Elevated intraocular pressure decreases response sensitivity of inner retinal neurons in experimental glaucoma mice.

Glaucoma is the second leading cause of blindness in the United States and the world, characterized by progressive degeneration of the optic nerve and retinal ganglion cells (RGCs). Glaucoma patients exhibit an early diffuse loss of retinal sensitivity followed by focal loss of RGCs in sectored patterns. Recent evidence has suggested that this early sensitivity loss may be associated with dysfunctions in the inner retina, but detailed cellular and synaptic mechanisms underlying such sensitivity changes are largely unknown. In this study, we use whole-cell voltage-clamp techniques to analyze light responses of individual bipolar cells (BCs), AII amacrine cells (AIIACs), and ON and sustained OFF alpha-ganglion cells (ONαGCs and sOFFαGCs) in dark-adapted mouse retinas with elevated intraocular pressure (IOP). We present evidence showing that elevated IOP suppresses the rod ON BC inputs to AIIACs, resulting in less sensitive AIIACs, which alter AIIAC inputs to ONαGCs via the AIIAC→cone ON BC→ONαGC pathway, resulting in lower ONαGC sensitivity. The altered AIIAC response also reduces sOFFαGC sensitivity via the AIIAC→sOFFαGC chemical synapses. These sensitivity decreases in αGCs and AIIACs were found in mice with elevated IOP for 3-7 wk, a stage when little RGC or optic nerve degeneration was observed. Our finding that elevated IOP alters neuronal function in the inner retina before irreversible structural damage occurs provides useful information for developing new diagnostic tools and treatments for glaucoma in human patients.

Direct Costs of Second Aqueous Shunt Implant Versus Transscleral Cyclophotocoagulation (The Assists Trial).

PRCIS: The cost of cyclophotocoagulation is less than the cost of a second glaucoma drainage device. PURPOSE: To compare the total direct costs of implantation of a second glaucoma drainage device (SGDD) with transscleral cyclophotocoagulation (CPC) for patients with inadequately controlled intraocular pressure (IOP) reduction, despite the presence of a preexisting glaucoma drainage device in the ASSISTS clinical trial. METHODS: We compared the total direct cost per patient, including the initial study procedure, medications, additional procedures, and clinic visits during the study period. The relative costs for each procedure during the 90-day global period and the entire study period were compared. The cost of the procedure, including facility fees and anesthesia costs, were determined using the 2021 Medicare fee schedule. Average wholesale prices for self-administered medications were obtained from AmerisourceBergen.com. The Wilcoxon rank sum test was used to compare costs between procedures. RESULTS: Forty-two eyes of 42 participants were randomized to SGDD (n=22) or CPC (n=20). One CPC eye was lost to follow-up after initial treatment and was excluded. The mean (±SD, median) duration of follow-up was 17.1 (±12.8, 11.7) months and 20.3 (±11.4, 15.1) months for SGDD and CPC, respectively ( P =0.42, 2 sample t test). The mean total direct costs (±SD, median) per patient during the study period were $8790 (±$3421, $6805 for the SGDD group) and $4090 (±$1424, $3566) for the CPC group ( P <0.001). Similarly, the global period cost was higher in the SGDD group than in the CPC group [$6173 (±$830, $5861) vs. $2569 (±$652, $2628); P <0.001]. The monthly cost after the 90-day global period was $215 (±$314, $100) for SGDD and $103 (±$74, $86) for CPC ( P =0.31). The cost of IOP-lowering medications was not significantly different between groups during the global period ( P =0.19) or after the global period ( P =0.23). CONCLUSION: The total direct cost in the SGDD group was more than double that in the CPC group, driven largely by the cost of the study procedure. The costs of IOP-lowering medications were not significantly different between groups. When considering treatment options for patients with a failed primary GDD, clinicians should be aware of differences in costs between these treatment strategies.

Outcomes of the Second Aqueous Shunt Implant Versus Transscleral Cyclophotocoagulation Treatment Study: A Randomized Comparative Trial.

