We propose an integrated model of aqueous outflow control that employs a pump-conduit system in this article. Our model exploits accepted physiologic regulatory mechanisms such as those of the arterial, venous, and lymphatic systems. Here, we also provide a framework for developing novel diagnostic and therapeutic strategies to improve glaucoma patient care. In the model, the trabecular meshwork distends and recoils in response to continuous physiologic IOP transients like the ocular pulse, blinking, and eye movement. The elasticity of the trabecular meshwork determines cyclic volume changes in Schlemm's canal (SC). Tube-like SC inlet valves provide aqueous entry into the canal, and outlet valve leaflets at collector channels control aqueous exit from SC. Connections between the pressure-sensing trabecular meshwork and the outlet valve leaflets dynamically control flow from SC. Normal function requires regulation of the trabecular meshwork properties that determine distention and recoil. The aqueous pump-conduit provides short-term pressure control by varying stroke volume in response to pressure changes. Modulating TM constituents that regulate stroke volume provides long-term control. The aqueous outflow pump fails in glaucoma due to the loss of trabecular tissue elastance, as well as alterations in ciliary body tension. These processes lead to SC wall apposition and loss of motion. Visible evidence of pump failure includes a lack of pulsatile aqueous discharge into aqueous veins and reduced ability to reflux blood into SC. These alterations in the functional properties are challenging to monitor clinically. Phase-sensitive OCT now permits noninvasive, quantitative measurement of pulse-dependent TM motion in humans. This proposed conceptual model and related techniques offer a novel framework for understanding mechanisms, improving management, and development of therapeutic options for glaucoma.

Glaucoma is a leading cause of blindness worldwide and results from damage to the optic nerve. Currently, intraocular pressure is the only treatable risk factor. Changes in aqueous outflow regulate pressure; regulation becomes abnormal in glaucoma. From inside the eye aqueous flows out through the trabecular meshwork into a venous sinus called Schlemm's canal, next into collector channels and finally returns to the episcleral vessels of the venous system. The location of aqueous outflow regulation is unknown. Ex vivo and in vivo studies implicate both pressure-dependent trabecular tissue motion and tissues distal to Schlemm's canal in regulation of aqueous outflow. Technologies have not previously been available to study these issues. New ex vivo imaging in human eyes identifies hinged flaps or leaflets at collector channel entrances using a high-resolution spectral domain optical coherence tomography (SD-OCT) platform. The hinged flaps open and close in synchrony with pressure-dependent trabecular meshwork motion. The SD-OCT platform images from the trabecular meshwork surface while experimentally changing transtrabecular pressure gradients. New in vivo imaging in human eyes uses a motion sensitive technology, phase-sensitive OCT to quantitate real-time pulse-dependent trabecular tissue motion as well as absence of such motion when aqueous access to the outflow system is blocked. The recent studies suggest that aqueous outflow regulation results from synchronous pressure-dependent motion involving a network of interconnected tissues including those distal to Schlemm's canal. The new imaging technologies may shed light on glaucoma mechanisms and provide guidance in the management of medical, laser and surgical decisions in glaucoma.

Objective To compare the efficacy and safety of ab interno canaloplasty (ABiC) with gonioscopy-assisted transluminal trabeculotomy (GATT) in patients with open-angle glaucoma (OAG). Method This randomised clinical trial recruited eyes with OAG and no previous incisional ocular surgery, among which 38 were randomised to ABiC and 39 to GATT. Follow-ups were performed at 1, 3, 6 and 12 months postoperatively. The primary outcome measures were intraocular pressure (IOP) and use of glaucoma medication at 12 months postoperatively. The secondary outcome measure was complete surgical success (not requiring glaucoma surgery, IOP ≤21 mm Hg and non-use of glaucoma medications). Results Both groups had similar demographic and ocular characteristics. A total of 71 of the 77 subjects (92.2%) completed 12-month follow-up. At 12 months, mean IOP was 19.0±5.2 mm Hg in the ABiC group and 16.0±3.1 mm Hg in the GATT group (p=0.003). Overall, 57.2% of ABiC patients and 77.8% of GATT patients were medication free (p=0.06). The number of glaucoma medications was 0.9±1.3 in the ABiC group and 0.6±1.2 in the GATT group (p=0.27). The 12-month cumulative rate of complete surgical success was 56% in the ABiC group and 75% in the GATT group (p=0.09). Three eyes in the ABiC group and one eye in the GATT group required additional glaucoma surgery. Hyphema (87% vs 47%) and supraciliary effusion (92% vs 71%) were noted more often in the GATT group than in the ABiC group. Conclusions The preliminary result showed that GATT had an advantage over ABiC in IOP reduction for OAG patients, accompanied by favourable safety at 12-month postoperatively. Trial registration number ChiCTR1800016933.

