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To evaluate a new animal model of chronic glaucoma induced using a single injection of fibronectin-loaded biodegradable PLGA microspheres (Ms) to test prolonged therapies. 30 rats received a single injection of fibronectin-PLGA-Ms suspension (MsF) in the right eye, 10 received non-loaded PLGA-Ms suspension (Control), and 17 were non-injected (Healthy). Follow-up was performed (24 weeks), evaluating intraocular pressure (IOP), optical coherence tomography (OCT), histology and electroretinography. The right eyes underwent a progressive increase in IOP, but only induced cohorts reached hypertensive values. The three cohorts presented a progressive decrease in ganglion cell layer (GCL) thickness, corroborating physiological age-related loss of ganglion cells. Injected cohorts (MsF > Control) presented greater final GCL thickness. Histological exams explain this paradox: the MsF cohort showed lower ganglion cell counts but higher astrogliosis and immune response. A sequential trend of functional damage was recorded using scotopic electroretinography (MsF > Control > Healthy). It seems to be a function–structure correlation: in significant astrogliosis, early functional damage can be detected by electroretinography, and structural damage can be detected by histological exams but not by OCT. Males presented higher IOP and retinal and GCL thicknesses and lower electroretinography. A minimally invasive chronic glaucoma model was induced by a single injection of biodegradable Ms. [ABSTRACT FROM AUTHOR]

This report describes the clinical and histological findings, genetic study, and treatment in a 1.3-year-old rhesus macaque with bilateral cataracts and unilateral secondary glaucoma. Intravitreal injection of gentamicin decreased the intraocular pressure from 56 to

Painful-blind eye (PBE) is a challenging and debilitating condition that greatly affects the quality of life of patients. Although PBE can result from a variety of etiologies, currently there is no guideline or consensus on how to approach therapeutically these patients, and most treatments are experience-based. We summarized the evidence from available studies to investigate the current state of PBE treatment strategies. This review revealed that the information available about therapeutic approaches in patients with PBE is insufficient and outdated, therefore, new experimental and larger studies are needed to reach an agreement about this condition. [ABSTRACT FROM AUTHOR]

Painful-blind eye (PBE) is a challenging and debilitating condition that greatly affects the quality of life of patients. Although PBE can result from a variety of etiologies, currently there is no guideline or consensus on how to approach therapeutically these patients, and most treatments are experience-based. We summarized the evidence from available studies to investigate the current state of PBE treatment strategies. This review revealed that the information available about therapeutic approaches in patients with PBE is insufficient and outdated, therefore, new experimental and larger studies are needed to reach an agreement about this condition.

To evaluate a new animal model of chronic glaucoma induced using a single injection of fibronectin-loaded biodegradable PLGA microspheres (Ms) to test prolonged therapies. 30 rats received a single injection of fibronectin-PLGA-Ms suspension (MsF) in the right eye, 10 received non-loaded PLGA-Ms suspension (Control), and 17 were non-injected (Healthy). Follow-up was performed (24 weeks), evaluating intraocular pressure (IOP), optical coherence tomography (OCT), histology and electroretinography. The right eyes underwent a progressive increase in IOP, but only induced cohorts reached hypertensive values. The three cohorts presented a progressive decrease in ganglion cell layer (GCL) thickness, corroborating physiological age-related loss of ganglion cells. Injected cohorts (MsF > Control) presented greater final GCL thickness. Histological exams explain this paradox: the MsF cohort showed lower ganglion cell counts but higher astrogliosis and immune response. A sequential trend of functional damage was recorded using scotopic electroretinography (MsF > Control > Healthy). It seems to be a function–structure correlation: in significant astrogliosis, early functional damage can be detected by electroretinography, and structural damage can be detected by histological exams but not by OCT. Males presented higher IOP and retinal and GCL thicknesses and lower electroretinography. A minimally invasive chronic glaucoma model was induced by a single injection of biodegradable Ms.

