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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., (© 2022. The Author(s).)

Objective: To determine the incidence and risk factors for steroid response in patients undergoing combined phacoemulsification cataract extraction (PCE) and microinvasive glaucoma surgery with either trabecular microbypass stent implantation (iStent) or ab interno trabeculectomy (Trabectome)., Design: Retrospective, noncomparative, single-institutional observational chart review., Participants: Consecutive patients with open-angle glaucoma who underwent PCE with iStent or Trabectome with 3 months of follow-up., Methods: Data were collected from patient charts, including pre- and postoperative intraocular pressure (IOP) following application of topical corticosteroid on postoperative visits for at least 3 months. A steroid response was defined as an IOP rise of greater than 5 mm Hg beginning at least 3 days after surgery with no other obvious explanation and with IOP < 20 mm Hg following rapid tapering or withdrawal of the steroid., Results: A total of 118 eyes from 89 patients, average age of 71.4 ±12.1 years, were included. Overall, a steroid response was seen in 12.7% of eyes (n = 15), and no difference was noted between Trabectome (11.8%) and iStent (13.6%, p = 0.782) eyes. Axial length (AL; p = 0.01), younger age (p = 0.009), traumatic glaucoma (p = 0.004), and normal-tension glaucoma (NTG; p = 0.0048) were significant predictors of steroid response in a multivariate analysis. In eyes with AL ≥ 25 mm, the steroid response rate was 40%, in contrast to eyes with AL < 25 mm, where it was 10.2%., Conclusion: A steroid response develops in approximately 1 in 8 patients undergoing PCE with Trabectome or iStent. Young age, AL > 25 mm, traumatic glaucoma, and NTG were found to be significant predictors of steroid response., (Copyright © 2021 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Exfoliation syndrome is generally considered a progressive age-related systemic disorder of the extracellular matrix, which is clinically characterized through the observation of flaky white aggregates on ocular tissues. Exfoliation syndrome is directly linked to exfoliative glaucoma in elderly patients, where it is known as the most common identifiable cause of open-angle glaucoma. Despite the identification of various risk factors associated with exfoliation syndrome, the exact pathogenesis of this syndrome has not been fully elucidated. There is a growing number of genome-wide association studies in different populations around the world to identify genetic factors underlying exfoliation syndrome. Besides variants in LOXL1 and CACNA1A genes, new loci have been recently identified which are believed to be associated with exfoliation syndrome. Among different genetic factors, functional variants might help to better understand mechanisms underlying this systemic disorder. Besides genetic factors, epigenetic regulation of different gene expression patterns has been thought to play a role in its pathogenesis. Other factors have been also considered to be involved in the development of exfoliation syndrome at cellular organelles level where mitochondrial impairment and autophagy dysfunction have been suggested in relation to exfoliation syndrome. This review addresses the most recent findings on genetic factors as well as cellular and molecular mechanisms involved in both the development and progression of exfoliation syndrome., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

