REVIEW URRENT C OPINION
Clinical management of vitreomacular traction Mohammed Ali Khan and Julia A. Haller
Purpose of review To describe recent evidence regarding the clinical management of vitreomacular traction (VMT). Recent findings Recent studies have reported favorable outcomes in patients with VMT managed with observation, pharmacologic vitreolysis with ocriplasmin, and intravitreal perfluoropropane gas. Subgroup analysis has identified features associated with spontaneous release of VMT as well as features associated with successful pharmacologic release of VMT with ocriplasmin. Summary Observation may be an appropriate initial recommendation for patients with mild VMT. When treatment is necessary, pharmacologic vitreolysis with ocriplasmin is an effective nonsurgical therapeutic option. Careful patient selection improves success rates with ocriplasmin. Further study is necessary to establish the efficacy of intravitreal perfluoropropane gas for VMT as well as the efficacy of ocriplasmin in patients with VMT and concurrent retinal disease. As these treatments are more widely used, prospective data will continue to clarify their risk/benefit profile. Keywords macular hole, ocriplasmin, vitreomacular adhesion, vitreomacular traction
INTRODUCTION Vitreomacular traction (VMT) is a disorder of the vitreomacular interface that results from incomplete separation of the vitreous from the macula. Resulting alterations in retinal morphology may lead to symptomatic metamorphopsia, decreased visual acuity, and/or visual field defect [1]. Following the US Food and Drug Administration approval of intravitreal ocriplasmin for the treatment of VMT in 2012, therapeutic options have expanded. The recent literature offers information regarding the natural history of VMT, clinical outcomes in patients treated with ocriplasmin and perfluoropropane (C3F8) gas, and factors predictive of both spontaneous and pharmacologic VMT release. These topics are reviewed below.
a 3-mm radius of the fovea without detectable changes in retinal morphology. VMT is differentiated from VMA by the presence of retinal morphologic changes but without full-thickness defect. Both VMA and VMT can be focal (1500 mm) or diffuse (>1500 mm), as well as isolated or concurrent (presence of other vitreomacular macular disease). Full-thickness macular hole (FTMH) was defined as a foveal lesion including all retinal layers from the internal limiting membrane to the retinal pigment epithelium. Size of the FTMH, measured at the narrowest width, was defined as small (250 mm), medium (>250 and 400 mm), or large (>400 mm). FTMH was further classified as primary (due to VMT) or secondary (associated trauma or other cause).
EPIDEMIOLOGY CLASSIFICATION OF VITREOMACULAR INTERFACE DISEASE In 2013, the International Vitreomacular Traction Study Group developed an anatomic, optical coherence tomography (OCT)-based system for the classification of vitreomacular interface disease. The following criteria were established [2]. Vitreomacular adhesion (VMA) was defined as macular attachment of the vitreous cortex within
Data on the prevalence of FTMH in the USA are available from two large epidemiologic studies. The Retina Service, Wills Eye Hospital, Philadelphia, Pennsylvania, USA Correspondence to Julia A. Haller, MD, Wills Eye Hospital, 840 Walnut Street, Suite 1020, Philadelphia, PA 19107, USA. Tel: +1 215 928 3073; fax: +1 215 928 3853; e-mail: [email protected] Curr Opin Ophthalmol 2015, 26:143–148 DOI:10.1097/ICU.0000000000000149
1040-8738 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-ophthalmology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Retinal, vitreous and macular disorders
KEY POINTS Observation may be an effective initial treatment strategy in patients with mild VMT and good presenting visual acuity. When treatment is necessary, pharmacologic vitreolysis with ocriplasmin is an effective therapy for VMT release. The efficacy of intravitreal gas is deserving of further study. Careful patient selection improves VMT release: success rates in patients treated with ocriplasmin. The following features favor release adhesion diameter or less 1500 mm, absence of ERM, phakic status, and age younger than 65. For eyes with FTMH, small diameter is most favorable. Further study is anticipated regarding the long-term effects, if any, of ellipsoid layer and ERG changes in patients receiving ocriplasmin. Further advancements in intraoperative imaging and adjunctive pharmacologic vitreolysis may improve surgical outcomes in patients undergoing vitrectomy for VMT.
Beaver Dam Eye Study reported that the prevalence of FTMH was 0.29% in that population [3] and when present, FTMH was more frequent in eyes with epiretinal membrane (ERM) compared with eyes without ERM (odds ratio ¼ 16.10; 95% confidence interval 5.37–48.42) [4]. In the Baltimore Eye Study, the prevalence of visual impairment because of FTMH was 0.11%; however, the prevalence of FTMH was not reported [5]. The only estimate of FTMH incidence is based on a population-based chart review of residents in Olmsted County, Minnesota, USA, from 1992 to 2002, in which the age-adjusted and sex-adjusted annual incidence was 0.0087% for any FTMH and 0.0078% for idiopathic FTMH [3]. Less information exists regarding the epidemiology of VMA and non-FTMH-related VMT, likely explained by lower rates of clinical detection in the pre-OCT era.
NATURAL HISTORY OF VITREOMACULAR ADHESION AND VITREOMACULAR TRACTION Recent studies have reported visual outcomes and rates of spontaneous resolution in patients with VMA or VMT. Theodossiadis et al. [6] prospectively followed 192 eyes with idiopathic, isolated VMA detected on routine exam and found the majority of patients do not progress to VMT. Patients were followed over a 4-year period with OCT examinations every 3 months. Mean presenting visual acuity was the 144
www.co-ophthalmology.com
logarithm of the minimum angle of resolution (logMAR) 0.105 (20/25 Snellen equivalent). Of these 192 eyes, 69 (35.9%) worsened to VMT, 65 (33.9%) remained stable, and 58 (30.2%) exhibited spontaneous release of VMA with complete posterior vitreous detachment. After analysis, the authors could not predict which patients with VMA would progress to VMT. John et al. [7] retrospectively reviewed outcomes of 106 eyes of 81 patients with VMT in which observation was recommended at initial evaluation by the treating vitreoretinal specialist. Mean presenting visual acuity was logMAR 0.269 (20/37 Snellen equivalent). At mean follow-up of 23 months, spontaneous release of VMT was observed in 34 eyes (32%) whereas worsening of VMT was observed in 17 eyes (16%). Five eyes (4.7%) underwent pars plana vitrectomy (PPV) for either FTMH development or worsening visual acuity. Across all patients, mean logMAR visual acuity slightly improved from 0.269 (Snellen 20/37) initially to 0.251 (Snellen 20/35) at final follow-up. Dimopoulos et al. [8] similarly reported favorable spontaneous release rates in 46 patients who presented with VMT measuring less than 1500 mm managed with observation. FTMH or ERM on initial exam, intravitreal injection, laser treatment, or intraocular surgery within the last 3 months, proliferative diabetic retinopathy, high myopia, and history of PPV were exclusion criteria. Mean logMAR visual acuity was 0.26 (20/36 Snellen equivalent), and all were followed for a minimum of 1 year. Of these eyes, 20 of 46 (43%) exhibited spontaneous release of VMT at a median of 374 days (range 9–1008 days) following VMT diagnosis. Seven of 46 eyes (15%) ultimately underwent PPV. In the 19 eyes without spontaneous resolution that did not undergo PPV, a decline of 0.03 0.05 logMAR visual acuity was observed, corresponding to an average of one Early Treatment Diabetic Retinopathy Study letter lost per year. In these cohorts of patients with VMA or VMT and good initial visual acuity, the minority of patients exhibited disease progression and visual acuity remained stable with observation.
