Aging Effects on Optic Nerve Neurodegeneration.

Common risk factors for many ocular pathologies involve non-pathologic, age-related damage to the optic nerve. Understanding the mechanisms of age-related changes can facilitate targeted treatments for ocular pathologies that arise at any point in life. In this review, we examine these age-related, neurodegenerative changes in the optic nerve, contextualize these changes from the anatomic to the molecular level, and appreciate their relationship with ocular pathophysiology. From simple structural and mechanical changes at the optic nerve head (ONH), to epigenetic and biochemical alterations of tissue and the environment, multiple age-dependent mechanisms drive extracellular matrix (ECM) remodeling, retinal ganglion cell (RGC) loss, and lowered regenerative ability of respective axons. In conjunction, aging decreases the ability of myelin to preserve maximal conductivity, even with "successfully" regenerated axons. Glial cells, however, regeneratively overcompensate and result in a microenvironment that promotes RGC axonal death. Better elucidating optic nerve neurodegeneration remains of interest, specifically investigating human ECM, RGCs, axons, oligodendrocytes, and astrocytes; clarifying the exact processes of aged ocular connective tissue alterations and their ultrastructural impacts; and developing novel technologies and pharmacotherapies that target known genetic, biochemical, matrisome, and neuroinflammatory markers. Management models should account for age-related changes when addressing glaucoma, diabetic retinopathy, and other blinding diseases.

The Short-term Effects of Artificial Tears on the Tear Film Assessed by a Novel High-Resolution Tear Film Imager: A Pilot Study.

PURPOSE: The purpose of this study was to investigate the effects of artificial tears (AT) on the sublayers of the tear film assessed by a novel tear film imaging (TFI) device. METHODS: The mucoaqueous layer thickness (MALT) and lipid layer thickness (LLT) of 198 images from 11 healthy participants, 9 of whom had meibomian gland disease, were prospectively measured before and after exposure to 3 different AT preparations (Refresh Plus; Retaine [RTA]; Systane Complete PF [SYS]), using a novel nanometer resolution TFI device (AdOM, Israel). Participants were assessed at baseline and at 1, 5, 10, 30, and 60 minutes after instilling 1 drop of AT during 3 sessions on separate days. Repeated-measures analysis of variances were used for comparisons with P < 0.05 considered significant. RESULTS: For all ATs, the mean MALT was greatest 1 minute after drop instillation, with an increase of 67%, 55%, and 11% above the baseline for SYS, Refresh Plus, and RTA, respectively. The SYS formulation demonstrated the highest percentage increases in mean MALT and LLT at most postdrop time points. The MALT differences were significantly higher in the SYS than in the RTA (P = 0.014). After 60 minutes, no AT group demonstrated statistically significant changes in MALT or LLT compared with baseline. CONCLUSIONS: We report, for the first time, the effects of AT on MALT and LLT using a high-resolution TFI. A substantial acute mean MALT increase occurs 1 minute after AT instillation with all agents tested, but there were clear differences in response and durability, suggesting the benefits of choosing specific AT according to the needs of each patient.

Metabolic blood flow regulation in a hybrid model of the human retinal microcirculation.

The retinal vascular network supplies perfusion to vital visual structures, including retinal ganglion cells responsible for vision. Impairments in retinal blood flow and oxygenation are involved in the progression of many ocular diseases, including glaucoma. In this study, an established theoretical hybrid model of a retinal microvascular network is extended to include the effects of local blood flow regulation on oxygenation. A heterogeneous representation of the arterioles based on confocal microscopy images is combined with a compartmental description of the downstream capillaries and venules. A Green's function method is used to simulate oxygen transport in the arterioles, and a Krogh cylinder model is applied to the capillary and venular compartments. Acute blood flow regulation is simulated in response to changes in pressure, shear stress, and metabolism. Model results predict that both increased intraocular pressure and impairment of blood flow regulation can cause decreased tissue oxygenation, indicating that both mechanisms represent factors that could lead to impaired oxygenation characteristic of ocular disease. Results also indicate that the metabolic response mechanism reduces the fraction of poorly oxygenated tissue but that the pressure- and shear stress-dependent response mechanisms may hinder the vascular response to changes in oxygenation. Importantly, the heterogeneity of the vascular network demonstrates that traditionally reported average values of tissue oxygen levels hide significant localized defects in tissue oxygenation that may be involved in disease processes, including glaucoma. Ultimately, the model framework presented in this study will facilitate future comparisons to sectorial-specific clinical data to better assess the role of impaired blood flow regulation in ocular disease.

