This document summarizes a presentation on surgical techniques for treating macular pucker. It discusses the history of macular pucker surgery, comparisons of outcomes between traditional membrane peeling versus internal limiting membrane peeling techniques, debates around the use of dyes like indocyanine green, and proposals for future studies. The presentation concludes that en bloc removal of the internal limiting membrane and epiretinal membrane complex may reduce recurrence rates compared to membrane peeling alone, but larger multicenter trials are still needed to definitively determine differences in visual and anatomical outcomes.

1. Thomas M. Aaberg, Jr. M.D.
Retina Specialists of Michigan
Michigan State University

2. Disclosures
 Synergetics-consultant.
 Allergan-speaker.

3. Macular Pucker Surgery
The surgical removal of epiretinal macular
membranes (macular puckers)
Klin Monbl Augenheilkd
Robert Machemer, M.D.
1978 July; 173:36-42
 6 patients with macular puckers
 3 “spontaneous puckers”
 3 after retinal detachment surgery

4. VITRECTOMY, Second Ed (1979)
Robert Machemer, M.D.
Thomas M. Aaberg {Sr}, M.D.
Page 78… “The procedures about to be
described are the most delicate in
vitreous surgery and should be
attempted only when the surgeon has
mastered all other techniques.
Simultaneously, they represent an
aggressive attitude and are highly risky.”

5. Today…Surgical Results
 In general, patients can expect improvement
in metamorphopsia and regaining
approximately half of the vision lost due to
the pucker.
 Idiopathic Epiretinal Membranes
○ 80-90%: vision improves > 2 lines
 After Retinal Tears or Detachments
○ 65-90%: vision improves > 2 lines
RETINA. Ryan 4th Edition. 2006. Chapter 147 (McDonald, HR)

6. Today…Surgical Results
 However… we can expect visually
significant recurrent EMM in up to 5% of
eyes.
RETINA. Ryan 4th Edition. 2006. Chapter 147 (McDonald, HR)

7. Can we reduce the 5% visually
significant recurrence rate?

8. Medical management
 Topical steroids or NSAIDs.
 Intraocular steroids
 Intraocular chemotherapeutic
 Example: Methotrexate

9. Surgical Management
 Evidence to show that proliferating cells
requires the appropriate surface/scaffold.
 Retina: ILM is the scaffold.

10. Surgical Management
 Does removing the internal limiting
membrane…
 eliminates the scaffolding for gliotic proliferation?
 result in anatomic or functional benefit or harm?

11. Should we remove the ILM at all?
 Trese, Chandler and Machemer (Graefes
1983)
○ Fragments of ILM found in 20 removed epimacular
membranes with neurosensory retina cells on the
retinal side of the ILM.
 Similar histologic findings confirmed by other
investigators

12. Case of a 77-year-old woman
undergoes vitrectomy for
macular pucker in her right eye
PAS 25x
PAS 100x
Courtesy of Hans Grossniklaus, MD

13. Case 8. 69 year old woman with
surface wrinkling retinopathy
undergoes vitrectomy
OCT appearance
PAS 25XCourtesy of Hans Grossniklaus, MD

14. Should we remove the ILM?
 ILM is the Mueller cell’s basement
membrane.
 The Mueller cells are integral cells
providing structure to the retinal
anatomy.
 Dysfunctional Mueller cells are thought
to contribute to retinoschisis.

15. Foveola non-peeling internal limiting membrane
surgery to prevent inner retinal damages in early
stage 2 idiopathic macula hole.
Ho TC, et al. Graefes Arch Clin Exp Ophthalmol. 2014 Mar 23.
 28 eyes with stage 2 macular hole
 Group 1: foveolar ILM nonpeeling group (14
eyes). A donut-shaped ILM was peeled off,
leaving a 400-μm-diameter ILM over fovea.
 Group 2: total peeling of foveal ILM group (14
eyes).

16. Foveola non-peeling internal limiting membrane
surgery to prevent inner retinal damages in early
stage 2 idiopathic macula hole.
Ho TC, et al. Graefes Arch Clin Exp Ophthalmol. 2014 Mar 23.
 RESULTS:
 Smooth and symmetric umbo foveolar
contour was restored without inner retinal
dimpling in all eyes in group 1, but not in
group 2.

