Intraocular Pressure (intraocular + pressure)

Distribution by Scientific Domains

Kinds of Intraocular Pressure

  • elevated intraocular pressure

  • Selected Abstracts

    Ocular complications of neurological therapy

    S. Hadjikoutis
    Treatments used for several neurological conditions may adversely affect the eye. Vigabatrin-related retinal toxicity leads to a visual field defect. Optic neuropathy may result from ethambutol and isoniazid, and from radiation therapy. Posterior subcapsular cataract is associated with systemic corticosteroids. Transient refractive error changes may follow treatment with acetazolamide or topiramate, and corneal deposits and keratitis with amandatine. Intraocular pressure can be elevated in susceptible individuals by anticholinergic drugs, including oxybutynin, tolterodine, benzhexol, propantheline, atropine and amitriptyline, and also by systemic corticosteroids and by topiramate. Nystagmus, diplopia and extraocular muscle palsies can occur with antiepileptic drugs, particularly phenytoin and carbamazepine. Ocular neuromyotonia can follow parasellar radiation. Congenital ocular malformations can result from in utero exposure to maternally prescribed sodium valproate, phenytoin and carbamazepine. Neurologists must be aware of potential ocular toxicity of these drugs, and appropriately monitor for potential adverse events. [source]

    2424: Pulsatile haemodynamics: potential for end-organ damage?

    Purpose Increases in velocity pulse wave amplitude, or max:min velocity ratio, represent early haemodynamic disturbances associated with diabetic retinopathy (DR) and age-related macular degeneration. This change reflects an increase in vessel wall rigidity that is generally accepted to occur in the central vasculature but the peripheral vasculature is also implicated in this process. This presentation will highlight the implications of these changes in terms of end-organ damage in DR. Methods The sample comprised 4 groups: Group 1: 50 non-diabetic control subjects. Group 2: 56 diabetic patients without clinically visible DR. Group 3: 54 diabetic patients with micro-aneurysms and / or hard exudates within 2 disc diameters of the fovea in the absence of clinically manifest diabetic macular edema (DME). Group 4: 40 patients with clinically manifest DME. The diabetic patients were predominantly type 2. Retinal hemodynamics were assessed in the superior temporal retinal arteriole using the Canon Laser Blood Flowmeter. Intraocular pressure, blood pressure and relevant systemic markers of diabetes control and complications were also assessed. Results The velocity pulse wave amplitude was elevated with increasing risk of DME (p<0.0001). No significant differences were found between the groups with respect to diameter, velocity or flow. Pulse wave amplitude was correlated to age, duration of diabetes, blood pressure, pulse rate, IOP and serum potassium levels. Conclusion The increase in velocity pulse wave amplitude will induce excessive pressure pulsatility in the retinal arterioles and capillaries, changes in vascular function (e.g. loss of vascular regulation) and changes in vessel structure. Commercial interest [source]

    Evaluation of anterior segment parameter changes using the Pentacam after uneventful phacoemulsification

    Selim Doganay
    Abstract. Purpose:, This study set out to evaluate the influences of uneventful phacoemulsification on the anterior segment parameters obtained with the Pentacam rotating Scheimpflug camera and intraocular pressure (IOP). Methods:, A total of 42 eyes of 34 patients (26 men, eight women) were evaluated preoperatively, and at 1, 3 and 6 months postoperatively with the Pentacam. Intraocular pressure was measured with the Goldmann applanation tonometer. The non-parametric paired t -test was used to compare preoperative and 1-, 3- and 6-month postoperative measurements of anterior chamber depth (ACD), anterior chamber volume (ACV), anterior chamber angle (ACA) width, central corneal thickness (CCT), the central 3-, 5- and 7-mm corneal volume (CV), pupil size, and IOP. Pearson's correlation test was used to evaluate the relationships between IOP and ACD, ACV and ACA width. Results:, The differences between ACD, ACV, ACA and IOP values taken preoperatively and those taken postoperatively at 1, 3 and 6 months were statistically significant (p < 0.05). The differences between CCT, central 3-, 5- and 7-mm CV, and pupil size measurements taken preoperatively and those taken postoperatively at 1, 3 and 6 months were not statistically significant (p > 0.05). The decrease in IOP was not correlated with the changes in ACD, ACV and ACA (p > 0.05). Conclusions:, Uneventful phacoemulsification significantly reduced IOP, increased ACD and ACV, and widened the ACA. However, alterations in CV, CCT and pupil size values were not statistically significant. Alterations in ACD, ACV, ACA and IOP remain stable after the first month of surgery. [source]