FACTORS PREDICTIVE OF SPONTANEOUS VITREOMACULAR TRACTION RELEASE Three studies sought to identify factors predictive of spontaneous VMT release. Reported factors were the following: &
(1) Adhesion diameter less than 400 mm [9 ]. (2) Wide angle between the vitreous surface and nasal and temporal macula (vitreomacular angle) [9 ]. &
Volume 26 Number 3 May 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Clinical management of vitreomacular traction Khan and Haller &
(3) Isolated inner retinal layer distortion [10 ]. (4) Treatment of concurrent retinal diseases with intravitreal injections [10 ]. (5) ‘Vitreomacular interface area’ value less than 101 002 mm2 as calculated by optical coherence tomography [11]. &
&
Theodossiadis et al. [9 ] reviewed outcomes of 46 eyes with idiopathic VMT followed over 3 years. In this study, 12 of 46 (26%) eyes experienced spontaneous resolution of VMT. On univariate analysis, VMT diameter or less 400 mm (P < 0.001) was associated with spontaneous VMT resolution. The angle between the vitreous surface and the nasal (P ¼ 0.01) and temporal (P < 0.01) fovea was also associated with spontaneous resolution; meaning, the wider the vitreofoveal angle (approaching 908), the greater the likelihood of spontaneous resolution. Mean time with VMT prior to spontaneous resolution was 8.75 months. In the 12 eyes with spontaneous resolution, logMAR visual acuity improved from logMAR 0.30 0.11 to 0.19 0.10 following VMT release; however, it did not achieve the baseline acuity level (logMAR 0.14 0.06) prior to VMT development. Almeida et al. [10 ] similarly reviewed outcomes in 61 eyes with isolated or concurrent VMT. In this study, 21 of 61 eyes (35%) experienced spontaneous VMT release. Factors predictive of spontaneous release included isolated inner retinal layer distortion (P ¼ 0.01) and treatment of concurrent retinal disease with intravitreal injections (P ¼ 0.02). The difference in intravitreal injection rate between eyes with or without spontaneous release was notable. Of the 21 eyes with spontaneous release, 11 eyes received a mean of 9.1 intravitreal injections. Alternatively, of the 40 eyes without release, 5 eyes received a mean of 2.8 intravitreal injections. Other authors have developed OCT models to better predict VMT release patterns. Codenotti et al. [11] calculated an OCT derived ‘vitreomacular interface area’ for 26 eyes with VMT. The authors reported that a calculated adhesion surface area below 101 002 mm2 was associated with a higher rate of spontaneous VMT release (P < 0.001). Given the modest patient volume in these retrospective studies, and the potential for selection bias, further confirmation of the reported predictive factors in larger, prospective studies is warranted. &
MEDICAL THERAPY: OCRIPLASMIN The 2012 approval by the US Food and Drug Administration of intravitreal ocriplasmin (Jetrea; ThromboGenics, Inc., Iselin, New Jersey, USA) for the treatment of symptomatic VMT offered a potential
paradigm shift in the management of patients with VMT. Data from two phase III trials evaluating the efficacy of ocriplasmin for symptomatic VMA/ VMT, collectively referred to as the microplasmin for intravitreal injection – traction release without surgical treatment (MIVI-TRUST) studies, showed statistically significant nonsurgical achievement of primary endpoints in symptomatic eyes treated with a single injection of ocriplasmin compared with vehicle injection [12]. In total, 652 eyes were included, 464 of which received a single intravitreal injection of 0.125 mg ocriplasmin. At the day 28 postintravitreal injection primary endpoint, patients receiving ocriplasmin were more likely to exhibit release of VMA (26.5 vs. 10.1%, P < 0.001), closure of macular hole (40.6 vs. 10.6%, P < 0.001), and full posterior vitreous detachment (13.4 vs. 3.7%, P < 0.001) compared with controls. Subgroup analysis of the MIVI-TRUST data revealed additional insights [13 ]. Resolution of VMA at day 28 was associated with age younger than 65, adhesion diameter or less 1500 mm, phakic status, presence of FTMH, and absence of ERM. In eyes with FTMH treated with ocriplasmin, nonsurgical hole closure at month 6 was more likely in eyes with smaller holes, achieved in 58.3% of holes or less 250 mm, 36.8% of holes greater than 250 and or less 400 mm, and in 0% of holes greater than 400 mm. Visual acuity improvement of at least two lines at month 6 was associated with age younger than 65 and in patients with lower baseline visual acuity. &
‘Real-world’ clinical outcomes Singh et al. [14] reported outcomes of 17 eyes receiving intravitreal ocriplasmin. At day 28 postinjection, 8 of 17 eyes (47.1%) achieved release of VMT, a response rate better than to be predicted by the MIVI-TRUST data. This release rate improved to 50% if three of the following four criteria were met: adhesion diameter or less 1500 mm, absence of ERM, phakic status, and age younger than 65. If all four criteria were met, the release rate was 75% (3/4 eyes). Macular hole closure was observed in 4 of 5 eyes (80%). Snellen visual acuity remained stable at a mean 20/49 preinjection and mean 20/46 at final follow-up. Kim et al. [15] reported similar outcomes in a retrospective review of 19 eyes treated with ocriplasmin. Overall VMT release was observed in 42.1% (8/19 eyes), and macular hole closure was observed in 50% (3/6 eyes). Adhesion diameter of 1500 mm or less, absence of ERM, phakic status, and age younger than 65 were also associated with VMT release in this study.
1040-8738 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-ophthalmology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
145
Retinal, vitreous and macular disorders
More recently, Warrow et al. [16] reported outcomes in 35 eyes receiving ocriplasmin. At a mean of 10 days postinjection, 15 of 35 eyes (43%) exhibited release of VMT. Macular hole closure rate, however, was modest (1/6 eyes, 17%). Factors associated with release of VMT were small adhesion diameter (mean 346 vs. 730 mm, P ¼ 0.05), transient outer layer abnormalities on OCT (P ¼ 0.008), younger age (P ¼ 0.04), shorter duration of VMT (mean 4.6 vs. 10.4 months, P ¼ 0.03), and absence of concurrent retinal disease (P ¼ 0.02). Across all patients, mean logMAR visual acuity improved from 0.46 to 0.33 at final follow-up. Although ‘real-world’ ocriplasmin treatment outcomes are promising and offer criteria to maximize VMT release rates, these series are small and may reflect a post-hoc selection bias. Larger reports will be helpful to further refine selection criteria and success rates. Reported factors associated with successful pharmacologic VMT release with ocriplasmin (0.125 mg) are summarized below: &
(1) Phakic status [13 ,14,15]. (2) Age younger than 65 years [13 ,14–16]. (3) Small adhesion diameter (1500 mm) [13 ,14– 16]. (4) Presence of FTMH [13 ,15]. (5) Absence of epiretinal membrane [13 ,14,15]. (6) Absence of concurrent retinal disease [16]. (7) Shorter duration of VMT [16]. (8) Transient outer retinal layer abnormalities on OCT [16].
also suggestive of alterations in the photoreceptor complex. Three of the four cases reported reversal of the ellipsoid layer changes [17,19,20], whereas one case did not report follow-up findings [18]. Larger case series have similarly observed transient ellipsoid layer abnormalities on OCT in 29–41% of treated patients [14,16], with OCT changes more common in patients with VMT release [16]. An example of transient ellipsoid layer alteration following ocriplasmin is illustrated in Fig. 1. Long-term ramifications of these OCT and ERG abnormalities are unknown and continue to be investigated. To date, cases with reported long-term follow-up have been transient with restoration of visual acuity [17,19,20].