PRCIS: Short-term overall success rates were high with either SGDD or CPC. However, SGDD was associated with more clinic visits and an increased risk of additional glaucoma surgery. Both treatments were reasonable options for eyes with inadequately controlled IOP after a single GDD. PURPOSE: The purpose of this study is to compare the implantation of a second glaucoma drainage device (SGDD) and transscleral cyclophotocoagulation (CPC) in eyes with inadequately controlled intraocular pressure (IOP), despite the presence of a preexisting glaucoma drainage device. METHODS: Patients with inadequately controlled IOP, despite the medical therapy and a preexisting glaucoma drainage device, were enrolled at 14 clinical centers and randomly assigned to treatment with a SGDD or CPC. MAIN OUTCOME MEASURES: Surgical failure was defined as: (1) IOP ≤5 mm Hg or >18 mm Hg or <20% reduction below baseline on maximum tolerated topical ocular hypotensive therapy, (2) reoperation for glaucoma, or (3) loss of light perception. The primary outcome measure was overall success with or without adjunctive medical therapy. RESULTS: Forty-two eyes of 42 participants were randomized to SGDD (n=22) or CPC (n=20). Mean duration of follow-up was 18.6 (±12.1; range: 1.1-38.6) months. The cumulative success rate was 79% for SGDD and 88% for CPC at 1 year ( P =0.63). Although the study was underpowered, no significant differences in IOP, postoperative number of IOP-lowering medications, or adverse events were observed. The number of additional glaucoma surgeries ( P =0.003), office visits during the first 3 months ( P <0.001), and office visits per month after month 3 ( P <0.001) were greater in the SGDD group. CONCLUSIONS: Short-term overall success rates were high with either SGDD or CPC. However, SGDD was associated with more clinic visits and an increased risk of additional glaucoma surgery.

Assessing the Reliability of Intraocular Pressure Measurements Using Rebound Tonometry.

PRECIS: In a trio of prospective studies, the iCare rebound tonometer demonstrated significantly lower test-retest variability than Goldmann tonometry with good interoperator and interdevice reproducibility, supporting its value in monitoring intraocular pressure (IOP) changes over time. PURPOSE: The purpose of this study was to characterize intraoperator and interoperator and interdevice reliability of IOP measurements with rebound tonometry (RT, ic100). METHODS: Three prospective cross-sectional studies were conducted in distinct sample of adult patients with established glaucoma, suspected glaucoma, or no glaucoma at the West Virginia University Eye Institute. Participants in study 1 underwent 5 RT measurements in one randomly selected eye and 5 Goldmann tonometry measurements in the fellow eye by 1 operator; intraoperator variability was compared using the F test. In study 2, 3 operators each obtained 3 RT measurements in participants in randomized operator order. In study 3, a single operator collected 3 measurements each with 3 RTs in randomized device order. Between-operator and between-device reproducibility were characterized using intraclass correlation coefficients (ICCs). RESULTS: Overall, 28, 19, and 25 subjects participated in the 3 respective studies. Within-subject variance across subjects was 0.757 in RT measurements and 2.471 in Goldmann measurements (P=0.0035). Interoperator reproducibility of RT measurements was good in both eyes [ICC for right eyes 0.78, 95% confidence interval (CI): 0.60-0.85; ICC for left eyes 0.75, 95% CI: 0.50-0.83]. Interdevice reproducibility of RT measurements was good approaching excellent (ICC for right eyes 0.87, 95% CI: 0.83-0.90; ICC for left eyes 0.89, 95% CI: 0.86-0.91). CONCLUSIONS: The RT's lower measurement variability and good interoperator and interdevice reproducibility suggest that it can characterize IOP changes over time more robustly than Goldmann tonometry, aiding clinicians in assessing the effectiveness of glaucoma therapy and the consistency of IOP control.

Duration of IOP reduction with travoprost BAK-free solution.

