Outflow enhancement by three different ab interno trabeculectomy procedures in a porcine anterior segment model

Dang, Yalong; Wang, Chao; Shah, Priyal; Waxman, Susannah; Loewen, Ralitsa T.; Hong, Ying; Esfandiari, Hamed; Loewen, Nils A.

doi:10.1007/s00417-018-3990-0

Cited by 29 publications

(31 citation statements)

References 46 publications

(66 reference statements)

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“…Consistent with our prior experience, 21,23,24,34,41,42 the perfused porcine anterior segments did not experience the amount of corneal edema reported with other culture techniques. 43 With intact TM, nitric oxide increased the facility by approximately 45% in group NO compared to the control group, C. After 360° AIT in experiment 2, we found a facility difference of approximately 60% between AIT-NO and AIT-C, in line with the findings reported by McDonnell et al 37 This difference persisted throughout experiments 1 and 2 but declined toward the end of experiment 1, possibly due to a decreasing TM facility response to NO.…”

Section: Discussionsupporting

confidence: 86%

“…The TM makes for a significant contribution to outflow resistance, but not in experiment 2 where the facility enhancement is TM-independent. Trabectome-mediated TM ablation results in an approximately 300 micron-wide excision down to the bare sclera 24,[31][32][33][34]41,44 where the opening of the collector channels are located without significant trauma or thermal injury. Like DETA-NO, cromakalim treatment of mouse eyes lowered episcleral venous pressures, and in TM-free human anterior segment cultures, lowered IOP.…”

Section: Discussionmentioning

confidence: 99%

“…Eyes were perfused before and after AIT, in groups AIT-NO and AIT-C as in our prior experiments. [31][32][33][34][35] One eye had to be excluded due to contamination (N: AIT-NO=7, AIT-C=8). Baseline facility measures in AIT-NO and AIT-C were not different (p=0.37).…”

Section: Outflow Facility Increase By No Before and After Tm Ablationmentioning

confidence: 99%

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Structure-Function Changes of the Distal Outflow Tract in Response to Nitric Oxide

Waxman¹,

Wang²,

Dang³

et al. 2018

Preprint

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Purpose: To correlate outflow function and outflow tract vessel diameter changes induced by nitric oxide (NO).Methods: In a porcine anterior segment perfusion model, the effects of a nitric oxide donor (100 µM DETA-NO) on outflow facility were compared to controls (n=8 per group) with trabecular meshwork (TM) and after circumferential ab interno trabeculectomy (AIT). Outflow structures were assessed with spectral domain optical coherence tomography (SD-OCT) before and after NO, or an NO synthase inhibitor (100 µM L-NAME) and the vasoconstrictor, endothelin-1 (100 pg/mL ET-1). Scans were processed with a custom macro script and aligned for automated reslicing and quantification of cross-sectional outflow tract areas (CSA). Results:The facility increased after DETA-NO (0.189±0.081 μL/min·mmHg, p=0.034) and AIT (0.251±0.094 μL/min·mmHg, p=0.009), respectively. Even after AIT, DETA-NO increased the facility by 61.5% (0.190±0.074 μL/min·mmHg, p=0.023) and CSA by 13.9% (p<0.001). L-NAME + ET-1 decreased CSA by -8.6% (p<0.001). NO increased the diameter of focal constrictions 5.0±3.8 fold.Conclusions: NO can dilate vessels of the distal outflow tract and increase outflow facility in a TMindependent fashion. There are short, focally constricting vessel sections that display large diameter changes and may have a substantial impact on outflow.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

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Structure-Function Changes of the Distal Outflow Tract in Response to Nitric Oxide

Waxman¹,

Wang²,

Dang³

et al. 2018

Preprint

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“…Eyes were perfused before and after AIT, in groups AIT-NO and AIT-C as in our prior experiments. 38 – 42 One eye had to be excluded due to contamination (N: AIT-NO = 7, AIT-C = 8). Baseline facility measures in AIT-NO and AIT-C were not different ( P = 0.37).…”

Section: Resultsmentioning

confidence: 99%

Structure–Function Changes of the Porcine Distal Outflow Tract in Response to Nitric Oxide

Waxman

Wang

Dang

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeTo correlate outflow function and outflow tract vessel diameter changes induced by nitric oxide (NO).MethodsIn a porcine anterior segment perfusion model, the effects of a nitric oxide donor (100 μM DETA-NO) on outflow facility were compared with controls (n = 8 per group) with trabecular meshwork (TM) and after circumferential ab interno trabeculectomy (AIT). Outflow structures were assessed with spectral-domain optical coherence tomography (SD-OCT) before and after NO, or an NO synthase inhibitor (100 μM L-NAME) and the vasoconstrictor, endothelin-1 (100 pg/mL ET-1). Scans were processed with a custom macroscript and aligned for automated reslicing and quantification of cross-sectional outflow tract areas (CSA).ResultsThe facility increased after DETA-NO (Δ of 0.189 ± 0.081 μL/min·mm Hg, P = 0.034) and AIT (Δ of 0.251 ± 0.094 μL/min·mm Hg, P = 0.009), respectively. Even after AIT, DETA-NO increased the facility by 61.5% (Δ of 0.190 ± 0.074 μL/min·mm Hg, P = 0.023) and CSA by 13.9% (P < 0.001). L-NAME + ET-1 decreased CSA by −8.6% (P < 0.001). NO increased the diameter of focal constrictions 5.0 ± 3.8-fold.ConclusionsNO can dilate vessels of the distal outflow tract and increase outflow facility in a TM-independent fashion. There are short, focally constricting vessel sections that display large diameter changes and may have a substantial impact on outflow.

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“…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).…”

Section: Introductionmentioning

confidence: 99%

Dose-dependent effects of netarsudil, a Rho-kinase inhibitor, on the distal outflow tract

Chen

Waxman

Wang

et al. 2020

Preprint

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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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Outflow enhancement by three different ab interno trabeculectomy procedures in a porcine anterior segment model

Abstract: T, G, and K significantly increased the outflow facility. In this model, T had a larger effect than G and K.

Cited by 29 publications

References 46 publications

Structure-Function Changes of the Distal Outflow Tract in Response to Nitric Oxide

Structure-Function Changes of the Distal Outflow Tract in Response to Nitric Oxide

Structure–Function Changes of the Porcine Distal Outflow Tract in Response to Nitric Oxide

Dose-dependent effects of netarsudil, a Rho-kinase inhibitor, on the distal outflow tract

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