    Effect of acute postural variation on diabetic macular oedema

    Martin Vinten
    Abstract. Purpose:, This study aimed to study the pathophysiology of diabetic macular oedema (DMO) by analysis of concomitant changes in macular volume (MV), mean arterial blood pressure (MABP), intraocular pressure (IOP), and retinal artery and vein diameters in response to acute postural changes in patients with DMO and healthy subjects. Methods:, Thirteen patients with DMO (13 eyes) and five healthy subjects (five eyes) were examined after resting in a chair for 15 mins using optical coherence tomography to measure MV and fundus photography to assess retinal vessel diameters. The patients then lay down for 60 mins, during which they were examined repeatedly before they were reseated and examined again. Intraocular pressure was measured using pulse-air tonometry, arterial blood pressure by sphygomanometry and fluid columns using rulers and a spirit level. Results:, In healthy subjects, retinal artery (p = 0.02) and vein (p = 0.001) diameters decreased when subjects lay down, whereas MV remained stable. In patients with DMO, no orthostatic variation in retinal vessel diameters could be demonstrated, whereas MV had increased by 2.4 ± 0.6% (mean ± standard error of the mean; p = 0.006) 50 mins after assuming a recumbent position. In both healthy subjects and DMO patients, MABP decreased and IOP increased in a recumbent position, with no significant difference between the groups. Conclusions: The increase in MV that occurs in DMO when changing from a seated to a recumbent position is associated with a failure of retinal artery contraction, a response seen in healthy subjects that appears to counter-regulate the increase in ocular perfusion pressure caused by assuming a recumbent position. [source]

    Longterm follow-up of diode laser transscleral cyclophotocoagulation in the treatment of refractory glaucoma

    Paolo Frezzotti
    Abstract. Purpose:, This prospective study was conducted to evaluate the efficacy and safety of transscleral diode laser cyclophotocoagulation (TDLCP) in advanced refractory glaucoma. Methods:, A total of 124 eyes in 121 patients with advanced glaucoma refractory to medical treatment were treated consecutively with TDLCP. Success was defined as final intraocular pressure (IOP) of 5,21 mmHg in eyes with visual acuity (VA) of more than hand movements (HM) and relief of pain in eyes with VA of HM or less, including blind eyes. Results:, Mean patient age was 65.6 ± 17.1 years (range 14,91 years). Mean follow-up was 17 ± 14.6 months (range 3,42 months). Mean pretreatment IOP was 29.9 ± 8.4 mmHg (range 17,58 mmHg) and IOP at last follow-up was 20.8 ± 8 mmHg (range 6,45 mmHg) (p < 0.001). The number of laser applications (mean 9.2 ± 2.8, range 4,15) and maximal laser power (mean 2.01 ± 0.22 mW, range 1.3,3.0 mW) were not associated with lower postoperative IOP. Intraocular pressure of , 21 mmHg was recorded in 63.0% of eyes at the last follow-up visit. Overall, 28 (21.7%) eyes required at least one retreatment. No phthisis bulbi or persistent hypotonia developed. Conclusions:, TDLCP is an effective and safe method for the treatment of advanced refractory glaucoma, although repeated treatments are often necessary. [source]

    Changes in optic nerve head blood flow induced by the combined therapy of latanoprost and beta blockers

    Tetsuya Sugiyama
    Abstract. Purpose, To assess the effects of combined therapy with latanoprost and beta blockers on optic nerve head (ONH) blood flow in normal-tension glaucoma (NTG) patients. Methods, Intraocular pressure (IOP), ONH blood flow (laser speckle flowgraphy) and blood pressure were measured in 15 eyes of 15 NTG patients (41,76 years old) before treatment or after a 1-month washout period. Similar measurements were performed at 2 months after the commencement of treatment with latanoprost and at 3 months after the start of combined therapy of latanoprost with 0.5% timolol or 2% carteolol in a crossover study using the envelope method. Measurement was carried out 2,3 hr after the morning application of eyedrops. Results, Latanoprost decreased IOP with no significant change in ONH blood flow. Concomitant use of timolol or carteolol further decreased IOP with no significant difference between these two drugs. Only the combined therapy of latanoprost with carteolol significantly (p < 0.01) increased ONH blood flow by approximately 10%, compared to initial levels. There was no significant change in mean blood pressure, ocular perfusion pressure or pulse rate as a result of these therapies. Conclusion:, Topical latanoprost,carteolol combined therapy increased ONH blood flow in NTG patients, unlike latanoprost,timolol therapy. Because ocular perfusion pressure was unchanged, direct vasodilative effects were suspected as the mechanism. [source]

    Consequences of dietary omega-3 polyunsaturated fatty acid deficiency on retinal function and intraocular pressure in the rat

    Purpose Omega-3 polyunsaturated fatty acids (,3) are key components in nervous structures but their dietary intakes in the overall population are often below nutritional requirements. A chronic deficiency in ,3 is recognized to be associated with functional impairment of the retina. At the opposite, ,3 supplementation is associated with a reduced risk for AMD. The consequences of ,3 deficiency on other eye structures than the retina, such as ciliary bodies, are scarce. The purpose of our study was to compare the response of the retina and ciliary bodies to dietary ,3 deficiency in terms of fatty acid profile and eye functionality. Methods Two successive generations of Lewis rats (G1 and G2) were obtained under either a standard or ,3-deficient diet. Intraocular pressure (IOP) was measured by rebound tonometry throughout the experiment. Retinal functionality was assessed by scotopic electroretinography (ERG). Gas chromatography was used to determine the fatty acid profile of the ciliary bodies and retina. Results A 2-fold fall in DHA content of the retina was observed in ,3-deficient G1 animals. This decrease was accentuated in G2 (-66%) and counterbalanced by an increase in DPA,6 in the retina. The b-wave amplitude of the ERG was decreased by 50% at 9mcds/m² in ,3-deficient rats. In ciliary body DHA was reduced by 80% in ,3-deficient in G1 animals but not in G2. Meanwhile, animals from the ,3-deficient diet had increased IOP (18 vs 12mmHg, p<0.0001). Conclusion The crucial role of ,3 in retinal function was confirmed. The most relevant finding from our study is the rise in IOP, the major risk factor for glaucoma, which was observed in animals reared under dietary deficiency in ,3. [source]

    Intraocular pressure and associated factors in a Central Indian population.