PURPOSE: To compare the duration of action of travoprost ophthalmic solution 0.004% (Travatan Z) formulated without benzalkonium chloride (BAK) to travoprost ophthalmic solution 0.004% formulated with BAK (Travatan). METHODS: This was a prospective, randomized, double-masked study. Patients with open-angle glaucoma or ocular hypertension were randomized to receive 2 weeks of once-daily therapy with travoprost BAK-free or travoprost with BAK. Patients received the last dose of medication on day 13 and then intraocular pressure (IOP) was assessed every 12 hours for 60 hours. Statistical analysis included change in IOP from baseline for each group and comparison of mean IOP between groups. RESULTS: Of the 109 patients enrolled, 106 patients completed the study. Untreated mean baseline IOP at 8 AM was 26.9 mm Hg in the travoprost BAK-free group and 27.1 mm Hg in the travoprost with BAK group. At 12, 24, 36, 48, and 60 hours after the last dose, mean IOP in the travoprost BAK-free group was 18.7, 17.2, 19.5, 18.7, and 20.8 mm Hg, respectively; whereas mean IOP in the travoprost with BAK group was 18.5, 16.8, 19.7, 18.0, and 20.8 mm Hg, respectively. Mean IOP at all time points after the last dose of medication was >6 mm Hg lower than the 8 AM baseline in both groups. Between-group differences were within +/-0.6 mm Hg at all postdose time points. There were no statistically significant differences between the 2 treatment groups at baseline or at any postdose time point. Drug-related side effects were uncommon, mild in intensity, and comparable between groups. CONCLUSIONS: Travoprost without BAK has similar IOP-lowering efficacy and safety compared with travoprost preserved with BAK. Both formulations of travoprost have a prolonged duration of action, with statistically and clinically significant reductions from baseline persisting up to 60 hours after the last dose.

Novel use of fibrin sealant for scleral suture free placement of a glaucoma drainage device in advanced scleral thinning.

PURPOSE: This reports a case using fibrin glue to secure a glaucoma drainage device plate to the sclera where there is a concern with the use of suture. OBSERVATIONS: A 13-year-old patient with congenital aniridia and associated glaucoma refractory to topical medications underwent implantation of a glaucoma drainage device (GDD) for improved intraocular pressure (IOP) control. The patient had substantial scleral thinning with staphyloma formation, potentially making the use of traditional suturing techniques problematic. Fibrin glue was used to attach the GDD plate, as well the tube and patch graft which has been previously described, without sutures. The patient tolerated the procedure well with a 41% reduction in IOP at six months follow-up with no migration of the GDD from its original position. CONCLUSIONS AND IMPORTANCE: The use of fibrin glue in ophthalmology can be expanded to include attachment of the GDD plate to the sclera in patients with suturing contraindications.

Comparison of the ocular hypotensive efficacy of adjunctive brimonidine 0.15% or brinzolamide 1% in combination with travoprost 0.004%.

PURPOSE: To compare efficacies of adjunctive therapy with brimonidine 0.15% and adjunctive therapy with brinzolamide 1% in combination with travoprost 0.004%. DESIGN: Three-month randomized, parallel-group, double-masked, multicenter clinical trial. PARTICIPANTS: Patients with primary open-angle glaucoma, exfoliation glaucoma, or ocular hypertension with intraocular pressure (IOP) > 18 mmHg on monotherapy with travoprost (N = 163). METHODS: Patients were randomized to receive adjunctive therapy with twice-daily brimonidine (N = 79) or twice-daily brinzolamide (N = 84). Treatment efficacy was assessed after 1 and 3 months of combination therapy. Intraocular pressure was measured at 8 am, noon, and 4 pm at baseline (on travoprost monotherapy) and after 3 months of combination therapy. Mean diurnal IOP was defined as the average of the IOP measurements at these 3 time points. Adverse events were recorded at each visit. MAIN OUTCOME MEASURE: Difference between treatment groups in mean diurnal IOP at month 3, adjusted for difference in baseline IOP, using analysis of covariance. RESULTS: Mean diurnal IOPs (+/- standard error of the mean) at baseline were 21.7+/-0.33 mmHg in the brimonidine group and 21.1+/-0.29 mmHg in the brinzolamide group (P = 0.16). Mean diurnal IOPs at month 3 were 19.6+/-0.41 mmHg in the brimonidine group and 18.4+/-0.33 mm Hg in the brinzolamide group (P = 0.019). At month 3, mean diurnal IOPs, adjusted for difference in baseline IOP, were 19.3+/-0.27 in the brimonidine group and 18.6+/-0.25 in the brinzolamide group (P = 0.035). CONCLUSIONS: The combination of travoprost and brinzolamide was statistically significantly more efficacious than the combination of travoprost and brimonidine in lowering IOP. The clinical significance of this difference is uncertain.

Effects of elevated intraocular pressure on mouse retinal ganglion cells.

