Imaging of the Lamina Cribrosa using Swept-Source Optical Coherence Tomography.

The lamina cribrosa (LC) is the presumed site of axonal injury in glaucoma. Its deformation has been suggested to contribute to optic neuropathy by impeding axoplasmic flow within the optic nerve fibers, leading to apoptosis of retinal ganglion cells. To visualize the LC in vivo, optical coherence tomography (OCT) has been applied. Spectral domain (SD)-OCT, used in conjunction with recently introduced enhanced depth imaging (EDI)-OCT, has improved visualization of deeper ocular layers, but in many individuals it is still limited by inadequate resolution, poor image contrast and insufficient depth penetrance. The posterior laminar surface especially is not viewed clearly using these methods. New generation high-penetration (HP)-OCTs, also known as swept-source (SS)-OCT, are capable to evaluate the choroid in vivo to a remarkable level of detail. SS-OCTs use a longer wavelength (1,050 nm instead of 840 nm) compared to the conventional techniques. We review current knowledge of the LC, findings from trials that use SD-OCT and EDI-OCT, and our experience with a prototype SS-OCT to visualize the LC in its entirety. Key Points What is known? •     The LC is the presumed site of axonal injury in glaucoma •     Compared to spectral domain-OCT, enhanced depth imaging-OCT improves imaging of the LC •     Even so, currently used SD-OCT techniques are restricted by poor wavelength penetrance of the deeper ocular layers What our findings add? •    SS-OCT may be a superior imaging modality for deep ocular structures •    Prior studies used SS-OCT to evaluate choroidal thickness in both healthy and 'normal tension glaucoma' eyes •    SS-OCT enables good evaluation of three-dimension (3D) lamina cribrosa morphology. How to cite this article: Nuyen B, Mansouri K, Weinreb RN. Imaging of the Lamina Cribrosa using Swept-Source Optical Coherence Tomography. J Current Glau Prac 2012;6(3): 113-119

Aqueous Humor Outflow Structure and Function Imaging At the Bench and Bedside: A Review.

Anterior segment glaucoma clinical care and research has recently gained new focus because of novel imaging modalities and the advent of angle-based surgical treatments. Traditional investigation drawn to the trabecular meshwork now emphasizes the entire conventional aqueous humor outflow (AHO) pathway from the anterior chamber to the episcleral vein. AHO investigation can be divided into structural and functional assessments using different methods. The historical basis for studying the anterior segment of the eye and AHO in glaucoma is discussed. Structural studies of AHO are reviewed and include traditional pathological approaches to modern tools such as multi-model two-photon microscopy and optical coherence tomography. Functional assessment focuses on visualizing AHO itself through a variety of non-real-time and real-time techniques such as aqueous angiography. Implications of distal outflow resistance and segmental AHO are discussed with an emphasis on melding bench-side research to viable clinical applications. Through the development of an improved structure: function relationship for AHO in the anterior segment of the normal and diseased eye, a better understanding of the eye with improved therapeutics may be developed

Current Knowledge and Attitudes Concerning Cost-Effectiveness in Glaucoma Pharmacotherapy: A Glaucoma Specialists Focus Group Study.

Background:Rising healthcare costs motivate continued cost-reduction efforts. To help lower costs associated with open-angle glaucoma (OAG), a prevalent, progressive disease with substantial direct and indirect costs, clinicians need to understand the cost-effectiveness of intraocular pressure (IOP)-lowering pharmacotherapies. There is little published information on clinicians' knowledge and attitudes about cost-effectiveness in glaucoma treatment. Purpose:This pilot focus group study aimed to explore clinician attitudes and perspectives around the costs and cost drivers of glaucoma therapy; the implementation of cost-effectiveness decisions; the clinical utility of cost-effectiveness studies; and the cost-effectiveness of available treatments. Methods:Six US glaucoma specialists participated in two separate teleconferencing sessions (three participants each), managed by an independent, skilled moderator (also a glaucoma specialist) using a discussion guide. Participants reviewed recent publications (n=25) on health economics outcomes research in glaucoma prior to the sessions. Results:Participants demonstrated a clear understanding of the economic burden of glaucoma therapy and identified medications, diagnostics, office visits, and treatment changes as key cost drivers. They considered cost-effectiveness an appropriate component of treatment decision-making but identified the need for additional data to inform these decisions. Participants indicated that there were only a few recent studies on health economics outcomes in glaucoma which evaluate parameters important to patient care, such as quality of life and medication adherence, and that longitudinal data were scant. In addition to efficacy, participants felt patient adherence and side-effect profile should be included in economic evaluations of glaucoma pharmacotherapy. Recently approved medications were evaluated in this context. Conclusion:Clinicians deem treatment decisions based on cost-effectiveness data as clinically appropriate. Newer IOP-lowering therapies with potentially greater efficacy and favorable side-effect and adherence profiles may help optimize cost-effectiveness. Future studies should include: clinicians' perspectives; lack of commercial bias; analysis of long-term outcomes/costs; more comprehensive parameters; real-world (including quality-of-life) data; and a robust Markov model