    Medical Study, The Central India Eye
    Purpose To evaluate the intraocular pressure (IOP) and its associated factors in the adult population of rural India. . Methods The Central India Eye and Medical Study is a population-based study performed in a rural region close to Nagpur in Central India. It included 4711 subjects (aged 30+ years) out of 5885 eligible subjects (response rate: 80.1%). The participants underwent a detailed ophthalmic and medical examination. This study was focused on the IOP. Results Out of the 4711 subjects (9422 eyes), IOP measurements were available for 9338 (99.1%) eyes of 4686 (99.5%) subjects. The mean IOP was 13.6±3.4 mm Hg (median: 14 mm Hg; range: 2,56 mm Hg). Assuming a Gaussian distribution curve, the normal range of IOP, defined as mean ± two standard deviations, was from 6.8 mm Hg to 20.4 mm Hg. In multivariate analysis, IOP was significantly associated with the systemic parameters of higher diastolic blood pressure (P<0.001), higher pulse rate (P=0.004), and higher body mass index (P=0.007); the socioeconomic parameters of higher level of education (P=0.004), higher cast (P=0.002), and no livestock ownership (P=0.01); and the ocular parameters of higher corneal refractive power (P<0.001), lower central corneal thickness (P=0.002) and higher myopic refractive error (P=0.002). Conclusion The normal range of IOP was from 7 mm Hg to 20 mm Hg. Determinants of IOP were higher diastolic blood pressure, higher pulse rate, higher body mass index, higher level of education, higher cast, higher corneal refractive power, lower central corneal thickness and higher myopic refractive error. [source]

    Trabeculectomy with an active postoperative regimen: results and resource utilization

    Amelie B. Taube
    Abstract. Purpose:, To evaluate intraocular pressure (IOP) and resource utilization after trabeculectomy, using an active postoperative regimen, in a Swedish population. Methods:, A retrospective analysis was performed on the patient charts of all patients who underwent trabeculectomy in a Swedish university hospital during 1 year (November 2000,December 2001). Trabeculectomy was performed in 34 eyes and trabeculectomy in combination with phacoemulsification in 10 eyes. Intraocular pressure, visual acuity, complications and numbers of injections of 5-fluorouracil, suture removal, needling procedures and visits to ophthalmologists were recorded for 2 years. Results:, Mean IOP before surgery was 30.4 mmHg (standard deviation [SD] 9.5) in eyes with capsular glaucoma and 28.7 mmHg (SD 9.3) in eyes with primary open-angle glaucoma. Mean IOP after 2 years was 15.3 mmHg (SD 3.9) in all eyes. Intraocular pressure of < 18 mmHg was achieved in 65% of the eyes after 2 years, as was IOP , 13 mmHg in 37%. Flap or suture manipulation was performed in 41 of 44 eyes. Needling procedures were carried out a mean of 2.3 times in 31 eyes. The mean number of visits to an ophthalmologist was 14.1 during the first postoperative year and 4.4 during the second. Conclusions:, The results were encouraging, with few complications and modest resource utilization. [source]

    Effect of bromfenac ophthalmic solution on ocular inflammation following cataract surgery

    Masaru Miyanaga
    Abstract. Purpose:, This study compared the post-cataract surgery anti-inflammatory effects of topical treatment with 0.1% bromfenac, 0.1% betamethasone or both on postoperative anterior chamber inflammation and corneal swelling. Methods:, Seventy-two patients with no eye disease other than cataract were enrolled in a prospective, randomized study to undergo phacoemulsification combined with intraocular lens implantation. After cataract surgery, patients were randomized to treatment with bromfenac, betamethasone or both agents. Twenty-five eyes were assigned to bromfenac, 23 to betamethasone and 24 to the combined treatment group. Inflammatory reactions in the anterior chamber were measured with laser flare photometry preoperatively and at 1 and 3 days, 1 and 2 weeks, and 1 and 2 months postoperatively. Intraocular pressure (IOP) and corneal thickness were measured at the same time-points. Best corrected visual acuity (BCVA) was measured preoperatively and at 2 days, 1 and 2 weeks, and 1 and 2 months postoperatively. Specular microscope endothelial photography of the central region of the cornea was performed preoperatively and at 3 months after surgery. Results:, There were no significant differences among the bromfenac, betamethasone and combined treatment groups in BCVA, IOP, aqueous flare or corneal thickness. Cystoid macular oedema was present in one eye treated with betamethasone. Conclusions:, There were no significant differences in anti-inflammatory effects among the three treatments. These findings suggest that bromfenac is as effective as betamethasone in minimizing inflammatory reactions after cataract surgery. [source]

