Cytomegalovirus as a cause of recurrent corneal endotheliitis in the Canadian population.

OBJECTIVE: To report the clinical manifestations, response to antiviral treatment, and long-term visual outcomes of cytomegalovirus endotheliitis in a Canadian population. DESIGN: Retrospective case series. PARTICIPANTS: A total of 9 eyes of 7 patients referred to a cornea subspecialty clinic in a major Canadian centre with corneal endotheliitis. METHODS: A retrospective review of all patients presenting with corneal endotheliitis to 1 corneal surgeon was completed. Patients underwent anterior chamber biopsy with positive cytomegalovirus polymerase chain reaction. All patients received systemic valganciclovir for a minimum of 3 months. Primary outcomes included visual acuity, intraocular pressure control, medication dependence, and corneal status. RESULTS: The average follow-up was 76.4 ± 11.8 months. Two patients had bilateral disease. Corneal manifestations included linear, disciform, and circinate patterns of endotheliitis. Best-corrected visual acuity improved from a mean of 0.48 ± 0.19 logMAR at presentation to 0.24 ± 0.11 logMAR at last follow-up. Intraocular pressure decreased from a peak of 35 ± 3.1 mm Hg to 14.2 ± 4.3 mm Hg. Antiglaucoma medications were reduced from 2.6 ± 0.45 to 0.89 ± 0.29 agents. Two eyes required endothelial transplantation. Valganciclovir therapy was well tolerated by all patients; at the time of last follow-up, all patients were stable on low-dose valganciclovir at an average dose of 1395 mg per week. CONCLUSIONS: Cytomegalovirus is an uncommon but clinically significant cause of corneal endotheliitis that must be considered in the differential diagnosis of corneal endotheliitis, even in the immunocompetent population. Our results support prior findings that this entity responds robustly to oral valganciclovir and demonstrate for the first time the efficacy of chronic low-dose antiviral maintenance therapy.

Towards preventing exfoliation glaucoma by targeting and removing fibrillar aggregates associated with exfoliation syndrome.

Exfoliation syndrome presents as an accumulation of insoluble fibrillar aggregates that commonly correlates with age and causes ocular complications, most notably open-angle glaucoma. Despite advances in understanding the pathogenesis and risk factors associated with exfoliation syndrome, there has been no significant progress in curative pharmacotherapy of this disease. It is thought that the ability to target the fibrillar aggregates associated with exfoliation may offer a new therapeutic approach, facilitating their direct removal from affected tissues. Phage display techniques yielded two peptides (LPSYNLHPHVPP, IPLLNPGSMQLS) that could differentiate between exfoliative and non-affected regions of the human lens capsule. These peptides were conjugated to magnetic particles using click chemistry to investigate their ability in targeting and removing exfoliation materials from the anterior human lens capsule. The behavior of the fibrillar materials upon binding to these magnetic particles was assessed using magnetic pins and rotating magnetic fields of various strengths. Ex vivo studies showed that the magnetic particle-peptide conjugates could generate enough mechanical force to remove large aggregates of exfoliation materials from the lens capsule when exposed to a low-frequency rotating magnetic field (5000 G, 20 Hz). Biocompatibility of targeting peptides with and without conjugated magnetic particles was confirmed using MTT cell toxicity assay, live/dead cell viability assay, and DNA fragmentation studies on primary cultured human trabecular meshwork cells. This is a novel, minimally invasive, therapeutic approach for the treatment of exfoliation glaucoma via the targeting and removal of exfoliation materials that could be applied to all tissues within the anterior segment of the eye.

Stabilization of refractive error and associated factors following small incision phacoemulsification cataract surgery.

