The Effect of Yoga on Intraocular Pressure Using the "iCare HOME2" Tonometer.

BACKGROUND: Various yoga positions may have an unfavorable impact on intraocular pressure (IOP) and may therefore be seen as a potential risk factor for the progression of glaucoma. The new "iCare HOME2" is a handheld self-tonometer for IOP measurements outside clinical settings. This is the first study to evaluate the immediate effect of common yoga postures on the IOP of healthy and glaucomatous eyes using the "iCare HOME2" self-tonometer and to compare the time of IOP recovery in both groups. METHODS: This is a single-center, prospective, observational study including 25 healthy and 25 glaucoma patients performing the following yoga positions: "legs up" (Viparita Karani), "bend over" (Uttanasana), "plough pose" (Halasana), and the "down face dog" (Adho Mukha Svanasana) for 90 s each, with a 2-min break in between. IOP was measured with the "iCare HOME2" before, during, and after each position. RESULTS: IOP significantly increased in all eyes in all positions (p < 0.05), showing no statistically significant difference between healthy or glaucomatous eyes (p > 0.05). The mean rise in IOP in healthy subjects was 1.6 mmHg (SD 1.42; p = 0.037), 14.4 mmHg (SD 4.48; p < 0.001), 7.5 mmHg (SD 4.21; p < 0.001), and 16.5 mmHg (SD 3.71; p < 0.001), whereas in glaucoma patients, IOP rose by 2.8 mmHg (SD 2.8; p = 0.017), 11.6 mmHg (SD 3.86; p < 0.001), 6.0 mmHg (SD 2.24; p < 0.001), and 15.1 mmHg (SD 4.44; p < 0.001) during the above listed yoga positions, repsectively. The highest increase in IOP was seen in the down face position, reaching mean IOP values above 31 mmHg in both study groups. IOP elevation was observed immediately after assuming the yoga position, with no significant change during the following 90 s of holding each pose (p > 0.05). All IOP values returned to baseline level in all individuals, with no significant difference between healthy and glaucoma participants. CONCLUSION: Our data show that common yoga positions can lead to an acute IOP elevation of up to 31 mmHg in healthy as well as glaucoma eyes, with higher IOP values during head-down positions. Given that IOP peaks are a major risk factor for glaucomatous optic neuropathy, we generally advise glaucoma patients to carefully choose their yoga exercises. If and to what extent practicing yoga leads to glaucoma progression, however, remains unclear and warrants further research.

Role of Choline in Ocular Diseases.

Choline is essential for maintaining the structure and function of cells in humans. Choline plays an important role in eye health and disease. It is a precursor of acetylcholine, a neurotransmitter of the parasympathetic nervous system, and it is involved in the production and secretion of tears by the lacrimal glands. It also contributes to the stability of the cells and tears on the ocular surface and is involved in retinal development and differentiation. Choline deficiency is associated with retinal hemorrhage, glaucoma, and dry eye syndrome. Choline supplementation may be effective for treating these diseases.

The acts of opening and closing the eyes are of importance for congenital blindness: Evidence from resting-state fMRI.

Volitional eye closure is observed only in conscious and awake humans, and is rare in animals. It is believed that eye closure can focus one's attention inward and facilitate activities such as meditation and mental imagery. Congenital blind individuals are also required to close their eyes for these activities. Resting-state functional magnetic resonance imaging (RS-fMRI) studies have found robust differences between the eyes-closed (EC) and eyes-open (EO) conditions in some brain regions in the sighted. This study analyzed data from 21 congenital blind individuals and 21 sighted controls by using amplitude of low-frequency fluctuation (ALFF) of RS-fMRI. The blind group and the sighted group shared similar pattern of differences between the EC and EO condition: ALFF was higher in the EC condition than the EO condition in the bilateral primary sensorimotor cortex, bilateral supplementary motor area, and inferior occipital cortex, while ALFF was lower in the EC condition than the EO condition in the medial prefrontal cortex, highlighting the "nature" effect on the difference between the EC and EO conditions. The results of other matrices such as fractional ALFF (fALFF) and regional homogeneity (ReHo) showed similar patterns to that of ALFF. Moreover, no significant difference was observed between the EC-EO pattern of the two subgroups of congenital blind (i.e., with and without light perception), suggesting that the EC-EO difference is irrespective of residual light perception which reinforced the "nature" effect. We also found between-group differences, i.e., more probably "nurture effect", in the posterior insula and fusiform. Our results suggest that the acts of closing and opening the eyes are of importance for the congenital blind, and that these actions and their differences might be inherent in the nature of humans.