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., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the efficacy and safety of ab interno trabeculectomy with the Trabectome combined with cataract surgery (phaco-AIT) versus Trabeculectomy with mitomycin C combined with cataract surgery (phaco-Trab) in open-angle glaucoma., Methods: A prospective randomized controlled trial with a single surgeon and surgical center was undertaken. Patients were recruited from July 2009 to October 2014. Primary outcomes were mean intraocular pressure (IOP) at 6 months and surgical complications. Secondary outcomes were mean IOP at 12 months, achievement of target IOP, number of glaucoma medications, and rate of secondary surgery., Results: The trial was ended early before achieving our intended sample size due to difficulties in recruitment and lack of clinical equipoise over time. Nineteen patients were enrolled, 10 phaco-AIT and 9 phaco-Trab. Baseline IOP was 20.0 ± 5.3 in phaco-AIT and 23.1 ± 6.4 mm Hg in phaco-Trab (p = 0.22). IOP decreased to 17.5 ± 3.8 and 16.0 ± 6.0 mm Hg at 6 months (p = 0.54), and 16.8 ± 2.7 and 17.1 ± 5.0 mm Hg at 1 year (p = 0.57), respectively. Mean number of glaucoma medications at baseline was 1.8 ± 1.3 in phaco-AIT and 1.4 ± 1.1 in phaco-Trab (p = 0.59). Mean number of glaucoma medications decreased to 0.78 ± 1.39 and 0.38 ± 0.74 at 6 months (p = 0.68), and 0.44 ± 0.88 and 0.75 ± 0.89 at 1 year (p = 0.41), respectively. Mild and moderate complications were seen in both treatment groups, but severe complications were seen only in phaco-Trab. One secondary glaucoma procedure was required in the phaco-AIT group., Conclusions: Phaco-AIT achieved similar IOP lowering at 6 and 12 months compared with phaco-Trab with a similar number of glaucoma medications required at 1 year, and no serious complications were identified in the Phaco-AIT group., (Copyright © 2018 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the efficacy and safety of ab interno trabeculectomy with Trabectome in juvenile open-angle glaucoma (JOAG) patients., Design: Prospective cohort study., Methods: Evaluation of the 12-month results of 2 patient groups receiving ab interno trabeculectomy: group 1, eyes with no prior incisional surgery; group 2, eyes that had prior incisional cataract or glaucoma surgery., Results: Group 1, 40 eyes (average age 31 ± 7 years), had a significant reduction in intraocular pressure (IOP) of 10.6 mm Hg at 12 months from a baseline of 27.4 mm Hg (p = 0.01), and the number of glaucoma medications reduced by 0.4 (p = 0.80). Four eyes (10%) within the study period required a secondary glaucoma surgery. Group 2, 20 eyes (average age 27 ± 8 years), had a significant reduction in IOP of 8.8 mm Hg from a baseline of 27.1 mm Hg (p = 0.06), and the number of glaucoma medications reduced by 1.4 (p = 0.36). Five eyes (25%) from this group underwent a secondary glaucoma surgery within 12 months., Conclusion: After 1 year of follow-up, ab interno trabeculectomy appears to be an effective and safe intervention for patients with JOAG; however, a reduction in use of topical medications may not be observed in those receiving ab interno trabeculectomy as a primary procedure., (Copyright © 2018 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the intraocular pressure-lowering efficacy and complication rate of ab interno trabeculectomy with the Trabectome between African American (AA) and Caucasian patients with open-angle glaucoma., Methods: A total of 164 patients (82 AA and 82 Caucasian) who underwent ab interno trabeculectomy over an 8-year period were included in this prospective, case-control study. The Neomedix database was used to look for AA or Caucasian patients with open-angle glaucoma who underwent Trabectome with or without phacoemulsification., Results: The average IOP of AA patients was reduced from 21.2 ± 6.8 mm Hg to 16.1 ± 4.1 mm Hg at 12 M (p < 0.01), and the mean number of glaucoma medications was reduced from 2.4 ± 1.3 to 2.0 ± 1.4 (p = 0.13). Among Caucasians, the mean IOP was reduced from 21.2 ± 6.8 mm Hg to 15.7 ± 4.2 mm Hg at 12 M (p < 0.01), and the number of medications dropped from 2.4 ± 1.2 to 1.7 ± 1.3 (p < 0.01). No statistically significant difference was found between these 2 race groups in IOP, number of medications, and complications. For complications with Trabectome alone, 13% of AA and 9% of Caucasian patients needed secondary surgery. There was only 1 case of hypotony which was in the AA group. For complications with Trabectome combined with phacoemulsification, 4% of AA as well as 4% of Caucasian patients required secondary surgery. There was only 1 case of hypotony which was in the Caucasian group., Conclusion: Ab interno trabeculectomy with Trabectome is associated with a reduction in IOP in both race groups with a similar complication and survival profiles., (Copyright © 2018 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Argon laser trabeculoplasty as well as selective laser trabeculoplasty can be used in patients with exfoliation syndrome with similar safety and efficacy. However, treatment effect may abruptly reverse and patients need to be followed regularly to monitor intraocular pressure control. Newer laser treatment modalities including micropulse laser trabeculoplasty, titanium sapphire laser trabeculoplasty and pattern scanning trabeculoplasty show promising results but need to be studied in exfoliation patients. For exfoliation patients with angle closure, peripheral iridectomy, iridoplasty or cataract extraction can be very helpful. For refractory exfoliation glaucoma, transscleral diode laser cyclophotocoagulation offers a reasonable option to lower intraocular pressure. Other approaches to cyclophotocoagulation such as micropulse transcleral diode laser need to be studied further in exfoliation patients.

Synopsis: Clinicians can feel confident compressed three-dimensional digital (3DD) and two-dimensional digital (2DD) imaging evaluating important features of glaucomatous disc damage is comparable to the previous gold standard of stereoscopic slide film photography, supporting the use of digital imaging for teleglaucoma applications., Background/aims: To compare the sensitivity and specificity of 3DD and 2DD photography with stereo slide film in detecting glaucomatous optic nerve head features., Methods: This prospective, multireader validation study imaged and compressed glaucomatous, suspicious or normal optic nerves using a ratio of 16:1 into 3DD and 2DD (1024×1280 pixels) and compared both to stereo slide film. The primary outcome was vertical cup-to-disc ratio (VCDR) and secondary outcomes, including disc haemorrhage and notching, were also evaluated. Each format was graded randomly by four glaucoma specialists. A protocol was implemented for harmonising data including consensus-based interpretation as needed., Results: There were 192 eyes imaged with each format. The mean VCDR for slide, 3DD and 2DD was 0.59±0.20, 0.60±0.18 and 0.62±0.17, respectively. The agreement of VCDR for 3DD versus film was κ=0.781 and for 2DD versus film was κ=0.69. Sensitivity (95.2%), specificity (95.2%) and area under the curve (AUC; 0.953) of 3DD imaging to detect notching were better (p=0.03) than for 2DD (90.5%; 88.6%; AUC=0.895). Similarly, sensitivity (77.8%), specificity (98.9%) and AUC (0.883) of 3DD to detect disc haemorrhage were better (p=0.049) than for 2DD (44.4%; 99.5%; AUC=0.72). There was no difference between 3DD and 2DD imaging in detecting disc tilt (p=0.7), peripapillary atrophy (p=0.16), grey crescent (p=0.1) or pallor (p=0.43), although 3D detected sloping better (p=0.013)., Conclusions: Both 3DD and 2DD imaging demonstrates excellent reproducibility in comparison to stereo slide film with experts evaluating VCDR, notching and disc haemorrhage. 3DD in this study was slightly more accurate than 2DD for evaluating disc haemorrhage, notching and sloping., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To investigate efficacy and safety of phaco-trabectome (PT) versus phaco-iStent (Pi) for intraocular pressure (IOP) control in open-angle glaucoma (OAG)., Design: Retrospective comparative case series., Participants: A total of 70 eyes of 55 patients with OAG underwent either PT surgery by a single surgeon or Pi (insertion of 2 stents) by another surgeon in Canada between January 2010 and December 2012., Methods: The medical records of consecutive adult patients who underwent either PT or Pi surgery were reviewed. All patients who satisfied both the inclusion and exclusion criteria were included in the outcomes analyses. IOP reduction, reduction in glaucoma medication, safety profile, and best-corrected visual acuity were evaluated., Results: Thirty-six eyes of 30 patients had PT and 34 eyes of 25 patients had Pi. Baseline IOP was higher in the PT group (20.92 ± 5.07 mm Hg) than in the Pi group (17.47 ± 4.87 mm Hg; p = 0.026). At 12 months there was no significant difference between groups in relative reduction of mean IOP (PT -5.09 ± 5.73, 24% relative reduction vs. Pi -3.84 ± 3.80, 22% relative reduction; p = 0.331) or glaucoma medication use (PT -0.49 ± 1.17 vs. Pi -0.26 ± 0.73; p = 0.168) from baseline. However, Pi had significantly fewer individual complications (PT 20 vs. Pi 5; p < 0.0001) throughout the postoperative period., Conclusion: At 12 months of follow-up, both techniques significantly lowered IOP, but fewer complications were observed in the Pi group., (Copyright © 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

