Downloaded from http://bjo.bmj.com/ on August 30, 2016 - Published by group.bmj.com Clinical science After ocriplasmin for VitreOmacular adhesion Or Macular hole (VAVOOM) study Margaret A Greven,1,2 Sunir Garg,1 Bing Chiu,3 Sumit P Shah,3,4 Jeremy Wolfe,5 Howard F Fine,3,4 Daniel B Roth,3,4 Joshua Robinson,6 Jacob Mong,7 Jason Hsu,1 Carl Regillo,1 Allen Ho,1 Julia A Haller1

1Mid Atlantic , The ABSTRACT Intravitreous Injection-Traction Release Without Retina Service of Wills Eye Background/aims To describe the results of pars Surgical Treatment (MIVI-TRUST) trials, eyes Hospital, Philadelphia, Pennsylvania, USA plana vitrectomy (PPV) for persistent symptomatic treated with ocriplasmin injection had a higher rate 2Byers Eye Institute, Stanford vitreomacular traction (VMT) with or without macular of VMA release as well as MH closure compared University School of Medicine, hole (MH) after intravitreal ocriplasmin injection. with placebo.2 Some eyes in the MIVI-TRUST trials Palo Alto, California, USA 3 Methods Multicentre retrospective study of eyes that that underwent injection of ocriplasmin did not Rutgers, Robert Wood received intravitreal ocriplasmin between January 2013 have resolution of and subsequently went Johnson Medical School, New Brunswick, New Jersey, and January 2014 for symptomatic VMT with or without on to PPV; however, little information regarding the 2 USA MH, and then went on to PPV (ocriplasmin-treated outcomes of those patients is available. The 4NJ Retina, New Brunswick, group) for persistent pathology, compared with a control purpose of this study is to investigate the outcomes New Jersey, USA group of patients with symptomatic VMT with or without of eyes that received ocriplasmin for persistent 5Associated Retinal Consultants, Royal Oak, MH who were offered ocriplasmin injection but sVMA with or without MH and went on to PPV for Michigan, USA proceeded directly to PPV (PPV-only group). persistent pathology compared with a similar group 6Emory Eye Center, Atlanta, Intraoperative characteristics, visual acuity (VA) outcomes of eyes that underwent PPVonly. Georgia, USA 7 and spectral-domain optical coherence tomography Eye Clinic of Wyandotte, images were reviewed for the two groups. Primary Wyandotte, Michigan, USA outcome measure was VA after PPV. MATERIALS AND METHODS A multicentre retrospective review was performed Correspondence to Results 51 eyes of 51 patients underwent PPV after Dr Sunir Garg, MidAtlantic receiving ocriplasmin, and 22 eyes of 22 patients of all eyes that received ocriplasmin with subsequent Retina, The Retina Service of proceeded directly to PPV. Although VA was significantly PPV from three centres (Wills Eye Hospital/Mid Wills Eye Hospital, 840 Walnut better at all time points in the PPV-only compared with Atlantic Retina, Philadelphia, Pennsylvania; NJ Street, Suite 1020, Retina, New Brunswick, New Jersey; and Associated Philadelphia, PA 19107, USA; the ocriplasmin-treated group, at 3 and 6 months after [email protected] PPV