Higher Peak Intraocular Pressure Research Articles

Ophthalmic suspension of Brimonidine for sustained delivery using nano-resin/drug complex technique

Brimonidine is used to lower intraocular pressure (IOP) in glaucoma patients. An ophthalmic Brimonidine formulation was developed to reduce the dosing frequency from three times a day to once a day using a drug/nanoresin complex suspension. Cationic Brimonidine forms complex with Amberlite™ IRP69 resin in an aqueous medium. The resin was milled to nanosize range and characterized for simulated mucous interaction and drug complexation. The drug/nanoresin complex was amorphous and showed ion-triggered release of Brimonidine in presence of tear salts. Nano-resin/drug ophthalmic suspension of 0.35% strength was formulated with excipients that did not interfere with drug/nanoresin complexation. The Brimonidine ophthalmic suspension had a pH value of 6.8–7.2, viscosity value ∼40–80cps, osmolality ∼280–350 mOsm/kg, D50 of 0.190 μm and complied with pharmacopoeial antimicrobial efficacy test. In-vitro release of Brimonidine from nano-resin complex formulation was slower in water than simulated tear fluid. The suspension was stable for 18 months at room temperature. In-vivo animal study showed comparable efficacy of once a day 0.35% nano-resin formulation to three times a day 0.15% solution formulation. There was improved absorption of the drug in aqueous humor which translated to a significantly high peak IOP reduction for a sustained period.

Factors associated with choroidal microvascular dropout change

Background/aimsTo investigate the factors associated with choroidal microvasculature drop-out (MvD) enlargement detected by optical coherence tomography angiography (OCT-A) in glaucomatous eyes.MethodsNinety-one eyes of 68 primary open-angle glaucoma patients were enrolled....

Relative factors analysis of visual field defect in advanced primary glaucoma

Objective: To explore the relative factors of visual field defect in advanced primary glaucoma. Methods: A retrospective case-control study. The data of patients with primary advanced glaucoma who had the central 5 to 10 degrees of the visual field or the temporal peripheral field and were treated at Eye & ENT Hospital of Fudan University from January 2014 to December 2019 were reviewed. The patients were divded into the central visual field group and the temporal peripheral field group according to the type of visual field defect. Statistical analyses of single-factor (Chi square test or independent sample t test) and multivariate logistic regression were performed to analyze the correlation between the remaining visual field and the risk factors including age, gender, left/right eye, type of glaucoma, baseline glaucoma stage, peak intraocular pressure (IOP), mean IOP, number of operations, family history, high myopia, diabetes, hypertension, hypotension and migraine. Results: A total of 287 patients (287 eyes) were included. There were 101 patients [mean age, (61±15) years; 48 males, 53 females] with the central 5 to 10 degrees of the visual field and 186 patients [mean age, (59±17) years; 107 males, 79 females] with the temporal peripheral field. There was no statistically significant difference between the two groups with respect to age, gender, left/right eye, age of onset, number of operations, family history and history of combined systemic diseases (all P>0.05). Primary open-angle glaucoma, chronic primary angle-closure glaucoma (CPACG) and acute primary angle-closure glaucoma were found in 26, 34 and 41 patients, respectively, in the central visual field group, and in 61, 78 and 47 patients, respectively, in the temporal peripheral field group. The baseline glaucoma was in the moderate stage in 30 and 32 patients, and in the advanced stage in 71 and 154 patients, respectively, in the two groups. The peak IOP was (31.94±4.11) mmHg (1 mmHg=0.133 kPa) and (34.58±6.47) mmHg, and the mean IOP was (22.48±3.99) mmHg and (24.01±4.30) mmHg, respectively, in the two groups. High myopia occurred in 5 and 28 patients, respectively, in the two groups. The differences in the type of glaucoma (χ²=7.24), baseline glaucoma stage (χ²=6.04), peak IOP (t=4.22), mean IOP (t=2.96) and high myopia (χ²=6.57) between the two groups were statistically significant (all P<0.05). In the multivariable model, CPACG (OR=2.021, 95%CI: 1.020 to 4.001), higher peak IOP (OR=1.128, 95%CI: 1.038 to 1.226) and high myopia (OR=5.090, 95%CI: 1.556 to 16.651) increased the risks for the progression to the temporal peripheral field. Conclusion: CPACG, higher peak IOP and concurrent high myopia are all relative factors for the progression to the temporal peripheral field in advanced primary glaucoma.