BACKGROUND: Accumulating evidence suggests that refractive stabilization occurs rapidly following small incision cataract surgery. Nonetheless, many guidelines still suggest waiting four to 6 weeks before prescribing corrective lenses. This study was undertaken to supplement the existing literature regarding refractive stabilization, and evaluate multiple contributing factors that could dissuade clinicians from confidently correcting refractive error in the early post-operative course following routine cataract surgeries. METHODS: Adult patients undergoing phacoemulsification cataract surgery with uncomplicated surgeries and post-surgical courses at the Calgary Ophthalmology Centre (Calgary, Alberta, Canada) were included in this prospective observational case series. Exclusion criteria included known corneal dystrophies, infectious keratitis, complicated surgery or toric/multifocal IOLs. Data was collected at weekly intervals for a total of 6 weeks. Collected data included autorefraction, visual acuity, corneal pachymetry, and effective lens position. RESULTS: One hundred six eyes of 104 patients were included in this study. Post-operative sphere, cylinder and spherical equivalent were not significantly different at any post-operative week compared with week six, and 80-86% of patients were within 0.5D of last follow-up spherical equivalent at any week. The secondary outcomes of central corneal thickness, effective lens position and visual acuity did, however, exhibit significant differences between early post-operative weeks and last follow-up values. CONCLUSIONS: These data suggest that refractive error can be effectively measured and corrected as early as one-week post-operatively in the majority of patients, though other measures of post-operative stability including central corneal thickness, effective lens position and visual acuity can require up to 4 weeks to stabilize. Thus a conservative and pragmatic approach may be to wait until 4 weeks post-operatively prior to obtaining refractive correction following uncomplicated phacoemulsification cataract surgery.

Analysis of Efficacy and Safety of Pediatric Ahmed Glaucoma Valve (FP8) in Advanced Age Populations.

PRECIS: The FP8 glaucoma valve was demonstrated to be reasonably safe with reliable results in an advanced age patient population. PURPOSE: As life expectancy increases, a growing number of patients with glaucoma are of an advanced age. There are little to no data looking at glaucoma surgical treatment options in patients over the age of 85. Our study describes the safety and efficacy of the FP8 Ahmed glaucoma valve in this patient population. MATERIALS AND METHODS: This was a retrospective study of patients over 85 years of age undergoing FP8 Ahmed glaucoma valve implantation. Preoperative age, sex, intraocular pressure (IOP), and number of glaucoma medications were recorded. Primary outcome variables were IOP and number of medications. Secondary outcome variables included any intraoperative or postoperative complications. RESULTS: Mean IOP preoperatively was 26 mm Hg on an average of 3 glaucoma medications (n=56). IOP was significantly reduced at all time points in follow-up for an overall reduction of 42% at 1 year and 46% at 2 years. Mean IOP at 1 year follow-up was 15 mm Hg and 14 mm Hg at 2 years follow-up. Glaucoma medications were reduced from a mean of 3 preoperatively to 2 postoperatively. CONCLUSIONS: Implantation of an FP8 Ahmed glaucoma valve is a relatively safe procedure to achieve satisfactory IOP and decreased reliance on glaucoma medications in an advanced age population.

Utilizing a responsive web portal for studying disc tracing agreement in retinal images.

Glaucoma is a leading cause of blindness worldwide whose detection is based on multiple factors, including measuring the cup to disc ratio, retinal nerve fiber layer and visual field defects. Advances in image processing and machine learning have allowed the development of automated approached for segmenting objects from fundus images. However, to build a robust system, a reliable ground truth dataset is required for proper training and validation of the model. In this study, we investigate the level of agreement in properly detecting the retinal disc in fundus images using an online portal built for such purposes. Two Doctors of Optometry independently traced the discs for 159 fundus images obtained from publicly available datasets using a purpose-built online portal. Additionally, we studied the effectiveness of ellipse fitting in handling misalignments in tracing. We measured tracing precision, interobserver variability, and average boundary distance between the results provided by ophthalmologists, and optometrist tracing. We also studied whether ellipse fitting has a positive or negative impact on properly detecting disc boundaries. The overall agreement between the optometrists in terms of locating the disc region in these images was 0.87. However, we found that there was a fair agreement on the disc border with kappa = 0.21. Disagreements were mainly in fundus images obtained from glaucomatous patients. The resulting dataset was deemed to be an acceptable ground truth dataset for training a validation of models for automatic detection of objects in fundus images.

Management of Ocular Surface Disease in Glaucoma: A Survey of Canadian Glaucoma Specialists.

