. Graefes arch Clin Exp Ophthalmol. 1998;236(4):248–254. doi:10.1007/s004170050072 [CrossRef]
  24. Ishida S, Yamazaki K, Shinoda K, Kawashima S, Oguchi Y. Macular hole retinal detachment in highly myopic eyes: ultrastructure of surgically removed epiretinal membrane and clinicopathologic correlation. Retina. 2000;20(2):176–83. doi:10.1097/00006982-200002000-00011 [CrossRef]
  25. Smiddy WE, Maguire AM, Green WR, et al. Idiopathic Epiretinal Membranes. Ultrastructural Characteristics and Clinicopathologic Correlation. Ophthalmology. 1989;96(6):811–821. doi:10.1016/S0161-6420(89)32811-9 [CrossRef]
  26. Kampik A, Kenyon KR, Michels RG, Green WR, de la Cruz ZC. Epiretinal and vitreous membranes: comparative study of 56 cases. Arch Ophthalmol. 1989;99(8):1445–1454. doi:10.1001/archopht.1981.03930020319025 [CrossRef]
  27. Lesnik Oberstein SY, Lewis GP, Chapin EA, Fisher SK. Ganglion cell neuritis in human idiopathic epiretinal membranes. Br J Ophthalmol. 2008;92(7):981–985. doi:10.1136/bjo.2007.132332 [CrossRef]
  28. Clarkson JG, Green WR, Massof D. A histopathologic review of 168 cases of preretinal membrane. Am J Ophthalmol. 1977;84(1):1–17.
  29. Chang S. Controversies regarding internal limiting membrane peeling in idiopathic epiretinal membrane and macular hole. Retina. 2012;32(8):S200–204. doi:10.1097/IAE.0b013e31825bc02b [CrossRef]
  30. Kumagai K, Ogino N, Furukawa M, et al. Retinal thickness after vitrectomy and internal limiting membrane peeling for macular hole and epiretinal membrane. Clinical Ophthalmol. 2012;6:679–688. doi:10.2147/OPTH.S30288 [CrossRef]
  31. Ray R, Baranano DE, Fortun JA, et al. Intraoperative Microscope-Mounted Spectral Domain Optical Coherence Tomography for Evaluation of Retinal Anatomy during Macular Surgery. Amer Acad of Ophthalmol. 2011;118(11):2212–2217.
  32. Christensen UC, Kroyer K, Sander B, Jorgensen TM, Larsen M, la Cour M. Macular morphology and visual acuity after macular hole surgery with or without internal limiting membrane peeling. Br J Ophthalmol. 2010;94(1):41–47. doi:10.1136/bjo.2009.159582 [CrossRef]
  33. Lee JW, Kim IT. Outcomes of Idiopathic Macular Epiretinal Membrane Removal with and Without Internal Limiting Membrane Peeling: A Comparative Study. Jpn J Ophthalmol. 210;54(2):129–134. doi:10.1007/s10384-009-0778-0 [CrossRef]

Clinical Versus Histologic Diagnoses

Histologic Diagnosisn (%)P Value
Clinical diagnosis: ERM (n = 93)< .001*
  ERM19 (20.43)
  ILM2 (2.15)
  ERM + ILM60 (64.5)
  Inadequate4 (4.30)
  No specimen3 (3.23)
  Other5 (5.37)
Clinical diagnosis: ILM (n = 100)< .001
  ERM4 (4.00)
  ILM25 (25.0)
  ERM + ILM50 (50.0)
  Inadequate9 (9.00)
  No specimen11 (11,0)
  Other1 (1.00)
Clinical diagnosis: ERM + ILM (n = 299)< .001
  ERM24 (8.03)
  ILM11 (3.68)
  ERM + ILM233 (77.93)
  Inadequate15 (5.02)
  No specimen11 (3.68)
  Other5 (1.67)

10.3928/23258160-20140411-01

Sign up to receive

Journal E-contents