Abstract
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.
Highlights
Our clinical studies of plasma-mediated ab interno trabeculectomy (AIT) show that the outflow resistance distal to the trabecular meshwork (TM) is higher in eyes with glaucoma.[6,7,8,9]
In experiment 2, eyes with TM removed circumferentially by AIT were perfused at 6 μL/min, in order to make a facility change easier to detect after a significant portion of the outflow resistance has been eliminated
DETA-nitric oxide (NO) increased cross-sectional outflow tract areas (CSA) by an average of 13.9% and L-NAME+ ET-1 decreased CSA by an average of 8.6% (Fig. 5, p
Summary
The trabecular meshwork (TM) has long been considered the primary site of outflow resistance, its surgical removal or bypass does not lower the intraocular pressure (IOP) to the predicted level of episcleral venous pressure.[1,2,3] Recent laboratory studies showed that about 50% of outflow resistance is located further downstream.[4,5] Our clinical studies of plasma-mediated ab interno trabeculectomy (AIT) show that the outflow resistance distal to the TM is higher in eyes with glaucoma.[6,7,8,9] Only a small fraction of patients (about 0.3%) achieve the expected intraocular pressure (IOP).[9]. The pre- and post-operative IOP in AIT are correlated,[6] indicating an increased post-TM outflow resistance in eyes with a higher IOP This suggests an incomplete understanding of outflow distal to the TM, and an avenue for new, targeted therapies. A single vessel of this diameter could carry the entire flow,[5] a principle applied to ab interno micro gel stents to allow for a slow and safe aqueous humor drainage from the anterior chamber to the subconjunctival space.[15] CC diameter changes from IOP variations[16] and with the cardiac pulse wave[17] do not explain the remaining distal outflow resistance, nor do valves at the orifices of collector channels[18] as their removal by deep sclerotomy fails to reduce IOP further.[19,20]
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