Mathematical Modeling of Outflow Facility Increase With Trabecular Meshwork Bypass and Schlemm Canal Dilation.

PURPOSE: To mathematically model the conventional aqueous humor outflow system with trabecular meshwork (TM) bypass and Schlemm canal (SC) dilation. METHODS: The SC was modeled as a rectangular channel with the TM modeled as a permeable membrane. The collector channels (CCs) were modeled as fluid sinks distributed along the outer wall of SC. Two different implants were investigated in this study. The Hydrus Microstent (scaffold) was modeled with a TM bypass and a dilated region in SC that was 7 or 15 mm long and approximately 5-fold larger than the normal height of SC (h0). The iStent trabecular microbypass was modeled with a similar structure except that the dilated region in SC was 1 mm long and 25% larger than h0. RESULTS: Creation of a TM bypass structure would increase the pressure in the surrounding regions inside the SC and make it close to the intraocular pressure. SC dilation would increase the pressure more uniformly in the dilated region. The pressure increase led to higher flow rates in SC and CCs, and subsequently increased outflow facility (C). If CCs were uniformly distributed, the increase in C was the smallest after implantation of 1 microbypass, compared with that after implantation of 2 microbypasses or 1 scaffold. If CCs were nonuniformly distributed, the magnitude of increase in C was sensitive to the location of implant, and the sensitivity was higher for the microbypass than the scaffold. CONCLUSION: The study showed that creation of TM bypass and SC dilation significantly increased outflow facility, and the amount of increase correlated with the length of dilated regions in SC.

A Novel Schlemm's Canal Scaffold: Histologic Observations.

PURPOSE: To assess the biocompatibility of a novel implant made of Nitinol (nickel-titanium alloy), designed to improve aqueous humor outflow. MATERIALS AND METHODS: In the first arm of biocompatibility testing, microstents were surgically inserted into Schlemm's canal (SC) of 2 non-human primates (NHPs), and a third NHP served as a surgical sham control. After 13 weeks the animals were killed, and the eyes were examined by light and scanning electron microscopy. Two masked investigators evaluated the histology sections. The second arm utilized 8 New Zealand white rabbits; each rabbit received a microstent inserted into the sclera and subconjunctival space by means of passage across the anterior chamber thus providing contact with several representative ocular tissues. The fellow eye of each rabbit underwent a sham procedure without microstent insertion. The rabbits were killed after 26 weeks, and a trained ocular pathologist examined the specimens using light microscopy. RESULTS: Histologic and scanning electron microscopy analysis of the NHPs demonstrated that the microstents were located in SC. There was no evidence of an acute or chronic inflammatory response, granulation response, or fibrosis in the outflow system or in adjacent tissues. Rabbit eyes showed minimal mononuclear cell infiltration and minimal fibrotic responses at the site of the implants when compared with sham-treated control eyes. CONCLUSIONS: The Hydrus Microstent was associated with minimal inflammation in both NHP and rabbit eyes with extended follow-up. These preclinical studies demonstrate that the Hydrus Microstent appears to have excellent long-term biocompatibility.

Effects of a Schlemm canal scaffold on collector channel ostia in human anterior segments.

This study evaluates the morphologic effect of the implantation of two different sizes of the Hydrus microstent on the outer wall of Schlemm's canal (SC) and collector channel (CC) ostia. Twelve human eyes were dissected at the equator removing the iris, lens, ciliary body and vitreous. The cornea was excised with a corneal trephine exposing a direct view of the angle while leaving the trabecular meshwork (TM) intact. The Hydrus delivery system was used to deliver microstents of 8 mm and 15 mm in length into SC. Following delivery, the tissues were immediately immersed in fixative. After tissue fixation, the microstents were gently lifted out of SC through the TM leaving a small slit opening in the TM. The slit opening was widened by gently dissecting the entire TM. Control eyes underwent dissection before fixation by gently removing the TM exposing the outer wall of SC. The tissues were prepared for scanning electron microscopy (SEM). The external wall of SC was imaged using SEM and were reviewed with particular attention focused on the distribution of irregular particulate matter (IPM), the shape of the CC ostia and the health of the SC endothelium. Three eyes received the 8 mm microstent, two the 15 mm microstent and 6 eyes served as controls. Five of the controls had reported histories of glaucoma while all other eyes were normal. All eyes showed evidence of removal of the trabecular meshwork revealing the external wall of SC. CCs were regularly visible in all eyes and were not obstructed, compressed or their margins disrupted. Nuclear profiles were oriented circumferentially in SC except at regions of CC ostia where they assumed a radial configuration oriented toward the lumen of the CC. The area of microstent contact with SC external wall was examined with SEM and a comparison made between the 8 and 15 mm microstent showing a smaller area of indentation with the 8 mm microstent. The indentations were generally free of particulate debris, were smooth and were devoid of nuclear profiles. In bridged areas adjacent to areas of microstent contact, CCs were identified, appearing patent and intact like those of the control eyes. The eyes receiving 8 mm and 15 mm Hydrus microstents both maintained CC ostia patency but a smaller area of external wall contact was evident from insertion of the 8 mm microstent.

A novel Schlemm's Canal scaffold increases outflow facility in a human anterior segment perfusion model.

PURPOSE: An intracanalicular scaffold (Hydrus microstent) designed to reduce intraocular pressure as a glaucoma treatment was tested in human anterior segments to determine changes in outflow facility (C). METHODS: Human eyes with no history of ocular disease or surgeries were perfused within 49 hours of death. The anterior segments were isolated and connected to a perfusion system. Flow rates were measured at pressures of 10, 20, 30, and 40 mm Hg. The scaffold was inserted into Schlemm's canal of the experimental eye, while a control eye underwent a sham procedure. Flow rate measurements were repeated at the four pressure levels. Individual C values were computed by dividing the flow rate by its corresponding pressure, and by averaging the four individual C measurements. The change in C between control and experimental eyes was assessed by the ratio of the baseline and second C measurement. In two eyes, the placement of the scaffold was evaluated histologically. RESULTS: After scaffold implantation in the experimental eyes, the average C increased significantly from baseline (n = 9, P < 0.05). Ratios of C at all pressure levels, except for 10 mm Hg, were significantly higher in experimental eyes (n = 9) than control eyes (P < 0.05, n = 7). Histologically, the scaffold dilated Schlemm's canal with no visible damage to the trabecular meshwork. CONCLUSIONS: The Hydrus Microstent provided an effective way to increase outflow facility in human eyes ex vivo.