Risk Factors for Fast Visual Field Progression in Glaucoma

To identify baseline and longitudinal risk factors for fast visual field (VF) decay in patients with open-angle glaucoma. Retrospective cohort study. Patients with open-angle glaucoma with ≥6 VFs and ≥4 years of follow-up were included. VF decay rates were measured with the following methods: mean deviation (MD) rate, VF index (VFI) rate, and the Glaucoma Rate Index (GRI). The relationship between VF rates and clinical variables were investigated with linear mixed models. Logistic regression analysis was performed to determine which factors were associated with fast progression. A total of 1317 eyes of 745 patients with a mean (± SD) age of 63.3 (±10.9) years and a median (interquartile range) MD-2.4 (-0.7 to-5.6) dB at baseline were analyzed. The median (interquartile range) number of VFs was 12 (9 to 16), and mean follow-up duration was 11.5 (±3.7) years. Older age (P < .001), higher peak intraocular pressure (IOP) (P < .001), and glaucoma surgery during the study period (P < .001) were associated with faster rates of progression regardless of the method used. Worse baseline MD was associated with MD rate (P= .02), but neither with VFI rate (P=.37) nor GRI (P= .31); whereas pseudoexfoliative glaucoma was associated with faster rates of progression with MD (P = .008) and VFI (P = .01) rates, but not with GRI. Higher peak IOPs (P= .005) was a significant predictor for fast progression. In this cohort, older age, peak IOP, pseudoexfoliative glaucoma, and baseline MD were associated with the rate of glaucomatous VF worsening. Fast progressors had a higher peak IOP than non-fast progressors. The identification and appropriately aggressive treatment of fast progressors would reduce visual disability from glaucoma.

Influence of irrigation dynamic pressure-assisted hydrodissection on intraocular pressure and the posterior chamber-anterior hyaloid membrane barrier during cataract surgery.

To evaluate the effects of irrigation dynamic pressure-assisted hydrodissection (irrigation-hydro: iH) on intraocular pressure (IOP) and the posterior chamber-anterior hyaloid membrane (PC-AHM) barrier in porcine eyes. Experimental. In Experiment 1, IOP was recorded while irrigating the anterior chamber (AC), during iH, and during phacoemulsification and aspiration in 20 porcine eyes using bottle heights of 50, 70, and 90cm. Under the same conditions, IOP was recorded during conventional manual cortical cleaving hydrodissection (manual hydro: mH) in 20 porcine eyes. In Experiment 2, after iH, ACs were perfused for 5 seconds with balanced salt solution containing 1.0-μm fluorescein beads in 20 porcine eyes using bottle heights of 70, 118, and 169cm. PC-AHM barrier staining grade was evaluated by the Miyake-Apple view. iH proved successful in all cases. In Experiment 1, IOP during iH was relatively stable and peak IOP was below the baseline bottle height-dependent pressure. No eyes showed a peak IOP > 75mmHg during iH, but 8 eyes showed a peak IOP > 75mmHg during mH. In Experiment 2, neither AHT nor ruptured capsules were observed at any bottle height. Unlike mH, IOP during iH was relatively stable without any high peak IOP. Thus, iH offers a simple technique for reducing peak IOP and avoiding disturbance of the PC-AHM barrier.

Influence of Vitrectomy-related Factors on the Outcome of Ahmed Glaucoma Valve Implantation.