A combined convolutional and recurrent neural network for enhanced glaucoma detection.

Glaucoma, a leading cause of blindness, is a multifaceted disease with several patho-physiological features manifesting in single fundus images (e.g., optic nerve cupping) as well as fundus videos (e.g., vascular pulsatility index). Current convolutional neural networks (CNNs) developed to detect glaucoma are all based on spatial features embedded in an image. We developed a combined CNN and recurrent neural network (RNN) that not only extracts the spatial features in a fundus image but also the temporal features embedded in a fundus video (i.e., sequential images). A total of 1810 fundus images and 295 fundus videos were used to train a CNN and a combined CNN and Long Short-Term Memory RNN. The combined CNN/RNN model reached an average F-measure of 96.2% in separating glaucoma from healthy eyes. In contrast, the base CNN model reached an average F-measure of only 79.2%. This proof-of-concept study demonstrates that extracting spatial and temporal features from fundus videos using a combined CNN and RNN, can markedly enhance the accuracy of glaucoma detection.

Herbal Medicines in Glaucoma Treatment.

Glaucoma is the leading cause of irreversible blindness worldwide. Optimizing treatment is important to protecting vision. The current standard of therapy for glaucoma involves lowering the intraocular pressure (IOP) through medical, laser, and/or surgical therapy. Nevertheless, there are an increasing number of glaucoma patients that use alternative medicines to treat their glaucoma or supplement their traditional glaucoma management. Ginkgo biloba, bilberry, and medical marijuana are amongst the most commonly used medicinal plants by glaucoma patients. We reviewed the literature to determine the benefits, safety, and efficacy of these herbal remedies. Though ginkgo biloba and bilberry may prevent or slow down retinal ganglion cell death, there is no evidence yet to suggest that they alter the course of glaucoma. Medical marijuana has shown IOP lowering effect in some individuals, but its short duration of action, significant adverse effects, and addictive potential have rendered it an inappropriate standard therapeutic agent for glaucoma. Larger studies with longer durations that investigate the effect of herbal medicines on the course of glaucoma in comparison to the current standard of care are needed to elucidate their benefits in glaucoma treatment.

Nicotinamide-Rich Diet in DBA/2J Mice Preserves Retinal Ganglion Cell Metabolic Function as Assessed by PERG Adaptation to Flicker.

Flickering light increases metabolic demand in the inner retina. Flicker may exacerbate defective mitochondrial function in glaucoma, which will be reflected in the pattern electroretinogram (PERG), a sensitive test of retinal ganglion cell (RGC) function. We tested whether flicker altered the PERG of DBA/2J (D2) glaucomatous mice and whether vitamin B3-rich diet contributed to the flicker effect. D2 mice fed with either standard chow (control, n = 10) or chow/water enriched with nicotinamide (NAM, 2000 mg/kg per day) (treated, n = 10) were monitored from 3 to 12 months. The PERG was recorded with superimposed flicker (F-PERG) at either 101 Hz (baseline) or 11 Hz (test), and baseline-test amplitude difference (adaptation) evaluated. At endpoint, flat-mounted retinas were immunostained (RBPMS and mito-tracker). F-PERG adaptation was 41% in 3-month-old D2 and decreased with age more in control D2 than in NAM-fed D2 (GEE, p < 0.01). At the endpoint, F-PERG adaptation was 0% in control D2 and 17.5% in NAM-fed D2, together with higher RGC density (2.4×), larger RGC soma size (2×), and greater intensity of mitochondrial staining (3.75×). F-PERG adaptation may provide a non-invasive tool to assess RGC autoregulation in response to increased metabolic demand and test the effect of dietary/pharmacological treatments on optic nerve disorders.