17. Foveola non-peeling internal limiting membrane
surgery to prevent inner retinal damages in early
stage 2 idiopathic macula hole.
Ho TC, et al. Graefes Arch Clin Exp Ophthalmol. 2014 Mar 23.
 RESULTS:
 The final vision was better in group 1 (P = 0.011).
 100% group 1 versus 50% group 2 regained the
inner segment/outer segment (IS/OS) line.
 Restoration of the umbo light reflex was found in
12 of 14 eyes in group 1 (86 %) but none in group
2 (0 %).

18. Reducing the 5% visually
significant recurrence
 Park DW et al (Ophthalmol 2003). Macular pucker
removal with and without internal limiting membrane
peeling: pilot trial
 Two surgeons, EMM Peel versus “Double Peel”
No ILM Peel ILM Peel
Vision Improved 80% 100%
5 line gainers 25% 30%
Recurrence 21% 0%

19. Reducing the 5% visually
significant recurrence
 Haritoglou et al. The effect of indocyanine-green on
functional outcome of macular pucker surgery. AJO 2003.
 EMM peel vs “Double peel” with ICG assistance
No ILM Peel ILM Peel
Vision Improved 86% 55%
Visual field
defects
0% 35%
Recurrence NA NA

20. ICG Saga
 2000: Kadonosono et al (Arch Ophtho)
 Staining the Internal Limiting Membrane
Facilitates ILM removal
 2001: Sippy et al (AJO)
 ICG toxic effect on cultured RPE cells
 2002: Engelbrecht et al (AJO)
 Potential RPE ICG toxicity in macular hole pts
 2003: Uemura et al (AJO)
 Visual field defects in 44% of ICG assisted
macular hole surgeries compared to 0% of non-
ICG cases.

21. Comparative evaluation of no dye assistance, indocyanine
green and triamcinolone acetonide for internal limiting
membrane peeling during macular hole surgery.
Tsipursky MS, et al. Retina. 2013 Jun;33(6):1123-31.
 Retrospective, comparative
interventional case series of PPV/ILM
peel.
 435 eyes with macular hole assigned to
3 groups:
 Group 1: no dye assistance
 Group 2: ICG –assisted
 Group 3: Triamcinolone-assisted.

22. Comparative evaluation of no dye assistance, indocyanine
green and triamcinolone acetonide for internal limiting
membrane peeling during macular hole surgery.
Tsipursky MS, et al. Retina. 2013 Jun;33(6):1123-31.
 RESULTS:
 Closure rate with a single surgery
 Group 1: 95 %
 Group 2: 94 %
 Group 3: 96 %
 Visual Acuity of 20/50 or better
 Group 1: 78 %
 Group 2: 66 %
 Group 3: 81 %

23. Comparisons of cone electroretinograms after indocyanine
green-, brilliant blue G-, or triamcinolone acetonide-
assisted macular hole surgery.
Machida S, et al. Graefes Arch Clin Exp Ophthalmol. 2014 Mar 2
 To compare the function of retinal ganglion
cells (RGCs) using the photopic negative
response (PhNR) in patients who had
 ICG-assisted
 Brilliant blue G assisted, OR
 Triamcinolone assisted
IILM peeling during macular hole surgery.

24. Comparisons of cone electroretinograms after indocyanine
green-, brilliant blue G-, or triamcinolone acetonide-
assisted macular hole surgery.
Machida S, et al. Graefes Arch Clin Exp Ophthalmol. 2014 Mar 2
 RESULTS:
 All macular holes were closed
 Visual improvement similar amongst the groups.
 No significant difference between the
preoperative and postoperative RNFL thickness.

25. Comparisons of cone electroretinograms after indocyanine
green-, brilliant blue G-, or triamcinolone acetonide-
assisted macular hole surgery.
Machida S, et al. Graefes Arch Clin Exp Ophthalmol. 2014 Mar 2
 BUT:
 The implicit times of the a-waves and b-waves
were significantly prolonged in all groups
 Oscillatory potential amplitude were significantly
decreased postoperatively in all groups.
 The postoperative photopic negative response
amplitudes was significantly lower in the ICG
group than in the BBG or TA

26. Comparisons of cone electroretinograms after indocyanine
green-, brilliant blue G-, or triamcinolone acetonide-
assisted macular hole surgery.
Machida S, et al. Graefes Arch Clin Exp Ophthalmol. 2014 Mar 2
 Suggests removing ILM may change retinal
function.
 Suggests ICG may have toxic effects.