    Protocol for mitomycin C use in glaucoma surgery

    J. A. Maquet
    Abstract. Purpose:,To evaluate the results of a protocol described for mitomycin C (MMC) use in trabeculectomy or combined surgery (phacoemulsification and trabeculectomy). Methods:,A total of 143 eyes (60 trabeculectomies and 83 combined surgeries) of 124 patients were divided into four groups: group 1 (without MMC); group 2 (with 0.1 mg/ml MMC); group 3 (with 0.2 mg/ml MMC), and group 4 (with 0.4 mg/ml MMC). Two-minute MMC was used in every case in groups 2, 3 and 4. The results were analysed after 1 year of follow-up. Intraocular pressure (IOP) and complications were evaluated. Successful IOP control was defined when IOP was <21 mmHg and <16 mmHg if advanced glaucoma was present, always without additional medical treatment. Results:,Mean preoperative IOP decreased from 24.60 mmHg (SD 1.40 mmHg) to 13.47 mmHg (SD 0.37 mmHg) (p < 0.00001), 12 months postoperatively. Control in IOP was achieved in 79.02% of eyes. No significant differences were found in final mean IOP values (p > 0.196) or in postoperative complications (p > 0.120) in groups 2, 3 and 4. Conclusion:,With the protocol described, a selection of concentration of MMC has been made in different clinical forms of glaucoma. No significant differences in IOP control and postoperative complications were noticed among the groups. [source]

    The short-term effect of latanoprost on intraocular pressure and pulsatile ocular blood flow

    Gerasimos T. Georgopoulos
    ABSTRACT. Purpose:, There is evidence that ocular blood flow plays a critical role in the clinical course of glaucoma. Any reduction in ocular blood flow due to topical antiglaucoma treatment should therefore be avoided. This study aimed to evaluate the short-term effect of local latanoprost application on ocular hemodynamics. Methods:, Intraocular pressure (IOP), ocular pulse amplitude (OPA), ocular pulse volume (OPV), systemic blood pressure, heart rate and the pulsatile component of ocular blood flow (POBF) were recorded using a pneumotonometer linked to the Langham Ocular Blood Flow System in 24 patients in a prospective, open-label study before and after 1 week of topical latanoprost application in both eyes. Twenty of the subjects had primary open-angle glaucoma and four had ocular hypertension. Results:, After 1 week of latanoprost treatment, IOP decreased significantly 6.2 ± 2.9 mmHg in OD (P < 0.001) and 6.2 ± 3.2 mmHg in OS (P < 0.001). Pulsatile OBF increased significantly by 201.2 ± 167.4 µL/min in OD (P < 0.001) and 203.8 ± 187.3 µL/min in OS (P < 0.001). Ocular pulse amplitude and OPV showed statistically significant increases (P < 0.05 and P < 0.001 respectively). Blood pressure and heart rate did not change significantly. Conclusion:, Our results indicate that 1 week after latanoprost application, POBF, OPA and OPV were significantly increased in the eyes treated. More information on the perfusion of the optic nerve head is needed before the relevance of these findings to optic nerve head blood flow can be interpreted correctly. [source]

    Intraocular pressure and progression in exfoliative eyes with ocular hypertension or glaucoma

    Mika Harju
    ABSTRACT. Purpose: This retrospective study was conducted in exfoliative eyes in order to study the influence of IOP and other possible factors on the conversion from ocular hypertension (OHT) to glaucoma and progression of glaucoma. Methods: 139 patients with exfoliation OHT or glaucoma with exfoliation syndrome were included (mean follow-up 5.2±3.6 years). The effects of age, gender, weighted mean IOP, maximum IOP, stage of glaucoma at the first visit, refraction, glaucoma medication, and interventions on the hazard of progression were studied by multivariate survival analysis. Results: Conversion from OHT to glaucoma or progression of glaucoma was detected in 63 eyes (45.3%). A significant association with progression was found for age (relative risk 1.042; p-value 0.043), weighted mean IOP (1.076; <0.001), and stage of glaucoma (1.436; <0.001). History of trabeculectomy (0.360; 0.002) related to a decreased risk. Conclusion: The risk of conversion from OHT to glaucoma and progression of glaucoma increased in exfoliative eyes with severity of stage of glaucoma, weighted mean IOP, and the age of the patient. A history of trabeculectomy was related to decreased risk of progression. [source]

    Inadvertent sclerostomy with encysted bleb following trans-scleral contact diode laser cyclophotocoagulation

    Viney Gupta MD
    Abstract A 22-year-old woman underwent 360° trans-scleral contact diode laser cyclophotocoagulation for refractory glaucoma. Conjunctival burns and scleral thinning were noticed inferonasally at the last laser application. Intraocular pressure in the first week was normal. Six months later the patient presented with encysted filtering bleb and high intraocular pressure. Ultrasound biomicroscopy revealed a full thickness sclerostomy. This report suggests that inadvertent sclerostomy may present with encysted bleb months after trans-scleral contact diode laser cyclophotocoagulation. [source]

    Intraocular pressure: relevant or redundant?