The role of lamina cribrosa tissue stiffness and fibrosis as fundamental biomechanical drivers of pathological glaucoma cupping.

The primary biomechanical driver of pathological glaucomatous cupping remains unknown. Finite element modeling indicates that stress and strain play key roles. In this article, primarily a review, we utilize known biomechanical data and currently unpublished results from our lab to propose a three-stage, tissue stiffness-based model to explain glaucomatous cupping occurring at variable levels of translaminar pressure (TLP). In stage 1, a short-term increase in TLP gradient induces a transient increase in lamina cribrosa (LC) strain. Beyond a critical level of strain, the tissue stiffness rises steeply provoking cellular responses via integrin-mediated mechanotransduction. This early mechanoprotective cellular contraction reduces strain, which reduces tissue stiffness by return of the posteriorly deflected LC to baseline. In stage 2 a prolonged period of TLP increase elicits extracellular matrix (ECM) production leading to fibrosis, increasing baseline tissue stiffness and strain and diminishing the contractile ability/ability to return to the baseline LC position. This is supported by our three-dimensional collagen contraction assays, which show significantly reduced capacity to contract in glaucoma compared with normal LC cells. Second, 15% cyclic strain in LC cells over 24 h elicits a typical increase in ECM profibrotic genes in normal LC cells but a highly blunted response in glaucoma LC cells. Stage 3 is characterized by persistent fibrosis causing further stiffening and inducing a feed-forward ECM production cycle. Repeated cycles of increased strain and stiffness with profibrotic ECM deposition prevent optic nerve head (ONH) recoil from the new deflected position. This incremental maladaptive modeling leads to pathological ONH cupping.

Efficacy and safety of Bujing Yishi tablet for glaucoma with controlled IOP: study protocol for a multi-centre randomized controlled trial.

BACKGROUND: As an irreversible, intractable disease with vision loss, glaucoma leads to permanent and progressive damage of visual function. Lowering high intraocular pressure (HIOP) is the first choice for treating glaucoma; however, the control of HIOP is not enough to prevent progressive vison loss. Currently, the therapies to treat glaucoma with controlled IOP (GPCI) are unsatisfactory. Chinese medicine is effective for improving visual function in patients with GPCI. Bujing Yishi tablets (BJYSP) have been the standard preparation for treating GPCI in our hospital for decades. However, no rigorous randomized controlled clinical studies have investigated its effects and safety. METHODS: This study will be a 6-month, multicenter, stratified trial following a prospective, randomized, open-label, blinded endpoint (PROBE) protocol. A total of 216 eligible GPCI patients aged 18-75 years will be stratified according to the early, moderate, and advanced stages of glaucoma. After stratifying, the participants will be randomly assigned to the BJYSP group or control group at a ratio of 1:1. Following randomization, participants in the BJYSP group and control group will receive BJYSP and mecobalamin tablets, respectively, for the same 6-month period. The primary outcomes will include the best-corrected visual acuity (BCVA), visual field assessment, visual evoked potential (VEP) test, and Heidelberg retina tomography II (HRT II); the secondary outcomes will include intraocular pressure (IOP) and Traditional Chinese medicine (TCM) clinical symptom scales. The primary and secondary outcomes will be measured at baseline and 8, 16, and 24 weeks thereafter. Safety assessments will also be evaluated at baseline and 12 and 24 weeks thereafter. DISCUSSION: This study will be a standardized, scientific, clinical trial designed to evaluate the therapeutic effects and safety of BJYSP as a novel therapeutic strategy for improving visual function in patients with GPCI. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800016431. Registered on 1 June 2018.

