Abstract:Increasing prevalence and cost of glaucoma have increased the demand for surgeons well trained in newer, microincisional surgery. These procedures occur in a highly confined space, making them difficult to learn by observation or assistance alone as is currently done. We hypothesized that our ex vivo outflow model is sensitive enough to allow computing individual learning curves to quantify progress and refine techniques. Seven trainees performed nine trabectome-mediated ab interno trabeculectomies in pig eyes… Show more
“…One possible explanation for this observation was that, once the minimum TM removal required to maintain the circumferential aqueous outflow in the Schlemm's canal was established, the additional arc of TM removal became less important. Despite no continuous Schlemm's canal in the pig, there is circumferential flow as our prior studies demonstrated [13,14,16], presumably because the Schlemm's canal-like segments are connected. Limited access to angle structures, highlighted by the microsphere canalograms are sufficient to provide outflow beyond the ablated TM.…”
Section: Discussionmentioning
confidence: 98%
“…Although separate studies have assessed and confirmed the efficacy of T and K, no study to date has evaluated G or performed a comprehensive comparison of the three techniques. In the past, outflow tracers were the primary method of examining flow [12][13][14][15][16] and the impact on the outflow facility was not assessed. The purpose of this study was to compare the increase of outflow facility in a porcine perfusion model by each.…”
Objective: To evaluate three different microincisional ab interno trabeculectomy procedures in a porcine eye perfusion model.
Methods:In perfused porcine anterior segments, 90 degrees of trabecular meshwork (TM) were ablated using the Trabectome (T; n=8), Goniotome (G; n=8), or Kahook device (K; n=8). After 24 hours, additional 90 degrees of TM were removed. Intraocular pressure (IOP) and outflow facility were measured at 5 µl/min and 10 µl/min perfusion to simulate an elevated IOP. Structure and function were assessed with canalograms and histology.Results: At 5 µl/min infusion rate, T resulted in a greater IOP reduction than G or K from baseline (76.12% decrease versus 48.19% and 47.96%, P=0.013). IOP reduction between G and K was similar (P=0.420). Removing another 90 degrees of TM caused an additional IOP reduction only in T and G but not in K. Similarly, T resulted in the largest increase in outflow facility at 5 µl/min compared with G and K (first ablation: 3.41 times increase versus 1.95 and 1.87; second ablation: 4.60 versus 2.50 and 1.74) with similar results at 10 µl/min (first ablation: 3.28 versus 2.29 and 1.90 (P=0.001); second ablation: 4.10 versus 3.01 and 2.01 (P=0.001)). Canalograms indicated circumferential flow beyond the ablation endpoints.Conclusions: T, G and K significantly increased the outflow facility. In this model, T had a larger effect than G and K.
“…One possible explanation for this observation was that, once the minimum TM removal required to maintain the circumferential aqueous outflow in the Schlemm's canal was established, the additional arc of TM removal became less important. Despite no continuous Schlemm's canal in the pig, there is circumferential flow as our prior studies demonstrated [13,14,16], presumably because the Schlemm's canal-like segments are connected. Limited access to angle structures, highlighted by the microsphere canalograms are sufficient to provide outflow beyond the ablated TM.…”
Section: Discussionmentioning
confidence: 98%
“…Although separate studies have assessed and confirmed the efficacy of T and K, no study to date has evaluated G or performed a comprehensive comparison of the three techniques. In the past, outflow tracers were the primary method of examining flow [12][13][14][15][16] and the impact on the outflow facility was not assessed. The purpose of this study was to compare the increase of outflow facility in a porcine perfusion model by each.…”
Objective: To evaluate three different microincisional ab interno trabeculectomy procedures in a porcine eye perfusion model.
Methods:In perfused porcine anterior segments, 90 degrees of trabecular meshwork (TM) were ablated using the Trabectome (T; n=8), Goniotome (G; n=8), or Kahook device (K; n=8). After 24 hours, additional 90 degrees of TM were removed. Intraocular pressure (IOP) and outflow facility were measured at 5 µl/min and 10 µl/min perfusion to simulate an elevated IOP. Structure and function were assessed with canalograms and histology.Results: At 5 µl/min infusion rate, T resulted in a greater IOP reduction than G or K from baseline (76.12% decrease versus 48.19% and 47.96%, P=0.013). IOP reduction between G and K was similar (P=0.420). Removing another 90 degrees of TM caused an additional IOP reduction only in T and G but not in K. Similarly, T resulted in the largest increase in outflow facility at 5 µl/min compared with G and K (first ablation: 3.41 times increase versus 1.95 and 1.87; second ablation: 4.60 versus 2.50 and 1.74) with similar results at 10 µl/min (first ablation: 3.28 versus 2.29 and 1.90 (P=0.001); second ablation: 4.10 versus 3.01 and 2.01 (P=0.001)). Canalograms indicated circumferential flow beyond the ablation endpoints.Conclusions: T, G and K significantly increased the outflow facility. In this model, T had a larger effect than G and K.