both groups had similar amount of visual Retinal Consultants, Royal Oak, Michigan) for per- improvement. Both groups had similar rates of pathology sistent VMA and/or presence of MH (ocriplasmin- Received 19 August 2015 resolution; 50/51 (98%) eyes in the ocriplasmin group treated group) between January 2013 and January Revised 1 November 2015 and 22/22 (100%) eyes in the PPV-only group had 2014. The charts of all patients at Wills Eye Accepted 8 November 2015 Hospital and at Associated Retinal Consultants who Published Online First release of VMT and/or MH closure after PPV. The two 9 December 2015 groups had similar PPV-related complication rates. were offered but did not receive ocriplasmin for Conclusions Eyes with persistent symptomatic VMT VMA with or without MH and then went on to PPV and/or MH have similarly high rates of pathology were also reviewed (PPV-only group). The institu- resolution as well as similar VA gains regardless of tional review boards of all three centres approved whether they received ocriplasmin prior to PPV. the study. Data collection and reporting was in com- pliance with all Health Insurance Portability and Accountability Act regulations. Baseline patient characteristics including age, INTRODUCTION gender, visual acuity (VA), phakic status and pres- The vitreous is primarily composed of water, pro- ence of (ERM) or other visu- teoglycans and , and is attached to the ally significant pathology were recorded. In the macula by extracellular matrix proteins including ocriplasmin group, Snellen VA (including pinhole laminin and fibronectin.1 Over time, the vitreous VA when available) was recorded at the following liquefies and separates from the retina, resulting in time points: preocriplasmin injection, postocriplas- a posterior vitreous detachment (PVD).1 min but pre-PPV and 1, 3 and 6 months post-PPV. Vitreomacular adhesion (VMA) occurs when the For PPV-only patients, Snellen VA (including vitreous remains attached to the macula.1 VMA can pinhole VA) was recorded pre-PPV, and 1, 3 and cause symptoms including , 6 months post-PPV. VA (pinhole if available) was blurred vision and central visual field defects, and converted to LogMAR for data analysis. can result in macular distortion, oedema and full Operative reports were reviewed for all patients. thickness macular holes (MHs).2 The intraoperative use of indocyanine green (ICG) Previously, the only therapy for symptomatic 5 mg/mL, peeling of an ERM and/or of the internal VMA (sVMA) was pars plana vitrectomy (PPV). limiting membrane (ILM), air or type of gas tam- To cite: Greven MA, Recently, ocriplasmin, a proteolytic enzyme with ponade, and intraoperative and postoperative com- Garg S, Chiu B, et al. Br J activity against fibronectin and laminin, gained plications were recorded. Ophthalmol approval for non-surgical treatment of sVMA with Spectral-domain optical coherence tomography – 2016;100:1211 1215. or without an MH. In the Microplasmin for (SD-OCT) preocriplasmin injection, pre-PPV and