Surgical outcomes of Glaucoma associated with Axenfeld-Rieger syndrome.

BACKGROUND: The surgical management of glaucoma associated with Axenfeld-Rieger Syndrome (ARS) is poorly described in the literature. The goal of this study is to compare the effectiveness of various glaucoma surgeries on intraocular pressure (IOP) management in ARS. METHODS: Retrospective cohort study at a university hospital-based practice of patients diagnosed with ARS between 1973 and 2018. Exclusion criterion was follow-up less than 1 year. The number of eyes with glaucoma (IOP ≥ 21 mmHg with corneal edema, Haabs striae, optic nerve cupping or buphthalmos) requiring surgery was determined. The success and survival rates of goniotomy, trabeculotomy±trabeculectomy (no antifibrotics), cycloablation, trabeculectomy with anti-fibrotics, and glaucoma drainage device placement were assessed. Success was defined as IOP of 5-20 mmHg and no additional IOP-lowering surgery or visually devastating complications. Kaplan-Meier survival curves and the Wilcoxon test were used for statistical analysis. RESULTS: In 32 patients identified with ARS (median age at presentation 6.9 years, 0-58.7 years; median follow-up 5.4 years, 1.1-43.7 years), 23 (71.9%) patients were diagnosed with glaucoma at median age 6.3 years (0-57.9 years). In glaucomatous eyes (46 eyes), mean IOP at presentation was 21.8 ± 9.3 mmHg (median 20 mmHg, 4-45 mmHg) on 1.0 ± 1.6 glaucoma medications. Thirty-one eyes of 18 patients required glaucoma surgery with 2.2 ± 1.2 IOP-lowering surgeries per eye. Goniotomy (6 eyes) showed 43% success with 4.3 ± 3.9 years of IOP control. Trabeculotomy±trabeculectomy (6 eyes) had 17% success rate with 14.8 ± 12.7 years of IOP control. Trabeculectomy with anti-fibrotics (14 eyes) showed 57% success with 16.5 ± 13.5 years of IOP control. Ahmed© (FP7 or FP8) valve placement (8 eyes) had 25% success rate with 1.7 ± 1.9 years of IOP control. Baerveldt© (250 or 350) device placement (8 eyes) showed 70% success with 1.9 ± 2.3 years of IOP control. Cycloablation (4 eyes) had 33% success rate with 2.7 ± 3.5 years of IOP control. At final follow-up, mean IOP (12.6 ± 3.8 mmHg, median 11.8 mmHg, 7-19 mmHg) in glaucomatous eyes was significantly decreased (p < 0.0001), but there was no difference in number of glaucoma medications (1.6 ± 1.5, p = 0.1). CONCLUSIONS: In our series, greater than 70% of patients with ARS have secondary glaucoma that often requires multiple surgeries. Trabeculectomy with anti-fibrotics and Baerveldt glaucoma drainage devices showed the greatest success in obtaining IOP control.

Oral consumption of Garcinia kola(Bitter kola) lowers intraocular pressure.

PURPOSE: Garcinia kola (bitter kola) is locally ingested across the West African subregion. It has ocular hypotensive effects similar to some commonly used glaucoma medications when administered topically. The study assessed the effect of oral ingestion of G. kola on intraocular pressure (IOP). METHOD: A randomized, single-blind, placebo-controlled, cross-over design was used in this study. Forty-six healthy subjects, aged between 19 and 27 years were recruited and randomized into two groups (A and B). Subjects in group A ingested 100 mg/kg body weight bitter kola in a 200 ml solution on their first visit and group B ingested 200 ml of water. On the second visit, the order of treatment was reversed, IOP was measured at baseline and every 45 min interval for 135 min. The mean difference between the baseline and post-treatment IOP measurements were tested for statistical significance using repeated-measures analysis of variance (95% confidence intervals [CIs]). RESULTS: Mean IOP measurements decreased by 7.9, 18.2 and 20.6% at 45, 90 and 135 min, respectively, after G. kola treatment. The reduction, though variable across subjects, was statistically significant (F [2.13, 95.62] = 90.35, p < 0.0001) across the respective time points. Repetition of an identical protocol without G. kola caused clinically negligible changes in IOP. There was no statistically significant influence of gender or age in G. kola effect on IOP reading. CONCLUSION: Oral ingestion of G. kola lowered the intraocular pressure of healthy young adults by 21%. Such an effect may be of therapeutic benefit to patients with POAG or ocular hypertension in low-income settings.

