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Vitreomacular Adhesion And A New Treatment Option… Jetrea®

AN INTRODUCTION TO A NOVEL TECHNOLOGY

Written by Jay M. Haynie, OD, FAAO, Larry J Alexander OD FAAO Monday, 10 March 2014

The vitreoretinal interface (VRI) contains a diverse mix of extracellular molecules, including collagen, laminin, and fibronectin, that facilitate the adhesion between the vitreous cortex and the innermost retinal layer (the internal limiting membrane—ILM).

Recent imaging advances in optical coherence tomography (spectral domain; SD-OCT) have advanced the accuracy with which diseases of the VRI are diagnosed and managed. Even though patients may be totally asymptomatic, issues such as vitreomacular adhesion and vitreomacular traction may be present. While many do not warrant consultation for possible intervention, the primary-care practitioner will nonetheless uncover the “sleeping condition” with spectral domain optical coherence tomography (SD-OCT) and will need to make decisions.

DOCTOR, WHAT DO YOU DO WITH THIS “SURPRISE FINDING”?

Vitreoretinal interface issues continue to be a significant consideration in the compromise of vision function, and any potential solution could be of benefit to the patient, especially with the timely discovery of the problem.

SYMPTOMATIC VITREOMACULAR ADHESION (VMA)

Symptomatic VMA is a progressive and potentially sight-threatening condition that is a result of an incomplete separation of the posterior hyaloid from the retinal surface at the macula. Symptoms, including metamorphopsia; image size disparity, or macropsia; diminished central visual acuity; and a possible central visual field defect discovered with Amsler grid testing, may appear when the tractional forces of VMA pull on the macula, causing disruption or distortion of the underlying architecture. 

VMA that disturbs the foveal contour or disrupts the retinal architecture is defined as vitreomacular traction (VMT). Jay Haynie states, “When managing VRI anomalies such as VMA and VMT, doctors need to consider the natural history of a macular hole. The incidence of a macular hole is 0.02% to 0.8%, and in this setting, simple observation may be the best medicine for many patients. It is notable, however, that the incidence of bilateral macular holes is 11%, so this is a group of patients (those with a history of a macular hole in one eye) to monitor more closely. Having said this, it has been my experience that patients at risk for a macular hole are the ones with VMT that results in an anterior displacement of the foveal architecture. I have them trained on the use of an Amsler grid and see them more frequently.”

CLASSIFICATION OF VMA/VMT

The International Vitreomacular Traction Study (IVTS) Group has developed an OCTbased anatomic classification system for diseases of the vitreomacular interface (Duker, 2013). International Classification System definitions include: 

  • VMA: perifoveal vitreous separation with remaining vitreomacular attachment and unperturbed foveal morphologic features
  • VMT: anomalous posterior vitreous detachment accompanied by anatomic distortion of the fovea
    • Focal: attachment of 1500 μm or less
    • Broad: attachment of more than 1500 μm

HOW JETREA® WORKS

For diseases of the vitreomacular interface, a breakthrough pharmacological treatment for symptomatic VMA/VMT is now available. JETREA® is a truncated form of human plasmin that has activity against the components of the vitreous body and the VRI (fibronectin, collagen, and laminin). In two pivotal phase 3 clinical trials, JETREA® was shown to be efficacious for the resolution of VMA, the closure of full-thickness macular hole (FTMH), and the improvement of best corrected visual acuity (BCVA) in a greater percentage of patients when compared to placebo (Stalmans, 2012).

WHEN IS JETREA® A POTENTIAL OPTION?

Previous clinical approaches to treating symptomatic VMA/VMT include watchful waiting or pars plana vitrectomy. Watchful waiting has the disadvantage of potentially “missing” the therapeutic window for treatment, leading to poorer prognosis and
potentially irreversible vision loss, while pars plana vitrectomy is associated with intraoperative risks, including retinal tears, and postoperative complications, including cataract formation. Due to the availability of a new treatment that can be effective in the early stages of VMA/ VMT, early intervention with JETREA® is an important option to
consider. 

WHAT ARE THE POSITIVE PREDICTORS OF A GOOD RESPONSE WITH JETREA® ?

A key consideration is patient selection. Analysis of the clinical trial data and postmarketing experience revealed which patient populations had the best response to JETREA® treatment. These included patients with the presence of focal attachment (≤1500 μm), the absence of an epiretinal membrane (ERM), or VMT associated with macular holes smaller than 400 micrometers (Ray, 2012; Singh, 2014). Understanding the best patient population for JETREA® treatment is important for optimizing patient outcomes. Haynie states, “I agree that the differentiation in the width of the adhesion is critical in choosing candidates for Jetrea®, as we will typically not consider treatment for an attachment over 1500 microns or ones that are associated with an ERM.” Haynie further states, “Technique of treatment has also been noted to be a part of increased success, in that the Jetrea® molecule needs to be directed to the point of attachment. For this reason, patients should be instructed to lie flat on their back for 15–30 minutes after the treatment in order to put the compound where needed per se.”

OCT scans illustrating patients presenting with VMA/VMT who would be potential candidates for treatment with JETREA® 

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Focal VMA with normal foveal contour and retina morphology. Image from Stalmans, P., et al., Retina 0:1-9, 2013

jetrea2

Vitreomacular traction with minor distortion of the foveal contour (arrows). Image from Stalmans, P., et al., Retina 0:1-9, 2013

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Vitreomacular traction with distorted foveal contour and intraretinal cyst. Image from Stalmans, P., et al., Retina 0:1-9, 2013

CONCLUSION

This introduction to a possible alternative management plan for vitreoretinal-interface disorders becomes important in the wake of the increasing discovery of these clinical conditions with the continued development and application of spectral domain optical coherence tomography (SD-OCT). These conditions often are not visible with standard fundus-evaluation techniques and even “hide” with high-resolution fundus photography. Studies are now under way to determine how often the clinician can expect these conditions in patients. However, if a patient presents with symptomatic uncorrected vision, distortions, macropsia, or metamorphopsia, the use of OCT would be indicated to uncover the possibility of VRI anomalies.

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About the Author(s)

Jay M. Haynie, OD, FAAO

Jay M. Haynie, OD, FAAO

Dr. Jay M. Haynie is the Executive Clinical Director of Retina and Macula Specialists with offices in Washington State. He graduated from Pacific University College of Optometry and completed a residency at American Lake Veterans Hospital in Tacoma, WA. He has been a clinical investigator for Rainier Research, providing ocular examinations for patients undergoing experimental drug therapy for diabetes, cholesterol and diabetic neuropathy. He serves as Adjunct Assistant Professor at Pacific University College of Optometry, a Fellow of the American Academy of Optometry and a member of the Optometric Retina Society. He is a published author and has become a nationally recognized speaker on new technology and treatment of retinal and macular disease.

Larry J Alexander OD FAAO

Larry J Alexander OD FAAO

Dr. Alexander (1948-2016) was a 1971 graduate of Indiana University School of Optometry. He served in the US Navy then served as a Professor at the University of Alabama Birmingham School of Optometry. Larry contributed to a number of chapters in textbooks and has published three editions of Primary Care of the Posterior Segment, as well as contributed to the professional literature. He also lectured extensively in the area of ocular and systemic disease. His areas of special interest included dysfunctional tear syndrome, glaucoma and macular degeneration.  His lessons are the basis for this site and he will be dearly missed. 

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