Clinical efficacy and neuroprotective effects of brimonidine in the management of glaucoma and ocular hypertension

Elevated intraocular pressure (IOP) is a significant risk factor for the development and progression of glaucomatous optic neuropathy, but increasingly we appreciate that non-pressure dependent factors, are key to our understanding of the pathophysiology of these neurodegenerative diseases, that target the retinal ganglion cell. As we try to expand therapy beyond IOP control, medications are being assessed for their neuroprotective abilities. Brimonidine is an effective ocular hypotensive treatment both as a first and second line agent, in the management of glaucoma and ocular hypertension. Brimonidine tartrate 0.2% is generally safe and well tolerated, with its safety profile further enhanced in the altered formulation brimonidine-Purite™ 0.1%. Beyond brimonidine’s pressure lowering capacity, laboratory and early clinical evidence supports its neuroprotective potential. We await validation of this in human clinical trials

An Intraocular Pressure Polygenic Risk Score Stratifies Multiple Primary Open-Angle Glaucoma Parameters Including Treatment Intensity

Purpose: To examine the combined effects of common genetic variants associated with intraocular pressure (IOP) on primary open-angle glaucoma (POAG) phenotype using a polygenic risk score (PRS) stratification. Design: Cross-sectional study. Participants: For the primary analysis, we examined the glaucoma phenotype of 2154 POAG patients enrolled in the Australian and New Zealand Registry of Advanced Glaucoma, including patients recruited from the United Kingdom. For replication, we examined an independent cohort of 624 early POAG patients. Methods Using IOP genome-wide association study summary statistics, we developed a PRS derived solely from IOP-associated variants and stratified POAG patients into 3 risk tiers. The lowest and highest quintiles of the score were set as the low- and high-risk groups, respectively, and the other quintiles were set as the intermediate risk group. Main Outcome Measures: Clinical glaucoma phenotype including maximum recorded IOP, age at diagnosis, number of family members affected by glaucoma, cup-to-disc ratio, visual field mean deviation, and treatment intensity. Results: A dose–response relationship was found between the IOP PRS and the maximum recorded IOP, with the high genetic risk group having a higher maximum IOP by 1.7 mmHg (standard deviation [SD], 0.62 mmHg) than the low genetic risk group (P = 0.006). Compared with the low genetic risk group, the high genetic risk group had a younger age of diagnosis by 3.7 years (SD, 1.0 years; P < 0.001), more family members affected by 0.46 members (SD, 0.11 members; P < 0.001), and higher rates of incisional surgery (odds ratio, 1.5; 95% confidence interval, 1.1–2.0; P = 0.007). No statistically significant difference was found in mean deviation. We further replicated the maximum IOP, number of family members affected by glaucoma, and treatment intensity (number of medications) results in the early POAG cohort (P ≤ 0.01). Conclusions: The IOP PRS was correlated positively with maximum IOP, disease severity, need for surgery, and number of affected family members. Genes acting via IOP-mediated pathways, when considered in aggregate, have clinically important and reproducible implications for glaucoma patients and their close family members

Prevalence and type of artefact with spectral domain optical coherence tomography macular ganglion cell imaging in glaucoma surveillance

PURPOSE:The ganglion cell analysis (GCA) of the CIRRUSTM HD-OCT (Carl Zeiss, Meditec; Dublin, CA) provides measurement of the macular ganglion cell-inner plexiform layer (GCIPL) thickness. This study determined the frequency of scan artefacts and errors in GCIPL imaging in individuals undergoing HD-OCT surveillance for glaucoma. METHOD:A total of 1439 eyes from 721 subjects enrolled in a prospective study assessing predictors of glaucoma progression underwent macular GCIPL imaging with the CIRRUS HD-OCT at recruitment. The prevalence of acquisition errors, segmentation errors, and co-morbid macular pathology was determined. RESULTS:A total of 87 (6.0%) of the 1439 scans had either acquisition errors, segmentation artefacts, or other macular pathology. The most common co-morbid macular pathology was epiretinal membrane in 2.2% of eyes. CONCLUSION:The macular GCIPL scan was artefact free in 94% of eyes. However, epiretinal membrane and high myopia can cause scan artefact and should be considered when interpreting the results.Mona S. Awadalla, Jude Fitzgerald, Nicholas H. Andrew, Tiger Zhou, Henry Marshall, Ayub Qassim, Mark Hassall, Robert J. Casson, Stuart L. Graham, Paul R. Healey, Ashish Agar, Anna Galanopoulos, Simon Phipps, Angela Chappell, John Landers, Jamie E. Crai

Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression

Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases and modifies penetrance of the MYOC variant encoding p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile and are at 15-fold increased risk of developing advanced glaucoma (top 10% versus remaining 90%, odds ratio = 4.20). The PRS predicts glaucoma progression in prospectively monitored, early manifest glaucoma cases (P = 0.004) and surgical intervention in advanced disease (P = 3.6 × 10). This glaucoma PRS will facilitate the development of a personalized approach for earlier treatment of high-risk individuals, with less intensive monitoring and treatment being possible for lower-risk groups

Suppurative granulomatous myositis of an extra-ocular muscle in Crohn's disease

Igal Leibovitch, Anna Galanopoulos and Dinesh Selv

Profile of Transhumant Sheep and Goat Greek Farmer in Central Greece

Transhumance is traditional extensive farming system that involves the seasonal migration of animal husbandry between winter and summer rangelands. The purpose of this paper was to study the profile of the Greek transhumant herder and to construct a typology that could be used by the decision makers to improve the strategies used to determine and preserve the system. The required information was obtained from totally 140 Greek transhumant producers of the region of Central Greece. A Principal Component Analysis gave three components related to the “education of the producer”, “the future of the system” and the “type of the herds”. Using multivariate techniques, a farm typology was established with three categories. The first defined as the “younger and more educated”, the second group “the elder traditional producer” and the third group the “more experienced” group. Interestingly the results highlighted the future of transhumant farms being doubtful for a number of farmers originated mainly by the first group, the negative connection of future of the system with the younger, higher education and more innovative producers, emerging the need for protection and preserving its extensive character

Reproductive Management of Transhumant Farming System in Greece

Transhumance is a traditional farming system present in Greece for many centuries including the seasonal migration of people and their livestock that follows predetermined area-specific practices. Purpose of this paper was to record the practices performed during movement to uplands and of the strategies applied during reproduction in order to reveal differences among the studied areas as well as to record the degree the system has evolved. Non-parametric statistical methods in a sample of 551 herders were applied to depict management practices while the regions were separated into four groups according to climate and geographical features. The results revealed differences among the studied areas revealing separation of males and females, uncontrolled mating for the majority of the herds, early weaning and adoption of strategies such as oestrus synchronization, reflecting the effort of the producers to correspond to the seasonal needs of the market for lambs/kids as well as to improve the performance of their animals

A Nutritional Management Analysis of the Transhumant Sheep and Goat Farms in the Region of Sterea Ellada-Greece

Transhumance is the seasonal movement of herds between different summer and winter pastures. The main reason of practice of this farming system is the need for a more efficient exploitation of vegetation to meet the nutritional needs of the reared animals. The aim of this paper is to investigate nutritional management practices of transhumant herds in the region of Sterea Ellada.  In the analysis, emphasis is given in the calculation of the coverage of nutritional needs of the reared animals by supplementary feed, translated as Metabolized energy (ME), Digestible Crude Protein (DGP) and Dry Matter (DM). Nutritional management is studied in four basic productive stages of ewes and dams. All necessary data were collected from a sample of 140 transhumant herders, via an exhaustive questionnaire that covered all aspects of the production of the farms and managerial practices. Data were subsequently analyzed with descriptive statistic methods. Analysis reveals that grazing tends to be the main nutritional source as approximately 30-50% of the needs of the reared animals on lowlands and more than 90% on uplands is considered to be covered by grazin

Transhumant Sheep and Goat Farming Sector in the Region of Sterea Ellada-Greec

Transhumance connects highlands and lowlands creating that way a farming system with important social, cultural, economic, landscape and environmental effects. Despite the continuous reduction of the number of transhumant herds in Greece the later years, this farming system still preserves a considerable position in country’s animal husbandry. Aim of this paper is the study of management practices and the nomination of productivity indicators of the transhumant reared animals in the region of Sterea Ellada. The necessary data were collected through a specially conducted questionnaire from totally 140 transhumant herders. The results reveal average herd size of 364.40, with herd sizes that exceeds one thousand, especially for goat herds, and residence on mountainous, semi-mountainous areas for at least 5 months. The main source of income is the trade of milk, but it should be noted that a small proportion of the herders process milk and trade only feta and/or other traditional kinds of cheese complementary of meat trade. In addition average traded milk production and prolificacy reveal the influence of more intense farming practices, such as crossbreeding and/or rational feed and the continuous effort of the producers and correspond to consecutive increase of the needs of the market