Eyeworld

75 EW GLAUCOMA February 2017 trying to see and the background noise. Visualization of structure also presents us with a noisy signal, and it is very difficult to discern the edges of outflow structures versus the surrounding tissues, making segmentation challenging." Taking imaging to a 3-D level, Dr. Kagemann used spectral domain OCT to successfully track the prima- ry outflow pathway in seven donor eyes 2 followed by imaging in one eye in each of six healthy subjects 3 from Schlemm's canal through to the episcleral veins. The more superficial structures of the aqueous outflow pathways had sufficient contrast to be optically isolated and cast in situ in 360 degrees. He said, "There is nothing inherent in the OCT image that allows us to look at a void with- in the tissue and say that this is or this isn't part of the aqueous humor outflow pathway. We need to use connectivity and 3-D morphology to compile evidence to convince our- selves that we are seeing an outflow pathway. Imagine a clear fluid going through a slightly reflective tissue; the result in an OCT image is dark openings (voids) within the tissue space. If we assemble these voids into a 3-D volumetric scan, however, it will show the formation of a vas- cular pathway with a morphology consistent with what we have seen in published castings, suggesting that it is outflow tissue. Beyond that we can also see connectivity through these vascular networks bound to Schlemm's canal, again supporting the conjecture that we have visual- ized the outflow tract." In an ongoing project, Dr. Kagemann compared OCT with angiography, mapping the dark openings seen on OCT and ap- plying angiographic techniques. "There are newer OCT angiography techniques that, instead of using structure, look at the movement of reflective particles from one mo- ment in time to another to create angiograms. The challenge is, when we get to the most proximal aspect of the outflow pathway, adjacent to the Schlemm's canal, there is not enough reflective material to create angiographic 'signals.' Slightly distal to that, vessels begin to appear in the angiogram. That is the project that we are working on, comparing angiographic and structural imagery of the outflow pathway to assess the utility of angiography in the visual- ization of the outflow tracts. If we want to see Schlemm's canal and the immediate connecting vasculature, we'll need to use OCT to look at the tissue voids containing aqueous. If we want to see the more distal vasculature, if we are trying to plan a surgical procedure and just need to know where the primary drainage is, the angiographic technique may be sufficient," he said. Bedside to bench to bedside Alternatively, aqueous angiography is a different angiographic method that introduces tracers for visu- alizing aqueous humor outflow. Aqueous angiography is expected to show details of the aqueous outflow pathways that even OCT can't show. A recent investigation simulated live outflow imaging in real time under physiologic aqueous pressure in 46 pig and six human enucleated eyes. 4 The study showed the segmental, non-360 degree uniform nature of aqueous humor outflow pathways, which the investigators think may be responsible for some of the variability seen in MIGS pressure-re- ducing outcomes. Speaking with EyeWorld on the topic, investigator Alex Huang, MD, assistant profes- sor, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Ange- les, said that aqueous angiography provides functional information about outflow as opposed to the strictly structural information from OCT. He explained, "Aqueous hu- mor outflow tracking can be divid- ed into structural and functional assessments. The approach that we take is a combined structure/func- tion analysis. With OCT alone, we do not always know what the results mean; for instance, if Schlemm's canal appears extra large, does that always mean that there is more flow, or does it always mean that there is a stagnant pocket of fluid that is trapped, or could both be true under slightly different circumstances?" While studies have shown that Schlemm's canal is smaller in glau- coma patients compared to normal subjects, 1,5 implying that there is less flow, Dr. Huang thinks that it is diffi- cult to necessarily correlate structure to function. The lack of an equation continued on page 76

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