Michael Coote

The safety and efficacy of brinzolamide 1%/timolol 0.5% fixed combination versus dorzolamide 2%/timolol 0.5% in patients with open-angle glaucoma or ocular hypertension.

PurposeThis study compared the intraocular pressure (IOP)-lowering efficacy of 2 fixed combination products, brinzolamide 1%/timolol 0.5% suspension (Azarga, Brinz/Tim) and dorzolamide 2%/timolol 0.5% solution (Dorz/Tim), in patients with open-angle glaucoma or ocular hypertension who required a change in therapy due to elevated IOP while receiving IOP-lowering medication. MethodsThis was a one-year, multicenter, randomized, double-masked, active-controlled, parallel-group trial of Brinz/Tim and Dorz/Tim. IOP assessments were taken at 8 and 10 AM at week 2 and months 3 and 9, and at 8 AM, 10 AM, and 4 PM at months 6 and 12. Primary efficacy was a noninferiority comparison of mean IOP at the three month 6 time points. ResultsOf the 437 patients enrolled, 220 dosed Brinz/Tim whereas 217 dosed Dorz/Tim twice daily. Brinz/Tim produced IOP-lowering efficacy comparable to Dorz/Tim, with the upper 95% confidence limits for the differences between groups within +1.5 mm Hg at all assessment times, including the month 6 primary efficacy time points, establishing noninferiority. Differences in means numerically favored Brinz/Tim at 9 of 12 study visits and times. The IOP reductions ranged from 7.2 to 9.2 mm Hg for Brinz/Tim and from 7.4 to 8.9 mm Hg for Dorz/Tim. Although a similar overall safety profile was observed between the 2 treatment groups, Brinz/Tim showed significantly less ocular irritation (2.7% vs. 10.6%; P=0.0009) than Dorz/Tim. ConclusionsBrinz/Tim suspension provides statistically significant and clinically relevant IOP-lowering efficacy that is noninferior to Dorz/Tim. Additionally, Brinz/Tim affords an ocular comfort advantage compared with Dorz/Tim.

Antifibrotic Activity of Bevacizumab on Human Tenon's Fibroblasts In Vitro

PURPOSE To evaluate the effect of the anti-VEGF-A monoclonal antibody bevacizumab on primary human Tenons capsule fibroblasts (HTFs) in an in vitro model of wound healing. METHODS Fibroblasts were cultured in RPMI media, and bevacizumab was administered at a concentration ranging from 0.25 to 12.5 mg/mL. Fibroblast viability and cell death were assessed using the MTT colorimetric assay, lactate dehydrogenase assay, BrdU assay, and live/dead assay. Fibroblast contractility was assessed in floating collagen gels. Morphologic changes were assessed by transmission electron microscopy. Antifibrosis activities were compared with 5-fluorouracil. RESULTS Bevacizumab induced a significant dose-related reduction of HTF cell number at 12.5 mg/mL at 72 hours (P < 0.05). Under serum-free conditions, bevacizumab induced significant fibroblast cell death at concentrations greater than 7.5 mg/mL (P < 0.05). Bevacizumab caused a moderate inhibition of fibroblast gel contraction from baseline (P < 0.05). Scanning electron microscopy revealed marked vacuolization in bevacizumab-treated fibroblasts. CONCLUSIONS Bevacizumab disrupted fibroblast proliferation, inhibited collagen gel contraction ability, and induced fibroblast cell death at concentrations greater than 7.5 mg/mL in serum-free conditions. These results demonstrated that bevacizumab inhibited a number of fibrosis activities in culture. These activities may underpin the antifibrosis effect proposed in vivo.