PurposeTo evaluate the outcome of Ahmed glaucoma valve (AGV) implantation in eyes with refractory secondary glaucoma following pars plana vitrectomy (PPV) and the associated prognostic factors.MethodsA total of 146 eyes in 146 patients who underwent AGV implantation after PPV (followed up for ≥1 year) were included. AGV implantation was considered successful when the intraocular pressure (IOP) was 6 to 21 mmHg regardless of using IOP-lowering medication. The hazard ratios (HRs) associated with surgical failure were determined with Cox proportional analysis.ResultsThe most common cause for PPV was complications of proliferative diabetic retinopathy (50%). The mean and peak IOPs between PPV and AGV implantation were 26.9 ± 6.6 and 35.9 ± 10.2 mmHg, respectively. AGV implantation was performed on average 18.7 months after PPV, and its overall success rate was 80.1% during a mean follow-up period of 43.6 months. In multivariate analyses, rubeosis observed before AGV implantation (HR, 4.07; 95% confidence interval, 1.57 to 10.6; p = 0.004) and higher peak IOP before AGV (HR, 1.04; 95% confidence interval, 1.00 to 1.07; p = 0.034) were predictive of failure. However, no PPV-related factors were associated with the surgical outcome of AGV implantation.ConclusionsThe outcome of AGV implantation is good in refractory glaucoma following PPV. Rubeosis after PPV and higher peak IOP before AGV are risk factors for poor outcomes. Patients who undergo PPV should be followed for the development of rubeosis and IOP control.

Raised Intraocular Pressure in Nonjuvenile Idiopathic Arthritis-Uveitis Children: Risk Factors and Effect on Retinal Nerve Fiber Layer.

To determine risk factors for intraocular pressure (IOP) elevation and glaucoma in children with nonjuvenile idiopathic arthritis-related uveitis and any IOP-related changes in the retinal nerve fiber layer (RNFL) thickness. Clinical data were collected from children attending a tertiary referral uveitis clinic between May 2010 and October 2012. We assigned 206 eyes of 103 children into 32 normal eyes, 108 normotensive uveitics (NU), 41 hypertensive uveitics (HU: raised IOP without glaucomatous disc), and 25 glaucomatous uveitics (GU: raised IOP with glaucomatous disc). Risk factors for raised IOP, glaucoma and steroid response (SR) were evaluated and RNFL thickness across groups was compared with determine changes related to raised IOP. IOP elevation occurred in 40 patients (38.8%) or 66/174 eyes with uveitis (37.9%); and SR occurred in 35.1% of all corticosteroid-treated eyes. Chronic uveitis was a significant risk factor for raised IOP [odds ratio (OR)=9.28, P=0.001], glaucoma, and SR (OR=8.4, P<0.001). Higher peak IOP was also a risk factor for glaucoma (OR=1.4, P=0.003). About 70% of SR eyes were high responders (IOP increase >15 mm Hg from baseline), associated with younger age and corticosteroid injections. Although no significant RNFL thinning was detected between HU and NU eyes, significant thinning was detected in the inferior quadrant of GU (121.3±28.9 μm) compared with NU eyes (142.1±32.0 μm, P=0.043). Children with chronic uveitis are at higher risk of raised IOP and glaucoma. Thinning of the inferior RNFL quadrant may suggest glaucomatous changes in uveitic children with raised IOP.

Long-term (>8 years) evaluation of progression in patients with low-pressure glaucoma.

