Eyeworld

61 EW GLAUCOMA October 2018 Contact information Huang: AAHuang@mednet.ucla.edu Johnstone: johnstone.murray@gmail.com (CC) entrances. They found that the motion of these flaps was synchro- nous with TM pressure-dependent motion and that TM motion could be imaged by phase OCT images and was synchronous with the cardiac pulse. 6 Spectral domain OCT (SD OCT) has provided additional structural insights to the outflow pathway. "Recent innovations in platforms to study aqueous outflow dynamics with high resolution OCT teach us that the TM, the structures attach- ing the TM to the SC external wall and intrascleral channels all move in unison. The TM that senses IOP by changing shape is able to control CC lumen dimensions by means of the transcanalicular attachments, providing a dynamic means for the TM to sense pressure and to control flow through changes in dimensions of the CC lumen," he said. Phase sensitive OCT demon- strates that the outflow structures change shape in milliseconds and can thus easily track the ocular pulse. This recent innovation permits direct observation of pulse induced TM and collector channel motion that responds synchronous with the ocular pulse. 7 "These recent discoveries together suggest that the aqueous outflow is controlled by an ex- tremely sophisticated organ system entirely unlike the passive TM filter envisioned in the older textbooks," Dr. Johnstone explained. "Although MIGS may not currently address the normal regulatory mechanisms of the organ system, they are of value in reducing IOP. While not perfect, they may well work by providing direct access to collector channels. In the course of scarring following the procedures, some CC entrances may scar in a relatively open posi- tion, while others may have ongo- ing remodeling that causes them to gradually close, a phenomenon all too familiar to those doing filtering surgery." Addressing the pathophysiol- ogy of TM damage, Dr. Johnstone explained, "In the vascular sys- tem, channels retain their normal structure by virtue of sensing flow that induces shear stress, partic- ularly cyclic pulse-induced flow. Nitric oxide (NO) is a key player in modulating transient responses as well as optimizing long-term vascular wall dimensions. Recent- ly NO has been found to have a profound effect on resistance in the distal pathways. 8 In the absence of normal flow, cytokines are released that cause alterations in vascular walls leading to eventual closure of the vessel lumen. Due to variability in healing, some collector channels may be exposed to relatively normal flow patterns after MIGS procedures. In other cases, access to normally directed pulsatile flow may be ab- sent or become abnormal as a result of remodeling leading to abnormal responses and increased resistance within the distal vessel walls." Dr. Johnstone thinks that a great deal of work still needs to be done to fully characterize the normal dynamic behavior of the outflow system. Such work can be pursued using PhS-OCT, which allows direct in-office observation of TM and CC motion in glaucoma patients before surgery. EW References 1. Rosenquist R, et al. Outflow resistance of enucleated human eyes at two different per- fusion pressures and different extents of tra- beculotomy. Curr Eye Res. 1989;8:1233–40. 2. Huang AS, et al. Fluorescein aqueous angiography in live normal human eyes. J Glaucoma. 2018. Epub ahead of print. 3. Huang AS, et al. Aqueous angiogra- phy: aqueous humor outflow imaging in live human subjects. Ophthalmology. 2017;124:1249–1251. 4. Huang AS, et al. Aqueous angiography- mediated guidance of trabecular bypass improves angiographic outflow in human enucleated eyes. Invest Ophthalmol Vis Sci. 2016;57:4558–65. 5. Huang AS, et al. Aqueous angiography in living nonhuman primates shows segmen- tal, pulsatile, and dynamic angiographic aqueous humor outflow. Ophthalmology. 2017;124:793– 803. 6. Xin C, et al. Aqueous outflow regulation: optical coherence tomography implicates pressure-dependent tissue motion. Exp Eye Res. 2017;158:171–186. 7. Xin C, et al. Quantification of pulse-depen- dent trabecular meshwork motion in normal humans using phase-sensitive OCT. Invest Ophthalmol Vis Sci. 2018;59:3675–3681. 8. Aliancy J, et al. A review of nitric oxide for the treatment of glaucomatous disease. Ophthalmol Ther. 2017;6:221–232. Editors' note: Dr. Huang has financial interests with Aerie Pharmaceuticals (Durham, North Carolina), Heidelberg Engineering (Heidelberg, Germany), Glaukos (San Clemente, California), and Diagnosys (Lowell, Massachu- setts). Dr. Johnstone has no financial interests related to his comments.

• Cover