27. Question:
Compared to traditional macular pucker
surgery will en bloc removal of ILM and
EMM using ICG dye assistance
1) Have any affect (detrimental or beneficial)
2) Reduce visually significant recurrence rate

28. Minimizing Risk of ICG
 Dilute concentration
 Osmolarity
 Avoiding “bare retina” or “bare RPE”
 Perhaps the cellular EMM is a protective
barrier between ICG and macular retina
 No re-staining retina after membrane peel

29. Study Design
 Inclusion criteria
 Macular puckers
○ Idiopathic
○ Post RD
○ Vitreomacular traction with surface gliosis
 Follow-up greater than 3 months
 Exclusion
 Concurrent eye disease which may
confound outcomes (ex: advanced
glaucoma, AMD, AION, etc)

30. Surgical Procedure
 Two site study
 Surgeon 1 (Group 1): PPV/MP
 Surgeon 2 (Group 2): PPV/en bloc ILM-MP
 ICG preparation
 2mg ICG dye mixed with 2 cc of sterile water. An
additional 3 cc of BSS added to ICG mixture for a
final concentration of 0.4 mg/cc.
 Intra-operative use of ICG
 Delivered in a fluid filled eye
 Gently irrigated over macula
 Allowed to reside in eye within the time it takes to
exchange the dye cannula for the vitrectomy
instrument and evacuate the excess.

32. Results
 Total number of patients: 117
 Group 1: 37
 Group 2: 80
 Preop Visual Acuity
 Group 1: .53 logMAR (20/68)
 Group 2: .58 logMAR (20/74)
○ p = 0.374
 Follow-up period
 Group 1: mean of 12 months
 Group 2: mean of 7 months

33. Results: Final Visual Acuity
 Group 1: .36 logMAR (20/46)
 Group 2: .34 logMAR (20/44)
 p = 0.727
8037 8037N =
en bloc (Y/N)
YN
2.0
1.5
1.0
.5
0.0
-.5
Pre-op VA
Final LogMAR VA
117115
75
106
21
15
7551
321
2410812
Group 1 Group 2

34. Results: Recurrence Rates
 Overall recurrence rates
 Group 1: 6 (16%)
 Group 2: 1 (1.3%)
○ p = 0.002 (chi-square), 0.004 (fisher’s)
 Visually Significant (requiring reop)
 Group 1: 1 (3%)
 Group 2: 0 (0%)
○ p = 0.140 (chi-square), 0.316 (fisher’s)

35. Results: Complications
 Group 1: None
 Group 2: Macular hole (one patient).
 Visual field defects
 Formal fields not done
 None reported
 RPE alterations
 None noted

36. Other Studies
 Double Peel
○ Shimada H, et al. Ophthalmol, 2009
○ Feldman A, et al. Eur J Ophthalmol, 2008
○ Lai TY, et al. Graefe’s. 2007
○ Kwok A, et al. Clin Exp Ophthalmol. 2005
○ Kwok A, et al. Eye, 2004
○ Haritoglou C, et al. Am J Ophthalmol. 2003
○ Stalmans P, et al. Br J Ophthalmol. 2003
○ Park DW, et al. Ophthalmol. 2003
 Close to En Bloc
○ Hillenkamp J, et al. Graefe’s, 2007
 Goal of EMM peel only though ILM often removed
○ Koestinger A, et al. Eur J Ophthalmol, 2005

37. Overall conclusions when comparing
EMM without and with ILM peel
 Double Peel
○ Vision statistically no different (majority)
 One study reported visual improvement with ILM peel
 One study reported worsen of vision with ILM peel
○ Recurrence rate statistically no different or
reduced with ILM peel
 Close to En Bloc
○ No statistical difference in visual outcomes
○ No statistical difference in recurrence rate
○ Potential toxicity in ICG cases
 Visual field defects

38. Comment
 Intuitively, en bloc removal of ILM-EMM
complex seems less traumatic and more
efficient than performing a “double-peel.”
 ILM removal appears to reduce the
recurrence rate of epimacular
membrane re-proliferation.
 Visual significance … perhaps none.

39. Patient’s Perspective
 “I want to see as clearly as possible”
 Acuity
 Lack of Distortion
 “I do not want to have complications”
 “I do not want repeat surgery”

40. Need for a Definitive Answer
 Surgical Consortium
 Multicenter group of vitreoretinal surgeons
 Surgical procedure will be assigned by physician’s
preference.
 Based on pilot data for a 2-arm trial, a total of 550
patients will need to be enrolled (275 patients per
arm).
○ Study visions
○ Contrast sensitivity
○ Formal visual fields
○ OCT
○ Cost analysis (surgical time, equipment, etc)
○ +/- ERG testing

41. You are all welcome in Michigan
Thank You !Thank You !