We developed and characterized a mouse model of elevated intraocular pressure (IOP) to investigate the underlying cellular and genetic mechanisms of retinal ganglion cell (RGC) death. IOP was unilaterally increased in C57BL/6J mice by photocoagulation of the episcleral and limbal veins. IOP was measured using an indentation tonometer. RGC survival was measured by retrograde labeling using DiI applied to the superior colliculous. The mechanism of RGC death was investigated using TUNEL staining, immunostaining for cleaved caspase-3, and Western blot for Bcl-2 and Bax expression. RT-PCR was used to measure changes in Bcl-2, Bax, Bad, Bak, P53, ICE and Fas. Mean IOP was increased in the treated eyes from 13+/-1.8 to 20.0+/-2.8 mmHg at four weeks and 17+/-2.2 mmHg at eight weeks. RGC loss was 15.6+/-3.4% at two weeks and 27.3+/-4.5% at four weeks after laser photocoagulation. TUNEL staining and caspase-3 positive cells were increased in the ganglion cell layer (GCL) in the treated eyes and seldom found in the control eyes. Bcl-2 expression in control group was higher than in the experimental group, while Bax expression in the control group was less than in experimental group. This mouse model resulted in a consistent, sustained increase in IOP with a reduction in the number of RGCs in the treated eye. The RGCs in eyes with elevated IOP were TUNEL-positive, with increased caspase-3 and decreased Bcl-2, consistent with apoptosis as the mechanism of neuronal cell death.

Blue light-induced generation of reactive oxygen species in photoreceptor ellipsoids requires mitochondrial electron transport.

PURPOSE: To investigate whether photoreceptor ellipsoids generate reactive oxygen species (rOx) after blue light illumination. METHODS: Cultured salamander photoreceptors were exposed to blue light (480 +/- 10 nm; 10 mW/cm(2)). The light-induced catalytic redox activity in the culture was monitored with the use of 3,3'-diaminobenzidine (DAB). Tetramethylrhodamine ethyl ester (TMRE) and 2',7'-dichlorodihydro-fluorescein acetate (DHF-DA) were used as probes to measure the mitochondrial membrane potential and intracellular rOx, respectively. RESULTS: A significant deposit of DAB polymers was found in the culture after exposure to blue light. Basal levels of rOx were observed in photoreceptor ellipsoids when cells were stained with DHF-DA. This staining colocalized with TMRE. After exposure to blue light, a sharp increase of rOx immediately occurred in the ellipsoids of most photoreceptors. When the light intensity was reduced, the response kinetics of rOx generation were slowed down; however, comparable amounts of rOx were generated after a standard time of exposure to light. The production of rOx in photoreceptors was markedly decreased when an antioxidant mixture was included in the medium during exposure to light. Rotenone or antimycin A, the respiratory electron transport blockers at complex I and III, respectively, significantly suppressed the light-evoked generation of rOx. CONCLUSIONS: A robust amount of rOx is produced in the ellipsoid when photoreceptors are exposed to blue light. This light-induced effect is antioxidant sensitive and strongly coupled to mitochondrial electron transport. The cumulative effect of light on rOx generation over time may implicate a role for mitochondria in light-induced oxidative damage of photoreceptors.

One-year, randomized study comparing bimatoprost and timolol in glaucoma and ocular hypertension.

OBJECTIVE: To compare bimatoprost with timolol maleate in patients with glaucoma or ocular hypertension. METHODS: In 2 identical, multicenter, randomized, double-masked, 1-year clinical trials, patients were treated with 0.03% bimatoprost once daily (QD) (n = 474), 0.03% bimatoprost twice daily (BID) (n = 483), or 0.5% timolol maleate BID (n = 241). MAIN OUTCOME MEASURES: Diurnal intraocular pressure (IOP) at 8 AM, 10 AM, and 4 PM and safety variables (IOP was also measured at 8 PM at selected sites). RESULTS: Bimatoprost QD provided significantly lower mean IOP than timolol at every time of the day at each study visit (P<.001). This was also true for bimatoprost BID at most time points, but the efficacy was not as good as that of the QD regimen. At 10 AM (peak timolol effect) at month 12, the mean reduction in IOP from baseline was 7.6 mm Hg (30%) with bimatoprost and 5.3 mm Hg (21%) with timolol (P<.001). A significantly higher percentage of patients receiving bimatoprost QD (58%) than timolol (37%) achieved IOPs at or below 17 mm Hg (10 AM, month 12; P<.001). The most common adverse effect with bimatoprost was hyperemia (significantly higher with bimatoprost QD than timolol; P<.001). CONCLUSIONS: Bimatoprost QD provides sustained IOP lowering superior to timolol or bimatoprost BID and achieves low target IOPs in significantly more patients.

