One of the most fulfilling aspects of the science of medicine is participating in new discoveries that lead to improved treatment modalities for our patients. The last few years have led to significant advances in our understanding of the vitreous of the eye. The transparent nature of the vitreous combined with inadequate imaging capabilities resulted in diagnoses of vitreomacular adhesion (VMA) or vitreomacular traction (VMT) based on visual disturbances rather than actual pathology. The evolution from B-scan ultrasound to spectral-domain optical coherence tomography (SD-OCT), however, can be compared to the leap from analog to high-definition television. The improvements in image detail and quality have opened the door to studying the natural pathology.

Understanding the Pathology

SD-OCT allows evaluation at the microstructural level of changes that are happening within the retina. It is now possible to view each of the 10 layers of the retina to evaluate deformations of the fovea, cystic changes, or the presence of subretinal fluid. The physician can identify if there is a problem at the inner-segment/outer- segment junction or in the retinal pigment epithelium, as well as measure the size of an adhesion or macular hole. As the vitreous liquefies and goes through the process of detaching from the retina, it may remain attached at certain places. If those adhesions are in the area of the macula and causing visual disturbances, we label this pathology symptomatic VMA, which is synonymous with the older term VMT. VMA and VMT were likely grossly underdiagnosed in the past. Now we have the ability to study these adhesions and determine which morphologic characteristics are most likely to lead to spontaneous resolution and which are not. A working group has now convened to classify the severity of VMA based on OCT images, and a manuscript is expected sometime in 2013.

New Treatment Options

The ability to visualize pathology has coincided with the availability of a pharmacologic agent for treating it. Ocriplasmin (Jetrea, ThromboGenics) was approved by the US Food and Drug Administration in October 2012 for the treatment of symptomatic VMA. A single injection of 125 μg of this proteolytic enzyme resolved VMA in 26.5% of treated eyes compared with 10.1% of eyes that received sham injection (P < .001).1 Nonsurgical closure of macular hole was achieved in 40.6% of ocriplasmin-injected eyes, as compared with 10.6% of placebo-injected eyes (P < .001). Subgroup analysis of this study shows that patients with adhesions smaller than 1500 µm and macular holes smaller than 400 µm had even better results. Improved imaging capabilities even since the inception of the studies on ocriplasmin have shown that accurate measurements of macular hole sizes and adhesion spots are directly related to the efficacy of the drug. We are now able to predict that it works best in patients with smaller macular holes and adhesions and no epiretinal membranes.

Although the understanding of the natural pathology of VMA is still in its infancy, ocriplasmin study results are encouraging. The alternative to an injection is vitrectomy, a surgery for which the risk-to-benefit ratio cannot be justified unless visual acuity is significantly decreased. An important finding in the ocrisplasmin study was that successful pharmacologic treatment manifested in less than 28 days in the majority of patients, and, in those who did not achieve posterior vitreous detachment (PVD), vitrectomy surgery was not precluded or hindered in any way. In fact, data indicate an improvement in stage gradation of PVD after ocriplasmin administration, perhaps making it less work for the surgeon to achieve PVD with vitrectomy.

In my opinion, the ideal case in which to use ocriplasmin is a younger phakic patient with a small stage 2 macular hole. The potential is high for such a patient to avoid vitrectomy surgery, with a difficult recovery period and the potential side effect of cataract formation.

Effective October 1, 2011, the ICD-9-CM diagnosis code 379.27 was created for VMA and VMT. This code can be used in addition to the code for macular hole, enabling a surgeon to first treat with ocriplasmin and, if the pathology does not resolve, to then perform vitrectomy surgery.

Conclusion

There is still a lot to learn about this pathology; thankfully, many studies are currently under way. The OASIS study (clinical trials.gov: NCT01429441) is one of the largest studies in the public domain that will improve our understanding of the natural history of VMA and improve knowledge regarding who is most likely to respond positively to treatment. Studies have also been initiated to see if treatment with ocriplasmin can help quiet the disease process in age-related macular degeneration. Great progress has been made, and I look forward to continued clinical and study results.

David S. Boyer, MD, is a Clinical Professor of Ophthalmology at the University of Southern California Keck School of Medicine, Department of Ophthalmology, in Los Angeles. He is a Retina Today Editorial Board member. Dr. Boyer may be reached at +1 310 854 6201; or via email at vitdoc@aol.com.

  1. 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.