Changes in Macular Thickness after Cataract Surgery in Patients with Open Angle Glaucoma.

BACKGROUND: The purpose of this study was to examine the changes in IOP, total macular and RNFL, ganglion cell layer (GCL) thickness, and aqueous humour flare in open angle glaucoma (OAG) patients before and 6 months after cataract surgery. METHODS: This was a prospective observational case-control age- and gender-matched study. Groups: 40 subjects in a controlled OAG (OAGc) group, 20 subjects in an uncontrolled OAG (OAGu) group, and 60 control group subjects. EXAMINATION: complete ophthalmic evaluation, IOP measurement, anterior and posterior segment Optical Coherence Tomography (OCT), and laser flare photometry before and 6 months postoperatively. RESULTS: Six months postoperatively IOP decreased in all groups. An increase in macular thickness was found postoperatively in all groups. Preoperative aqueous humour flare was higher in the OAGc group than in the control group. After cataract surgery, aqueous humour flare was higher in the control group compared to the preoperative result. CONCLUSIONS: Changes in IOP following cataract surgery were strongly negatively correlated with preoperative IOP. An increase in macular thickness was observed 6 months postoperatively in all groups. Aqueous humour flare did not differ in OAGc and OAGu groups pre- and postoperatively but significantly increased in the control group postoperatively.

The role of conventional and unconventional adaptive routes in lowering of intraocular pressure: Theoretical model and simulation.

In this article, we propose a theoretical model leveraging the analogy between fluid and electric variables to investigate the relation among aqueous humor (AH) circulation and drainage and intraocular pressure (IOP), the principal established risk factor of severe neuropathologies of the optic nerve such as glaucoma. IOP is the steady-state result of the balance among AH secretion (AHs), circulation (AHc), and drainage (AHd). AHs are modeled as a given volumetric flow rate electrically corresponding to an input current source. AHc is modeled by the series of two linear hydraulic conductances (HCs) representing the posterior and anterior chambers. AHd is modeled by the parallel of three HCs: a linear HC for the conventional adaptive route (ConvAR), a nonlinear HC for the hydraulic component of the unconventional adaptive route (UncAR), and a nonlinear HC for the drug-dependent component of the UncAR. The proposed model is implemented in a computational virtual laboratory to study the value attained by the IOP under physiological and pathological conditions. Simulation results (i) confirm the conjecture that the UncAR acts as a relief valve under pathological conditions, (ii) indicate that the drug-dependent AR is the major opponent to IOP increase in the case of elevated trabecular meshwork resistance, and (iii) support the use of the model as a quantitative tool to complement in vivo studies and help design and optimize medications for ocular diseases.

Artificial Intelligence to Aid Glaucoma Diagnosis and Monitoring: State of the Art and New Directions.

Recent developments in the use of artificial intelligence in the diagnosis and monitoring of glaucoma are discussed. To set the context and fix terminology, a brief historic overview of artificial intelligence is provided, along with some fundamentals of statistical modeling. Next, recent applications of artificial intelligence techniques in glaucoma diagnosis and the monitoring of glaucoma progression are reviewed, including the classification of visual field images and the detection of glaucomatous change in retinal nerve fiber layer thickness. Current challenges in the direct application of artificial intelligence to further our understating of this disease are also outlined. The article also discusses how the combined use of mathematical modeling and artificial intelligence may help to address these challenges, along with stronger communication between data scientists and clinicians.

Tear Film, Conjunctival and Corneal Modifications Induced by Glaucoma Treatment.

Ocular surface disease is characterized by tear film instability and histopathologic and clinical changes of the ocular surface. Glaucoma patients often suffer from ocular surface disease caused by the chronic use of preserved medical treatment to reduce intraocular pressure. Benzalkonium chloride is the preservative most frequently used in glaucoma medications. Its effect on tear film, conjunctiva and cornea and the consequences in glaucoma management are discussed in this mini-review.