Purpose: To explore the effects of chronic, uncontrolled glaucoma on pressure sensitivity in dogs before and after enucleation of the painful globe. Methods: Client‐owned dogs undergoing enucleation for chronic glaucoma with no other sources of pain were enrolled. Normal dogs of similar breeds and skull morphology were enrolled as controls. Craniofacial ratio (CFR) and relative palpebral fissure width (RPFW) were assessed in all patients. Serial mechanical quantitative sensory testing (QST) was performed the day before surgery, and 14, 30, 60, and 120 days after surgery. QST consisted of electronic Von Frey (eVF), and blunt algometry (BA) performed above and below the nonglaucomatous eye, the metacarpus, and metatarsus. Cochet‐Bonnet esthesiometry (CB) was also performed on the remaining eye. Results: Twelve dogs (6 per group) were included. Compared to baseline values, sensitivity tended to decrease over time (increased thresholds) in treatment dogs while it stayed constant or increased slightly in control dogs. The difference in change from baseline sensitivity between control and treatment groups was significant at day 120 using BA at supraorbital (P =.0153), infraorbital (P =.0209), and metacarpal sites (P =.007) and overall (P =.0470). This divergence was also significant using CB (P =.0470) on the opposite cornea. As patient CFR and RPFWV increased, both eVF (P =.005‐.023) and BA (P =.004‐.041) increased. Conclusions: Sensitivity to mechanical stimuli decreased both locally and at remote sites in dogs following enucleation for painful chronic glaucoma. Cranial conformation is associated with differences in sensitivity. [ABSTRACT FROM AUTHOR]

To evaluate a new animal model of chronic glaucoma induced using a single injection of fibronectin-loaded biodegradable PLGA microspheres (Ms) to test prolonged therapies. 30 rats received a single injection of fibronectin-PLGA-Ms suspension (MsF) in the right eye, 10 received non-loaded PLGA-Ms suspension (Control), and 17 were non-injected (Healthy). Follow-up was performed (24 weeks), evaluating intraocular pressure (IOP), optical coherence tomography (OCT), histology and electroretinography. The right eyes underwent a progressive increase in IOP, but only induced cohorts reached hypertensive values. The three cohorts presented a progressive decrease in ganglion cell layer (GCL) thickness, corroborating physiological age-related loss of ganglion cells. Injected cohorts (MsF > Control) presented greater final GCL thickness. Histological exams explain this paradox: the MsF cohort showed lower ganglion cell counts but higher astrogliosis and immune response. A sequential trend of functional damage was recorded using scotopic electroretinography (MsF > Control > Healthy). It seems to be a function-structure correlation: in significant astrogliosis, early functional damage can be detected by electroretinography, and structural damage can be detected by histological exams but not by OCT. Males presented higher IOP and retinal and GCL thicknesses and lower electroretinography. A minimally invasive chronic glaucoma model was induced by a single injection of biodegradable Ms.

Presynaptic modulation of γ-aminobutyric acid (GABA) release by an alpha7 nicotinic acetylcholine receptor (α7-nAChR) agonist promotes retinal ganglion cell (RGC) survival and function, as suggested by a previous study on a chronic glaucomatous model from our laboratory. However, the role of excitatory and inhibitory amino acid receptors and their interaction with α7-nAChR in physiological and glaucomatous events remains unknown. In this study, we investigated GABAA and N-methyl-D-aspartate (NMDA) receptor activity in control and glaucomatous retinal slices and the regulation of amino acid receptor expression and function by α7-nAChR. Whole-cell patch-clamp recordings from RGCs revealed that the α7-nAChR specific agonist PNU-282987 enhanced the amplitude of currents elicited by GABA and reduced the amplitude of currents elicited by NMDA. The positive modulation of GABAA receptor and the negative modulation of NMDA receptor (NMDAR) by PNU-282987-evoked were prevented by pre-administration of the α7-nAChR antagonist methyllycaconitine (MLA). The frequency and the amplitude of glutamate receptor-mediated miniature glutamatergic excitatory postsynaptic currents (mEPSCs) were not significantly different between the control and glaucomatous RGCs. Additionally, PNU-282987-treated slices showed no alteration in the frequency or amplitude of mEPSCs relative to control RGCs. Moreover, we showed that expression of the α1 subunit of the GABAA receptor was downregulated and the expression of the NMDAR NR2B subunit was upregulated by intraocular pressure (IOP) elevation, and the changes of high IOP were blocked by PNU-282987. In conclusion, retina GABAA and NMDARs are modulated positively and negatively, respectively, by activation of α7-nAChR in in vivo chronic glaucomatous models.