Two-year double-masked comparison of bimatoprost with timolol in patients with glaucoma or ocular hypertension.

The object of this study was to compare the long term efficacy and safety of bimatoprost with timolol in patients with glaucoma or ocular hypertension. In a 12-month extension of two identically designed 1-year, multicenter, randomized, double-masked clinical trials, patients were treated topically with bimatoprost 0.03% QD (n=167), bimatoprost 0.03% BID (n=131), or timolol 0.5% BID (n=81). Main outcome measures were IOP at 8 am and 10 am and safety parameters. Bimatoprost QD provided significantly greater mean reduction from baseline IOP than did timolol at both measurements at each study visit (P< or =.001). At 10 am (peak timolol effect) at month 24, the mean reduction from baseline IOP was 7.8 mm Hg with bimatoprost QD and 4.6 mm Hg with timolol (P<.001). Patients treated with bimatoprost QD also sustained significantly lower mean IOP than timolol-treated patients at every follow-up visit throughout the 2-year study period (P< or =.006). At 10 am at month 24, a significantly greater proportion of bimatoprost QD than timolol patients achieved target pressures of < or =13-18 mm Hg (P< or =.010). Bimatoprost sustained an excellent safety profile during the second year of treatment. Most adverse events were mild, and there were no reports of increased iris pigmentation, uveitis, or CME. The incidence of hyperemia was significantly higher with bimatoprost QD (13.8%) than with timolol (2.5%) (P=.006). Mean reduction from baseline IOP with bimatoprost BID was not significantly different from that with timolol at month 24 at 10 am (P=.474). We conclude that bimatoprost QD provides superior IOP lowering to timolol, and is safe and well tolerated over 24 months of treatment.

Effects of beta-adrenergic blockers on glutamate-induced calcium signals in adult mouse retinal ganglion cells.

Betaxolol, a selective beta(1)-adrenoceptor antagonist, is an antiglaucoma drug commonly used to lower the intraocular pressure (IOP) in treatment of glaucoma. Recent evidence has also shown that it attenuates ligand- and voltage-gated currents in retinal ganglion cells, which may lead to reduction of intracellular calcium and prevention of glutamate-induced ganglion cell damage in glaucoma. In the present study, we examined the effectiveness of betaxolol and other beta-adrenergic blockers on glutamate-induced calcium signals. Dissociated adult mouse retinal ganglion cells were immuno-labeled with antibody CD90.2 and loaded with Fura-2AM. Calcium signals were recorded with optical recording techniques. Low doses of glutamate cause an increase in intracellular calcium that may result in pathological changes in ganglion cells. The action of glutamate could be reversibly suppressed by beta-adrenergic blockers and the order of inhibitory potency is (s)(-)-propranolol>betaxolol>>timolol, with average IC(50) of 78.05, 235.7 and 2167.05, microM, respectively. Betaxolol compressed the dose-response curve of glutamate. The EC(50) of glutamate was shifted from 6.19 to 23.53 microM, indicating that betaxolol acts as a non-competitive inhibitor of glutamate response in retinal ganglion cells. Our data are consistent with previous reports that betaxolol and other beta-adrenergic blockers may exert its neuroprotective action by suppression of glutamate-induced intracellular calcium increase in retinal ganglion cells.

Pooled-data analysis of three randomized, double-masked, six-month studies comparing intraocular pressure-reducing effects of latanoprost and timolol in patients with ocular hypertension.

PURPOSE: To assess retrospectively the intraocular pressure (IOP)-reducing effect of latanoprost compared with timolol in the subset of patients with ocular hypertension (OH). METHODS: Three randomized, double-masked, multicenter, parallel group, 6-month studies conducted in the United States, United Kingdom, and Scandinavia compared the efficacy and safety of latanoprost and timolol. The present study represents an analysis of the pooled data for the subset of OH patients. Intent-to-treat analyses were based on all randomized OH patients. RESULTS: Of the 441 patients with OH, 247 were treated with latanoprost and 194 were treated with timolol. Baseline mean diurnal IOP levels were 24.4 +/- 0.2 mm Hg (mean +/- standard error of the mean) in the latanoprost group and 24.2 +/- 0.2 mm Hg in the timolol group. Overall, latanoprost lowered mean diurnal IOP by 1.1 +/- 0.2 mm Hg (95% CI: 1.6 to 0.7 mm Hg, P < 0.001) more than timolol. The difference in IOP-lowering ability between the two drugs was not shown to be related to patient sex, age, race, presence or absence of previous treatment of OH, time elapsed since ocular diagnosis, or family history of glaucoma/OH. Percentage reductions from baseline in diurnal IOP levels of at least 20% were achieved by 83% of patients treated with latanoprost versus 62% of those receiving timolol. CONCLUSION: Latanoprost provides superior IOP reduction compared with timolol in patients with OH.