Risk factors for delayed suprachoroidal haemorrhage following glaucoma surgery

Aim: To determine the incidence, risk factors and outcomes of delayed suprachoroidal haemorrhage (DSCH) after glaucoma surgery. Methods: A retrospective case-control study was performed at a tertiary referral eye hospital on patients who presented with DSCH following glaucoma surgery. Cases were compared with a matched-control population that underwent equivalent procedures but did not develop DSCH. The main outcome parameters were incidence of DSCH, risk factors associated with its occurrence, visual outcome and prognostic factors. Results: Of the 2752 glaucoma surgeries performed during the 10-year recruitment period, 29 cases of DSCH (1%) were identified. An increased incidence of DSCH was observed after glaucoma drainage device implantation compared with trabeculectomy-associated DSCH (p<0.0001; odds ratio 3.4; 95% CI 1.9 to 5.4). Risk factors for DSCH included low postoperative intraocular pressure (⩽3 mm Hg; p<0.001), aphakia (p<0.001), prior intraocular surgery (p<0.002), hypertension (p<0.001), anticoagulation (p = 0.002), ischaemic heart disease (p = 0.001) and respiratory disease (p = 0.008). The visual outcome of patients with haemorrhage was poor (logMAR 1.34 (SD 0.41)) and was significantly worse when compared with the control group (p = 0.002). Conclusions: In this study cohort, DSCH occurred more frequently after glaucoma drainage device implantation compared with trabeculectomy. Caution should be exercised when operating on patients with known ocular and systemic risk factors.

Australian and New Zealand Registry of Advanced Glaucoma: methodology and recruitment

Background:  Glaucoma is a sight‐threatening disease affecting 3% of the population over the age of 50. Glaucoma is treatable, and severe vision loss can usually be prevented if diagnosis is made at an early stage. Genetic factors play a major role in the pathogenesis of the condition, and therefore, genetic testing to identify asymptomatic at‐risk individuals is a promising strategy to reduce the prevalence of glaucoma blindness. Furthermore, unravelling genetic risk factors for glaucoma would also allow a better understanding of the pathogenesis of the condition and the development of new treatments.

Comparison of a travoprost BAK-free formulation preserved with polyquaternium-1 with BAK-preserved travoprost in ocular hypertension or open-angle glaucoma.

Purpose To demonstrate that the intraocular pressure (IOP)–lowering effect of travoprost 0.004% preserved with polyquaternium-1 (travoprost benzalkonium chloride [BAK]-free) is non-inferior to that of travoprost 0.004% preserved with benzalkonium chloride (travoprost BAK) in patients with ocular hypertension or open-angle glaucoma. Methods A total of 371 patients randomly received travoprost BAK-free (n=185) or travoprost BAK (n=186) dosed once daily in the evening for 3 months. Patients were evaluated at 9 AM, 11 AM, and 4 PM at baseline, weeks 2 and 6, and month 3. Intraocular pressure was also evaluated 36 and 60 hours after the month 3 visit. Results Travoprost BAK-free is non-inferior to travoprost BAK. The 95% upper confidence limits for the difference in mean IOP at month 3 (primary efficacy) were 0.5 mmHg, 0.6 mmHg, and 0.5 mmHg, at 9 AM, 11 AM, and 4 PM, respectively. Mean IOP reductions from baseline ranged from 7.6 to 8.7 mmHg in the travoprost BAK-free group and from 7.7 to 9.2 mmHg in the travoprost BAK group. At 36 and 60 hours after the last dose, mean IOP remained 6.8 mmHg and 5.7 mmHg below baseline in the travoprost BAK-free group, vs 7.3 mmHg and 6.0 mmHg in the travoprost BAK group, respectively. The safety profile of travoprost BAK-free was similar to that of travoprost BAK. Conclusions Travoprost BAK-free safely and effectively lowers IOP in eyes with open-angle glaucoma or ocular hypertension. This BAK-free formulation has comparable safety, efficacy, and duration of IOP-lowering effect to travoprost preserved with BAK. Travoprost BAK-free is an effective option for IOP reduction while avoiding BAK exposure.

Vascular changes after intra-bleb injection of bevacizumab.

PurposeTo illustrate changes in bleb vascularity after subconjunctival bevacizumab injection. MethodsLongitudinal changes in bleb vascularity were followed over 6 months pre and postbevacizumab injection. ResultsBleb vascularity associated with increased scarring activity was observed 10 days postcataract surgery in an eye that had undergone trabeculectomy 3 months previously. A single subconjunctival avastin injection led to a dramatic reduction in bleb vascularity for 6 weeks. With continued steroids, a diffuse, healthy, well functioning bleb with minimal scar tissue was present at 6 months. ConclusionsSubconjunctival injection of bevacizumab reduced bleb vascularity and may provide an adjunct to current antifibrosis therapy. Further studies to establish the effect of bevacizumab on postoperative scaring are warranted.