Mesenchymal stem cells have neuroprotective effects that limit damage to the retina and photoreceptors, and which may be mediated by extracellular vesicles (or exosomes) released by mesenchymal stem cells. To investigate the neuroprotective effect of extracellular vesicles derived from umbilical cord mesenchymal stem cells on glaucoma, we established rat models of chronic ocular hypertension by injecting conjunctival fibroblasts into the anterior chamber to mimic optic nerve injury caused by glaucoma. One week after injury, extracellular vesicles derived from umbilical cord-derived mesenchymal stem cells were injected into the vitreous cavity. We found that extracellular vesicles derived from mesenchymal stem cells substantially reduced retinal damage, increased the number of retinal ganglion cells, and inhibited the activation of caspase-3. These findings suggest that mesenchymal stem cell-derived extracellular vesicles can help alleviate optic nerve injury caused by chronic ocular hypertension, and this effect is achieved by inhibiting cell apoptosis., Competing Interests: None

High intraocular pressure (IOP) not responding to systemic and topical anti-glaucoma medications renders the eye at risk for both intra- and post-operative complications of glaucoma filtration surgery. Laser cyclophotocoagulation is able to lower IOP in such refractory glaucoma eyes and may make the surgical event safer. This study assessed diode laser cyclophotocoagulation (DLCP) when used as a temporary measure for lowering IOP prior to performing trabeculectomy. This study is a retrospective analysis of cases planned for trabeculectomy surgery, uncontrolled on maximally tolerable systemic anti-glaucoma medications. They were analysed for response to DLCP in terms of IOP control, vision-related complications, increased inflammation, post-trabeculectomy hypotony and chances of phthisis and ciliary shutdown. Twelve eyes of ten patients aged 35-65 years were identified and all followed up for at least 2 years. One week following DLCP, the IOP (mean ± SD) declined by 51 % from 46.8 ± 5.4 to 22.8 ± 3.3 mmHg. The IOP was further reduced to 15.4 ± 2.7 mmHg at 4 weeks after trabeculectomy; it remained in the mid-teens for a minimum of 2 years in all cases. The mean (±SD) visual acuity improved from 1.4 ± 0.4 to 0.8 ± 0.4 LogMAR equivalents following trabeculectomy. In four eyes, phacoemulsification was performed 5-7 months after trabeculectomy with improvement in best-corrected visual acuity. One patient developed transient hypotony, post-trabeculectomy, which resolved by 6 days. There were no other complications like increased inflammation, prolonged hypotony or suprachoroidal haemorrhage. DLCP is, thus, effective and safe for temporarily controlling IOP; thereby trabeculectomy can be performed in a quieter ocular milieu. [ABSTRACT FROM AUTHOR]

Purpose: To devise and evaluate a screening algorithm for glaucoma in clinical settings. Methods: Screening included examination of the optic disc for vertical cupping (≥0.4) and asymmetry (≥0.15), Goldmann applanation tonometry (≥21 mmHg, adjusted or unadjusted for central corneal thickness), and automated perimetry. In the diagnostic step, retinal nerve fiber layer imaging was performed using scanning laser polarimetry. Performance of the screening protocol was assessed in an eye hospital-based program in which 124 non-physician personnel aged 40 years or above were examined. A single ophthalmologist carried out the examinations and in equivocal cases, a glaucoma subspecialist′s opinion was sought. Results: Glaucoma was diagnosed in six cases (prevalence 4.8%; 95% confidence interval, 0.01-0.09) of whom five were new. The likelihood of making a definite diagnosis of glaucoma for those who were screened positively was 8.5 times higher than the estimated baseline risk for the reference population; the positive predictive value of the screening protocol was 30%. Screening excluded 80% of the initial population. Conclusion: Application of a formal screening protocol (such as our algorithm or its equivalent) in clinical settings can be helpful in detecting new cases of glaucoma. Preliminary performance assessment of the algorithm showed its applicability and effectiveness in detecting glaucoma among subjects without any visual complaint.