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.

Objective: To review the diagnostic outcomes and clinical referral pathways of patients assessed and managed through a collaborative care patient-centred teleglaucoma program., Study Design: Retrospective cohort study., Methods: Eligible patients were those assessed by the referring optometrist or ophthalmologist to be open-angle glaucoma suspects or to have definite early open-angle glaucoma. A glaucoma specialist graded each case through virtual consultation. Clinical referral pathways were noted: in-person consultation with glaucoma specialist, repeat teleconsultation, collaborative glaucoma management with optometrist, or referral for nonglaucomatous ophthalmic pathology., Results: A total of 247 patients were referred to the program from 2008 to 2012. Of all teleconsults, 31.1% were diagnosed with glaucoma, 42.1% were suspects, and 26.7% were unaffected. Of all patients, 27% were referred for in-person glaucoma evaluation; 69% of patients could be managed by their referring optometrist, with 48% of patients requiring repeat teleconsultation. Treatment was initiated before being seen for 87% of patients with definite glaucoma and 28% of glaucoma suspects., Conclusions: Of all patients seen through the remote teleglaucoma program, most did not require an in-person consultation with an ophthalmologist and could be managed through distance collaboration. For the approximately one third who were diagnosed with glaucoma based on virtual assessment, medication was started in the majority of cases and in-person consultation was arranged. Further studies to validate and consider cost-effectiveness of this system are under way., (© 2013 Canadian Ophthalmological Society Published by Canadian Ophthalmological Society All rights reserved.)

Objective: To compare the efficacy of scanning laser ophthalmoscope microperimetry (SLO-MP) and Humphrey visual fields in detecting macular sensitivity changes in advanced glaucoma., Design: Prospective cohort study., Participants: 25 patients with advanced primary open angle glaucoma and 2 consecutive abnormal Humphrey 10-2 SITA Standard visual field tests., Methods: Thirty-six eyes of 25 patients with 2 consecutive abnormal Humphrey 10-2 SITA Standard (H10) visual fields were retested with a modified 10-2 SLO-MP within 3 months of the last reliable H10. A standardized grid was used to mark the macula. Primary outcome was change in mean macular sensitivity (dB; H10 and SLO-MP) in relation to mean macular retinal nerve fibre layer (RNFL) thickness (µm) by SLO- optical coherence tomography (SLO-OCT). Secondary outcome was comparison of reliability indices for both tests. Linear regression was used for analysis., Results: Mean macular sensitivity was significantly lower in SLO-MP (9.33 ± 3.37 dB) than H10 (18.83 ± 6.46 dB; p < 0.0001). Mean macular RNFL thickness correlated significantly with retinal sensitivity by both SLO-MP (r = 0.39, p < 0.02) and H10 (r = 0.37, p < 0.03). Fixation losses were better controlled in SLO-MP (0.38 ± 1.1) than H10 (4.28 ± 7.9; p = 0.008). False-positive responses were similar (SLO-MP: 2.25 ± 4.53, H10: 1.78 ± 3.33; p = 0.80). A statistically significant difference was noted in the false-negative responses (SLO-MP: 26.87 ± 25.24, H10: 5.33 ± 9.70; p < 0.0001)., Conclusions: Macular sensitivity determined by both H10 and SLO-MP correlates significantly with mean macular RNFL thickness measured by SLO-OCT. Precise localization of the macula in SLO-MP results in lower fixation losses. Detection of denser field defects by SLO-MP results in higher false-negative responses. A larger sample size is needed to further study the value of this diagnostic tool., (© 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: While the effectiveness of teleophthalmology is generally accepted, its ability to diagnose glaucomatous eye disease remains relatively unknown. This study aimed to compare a web-based teleophthalmology assessment with clinical slit lamp examination to screen for glaucoma among diabetics in a rural African district., Materials and Methods: Three hundred and nine diabetic patients underwent both the clinical slit lamp examination by a comprehensive ophthalmologist and teleglaucoma (TG) assessment by a glaucoma subspecialist. Both assessments were compared for any focal glaucoma damage; for TG, the quality of photographs was assessed, and vertical cup-to-disk ratio (VCDR) was calculated in a semi-automated manner. In patients with VCDR > 0.7, the diagnostic precision of the Frequency Doubling Technology (FDT) C-20 screening program was assessed., Results: Of 309 TG assessment photos, 74 (24%) were deemed unreadable due to media opacities, patient cooperation, and unsatisfactory photographic technique. While the identification of individual optic nerve factors showed either fair or moderate agreement, the ability to diagnose glaucoma based on the overall assessment showed moderate agreement (Kappa [κ] statistic 0.55% and 95% confidence interval [CI]: 0.48-0.62). The use of FDT to detect glaucoma in the presence of disc damage (VCDR > 0.7) showed substantial agreement (κ statistic of 0.84 and 95% CI 0.79-0.90). A positive TG diagnosis of glaucoma carried a 77.5% positive predictive value, and a negative TG diagnosis carried an 82.2% negative predicative value relative to the clinical slit lamp examination., Conclusion: There was moderate agreement between the ability to diagnose glaucoma using TG relative to clinical slit lamp examination. Poor quality photographs can severely limit the ability of TG assessment to diagnose optic nerve damage and glaucoma. Although further work and validation is needed, the TG approach provides a novel, and promising method to diagnose glaucoma, a major cause of ocular morbidity throughout the world.