Concurrent retinal disease Novack et al. [21] recently reported outcomes of a phase II trial evaluating the safety of ocriplasmin for VMT in patients with concurrent exudative agerelated macular degeneration. One-hundred eyes were randomized, and safety outcomes were
&
&
&
(a)
&
(b)
Visual disturbance Ocular adverse events after the use of ocriplasmin have received attention. In the phase III MIVITRUST trials, patients receiving ocriplasmin were more likely to experience blurred vision (8.6 vs. 3.2%, P ¼ 0.01) and visual impairment (5.4 vs. 1.6%, P ¼ 0.02) compared with controls [12]. Recent case reports have sought to characterize these visual sequelae with anatomic and physiologic correlates using OCT and electroretinography (ERG) [17–20]. In two cases, one with and one without FTMH, a full-field ERG was completed [17,18]. Findings were notable for reduction in B wave amplitudes during the scotopic ERG. Although A wave and photopic abnormalities were also present, ERG findings were thought to be most consistent with bipolar cell dysfunction and reduced activity in primarily rod photoreceptors. The authors suggested the protease activity of ocriplasmin on laminin present in the photoreceptor layer as a possible etiologic factor. In all four cases, abnormalities of the ellipsoid layer were observed on OCT, 146
www.co-ophthalmology.com
(c)
FIGURE 1. Spectral domain optical coherence tomography immediately before (a), 10 days following (b), and 4 weeks following intravitreal injection of ocriplasmin (c) in a 63-yearold female. (a) Prior to treatment, visual acuity was 20/40 with symptomatic visual distortion. SD-OCT reveals significant vitreomacular traction (VMT) with near fullthickness macular hole, inner layers remain intact). (b) Ten days following treatment, release of VMT, presence of submacular fluid, and disruption of the ellipsoid layer (arrows) are noted. Visual acuity was 20/30. (c) Four weeks later, integrity of the ellipsoid layer is improved with resolution of submacular fluid with subsequent improvement of visual acuity to 20/25. Final visual acuity 177 days postocriplasmin injection was 20/20. Volume 26 Number 3 May 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Clinical management of vitreomacular traction Khan and Haller
consistent with that of the phase III MIVI-TRUST data. Patients treated with ocriplasmin were more likely have VMT resolution at day 28 (P ¼ 0.262). Also interestingly, the mean number of intravitreal antivascular endothelial growth factor injections decreased 28% (4.4 injections) in the ocriplasmin group over the treatment period. Trials regarding VMT release in patients with diabetic macular edema [22] and pediatric vitreoretinopathies [22,23] are currently ongoing. Larger, prospective trials are necessary to establish efficacy of ocriplasmin use in patients with concurrent retinal disease, and whether alterations in the vitreomacular interface will affect treatment burden for these conditions.
MEDICAL THERAPY: PERFLUOROPROPANE GAS
improved from 0.75 0.27 (Snellen 20/112) prior to ocriplasmin injection to 0.58 0.30 (Snellen 20/76) at 6 months post-PPV. The authors did not report intraoperative or postoperative complications attributable to prior use of ocriplasmin. Further studies regarding surgical outcomes in patients with prior treatment with ocriplasmin and/or C3F8 gas for VMT will be necessary to determine whether specific surgical considerations, if any, exist in this patient population. Looking forward, intraoperative OCT may provide surgeons with additional information to guide surgical decision-making. In a retrospective review of 12 eyes undergoing vitrectomy for VMT, findings from intraoperative OCT prompted change in intraoperative management in 5 of 12 eyes (42%), including decisions regarding the need for internal limiting membrane peeling and use of gas tamponade [29].
&
Rodrigues et al. [24 ] reported the efficacy of intravitreal injection of 0.3 ml of 100% C3F8 gas for the treatment of VMT in 15 eyes of 14 patients. All patients had persistent VMT of greater than 3 months duration, and 6 of 15 eyes had concurrent diabetic retinopathy. VMT release was observed in 6 of 15 eyes (40%) at 1 month and 9 of 15 eyes (60%) at 6 months, with the remaining 6 eyes offered PPV at 6 months. The authors report maximal foveal thickness of less than 500 mm, low vitreous face reflectively, and maximal horizontal VMA less than 750 mm as factors predictive of VMT release at 1 month. Mean visual acuity, however, did not improve, which the authors suggest may be secondary to damage related to VMT or coexisting diabetic retinopathy.
SURGICAL MANAGEMENT PPV remains the mainstay of VMT treatment when observation and/or medical therapy are either unsuccessful or not indicated [25]. Known adverse effects of PPV for VMT include cataract progression, ERM formation, and retinal detachment, but in general, PPV has been shown to be a well tolerated, effective, and cost-effective option for this patient population [26,27]. Of interest is whether prior ocriplasmin injection affects intraoperative complication rate or surgical outcomes in patients undergoing PPV for persistent VMT. Early reports suggest complication rates and surgical outcomes do not differ. Greven [28] reported outcomes of 39 eyes that underwent PPV for persistent VMT after treatment with ocriplasmin. Of these eyes, 36 of 39 (92%) underwent indocyanine green angiography assisted membrane peel intraoperatively. Mean logMAR visual acuity
CONCLUSION Options for the management of VMT include observation, medical therapy (intravitreal ocriplasmin and C3F8 gas), and vitrectomy. Recent studies have helped elucidate baseline features of eyes with the best outcomes from pharmacologic vitreolysis with ocriplasmin, affording patients and physicians more information to guide therapeutic decisionmaking. Additional investigation into the risk/ benefit profile of intravitreal gas is needed to clarify its role in treatment recommendations. Physicians and patients will also benefit from study of the efficacy and safety of ocriplasmin in a broader spectrum of patients, including those with concurrent retinal disease. Acknowledgements None. Financial support and sponsorship None. Conflicts of interest J.A.H., MD, has been a consultant for ThromboGenics, Inc. M.A.K., MD, has no conflicts of interest.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Gass J. Stereoscopic atlas of macular diseases: diagnosis and treatment. 4th ed. St. Louis, MO: Mosby; 1997. 2. Duker JS, Kaiser PK, Binder S, et al. The International Vitreomacular Traction Study Group classification of vitreomacular adhesion, traction, and macular hole. Ophthalmology 2013; 120:2611–2619.