“…The number of eyes had to be limited in this explorative study due to the intense computational requirements to process several terabytes of data in millions of confocal images. Canalogram studies of human eyes suggested a perilimbal, proximal vessel network with a density [15] similar to that of porcine eyes [16][17][18][19] . We hypothesized that an RSCM analysis of the lectin-labeled outflow tract of human eyes would match our findings in porcine eyes.…”
Section: Introductionmentioning
confidence: 81%
“…These results indicate that human eyes not only have far fewer collector channels but that their anatomy differs fundamentally by spanning several clock hours and having a 50% greater CSA. This came as a surprise because recent lower resolution canalogram studies of perilimbal outflow structures suggested a density and function of outflow vessels in human eyes [15] similar to that in porcine eyes [16][17][18][19] . The smaller number, longer course, and flatter, collapsible nature of CCs in human eyes may increase the risk of outflow failure and IOP elevation in glaucoma.…”
PurposeRisk for glaucoma is driven by the microanatomy and function of the anterior segment. We performed a computation-intense, high-resolution, full-thickness ribbon-scanning confocal microscopy (RSCM) of the outflow tract of two human eyes. We hypothesized this would reveal important species differences when compared to existing data of porcine eyes, an animal that does not spontaneously develop glaucoma.MethodsAfter perfusing two human octogenarian eyes with lectin-fluorophore conjugate and optical clearance with benzyl alcohol benzyl benzoate (BABB), anterior segments were scanned by RSCM and reconstructed in 3D for whole-specimen rendering. Morphometric analyses of the outflow tract were performed for the trabecular meshwork (TM), limbal, and perilimbal outflow structures and compared to existing porcine data.ResultsRSCM provided high-resolution data for IMARIS-based surface reconstruction of outflow tract structures in 3D. Different from porcine eyes with an abundance of highly interconnected, narrow, and short collector channels (CCs), human eyes demonstrated fewer CCs which had a 1.5x greater cross-sectional area (CSA) and 2.6x greater length. Proximal CC openings at the level of Schlemm’s canal (SC) had a 1.3x larger CSA than distal openings into the scleral vascular plexus (SVP). CCs were 10.2x smaller in volume than the receiving SVP vessels. Axenfeld loops, projections of the long ciliary nerve, were also visualized.ConclusionIn this high-resolution, volumetric RSCM analysis, human eyes had far fewer outflow tract vessels than porcine eyes. Human CCs spanned several clock-hours and were larger than in porcine eyes. These species differences may point to factors downstream of the TM that increase our vulnerability to glaucoma.Grant informationNational Eye Institute K08EY022737 (NAL); Initiative to Cure Glaucoma of the Eye and Ear Foundation of Pittsburgh (NAL); Wiegand Fellowship of the Eye and Ear Foundation of Pittsburgh (YD); P30-EY08098 (NAL); Department grant by Research to Prevent Blindness (NAL); an unrestricted fellowship grant from the Xiangya Hospital of Central South University (SC).
“…Increased, optic nerve-damaging intraocular pressure (IOP) in POAG was long thought to be only caused by outflow resistance at the trabecular meshwork (TM), which guards the drainage system of the eye. However, data from clinical TM ablation in thousands of patients show it fails to lower IOP to the pressure level in the recipient episcleral veins [4][5][6][7][8] . The data suggests that over half of resistance resides in the distal outflow tract (OT), downstream of the TM and Schlemm's canal (SC).…”
AbstractPurposeTo characterize the effects of netarsudil on the aqueous humor outflow tract distal to the trabecular meshwork (TM). We hypothesized that netarsudil increases outflow facility in eyes with and without circumferential ab interno trabeculectomy (AIT) that removes the TM.Methods64 porcine anterior segment cultures were randomly assigned to groups with (n=32) and without circumferential AIT (n=32). Cultures were exposed to 0.1, 1, and 10 μM netarsudil (N= 8 eyes per concentration). For each concentration, IOP and vessel diameters were compared to their respective pretreatment baselines. Outflow tract vessel diameters were assessed by spectral-domain optical coherence tomography (SDOCT) and rendered in 4D (XYZ time-series).ResultsNetarsudil at 1 μM reduced IOP in both eyes with TM (−0.60±0.24 mmHg, p = 0.01) and in eyes without TM (−1.79±0.42 mmHg, p<0.01). At this concentration, vessels of the distal outflow tract dilated by 72%. However, at 0.1 μM netarsudil elevated IOP in eyes with TM (1.59±0.36 mmHg, p<0.001) as well as in eyes without TM (0.23±0.32 mmHg, p<0.001). Vessels of the distal outflow tract constricted by 31%. Similarly, netarsudil at a concentration of 10 μM elevated IOP both in eyes with TM (1.91±0.193, p<0.001) and in eyes without TM (3.65±0.86 mmHg, p<0.001). At this concentration, outflow tract vessels constricted by 27%.ConclusionIn the porcine anterior segment culture, the dose-dependent IOP changes caused by netarsudil matched the diameter changes of distal outflow tract vessels. Hyper- and hypotensive properties of netarsudil persisted after TM removal.
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