Endothelin-1 Mediated Decrease in Mitochondrial Gene Expression and Bioenergetics Contribute to Neurodegeneration of Retinal Ganglion Cells.

Endothelin-1 (ET-1) is a vasoactive peptide that is elevated in aqueous humor as well as circulation of primary open angle glaucoma (POAG) patients. ET-1 has been shown to promote degeneration of optic nerve axons and apoptosis of retinal ganglion cells (RGCs), however, the precise mechanisms are still largely unknown. In this study, RNA-seq analysis was used to assess changes in ET-1 mediated gene expression in primary RGCs, which revealed that 23 out of 156 differentially expressed genes (DEGs) had known or predicted mitochondrial function, of which oxidative phosphorylation emerged as the top-most enriched pathway. ET-1 treatment significantly decreased protein expression of key mitochondrial genes including cytochrome C oxidase copper chaperone (COX17) and ATP Synthase, H+ transporting, Mitochondrial Fo Complex (ATP5H) in primary RGCs and in vivo following intravitreal ET-1 injection in rats. A Seahorse ATP rate assay revealed a significant decrease in the rate of mitochondrial ATP production following ET-1 treatment. IOP elevation in Brown Norway rats showed a trend towards decreased expression of ATP5H. Our results demonstrate that ET-1 produced a decrease in expression of vital components of mitochondrial electron transport chain, which compromise bioenergetics and suggest a mechanism by which ET-1 promotes neurodegeneration of RGCs in glaucoma.

Bio-tactics for neuroprotection of retinal ganglion cells in the treatment of glaucoma.

Glaucoma, a neurodegenerative disorder is characterized by damage of ganglion cells of retina and also its axons. The manner of progression of disease and retinal ganglion cells death in glaucoma still remains unknown and hence many mechanisms are put forward to understand the disease. Clinical developments have suggested that in every single patient decreasing intraocular pressure (IOP) is not the solution to prevent glaucoma which suggests on the fact that there are other risk factors affecting the disease. The demand for substitute unconventional treatments gives rise to the need to understand the biologically based tactics (bio-tactics) for stopping the progression of disease. Pragmatic findings of past years have supported novelty of inventive molecules with hallmark of neuroprotection in gene therapy. On the other hand, transformation of the latest drugs to clinic has not been of much fruitful substantially for the reason that it lacked dependability while measuring in vivo retinal injury. This as a consequence thwarted the high quality healing possibility of neuroprotectants whether administered single-handedly or given complimentary with other IOP reducing agents. Advancement in research is crucial to grasp the underlying mechanisms concerned with glaucoma and apply it in clinical field to develop neuroprotective agents. In this context, the present review is to bring forth an update on up to date progress in the domain of neuroprotection of retinal ganglion cells for treating glaucoma.

Reversal of cupping em glaucoma juvenil tratado com análogo de prostaglandina tópica / Reversal of cupping in juvenile glaucoma treated with topical prostaglandin analogue

Resumo A reversão da escavação é uma entidade rara que se refere à redução da escavação do disco óptico em resposta à diminuição sustentada dos níveis de pressão intra-ocular (PIO), em cerca de 25% da PIO basal. A ocorrência deste fenômeno apenas com o tratamento clínico é pouco relatada na literatura, Este estudo relata um caso de um paciente com glaucoma juvenil, que apresentou à gonioscopia ângulo aberto e tomografia de coerência óptica (OCT) com uma diminuição significativa na camada de fibras nervosas retinianas em ambos os olhos. Após um ano utilizando análogos de prostaglandina tópica e manutenção de níveis baixos de PIO, ocorreu diminuição da escavação do nervo óptico, que foi confirmada pelos padrões topográficos da OCT. O "reversal of cupping" é um sinal da diminuição da tensão ao nível da lâmina crivosa e está provavelmente associada a uma redução do risco para a progressão do glaucoma a longo prazo, sem melhora da função visual.