Greven MA, et al. Br J Ophthalmol 2016;100:1211–1215. doi:10.1136/bjophthalmol-2015-307701 1211 Downloaded from http://bjo.bmj.com/ on August 30, 2016 - Published by group.bmj.com Clinical science

USA), and two-sided p<0.05 was considered to be statistically Table 1 Baseline patient characteristics significant. Ocriplasmin-treated PPV only (N=51) (N=22) p Value RESULTS Gender: male (%) 14 (27.5) 10 (45.5) 0.18 Baseline patient characteristics Age (years): mean (SD) 66.9 (19.1) 69.2 (9.8) 0.29 Fifty-one eyes underwent PPV after receiving ocriplasmin, and Phakic (%) 30 (58.8) 13 (59.1) 1 22 eyes underwent primary PPV. The ocriplasmin-treated group Epiretinal membrane (%) 21 (41.2) 3 (13.6) 0.03 and PPV-only group were similar at baseline with regards to Other visually significant 27 (52.9) 10 (45.5) 0.62 gender, age, phakic status and VA. There were 32/51 (62.7%) pathology (%) eyes in the ocriplasmin group with full thickness MH and 15/22 LogMAR VA mean (SD) 0.71 (0.35) 0.62 (0.31) 0.29 (68.2%) eyes in the PPV-only group with full thickness MH LogMAR VA pre-PPV mean (SD) 0.83 (0.35) (p=0.79). There were a significantly higher number of eyes in PPV, pars plana vitrectomy, VA, visual acuity. the ocriplasmin group with ERM 21/51 (41.2%) compared with the PPV-only group 3/22 (13.6%) (p=0.03). There was also a higher number of eyes with ellipsoid zone disruption at baseline post-PPV of all eyes at all available time points were reviewed. in the ocriplasmin group 18/51 (35.3%) compared with the Presence of VMA and/or MH and stage of the hole based on PPV-only group 2/21 (9.1%) (p=0.02). Baseline characteristics the International Vitreomacular Traction Study (VMT) Group are listed in table 1. classification system was recorded for each SD-OCT image.3 VMT with vitreous attachment diameter of 1500 μm or less was VA outcomes classified as focal adhesion and greater than 1500 μm was classi- In the ocriplasmin group, mean VA prior to ocriplasmin injec- fied as broad adhesion. Full-thickness MHs were classified as tion was LogMAR 0.71±0.35 (Snellen 20/103), and postocri- small (0–250 μm), medium (250–500 μm) or large (>500 μm) plasmin but previtrectomy the LogMAR VA was 0.83±0.35 and with or without VMT. Measurement of size of vitreous (Snellen 20/135). Mean VA after PPV was: 1 month post-PPV adhesion, MH diameter at the narrowest point and presence 0.78±0.56 (Snellen 20/120), 3 months post-PPV 0.61±0.33 and height of subretinal fluid (distance from retinal pigment epi- (Snellen 20/81) and 6 months post-PPV 0.56±0.32 (Snellen 20/ thelium to photoreceptors) was performed for each image using 73). In the PPV-only group, mean VA was: pre-PPV 0.62±0.31 the calliper function on the Heidelberg Spectralis software (Snellen 20/83), 1 month post-PPV 0.43±0.22 (Snellen 20/54), (Heidelberg Engineering, Carlsbad, California, USA) or Cirrus 3 months post-PPV 0.41±0.19 (Snellen 20/51) and 6 months HD-OCT (Carl Zeiss Meditec, Dublin, California, USA). post-PPV 0.40±0.23 (Snellen 20/50). Although VA was statistic- Comparisons between the baseline characteristics and treat- ally significantly better in the PPV-only group compared with ment outcomes of the two groups were performed using a two the ocriplasmin-treated group at all time points after PPV, both group t test for comparison of means, and Fisher’s exact test for groups had significant improvement in VA at 3 and 6 months comparison of proportions. The comparison of change in VA after PPV (see figure 1). pretreatment versus post-treatment was performed using paired Average change in VA compared with baseline was calculated t test. The comparison of VA change over time between treat- for each group for all time points. At 1 month post-PPV, the ment groups was analysed using analysis of variance with ocriplasmin-treated group had worsening of LogMAR VA of repeated measures. All the statistical comparisons were per- 0.06±0.53 while the PPV-only group had improvement of 0.19 formed using SAS V.9.3 (SAS Institute, Cary, North Carolina, ±0.29 compared with baseline (p=0.01). However, at months

Figure 1 LogMAR visual acuity over time in ocriplasmin-treated compared with pars plana vitrectomy (PPV)-only eyes.

1212 Greven MA, et al. Br J Ophthalmol 2016;100:1211–1215. doi:10.1136/bjophthalmol-2015-307701 Downloaded from http://bjo.bmj.com/ on August 30, 2016 - Published by group.bmj.com Clinical science

