Chapter 34 Internal limiting membrane peeling in macular surgery Rizwan A Cheema and Ewan A Fraser Introduction ‘There are an increasing number of conditions in which ‘manipulation of the vitreoreinal interface, and in particular peeling of the internal limiting membrane (ILM) from the retina, may be desirable, Idiopathic macular hole surgery has attracted the most auention, There are questions as 0 whether to peel the ILM in any or all cases of macular holes, depending on the age or size of the hole. The technique of ILM peeling has also been undercaken in the surgical rreat- ment of traumatic macular holes, macular holes causing ‘extensive retinal detachment, retinal detachment with pro- liferative vitreoretinopathy (PVR), epiretinal membranes (ERMBs), diabetic cystoid macular edema, and pseudophakic cystoid macular edema. A variety of techniques and aids to visualization have been advocated to undertake the dificule task of ILM peeling, and these will be explored in this chapter. Surgical technique: ILM peeling in idiopathic macular holes ‘The following description is based on the technique used by the precent authors for ILM pesling in che presence of an idiopathic macular hole. ‘The choice of local or general anesthesia is made hased on. the patient's abiligy teasain stil aud ow dicts goustal health, The eye is prepared with povidone-iodine 5% or equivalent and covered with sterile drapes as for other intraocular surgery. three-port pars plana vitrectomy is undertaken with 2 wide-angle viewing system, the binocular inditect ophthalmomicroscope (BIOM, Insighe Instruments, Inc. Stuart, HL). A core vitrectomy is perlormed, followed bby the induction ofa posterior vitreous detachment (PVD) if icisstil attached, Posterior hyaloid separationis grealy assisted by use of intraoperative intravitreal triamcinolone acetonide, as described by Peyman eral.! The edges ofthe macular hole frequently become elevated as the vitreous from around the hole is removed; the edge of the hole drops back as the anteroposterior traction is removed. The peripheral vitreous is then trimmed, with an assistant indenting the sclera A higher magnification sewn-in lens, such asthe Landes Jens, is put in place to provide 2 more detailed view of the macula. While some authors report good results without using an ILM sain, we bave found the procedure 0 be much safer and more repeatable if a staining agene is used. ‘The ILM is thin and transparent, and can be difficult to peel and grasp in a smooth curvilinear manner, similar to that of the anterior lens eapsule in cataract surgery. Widely varying techniques, as well as concenerations and volumes of indocyanine green (ICG) used to stain the ILM for visualization during peeling, have been reported.** We use 0.2 ml of 0.1-0.5 mg/ml ICG, which is injected with- out performing a fluid-air exchange (Fig, 34.1). The ICG. injected over the optic disc and setles readily on the poster jor pole, Cate is taken co avoid injecting ICG through the Figure 34.1 indocyanine geen ((CG) i injected ove the posterior pole and removed with 2 fute needle, leaving stained intemal living membrane (ILM), Peeing of the ILM is inated, and is completed with ené-gripping forceps to continue the tar centered on the fovea ina orcular fishon,ko INTERNAL LIMITING MEMBRANE PEELING IN MACULAR SURGERY ‘macular hole into the subretinal space. After 1 minute, asp ration using che vitrectomy probe removes any IC not bound to the ILM. If triamcinolone acetonide is the agent used to facilitate [LM visualization, 0.2 ml i injected over the posterior pole of the vitrectomized, fluid-filled eye before being allowed to settle for 30 seconds (Figs 34.2 and 34,3) Aspiration using the nonadherent triamcinolone acetonide particles, leaving. an interrupted white coating over the ILM to aid visualization; the ILM is more easily seen as it is elevated, avoiding attempted ILM peeling in areas thar have already een treated. Trypan blue,*? which has been used in ILM peeling at concentrations of 0.06-0.2%, ie injected after fluid air itrectomy probe will remove all exchange and lelt to stain the membrane for 2 minutes before being washed out by aspiration of dye with a flute needle followed by air-fluid exchange. ‘There is a debate as to whether trypan blu lying ERM.’ In our experience, this preparation isthe lease effective ofthe three described for the purpose of ILM peeling Adia movement over the surface of the retina to elevate the ILM at least one dise diameter fiom the center ofthe fovea. Iti wise to start the ILM peel away from the papillomacular bbundle and in an area in which there are no blood vessels that could be inadvertently transected wich the instrument. A microviteeoretinal (MVR) blade with the tip bent co approximately 45° can be used to incise and elevace the ILM. scains the ILM or merely the over~ nond- eyes that were treated with vit- rectomy plus ILM peeling for idiopathic macular holes of {greater than 6 months’ duration were also considered. While this study is limited by 2 number of factors (most notably the fact that the non-ILM-peeled group formed the earlier ‘group of patients ro be treated and would have been on the surgeon’s learning curve), relatively large numbers ‘were included and there was a minimum follow-up period of 18 months Primary anatomic closure was achieved in 36 of 44 holes (82%) in the non-ILM-peeling group, versus 116 of 116 hholes (100%) in the ILM-pecling group. OF che 36 rucces- ful macular hole closures inthe non-ILM-pecling group, 9 reopened in the frst 6 months following surgery, whereas there was no reopening of the successfully treated holes in the ILM-peeling group. This study had an anatomic success rate of 61% in non-{LM-peeled eyes, compared with 100% anatomic success in the ILM-peeled group; 63 of 69 eyes (97%6) with macular holes of greater than 6 months’ duration ‘were successflly closed using the ILM peeling technique.362_ INTERNAL LIMITING MEMBRANE PEELING IN MACULAR SURGERY Interestingly, the visual acuity in the succesfully closed ‘macular holes without ILM peeling was the same as that in the successfully closed macular holes with ILM peeling, ‘which suggests that, in this series, peeling of the ILM was ‘not an intrinsically damaging technique. ‘A meta-analysis undertaken by Mester and Kuha““exam- ined LL studies with a total of 696 patients on whom mac- ular hole surgery had been performed without the use of Table 34. adjuvants or ILM peeling (Table 34.1), and compared this with four studies wich a coral of 221 patients in whom mac- lular hole surgery had been underraken with ILM. pecling and no adjuvant use (Table 34.2). While the limitations of interstudy comparisons must be kept in mind, the ILM- peeled group had an average anatomic success rate ot 96%, ‘compared with a success rate of 76% in the non-ILM-peeled group. Macular hole surgery without adjuvant use or internal limiting membrane peeling “Thompson et al! (1998) sya Minha et aP" (1997) 22a Freeman et af (1997) 914 Smiddy et a" (1997) a 14 Pendergast and McCuen"® (1996) 50. 2-4 Wilis and Garcia-Cosio® (1996) 132, 2-4 Ruby et al (1994) eas Ryan and Gilbert (1994) a) Wendel ee at (1993) 17% 34 ‘Orellana and Liebermann” (1993) 23 Kelly and Wendel (1991), S23 Total 6 © PFC, perfuorocarbon: SF sulfur hexafluoride, ® With one surgery snd defined as dsappearance ofthe ful cut «Defined as an improvement of2 or more Snellen ines. te PFC 6! 0 20% SF, % 38 1656 PEC ° 9 1696 PC él 65 30% SFor 88 36 = 20% PFC 49% 5, 31 B Nonexpanding 67 si ts 16% PECor 71 6 =UESF, Typlely SF, 77 56 20% SF, 38 38 Nonexpanding $8 a ns = 7 55 Table 34.2 Macular hole surgery with internal limiting membrane peeling but without adjuvant use ‘Mester and Kuhn (2000) 4% 14 ‘Da Mata et al (2001) er! Lochhead eta (2004) “14 Tora 104 © SF, slr hexauri. * With one surgery and defined as disappearance ofthe uid cul. «Defined ae an inpravemant of? or mare Snalen Hes SHKSF, 9% 85 = 8 % 912 17‘The basal lamina of the Miller cells is involved in the generation of the electroretinogram bewwave it would here> fore