    Helen V Danesh-Meyer FRANZCO
    No abstract is available for this article. [source]

    Relationship between intraocular pressure and systemic health parameters in a Korean population

    Jong Soo Lee MD
    Abstract Purpose: This study aimed to evaluate the relationship between intraocular pressure (IOP) and age and obesity, adjusted for systemic health parameters such as sex and mean blood pressure, in a Korean population. Methods: A total of 13 212 healthy participants underwent automated multiphasic tests, including tonometry, automated perimetry, fundus photography, blood pressure and body mass index (BMI). Six age groups were used, divided by decades ranging from 20,29 years to 70+ years. The association between IOP and systemic health para­meters was examined using cross-sectional analysis. Results: The median age of participants was 47.6 years (range 20,84 years), and 6684 (50.6%) of participants were men. The mean IOP of participants was 15.5 mmHg. The mean IOP, blood pressure and BMI values were significantly higher in men than in women (P < 0.05). The overall prevalence of ocular hypertension, defined as IOP >21 mmHg without signs of glaucomatous visual field loss or optic disc damage, was 6.1% in men and 2.5% in women. Intraocular pressure was associated with mean blood pressure, sex, age and BMI by multiple regression analysis (P < 0.05). The relationship between IOP and age adjusted for sex, mean blood pressure and BMI had a significantly negative tendency for both sexes (P < 0.05). Body mass index had a significantly positive relation with IOP after controlling for age, sex and mean blood pressure in men (P < 0.05), but not in women. Conclusions: In this Korean population, after multiple adjust­ment, IOP was found to decrease with age and to increase with BMI in men. [source]

    Comparison of dynamic contour tonometry with Goldmann applanation tonometry in glaucoma practice

    Ioannis Halkiadakis
    Abstract. Purpose:, To compare intraocular pressure (IOP) readings taken using dynamic contour tonometry (DCT) with IOP readings taken with Goldmann applanation tonometry (GAT) in eyes with glaucoma or ocular hypertension. Methods:, The present study included 100 eyes in 100 patients with glaucoma or ocular hypertension. After pachymetry DCT and GAT were performed. Intraocular pressures as measured with DCT and GAT were compared with one another and with central corneal thickness (CCT). Results:, Mean DCT IOP measurements (20.1 ± 4.3 mmHg) were significantly (p < 0.001) higher than GAT IOP values (17.9 ± 4.7 mmHg). The mean difference between DCT and GAT measurements was 2.1 mmHg (range , 3.4 to 9.7 mmHg). The difference followed a normal distribution. Measurements made with DCT and GAT correlated significantly with one another (Spearman's rho = 0.761, p < 0.001). Neither GAT nor DCT measurements showed a significant correlation with CCT (537 ± 39 ,m, range 458,656 ,m). Multivariate regression analysis has shown that the difference between DCT and GAT is influenced significantly by ocular pulse amplitude (r = , 0.334, p = 0.001) and it is not influenced by CCT (r = , 0.106, p = 0.292). Conclusions:, In eyes with glaucoma or ocular hypertension, DCT facilitates suitable and reliable IOP measurements which are in good concordance with GAT readings. Variation in CCT cannot by itself explain the differences in measurements taken with DCT and GAT in a number of eyes. [source]

    Efficacy and safety of timolol maleate/latanoprost fixed combination versus timolol maleate and brimonidine given twice daily

    William C. Stewart
    Abstract. Purpose:, To evaluate the efficacy and safety of the timolol maleate/latanoprost fixed combination (TLFC) given once each evening versus brimonidine and timolol solution given twice daily as concomitant therapy in primary open-angle glaucoma or ocular hypertension patients. Methods:, Qualified subjects were begun on timolol alone twice daily for 1 month and then randomized to either TLFC or brimonidine and timolol concomitant therapy for 6 weeks. Patients were then switched to the other treatment regimen. Intraocular pressures (IOPs) were measured every 2 hours between 08 : 00 and 20 : 00 hours at baseline and at the end of periods 1 and 2. Results:, This study found that in 32 subjects the IOP diurnal curve on timolol alone (20.9 ± 2.8 mmHg) decreased to 17.9 ± 3.2 mmHg when patients were treated with TLFC and to 19.0 ± 2.4 mmHg when patients were treated with brimonidine and timolol (p = 0.02). Intraocular pressures at individual time-points were statistically similar between the groups at the 08 : 00 trough and 2 and 4 hours after dosing. However, beyond 4 hours after dosing, TLFC-treated subjects demonstrated a trend towards lower IOPs at each 2-hour time-point that was not statistically significant after a Bonferroni correction (p , 0.05). The incidence of both solicited and unsolicited side-effects was similar between groups. Conclusion:, This study suggests that TLFC given in the evening reduces the mean daytime diurnal IOP more than brimonidine and timolol given concomitantly twice daily. [source]

    Diadenosine tetraphosphate protects sympathetic terminals from 6-hydroxydopamine-induced degeneration in the eye

    ACTA PHYSIOLOGICA, Issue 2 2010
    C. H. V. Hoyle
    Abstract Aims:, To examine diadenosine tetraphosphate (Ap4A) for its ability to protect the eye from neurodegeneration induced by subconjunctival application of 6-hydroxydopamine (6-OHDA). Methods:, Intraocular neurodegeneration of anterior structures was induced by subconjunctival injections of 6-OHDA. Animals were pre-treated with topical corneal applications of Ap4A or saline. Results:, 6-OHDA caused miosis, abnormal pupillary light reflexes, a precipitous drop in intraocular pressure and loss of VMAT2-labelled (vesicle monoamine transporter-2, a marker for sympathetic neurones) intraocular neurones. Pre-treatment with Ap4A prevented all of these changes from being induced by 6-OHDA, demonstrably preserving the sympathetic innervation of the ciliary processes. This neuroprotective action of Ap4A was not shared with the related compounds adenosine, ATP or diadenosine pentaphosphate. P2-receptor antagonists showed that the effects of Ap4A were mediated via a P2-receptor. Conclusion:, Ap4A is a natural component of tears and aqueous humour, and its neuroprotective effect indicates that one of its physiological roles is to maintain neurones within the eye. Ap4A can prevent the degeneration of intraocular nerves, and it is suggested that this compound may provide the basis for a therapeutic intervention aimed at preventing or ameliorating the development of glaucoma associated with neurodegenerative diseases. Furthermore, subconjunctival application of 6-OHDA provides a useful model for studying diseases that cause ocular sympathetic dysautonomia. [source]