Phakic status Table 2 Change in LogMAR visual acuity from pretreatment At baseline, 21/51 (41.2%) eyes were pseudophakic in the ocri- Ocriplasmin-treated PPV only plasmin group and (40.9%) in the PPV-only group (p=1.00). (N=47) (N=20) p Value During the study, 15/51 eyes in the ocriplasmin group had cata- 1 month Mean (SD) 0.06 (0.53) −0.19 (0.29) 0.01 ract extraction so that 36/51 (70.5%) were pseudophakic at p Value* 0.40 0.006 6 months’ follow-up. In the PPV-only group, 6/22 eyes had cata- 3 months Mean (SD) −0.12 (0.40) −0.22 (0.29) 0.34 ract extraction in the PPV-only group so that 15/22 (66.7%) p Value* 0.04 0.003 were pseudophakic at 6 months follow-up (p=1). 6 months Mean (SD) −0.17 (0.38) −0.23 (0.37) 0.57 p Value* 0.004 0.02 Longitudinal Mean (SD) −0.08 (0.37) −0.21 (0.30) 0.099 SD-OCT results analysis of all p Value 0.15 0.0007 Baseline SD-OCT analysis demonstrated that VMA size and hole time points data† size were similar between both groups (table 3). At baseline, sig- nificant differences were present in terms of ERM, which was *For test to determine whether change from pretreatment is statistically significant. †From analysis of variance with repeated measures using generalised estimating present in 21/51 (41.2%) eyes in the ocriplasmin-treated group equations. but only in 3/21 (13.6%) in the PPV-only group (p=0.03) and PPV, pars plana vitrectomy. inner-segment–outer-segment (IS–OS) disruption which was present in 18/51 (35.3%) eyes in the ocriplasmin-treated group versus 2/22 (9.1%) eyes in the PPV-only group (p=0.02). 3 and 6, both groups had significant improvement in VA and After ocriplasmin injection, 22/51 (43.1%) eyes had release of similar rates of improvement compared with baseline as shown VMT on OCT. Table 3 shows OCT characteristics postocriplas- in table 2. min injection. After vitrectomy, 50/51 (98%) eyes in ocriplasmin-treated group had resolution of pathology. One eye Operative intervention and treatment/surgical complications with persistent stage 4 MH post-PPV in the ocriplasmin-treated All eyes underwent PPV with 47/51 (92.2%) eyes in the group had a long-standing large stage 4 MH that did not close ocriplasmin-treated and 22/22 (100%) of the PPV-only eyes after vitrectomy. All eyes (22/22) in the PPV-only group had having ICG-assisted ILM peeling. All surgeries were performed resolution of pathology, which is not significantly different from with either 23-gauge or 25-gauge vitrectomy systems. Two eyes the eyes in the ocriplasmin-treated group (p=1). Figure 2 shows in the ocriplasmin-treated group developed a rhegmatogenous a representative patient in the ocriplasmin-treated group with after injection and underwent PPV for resolution of pathology after PPV. Figure 3 shows a representa- retinal detachment repair. One of these eyes developed prolif- tive patient from the PPV-only group with resolution of path- erative vitreoretinopathy (PVR) requiring repeat PPV. Two eyes ology after PPV. Table 3 shows final OCT characteristics. in the ocriplasmin-treated group and one eye in the PPV-only group developed intraoperative retinal tears that were success- fully treated with endolaser. One additional eye in the DISCUSSION ocriplasmin group developed a PVR detachment 1 month This study of eyes that received ocriplasmin for VMA with or after PPV that was repaired with one additional surgery. No without MH and then went on to PPV compared with eyes that eyes in the PPV only group developed a rhegmatogenous had PPV only for similar pathology found comparable VA retinal detachment. All patients were included in the statistical improvement regardless of whether eyes received prior ocriplas- analysis. min injection.

Table 3 OCT characteristics at baseline, postocriplasmin injection, and post-PPV Baseline Post-PPV Post-ocriplasmin Ocriplasmin-treated PPV only Ocriplasmin-treated Ocriplasmin-treated PPV only (N=51) (N=22) p Value (N=51) (N=51) (N=22) p Value