To describe the long-term clinical course of patients with low-pressure glaucoma (LPG) and to assess the risk factors for disease progression. The Wills Eye Glaucoma Research Center retrospectively reviewed the charts of LPG patients with documented follow-up of &gt;8 years between 2000 and 2013. Medical records were evaluated for systemic diseases, family history of glaucoma, best-corrected visual acuity, refractive error, treatments, central corneal thickness (CCT), intraocular pressure (IOP), IOP change after pupil dilation, optic disc evaluation, visual field (VF) mean deviation (MD), VF grading, and time to progression. Progression was determined when both disc and VF appeared to have worsened. From 850 charts classified as LPG between 2000 and 2013, 49 eyes of 49 patients were included in our analysis. The mean ( ± SD) follow-up time was 9.3 ( ± 1.9) years. Glaucoma progressed in 25 eyes and remained stable in 24 eyes over the follow-up period. Eyes with progression had higher peak IOP (p = 0.043). There was a trend towards progression in patients with thinner CCT (p = 0.085) and disc hemorrhage (p = 0.098). Estimated annual change in MD was -0.57 dB in the progressing group and -0.10 dB in the stable group (p&lt;0.0001). Nearly half of the patients with LPG showed glaucoma progression despite treatment after &gt;8 years. High peak IOP was a significant risk factor for progression. Identifying patients at risk may warrant closer follow-up and more aggressive treatment in order to preserve visual function in patients with LPG.

Risk factors for predicting visual field progression in Chinese patients with primary open-angle glaucoma: A retrospective study

BackgroundGlaucoma is a leading cause of irreversible blindness worldwide. It is characterized by progressive deterioration of the visual field (VF) that results in a complete loss of vision. This study aimed to determine the risk factors associated with VF progression in Chinese patients with primary open-angle glaucoma (POAG). MethodsWe reviewed the charts of POAG patients who visited our clinic between July 2009 and June 2010. We included patients with five or more reliable VF tests using the Humphrey Field Analyzer (Humphrey Instruments, San Leandro, CA, USA) during a period of at least 2 years. The scoring system of the Collaborative Initial Glaucoma Treatment Study (CIGTS) was used to code the VF. Progression was defined as an increasing score ≥3, compared to the averaged baseline data. Univariate and multivariate logistic regression analyses were performed to identify the risk factors of VF progression. ResultsThere were 92 patients (representing 92 eyes) with an average of 8.9 reliable VFs over a mean follow up of 5.4 years. Multivariate logistic regression showed that eyes with more VF tests [odds ratio (OR) = 1.500, p < 0.010] and either increased peak intraocular pressure (IOP) (OR = 1.235, p = 0.044) or a wide IOP range (OR = 1.165, p = 0.041) favored VF progression. High myopia (less than −6.0 D) was not a risk factor (OR = 1.289, p = 0.698) for VF progression in this study. ConclusionIn addition to a greater number of VF tests, Chinese patients with treated POAG who experienced a high peak IOP or a wide range of IOP during follow up were more likely to have VF deterioration.

The effect of intraocular pressure on visual field after trabeculectomy in patients with primary open angle glaucoma

To compare the mean intraocular pressure (IOP), peak IOP and percentage reduction in IOP in the first five years following trabeculectomy between the patients with progressed visual field loss and the patients with stable visual fields. Thirty-six eyes of 36 patients were followed for five years after their first trabeculectomy with tonometry and automated perimetry (Octopus 500EZ, program G1). The rate of change of the visual field was measured by linear regression analysis of the mean sensitivity value (dB) of each field test versus time (month). Based on the statistical significance of the slope of the regression line (Spearman p value of the correlation coefficient less than 0.05), patients were divided into two groups: with significant negative slope of the regression line (group with progressed visual field loss) and with non-significant slope of the regression line (group with stable visual field). The mean IOP values and percentage of IOP reduction at the end of each of the first five years after surgery were compared between the group with progressed field loss and group with stable fields by using Mann-Whitney U test. Patients with progressed visual field loss had higher mean IOP, higher peak IOP and less reduction in pressure after the operation than patients with stable visual field. The mean IOP at end of the two year postoperative period was significantly higher in patients with progressed visual field loss (21.98 +/- 3.38 mmHg) than in those with stable fields (17.48 +/- 4.80 mmHg). The mean percentage reduction in IOP at the end of two year postoperative period was significantly less in patients that showed progression of field loss (21.84%) than in those with stable fields (41.0%). Prognosis for further field loss seems to be better if postoperative pressure is at lower levels and greater percent reduction of IOP is obtained after surgery. The data that predict better prognosis is the mean postoperative IOP value of approximately 18 mmHg or less resulting from at least 35% of IOP reduction.