be reasonable to expect an alteration in retinal physiol- ogy and function caused by removal of areas of this tissue. Indeed, a prospective tial by Terasaki et al!? found thatthe percentage increase in the b-wave amplicude 6 months after macular hole surgery was significandly higher ia dhe non- ILM-peeled group (44.0%; n=19) than in the ILM-pecled group (15.0955 #30). The removal of the ILM had no adverse effect on visual acuity. However, the selective delay of recovery of the electrorerinographic bewave 6 months afer surgery suggests an alteration of retinal physiology in the macular region. Improvements in vision in 2 patients with chronic pseudophakic cyscold macular edema following ILM pecl- ing?” and in 11 of 12 patients with chronie diabetic macu- lar edema" have been described. Further study is merited to ascertain the role of ILM peeling in macular edema, and in particular to provide guidance for patient selection. In traumatic macular holes, vitrectomy with ILM peeling led to.a 100% (17 of 17) closure rate, with 2 94% (16 of 17) improvement in visual acuity in a recent study by Kuhn ec al ILM peeling and dye-associated retinal toxicity AA recent concen has been that ICG, which is the most ffec- tive ILM stain, may cause recinal damage” Conflicting reports have been published, some of which report good rates of anatomic closure of macular holes following ILM peeling but wich lice or no vial improvement,” whscas ‘others report anatomic and functional success following 1CG-assisted ILM peeling.” Tokuda et a have recently reported that ICG exposure caused damage in every retinal layer in isolated rat retinal ts- sue and higher release of lactate dehydrogenase in an exper- imental model. Gandorfer et al reported less favorable visual results and Hlaitoglou etal reported no statistically significant improvement of visual acuity wich the use of ICG, Ando et al? reported thar ICG-assiseed ILM peeling sproved the anatomic success rate in macular hole surgery, bbue may lead 10 an unfavorable visual acuity outcome and peripheral visual field loss. Hovsever, another clinical study reported comparable visual and macular hole closure results with and without the use of ILM peeling augmented with ICG. Da Mata ee aP* concluded in their study char ICG-asssted [LM peeling i safe CONCLUSIONS 363 during macular hole surgery, because it was associaced with ‘good anatomic and visual results and showed no clinical or angiographic evidence of roxicity Proposed mechanisms for retinal damage include induc- tion of apoptosis and alteration ofthe cleavage plane berween the ILM and the neurosensory retina, resulting in issue dam- age, Other proposed hypotheses implicate direct neuroreinal and pigment epithelium toxicity" caused by the solution osmolariey, ancl pl), ax well ax enhanced light tonicity” resulting from increased uptake of light from the fiberoptic probes in areas of stained retinal surface. While studies have been undertaken wo evaluate the effective minimum doses of ICG for ILM staining? che safe concentration, technique, and time of exposure for ICG have not been determined, In our clinical practice, we use a formulation ro achieve a 0.1% ICG concentration with an osmolarity of 290-300 mOsm/kg and a pH of 5.8. This preparation is theoretically less likely to have toxic effects on the retina, because of che low concentration ofthe drug and the ‘physiologic’ osmolar- ity. We use [CG only in eyes filled with balanced saline sol tion and wash our the surplus dye immediately: we limit che amount of dye applied to the posterior pole and retract the endbolight probe as far from the retina as possible in order co avoid photoroxicty. In a recene study, Ho et ab* have described 2 formulation in which sodium is removed from the solvent: this modification was associated with reduced ICG uptake and reduced cytoroxicity, which may be seal in preventing {CG-associated intraocular toxicity. Further clinical and Tahorstary sndiee are needed co evaluate che safery of ICG in vitreoretinal surgery Conclusions