Abstract Reversal of cupping is a rare entity, characterized by the reduction of optical disc cupping in response to sustained decrease in intraocular pressure (IOP) levels by 25% of the basal IOP. The occurrence of this phenomenon with clinical treatment is rarely reported in the literature. This study reports a case of a patient with juvenile glaucoma with augmented cupping, significant decrease in the retinal nerve fiber layer in both eyes and altered topografic measures in optical coherence tomography (OCT). After one year using topical prostaglandin analog and keeping low IOP levels, a decrease in optic nerve cupping was detected in rethinography, confirmed by the improvement of OCT topographic measures. Reversal of cupping is a sign of decreased tension at the level of the lamina cribosa and is probably associated with a reduced risk for long-term progression of glaucoma without improvement of visual function.

Meditation: A Polypill for Comprehensive Management of Glaucoma Patients.

Meditation is an ancient behavioral intervention, however, its benefits for achieving holistic health have been highlighted in recent times with rigorous scientific studies revealing its benefits in many chronic diseases. It has been specially found useful in neurodegenerative diseases and recent evidence points to the positive effects of meditation in preserving gray and white matter in the adult brain. It is also a potential therapy to downregulate processes implicated in brain aging and confer "neuroprotection"-something we all look forward to for our glaucoma patients. In the current review, we evaluate the benefits of meditation practice for the glaucoma patient and support for its candidature as adjunctive therapy for glaucoma patients. It has multiple potential benefits for normal-pressure and high-pressure glaucoma patients including a reduction in intraocular pressure, increasing cerebral blood flow and oxygenation, and decreasing action of the sympathetic nervous system with a corresponding increase in parasympathetic nervous system activity. Meditation leads to a "relaxation response" mediated by nitric oxide with decrease in the stress hormone cortisol, increase in neurotrophins and mitochondrial energy production, and improves the overall quality of life of glaucoma patients. It can also benefit caregivers of glaucoma patients and health care providers. It appears that meditation can function as a multifaceted management approach for glaucoma using the natural potential of the human body and target not only the eye but the patient behind the eye to ameliorate this "sick eye in a sick body" condition.

Development of a Novel Intraocular-Pressure-Lowering Therapy Targeting ATX.

Elevated intraocular pressure (IOP) is the major cause of glaucoma, which is the second leading cause of blindness. However, current glaucoma treatments cannot completely regulate IOP and progression of glaucoma. Our group recently found that autotaxin (ATX) activity in human aqueous humor (AH) was positively correlated with increased IOP in various subtypes of glaucoma. To develop new IOP-lowering treatments, we generated a novel ATX inhibitor as an ophthalmic drug by high-throughput screening, followed by inhibitor optimization. Administration of the optimized ATX inhibitor (Aiprenon) reduced IOP in laser-treated mice exhibiting elevated IOP and higher level of ATX activity in AH and normal mice in vivo. The stimulation of ATX induced outflow resistance in the trabecular pathway; however, administration of Aiprenon recovered the outflow resistance in vitro. The in vitro experiments implied that the IOP-lowering effect of Aiprenon could be correlated with the altered cellular behavior of trabecular meshwork (TM) and Schlemm's canal endothelial (SC) cells. Overall, our findings showed that ATX had major impact in regulating IOP as a target molecule, and potent ATX inhibitors such as Aiprenon could be a promising therapeutic approach for lowering IOP.

Possible therapeutic effect of magnesium in ocular diseases.