Se efectuó un estudio descriptivo y transversal de 73 pacientes con baja visión, que asistieron a la consulta del Centro Oftalmológico del Hospital General Docente "Dr. Juan Bruno Zayas Alfonso" de Santiago de Cuba, desde julio hasta diciembre del 2009, a fin de describir algunas características clínicas y demográficas. La degeneración macular asociada a la edad primó en más de 25,0 % de los integrantes de la casuística, seguida por el glaucoma crónico simple y la miopía degenerativa y, según lugar de procedencia, los pertenecientes al municipio de Santiago de Cuba representaron 73,0 % del total. Se logró rehabilitar a 89,0 % de los pacientes examinados y tratados.A descriptive and cross sectional study of 73 patients with low vision who visited the Ophthalmologic Center at "Dr. Juan Bruno Zayas Alfonso" Teaching General Hospital in Santiago de Cuba was carried out from July to December 2009 in order to describe some clinical and demographic characteristics. Macular degeneration associated with age prevailed in more than the 25,0% of the case material, followed by simple chronic glaucoma and degenerative myopia and, according to origin place, those belonging to Santiago de Cuba municipality represented 73,0% of the total. It was possible to rehabilitate the 89,0% of the examined and treated patients.

Background: Phacoemulsification is a common cataract operation nowadays. During phacoemulsification, variation in intraocular pressure (IOP) may occur, which might change the retinal nerve fiber layer (RNFL) thickness. This study was aimed to evaluate the change in peripapillary RNFL thickness and mean deviation (MD) of visual field after phacoemulsification in chronic primary glaucoma and nonglaucoma patients. Methods: Cohort prospective study was done on 26 patients (13 chronic glaucoma eyes and 13 non-glaucoma eyes) who underwent phacoemulsification. The changes in peripapillary RNFL thickness and MD of visual field were measured as the primary outcome. Comparison between pre- and post-surgery was analyzed with paired t-test, while unpaired t-test was used for comparison between groups. Results: There were no significant changes in RNFL thickness on both groups. Average RNFL thickness in glaucoma group before and after phacoemulsification were 94.9±20.0 μm and 99.1±21.3 μm, respectively (p>0.05). Average RNFL thickness in non-glaucoma group were 100.2±11.1 μm and 101.7±6.8 μm, respectively (p>0.05). Glaucoma patients yielded decreasing mean deviation (MD) of visual field, but it was not statistically significant (p=0.071). In contrast, the MD of visual field after surgery was significantly increased in non-glaucoma group (p=0.005). Conclusion: Phacoemulsification tended to increase peripapillary RNFL thickness in glaucoma or non-glaucoma patients. The visual field tended to decrease in glaucoma patients, but was significantly increased in non-glaucoma patients. [ABSTRACT FROM AUTHOR]