1040-8738 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-ophthalmology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
147
Retinal, vitreous and macular disorders 3. McCannel CA, Ensminger JL, Diehl NN, Hodge DN. Population-based incidence of macular holes. Ophthalmology 2009; 116:1366–1369. 4. Klein R, Klein BE, Wang Q, Moss SE. The epidemiology of epiretinal membranes. Trans Am Ophthalmol Soc 1994; 92:403–425; discussion 425-30. 5. Rahmani B, Tielsch JM, Katz J, et al. The cause-specific prevalence of visual impairment in an urban population. The Baltimore Eye Survey. Ophthalmology 1996; 103:1721–1726. 6. Theodossiadis GP, Chatziralli IP, Sergentanis TN, Datseris I, Theodossiadis PG. Evolution of vitreomacular adhesion to acute vitreofoveal separation with special emphasis on a traction-induced foveal pathology. A prospective study of spectral-domain optical coherence tomography. Graefes Arch Clin Exp Ophthalmol 2014. [Epub ahead of print] 7. John VJ, Flynn HW, Smiddy WE, et al. Clinical course of vitreomacular adhesion managed by initial observation. Retina 2014; 34:442–446. 8. Dimopoulos S, Bartz-Schmidt K-U, Gelisken F, et al. Januschowski K, Ziemssen F. Rate and timing of spontaneous resolution in a vitreomacular traction group: Should the role of watchful waiting be re-evaluated as an alternative to Ocriplasmin therapy? Br J Ophthalmol 2015; 99:350– 353. 9. Theodossiadis GP, Grigoropoulos VG, Theodoropoulou S, et al. Sponta& neous resolution of vitreomacular traction demonstrated by spectral-domain optical coherence tomography. Am J Ophthalmol 2014; 157:842.e1– 851.e1. Prospective, observational case series of 46 eyes with idiopathic VMT followed over 3 years. On univariate analysis, VMT diameter or less 400 mm (P < 0.001) and the angle between the vitreous surface and the nasal (P ¼ 0.01) and temporal (P < 0.01) fovea was also associated with spontaneous VMT release. Meantime with VMT prior to spontaneous resolution was 8.75 months. 10. Almeida DRP, Chin EK, Rahim K, et al. Factors associated with spontaneous & release of vitreomacular traction. Retina 2014; 35:492–497. Retrospective, case-controlled series of 61 eyes with isolated or concurrent VMT. Found that factors predictive of spontaneous release included isolated inner retinal layer distortion (P ¼ 0.01) and treatment of concurrent retinal disease with intravitreal injections (P ¼ 0.02). Of the 21 eyes with spontaneous release, 11 eyes received a mean of 9.1 intravitreal injections. Alternatively, of the 40 eyes without spontaneous release, 5 eyes received a mean of 2.8 intravitreal injections. 11. Codenotti M, Iuliano L, Fogliato G, et al. A novel spectral-domain optical coherence tomography model to estimate changes in vitreomacular traction syndrome. Graefes Arch Clin Exp Ophthalmol 2014; 252:1729–1735. 12. Stalmans P, Benz MS, Gandorfer A, et al. Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular holes. N Engl J Med 2012; 367:606–615. 13. Haller JA, Stalmans P, Benz MS, et al. Efficacy of intravitreal ocriplasmin for & treatment of vitreomacular adhesion: subgroup analyses from two randomized trials. Ophthalmology 2015; 122:117–122. Subgroup analysis of the phase III MIVI-TRUST data. Analysis revealed resolution of VMA at day 28 was associated with age younger than 65, adhesion diameter or less 1500 mm, phakic status, presence of FTMH, and absence of ERM. Observed that nonsurgical hole closure at month 6 was more likely in eyes with smaller holes, achieved in 58.3% of holes or less 250 mm, 36.8% of holes greater than 250 and or less 400 mm, and in 0% of holes greater than 400 mm.
148
www.co-ophthalmology.com
14. Singh RP, Li A, Bedi R, et al. Anatomical and visual outcomes following ocriplasmin treatment for symptomatic vitreomacular traction syndrome. Br J Ophthalmol 2014; 98:356–360. 15. Kim BT, Schwartz SG, Smiddy WE, et al. Initial outcomes following intravitreal ocriplasmin for treatment of symptomatic vitreomacular adhesion. Ophthalmic Surg Lasers Imaging Retina 2013; 44:334–343. 16. Warrow DJ, Lai MM, Patel A, et al. Treatment outcomes and spectral-domain optical coherence tomography findings of eyes with symptomatic vitreomacular adhesion treated with intravitreal ocriplasmin. Am J Ophthalmol 2015; 159:20.e1–30.e1. 17. Tibbetts MD, Reichel E, Witkin AJ. Vision loss after intravitreal ocriplasmin: correlation of spectral-domain optical coherence tomography and electroretinography. JAMA Ophthalmol 2014; 132:487–490. 18. Fahim AT, Khan NW, Johnson MW. Acute panretinal structural and functional abnormalities after intravitreous ocriplasmin injection. JAMA Ophthalmol 2014; 132:484–486. 19. Freund KB, Shah SA, Shah VP. Correlation of transient vision loss with outer retinal disruption following intravitreal ocriplasmin. Eye Lond Engl 2013; 27:773–774. 20. Quezada Ruiz C, Pieramici DJ, Nasir M, Rabena M, Avery RL. Severe acute vision loss, dyschromatopsia, and changes in the ellipsoid zone on SD-OCT associated with intravitreal ocriplasmin injection. Retin Cases Brief Rep 2014. [Epub ahead of print] 21. Novack RL, Staurenghi G, Girach A, Narendran N, Tolentino M. Safety of intravitreal ocriplasmin for focal vitreomacular adhesion in patients with exudative age-related macular degeneration. Ophthalmology 2014. [Epub ahead of print] 22. Song SJ, Smiddy WE. Ocriplasmin for symptomatic vitreomacular adhesion: an evidence-based review of its potential. Core Evid 2014; 9:51–59. 23. Wong SC, Capone A. Microplasmin (ocriplasmin) in pediatric vitreoretinal surgery: update and review. Retina 2013; 33:339–348. 24. Rodrigues IA, Stangos AN, McHugh DA, Jackson TL. Intravitreal injection of & expansile perfluoropropane (c(3)f(8)) for the treatment of vitreomacular traction. Am J Ophthalmol 2013; 155:270.e2–276.e2. A retrospective, interventional case series evaluating intravitreal injection of 0.3 ml of 100% C3F8 gas for the treatment of VMT in 15 eyes of 14 consecutive patients. VMT release was observed in 6 of 15 eyes (40%) at 1 month and 9 of 15 eyes (60%) at 6 months. 25. Moisseiev J, Moroz I, Katz G. Effect of ocriplasmin on the management of macular holes: assessment of the clinical relevance of ocriplasmin. JAMA Ophthalmol 2014; 132:709–713. 26. Jackson TL, Nicod E, Angelis A, et al. Pars plana vitrectomy for vitreomacular traction syndrome: a systematic review and meta-analysis of safety and efficacy. Retina 2013; 33:2012–2017. 27. Chang JS, Smiddy WE. Cost evaluation of surgical and pharmaceutical options in treatment for vitreomacular adhesions and macular holes. Ophthalmology 2014; 121:1720–1726. 28. Greven MA. Vitrectomy after ocriplasmin for vitreomacular adhesion or macular hole: the VAVOOM study. Podium presentation presented at: The Retina Society, Annual Meeting; 12 September 2014; Philadelphia, PA. 29. Ehlers JP, Tam T, Kaiser PK, et al. Utility of intraoperative optical coherence tomography during vitrectomy surgery for vitreomacular traction syndrome. Retina 2014; 34:1341–1346.