Patients with advanced glaucoma with controlled intraocular pressure and visually significant cataract: phacoemulcification vs combined surgery

AbstractPurpose cataract surgery alone may have a beneficial effect in glaucoma patients by mildly lowering the intraocular pressure but loss of intraocular pressure (IOP) control may occur after cataract operation. It has also been suggested that patients presenting with more advanced glaucoma may have better outcomes with surgery than medical treatment. The purpose of the study is to investigate the postoperative results of two surgical alternatives: phaco only versus combined phaco trab operation in eyes with advanced glaucoma and controlled IOP.Methods Prospective study of 78 patients with advanced open angle glaucoma (MD≥12 dB) with IOP≤21mmHg on topical medication and visually significant cataract (VA ranging from Hand Movements to 4/10). All patients were randomized to have either combined surgery (phaco‐trab, two‐sites, using adjustable sutures) (Group A, 39 eyes) or phaco only ( clear cornea temporal approach) (Group B, 39 eyes). Follow up for 6 months. VA, IOP and VF were measured regularly with appropriate IOP control. Postoperative complications were recorded.Results Phaco group showed faster visual recovery, higher peak IOP, greater IOP fluctuations and less MD difference than phaco_trab group, with the latter performing worse. Final VA didn't differ significantly between groups. Major complications: 9 choroidal detachments and 1 hyphema in Group A.Conclusion for the first 6mo postoperatibvely higher IOPs in phaco only patients do not seem to worsen glaucoma lesions given strict IOP control. Even more, phaco_only eyes show faster visual improvement and need less prolonged intensive postoperative monitoring than phaco_trab eyes.

Ocular hypertensive and anti‐inflammatory responses to different dosages of topical dexamethasone in children: a randomized trial

The purpose of the present study was to investigate the ocular hypertensive and anti-inflammatory responses to two different dosage schedules of 0.1% topical dexamethasone in a population of Chinese children undergoing strabismus surgery. Children undergoing bilateral strabismus surgeries were randomly assigned to receive topical 0.1% dexamethasone eye drops four times daily (group A) or twice daily (group B) for 4 weeks. Intraocular pressure (IOP) and anti-inflammatory responses were monitored for 8 weeks. A total of 137 children with mean age 6.5 years (SD, 1.9 years; range, 3-10 years) participated in the study. The IOP increased significantly after 4 weeks in both groups compared to the preoperative values (P < 0.001). Peak IOP ranged from 14.0 to 50.3 mmHg in group A and 11.0-41.3 mmHg in group B. Cases in group A (mean, 13.8 mmHg; SD, 8.4 mmHg) had a greater net increase in IOP than cases in group B (mean, 10.2 mmHg; SD, 6.2 mmHg; P = 0.004). Younger-aged children had higher peak IOP (r = -0.244, P = 0.048), and attained the peak IOP earlier (r = 0.252, P = 0.041) in group A. There was no significant difference in ocular inflammatory response between the two groups. Ocular hypertensive effect to topical 0.1% dexamethasone is dose and age dependent in children. Twice-daily 0.1% topical dexamethasone eye drops control inflammation after strabismus surgery as effectively as four-times-daily dosage, but induces less increase in IOP, and may be a better treatment schedule.

Glaucoma phenotype in pedigrees with the myocilin Thr377Met mutation.