    Dexamethasone alters F-actin architecture and promotes cross-linked actin network formation in human trabecular meshwork tissue

    CYTOSKELETON, Issue 2 2005
    Abbot F. Clark
    Abstract Elevated intraocular pressure is an important risk factor for the development of glaucoma, a leading cause of irreversible blindness. This ocular hypertension is due to increased hydrodynamic resistance to the drainage of aqueous humor through specialized outflow tissues, including the trabecular meshwork (TM) and the endothelial lining of Schlemm's canal. We know that glucocorticoid therapy can cause increased outflow resistance and glaucoma in susceptible individuals, that the cytoskeleton helps regulate aqueous outflow resistance, and that glucocorticoid treatment alters the actin cytoskeleton of cultured TM cells. Our purpose was to characterize the actin cytoskeleton of cells in outflow pathway tissues in situ, to characterize changes in the cytoskeleton due to dexamethasone treatment in situ, and to compare these with changes observed in cell culture. Human ocular anterior segments were perfused with or without 10,7 M dexamethasone, and F-actin architecture was investigated by confocal laser scanning microscopy. We found that outflow pathway cells contained stress fibers, peripheral actin staining, and occasional actin "tangles." Dexamethasone treatment caused elevated IOP in several eyes and increased overall actin staining, with more actin tangles and the formation of cross-linked actin networks (CLANs). The actin architecture in TM tissues was remarkably similar to that seen in cultured TM cells. Although CLANs have been reported previously in cultured cells, this is the first report of CLANs in tissue. These cytoskeletal changes may be associated with increased aqueous humor outflow resistance after ocular glucocorticoid treatment. Cell Motil. Cytoskeleton 60:83,95, 2005. © 2004 Wiley-Liss, Inc. [source]

    Effects of (,)-carveol and HPMC on the in vitro ocular transport and the in vivo intraocular pressure lowering effects of dorzolamide formulations in normotensive New Zealand rabbits

    Mohsen I. Afouna
    Abstract The objective of the current study was to maximize the ocular bioavailability of the carbonic anhydrase inhibitor, dorzolamide hydrochloride (DZD) via (a) enhancement of DZD corneal transport using terpene enhancers, (b) reducing pre-corneal loss of the installed dose via increased formulation viscosity, and (c) assessment of the in vivo intraocular pressure (IOP) lowering effects of test formulations using rabbit. DZD was formulated as a 2% ophthalmic solution containing different concentrations of HPMC as a viscosity improving agent (VIA), and (,)-carveol as a corneal penetration enhancer. The transport of DZD from test formulations was quantitatively determined using in vitro diffusion experiments, the permeability parameters were mathematically calculated, and the in vivo IOP lowering effects were assessed using a Tono-Pen XL® tonometer. The results revealed a good correlation between the in vitro permeability parameters and the in vivo ,IOP. The magnitude of the DZD-IOP lowering effects and durations of actions for DZD formulations were dependent on (a) the concentration of (,)-carveol, and (b) the contact period with ocular tissue which was found to be a single-valued function of the HPMC as VIA. Drug Dev Res 70, 2009. © 2009 Wiley-Liss, Inc. [source]

    Bimatoprost, a novel efficacious ocular hypotensive drug now recognized as a member of a new class of agents called prostamides

    Robert M. Burk
    Pursuit of a new FP-agonist prodrug led to the identification of an interesting series of neutral C1-substituted prostaglandin F2, analogues. Although these initial analogues were devoid of any inherent pharmacological activity at the FP-receptor, two compounds AGN-190910 and AGN-191129, were found to have pronounced effects in lowering intraocular pressure (IOP) in normotensive dogs and monkeys. The cat iris sphincter assay was quickly developed as a primary screen for these analogues, leading to rapid identification of AGN-192024 (17-phenyl PGF2, ethyl amide, bimatoprost). While bimatoprost is structurally similar to naturally occurring mammalian hormones of the prostanoid family, surprisingly it demonstrates no significant activity at any of the known prostanoid receptors. Furthermore, results of considerable additional pharmacological studies provide evidence that it may indeed act through a unique receptor yet to be identified. The effect of Bimatoprost on lowering IOP has also been found to be unique in comparison to prostanoids. Bimatoprost reduces human IOP by increasing aqueous humor outflow through a dual mechanism of action where it improves both pressure-dependent and pressure-independent outflow pathways. First introduced to the market in 2002, bimatoprost is currently the most potent single therapy available for control of ocular hypertension. Drug Dev Res 68:147,155, 2007. ©2007 Wiley-Liss, Inc. [source]

    The synthetic cannabinoid WIN55212-2 decreases the intraocular pressure in human glaucoma resistant to conventional therapies