Background: Primary open angle glaucoma is reported to blind 150,000 people in the Nigerian population and over 7000 in Rivers State, and requires constant follow-up. Compliance is a challenge, given that most inhabitants live below the poverty line. This study was performed to determine how Nigerian patients are affected economically by the disease. Methods: Consecutive adult patients attending the eye clinic of the University of Port Harcourt Teaching Hospital, Rivers State, Nigeria, with a diagnosis of primary open angle glaucoma and on outpatient antiglaucoma treatment in the first 6 months of 2006, were recruited for the study. The lowest paid government worker was on USD50 (N7500.00) per month and the gross domestic product per capita was USD1150 for the period under review. Results: We enrolled 120 consecutive patients of mean age 52.7 ± 10.4 years, with a male to female ratio of 2:3. The most common occupations were in the civil service (n = 56, 46.7%). All participants were on topical antiglaucoma treatment. The average cost of medical antiglaucoma medication was N6000 (USD40) per month. Computed to include indirect costs, including medical laboratory tests, transportation, and care by patient escorts, an average sum of USD105.4 (N15,810) was spent by each patient per month. Most of the patients (73.3%) were responsible for their own treatment costs. No patient accepted the cheaper option of surgery (USD275.4, N41,310). Eighty of the patients (66.7%) visited our eye clinic monthly. Direct and indirect loss to the economy was USD3,064587 per annum from those already blind. This was in addition to the USD 4.1 million being spent yearly on medical treatment by those who were visually impaired by glaucoma. Conclusion: Middle-income earners spent over 50% of their monthly income and low-income earners spend all their monthly earnings on treatment for glaucoma. This situation often resulted in noncompliance with treatment and hospital follow-up visits. To reduce the economic burden of glaucoma, trabeculectomy performed by experienced surgeons should be offered as first-line treatment for glaucoma in this country, rather than medical therapy. [ABSTRACT FROM AUTHOR]

Abstract: Glaucoma is a neurodegenerative disease of the visual system. While elevated intraocular pressure is considered to be a major risk factor, the primary cause and pathogenesis of this disease are still unclear. This study aims to employ in vivo proton magnetic resonance spectroscopy (1H MRS) to evaluate the metabolic changes in the visual cortex in a rat model of chronic glaucoma. Five Sprague–Dawley female rats were prepared to induce ocular hypertension unilaterally in the right eye by photocoagulating the episcleral and limbal veins using an argon laser. Single voxel 1H MRS was performed on each side of the visual cortex 6 weeks after laser treatment. Relative to the creatine level, the choline level was found to be significantly lower in the left glaucomatous visual cortex than the right control visual cortex in all animals. In addition, a marginally significant increase in glutamate level was observed in the glaucomatous visual cortex. No apparent difference was observed between contralateral sides of the visual cortex in T1-weighted or T2-weighted imaging. The results of this study showed that glaucoma is accompanied with alterations in the metabolism of choline-containing compounds in the visual cortex contralateral to the glaucomatous rat eye. These potentially associated the pathophysiological mechanisms of glaucoma with the dysfunction of the cholinergic system in the visual pathway. 1H MRS is a potential tool for studying the metabolic changes in glaucoma in vivo in normally appearing brain structures, and may possess direct clinical applications for humans. Measurement of the Cho:Cr reduction in the visual cortex may be a noninvasive biomarker for this disease. [Copyright &y& Elsevier]

Abstract: Glaucoma is a neurodegenerative disease of the visual system characterized by the elevation of intraocular pressure. While this elevated pressure is related to an increased resistance to the outflow of aqueous humor from the eye, their impacts to the etiology and pathogenesis of the disease are not fully understood. This study aims to employ in vivo Gd-DTPA enhanced magnetic resonance imaging to evaluate the ocular transport following an induction of ocular hypertension in a rat model of chronic glaucoma. An experimental ocular hypertension model was induced in adult rats using an argon laser to photocoagulate the episcleral and limbal veins on the surface of the eyeball. The enhancements of the MRI signal intensity in the anterior chamber and vitreous body were measured as a function of time following systemic administration of Gd-DTPA solution at 3mmol/kg. Results showed a progressive T1-weighted signal increase in the vitreous body of the glaucomatous eye but not the control eye. This increase occurred earlier in the anterior vitreous body than the preretinal vitreous. Further, there was an earlier Gd-DTPA transport into the anterior chamber in the majority of glaucomatous eyes. Our findings revealed the leakage of Gd-DTPA at the aqueous–vitreous interface, which was likely resulted from increased permeability of blood–aqueous or aqueous–vitreous barrier. These may explain the sources of changing biochemical compositions in the glaucomatous chamber components, which may implicate the cascades of neurodegenerative processes in the retina and the optic nerve. [Copyright &y& Elsevier]