Aspirin use in advanced uncontrolled glaucoma.

PURPOSE: To evaluate if aspirin use affects progression of primary open angle glaucoma (POAG). METHODS: A retrospective review of patients with uncontrolled glaucoma was performed. Incidence of aspirin use was noted by a one-time self-reporting survey. Controls were medically stable patients diagnosed with POAG. The primary outcome measure studied was a comparison of percentages of aspirin use in patients who have and have not undergone glaucoma filtering surgery (trabeculectomy). RESULTS: Forty-one percent (26/64) of the patients in the trabeculectomy group and 23% (17/74) of controls were using aspirin. Patients undergoing trabeculectomy were twice as likely to take aspirin (O.R., 2.29; 95% C.I., 1.10-4.79). Subgroup analyses demonstrated increased aspirin use in those operative patients who are current or former smokers (O.R., 3.71; 95% C.I., 1.10-12.56), have systemic hypertension (O.R., 3.30; 95% C.I., 1.02-22.58), or have joint disease (O.R., 4.60; 95% C.I., 1.34-15.82). CONCLUSION: A higher concurrence of aspirin use was observed in patients with POAG who required surgical management compared with patients having relatively medically stable glaucoma. This may be secondary to a higher rate of glaucoma surgery performed on patients with greater systemic illnesses, more of whom use aspirin.

A mouse model of elevated intraocular pressure: retina and optic nerve findings.

PURPOSE: To develop and characterize a mouse model of elevated intraocular pressure (IOP) as a means to investigate the underlying cellular and genetic mechanisms of glaucomatous optic neuropathy. METHODS: An experimental increase in IOP was induced in one eye of each adult C57BL/6J mouse by argon laser photocoagulation of the episcleral and limbal veins. The IOP of both eyes of each mouse was measured using an indentation tonometer prior to treatment and once a week thereafter. The mouse retinal ganglion cells (RGCs) were identified immunocytochemically using an antiserum against Thy1,2, CD90.2, and the number of RGCs was measured with confocal microscopy. The reduction in the number of RGCs was compared in the experimental and control eyes. The mechanism of RGC death after IOP elevation was investigated using TdT-mediated dUTP nick end labeling (TUNEL) staining. The pathologic changes of optic nerve following elevated IOP were characterized by light and electron microscopy. RESULTS: After laser treatment, mean IOP was increased in the treated eyes from the control mean of 13 +/- 1.8 mm Hg to 20.0 +/- 2.8 mm Hg at 4 weeks. Peak IOP was 32 +/- 2.5 mm Hg in the experimental group. RGC loss was 16.9% +/- 7.8% at 2 weeks (n = 6, P < .05) and 22.4% +/- 7.5% at 4 weeks (n = 6, P < .05) after laser photocoagulation. TUNEL staining showed that there were marked increases in the number of apoptotic nuclei in the ganglion cell layer in the treated eyes; moreover, these TUNEL-positive cells were mostly distributed in the peripheral areas of the retina. The optic nerve axons from the eyes with elevated IOP were observed to demonstrate greater degeneration compared with the control group. CONCLUSIONS: The magnitude and duration of the elevation of the IOP supports the use of this model as a surrogate for glaucomatous optic neuropathy. The presumed apoptotic mechanism of RGC death is consistent with this assumption. Laser-induced increased IOP appears to be a viable means for future investigations of the genetic mechanisms of glaucoma.

Elevated intraocular pressure causes inner retinal dysfunction before cell loss in a mouse model of experimental glaucoma.

