Intravitreal Gas for Vitreomacular Adhesion

Study Overview
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Brief Summary
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Vitreomacular adhesion causes symptoms of blurry vision, distortion, and double vision. It is due to an abnormal separation of the vitreous gel from the surface of the retina and macula. The current, gold-standard treatment for this condition involves surgery performed in the operating room that involves risk such as bleeding, infection, cataract, and retinal detachment. It has been previously shown that a less invasive intravitreal injection of a gas bubble performed in the office may also treat vitreomacular adhesion with less risk than surgery. The purpose of this study is to determine the effect of an office-based injection of an intravitreal gas bubble as a treatment for symptomatic vitreomacular adhesion.

Detailed Description
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Symptomatic vitreomacular adhesion (sVMA), also known as Vitreomacular traction (VMT) is thought to occur due to an anomalous or incomplete posterior vitreous detachment (PVD).1 Typical symptoms of VMT include decreased reading vision and metamorphopsia. Ultra-high resolution spectral-domain optical coherence tomography (SD-OCT) has greatly enhanced our understanding of the spectrum of the vitreomacular interface disorders ranging from focal adhesions, macular cysts, impending macular holes, full thickness macular holes, lamellar holes, and epiretinal membrane.2 Generally, pars plana vitrectomy (PPV) surgery is the preferred treatment for many of these conditions with high success rates.3 However, surgical intervention is not without risk and includes the potential for infection, retinal detachment, cataract progression, and patient discomfort from post-operative prone positioning in cases of macular hole.4 Despite the high success rate with vitrectomy, the risks of surgery have led researchers to search for non-surgical treatments of VMT such as pharmacologic vitreolysis. Ocriplasmin (JetreaTM, ThromboGenics, Inc. Iselin, NJ) was recently approved by the United States Food & Drug Administration (FDA) in October 2012 as a non-surgical, pharmacologic agent for the treatment of symptomatic VMA.5 Pooled data from two phase III clinical trials of ocriplasmin (MIVI-TRUST)5 demonstrated that approximately 26% of eyes treated with a single intravitreal injection of ocriplasmin (125 ug) compared to 10% of eyes treated with vehicle alone (placebo) resulted in resolution of VMA on OCT at 28 days. Potential side effects of ocriplasmin include transient floaters, zonular instability, and transient vision loss.6 Although the primary outcome of the study achieved a statistically significant result compared to placebo, the less than robust results compared to surgical intervention with the associated high cost of the medication have led retina specialists to question the clinical utility of this medication. Previous small case series' have demonstrated that an intravitreal gas bubble injection alone (i.e. pneumatic vitreolysis) may lead to macular hole closure through the induction of a PVD.7-9 Additional small cases series' have shown that an intravitreal gas bubble alone may induce a PVD in patients with non-proliferative diabetic retinopathy10 and diabetic macular edema11 in nearly 100% of cases. One small case series showed that an intravitreal gas bubble in combination with an anti-vascular endothelial growth factor agent can cause resolution of VMA in patients with wet macular degeneration in 4/4 (100%) of eyes.12 However, there is a paucity of literature on the specific treatment of isolated VMT with intravitreal gas alone. Recently, Rodriques et al13 demonstrated that a single intravitreal injection of perfluoropropane (C3F8) gas injection may cause VMT resolution in 5/7 (70%) eyes with isolated VMT and in 3/6 (50%) eyes with diabetic macular edema. Although this initial study demonstrated efficacy, the overall success rate of the procedure as well as the visual acuity benefit was limited due to the heterogeneous patient population. Pneumatic vitreolysis may offer a potential safe, low cost, and effective procedure that may pose an alternative to treatment in patients with symptomatic vitreomacular adhesion. The purpose of the present study is to evaluate the efficacy and safety of the administration of a single intravitreal injection of sulfa hexafluoride (SF6) gas for patients with symptomatic vitreomacular adhesion without concomitant macular hole. Key differences between the present study and that by Rodriques et al.10 are the use of a shorter acting gas bubble (SF6 vs C3F8) and the inclusion of a homogenous patient population with VMA alone.

Official Title
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Intravitreal Injection of Expansile Sulfa Hexafluoride Gas for Symptomatic Vitreomacular Adhesion

Conditions
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Vitreomacular Adhesion

Intervention / Treatment
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* Procedure: Intravitreal Injection of sulfahexafluoride gas


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 or older Able to provide written informed consent Patients with Symptomatic Vitreomacular Adhesion (sVMA) as defined by Clinical and SD-OCT findings: Clinical Findings: Symptoms: blurred vision, double vision, metamorphopsia, micropsia Snellen Visual Acuity: < 20/25 in study eye SD-OCT (Cirrus, Car Zeiss Meditec, Dublin, CA) Findings: Visible vitreous attachment within a 1,500 um radius of the foveal center causing antero-posterior vitreofoveal traction with associated microstructural retinal changes See Figure 1 (Image E) for representative candidates for inclusion. Observation period of 1 month prior to intervention allowing for spontaneous resolution Exclusion Criteria: Figure 1 (Images A, B, C, D, F, H, I) Any Macular Hole Epiretinal Membrane History of Diabetic Retinopathy (non-proliferative, proliferative, and/or diabetic macular edema) Macular Degeneration Retinal vascular occlusion Aphakia High myopia (> -8 diopters) Uncontrolled glaucoma Vitreous Opacification Retinal tear or retinal detachment Vitrectomy surgery Macular laser Figure 1: Refer to the following article: Stalmans P, Duker JS, Kaiser PK, et al. OCT-Based Interpretation of the Vitreomacular Interface and Indications for Pharmacologic Vitreolysis. Retina; 2013: Epub ahead of print

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravitreal Gas<br>Intravitreal injection of sulfahexafluoride gas | Procedure: Intravitreal Injection of sulfahexafluoride gas<br>* After the appropriate sterile and anesthetic preparation of the surgical field, the investigator will administer a single intravitreal injection of 0.3 to 0.5 cc of sulfahexafluoride gas in the study eye. An anterior chamber paracentesis may be performed if necessary. Following the procedure, the optic nerve will be monitored for perfusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with resolution of vitreomacular adhesion at Day 28 |  | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Visual Acuity |  | Day 14 | 
| Change in Visual Acuity |  | Day 28 | 
| Change in Visual Acuity |  | Day 90 | 
| Time to resolution of vitreomacular adhesion |  | Day 90 | 
| Proportion of patients requiring vitrectomy surgery | The investigator may consider vitrectomy surgery if: Decrease in Visual Acuity Worsening of vitreomacular adhesion on SD-OCT Progression of vitreomacular adhesion to macular hole No improvement of vitreomacular adhesion by Day 28 | Day 90 | 
| Incidence of Retinal Tears and Retinal Detachment |  | Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitreomacular adhesion, vitreomacular traction, macular hole, epiretinal membrane, intravitreal gas, sulfahexafluoride gas, perfluoropropane gas, ocriplasmin, vitrectomy