Purpose: To compare outcomes in exfoliation glaucoma versus primary open-angle glaucoma (POAG) after ab interno trabeculectomy alone (Trabectome) or in combination with cataract surgery and intraocular lens (IOL) implantation., Setting: Trabectome Study Group institutions., Design: Prospective nonrandomized cohort study., Methods: Outcomes included intraocular pressure (IOP), glaucoma medications, complications, secondary procedures, and success, defined as no secondary surgery and IOP less than 21 mm Hg and a greater than 20% reduction from baseline., Results: In the ab interno trabeculectomy-alone group, the mean preoperative IOP was 29.0 mm Hg ± 7.5 (SD) in exfoliation glaucoma cases and 25.5 ± 7.9 mm Hg in POAG cases (P<.01). At 1 year, the mean decrease in IOP was -12.3 ± 8.0 mm Hg and -7.5 ± 7.4 mm Hg, respectively (P<.01); the secondary procedure rate was 20.9% and 34.9%, respectively (P=.02); and the cumulative probability of success was 79.1% and 62.9%, respectively (P=.004). In the combined ab interno trabeculectomy-IOL group, the mean preoperative IOP was 21.7 ± 8.4 in exfoliation glaucoma cases and 19.9 ± 5.4 mm Hg in POAG cases (P=.06). At 1 year, the mean decrease in IOP was -7.2 ± 7.7 and -4.1 ± 4.6, respectively (P<.01); the secondary procedure rate was 6.7% and 6.1%, respectively (P=.88); and the cumulative probability of success was 86.7% and 91.0% (P=.73), respectively., Conclusion: Ab interno trabeculectomy using this new incisional procedure safely lowered IOP to the mid teens, with an overall greater reduction in exfoliation glaucoma and improved success when combined with cataract surgery., (Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Objective: Selective laser trabeculoplasty (SLT) and argon laser trabeculoplasty (ALT) are used to lower intraocular pressure (IOP) in patients with open-angle glaucoma (OAG). We report long-term follow-up data comparing SLT to ALT., Design: Follow-up of prospective randomized clinical trial., Participants: Patients with glaucoma from the practices of three ophthalmologists at the University of Ottawa., Methods: We randomized 176 eyes of 152 patients with uncontrolled IOP on maximal tolerated medical therapy (MTMT, with or without previous ALT) to undergo either SLT or ALT. Data were available for 142 eyes at 3 years, 134 eyes at 4 years, and 120 eyes at 5 years. The primary outcome was change in IOP from pretreatment baseline., Results: Comparison of baseline parameters was similar in the two groups. Lowering of IOP were similar at 3 years (SLT -6.7 ± 7.1 vs ALT -6.1 ± 5.1); at 4 years (SLT 7.0 ± 7.7 vs ALT -6.3 ± 5.0); and at 5 years (SLT -7.4 ± 7.3 vs ALT -6.7 ± 6.6). There was no statistically significant change in IOP in either of the two groups. Medication changes were equivalent in each group. A number of interventions were required in both groups, cumulatively, over the 5-year follow-up period (49 SLT and 33 ALT). Survival analysis indicated that the time to 50% failure in each group was approximately 2 years., Conclusions: The IOP-lowering effect of SLT and ALT was similar over 5 years in this group of patients with open-angle glaucoma on MTMT., (Copyright © 2011 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objective: To describe differences in axial length scan (A-scan) and ultrasound biomicroscopy (UBM) parameters in eyes with exfoliation syndrome (XFS) and occludable angles (XFSOc), XFS and open angles (XFSOp), and eyes with primary open-angle glaucoma (POAG)., Design: Cross-sectional descriptive study., Participants: Seventy-two eyes of 72 patients (mostly Caucasians) were identified through glaucoma clinics at the University of Ottawa;19 eyes had XFSOc, 31 eyes XFSOp, and 22 eyes POAG., Methods: After a detailed ophthalmic history and examination, A-scan biometry and UBM were done to assess anterior segment parameters: central anterior chamber depth (ACD), lens thickness, trabecular meshwork-iris angle, and angle opening distance (AOD). Lens/axial length factor and the relative lens position were calculated. The above measurements were compared across the 3 groups., Results: We found statistically significant differences in measurements among the groups. ACD was shallowest in eyes with XFSOc (1.88 [SD 0.07] mm), followed by XFSOp (2.37 [SD 0.05] mm), and POAG (2.64 [SD 0.08] mm). XFSOc had thicker lenses (5.28 [SD 0.09] mm) compared with the other groups: XFSOp (5.03 [SD 0.06] mm) and POAG (4.84 [SD 0.09] mm). Lens/axial length factor was highest in XFSOc (2.34 [SD 0.05] mm) versus XFSOp (2.12 [SD 0.03] mm) and POAG (2.02 [SD 0.05] mm); relative lens position was lowest in XFSOc (2.27 [SD 0.03] mm) versus XFSOp (2.31 [SD 0.02] mm) and POAG (2.36 [SD 0.03] mm)., Conclusions: Eyes with XFSOc in our study demonstrated lens thickening and shallow central ACD versus eyes with XFSOp and eyes with POAG. This suggests the possibility that cataract formation and (or) zonular weakness may contribute to the development of an occludable angle in eyes with XFS.

