Remodeling of the Lamina Cribrosa: Mechanisms and Potential Therapeutic Approaches for Glaucoma.

Glaucomatous optic neuropathy is the leading cause of irreversible blindness in the world. The chronic disease is characterized by optic nerve degeneration and vision field loss. The reduction of intraocular pressure remains the only proven glaucoma treatment, but it does not prevent further neurodegeneration. There are three major classes of cells in the human optic nerve head (ONH): lamina cribrosa (LC) cells, glial cells, and scleral fibroblasts. These cells provide support for the LC which is essential to maintain healthy retinal ganglion cell (RGC) axons. All these cells demonstrate responses to glaucomatous conditions through extracellular matrix remodeling. Therefore, investigations into alternative therapies that alter the characteristic remodeling response of the ONH to enhance the survival of RGC axons are prevalent. Understanding major remodeling pathways in the ONH may be key to developing targeted therapies that reduce deleterious remodeling.

A Novel Tree Shrew (Tupaia belangeri) Model of Glaucoma.

Purpose: Primates and rodents are used widely as animal models of glaucoma, but each has significant limitations. Researchers need additional animal models that closely resemble the relevant anatomy and pathologic features of the human disease to more quickly advance research. We validate a novel glaucoma animal model in tree shrews (Tupaia belangeri). Methods: Experimental glaucoma was induced in adult tree shrews (n = 8) by injecting 50 µL of a 25 mg/mL ferromagnetic bead solution into the anterior chamber. Beads were directed into the iridocorneal angle with a magnet to impede aqueous outflow. Animals were followed for 3 months with weekly IOP measurements and biweekly spectral domain optical coherence tomography (SD-OCT) images of the optic nerve head. Histopathology of the optic nerve and optic nerve axon counts were completed at the end of the study. Results: The 12-week average mean IOP was 22.7 ± 3.6 and 8.6 ± 2.9 mm Hg in the treated and control eyes, respectively. Longitudinal analysis showed significant retinal nerve fiber layer (RNFL) thinning throughout the study. Axon counts were significantly reduced (59.7%) in treated versus control eyes. SD-OCT imaging showed cupping and posterior displacement of the lamina cribrosa in glaucomatous eyes. RNFL thickness and optic nerve axon counts were reduced consistent with IOP elevation. Optic nerves demonstrated histopathology consistent with glaucomatous optic neuropathy. Conclusions: Tree shrews with experimental glaucoma show key pathologic characteristics of the human disease. The tree shrew model of glaucoma has the potential to help researchers accelerate our understanding of glaucoma pathophysiology.

Lamina cribrosa in glaucoma.

PURPOSE OF REVIEW: This article presents, summarizes, and interprets the most recent advances in the study and understanding of the lamina cribrosa in glaucoma, in the context of previous work. RECENT FINDINGS: The lamina is an active living structure that responds to strain by changing morphology at the micro-scale and macro-scale in glaucoma. Changes in lamina cribrosa morphology in glaucoma include posteriorization of the laminar insertion into the sclera, increased cupping or depth of the lamina cribrosa, and the development of focal lamina cribrosa defects. These lamina cribrosa changes are associated with disk hemorrhages and visual field damage, and are detectable with clinical imaging techniques such as optical coherence tomography. Glaucomatous changes in the lamina cribrosa are thought to be driven by cellular processes mediated by focal cyclical mechanical strain. Strain is eye specific and mediated by intraocular pressure, cerebrospinal fluid pressure, scleral and lamina cribrosa morphology, and structural stiffness; deleterious lamina cribrosa strains can occur at all levels of mean intraocular pressure. SUMMARY: Laminar morphology is ever changing in health and disease, and recent studies have identified several promising morphological changes that are indicative of glaucoma susceptibility, onset, and progression.

The association between self-reported glaucoma and ginkgo biloba use.

PURPOSE: To assess the association between Ginkgo biloba extract (GBE) use and glaucoma. METHODS: Self-reported data on the past 12 months of GBE use and the presence of glaucoma were obtained from the 2002 National Health Interview Survey, a nationally-representative population-based sample. Crude and adjusted associations between GBE use and glaucoma were estimated. RESULTS: Those who reported having glaucoma were 26% less likely to report GBE use; however, this was not statistically significant. After adjustment for potentially confounding demographic and medical characteristics, there was no difference in GBE use among those who did and did not report having glaucoma. CONCLUSIONS: The results of this study fail to support a significant relationship between GBE use over the past 12 months and having glaucoma, though this finding requires replication in a prospective study. Moreover, whether GBE is efficacious in treating glaucoma patients remains an issue for future research.

Environmental tilt illusion as the only symptom of a thalamic astrocytoma.

A 14-year-old girl experienced two episodes of environmental tilt illusion. During both episodes, which lasted less than 1 minute, she perceived all objects within view as rotated 45 degrees clockwise. There were no auras, accompanying symptoms, or sequelae. Neuro-ophthalmic examination findings were normal except for a right relative afferent pupil defect (RAPD). Imaging disclosed a cystic mass in the left posterior thalamus with compression of the brachium of the left superior colliculus. Stereotactic biopsy revealed a pilocytic astrocytoma. This is the first case documenting environmental tilt illusion as an isolated symptom of a thalamic lesion. Disruption of vestibular connections between the posterior thalamus and the posterior parietal cortex may be the cause of this visual perceptive disorder.