    Anna Porcella
    Abstract The search for new ocular hypotensive agents represents a frontier of current eye research because blindness due to optic neuropathy occurs insidiously in 10% of all patients affected by glaucoma. Cannabinoids have been proposed to lower intraocular pressure by either central or peripheral effects but a specific mechanism for this action has never been elucidated. We recently demonstrated the presence of the central cannabinoid receptor (CB1) mRNA and protein in the human ciliary body. In the present study we show that the synthetic CB1 receptor agonist, WIN 55212,2, applied topically at doses of 25 or 50 µg (n = 8), decreases the intraocular pressure of human glaucoma resistant to conventional therapies within the first 30 min (15 ± 0.5% and 23 ± 0.9%, respectively). A maximal reduction of 20 ± 0.7% and 31 ± 0.6%, respectively, is reached in the first 60 min. These data confirm that CB1 receptors have direct involvement in the regulation of human intraocular pressure, and suggest that, among various classes of promising antiglaucoma agents, synthetic CB1 receptor agonists should deserve further research and clinical development. [source]

    In vitro evaluation of reactive astrocyte migration, a component of tissue remodeling in glaucomatous optic nerve head

    GLIA, Issue 3 2001
    Gülgün Tezel
    Abstract In order to improve understanding of remodeling events in the glaucomatous optic nerve head, the migration of optic nerve head astrocytes was studied in vitro. Since elevated intraocular pressure is an important stress factor identified in glaucomatous eyes, optic nerve head astrocytes were incubated under physical stress created by elevated hydrostatic pressure. In addition, they were incubated in the presence of a chemical stimulus, lipolysaccharide (LPS). Migration of reactivated astrocytes in the presence of these stressors was examined using chambers in which cell migration through extracellular matrix-coated pores is only possible following proteolytic digestion of the matrix. We observed that the migratory ability of optic nerve head astrocytes was approximately 4,6 times greater following exposure to elevated hydrostatic pressure or LPS for up to 48 h. Phosphoinositide 3-kinase, protein kinase C, and tyrosine kinase were found to be involved in the signal transduction for activated migration of optic nerve head astrocytes in response to elevated hydrostatic pressure or LPS. In addition, we observed that the stress-induced migration of optic nerve head astrocytes, which is accompanied by proteolytic degradation, resulted in the formation of culture cavities containing mucopolysaccharides. These in vitro findings provide a clearer understanding of the pathophysiologic mechanisms of characteristic tissue remodeling events that occur, in vivo, in the glaucomatous optic nerve head. GLIA 34:178,189, 2001. © 2001 Wiley-Liss, Inc. [source]

    Myocilin allele-specific glaucoma phenotype database,

    HUMAN MUTATION, Issue 2 2008
    Alex W. Hewitt
    Abstract Glaucoma, a complex heterogenous disease, is the leading cause for optic nerve,related blindness worldwide. Since 1997, when mutations in the myocilin (MYOC) gene were identified as causing juvenile onset as well as a proportion of primary open-angle glaucoma (POAG), more than 180 variants have been documented. Approximately one in 30 unselected patients with POAG have a disease-causing myocilin mutation and it has been shown that firm genotype,phenotype correlations exist. We have compiled an online catalog of myocilin variants and their associated phenotypes. This locus-specific resource, to which future submissions can be made, is available online (; last accessed 28 August 2007). The database, constructed using MySQL, contains three related sheets that contain data pertaining to the information source, variant identified, and relevant study data, respectively. The website contains a list of all identified variants and summary statistics as well as background genomic information, such as the annotated sequence and cross-protein/species homology. Phenotypic data such as the mean±standard deviation (SD) age at POAG diagnosis, mean±SD maximum recorded intraocular pressure, proportion of patients requiring surgical intervention, and age-related penetrance can be viewed by selecting a particular mutation. Approximately 40% of the identified sequence variants have been characterized as disease causing, with the majority (,85%) of these being missense mutations. Preliminary data generated from this online resource highlight the strong genotype,phenotype correlations associated with specific myocilin mutations. The large-scale assimilation of relevant data allows for accurate comprehensive genetic counseling and the translation of genomic information into the clinic. Hum Mutat 29(2), 207,211, 2008. © 2007 Wiley-Liss, Inc. [source]

    Comparison of intravenous methylprednisolone therapy vs. oral methylprednisolone therapy in patients with Graves' ophthalmopathy

    . Aktaran
    Summary A prospective, randomised and single blind clinical trial was designed to compare intravenous methylprednisolone pulse (IVGC) with oral methylprednisolone (OGC) monotherapy in terms of effectiveness and tolerability in Graves' ophthalmopathy (GO). Fifty-two consecutive patients with untreated, moderately severe and active GO were randomly treated with either IVGC or OGC therapy for 12 weeks. IVGC therapy achieved a more rapid and significant improvement than OGC therapy according to clinical activity score (p < 0.01), proptosis (p < 0.038), lid width (p < 0.0001), extraocular muscle changes (p < 0.02), optic neuropathy. (p < 0.001), intraocular pressure (p < 0.04), visual acuity (p < 0.03), quality of life (p < 0.0001) and treatment response (p < 0.001). Diplopia was significantly improved in two groups but there was no difference between them (p < 0.6). Heavy smokers indicated alteration of ophthalmic signs with increased thyroid stimulating hormone (TSH)-receptor antibody during the therapy. In conclusion, IVGC therapy was more effective and better tolerated than OGC therapy in the management of GO. [source]