Background: To propose consensus working recommendations for the role of central corneal thickness in the management of open-angle glaucoma., Methods: This work is based on evidence from a review of the glaucoma literature, a Canadian consensus development workshop, and the personal clinical experience of the participating Canadian ophthalmologists., Results: Guidelines were developed to provide eye care practitioners and their patients with support in the decision-making process for management of glaucoma or those at risk for developing glaucoma., Interpretation: Further studies will be helpful in understanding the role of central corneal thickness in glaucoma management, and these guidelines will need to be revised periodically as new information becomes available.

Aims: To compare selective laser trabeculoplasty (SLT) and argon laser trabeculoplasty (ALT), in terms of intraocular pressure (IOP) lowering, in patients with open-angle glaucoma., Methods: 176 eyes of 152 patients were enrolled in this study, 89 in the SLT and 87 in the ALT groups. Patients were randomised to receive either SLT or ALT treatment to 180 degrees of the trabecular meshwork. Patients were followed up to 12 months after treatment. The main outcome measured was IOP lowering at 12 months after treatment, compared between the SLT and ALT groups., Results: No significant difference (p = 0.846) was found in mean decrease in IOP between the SLT (5.86 mm Hg) and ALT (6.04 mm Hg) groups at 1 year or at any other time points, nor were there any significant differences in the rate of early or late complications between the two groups., Conclusions: SLT is equivalent to ALT in terms of IOP lowering at 1 year, and is a safe and effective procedure for patients with open-angle glaucoma.

Introduction: Chronic open-angle glaucoma (COAG) is a leading cause of irreversible blindness worldwide, including in Canada. It presents a challenge in diagnosis, as disease often progresses without symptoms; an estimated 50% of cases are undetected., Sources of Information: MEDLINE searches, reference lists of articles, and expert knowledge from one of the authors (K.F.D.), a glaucoma specialist, were used., Main Message: A casefinding approach using early referral to optometrists and ophthalmologists for early detection of COAG is helpful for patients with risk factors such as age above 50, a positive family history, black race, and myopia. Moderate evidence for referral also exists for the following risk factors: hypertension, type 2 diabetes mellitus, hypothyroidism, and sleep apnea. Treatment with intraocular pressure-lowering medication can arrest or slow the course of the disease, permitting patients to retain good visual function. Family physicians should be aware that some intraocular pressure-lowering medications, particularly topical beta-blockers, can pose iatrogenic harm to patients and result in or exacerbate such conditions as asthma, cardiovascular disturbances, depression, and sexual dysfunction., Conclusion: Appropriate referral patterns and an understanding of common as well as serious side effects of glaucoma medications are important in optimizing management of patients at risk of developing, or who have, COAG.

Background/aims: The efficacy and safety of selective laser trabeculoplasty (SLT) has been found to be equivalent to argon laser trabeculoplasty (ALT). Since SLT produces significantly less disturbance to the trabecular meshwork and is theoretically more repeatable than ALT, it has potential to replace ALT as the standard procedure to treat medically uncontrolled open angle glaucoma. This study's objective is to determine factors that predict successful SLT at 1 year post-treatment., Methods: As part of a randomised clinical trial comparing the efficacy and safety of SLT to ALT, data on 72 SLT patients were collected, and successful SLT defined as having an SLT induced intraocular pressure (IOP) reduction of >or=20% at 1 year post-treatment follow up., Results: 43 out of the 72 patients who had completed their 1 year follow up visit had an IOP reduction of >or=20% from baseline. No glaucoma risk factors studied predicted successful SLT. The amount of trabecular meshwork pigmentation was not a significant predictor. However, it was discovered that baseline IOP strongly predicted SLT success (odds ratio=1.16; p=0.0001)., Conclusion: SLT success was significantly predicted by baseline IOP but not by age, sex, other glaucoma risk factors, type of open angle glaucoma, or by degree of trabecular meshwork pigmentation.