Risk Assessment for Glaucoma

Glaucoma is undergoing a paradigm shift and transitioning from merely disease staging to evidence-based risk assessment of in the individual patient

Rapid and Accurate Pressure Sensing Device for Direct Measurement of Intraocular Pressure.

PurposeIntraocular pressure (IOP) is the primary modifiable risk factor for glaucoma. Current devices measure IOP via the dynamic response of the healthy cornea and do not provide the accurate IOP measurements for patients with altered corneal biomechanics. We seek to develop and test an accurate needle-based IOP measurement device that is not cornea dependent.MethodsOur device combines a high-resolution pressure microsensor with 30- and 33-gauge Luer lock needles to provide IOP measurements via a microcontroller and USB interface to a computer. The device was calibrated in a membrane chamber and then tested and validated in the anterior chamber and post-vitrectomy vitreous chamber of rabbit eyes. The results were compared to Tonopen readings across a pressure range of 0 to 100 mm Hg, imposed in increments of 10 mm Hg.ResultsBoth the needle based sensor device and the Tonopen demonstrated a linear relationship with changes in imposed pressure. The Tonopen was found to consistently underestimate the IOP both in the anterior and vitreous chambers. The Tonopen exhibited a significantly greater error than our needle-based sensor device. With increased pressure (>30 mm Hg), the error of the Tonopen increased, whereas the error of our device did not. The 30-gauge needle produces an insignificant improvement in accuracy over the 33-gauge needle.ConclusionsA needle-based sensor device enables accurate IOP measurements over a broad range of induced IOP.Translational relevanceDirect measurement of IOP in the anterior chamber circumvents the influence of corneal parameters on IOP measurement

Matrix Metalloproteinases and Glaucoma Treatment.

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade extracellular matrix (ECM) components such as collagen and have important roles in multiple biological processes, including development and tissue remodeling, both in health and disease. The activity of MMPs is influenced by the expression of MMPs and tissue inhibitors of metalloproteinase (TIMPs). In the eye, MMP-mediated ECM turnover in the juxtacanalicular region of the trabecular meshwork (TM) reduces outflow resistance in the conventional outflow pathway and helps maintain intraocular pressure (IOP) homeostasis. An imbalance in the MMP/TIMP ratio may be involved in the elevated IOP often associated with glaucoma. The prostaglandin analog/prostamide (PGA) class of topical ocular hypotensive medications used in glaucoma treatment reduces IOP by increasing outflow through both conventional and unconventional (uveoscleral) outflow pathways. Evidence from in vivo and in vitro studies using animal models and anterior segment explant and cell cultures indicates that the mechanism of IOP lowering by PGAs involves increased MMP expression in the TM and ciliary body, leading to tissue remodeling that enhances conventional and unconventional outflow. PGA effects on MMP expression are dependent on the identity and concentration of the PGA. An intracameral sustained-release PGA implant (Bimatoprost SR) in development for glaucoma treatment can reduce IOP for many months after expected intraocular drug bioavailability. We hypothesize that the higher concentrations of bimatoprost achieved in ocular outflow tissues with the implant produce greater MMP upregulation and more extensive, sustained MMP-mediated target tissue remodeling, providing an extended duration of effect

Estimating the Risk of Developing Glaucoma

The issue of risk assessment in glaucoma has received increasing attention in the past few years since the publication of results from the Ocular Hypertension Treatment Study. Predictive models have been developed in order to estimate the risk that patients with ocular hypertension will develop glaucoma if left untreated. The purpose of this article is to review issues on the development and validation of predictive models to estimate risk of glaucoma development. Current models are reviewed and details about their development and validation are provided

Latanoprost with high precision, piezo-print microdose delivery for IOP lowering: clinical results of the PG21 study of 0.4 µg daily microdose.

