Eyeworld

EW GLAUCOMA 134 April 2016 by Michelle Dalton EyeWorld Contributing Writer U sing angiography to image the aqueous humor may one day improve glaucoma surgeries and help preserve vision, said Alex Huang, MD, PhD, assistant professor, Doheny Eye Institute, David Geffen School of Medicine, University of California, Los Angeles (UCLA). In a collaborative effort between physi- cians at UCLA and Robert Weinreb, Dr. Huang's group is trying to find a way for "any surgeon to clear- ly identify the outflow of collector channels and aqueous veins," he said. "It's customized surgery to the individual's anatomy." Ike Ahmed, MD, Toronto, has been telling surgeons about the im- portance of identifying the collector channels and aqueous veins and placing the iStent (Glaukos, Laguna Hills, California) near them. "Aqueous angiography will bet- ter enable us to do that," Dr. Francis said. "It may help determine the best place to put the stent," which may be in an area that already has flow, in an area that has potential flow, or some combination. Placement assumptions Dr. Huang noted "2 assumptions have guided MIGS placement. First, if aqueous humor outflow was uniform 360 degrees around the eye and that if you put the device in one place, everything would eventually communicate and be successful. Second, older evidence suggested that more collector channels were likely nasal. Because this comple- mented most anterior segment sur- geons' experience with temporally approached surgery like phaco, this led almost everyone to place MIGS nasally." But now researchers are ques- tioning assumptions about ocular anatomy, Dr. Huang said. For exam- ple, historical clues suggest outflow may be segmental and not uniform, "meaning it's segmentally different in different parts of the eye, and it may be segmentally different be- tween 2 people, or even between 1 person's 2 eyes." "If you think of Schlemm's canal as a continuous circle where you're going to get circumferential outflow, it's not. It's more like an incomplete circle," Dr. Francis said. Imaging aqueous outflow Developing a system to image the aqueous humor was straightforward, Dr. Huang said. They borrowed from their retina colleagues at Doheny Eye Institute who routinely con- ducted intravenous retinal vascular angiographies. "We took a Spectralis [Hei- delberg Engineering, Heidelberg, Germany], which is FDA approved for retinal optical coherence to- mography and retinal intravenous angiography, and instead of focusing the camera to image the retina, we pulled it back and focused on the front of the eye, and we introduced fluorescein dye to the front of the eye," Dr. Huang said. By introducing the dye into the anterior chamber of the eye, they were able to see the flow patterns occur in cadaver eyes (both human and pig). Although they're still in the early stages, the research will move to concentrate on live humans to gather information in real time, Dr. Huang said. "Historical methods have in- volved cutting sections and looking under a microscope," he said. "We wanted a real-time method. That's Aqueous humor outflow angiography shows promise I magine putting a coronary stent in a patient with no angiogram to show you the location of the blockage. That's essentially what we do with a MIGS device. Right now the iStent is the only FDA-ap- proved device. We know that overall outflow is impaired in glaucoma, and we also know that implanting an iStent will lower the pressure. But we don't know the basic outflow defect in open angle glaucoma or what the impairment is in a specific patient. Yet it is intuitive to think that if we could determine the specific outflow obstruction, we could place the stent in just the right location to enhance outflow and lower the pressure. Alex Huang, MD, and Brian Francis, MD, are trying to solve this outflow knowledge gap. We are fortunate in the "Glaucoma editor's corner of the world" to have them review their innovative studies on outflow angiography. One of the challenges is that the ocular outflow is very slow—not at all like blood flow. But as imaging has gotten more sophisticated and sensitive, the possibility grows for seeing even very slow movements of aqueous. Until we have a "canalogram" to guide our placement of MIGS devices, our primary goal should be to successfully place the iStent within the canal. A secondary goal may be to place the iStent in an area of increased trabecular pigment. But the assumption that pigment may be a proxy for increased outflow has not been proven. A case could be made that more robust flow may result in less pigment deposition in the meshwork. Further complicating the debate is the question of whether our goal should be to place the stent in an area of brisk flow or whether it would be better to place it in an area of lower flow in an effort to boost overall outflow. Reay Brown, MD, glaucoma editor Porcine aqueous angiography; segmental and perilimbal signal is segmental (arrows) separated by regions without signals (arrowheads); asterisks show distal signal Source: Alex Huang, MD Glaucoma editor's corner of the world MD, University of California, San Diego, aqueous angiography was developed as a novel system using a combination of fluorescent dyes and angiography to view aqueous humor outflow pathways in cadaver eyes. "Our technique uses physiologic pressures that, if confirmed in hu- man eyes, may have a role in help- ing us customize glaucoma surgeries to individual patients or eyes," said Dr. Huang. "Glaucoma is an outflow dis- ease, and the better that outflow process is understood, the better the patient can be treated, regardless of the type of glaucoma," said Brian Francis, MD, professor of clinical ophthalmology, Doheny Eye Insti- tute. Current treatments for glauco- ma are "cookie cutter," Dr. Huang said. "We treat everyone similar- ly, without customizing based on anatomy." If this theory is sustained after trials in humans, it may help explain why microinvasive glauco- ma surgery (MIGS) outcomes are not predictable. MIGS devices are "generally conducted in the nasal quadrant of the eye from a temporal clear cornea approach," Dr. Huang said. "But they're not always successful, and that's frustrating because they're so easy, quick, and safe." When performing the same surgery in the same way in 2 different people, there's no guarantee the outcomes will be the same; one hypothesis is that device location is key to success.

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