Although the evidence is far from complete in determining whether ILM peeling is unequivocally advantageous for patients undergoing surgery for the conditions detailed above, this is a common situation for practicing physicians. Information describing this technique and supporting its use should be analyzed in derail by surgeons contemplating offering ic to their patients. Reference must be made o the particular condition being treated, its duration, and the surgeon's own experience, In che absence of a randomized controlled trial, itis our view thae ILM peeling, while technically challenging, should bbe advocated forall macular hos except those that are small and of short duration, in ERM peeling, and in chronic ‘macular edema where other therapeutic options have been unsuccesfl,364 References INTERNAL LIMITING MEMBRANE PEELING IN MACULAR SURGERY 1. Peyman GA, Cheews R, Convay MD, Fang T. Trameinolone scewnide a an ad vo vsualation ofthe viucous and the posterior hyaloi daring pars plan viteeromy. Reina 2000,20:554-5, 2. Ko AK, Lai TY, Yew DT, Li WW. Interna limiting membrane staining with various concentrations of indocyaine green dye under at maculae surges. Ar | Ophthal 2003:136-228-30, 3. Kadam I; leat N, Ushio E, et a Sting of internal liming membrane in maculae hole surgery. Arch Ophthalmol 2H 1811168 4, Fear EA, Cheema RA, Rober MA, Tiircinolone scstonide sce peeing of retinal ineral Ring membrane for macular surgery Retina 2003:23.83-4 5. Kimura H, Kuroda S, Nagata M. Tlamcinolane acetonide asd peeling of the intral limiting membrane. Ar J Ophihalenel 200431971723 6. Tela FA, Mobr A, BcandeC, eta. Thypan blue staining in vieeore:inal surgery. Ophthalmology 2003110240912, 2. WK, Wong D, HliscoreP eal: Trypan blue staining of iemal Fimiing membrane and epireinal membrane ducing vec ‘iui esl and histopathologic! findings. 8- J Ophihalm 2m05387.216-9, 8, Rodrigues EB, Meyer CH, Schmid JC, Kell P. Trypan blue stains the epiretnal membrane but or he inkl ling membrane. Br J Ophtlenol 200387:1431-2 9. Sorcinali R. Surgical management of epzeinal membrane with indocyanine green-assised peeling. Ophchalmelogica 2003217:107-10, 10, Bran PD, Anau S, Dimas SA, Stangos TF, Removal ofthe cena liiting membrane under peruorocabon liquid to ‘acar macularbole-asociated rina dechmest, Am J Ophthal 200313589446 11, Lai CG, Chuang LH, Ku WC, e¢ a. Suga removal of the ‘tena imiing membrane forthe eeatment af a maclar hole (Chang Gung Med J 200225:819-25. 12, Uemura A. KandsS, Sokamoto ¥ Kit H. Viol field delet afer uneven vtecromy for epretnal membrane wit indocyanine zecn-asisted inter limiting membrane pecking. Am J Ophthalmol 203:136:252-7 13, Terasaki H, Mipake V; Nomura Rea. Foeal macular ERG in ‘je fet esoval of macaler ILM dusting rena hole gery Invest Ophthalmol Vi Sei 2001;12:229-34 14, Yoon KE, Sap MS. Macular hole afer poling of dhe incrl liming membrane in dabeic maculae ema. Ophshalic Sang Lasers Imaging 2003:34478-9. 15, Kelly NE, Wendel RT. Vitreous sugery for idiopathic macular holes Results of pilot stud. Arch Ophthalmol 1991:108.654-9. 16. Kim JW, Fecoan WR, Az SP, cc al, Prospective randomized tral of vizecony o observation for sage 2 macular holes. Vicectomy for Macular Hle Study Group. Am J Ophthal! 19961260514 17, Feoaman WR, Asin SP, Kim JW, etal, Vircrmy fi she treament of fillthikness sage 3 or 4 macular holes Results of rlicener randomized cna tl ‘The Virestomy for “Treament of Macale Hole Study Group. Arch Ophthal a. 2. 23 24, 2. 2. 28 2. 2. a1 2. 33 a. %. “Thompson JT, Smildy WE, Will GA, ct. Comparison of combinant eansorning prow factor-2 and plaecbo a an Adjunctive agen for maciar hole singery. Opathalmlogy 19985105:70-, Campochitr PA, Van Nil E, Vinores SA. Immunacyrochemicl labeling of elle in cota visu rom pains with premcule hole lesions. Arch Ophihalmel 1992:1103371-7, Gordor LW. Glaser BM, Le D, tal Ful thicknes mace hole formation ia jes with a pre-esting complete poserorvteous deuachrnent. Ophthalmology 1995:1021702-5, Broo HL Je. Macular hole suery with and without inal limiting membrane pesing. Ophthalmology 29003107:1939-28, Mester V Kuhn F Ince iting membrane eemoval ia the management of fll thicknest macolehole. Arn} Ophthalmol 0 29769-7 Peyman GA, CanakisC, LivirRalltas ©, Conway MC. The ect of ncernal liming membrane peling on chvonic recat pseudophakic cystoid macular edema epee of eo as. Arn J ‘Ophihilme! 