Abstract: Glaucoma is a neurodegenerative disease of the visual system. While elevated intraocular pressure is considered to be a major risk factor, the primary cause and pathogenesis of the disease are still unclear. This study aims to employ in vivo manganese-enhanced magnetic resonance imaging (MEMRI) to evaluate dynamically the Mn2+ enhancements in the visual components following an induction of ocular hypertension in a rat model of chronic glaucoma. The episcleral and limbal veins were photocoagulated unilaterally in the right eye using an argon laser to maintain a consistent elevation of intraocular pressure by about 1.6 times above the normal level. Two and six weeks after glaucoma induction, MnCl2 solution (50 mM, 3 μL) was injected intravitreally into both eyes, and MEMRI was performed 2 to 5 h after injection. Results showed a delayed increase in T1-weighted signal intensity in the glaucomatous optic nerve at 6 weeks but not 2 weeks after glaucoma induction. In addition, there was an accumulation of Mn2+ ions in the vitreous humour of the glaucomatous eye, with a high concentration of Mn2+ ions at the optic nerve head and the retina. These MEMRI findings may help understand the disease mechanisms, monitor the effect of drug interventions in glaucoma models and complement the conventional techniques in examining the glaucomatous visual components. [Copyright &y& Elsevier]

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Glaucoma is a multifactorial disease in which retinal ganglion cells (RGCs) undergo excitotoxic damage, leading to their degeneration. The α2-adrenoceptor (α2-AR) agonist brimonidine exerts a neuroprotective effect by regulating postsynaptic excitatory N- methyl-D-aspartate (NMDA) receptor activity in RGCs. However, researchers have not clearly determined whether or how brimonidine regulates inhibitory synaptic transmission in rat models of chronic glaucoma. Whole-cell voltage-clamp and current-clamp recordings were performed in ON- and OFF-type RGCs in retinal slices. Brimonidine directly and acutely enhanced γ-aminobutyric acidergic (GABAergic) transmission mediated by ionotropic GABA A receptors in ON- and OFF-type RGCs in rat retinal slices; this effect occurred at the synaptic terminals and was independent of action potentials and multi-synaptic connections. The highly selective α2-AR antagonist yohimbine blocked the effects of brimonidine. Regarding the postsynaptic GABA receptor sensitivity, brimonidine also increased the amplitude of the GABA-induced current. Additionally, compared to RGCs from the control group, the frequencies and amplitudes of spontaneous excitatory postsynaptic currents (sEPSCs) and miniature excitatory postsynaptic currents (mEPSCs) did not change after brimonidine gravity perfusion. Brimonidine significantly decreased the spontaneous firing frequency of rat RGCs with intact synaptic inputs and decreased the resting membrane potential of RGCs, changes that were blocked by the highly selective GABA A receptor antagonist SR95531. SR95531 alone increased spontaneous action potentials and the resting membrane potential. Based on these findings, an α2-AR agonist facilitated the frequency of the GABAergic inhibitory postsynaptic currents (IPSCs), directly increased the amplitude of the postsynaptic GABA-induced current (GABA receptor reactivity/sensitivity), suppressed the firing frequency of spontaneous action in RGCs with intact synaptic inputs and decreased the resting membrane potential of RGCs, thus deactivating RGCs from the neural network level and reducing the excitotoxic damage occurring during the pathological process of chronic glaucoma. • Brimonidine directly and acutely enhances GABAergic transmission. • Brimonidine increases the amplitude of GABA-induced currents in RGCs. • Brimonidine has no effect on the sEPSCs and mEPSCs. • Brimonidine decreases the fring frequency and the resting membrane potential of RGCs. • The effects of brimonidine were blocked by yohimbine and SR95531. [ABSTRACT FROM AUTHOR]