    New Glaucoma Medications in the Geriatric Population: Efficacy and Safety

    Gary D. Novack PhD
    Glaucoma can be considered a disease of the aging eye. Most medications used to treat glaucoma are in topical eyedrop form and may cause numerous untoward systemic effects in older persons. In recent years, several new ocular hypotensive medications have become available. These medications are being used more commonly because there is a growing trend by ophthalmologists to aggressively lower intraocular pressure. Therefore, geriatricians require a comprehensive knowledge of medications used to treat glaucoma, in addition to an understanding of their mechanism of action profiles of untoward effects and possible interactions with other diseases or medications. Therefore, we performed a review of the medications recently introduced into clinical practice. We selected drugs approved by the U.S. Food and Drug Administration between 1996 and September 2001. The safety profiles of these agents and their untoward side effects were reviewed by class: topical carbonic anhydrase inhibitors (brinzolamide: ocular tolerance, taste perversion), ,-adrenoceptor antagonists (timolol: bradycardia and bronchospasm), ,-adrenergic agonists (brimonidine: oral dryness, headache, and fatigue), and prostaglandin analogs (latanoprost, bimatoprost, travoprost, and unoprostone isopropyl: ocular hyperemia, iris color changes). The function of this review is to make geriatricians more aware of the efficacy and untoward effects of medications recently introduced into clinical practice. We recommend that geriatricians perform a medication review on all medications their patients use, including eye drops. [source]

    Subunits of the epithelial sodium channel family are differentially expressed in the retina of mice with ocular hypertension

    Frank M. Dyka
    Abstract Glaucoma is a prevalent cause of blindness, resulting in the apoptotic death of retinal ganglion cells and optic nerve degeneration. The disease is often associated with elevated intraocular pressure, however, molecular mechanisms involved in ganglion cell death are poorly understood. To identify proteins contributing to this pathological process, we analysed the retinal gene expression of DBA/2J mice that develop an elevated intraocular pressure by the age of 6 months with subsequent ganglion cell loss. In this study, we identified subunits of the epithelial sodium channel (ENaC) family that are specifically expressed under elevated intraocular pressure. Using reverse transcriptase polymerase chain reaction we observed a significant increase of ,-ENaC in the neuronal retina of DBA/2J mice when compared with control animals, while ,-ENaC and ,-ENaC were not detectable in this tissue. Specific immune sera to ENaC subunits showed up-regulation of ,-ENaC in synaptic and nuclear layers of the retina, and in the retinal pigment epithelium. Consistent with our polymerase chain reaction data, ,-ENaC was not detected by specific antibodies in the retina, while ,-ENaC was only present in the retinal pigment epithelium under ocular hypertension. Finally, the increase of ,-ENaC gene expression in the neuronal retina and the retinal pigment epithelium was not observed in other tissues of DBA/2J mice. Since the intraocular pressure is regulated by the transport of aqueous humour across epithelial structures of the eye that in turn is associated with ion flux, the specific up-regulation of ENaC proteins could serve as a protecting mechanism against elevated intraocular pressure. [source]

    Contribution of ROCK in contraction of trabecular meshwork: Proposed mechanism for regulating aqueous outflow in monkey and human eyes

    Emi Nakajima
    Abstract Aqueous outflow in the conventional outflow pathway is regulated by the contraction and relaxation of the ciliary muscle (CM) and the trabecular meshwork (TM). Rho-associated coiled coil-forming protein kinase (ROCK) is thought to regulate actomyosin-based contractility in many types of cells by phosphorylation of ROCK substrates. In animal models, ROCK inhibitor Y-39983 relaxed CM and TM and decreased intraocular pressure (IOP). Thus, ROCK is implicated in the regulation of aqueous outflow and IOP. However, the site of action of ROCK in monkey and man is unknown. In the present communication, RT-PCR analysis of monkey tissues showed higher levels of mRNAs for ROCK and ROCK substrates in TM compared to CM. Human TM also showed higher levels of mRNAs for ROCK and ROCK substrates compared to CM. Differences between TM and CM in human were not as high as in monkey. ROCK inhibitor Y-39983 led to a dose-dependent relaxation of carbachol-induced, contracted TM from monkey. In contrast, Y-39983 was only slightly effective in relaxing CM. Our results suggested that TM was one of the major sites for regulating IOP by ROCK. ROCK inhibitor Y-39983 might be a candidate drug for lowering IOP by increasing conventional outflow and producing fewer side effects on accommodation and miosis. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:701,708, 2005 [source]

    Cyclodextrin complexes of sulfonamide carbonic anhydrase inhibitors as long-lasting topically acting antiglaucoma agents

    Francesca Maestrelli
    Abstract Complexes of several 1,3,4-thiadiazole-2-sulfonamide derivatives possessing strong carbonic anhydrase (CA) inhibitory properties with ,-cyclodextrin and hydroxypropyl-,-cyclodextrin were obtained and characterized. Although the investigated CA inhibitors possessed very powerful inhibitory properties against the two CA isozymes involved in aqueous humor production within the eye, i.e., CA II and CA IV, these compounds were topically ineffective as intraocular pressure (IOP) lowering agents in normotensive/hypertensive rabbits, due to their very low water solubility. On the contrary, the cyclodextrin,sulfonamide complexes proved to be effective and long-lasting IOP lowering agents in the two animal models of glaucoma mentioned above. © 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:2211,2219, 2002 [source]