20023138571-2. GGandocir A, Messmer EMG, Ulbig MW, Kampik A. Resolution of Aidbecc maculir ecm air supa removal of dhe posttiog halo and che inner Kniing membrane: Retina 2000,20:126-33, Xun &, Moet B, Mester V, Wichespoon CD. Internal iting ‘membrane removal for taumtie macilar holes. Opal Song Lasers 2001 32308-15. GGandowir A, Menimer EM, Uhig MW, Karpik A. Indocyaine een selecvely stains che een limiting membrane. Am J (Ophuhalno! 2001:131:387-8 CGandovir A, Haopou C, Gast CA, eta. adocyanine green assted peling of dhe inca ining membane may use ‘etna damage. Am J Ophthalmol 20015152431-3, Engelbrecht NE, Feeman J, Sternberg P Js al Recnal pigment pth changes fer macular hoe sarge with indocyanine geet-ained internal lining membrane pling. Am J (Ophbalmal 2002:13389-04 ALAbdlla NA, Thompson JT, Sala RN. Resls of maculae bole aurgey wth and withous epirecaldinertion or iteoal lining membrane removal. Opbaleology 20081 1142-9 Lockned J, Jones Ey Chui Decal. Oucome of ICG-asited ILM peel in macular hole surgery. Eye 2004:18804-8, Tokuda K, Tsslamoro T, Fjisva S, Marukara M. Bsaluation of toxin de to weal sain in iota rt retinas Acta Ophthal Scand 20045218994 orig C. Canderer A, Gase CA, eal Indecyanine-aaiued peeling of the intemal ming membrane io macular bale surgery ‘lfecs vil oucome: «clinicopahologic creation, Am J Ophhalme! 200213483641 Ando F, Suano K, Ohba N, et al Anatomic and visual outcomes er indocpanine geenasived pesing of the rei intemal Teng cbeane i Ege macalar a: engey. Am Ophhatmol 2004;137:609-14 Da Mats AP, Burk SE, Riemann CD. ca indocyanine green ssid poling of dhe resnal intemal limiting membrane ding vizetomy surgery for macular hole pit, Opthalmology 2osn0s:1187-92, Sippy BD, Engelbrecht NE, Hubbard GB, ec. Indocynine geen effec on cultured human recnal pigment epthlalcell implications For macro ngery, Am J Ophslna 20916324488 5,3. a. 38. ». Salimans P, Van Aken EH, Veckener My etal Tonic eft of indocyanine geen on retinal pgmene epithelium clad eo ‘mode effcts of dhe solvents Arn J Ophthalmol na sae28ies, Hixitglou C, Gandorfe A, Sehaumberger Myc Li alsorbing properties and oslatiy of indocyanine green Arpending on conceaation and went medium [awet Ophtalmol Vis Sei 2003:442722-9, Ho JD, Tsai , Chen SN, Chen HC, Removal of sium fom the solvent reduces renal pigmeneeithelim roxiciy cased by indocyanine geen: implitions for macilar hole srgery. Br} (Ophthalmol 200688:556-9. Miniban M, Goggin M Clery PE, Surgical mangement of macular holes rll sing ga aponad alone, o in combination with aucogous platelet concentrate, or transforming growth factor 82. Br} Ophthal 1997:81:1073-9, Freeman WR. Aten SP, Kio JW, et a Viewecromy forthe tweatment oF fll thicknes stage 3 o¢ 4 macular hole, Reus of a rmuicentered eandowiced clini ial The Vitecomy for 4 2. 48. 4. REFERENCES 365 ‘Treatment of Macubr Hole Sudy Group. Arch Ophehalnol 1997s115211-21. Smid WE, Pimentel 8, Willams GA. Macular hoe surgery without luingaunctveadves. Ophthalmic Sug Lasers 1997,28:713-17. Pendergast SD, McCuen BW 2nd. Visual Feld Joss fer macule hole surgery. Ophthalmology 1996¢103:1069-7, Wills AW, Gaia Cosi JE. Macular hole auggery. Compation of longstanding versus recent wacular holes. Ophthalmology. 1996105181114 Ruby AJ, Wiliams DF, Geand MG, el. Par plan vetomy for treatment of stage 2 macular hoes. Ach Ophthalmol 1994:112359-64, yan EH Jf Gere HD. Resales of surgi reatment of rose fom fullthicknes idiopathic snus ll. Arch Ophhalmel ood 12154553 ‘Wendel RT, Patel AC, Kelly NE, ota, Vitro super for macular hols, Oshthalmalogy 1993:100:1671-6 (lana J Lieberman RM. Sage IT macular hole sargery. Be J Ophehalmol 1993:77555-8,