0.19 1 Broad VMT (%) 4 (7.84%) 2 (9.09%) 4 (7.84%) Focal VMT (%) 15 (29.4%) 5 (22.7%) 11 (21.6%) Small FTMH (%) 16 (31.4%) 6 (27.3%) 10 (15.5%) Medium FTMH (%) 11 (21.6%) 8 (36.3%) 13 (25.5%) Large FTMH (%) 4 (9.8%) 1 (4.55%) 10 (15.5%) Presence of VMT (%) 48 (94.1%) 19 (86.4%) 26 (50.1%) Pathology resolved (%) 50 (98.0%) 22 (100.0%) Unknown (%) 3 (5.88%) Adhesion size (Q1, Q3) 365 (233, 845) 321 (250, 538) 0.75 0 (0, 336) 0 (0, 0) 0 (0, 0) 1 Hole aperture size (Q1, Q3) 481 (0, 736) 464 (219, 637) 0.81 0 (0, 1368) 0 (0, 0) 0 (0, 0) 0.51 ERM (%) 22 (43.1%) 4 (18.2%) 0.06 18 (35.3%) 4 (7.74%) 0 (0.00%) 0.31 IS–OS disruption (%) 18 (35.3%) 2 (9.09%) 0.02 16 (31.4%) 33 (64.7%) 17 (77.3%) 0.41 Subretinal fluid (%) 8 (15.7%) 1 (4.55%) 0.26 6 (11.8%) 7 (13.6%) 0 (0.00%) 0.09 ERM, epiretinal membrane; FTMH, full thickness macular hole; IS–OS, inner-segment–outer-segment; OCT, optical coherence tomography; PPV, pars plana vitrectomy; VMT, vitreomacular traction.

Greven MA, et al. Br J Ophthalmol 2016;100:1211–1215. doi:10.1136/bjophthalmol-2015-307701 1213 Downloaded from http://bjo.bmj.com/ on August 30, 2016 - Published by group.bmj.com Clinical science

Figure 2 73-year-old woman with decreased vision to 20/100 in the left eye. One week prior to ocriplasmin injection, spectral-domain optical coherence tomography (SD-OCT) demonstrates vitreomacular traction with small full-thickness macular hole (top left). Two weeks after ocriplasmin injection, SD-OCT shows persistence of pathology (top right). The patient underwent pars plana vitrectomy, and SD-OCT 2 months after surgery shows macular hole closure (bottom). Visual acuity improved to Snellen 20/60.

Although there was no statistical difference in VA at baseline between the two groups and may have contributed to the slower between the two groups, there was a trend towards worse base- visual recovery in the ocriplasmin-treated group. line VA in the ocriplasmin-treated arm than the PPV-only arm. Postmarketing reports have also raised concern that ocriplas- At all time points after PPV,the vision was significantly worse in min may cause changes in the IS–OS junction (ellipsoid zone) the ocriplasmin-treated group compared with the PPV-only as well as depression of the electroretinogram shortly after group. The VA transiently worsened in the ocriplasmin-treated injection with restoration of vision and outer retinal anatomy – group after ocriplasmin injection and remained stable 1 month over time.4 7 Similar changes in our cohort may have contrib- after PPV, but then improved significantly at 3 and 6 months, uted to the initial decrease in vision after ocriplasmin injec- while the VA in the PPV-only group improved significantly at tion. As has been reported in earlier series, there was a month 1 and then plateaued. The ocriplasmin-treated group gradual visual improvement and no patients in our study had a significantly higher rate of ERM and IS–OS disruption at reported acute VA decline or darkening of vision after baseline, which may explain the difference in baseline VA ocriplasmin.

Figure 3 65-year-old woman with decreased vision to 20/400 in the right eye. Baseline spectral-domain optical coherence tomography (SD-OCT) shows vitreomacular traction with medium full-thickness macular hole (top). The patient underwent primary pars plana vitrectomy, and SD-OCT 3 months after surgery shows release of vitreomacular adhesion and macular hole closure (bottom). Vision improved to Snellen 20/40.

1214 Greven MA, et al. Br J Ophthalmol 2016;100:1211–1215. doi:10.1136/bjophthalmol-2015-307701 Downloaded from http://bjo.bmj.com/ on August 30, 2016 - Published by group.bmj.com Clinical science