PRéCIS:: Ocular surface disease (OSD) in glaucoma is an area for improvement in the management of patients with glaucoma. This study explores the knowledge of glaucoma subspecialists toward OSD in glaucoma, then provides a suggested treatment algorithm. PURPOSE: To assess the attitudes, knowledge, and level of comfort of Canadian glaucoma specialists with respect to the assessment and management of OSD among patients with glaucoma. METHODS: Ophthalmologist members of the Canadian Glaucoma Society with fellowship training in glaucoma were contacted to participate in this cross-sectional survey study. Responses were recorded to statements regarding attitudes toward OSD in glaucoma, and assessment and management modalities. These were recorded primarily in the form of a Likert scale rated 1 to 7 from "strongly disagree" to "strongly agree." Descriptive statistics were generated, and mean and SD for responses on Likert scales. RESULTS: Thirty-six responses were included. All respondents agreed that comprehensive management of OSD could improve quality of life, 97% agreed it could lead to better glaucoma outcomes, whereas only 22% agreed it is presently being adequately managed in glaucoma practices. Respondents were asked to list all treatment modalities they felt knowledgeable about, ranging from 100% for optimizing topical glaucoma therapies to 31% for serum tears. Nearly all respondents (92%) agreed that a suggested algorithm for the treatment of OSD in glaucoma could improve their approach to management. CONCLUSION: OSD is a common comorbidity of glaucoma. Although respondents overwhelmingly agreed that comprehensive management of OSD may lead to improved quality of life and glaucoma-related outcomes, only a small percentage felt it was presently adequately managed. Increasing knowledge related to the assessment and management of OSD in glaucoma may in the future improve patient care.

Ab Interno Canaloplasty in Open-angle Glaucoma Patients Combined With In Vivo Trypan Blue Aqueous Venography.

PURPOSE: To demonstrate canalogram patterns observed when trypan blue tracer is combined with oculoviscoelastic device during ab interno canaloplasty, and discuss surgical results and potential implications for diagnosis, prognosis, and treatment. METHODS: This is a retrospective small case series study. RESULTS: The authors performed this procedure on 5 patients with informed consent with 4 to 18 months of follow-up. All procedures have been complication free. The average preoperative intraocular pressure was 16.4 mm Hg with an average number of topical glaucoma medications being equal to 3.6. Postoperatively, the average intraocular pressure for the group was reduced to 13 mm Hg with a concurrent drop in the average number of topical medications used equaling 1.8. CONCLUSIONS: Currently, there are limited practical options to evaluate the patency of the aqueous outflow system in our patients. The primary purpose of this paper is to describe canalogram patterns observed during ab interno canaloplasty with trypan blue. This technique may allow us to further our understanding of the aqueous outflow system and its role in the underlying pathophysiology of glaucoma. Further research is required to evaluate the prognostic and diagnostic significance of this technique.

Structural polymorphisms in fibrillar aggregates associated with exfoliation syndrome.

Exfoliation syndrome is largely considered an age-related disease that presents with fibrillar aggregates in the front part of the eye. A growing body of literature has investigated structural diversity of amyloids and fibrillar aggregates associated with neurodegenerative disease. However, in case of exfoliation syndrome, there is a dearth of information on the biophysical characteristics of these fibrils and structural polymorphisms. Herein, structural diversity of fibrils isolated from the anterior lens capsule of patients was evaluated using transmission electron microscopy techniques. It was apparent that, despite having a low sample number of different patients, there exists a wide range of fibril morphologies. As it is not precisely understood how these fibrils form, or what they are composed of, it is difficult to postulate a mechanism responsible for these differences in fibril structure. However, it is apparent that there is a wider range of fibril structure than initially appreciated. Moreover, these data may suggest the variance in fibril structure arises from patient-specific fibril composition and/or formation mechanisms.

Selective Laser Trabeculoplasty versus Argon Laser Trabeculoplasty in Glaucoma Patients Treated Previously with 360° Selective Laser Trabeculoplasty: A Randomized, Single-Blind, Equivalence Clinical Trial.