Background:Topical high-precision piezo-print delivery of microdoses of latanoprost achieved significant IOP reduction consistent with the eyedropper effect but with a 75% reduced exposure to drugs and preservatives. Prostaglandin analogs are a mainstay glaucoma therapy. However, conventional eyedroppers deliver 30-50 µL drops that greatly exceed the physiologic 7-µL ocular tear film capacity. Eyedropper overdosing floods the eye with excess drug compounds and preservatives, resulting in ocular surface toxicity, periorbitopathy, and other well-characterized ocular side effects. Piezoelectric high-precision microdosing provides targeted delivery that can reduce exposure to both drug and preservatives compared to conventional eyedropper delivery, with the potential to deliver similar biologic effect. Methods:Both eyes (N=60) of 30 healthy volunteers received single 8-µL microdoses of 0.005% latanoprost (0.4 µg; µRx-latanoprost) on the morning of Days 1 and 2 using a high-precision, piezo-print horizontal delivery system. Diurnal IOP was measured before and 2 days after microdosing. Main efficacy outcomes were diurnal IOP change after µRx-latanoprost microdosing and accurate microdosing success rates, and the primary safety outcome was adverse event (AE) incidence. Results:µRx-latanoprost reduced baseline IOP by 26% and 30% at 1 and 2 days postadministration, respectively. Successful topical dosing was achieved in 100% of technician-assisted deliveries. All patients successfully self-administered microdoses after receiving training. Microdose administration was well tolerated and did not result in any AEs. Conclusion:Microdosing of 0.4 µg of µRx-latanoprost achieved significant IOP reduction. Lower ocular exposure with topical prostaglandin analog microdosing can enable new therapeutic opportunities for optimizing glaucoma treatment. Microdosing may also be beneficial in reducing ocular side effects associated with excessive drug product and preservatives often used to treat chronic ocular diseases such as glaucoma

Canaloplasty in the Treatment of Open-Angle Glaucoma: A Review of Patient Selection and Outcomes.

Canaloplasty is a relatively new non-penetrating surgery for the reduction of intraocular pressure in patients affected by glaucoma. The technique uses a microcatheter to perform a 360 º cannulation of Schlemm's canal and leaves in place a tension suture providing an inward distension. It aims to restore the physiological outflow pathways of the aqueous humour and is independent of external wound healing. Several studies have shown that canaloplasty is effective in reducing intraocular pressure and has a low rate of complications, especially compared with trabeculectomy, the gold standard for glaucoma surgery. Currently, canaloplasty is indicated in patients with open-angle glaucoma, having a mild to moderate disease, and the combination with cataract phacoemulsification may provide further intraocular pressure reduction. This article reviews canaloplasty indications, results and complications and analyses its outcomes compared with traditional penetrating and non-penetrating techniques

Angle stability and outflow in dual blade ab interno trabeculectomy with active versus passive chamber management.

PurposeTo compare intraoperative angle stability and postoperative outflow of two ab interno trabeculectomy devices that excise the trabecular meshwork with or without active aspiration and irrigation. We hypothesized that anterior segment optical coherence tomography (AS-OCT) allows for a quantitative comparison of intraoperative angle stability in a microincisional glaucoma surgery (MIGS) pig eye training model.MethodsTwelve freshly enucleated porcine eyes were measured with AS-OCT at baseline, at the beginning of the procedure and at its conclusion to determine the anterior chamber depth (ACD) and the nasal angle α in degrees. The right and left eye of pairs were randomly assigned to an active dual blade goniectome (aDBG) and a passive dual blade goniectome (pDBG) group, respectively. The aDBG had irrigation and aspiration ports while the pDBG required surgery under viscoelastic. We performed the procedures using our MIGS training system with a standard, motorized ophthalmic operating microscope. We estimated outflow by obtaining canalograms with fluorescent spheres.ResultsIn aDBG, the nasal angle remained wide open during the procedure at above 90° and did not change towards the end (100±10%, p = 0.9). In contrast, in pDBG, ACD decreased by 51±19% to 21% below baseline (p<0.01) while the angle progressively narrowed by 40±12% (p<0.001). Canalograms showed a similar extent of access to the outflow tract with the aDBG and the pDBG (p = 0.513). The average increase for the aDBG in the superonasal and inferonasal quadrants was between 27 to 31% and for the pDBG between 15 to 18%.ConclusionAS-OCT demonstrated that active irrigation and aspiration improved anterior chamber maintenance and ease of handling with the aDBG in this MIGS training model. The immediate postoperative outflow was equally good with both devices