Purpose: To report and assess the complication of intraocular pressure (IOP) elevations after selective laser trabeculoplasty (SLT) in patients with heavily pigmented trabecular meshworks., Design: Noncomparative, observational case series., Methods: Retrospective analysis of the medical files of four glaucoma patients with heavily pigmented trabecular meshwork, who presented with IOP elevations after SLT., Results: All four glaucoma patients presented with post-SLT IOP elevations. Three had features of pigmentary dispersion syndrome, and the fourth had a heavily pigmented trabecular meshwork. Two patients had previous argon laser trabeculoplasty (ALT) in the same eye in which SLT was performed, and one had a previous ocular trauma. Eventually, three of the patients required surgical trabeculectomy., Conclusions: This case series suggests that post-SLT IOP elevations can be a serious adverse event in some glaucomatous patients. It is recommended by the authors that patients with a deeply pigmented trabecular meshwork, taking multiple topical medications and having previous ALT treatment, should be considered at higher risk for this complication.

Purpose: To establish the age- and sex-specific prevalence of open-angle glaucoma (OAG) subsuming pseudoexfoliation (PEX) in the city of Reykjavik., Methods: Participants 50 years of age and older who were part of the Reykjavik Eye Study and classified as having glaucoma were divided into three categories:Category 1: two or more of the following based on optic nerve stereophotograph reading: vertical cup to disc ratio (VCDR) 97.5th percentile (>0.7), focal glaucomatous disc change, C/D asymmetry of 97.5th percentile difference between eyes (>0.2) as well as glaucomatous visual field defect (GVFD). Category 2: 99.5th percentile of VCDR (>0.8) and 99.5% percentile difference between eyes (>/=0.3), without a GVFD. Category 3: VA<3/60 and IOP>99.5th percentile or VA <3/60 and evidence of filtering surgery. For a glaucoma suspect, one of the following was present: VCDR>99.5th percentile (>0.8), focal glaucomatous disc change, C/D asymmetry of 99.5th percentile (> or =0.3), GVFD only, IOP> or =23 mmHg (97.5 percentile). PEX was diagnosed by the presence of a central shield and/or a peripheral band on the anterior lens capsule., Results: Of 42 persons (22 males and 20 females) with OAG, 13 (31.0%) had PEX. The minimum prevalence of OAG was 4.0% (42/1045) (95% CI 2.8-5.2) for those 50 years and older and 10.3% (95% CI 8.5-12.2) for PEX. The prevalence of OAG increases with age (OR=1.10/year, 95% CI 1.07-1.13, P=0.000) and the same applies for the prevalence of PEX, OR=1.10 (95% CI 1.07-1.12, P=0.000)., Conclusion: There is a 10% annual increase for both OAG and PEX in persons 50 years and older.

There is an abundance of evidence from recent randomized clinical trials showing that lowering the IOP is beneficial to the optic nerve and visual field. Setting and achieving a target IOP range is in keeping with evidence-based medicine. The benefits of reaching this target must be weighed against the risks of the treatment itself. Target IOP is a dynamic concept, needing constant reevaluation. What is lacking are established guidelines for determining the target IOP range that can be used in general ophthalmology practice.

Purpose: To evaluate the use of disk diameter as an indicator in the identification of glaucomatous optic neuropathy., Methods: We evaluated all available stereofundus photographs for 1,040 right eyes obtained in the Reykjavik Eye Study. Horizontal and vertical disk diameters were determined in a masked manner by a glaucoma specialist (K.F.D.). All disk diameters were corrected for refractive error., Results: There were significant differences (P <.05) between the corrected vertical disk diameters of normal subjects (0.189 +/- 0.018 inches) and those suspected of having glaucoma (0.202 +/- 0.020 inches) as well as between the normal and the glaucoma groups (0.206 +/- 0.029 inches). The corrected horizontal measurement showed the same pattern., Conclusions: In the Reykjavik Eye Study, optic disks meeting structural criteria for glaucoma are significantly larger than normal nerves.

Objective: In patients with dominant optic atrophy (DOA, Kjer type), excavation of the optic nerve develops, and these patients may be misdiagnosed as having normal tension glaucoma (NTG). This study examined disc morphologic features in patients with DOA and explored features that help distinguish this condition from NTG., Design: Noncomparative, observational case series., Participants: Patients with DOA who were seen at the Duke University Eye Center between 1987 and 1996 and who had bilateral optic nerve photographs., Methods: Retrospective chart review of the results of visual acuity testing, visual field testing by Goldmann perimetry, color vision testing, intraocular pressure measurement, and observation of bilateral optic nerve photographs., Main Outcome Measures: Appearance of the optic disc and peripapillary zone in patients with DOA., Results: Nine patients were identified. The mean age at the time of evaluation was 28 years (range, 11-62 years). Most patients had a mild to moderate reduction in visual acuity. Color vision as tested with Hardy-Rand-Rittler plates was reduced (4.0/10 +/- 4.2/10). A cup-to-disc ratio of more than 0.5 was observed in at least one eye of eight patients. A temporal wedge-shaped area of excavation was observed in 14 of the 18 eyes studied. Moderate to severe temporal pallor was observed in all of the eyes. Pallor of the remaining (noncupped) neuroretinal rim was also observed consistently, ranging from mild to moderate. A gray crescent and some degree of peripapillary atrophy were noted in all eyes., Conclusions: Several clinical features, including early age of onset, preferential loss of central vision, sparing of the peripheral fields, pallor of the remaining neuroretinal rim, and a family history of unexplained visual loss or optic atrophy, help to distinguish patients with DOA from those with NTG.