Magnesium (Mg2+) is one of the major elements required to maintain normal metabolism and ionic balances in ocular tissues. The physiological role of Mg2+ is mediated through maintaining the Na+-K+-ATPase on membrane, favoring energy-generating reactions, replication of DNA and protein synthesis. Despite the wide availability of this element, hypomagnesemia has been associated with many human ailments. Recent studies highlighted the association of hypomagnesemia and, thereby, supplementation of Mg2+ in the management of eye diseases. Glaucoma, senile cataract and diabetic retinopathy were associated with low level of extracellular Mg2+. The neurovascular protective effects of Mg2+ mediated through activation of endothelial nitric oxide synthase and inhibition of endothelin-1 eventually result in vasodilatation of retinal vessels. Mg2+ can maintain the lens sodium pump activity and antioxidant status and block the calcium channels and release of glutamate in nerve endings. Furthermore, it can prevent the apoptosis of retinal ganglion cells. All these effects contribute to its being a pharmacological agent against ocular diseases. However, clinical trials are scant. This article discusses the role of Mg2+ as a possible therapeutic agent in the management of glaucoma, cataract and diabetic retinopathy.

Rapid Development of Glaucoma Via ITV Nonselective ANGPT 1/2 Antibody: A Potential Role for ANGPT/TIE2 Signaling in Primate Aqueous Humor Outflow.

Purpose: Investigate a significant, dose-related increase in IOP, leading to glaucomatous damage to the neuroretina and optic nerve following intravitreal (ITV) administration of a bispecific F(ab')2 [anti-VEGF/Angiopoietins [ANGPT]F(ab')2] molecule in adult monkeys. Methods: ITV ocular tolerability and investigation of anti-VEGF/ANGPT F(ab')2 (blocking both ANGPT1 and ANGPT2) was done in monkeys; mechanistic studies were done in neonatal mice. Results: Following the second ITV dose of anti-VEGF/ANGPT F(ab')2, all 1.5- and 4-mg/eye treated monkeys developed elevated IOP, which eventually was associated with optic disc cupping and thinning of the neuroretinal rim. Histopathologic examination showed nonreversible axonal degeneration in the optic nerves of animals administered 1.5 mg/eye and higher that was considered secondary to high IOP. Anti-ANGPT Fab also caused elevated IOP in monkeys, but anti-VEGF Fab did not contribute to the IOP increase. In addition, an anti-ANGPT2-selective antibody did not change IOP. In mice simultaneous blockade of ANGPT1 and ANGPT2 impaired the expansion and formation of Schlemm's canal (SC) vessels, similar to genetic ablation of Angpt1/Angpt2 and their receptor TIE2. As previously reported, blocking ANGPT2 alone did not affect SC formation in mice. Conclusions: Dual inhibition of ANGPT1/ANGPT2, but not ANGPT2 alone, leads to increased IOP and glaucomatous damage in monkeys. This confirms a role for TIE2/ANGPT signaling in the control of IOP in adults, a finding initially identified in transgenic mice. Dual pharmacologic inhibition of ANGPT1/ANGPT2 may affect aqueous drainage and homeostasis in adult monkeys and may be useful in developing novel models of glaucoma.

Clinical, ultrasonographic and optical coherence tomography correlation of optic nerve head cupping in glaucoma patients.

