Intravitreal Gas for Vitreomacular Adhesion

Vitreomacular Adhesion Clinical Trial

— RELEASE  

Official title:

Intravitreal Injection of Expansile Sulfa Hexafluoride Gas for Symptomatic Vitreomacular Adhesion

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02001701
• Other study ID #: NCRVA - 2013 - RELEASE
• Status: Withdrawn
• Phase: N/A
• First received: November 24, 2013
• Last updated: January 30, 2016
• Start date: November 2013
• Est. completion date: June 2015

Study information

• Verified date: January 2016
• Source: Northern California Retina Vitreous Associates
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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:

1. Symptoms: blurred vision, double vision, metamorphopsia, micropsia

2. Snellen Visual Acuity: < 20/25 in study eye

• SD-OCT (Cirrus, Car Zeiss Meditec, Dublin, CA) Findings:

1. Visible vitreous attachment within a 1,500 um radius of the foveal center causing antero-posterior vitreofoveal traction with associated microstructural retinal changes

2. 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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Tissue Adhesions
• Vitreomacular Adhesion

Intervention

Procedure:
• Intravitreal Injection of sulfahexafluoride gas
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.

Locations

Country	Name	City	State
United States	Northern California Retina Vitreous Associates	Mountain View	California

Sponsors (1)

Lead Sponsor	Collaborator
Northern California Retina Vitreous Associates

Country where clinical trial is conducted

United States, 

References & Publications (13)

Chan CK, Wessels IF, Friedrichsen EJ. Treatment of idiopathic macular holes by induced posterior vitreous detachment. Ophthalmology. 1995 May;102(5):757-67. — View Citation

Chang LK, Fine HF, Spaide RF, Koizumi H, Grossniklaus HE. Ultrastructural correlation of spectral-domain optical coherence tomographic findings in vitreomacular traction syndrome. Am J Ophthalmol. 2008 Jul;146(1):121-7. doi: 10.1016/j.ajo.2008.03.001. Epub 2008 Apr 25. — View Citation

Freund KB, Shah SA, Shah VP. Correlation of transient vision loss with outer retinal disruption following intravitreal ocriplasmin. Eye (Lond). 2013 Jun;27(6):773-4. doi: 10.1038/eye.2013.94. Epub 2013 May 3. — View Citation

Jorge R, Costa RA, Cardillo JA, Uno F, Bonomo PP, Farah ME. Optical coherence tomography evaluation of idiopathic macular hole treatment by gas-assisted posterior vitreous detachment. Am J Ophthalmol. 2006 Nov;142(5):869-71. — View Citation

Kim YM, Lee SJ, Koh HJ. Gas-assisted release of vitreomacular adhesion in wet age-related macular degeneration. Retina. 2011 Nov;31(10):2123-4. doi: 10.1097/IAE.0B013E31822F5720. — View Citation

McHugh D, Gupta B, Saeed M. Intravitreal gas injection for the treatment of diabetic macular edema. Clin Ophthalmol. 2011;5:1543-8. doi: 10.2147/OPTH.S25348. Epub 2011 Oct 26. — View Citation

Mori K, Saito S, Gehlbach PL, Yoneya S. Treatment of stage 2 macular hole by intravitreous injection of expansile gas and induction of posterior vitreous detachment. Ophthalmology. 2007 Jan;114(1):127-33. Epub 2006 Oct 27. — View Citation

Ochoa-Contreras D, Delsol-Coronado L, Buitrago ME, Velasco-Barona C, Quiroz-Mercado H. Induced posterior vitreous detachment by intravitreal sulfur hexafluoride (SF6) injection in patients with nonproliferative diabetic retinopathy. Acta Ophthalmol Scand. 2000 Dec;78(6):687-8. — View Citation

Recchia FM, Scott IU, Brown GC, Brown MM, Ho AC, Ip MS. Small-gauge pars plana vitrectomy: a report by the American Academy of Ophthalmology. Ophthalmology. 2010 Sep;117(9):1851-7. doi: 10.1016/j.ophtha.2010.06.014. Review. — View Citation

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 Feb;155(2):270-276.e2. doi: 10.1016/j.ajo.2012.08.018. Epub 2012 Nov 17. — View Citation

Stalmans P, Benz MS, Gandorfer A, Kampik A, Girach A, Pakola S, Haller JA; MIVI-TRUST Study Group. Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular holes. N Engl J Med. 2012 Aug 16;367(7):606-15. doi: 10.1056/NEJMoa1110823. — View Citation

Stalmans P, Duker JS, Kaiser PK, Heier JS, Dugel PU, Gandorfer A, Sebag J, Haller JA. Oct-based interpretation of the vitreomacular interface and indications for pharmacologic vitreolysis. Retina. 2013 Nov-Dec;33(10):2003-11. doi: 10.1097/IAE.0b013e3182993ef8. Review. — View Citation

Witkin AJ, Patron ME, Castro LC, Reichel E, Rogers AH, Baumal CR, Duker JS. Anatomic and visual outcomes of vitrectomy for vitreomacular traction syndrome. Ophthalmic Surg Lasers Imaging. 2010 Jul-Aug;41(4):425-31. doi: 10.3928/15428877-20100525-07. Epub 2010 May 28. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with resolution of vitreomacular adhesion at Day 28		Day 28	No
Secondary	Change in Visual Acuity		Day 14	No
Secondary	Change in Visual Acuity		Day 28	No
Secondary	Change in Visual Acuity		Day 90	No
Secondary	Time to resolution of vitreomacular adhesion		Day 90	No
Secondary	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	No
Secondary	Incidence of Retinal Tears and Retinal Detachment		Day 28	Yes

External Links

•   Northern California Retina Vitreous Associates