Volume 26 Number 3 May 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Clinical management of vitreomacular traction Mohammed Ali Khan and Julia A. Haller
Purpose of review To describe recent evidence regarding the clinical management of vitreomacular traction (VMT). Recent findings Recent studies have reported favorable outcomes in patients with VMT managed with observation, pharmacologic vitreolysis with ocriplasmin, and intravitreal perfluoropropane gas. Subgroup analysis has identified features associated with spontaneous release of VMT as well as features associated with successful pharmacologic release of VMT with ocriplasmin. Summary Observation may be an appropriate initial recommendation for patients with mild VMT. When treatment is necessary, pharmacologic vitreolysis with ocriplasmin is an effective nonsurgical therapeutic option. Careful patient selection improves success rates with ocriplasmin. Further study is necessary to establish the efficacy of intravitreal perfluoropropane gas for VMT as well as the efficacy of ocriplasmin in patients with VMT and concurrent retinal disease. As these treatments are more widely used, prospective data will continue to clarify their risk/benefit profile. Keywords macular hole, ocriplasmin, vitreomacular adhesion, vitreomacular traction
INTRODUCTION Vitreomacular traction (VMT) is a disorder of the vitreomacular interface that results from incomplete separation of the vitreous from the macula. Resulting alterations in retinal morphology may lead to symptomatic metamorphopsia, decreased visual acuity, and/or visual field defect [1]. Following the US Food and Drug Administration approval of intravitreal ocriplasmin for the treatment of VMT in 2012, therapeutic options have expanded. The recent literature offers information regarding the natural history of VMT, clinical outcomes in patients treated with ocriplasmin and perfluoropropane (C3F8) gas, and factors predictive of both spontaneous and pharmacologic VMT release. These topics are reviewed below.
a 3-mm radius of the fovea without detectable changes in retinal morphology. VMT is differentiated from VMA by the presence of retinal morphologic changes but without full-thickness defect. Both VMA and VMT can be focal (1500 mm) or diffuse (>1500 mm), as well as isolated or concurrent (presence of other vitreomacular macular disease). Full-thickness macular hole (FTMH) was defined as a foveal lesion including all retinal layers from the internal limiting membrane to the retinal pigment epithelium. Size of the FTMH, measured at the narrowest width, was defined as small (250 mm), medium (>250 and 400 mm), or large (>400 mm). FTMH was further classified as primary (due to VMT) or secondary (associated trauma or other cause).
EPIDEMIOLOGY CLASSIFICATION OF VITREOMACULAR INTERFACE DISEASE In 2013, the International Vitreomacular Traction Study Group developed an anatomic, optical coherence tomography (OCT)-based system for the classification of vitreomacular interface disease. The following criteria were established [2]. Vitreomacular adhesion (VMA) was defined as macular attachment of the vitreous cortex within
Data on the prevalence of FTMH in the USA are available from two large epidemiologic studies. The Retina Service, Wills Eye Hospital, Philadelphia, Pennsylvania, USA Correspondence to Julia A. Haller, MD, Wills Eye Hospital, 840 Walnut Street, Suite 1020, Philadelphia, PA 19107, USA. Tel: +1 215 928 3073; fax: +1 215 928 3853; e-mail: [email protected] Curr Opin Ophthalmol 2015, 26:143–148 DOI:10.1097/ICU.0000000000000149
1040-8738 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-ophthalmology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Retinal, vitreous and macular disorders
KEY POINTS Observation may be an effective initial treatment strategy in patients with mild VMT and good presenting visual acuity. When treatment is necessary, pharmacologic vitreolysis with ocriplasmin is an effective therapy for VMT release. The efficacy of intravitreal gas is deserving of further study. Careful patient selection improves VMT release: success rates in patients treated with ocriplasmin. The following features favor release adhesion diameter or less 1500 mm, absence of ERM, phakic status, and age younger than 65. For eyes with FTMH, small diameter is most favorable. Further study is anticipated regarding the long-term effects, if any, of ellipsoid layer and ERG changes in patients receiving ocriplasmin. Further advancements in intraoperative imaging and adjunctive pharmacologic vitreolysis may improve surgical outcomes in patients undergoing vitrectomy for VMT.
Beaver Dam Eye Study reported that the prevalence of FTMH was 0.29% in that population [3] and when present, FTMH was more frequent in eyes with epiretinal membrane (ERM) compared with eyes without ERM (odds ratio ¼ 16.10; 95% confidence interval 5.37–48.42) [4]. In the Baltimore Eye Study, the prevalence of visual impairment because of FTMH was 0.11%; however, the prevalence of FTMH was not reported [5]. The only estimate of FTMH incidence is based on a population-based chart review of residents in Olmsted County, Minnesota, USA, from 1992 to 2002, in which the age-adjusted and sex-adjusted annual incidence was 0.0087% for any FTMH and 0.0078% for idiopathic FTMH [3]. Less information exists regarding the epidemiology of VMA and non-FTMH-related VMT, likely explained by lower rates of clinical detection in the pre-OCT era.
NATURAL HISTORY OF VITREOMACULAR ADHESION AND VITREOMACULAR TRACTION Recent studies have reported visual outcomes and rates of spontaneous resolution in patients with VMA or VMT. Theodossiadis et al. [6] prospectively followed 192 eyes with idiopathic, isolated VMA detected on routine exam and found the majority of patients do not progress to VMT. Patients were followed over a 4-year period with OCT examinations every 3 months. Mean presenting visual acuity was the 144
www.co-ophthalmology.com
logarithm of the minimum angle of resolution (logMAR) 0.105 (20/25 Snellen equivalent). Of these 192 eyes, 69 (35.9%) worsened to VMT, 65 (33.9%) remained stable, and 58 (30.2%) exhibited spontaneous release of VMA with complete posterior vitreous detachment. After analysis, the authors could not predict which patients with VMA would progress to VMT. John et al. [7] retrospectively reviewed outcomes of 106 eyes of 81 patients with VMT in which observation was recommended at initial evaluation by the treating vitreoretinal specialist. Mean presenting visual acuity was logMAR 0.269 (20/37 Snellen equivalent). At mean follow-up of 23 months, spontaneous release of VMT was observed in 34 eyes (32%) whereas worsening of VMT was observed in 17 eyes (16%). Five eyes (4.7%) underwent pars plana vitrectomy (PPV) for either FTMH development or worsening visual acuity. Across all patients, mean logMAR visual acuity slightly improved from 0.269 (Snellen 20/37) initially to 0.251 (Snellen 20/35) at final follow-up. Dimopoulos et al. [8] similarly reported favorable spontaneous release rates in 46 patients who presented with VMT measuring less than 1500 mm managed with observation. FTMH or ERM on initial exam, intravitreal injection, laser treatment, or intraocular surgery within the last 3 months, proliferative diabetic retinopathy, high myopia, and history of PPV were exclusion criteria. Mean logMAR visual acuity was 0.26 (20/36 Snellen equivalent), and all were followed for a minimum of 1 year. Of these eyes, 20 of 46 (43%) exhibited spontaneous release of VMT at a median of 374 days (range 9–1008 days) following VMT diagnosis. Seven of 46 eyes (15%) ultimately underwent PPV. In the 19 eyes without spontaneous resolution that did not undergo PPV, a decline of 0.03 0.05 logMAR visual acuity was observed, corresponding to an average of one Early Treatment Diabetic Retinopathy Study letter lost per year. In these cohorts of patients with VMA or VMT and good initial visual acuity, the minority of patients exhibited disease progression and visual acuity remained stable with observation.