The problem of overlapping glaucoma families in the Glaucoma Inheritance Study in Tasmania (GIST)

The Glaucoma Inheritance Study in Tasmania (GIST) is a population survey of Australias island state, Tasmania (population 450,000). Its aim is to find families with autosomal dominant, adult-onset, primary open angle glaucoma (POAG) suitable for genetic linkage analysis. POAG is relatively common, affecting around 3% of the Australian population. By finding the large families with POAG and identifying all the descendants in a captive population, it is possible that there may be overlap of different glaucoma pedigrees. Three of the first thirteen families in the study were composed of overlapping pedigrees. In one GIST family, GTas3, there has been intermarriage with other pedigrees with glaucoma on five occasions. The possibility of multiple genotypes was also reinforced by the inability to determine a single glaucoma phenotype in this family. When finding large families of POAG for linkage analysis, researchers must be aware of the risk of affected individuals inheriting their gene from the alternate parent. Thus, the alternate parents or their families must be examined, especially if the phenotype is atypical for the rest of the family.

Intraocular Pressure Lowering Is Associated with an Increase in the Photopic Negative Response (PhNR) Amplitude in Glaucoma and Ocular Hypertensive Eyes

PURPOSE The aim of our study was to determine whether IOP lowering in glaucomatous and ocular hypertensive (OHT) eyes leads to an improvement in the full-field photopic negative response (PhNR) of the electroretinogram. METHODS A prospective nonrandomized interventional cohort study was conducted. Patients with OHT or glaucomatous optic neuropathy were recruited, and photopic full-field electroretinograms (ERG) were performed at baseline and then repeated 1 to 2 months later. The change in PhNR amplitude was compared between those eyes that had a significant lowering in IOP (defined as >25% decrease from baseline or to a predetermined target IOP) during follow-up and those that did not. RESULTS From a cohort of 30 eyes, 18 eyes had a significant reduction in IOP during follow-up (n = 18) and 12 eyes had no significant change in IOP (<25% reduction in IOP, n = 12). A significant increase in PhNR amplitude and the PhNR/b-wave amplitude ratios was observed in the reduced IOP group, but not in the IOP stable group for the two flash intensities used (2.25 and 3.00 cd.s/m(2)). CONCLUSIONS The full-field PhNR amplitude provides a potentially reversible measure of inner retinal function that improves after IOP lowering. Further study now is required to assess its use as a measure of optic nerve health in glaucoma patients.

Topical prostaglandin analogues do not affect selective laser trabeculoplasty outcomes.

PurposeTo investigate the effect of topical prostaglandin analogue use on the efficacy of selective laser trabeculoplasty (SLT) intraocular pressure (IOP) lowering in patients with open-angle glaucoma.Patients and MethodsThis retrospective study included 123 consecutive patients who underwent 180° SLT for the first time. Eyes were grouped into those that received prostaglandin analogues before and after SLT (n=74) and those that did not (n=49). The main outcome measure was IOP lowering after SLT. Success was defined as ⩾20% reduction in IOP without further glaucoma intervention.ResultsThere was no significant difference in IOP lowering at 6 months post-laser between the prostaglandin and non-prostaglandin groups (3.9±4.8 vs4.6±3.6 mm Hg, P=0.43). Long-term SLT success rates were also not significantly different between the treatment groups (Kaplan–Meier survival analysis, P=0.68). IOP lowering at 6 months was similar in eyes that received no glaucoma medications, monotherapy with or without a prostaglandin analogue, or combination therapy with or without prostaglandin analogues (P=0.81). Logistic regression analysis showed that various patient characteristics including age, sex, type of glaucoma, previous glaucoma surgery, and other glaucoma risk factors did not predict a successful SLT outcome. However, higher pre-operative IOP was found to predict SLT success (odds ratio=1.12, 95% CI=1.02–1.24, P=0.02).ConclusionThe IOP lowering efficacy of SLT is not influenced by the use of topical prostaglandin analogues.

Bleb vascularity following post-trabeculectomy subconjunctival bevacizumab: a pilot study

Background:  To determine whether postoperative subconjunctival bevacizumab significantly alters bleb vascularity.