Approximately 4% of eyes developed a retinal tear or detach- Funding The Retina Service of Wills Eye Hospital and the J Arch McNamara Fund ment after ocriplasmin, which is slightly higher than reported for Retinal Research. rates of retinal tear formation the MIVI-TRUST (2%).1 Another Competing interests SG: consultant for Deciphera, XOMA, and Allergan, research 4% of eyes in the ocriplasmin arm developed a retinal tear grant support from Genentech, Regeneron, Eyegate, Santen, Lux, Biosciences, intraoperatively; this is similar to the nearly 4% of eyes in the Centocor, Xoma; JH: consultant for Xoma, Optovue, and Ophthotech, research fi support from Santen and Ophthotech. SPS: funding to attend meetings from DRCR PPV group who developed intraoperative tears. These ndings Network and Genentech; JW: consultant for Thrombogenics, Allergan, and are not unexpected since development or induction of a PVD is Genentech, research grant support from Thrombogenics, Allergan, Genentech; HFF: the leading cause of retinal tears.8 consultant for Allergan, Genentech, and Regeneron, research grant support from Based on SD-OCT analysis, there were similar rates of path- Allergan, Genentech, and Regeneron, co-founder, patent, and equity interest in Auris Surgical Robotics; DR: consultant for Allergan, Forsight Labs V4, Ohr ology resolution: all but one eye in the ocriplasmin-treated Pharmaceuticals, Regeneron, research grant support from Genentech, stockholder in group and all eyes in the PPV-only group had pathology reso- Forsight Labs V4 and Ohr Pharmaceuticals; CR: research grant support and lution. The one exception was an eye with a long-standing large consulting with Thrombogenics, Genentech, Regeneron, Allergan, Glaxo Smith Kline, stage 4 MH that did not close with ocriplasmin or vitrectomy. Acucela, and research grant support from Ophthotech, Ocata, and Santen; AH: As there was no baseline VMA, ocriplasmin injection was not consultant for Alcon, Allergan, EndoOptiks, Janssen/J&J, Genentech, ONL Therapeutics, Ophthotech, PanOptica, PRN, Regeneron, and research grant support indicated in this eye, but it was included in this consecutive from Alcon, Allergan, Avalanche, Janssen/J&J, Genentech, NEI/NIH, Ophthotech, series of all eyes that received ocriplasmin and went on to PPV. PRN, Regeneron, Second Sight; JAH: consultant for Thrombogenics, Merck, Lpath, In a small series of patients who underwent PPV after ocriplas- Kalvista, Second Sight, Genentech, Advanced Cell Technology, Regeneron. min injection, 4/4 patients achieved anatomic success after Ethics approval The IRB of Wills Eye Hospital, Rutgers, and Associated Retina surgery; however, these patients all had small-to-medium-sized Consultants of Royal Oak. MHs.9 Provenance and peer review Not commissioned; externally peer reviewed. The major limitations of this study are related to the retro- spective nature and comparatively small sample size, limited follow-up interval and non-standardised best-corrected VA mea- surements. In addition, there were differences in baseline REFERENCES 1 Jackson TL, Nicod E, Simpson A, et al. Symptomatic vitreomacular adhesion. Retina characteristics between the two groups with respect to several – – 2013;33:1503 11. factors, especially incidence of ERM and IS OS changes. 2 Stalmans P, Benz M, Gandorfer A, et al. Enzymatic vitreolysis with ocriplasmin for Although it is now understood that presence of ERM decreases vitreomacular traction and macular holes. N Engl J Med 2012;367:606–16. the likelihood of successful treatment with ocriplasmin, we 3 Duker JS, Kaiser PK, Binder S, et al. The International Vitreomacular Traction Study included all eyes that were treated at our institutions during the Group classification of vitreomacular adhesion, traction, and macular hole. – fi 10 2013;120:2611 19. rst year of commercial availability of ocriplasmin. Disruption 4 Tibbetts MD, Reichel E, Witkin AJ. Vision loss after intravitreal ocriplasmin: of the IS–OS layer is also known to be a poor prognostic indica- correlation of spectral-domain