FACTORS PREDICTIVE OF SPONTANEOUS VITREOMACULAR TRACTION RELEASE Three studies sought to identify factors predictive of spontaneous VMT release. Reported factors were the following: &
(1) Adhesion diameter less than 400 mm [9 ]. (2) Wide angle between the vitreous surface and nasal and temporal macula (vitreomacular angle) [9 ]. &
Volume 26 Number 3 May 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Clinical management of vitreomacular traction Khan and Haller &
(3) Isolated inner retinal layer distortion [10 ]. (4) Treatment of concurrent retinal diseases with intravitreal injections [10 ]. (5) ‘Vitreomacular interface area’ value less than 101 002 mm2 as calculated by optical coherence tomography [11]. &
&
Theodossiadis et al. [9 ] reviewed outcomes of 46 eyes with idiopathic VMT followed over 3 years. In this study, 12 of 46 (26%) eyes experienced spontaneous resolution of VMT. On univariate analysis, VMT diameter or less 400 mm (P < 0.001) was associated with spontaneous VMT resolution. The angle between the vitreous surface and the nasal (P ¼ 0.01) and temporal (P < 0.01) fovea was also associated with spontaneous resolution; meaning, the wider the vitreofoveal angle (approaching 908), the greater the likelihood of spontaneous resolution. Mean time with VMT prior to spontaneous resolution was 8.75 months. In the 12 eyes with spontaneous resolution, logMAR visual acuity improved from logMAR 0.30 0.11 to 0.19 0.10 following VMT release; however, it did not achieve the baseline acuity level (logMAR 0.14 0.06) prior to VMT development. Almeida et al. [10 ] similarly reviewed outcomes in 61 eyes with isolated or concurrent VMT. In this study, 21 of 61 eyes (35%) experienced spontaneous VMT release. Factors predictive of spontaneous release included isolated inner retinal layer distortion (P ¼ 0.01) and treatment of concurrent retinal disease with intravitreal injections (P ¼ 0.02). The difference in intravitreal injection rate between eyes with or without spontaneous release was notable. Of the 21 eyes with spontaneous release, 11 eyes received a mean of 9.1 intravitreal injections. Alternatively, of the 40 eyes without release, 5 eyes received a mean of 2.8 intravitreal injections. Other authors have developed OCT models to better predict VMT release patterns. Codenotti et al. [11] calculated an OCT derived ‘vitreomacular interface area’ for 26 eyes with VMT. The authors reported that a calculated adhesion surface area below 101 002 mm2 was associated with a higher rate of spontaneous VMT release (P < 0.001). Given the modest patient volume in these retrospective studies, and the potential for selection bias, further confirmation of the reported predictive factors in larger, prospective studies is warranted. &
MEDICAL THERAPY: OCRIPLASMIN The 2012 approval by the US Food and Drug Administration of intravitreal ocriplasmin (Jetrea; ThromboGenics, Inc., Iselin, New Jersey, USA) for the treatment of symptomatic VMT offered a potential
paradigm shift in the management of patients with VMT. Data from two phase III trials evaluating the efficacy of ocriplasmin for symptomatic VMA/ VMT, collectively referred to as the microplasmin for intravitreal injection – traction release without surgical treatment (MIVI-TRUST) studies, showed statistically significant nonsurgical achievement of primary endpoints in symptomatic eyes treated with a single injection of ocriplasmin compared with vehicle injection [12]. In total, 652 eyes were included, 464 of which received a single intravitreal injection of 0.125 mg ocriplasmin. At the day 28 postintravitreal injection primary endpoint, patients receiving ocriplasmin were more likely to exhibit release of VMA (26.5 vs. 10.1%, P < 0.001), closure of macular hole (40.6 vs. 10.6%, P < 0.001), and full posterior vitreous detachment (13.4 vs. 3.7%, P < 0.001) compared with controls. Subgroup analysis of the MIVI-TRUST data revealed additional insights [13 ]. Resolution of VMA at day 28 was associated with age younger than 65, adhesion diameter or less 1500 mm, phakic status, presence of FTMH, and absence of ERM. In eyes with FTMH treated with ocriplasmin, nonsurgical hole closure at month 6 was more likely in eyes with smaller holes, achieved in 58.3% of holes or less 250 mm, 36.8% of holes greater than 250 and or less 400 mm, and in 0% of holes greater than 400 mm. Visual acuity improvement of at least two lines at month 6 was associated with age younger than 65 and in patients with lower baseline visual acuity. &
‘Real-world’ clinical outcomes Singh et al. [14] reported outcomes of 17 eyes receiving intravitreal ocriplasmin. At day 28 postinjection, 8 of 17 eyes (47.1%) achieved release of VMT, a response rate better than to be predicted by the MIVI-TRUST data. This release rate improved to 50% if three of the following four criteria were met: adhesion diameter or less 1500 mm, absence of ERM, phakic status, and age younger than 65. If all four criteria were met, the release rate was 75% (3/4 eyes). Macular hole closure was observed in 4 of 5 eyes (80%). Snellen visual acuity remained stable at a mean 20/49 preinjection and mean 20/46 at final follow-up. Kim et al. [15] reported similar outcomes in a retrospective review of 19 eyes treated with ocriplasmin. Overall VMT release was observed in 42.1% (8/19 eyes), and macular hole closure was observed in 50% (3/6 eyes). Adhesion diameter of 1500 mm or less, absence of ERM, phakic status, and age younger than 65 were also associated with VMT release in this study.
1040-8738 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-ophthalmology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
145
Retinal, vitreous and macular disorders
More recently, Warrow et al. [16] reported outcomes in 35 eyes receiving ocriplasmin. At a mean of 10 days postinjection, 15 of 35 eyes (43%) exhibited release of VMT. Macular hole closure rate, however, was modest (1/6 eyes, 17%). Factors associated with release of VMT were small adhesion diameter (mean 346 vs. 730 mm, P ¼ 0.05), transient outer layer abnormalities on OCT (P ¼ 0.008), younger age (P ¼ 0.04), shorter duration of VMT (mean 4.6 vs. 10.4 months, P ¼ 0.03), and absence of concurrent retinal disease (P ¼ 0.02). Across all patients, mean logMAR visual acuity improved from 0.46 to 0.33 at final follow-up. Although ‘real-world’ ocriplasmin treatment outcomes are promising and offer criteria to maximize VMT release rates, these series are small and may reflect a post-hoc selection bias. Larger reports will be helpful to further refine selection criteria and success rates. Reported factors associated with successful pharmacologic VMT release with ocriplasmin (0.125 mg) are summarized below: &
(1) Phakic status [13 ,14,15]. (2) Age younger than 65 years [13 ,14–16]. (3) Small adhesion diameter (1500 mm) [13 ,14– 16]. (4) Presence of FTMH [13 ,15]. (5) Absence of epiretinal membrane [13 ,14,15]. (6) Absence of concurrent retinal disease [16]. (7) Shorter duration of VMT [16]. (8) Transient outer retinal layer abnormalities on OCT [16].
also suggestive of alterations in the photoreceptor complex. Three of the four cases reported reversal of the ellipsoid layer changes [17,19,20], whereas one case did not report follow-up findings [18]. Larger case series have similarly observed transient ellipsoid layer abnormalities on OCT in 29–41% of treated patients [14,16], with OCT changes more common in patients with VMT release [16]. An example of transient ellipsoid layer alteration following ocriplasmin is illustrated in Fig. 1. Long-term ramifications of these OCT and ERG abnormalities are unknown and continue to be investigated. To date, cases with reported long-term follow-up have been transient with restoration of visual acuity [17,19,20].