To investigate the phenotype and age-related penetrance of primary open-angle glaucoma (POAG) in Australian families with the myocilin mutation Thr377Met. Cross-sectional genetic study. Four unrelated pedigrees carrying the Thr377Met mutation were ascertained from more than 2000 consecutive cases of POAG in the Glaucoma Inheritance Study in Tasmania and from families with glaucoma referred to the study from throughout Australia. Index cases and available family members were examined for signs of glaucoma, and the presence of the GLC1A Thr377Met mutation was ascertained by single-strand conformation polymorphism analysis and subsequent direct sequencing. From the 4 pedigrees carrying the Thr377Met mutation, 23 individuals with either ocular hypertension (OHT) or POAG were found, with a mean +/- SD age at diagnosis of 41.2 +/- 11.5 years, and a mean peak intraocular pressure of 31.7 +/- 9.9 mm Hg. A further 9 mutation carriers older than 18 years were studied who as yet showed no signs of OHT or POAG (6 of these 9 were younger than 30 years). A single individual with POAG was identified who did not carry the Thr377Met mutation. For Thr377Met carriers, age-related penetrance for OHT or POAG was 88% at age 30 years. A positive family history of POAG was present for 3 of the 4 index cases. Thirteen (57%) of the 23 Thr377Met carriers with OHT or POAG had undergone glaucoma drainage surgery. Although the glaucoma in these families appears to be pressure dependent, 2 individuals showed optic disc cupping before detected elevation in intraocular pressure. One family was of British origin, with a different background haplotype from the other 3 families from Greece or Macedonia, who shared a common haplotype. The GLC1A Thr377Met mutation is associated with POAG that, in the pedigrees studied, had a younger age at onset and higher peak intraocular pressure than in pedigrees with the more common Gln368STOP mutation. In addition, patients with glaucoma with the Thr377Met mutation were more likely to have undergone glaucoma drainage surgery.

Evidence for genetic heterogeneity within eight glaucoma families, with the GLC1A Gln368STOP mutation being an important phenotypic modifier.

To investigate the phenotype and age-related penetrance of primary open-angle glaucoma (POAG) in Australian families with the most common Myocilin mutation (Gln368STOP). Cross-sectional genetic study. Eight pedigrees carrying the Gln368STOP mutation were ascertained from 1730 consecutive cases of POAG in the Glaucoma Inheritance Study in Tasmania. Index cases and available family members were examined for signs of glaucoma, and the presence of the GLC1A Gln368STOP mutation was ascertained by single-strand conformation polymorphism analysis and subsequent direct sequencing. From the eight pedigrees, 29 Gln368STOP mutation-carrying individuals with either ocular hypertension (OHT) or POAG were found, with a mean age at diagnosis of 52.4 +/- 12.9 years and a mean peak intraocular pressure (IOP) of 28.4 +/- 4.7 mmHg. A further 11 mutation carriers older than 40 years have been studied, who as yet show no signs of OHT or POAG. Within the 8 pedigrees, a further 31 individuals with OHT or POAG were identified who did not carry the Gln368STOP mutation. For these individuals the mean age at diagnosis was higher (62.3 +/- 13.7 years, P < 0.01), and the mean peak IOP was lower (25.4 +/- 6.4 mmHg, P = 0.01). For Gln368STOP carriers, age-related penetrance for OHT or POAG was 72% at age 40 years and 82% at age 65 years. A positive family history of POAG was present in all index cases. Five of the eight pedigrees had a positive family history on both maternal and paternal sides. Seven of the eight pedigrees had one or more individuals with POAG who did not carry the mutation. Eight of the 29 Gln368STOP carriers with OHT or POAG had undergone trabeculectomy. The GLC1A Gln368STOP mutation is associated with POAG, which in the pedigrees studied is of a younger age of onset and higher peak IOP than non-mutation glaucoma cases. In addition, Gln368STOP mutation glaucoma cases were more likely to have undergone glaucoma drainage surgery. We have not observed simple autosomal dominant inheritance patterns for POAG in these pedigrees. Other factors, as yet uncharacterized, are involved in expression of the POAG phenotype in Gln368STOP pedigrees.