Aim: To examine the distribution and clinical ophthalmic characteristics of pseudoexfoliation syndrome (pseudoexfoliation) and glaucoma in Icelandic families., Methods: Icelandic families containing three or more members aged 70 or older with at least one member with pseudoexfoliation were identified. All family members over age 45 were invited to participate. Visual acuity, Goldmann applanation tonometry, gonioscopy, slit lamp examination before and after dilatation, and dilated fundus examination were performed on all available family members. Pertinent data were obtained from medical records, including ophthalmic history and a medical history of cardiovascular disease, cerebrovascular disease, systemic hypertension, and diabetes mellitus. Participants were classified according to affected status for pseudoexfoliation, glaucoma, and age related macular degeneration., Results: Six families were identified who met the criteria for entry into the study. Of 94 family members who were invited to participate 82 were enrolled (87%). Of these 25 (30%) had pseudoexfoliation syndrome, 51 (62%) were unaffected, and six (7%) were suspects. At least one individual with pseudoexfoliation was identified in the second generation of every family. A parent with pseudoexfoliation was identified in all cases either by examination (4/6) or a review of ophthalmic records (2/6). In all cases the mother was the affected parent. The prevalence of glaucoma was significantly greater in the group with pseudoexfoliation (p <0.0001). Although the presence of age related macular degeneration (ARMD) was highly associated with the presence of pseudoexfoliation, the significance was lost after correction for age (p = 0.69). Although the sample size was small, no association between pseudoexfoliation affected status and cardiovascular disease, cerebrovascular disease, systemic hypertension, or diabetes mellitus was found., Conclusions: Multiple Icelandic families with pseudoexfoliation in two generations were identified. In all cases where determination was possible, transmission to the second generation was through an affected parent. In each case the affected parent was the mother. Pseudoexfoliation was strongly associated with the presence of glaucoma, but was not associated with either ARMD or systemic disease in this study. These data clearly indicate that pseudoexfoliation is a familial condition and although not conclusive, supports the hypothesis that pseudoexfoliation syndrome is genetically inherited.

We describe the coexistence of artefactual ocular hypertension due to increased central corneal thickness (CCT>585 microm), with primary open angle glaucoma (POAG) in a French Canadian kindred. Seventeen members of the family were examined and classified as to their glaucoma status. The mean CCT for our glaucoma patients (580 microm; n=5) and that for normals (552 microm; n=6) were within two standard deviations of the mean value provided in the literature (531 microm +/- SD=29 microm). The mean CCT of 611 microm for the suspect group (n=6) was considerably higher than for the glaucoma and normal groups. All but one of the suspects were classified as ocular hypertensives on the basis of high intraocular pressures (IOPs). When the IOPs for these patients (mean 22.6 mmHg) were corrected for their CCTs, all had pressures of <21 mmHg (mean 16.4 mmHg). Ten of the seventeen family members had thick CCTs, and transmission of thick corneas was seen in two generations. A number of individuals in this family had optic nerve head drusen (9/17) and the mean CCT of these individuals (601 microm) was higher than the mean CCT (560 microm) of the group without drusen (P=0.020 by t test). Artefactual ocular hypertension and POAG can be present in different members of the same family. The presence of a thick cornea appears to be an inherited trait and may be associated with the presence of optic nerve drusen. This association suggests a developmental relationship between thick corneas and optic nerve head drusen which needs to be studied further.

Objective: To describe the clinical features and identify the molecular etiology of childhood-onset primary open angle glaucoma (POAG) in a Canadian kindred., Methods: Members of a Canadian Caucasian family with POAG were examined and DNA obtained. Single-strand conformation polymorphism analysis was performed using reported primers from exon 3 of the myocilin gene. A single-stranded conformation polymorphism was characterized by polymerase chain reaction-based sequencing., Results: Two affected half-sibs had onset of severe glaucoma at age 3 and 9. Their mother had lost vision in one eye from glaucoma by age 17. All three affected subjects had undergone bilateral glaucoma filtering surgery. Both fathers were unaffected. A single-stranded conformation polymorphism was identified in the mother and the two affected daughters and was absent in one father. A single base change from C-->T at nucleotide position 1109 was identified in the affected members of the family by direct sequencing. This mutation, which causes a nonconservative amino acid change (Pro370Leu), was not found on 192 normal chromosomes from Caucasian individuals., Conclusion: We report a Canadian family with childhood-onset, severe POAG due to a mutation in the myocilin gene.