Concurrent retinal disease Novack et al. [21] recently reported outcomes of a phase II trial evaluating the safety of ocriplasmin for VMT in patients with concurrent exudative agerelated macular degeneration. One-hundred eyes were randomized, and safety outcomes were
&
&
&
(a)
&
(b)
Visual disturbance Ocular adverse events after the use of ocriplasmin have received attention. In the phase III MIVITRUST trials, patients receiving ocriplasmin were more likely to experience blurred vision (8.6 vs. 3.2%, P ¼ 0.01) and visual impairment (5.4 vs. 1.6%, P ¼ 0.02) compared with controls [12]. Recent case reports have sought to characterize these visual sequelae with anatomic and physiologic correlates using OCT and electroretinography (ERG) [17–20]. In two cases, one with and one without FTMH, a full-field ERG was completed [17,18]. Findings were notable for reduction in B wave amplitudes during the scotopic ERG. Although A wave and photopic abnormalities were also present, ERG findings were thought to be most consistent with bipolar cell dysfunction and reduced activity in primarily rod photoreceptors. The authors suggested the protease activity of ocriplasmin on laminin present in the photoreceptor layer as a possible etiologic factor. In all four cases, abnormalities of the ellipsoid layer were observed on OCT, 146
www.co-ophthalmology.com
(c)
FIGURE 1. Spectral domain optical coherence tomography immediately before (a), 10 days following (b), and 4 weeks following intravitreal injection of ocriplasmin (c) in a 63-yearold female. (a) Prior to treatment, visual acuity was 20/40 with symptomatic visual distortion. SD-OCT reveals significant vitreomacular traction (VMT) with near fullthickness macular hole, inner layers remain intact). (b) Ten days following treatment, release of VMT, presence of submacular fluid, and disruption of the ellipsoid layer (arrows) are noted. Visual acuity was 20/30. (c) Four weeks later, integrity of the ellipsoid layer is improved with resolution of submacular fluid with subsequent improvement of visual acuity to 20/25. Final visual acuity 177 days postocriplasmin injection was 20/20. Volume 26 Number 3 May 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Clinical management of vitreomacular traction Khan and Haller
consistent with that of the phase III MIVI-TRUST data. Patients treated with ocriplasmin were more likely have VMT resolution at day 28 (P ¼ 0.262). Also interestingly, the mean number of intravitreal antivascular endothelial growth factor injections decreased 28% (4.4 injections) in the ocriplasmin group over the treatment period. Trials regarding VMT release in patients with diabetic macular edema [22] and pediatric vitreoretinopathies [22,23] are currently ongoing. Larger, prospective trials are necessary to establish efficacy of ocriplasmin use in patients with concurrent retinal disease, and whether alterations in the vitreomacular interface will affect treatment burden for these conditions.
MEDICAL THERAPY: PERFLUOROPROPANE GAS
improved from 0.75 0.27 (Snellen 20/112) prior to ocriplasmin injection to 0.58 0.30 (Snellen 20/76) at 6 months post-PPV. The authors did not report intraoperative or postoperative complications attributable to prior use of ocriplasmin. Further studies regarding surgical outcomes in patients with prior treatment with ocriplasmin and/or C3F8 gas for VMT will be necessary to determine whether specific surgical considerations, if any, exist in this patient population. Looking forward, intraoperative OCT may provide surgeons with additional information to guide surgical decision-making. In a retrospective review of 12 eyes undergoing vitrectomy for VMT, findings from intraoperative OCT prompted change in intraoperative management in 5 of 12 eyes (42%), including decisions regarding the need for internal limiting membrane peeling and use of gas tamponade [29].
&
Rodrigues et al. [24 ] reported the efficacy of intravitreal injection of 0.3 ml of 100% C3F8 gas for the treatment of VMT in 15 eyes of 14 patients. All patients had persistent VMT of greater than 3 months duration, and 6 of 15 eyes had concurrent diabetic retinopathy. VMT release was observed in 6 of 15 eyes (40%) at 1 month and 9 of 15 eyes (60%) at 6 months, with the remaining 6 eyes offered PPV at 6 months. The authors report maximal foveal thickness of less than 500 mm, low vitreous face reflectively, and maximal horizontal VMA less than 750 mm as factors predictive of VMT release at 1 month. Mean visual acuity, however, did not improve, which the authors suggest may be secondary to damage related to VMT or coexisting diabetic retinopathy.
SURGICAL MANAGEMENT PPV remains the mainstay of VMT treatment when observation and/or medical therapy are either unsuccessful or not indicated [25]. Known adverse effects of PPV for VMT include cataract progression, ERM formation, and retinal detachment, but in general, PPV has been shown to be a well tolerated, effective, and cost-effective option for this patient population [26,27]. Of interest is whether prior ocriplasmin injection affects intraoperative complication rate or surgical outcomes in patients undergoing PPV for persistent VMT. Early reports suggest complication rates and surgical outcomes do not differ. Greven [28] reported outcomes of 39 eyes that underwent PPV for persistent VMT after treatment with ocriplasmin. Of these eyes, 36 of 39 (92%) underwent indocyanine green angiography assisted membrane peel intraoperatively. Mean logMAR visual acuity
CONCLUSION Options for the management of VMT include observation, medical therapy (intravitreal ocriplasmin and C3F8 gas), and vitrectomy. Recent studies have helped elucidate baseline features of eyes with the best outcomes from pharmacologic vitreolysis with ocriplasmin, affording patients and physicians more information to guide therapeutic decisionmaking. Additional investigation into the risk/ benefit profile of intravitreal gas is needed to clarify its role in treatment recommendations. Physicians and patients will also benefit from study of the efficacy and safety of ocriplasmin in a broader spectrum of patients, including those with concurrent retinal disease. Acknowledgements None. Financial support and sponsorship None. Conflicts of interest J.A.H., MD, has been a consultant for ThromboGenics, Inc. M.A.K., MD, has no conflicts of interest.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Gass J. Stereoscopic atlas of macular diseases: diagnosis and treatment. 4th ed. St. Louis, MO: Mosby; 1997. 2. Duker JS, Kaiser PK, Binder S, et al. The International Vitreomacular Traction Study Group classification of vitreomacular adhesion, traction, and macular hole. Ophthalmology 2013; 120:2611–2619.