Purpose: To ascertain if ultrasound (USG) B-scan examination of the optic nerve head (ONH) can be a useful tool to diagnose and quantify glaucomatous cupping. Methods: A cross-sectional observational study of 48 eyes of 48 patients with clear ocular media and cup-disc ratio of (CDR) ≥0.6 were included. The disc was studied by + 90D examination, USG B-scan and ONH Optical coherence tomography (OCT) by three masked observers. Observer-1 assessed the clinical CDR, observer-2recordedopticcup diameter on USG B-scan and observer-3performed ONH OCT to note the software computed average CDR. Measurements of cupping obtained by these 3 methods were compared and their relative strengths determined. The interdependency between variables was further studied using regression analysis. Results: Clinically assessed disc ratios of 0.6, 0.7, 0.8, 0.9, and total corresponded to USG cup measures of 1.02 ± 0.11 mm, 1.23 ± 0.14 mm, 1.35 ± 0.072 mm, 1.45 ± 0.084 mm, 1.75 ± 0.15 mm and OCT average CDR of 0.62 ± 0.087, 0.68 ± 0.060, 0.75 ± 0.078, 0.81 ± 0.036, 0.89 ± 0.038, respectively. There was an excellent correlation between the three arms, with Pearson's co-efficient (r) of 0.87, P < 0.001 between clinical and USG cupping; r = 0.89, P < 0.001 between clinical and OCT cupping; and r = 0.88, P < 0.001 between USG and OCT cupping. A relation of y = 1.64x + 0.03 was obtained between them, where y stands for USG cup diameter and x stands for the observed clinical CDR. Conclusion: Ultrasonographic measurement of optic cup diameter corresponds well to clinical ONH cupping. Therefore, it can reliably be used in quantifying ONH cupping in cases of media opacities which preclude optic disc visualization.

Neuroprotective and Anti-Inflammatory Effects of a Hydrophilic Saffron Extract in a Model of Glaucoma.

Glaucoma is a neurodegenerative disease characterized by the loss of retinal ganglion cells (RGCs). An increase in the intraocular pressure is the principal risk factor for such loss, but controlling this pressure does not always prevent glaucomatous damage. Activation of immune cells resident in the retina (microglia) may contribute to RGC death. Thus, a substance with anti-inflammatory activity may protect against RGC degeneration. This study investigated the neuroprotective and anti-inflammatory effects of a hydrophilic saffron extract standardized to 3% crocin content in a mouse model of unilateral, laser-induced ocular hypertension (OHT). Treatment with saffron extract decreased microglion numbers and morphological signs of their activation, including soma size and process retraction, both in OHT and in contralateral eyes. Saffron extract treatment also partially reversed OHT-induced down-regulation of P2RY12. In addition, the extract prevented retinal ganglion cell death in OHT eyes. Oral administration of saffron extract was able to decrease the neuroinflammation associated with increased intraocular pressure, preventing retinal ganglion cell death. Our findings indicate that saffron extract may exert a protective effect in glaucomatous pathology.

Neuroprotective Effect of Ginkgo Biloba Extract Against Hypoxic Retinal Ganglion Cell Degeneration In Vitro and In Vivo.

Hypoxia-induced oxidative stress and disturbed microvascular circulation are both associated with pathogenesis of glaucoma. Ginkgo biloba extract (GBE) has been reported to have positive pharmacological effects on oxidative stress and impaired vascular circulation. This study aimed to investigate the neuroprotective effect of GBE against hypoxic injury to retinal ganglion cells (RGCs) both in vitro and in vivo. The rat RGC line was used, and oxidative stress was induced by hydrogen peroxide (H2O2) in vitro. EGb 761, a standardized GBE, or vehicle was applied to RGCs. Hypoxic optic nerve injury in vivo was induced by clamping the optic nerve of rats with a "microserrefine clip" with an applicator, which was applied without crushing the optic nerve. This method is different from "optic nerve crush model" and does not involve elevation of intraocular pressure, and may serve as a possible normal tension glaucoma animal model. EGb 761 at various concentrations or vehicle was administered intraperitoneally. RGC density was measured to estimate the survival both in vitro and in vivo. The survival of RGCs was significantly (P < .001) higher upon treatment with 1 or 5 µg/mL of EGb 761 compared with vehicle after oxidative stress in vitro. RGC density upon treatment with EGb 761 of 100 mg/kg (1465.6 ± 175 cells/mm2) or 250 mg/kg (1307.6 ± 213 cells/mm2) was significantly higher (P < .01, P < .05, respectively) than that obtained with vehicle (876.3 ± 136 cells/mm2) in vivo. Our results suggest that GBE has neuroprotective effect on RGCs against hypoxic injury both in vitro and in vivo.