PURPOSE: The effectiveness of selective laser trabeculoplasty (SLT) was compared with argon laser trabeculoplasty (ALT) in a randomized clinical trial for patients with medically uncontrolled open-angle glaucoma who have previously received 360° SLT. DESIGN: An active equivalence parallel armed randomized control trial. PARTICIPANTS: Patients with open-angle glaucoma including pigmentary dispersion syndrome and pseudoexfoliation syndrome were enrolled into the study from 7 different sites across Canada. METHODS: One setting of 180° of either SLT or ALT was assigned randomly and applied to each participant. MAIN OUTCOME MEASURES: The change in intraocular pressure (IOP) from baseline to 12 months was compared between the 2 groups. RESULTS: A total of 132 patients were recruited, 2 of which dropped out early in the study, leaving 130 patients who completed the study as per protocol. For those, the study's primary outcome was calculated. The IOP change at 1 year in comparison to baseline for SLT vs. ALT was found to be different by 0.33 mmHg between the 2 groups (3.16 for SLT and 2.83 for ALT) and was not statistically significant (P = 0.71) Further analysis, though, showed that SLT had a significantly lower IOP reduction at early time points: 1 week and 1 month, but this effect was lost by 3 months. Corresponding to this finding was the strong trend for ALT to fail more quickly than SLT. Although repeatable, the first repeat SLT reduced IOP to only about half compared with initial SLT treatment. CONCLUSIONS: The comparison at 12 months following the laser therapy showed that both modalities lowered the IOP with approximately 3 mmHg, yet essentially all of the time-to-failure analyses favored SLT over ALT. The repeat SLT effect was found to be half of the initial treatment.

A randomized clinical trial of selective laser trabeculoplasty versus argon laser trabeculoplasty in patients with pseudoexfoliation.

PURPOSE: To evaluate the efficacy of selective laser trabeculoplasty (SLT) versus argon laser trabeculoplasty (ALT) in lowering the intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension secondary to pseudoexfoliation. DESIGN: Multicentered randomized clinical trial. PARTICIPANTS: A total of 76 eyes from 60 patients with pseudoexfoliation and uncontrolled IOP were recruited from 5 Canadian academic institutions. Patients with prior laser trabeculoplasty, ocular surgery within 6 months, previous glaucoma surgery, an advanced visual field defect, current steroid use, and monocular patients were excluded. METHODS: Eyes were randomized to receive either 180-degree SLT or 180-degree ALT by a nonblocked randomization schedule stratified by center. MAIN OUTCOME MEASUREMENT: The primary outcome was the change in IOP at 6 months versus baseline and secondary outcomes included change in number of glaucoma medications after laser. Baseline variables included age, sex, angle grade, angle pigmentation, and number of glaucoma medications. RESULTS: Of the 76 eyes, 45 eyes received SLT and 31 eyes received ALT. The overall age was 72.9 years (65% females). The baseline IOPs in the SLT and ALT groups were 23.1 and 25.2 mm Hg, respectively (P=0.03). The IOP reduction 6 months after SLT was -6.8 mm Hg and post-ALT was -7.7 mm Hg (P>0.05). The SLT group had reduced glaucoma medications by 0.16 medications at 6 months and the ALT group had no decrease in medications over the same time period (P=0.59). There were no postlaser IOP spikes in either group. DISCUSSION: ALT and SLT are equivalent in lowering IOP at 6 months posttreatment in patients with PXF.

Antimetabolites in cataract surgery to prevent failure of a previous trabeculectomy.

BACKGROUND: Patients having cataract surgery have often earlier undergone a trabeculectomy for glaucoma. However, cataract surgery may be associated with failure of the previous glaucoma surgery and antimetabolites may be used with cataract surgery to prevent such failure. There is no systematic review on whether antimetabolites with cataract surgery prevent failure of a previous trabeculectomy. OBJECTIVES: To assess the effects of antimetabolites with cataract surgery on functioning of a previous trabeculectomy. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 10 June 2014. We also searched the Science Citation Index database (July 2013) and reference lists of potentially relevant studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of antimetabolites with cataract surgery in people with a functioning trabeculectomy. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed the titles and abstracts from the electronic searches. Two review authors independently assessed relevant full-text articles and entered data. MAIN RESULTS: We identified no RCTs to test the effectiveness of antimetabolites with cataract surgery in individuals with the intention of preventing failure of a previous trabeculectomy. AUTHORS' CONCLUSIONS: There are no RCTs of antimetabolites with cataract surgery in people with a functioning trabeculectomy. Appropriately powered RCTs are needed of antimetabolites during cataract surgery in patients with a functioning trabeculectomy.

