Evidence for Menopause as a Sex-Specific Risk Factor for Glaucoma

Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive loss of visual function and retinal ganglion cells (RGC). Current epidemiological, clinical, and basic science evidence suggest that estrogen plays a role in the aging of the optic nerve. Menopause, a major biological life event affecting all women, coincides with a decrease in circulating sex hormones, such as estrogen. While 59% of the glaucomatous population are females, sex is not considered a risk factor for developing glaucoma. In this review, we explore whether menopause is a sex-specific risk factor for glaucoma. First, we investigate how menopause is defined as a sex-specific risk factor for other pathologies, including cardiovascular disease, osteoarthritis, and bone health. Next, we discuss clinical evidence that highlights the potential role of menopause in glaucoma. We also highlight preclinical studies that demonstrate larger vision and RGC loss following surgical menopause and how estrogen is protective in models of RGC injury. Lastly, we explore how surgical menopause and estrogen signaling are related to risk factors associated with developing glaucoma (e.g., intraocular pressure, aqueous outflow resistance, and ocular biomechanics). We hypothesize that menopause potentially sets the stage to develop glaucoma and therefore is a sex-specific risk factor for this disease. Graphical Abstract

Progression from Ocular Hypertension into Glaucoma

Ocular hypertension (OHT) is characterized by raised intraocular pressure (IOP) >21 mmHg without any visual field (functional) or optic nerve (structural) defect featuring glaucoma. Raised IOP is a major risk factor of glaucoma and a proportion of eyes with OHT progresses into primary open angle glaucoma. Glaucoma is a debilitating disease with potential for blindness if left untreated and associated reduction in the quality of life of the affected individual. It is challenging for the clinicians to decide whether an OHT will progress into glaucoma or not based on the risk factor model of the Ocular hypertension treatment study. Moreover, the question whether only IOP or a myriad of factors like central corneal thickness, baseline IOP, visual field, family history of glaucoma, ocular biomechanics are all important in determining the progression is yet to be answered. The rate of progression is also important and needs analysis for further discussion. Summarizing the landmark studies on ocular hypertension and glaucoma to date are imperative in this regard. This chapter presents the overview of OHT and its possible etiology and pathophysiology, risk factors, clinical tests evaluating OHT eyes and elaborates on the progression of OHT to glaucoma over time in relation to the treatment.

Experimental Assessment of the Spatial and Temporal Distribution of Non-Contact Tonometer Airflows

(1) The aim of the study was to investigate the spatial and temporal characteristics of the airflow created by two commercially available non-contact tonometers: the CorvisST and the Ocular Response Analyser (ORA). (2) The airflow pressure was measured using a microelectromechanical system (MEMS) pressure sensor to investigate the spatial and temporal distribution. The airflow from the CorvisST and Ocular Response Analyser were mapped to a 600 µm and a 1 mm resolution grid, respectively. (3) Central airflow pressure of the CorvisST (96.4 ± 1.4 mmHg) was higher than that of the Ocular Response Analyser (91.7 ± 0.7 mmHg). The duration of the air-puffs also differed, with the CorvisST showing a shorter duration (21.483 ± 0.2881 ms) than that of the ORA (23.061 ± 0.1872 ms). The rising edge of the CorvisST airflow pressure profile demonstrated a lower gradient (+8.94 mmHg/ms) compared to that of the Ocular Response Analyser (+11.00 mmHg/ms). Both had similar decay response edges: CorvisST −11.18 mmHg/ms, Ocular Response Analyser −11.65 mmHg/ms. (4) The study presents a valid method to investigate the physical dimensions of the airflow pressure of non-contact tonometers. Novel findings relating to the magnitude, duration and spatial characteristics of the respective airflow pressures are reported. It is anticipated that this information will better inform clinical studies and theoretical models relating to ocular biomechanics.

Experimental Assessment of the Spatial and Temporal Distribu-Tion of Non-contact Tonometer Airflows

(1) Aim of the study was to investigate the spatial and temporal characteristics of the airflow created by two commercially available non-contact tonometers, the CorvisST and the Ocular Re-sponse Analyser. (2) The airflow pressure was measured using a MEMS pressure sensor to inves-tigate the spatial and temporal distribution. The airflow from the CorvisST and Ocular Response Analyser were mapped to a 600µm and a 1mm resolution grid, respectively. (3) Central airflow pressure of the CorvisST (96.4 ± 1.4)mmHg was higher than the Ocular Response Analyser (91.7 ± 0.7)mmHg. The duration of the air-puffs also differed, with the CorvisST showing a shorter du-ration (21.483 ± 0.2881)ms than the ORA (23.061 ± 0.1872)ms. The rising edge of the CorvisST airflow pressure profile demonstrated a lower gradient (+8.94mmHg/ms) compared to the Oc-ular Response Analyser (+11.00mmHg/ms). Both had similar decay response edges; CorvisST -11.18mmHg/ms, Ocular Response Analyser -11.65mmHg/ms. (4) The study presents a valid method to investigate physical dimensions of the airflow pressure of non-contact tonometers. Novel findings relating to the magnitude, duration and spatial characteristics of the respective airflow pressures are reported. It is anticipated that this information will better inform clinical studies and theoretical models relating to ocular biomechanics.