Extraordinary progress has been made over the last 5 years in improving our understanding of the molecular causes of various glaucomas. Identification of the myocilin gene and of 5 additional genetic loci that play a role in development of primary open angle glaucoma provides us with an opportunity to reclassify this complex phenotype based on underlying cause of disease. Clinicians who obtain a detailed family history from their patients and who have referred families with glaucoma to laboratory investigators are at the forefront of this revolution in molecular genetics. As a result, all clinicians will soon be poised to profit from genetic discoveries by being able to order diagnostic tests that will identify specific genetic mutations. These mutations will provide a detailed understanding of the natural history of the patient's glaucoma, as well as information for genetic counseling. Individuals at risk in the family will be able to be identified, permitting closer follow-up and earlier institution of glaucoma therapy. A new understanding of pathophysiology is developing and will provide the basis for more rational pharmacological and gene therapy approaches in the future. The hope of primary prevention for various glaucomas, once a distant dream, may become reality within our lifetimes.

Aims: To compare the effectiveness of selective laser trabeculoplasty (SLT, a 532 nm Nd:YAG laser) with argon laser trabeculoplasty (ALT) in lowering the intraocular pressure (IOP) in patients with medically uncontrolled open angle glaucoma., Methods: A prospective randomised clinical trial was designed. Patients were randomised to treatment with either SLT or ALT and were evaluated at 1 hour, 1 week, 1, 3, and 6 months post-laser., Results: There were 18 eyes in each group. Baseline characteristics were similar in both groups. In the SLT group the mean IOP at baseline, 1, 3, and 6 months was 22.8 (SD 3.0), 20.1 (4.6), 19.3 (6.0), and 17.8 (4.8) mm Hg, respectively. In the ALT group, the mean IOP at baseline, 1, 3, and 6 months was 22.5 (3.6), 19.5 (4.7), 19.6 (5.6), and 17.7 (3.3) mm Hg, respectively. There was a greater anterior chamber reaction, 1 hour after SLT v ALT (p< 0.01). Patients with previous failed ALT had a better reduction in IOP with SLT than with repeat ALT (6.8 (2. 4) v 3.6 (1.8) mm Hg; p = 0.01)., Conclusion: SLT appears to be equivalent to ALT in lowering IOP during the first 6 months after treatment. There is a slightly greater anterior chamber reaction 1 hour after SLT. Patients with previous failed ALT had a significantly greater drop in IOP when treated with SLT v ALT. These results need to be confirmed with a larger sample size.

Glaucoma is one of the leading causes of irreversible blindness in the world and is characterized by elevated intraocular pressure, optic nerve atrophy, and progressive visual field loss. Primary open angle glaucoma (POAG) is the most common subtype of glaucoma in the United States. Recently, Stoilova and coworkers [Genomics 1996;36:142-150] identified a locus for POAG on chromosome 2 (2cen-q13) in families primarily located in the United Kingdom. We examined families with POAG identified within the US for linkage to the 2cen-q13 locus. A total of 18 families with POAG were used in the analysis. Of 77 family members, 46 were classified as affected and 31 were either glaucoma suspects or considered normal. Eight highly polymorphic and informative markers flanking and distributed throughout the region were used. Parametric lod score analysis was performed using both a dominant and recessive low penetrance or 'affecteds-only' model. Multipoint affected sibpair exclusion mapping was also performed. Lod score (both models) and sibpair analysis excluded linkage of the POAG phenotype to the 2cen-q13 region in these families. These data suggest that the chromosome 2cen-q13 locus does not explain a substantial amount of genetic variation in familial POAG.

Objective: To determine the relationship between central corneal thickness (CCT) and applanation intraocular pressure (IOP) in normal, glaucomatous, and ocular hypertensive eyes., Methods: One hundred nine subjects (184 eyes) were studied. Forty-eight patients (74 eyes) had glaucoma, 28 patients (51 eyes) had ocular hypertension, and 33 patients (59 eyes) were normal. Intraocular pressure as measured by applanation tonometry, refractive status, CCT, and axial length were measured for all subjects., Results: The CCT (mean +/- SD) of eyes with ocular hypertension was significantly greater (0.606 +/- 0.041 mm) than that of glaucomatous eyes (0.554 +/- 0.022 mm) (P < .001) or of normal controls (0.561 +/- 0.026 mm) (P < .001). There was no significant difference in CCT between normal and glaucomatous eyes (P = .40). The axial length (mean +/- SD) of eyes with ocular hypertension (23.54 +/- 1.34 mm) was not different compared with glaucomatous eyes (23.93 +/- 0.96 mm) (P = .13) or normal eyes (23.62 +/- 1.21 mm) (P = .83). There was no significant difference between the axial length for glaucomatous eyes compared with normal eyes (P = .18). Those eyes with glaucoma being treated with topical dorzolamide hydrochloride had a significantly increased CCT (0.560 +/- 0.025 mm) compared with those eyes with glaucoma not being treated with dorzolamide (0.551 +/- 0.20 mm) (P = .02)., Conclusions: The mean CCT is increased in eyes with ocular hypertension when compared with normal or glaucomatous eyes, which confirms the findings of other investigators. Increased CCT may give an artificially high IOP measurement by applanation tonometry. The CCT must be considered when developing a treatment approach for patients with ocular hypertension.