An observational study of bimatoprost 0.01% in patients on prior intraocular pressure-lowering therapy: the Canadian Lumigan(®) RC Early Analysis Review (CLEAR) trial.

PURPOSE: To evaluate the ocular hyperemia and intraocular pressure (IOP)-lowering efficacy of bimatoprost 0.01% in subjects with elevated IOP due to primary open-angle glaucoma (POAG) or ocular hypertension (OHT) in a real-world clinical setting. SUBJECTS AND METHODS: This open-label, 12-week, observational study was conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline, week 6, and week 12 using a standardized photographic 5-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes the subgroup of 268 subjects who had been previously treated with latanoprost 0.005%, bimatoprost 0.03%, travoprost 0.004%, and travoprost 0.004% with SofZia™ or nonselective beta-adrenergic receptor blockers prior to the study. RESULTS: After 12 weeks of treatment with 0.01% bimatoprost, ocular hyperemia was graded as none-to-mild hyperemia (grades 0, +0.5, or +1) for 94.1% of subjects and as moderate-to-severe hyperemia (grades +2 or +3) for 5.9%. No statistically significant shifts in ocular hyperemia ratings were observed at week 12 for any of the prior IOP-lowering therapies except bimatoprost 0.03%, in which 20.8% of subjects experienced an improvement. The mean percentage change from baseline IOP at week 12 following the switch to bimatoprost 0.01% monotherapy ranged from -2.3%±17.3% to -26.3%±12.4%. Furthermore, the decreased mean percentage change from baseline IOP was statistically significant across all prior IOP-lowering medications, except for bimatoprost 0.03% at the 6- and 12-week visits and travoprost 0.004% at the 6-week visit. CONCLUSION: This observational study demonstrates that bimatoprost 0.01% was well tolerated among POAG and OHT subjects who switched from prior IOP-lowering medication. Furthermore, a switch in ocular hypertensive treatment to bimatoprost 0.01% was associated with an additional 10%-15% reduction in IOP.

Two cases of spontaneous filtering blebs, one idiopathic and one associated with Terrien marginal degeneration.

PURPOSE: To report a case of an idiopathic unilateral filtering bleb in an otherwise well patient and a case of bilateral spontaneous filtering blebs in association with Terrien marginal degeneration. METHODS: In this retrospective observational study of 2 cases, clinical notes, ultrasound biomicroscopy and gonioscopy images were reviewed. RESULTS: Case 1: A 32-year-old woman presented with a 1-year history of a gradually growing cyst in her right eye. No changes in vision were reported. The patient had no previous ocular or systemic history, trauma, or surgical interventions. Slit-lamp examination revealed a multilobulated cyst at the supranasal limbus OD. Diagnosis was an idiopathic spontaneous limbal filtering bleb of unclear etiology because there was no inciting event or obvious cause. Case 2: A 31-year-old man, with 2 past episodes of spontaneous filtering bleb development, affecting the left, then the right, eye, presented with his third event in May 2012. The visual acuity was decreased to 20/400 OD. The right eye was hypotonous and ultrasound biomicroscopy confirmed a shallow anterior chamber, a superior peripheral corneal defect, and an echolucent space suggestive of subconjunctival fluid. Limbal thinning was noted bilaterally, consistent with Terrien marginal degeneration. CONCLUSIONS: This is a rare case of an idiopathic filtering bleb occurring in a healthy patient with no precipitating cause, other ocular abnormalities, or physical malformations, and the only reported case of bilateral sequential filtering blebs associated with an atypical presentation of Terrien marginal degeneration.