PURPOSE: We assessed the relationship among intraocular pressure (IOP), histology, and retinal function changes in a mouse model of induced, chronic, mild ocular hypertension. METHODS: IOP was elevated experimentally via anterior chamber injection of polystyrene beads and measured twice weekly with a rebound tonometer. Histology was assessed with a combination of neurobiotin (NB) retrograde labeling of retinal ganglion cells (RGCs) and TO-PRO3 staining. Retinal function was assessed with serial dark-adapted electroretinograms (ERGs) optimized for detection of the a-wave, b-wave, and positive and negative scotopic threshold responses (pSTR, nSTR). Comparisons between bead-injected and saline-injected (control) eyes were conducted. RESULTS: IOP remained elevated for at least 3 months following a single injection of polystyrene beads. Elevated IOP resulted in a mild, progressive reduction of RGCs, and a mild increase in axial length at 6 and 12 weeks after bead injection. The raw b-wave amplitude was increased shortly after IOP elevation, but the raw a-wave, pSTR, and nSTR amplitudes were unchanged. pSTR and nSTR amplitudes were normalized to the increased b-wave. With this normalization, the pSTR amplitude was decreased shortly after IOP elevation. CONCLUSIONS: Polystyrene bead injection results in a mild, chronic elevation of IOP that recapitulates several critical aspects of human ocular hypertension and glaucoma, and results in early changes in retinal electrical function that precede histologic changes. It is possible that glaucoma associated with elevated IOP involves the early disruption of a complex combination of retinal synapses.

Outcomes of surgical bleb revision for late-onset bleb leaks after trabeculectomy.

PURPOSE: To describe the outcome of surgical bleb revision for late-onset bleb leaks after trabeculectomy. PATIENTS AND METHODS: Appropriate cases were identified. Qualified and complete success required intraocular pressure of 21 mm Hg or less with and without glaucoma medication use, respectively. Bleb survival was determined using Kaplan-Meier survival analysis, and overall success rate was defined as qualified success at last follow-up. Preoperative and postoperative ocular parameters were compared using the signed-rank test. Age, sex, ethnicity, time between leak and revision, and surgeon type (attending vs. surgeons in training) were entered into a logistic regression analysis to assess the impact on surgical outcome. RESULTS: Seventy-eight eyes of 75 patients were included. The overall rate of successful bleb revision was 77%, and qualified and complete success at 24 months was 71% and 34%, respectively. Postoperative complications included early and late bleb leaks in 6% and 9% of the eyes, respectively; bleb-related infections in 4% of the eyes; and the need for additional glaucoma surgery in 10% of the eyes. There was no difference in preoperative and postoperative visual acuity (P=0.34) but there was an increase in intraocular pressure (P<0.0001) and the number of medications used (P<0.0001). The number of eyes that did not require glaucoma medication decreased (P=0.002). None of the variables examined had a significant impact on successful surgical outcome. CONCLUSION: Bleb revision showed a high success rate. About two-thirds of eyes required medication, 10% of eyes required additional glaucoma surgery, and there was a low risk for bleb-related infection following bleb revision.

Intraocular pressure control among patients transitioned from latanoprost to travoprost at a Veterans Affairs Medical Center Eye Clinic.

PURPOSE: To evaluate intraocular pressure (IOP) control and the ocular adverse effects resulting from a large-scale transition from latanoprost to travoprost among patients at a Veterans Affairs Medical Center (VAMC) Eye Clinic. METHODS: Retrospective chart review of patients transitioned from latanoprost to travoprost after a revision of the drug formulary used by the VAMC in Houston, Texas. IOP control after changing medications and the incidence of ocular adverse effects attributed to travoprost were the main outcomes measured. For patients who were using IOP-lowering medications bilaterally, the worse eye was used for all IOP analyses. Long-term retention in IOP control plus a cost-saving analysis were presented as a secondary assessment. RESULTS: Five hundred ninety-nine (599) patients with 1,041 treated eyes were evaluated. Mean IOP was 15.86 +/- 4.15 mmHg among patients using latanoprost prior to the prostaglandin analog transition. After transitioning to travoprost, the mean IOP was 15.78 +/- 4.38 mmHg. The mean within-eye change in IOP in the worse eye when transitioned from latanoprost to travoprost was -0.07 +/- 3.27 mmHg (P = 0.5914). Twenty-four (24) patients (4%) experienced an ocular adverse effect while using travoprost. In the long-term retention analysis at 1 year, mean change in IOP from the time of the original change to travoprost was +0.21 +/- 3.71 mmHg (P = 0.2683). CONCLUSIONS: The large-scale transition from latanoprost to travoprost maintained long-term IOP control. Only a small percentage of clinic patients experienced mild ocular adverse effects after being transitioned to the new prostaglandin analog.