optical coherence tomography and tor in patients undergoing ERM peeling.11 Both of these factors electroretinography. JAMA Ophthalmol 2014;132:487–90. would be expected to cause VA to be worse in the ocriplasmin- 5 Fahim AT, Khan NW, Johnson MW. Acute panretinal structural and functional treated group and may have affected longer term visual recovery abnormalities after intravitreous ocriplasmin injection. JAMA Ophthalmol 2014;132:484–6. in this study. Not all patients received ICG during PPV, a factor 6 Thanos A, Hernandez-Siman J, Marra KV, et al. Reversible vision loss and outer which could also affect visual recovery and pathology reso- retinal abnormalities after intravitreal ocriplasmin injection. Retin Cases Brief Rep – lution.12 14 Further, phakic eyes were not excluded from this 2014;8:330–2. study and the development of after PPV could affect 7 Freund KB, Shah SA, Shah VP. Correlation of transient vision loss with outer retinal fi disruption following intravitreal ocriplasmin. Eye (Lond) 2013;27:773–4. nal VA measures. Finally, there could also have been selection 8 Chung SE, Kim KH, Kang SW. Retinal breaks associated with the induction of bias in the control group, as eyes may not have received ocri- posterior vitreous detachment. Am J Ophthalmol 2009;147:1012–16. plasmin for a number of reasons, including cost issues, as well 9 Lee GD, Taney LS, Rogers AH, et al. Surgical outcomes for persistent macular hole as coexisting ocular/retinal pathology that in the mind of the after ocriplasmin. Ophthalmic Surg Lasers Imaging Retina 2015;46:732–6. fi treating physician would have led to less treatment success. 10 Haller JH, Stalmans P, Benz MS, et al.Ef cacy of intravitreal ocriplasmin for treatment of vitreomacular adhesion: subgroup analyses from two randomized trials. In conclusion, in this group of eyes considered for ocriplas- Ophthalmology 2015;122:117–22. min injection for symptomatic VMA, PPV resulted in compar- 11 Oster SF, Mojana F, Brar M, et al. Disruption of the photoreceptor inner segment/ able anatomic and visual improvement whether or not it was outer segment layer on spectral domain-optical coherence tomography is a predictor preceded by ocriplasmin injection. Additional studies are war- of poor visual acuity in patients with epiretinal membranes. Retina fi 2010;30:713–18. ranted to further substantiate these ndings. 12 Haritoglou C, Gandorfer A, Gass CA, et al. The effect of indocyanine-green on functional outcome of macular pucker surgery. Am J Ophthalmol Acknowledgements Statistical consultation Gui-shuang Ying, PhD, Department of 2003;135:328–37. Ophthalmology, University of Pennsylvania. 13 Shiono A, Kogo J, Klose G, et al. Effects of indocyanine green staining on the Contributors Design of the study: MAG, SG, BC, SPS, JW, HFF, DBR, JR, JM, CR, recovery of visual acuity and macular morphology after macular hole surgery. AH, JAH. Conduct of the study: MAG, SG, SPS, JW. Collection of data: MAG, BC, Ophthalmologica 2013;230:138–43. JR, JM. Management, analysis and interpretation of data: MAG, SG, SPS, JW, JH. 14 Haritoglou C, Gandorfer A, Gass CA, et al. Indocyanine green-assisted peeling of Preparation of manuscript, review and approval of manuscript: MAG, SG, BC, SPS, the internal limiting membrane in macular hole surgery affects visual outcome: a JW, HFF, DBR, JR, JM, JH, CR, AH, JAH. clinicopathologic correlation. Am J Ophthalmol 2002;134:836–41.

Greven MA, et al. Br J Ophthalmol 2016;100:1211–1215. doi:10.1136/bjophthalmol-2015-307701 1215 Downloaded from http://bjo.bmj.com/ on August 30, 2016 - Published by group.bmj.com

Vitrectomy After ocriplasmin for VitreOmacular adhesion Or Macular hole (VAVOOM) study Margaret A Greven, Sunir Garg, Bing Chiu, Sumit P Shah, Jeremy Wolfe, Howard F Fine, Daniel B Roth, Joshua Robinson, Jacob Mong, Jason Hsu, Carl Regillo, Allen Ho and Julia A Haller

Br J Ophthalmol 2016 100: 1211-1215 originally published online December 9, 2015 doi: 10.1136/bjophthalmol-2015-307701

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