Ocular surface tolerability of prostaglandin analogs and prostamides in patients with glaucoma or ocular hypertension.

INTRODUCTION: There has been increased attention on the potential impact of the preservative benzalkonium chloride (BAK) on the ocular surface. This study compared the ocular surface tolerability of once-daily bimatoprost 0.01% and latanoprost 0.005% (both preserved with 0.02% BAK), and travoprost 0.004% preserved with sofZia™. METHODS: A randomized, multicenter (15 sites), investigator-masked study enrolled patients with open-angle glaucoma or ocular hypertension who had received latanoprost monotherapy for at least 1 month. Patients were randomized to oncedaily bimatoprost (n = 56), travoprost (n = 53), or latanoprost (n = 55) monotherapy for 3 months. Follow-up visits were at weeks 1, 4, and 12. The primary outcome measure was physician-graded conjunctival hyperemia (scale 0 to 3) at week 12. Secondary outcomes included corneal staining (scale 0 to 3) and tear break-up time (TBUT). RESULTS: There were no significant differences in mean (standard deviation [SD]) outcome measures including conjunctival hyperemia (bimatoprost: 0.48 [0.52], travoprost: 0.49 [0.52], latanoprost: 0.51 [0.54]), corneal staining (bimatoprost: 0.31 [0.49], travoprost: 0.25 [0.46], latanoprost: 0.24 [0.45]), or TBUT (bimatoprost: 9.7 s [6.1], travoprost: 9.5 s [5.8], latanoprost: 9.8 s [5.0]) among subjects at latanoprost-treated baseline (P ≥ 0.664). At week 12, there were no significant differences in conjunctival hyperemia (bimatoprost: 0.42 [0.48], travoprost: 0.46 [0.44], latanoprost: 0.44 [0.57]), corneal staining (bimatoprost: 0.31 [0.45], travoprost: 0.32 [0.48], latanoprost: 0.22 [0.30]), or TBUT (bimatoprost: 9.7 s [5.7], travoprost 9.7 s [5.0], latanoprost: 9.3 s [4.0]) among the treatment groups (P ≥ 0.379). At week 1, there was a statistically significant among-group difference in mean change from baseline in hyperemia (+0.04, bimatoprost; +0.20, travoprost; 0.00, latanoprost; P = 0.018). There were no statistically significant among-group differences in mean corneal staining, mean TBUT, or change from baseline at any visit. CONCLUSIONS: Despite preservative differences, there were no significant differences in objective clinical measures of ocular surface tolerability after 3 months of treatment with bimatoprost (with 0.02% BAK), travoprost (with sofZia), and latanoprost (with 0.02% BAK).

Morning dosing of once-daily glaucoma medication is more convenient and may lead to greater adherence than evening dosing.

PURPOSE: To determine if adherence and convenience of once-daily glaucoma medication is greater in the morning or the evening. DESIGN: Prospective, randomized crossover treatment trial. PATIENTS AND METHODS: Thirty patients newly diagnosed with glaucoma or ocular hypertension requiring intraocular pressure (IOP) reduction were started on travoprost eye drops and randomized to either morning or evening administration for 1 month. They were then crossed over to the opposite dosing schedule for the following month. Adherence was monitored using an automated dosing aid. MAIN OUTCOME MEASURES: Adherence was compared between morning versus evening dosing and first versus second month dosing. Demographic characteristics were obtained, treatment effect was measured, and patients completed a post-study questionnaire regarding the convenience of the 2 dosing regimens. RESULTS: Patient adherence overall was good (89.3%). There was no statistically significant difference (P=0.07) in adherence between morning dosing (90.9%) and evening dosing (87.3%). Adherence in the first month (91.7%) was superior to the second month (86.5%). There was no significant difference in IOP response between morning and evening dosing. Patients found morning dosing more convenient than evening dosing. CONCLUSIONS: Early adherence to treatment with a prostaglandin analogue is good, but patients prefer morning administration to evening administration. This may lead to greater adherence with morning administration, particularly among men. Adherence decreases from the first to second month after initiation of treatment. IOP response to this treatment is not significantly affected by morning versus evening administration.