Takotsubo cardiomyopathy (TTC) causes sudden cardiac death and has garnered increased attention worldwide in recent years. However, few studies have clearly classified the risk factors for this disease, including gender, race and morbidity, as well as the physical and mental stressors that can exacerbate the disease, particularly in young patients. To better analyze the characteristics of young TTC patients, we performed a systematic review of reported cases involving young patients.A computer-assisted search was performed using prominent electronic medical information sources to identify literature published between January 1965 and December 2013. Relevant studies containing clinical data of young TTC patients were included.Ninety-six records that included information about 104 cases were ultimately selected for our review. Several of the following results were noted: First, physical stress was more likely to exacerbate TTC than was mental stress in young patients. Second, more female than male TTC patients were noted among both young patients and the general population. Third, ethnicity appears to play no role in the disease, as no significant differences were noted among individuals of different races with respect to clinical characteristics, morbidity or stressors. Fourth, the clinical manifestations of TTC were similar to those of other cardiac diseases, including coronary heart disease. However, TTC may be detected using the combination of echocardiography and ventriculography.Clinicians should consider TTC if young patients present with symptoms similar to those of coronary heart disease so that harmful treatments such as coronary artery stent placement may be avoided. Moreover, the answers to questions regarding the clinical diagnostic criteria, etiology, pathophysiology, and the management of this syndrome in youth remain unclear; therefore, further research is needed.

(1) Background: To investigate the value of pulsatile trabecular meshwork (TM) motion in predicting the diurnal intraocular pressure (IOP) fluctuation of primary open-angle glaucoma (POAG). (2) Methods: This cross-sectional study recruited 20 normal patients and 30 patients with POAG. Of the POAG group, 20 had stable diurnal IOP and 10 had high IOP fluctuation. A clinical prototype phase-sensitive optical coherence tomography (PhS-OCT) model was used to measure TM pulsatile motion with maximum velocity (MV) and cumulative displacement (CDisp). (3) Results: MV and CDisp were higher in the external region in both normal and POAG patients. All MV and CDisp reduced significantly in the POAG group (p < 0.001). In the POAG group, except MV in the external region (p = 0.085), MV and CDisp in the nasal area were significantly higher than those in the temporal area (p < 0.05). The MV and CDisp in the external region in the nasal area of POAG patients with high IOP fluctuation were much lower than those with stable IOP (p_EMV3 = 0.031, p_ECDisp3 < 0.001); (4) Conclusions: Pulsatile TM motion reduced in POAG patients relevant to the level of diurnal IOP fluctuation. This study presents the segmental variance of TM stiffness in human living eyes and suggests the clinical potential of the measurement of pulsatile TM motion with PhS-OCT for the evaluation of diurnal IOP fluctuation.

Herein, we provide evidence that human regulation of aqueous outflow is by a pump-conduit system similar to that of the lymphatics. Direct observation documents pulsatile aqueous flow into Schlemm’s canal and from the canal into collector channels, intrascleral channels, aqueous veins, and episcleral veins. Pulsatile flow in vessels requires a driving force, a chamber with mobile walls and valves. We demonstrate that the trabecular meshwork acts as a deformable, mobile wall of a chamber: Schlemm’s canal. A tight linkage between the driving force of intraocular pressure and meshwork deformation causes tissue responses in milliseconds. The link provides a sensory-motor baroreceptor-like function, providing maintenance of a homeostatic setpoint. The ocular pulse causes meshwork motion oscillations around the setpoint. We document valves entering and exiting the canal using real-time direct observation with a microscope and multiple additional modalities. Our laboratory-based high-resolution SD-OCT platform quantifies valve lumen opening and closing within milliseconds synchronously with meshwork motion; meshwork tissue stiffens, and movement slows in glaucoma tissue. Our novel PhS-OCT system measures nanometer-level motion synchronous with the ocular pulse in human subjects. Movement decreases in glaucoma patients. Our model is robust because it anchors laboratory studies to direct observation of physical reality in humans with glaucoma.