1040-8738 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-ophthalmology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
147
Retinal, vitreous and macular disorders 3. McCannel CA, Ensminger JL, Diehl NN, Hodge DN. Population-based incidence of macular holes. Ophthalmology 2009; 116:1366–1369. 4. Klein R, Klein BE, Wang Q, Moss SE. The epidemiology of epiretinal membranes. Trans Am Ophthalmol Soc 1994; 92:403–425; discussion 425-30. 5. Rahmani B, Tielsch JM, Katz J, et al. The cause-specific prevalence of visual impairment in an urban population. The Baltimore Eye Survey. Ophthalmology 1996; 103:1721–1726. 6. Theodossiadis GP, Chatziralli IP, Sergentanis TN, Datseris I, Theodossiadis PG. Evolution of vitreomacular adhesion to acute vitreofoveal separation with special emphasis on a traction-induced foveal pathology. A prospective study of spectral-domain optical coherence tomography. Graefes Arch Clin Exp Ophthalmol 2014. [Epub ahead of print] 7. John VJ, Flynn HW, Smiddy WE, et al. Clinical course of vitreomacular adhesion managed by initial observation. Retina 2014; 34:442–446. 8. Dimopoulos S, Bartz-Schmidt K-U, Gelisken F, et al. Januschowski K, Ziemssen F. Rate and timing of spontaneous resolution in a vitreomacular traction group: Should the role of watchful waiting be re-evaluated as an alternative to Ocriplasmin therapy? Br J Ophthalmol 2015; 99:350– 353. 9. Theodossiadis GP, Grigoropoulos VG, Theodoropoulou S, et al. Sponta& neous resolution of vitreomacular traction demonstrated by spectral-domain optical coherence tomography. Am J Ophthalmol 2014; 157:842.e1– 851.e1. Prospective, observational case series of 46 eyes with idiopathic VMT followed over 3 years. On univariate analysis, VMT diameter or less 400 mm (P < 0.001) and the angle between the vitreous surface and the nasal (P ¼ 0.01) and temporal (P < 0.01) fovea was also associated with spontaneous VMT release. Meantime with VMT prior to spontaneous resolution was 8.75 months. 10. Almeida DRP, Chin EK, Rahim K, et al. Factors associated with spontaneous & release of vitreomacular traction. Retina 2014; 35:492–497. Retrospective, case-controlled series of 61 eyes with isolated or concurrent VMT. Found that factors predictive of spontaneous release included isolated inner retinal layer distortion (P ¼ 0.01) and treatment of concurrent retinal disease with intravitreal injections (P ¼ 0.02). Of the 21 eyes with spontaneous release, 11 eyes received a mean of 9.1 intravitreal injections. Alternatively, of the 40 eyes without spontaneous release, 5 eyes received a mean of 2.8 intravitreal injections. 11. Codenotti M, Iuliano L, Fogliato G, et al. A novel spectral-domain optical coherence tomography model to estimate changes in vitreomacular traction syndrome. Graefes Arch Clin Exp Ophthalmol 2014; 252:1729–1735. 12. Stalmans P, Benz MS, Gandorfer A, et al. Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular holes. N Engl J Med 2012; 367:606–615. 13. Haller JA, Stalmans P, Benz MS, et al. Efficacy of intravitreal ocriplasmin for & treatment of vitreomacular adhesion: subgroup analyses from two randomized trials. Ophthalmology 2015; 122:117–122. Subgroup analysis of the phase III MIVI-TRUST data. Analysis revealed resolution of VMA at day 28 was associated with age younger than 65, adhesion diameter or less 1500 mm, phakic status, presence of FTMH, and absence of ERM. Observed that nonsurgical hole closure at month 6 was more likely in eyes with smaller holes, achieved in 58.3% of holes or less 250 mm, 36.8% of holes greater than 250 and or less 400 mm, and in 0% of holes greater than 400 mm.
148
www.co-ophthalmology.com
14. Singh RP, Li A, Bedi R, et al. Anatomical and visual outcomes following ocriplasmin treatment for symptomatic vitreomacular traction syndrome. Br J Ophthalmol 2014; 98:356–360. 15. Kim BT, Schwartz SG, Smiddy WE, et al. Initial outcomes following intravitreal ocriplasmin for treatment of symptomatic vitreomacular adhesion. Ophthalmic Surg Lasers Imaging Retina 2013; 44:334–343. 16. Warrow DJ, Lai MM, Patel A, et al. Treatment outcomes and spectral-domain optical coherence tomography findings of eyes with symptomatic vitreomacular adhesion treated with intravitreal ocriplasmin. Am J Ophthalmol 2015; 159:20.e1–30.e1. 17. Tibbetts MD, Reichel E, Witkin AJ. Vision loss after intravitreal ocriplasmin: correlation of spectral-domain optical coherence tomography and electroretinography. JAMA Ophthalmol 2014; 132:487–490. 18. Fahim AT, Khan NW, Johnson MW. Acute panretinal structural and functional abnormalities after intravitreous ocriplasmin injection. JAMA Ophthalmol 2014; 132:484–486. 19. Freund KB, Shah SA, Shah VP. Correlation of transient vision loss with outer retinal disruption following intravitreal ocriplasmin. Eye Lond Engl 2013; 27:773–774. 20. Quezada Ruiz C, Pieramici DJ, Nasir M, Rabena M, Avery RL. Severe acute vision loss, dyschromatopsia, and changes in the ellipsoid zone on SD-OCT associated with intravitreal ocriplasmin injection. Retin Cases Brief Rep 2014. [Epub ahead of print] 21. Novack RL, Staurenghi G, Girach A, Narendran N, Tolentino M. Safety of intravitreal ocriplasmin for focal vitreomacular adhesion in patients with exudative age-related macular degeneration. Ophthalmology 2014. [Epub ahead of print] 22. Song SJ, Smiddy WE. Ocriplasmin for symptomatic vitreomacular adhesion: an evidence-based review of its potential. Core Evid 2014; 9:51–59. 23. Wong SC, Capone A. Microplasmin (ocriplasmin) in pediatric vitreoretinal surgery: update and review. Retina 2013; 33:339–348. 24. Rodrigues IA, Stangos AN, McHugh DA, Jackson TL. Intravitreal injection of & expansile perfluoropropane (c(3)f(8)) for the treatment of vitreomacular traction. Am J Ophthalmol 2013; 155:270.e2–276.e2. A retrospective, interventional case series evaluating intravitreal injection of 0.3 ml of 100% C3F8 gas for the treatment of VMT in 15 eyes of 14 consecutive patients. VMT release was observed in 6 of 15 eyes (40%) at 1 month and 9 of 15 eyes (60%) at 6 months. 25. Moisseiev J, Moroz I, Katz G. Effect of ocriplasmin on the management of macular holes: assessment of the clinical relevance of ocriplasmin. JAMA Ophthalmol 2014; 132:709–713. 26. Jackson TL, Nicod E, Angelis A, et al. Pars plana vitrectomy for vitreomacular traction syndrome: a systematic review and meta-analysis of safety and efficacy. Retina 2013; 33:2012–2017. 27. Chang JS, Smiddy WE. Cost evaluation of surgical and pharmaceutical options in treatment for vitreomacular adhesions and macular holes. Ophthalmology 2014; 121:1720–1726. 28. Greven MA. Vitrectomy after ocriplasmin for vitreomacular adhesion or macular hole: the VAVOOM study. Podium presentation presented at: The Retina Society, Annual Meeting; 12 September 2014; Philadelphia, PA. 29. Ehlers JP, Tam T, Kaiser PK, et al. Utility of intraoperative optical coherence tomography during vitrectomy surgery for vitreomacular traction syndrome. Retina 2014; 34:1341–1346.
Volume 26 Number 3 May 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