An observational study of bimatoprost 0.01% in treatment-naïve patients with primary open angle glaucoma or ocular hypertension: the CLEAR trial.

BACKGROUND: This study was designed to evaluate the occurrence and severity of ocular hyperemia in subjects with elevated intraocular pressure (IOP) due to primary open angle glaucoma (POAG) or ocular hypertension (OHT) following treatment with bimatoprost 0.01% in a real-world clinical setting. METHODS: This was an open-label, observational study conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% topically as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline and weeks 6 and 12 using a photographic five-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes only the subgroup of 522 subjects who were naïve to IOP-lowering medication prior to the study. RESULTS: After 12 weeks of treatment with bimatoprost 0.01%, hyperemia was graded as none-to-mild (grades 0, +0.5, or +1) for 93.3% of subjects and as moderate-to-severe (grades +2 or +3) for 6.7%. At weeks 6 and 12, most subjects (93.2% and 93.5%) had no change in hyperemia grade from baseline. IOP was reduced by 7.4 mmHg (29.8%) at week 6 and 7.7 mmHg (30.9%) at week 12 from baseline. CONCLUSION: This real-world, observational study found that bimatoprost 0.01% instilled once daily reduced IOP by a mean of 30% from baseline without moderate or severe ocular hyperemia in 93% of treatment-naïve subjects with POAG or OHT.

Effectiveness of dorzolamide­timolol (COSOPT) in patients who were treatment naive for open-angle glaucoma or ocular hypertension: the COSOPT first-line study.

PURPOSE: The aim of this study was to assess the effectiveness of dorzolamide-timolol (DT) in the management of open-angle glaucoma (OAG) and ocular hypertension. METHODS: An open-label, 12-week, multicenter, Canadian study was conducted. Patients with untreated OAG or ocular hypertension received DT for 12 weeks to reduce intraocular pressure (IOP). If target IOP was not reached after the first 6-week treatment period, a prostaglandin (PG) (latanoprost) was added for the remaining 6 weeks. Primary outcome measures were changes in IOP from baseline to 6 and 12 weeks of treatment, and secondary outcome measures included the proportion of patients achieving target IOP and the proportion of patients achieving therapeutic response defined as a reduction of 5.0 mmHg or 20% in IOP from baseline. IOP values were the mean of 2 measures taken before and at least 2 h after patients administered the study medication. RESULTS: A total of 164 patients were enrolled. Mean [standard deviation (SD)] population age was 63.0 (12.3) years and 53.0% of the patients were men. At week 6, the mean (SD) absolute and percent change in IOP for the total population was (-11.1) (4.9) and (-36.4)% (13.9%), respectively, and 92.1% of the patients achieved a reduction in IOP of at least 5 mmHg. Therapeutic target was achieved by 136 (82.9%) patients (DT subgroup) at 6 weeks, whereas 28 (17.1%) patients were changed to a combination therapy of DT and latanoprost [DT plus PG (DT & PG) subgroup]. Between weeks 6 and 12, DT was effective in sustaining the IOP within therapeutic target, whereas addition of latanoprost reduced the IOP of the DT & PG subgroup by an additional 6.3 mmHg or 22.1% (20.1%). At week 12, patients in the DT subgroup experienced a clinically and statistically significant mean (SD) decrease in IOP from a baseline of 12.2 mmHg or 40.4% (11.9%) (P < 0.001), whereas these values corresponded to 13.4 mmHg and 39.7% (15.7%) (P < 0.001), respectively, in the DT & PG subgroup. The proportion of patients who achieved therapeutic response during the entire 12-week study period was over 82%. Treatment-related adverse events (AEs) were reported by 19 (14.0%) patients in the DT subgroup and by 6 (21.4%) patients in the combination subgroup. Eye disorders and nervous system disorders were among the most common treatment-related AEs in both subgroups. No serious AEs were reported during the study period. CONCLUSION: DT alone and DT in combination with a PG are effective in significantly reducing IOP in patients with untreated OAG or ocular hypertension. The treatment was safe and well tolerated with a low incidence of AEs.