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Background: Ophthalmology residents on call at the Royal Alexandra Hospital identified workplace disorganization and lack of standardization in emergency eye examination rooms as an impediment to efficient patient treatment., Objective: The aim of the study was to use the "6S Lean" model to improve workflow in eye examination rooms at the Royal Alexandra Hospital., Methods: With the assistance of quality improvement consultants, the "6S Lean" model was applied to the current operation of the emergency eye clinic examination rooms. This model, considering 8 waste categories, was then used to recommend and implement changes to the examination rooms and to workplace protocols to enhance efficiency and safety., Results: Eye examination rooms were improved with regards to setup, organization of supplies, inventory control, and maintenance. All targets were achieved, and the 5S audit checklist score increased by 33 points from 44 to 77., Conclusions: Implementation of the 6S methodology is a simple approach that removes inefficiencies from the workplace. The ophthalmology clinic removed waste from all 8 waste categories, increased audit results, mitigated patient and resident safety risks, and ultimately redirected resident time back to patient care delivery., (Copyright © 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Environmental factors, mainly oxidative stress and exposure to sunlight, induce the oxidation, cross-linking, cleavage, and deamination of crystallin proteins, resulting in their aggregation and, ultimately, cataract formation. Various denaturants have been used to initiate the aggregation of crystallin proteins in vitro. All of these regimens, however, are obviously far from replicating conditions that exist in vivo that lead to cataract formation. In fact, it is our supposition that only UV-B radiation may mimic the observed in vivo cause of crystallin alteration leading to cataract formation. This means of inducing cataract formation may provide the most appropriate in vitro platform for in-depth study of the fundamental cataractous fibril properties and allow for testing of possible treatment strategies. Herein, we showed that cataractous fibrils can be formed using UV-B radiation from α:β:γ crystallin protein mixtures. Characterization of the properties of formed aggregates confirmed the development of amyloid-like fibrils, which are in cross-β-pattern and possibly in anti-parallel β-sheet arrangement. Furthermore, we were also able to confirm that the presence of the molecular chaperone, α-crystallin, was able to inhibit fibril formation, as observed for 'naturally' occurring fibrils. Finally, the time-dependent fibrillation profile was found to be similar to the gradual formation of age-related nuclear cataracts. This data provided evidence for the initiation of fibril formation from physiologically relevant crystallin mixtures using UV-B radiation, and that the formed fibrils had several traits similar to that expected from cataracts developing in vivo.

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 report a rare case of congenital glaucoma in a patient with CHARGE syndrome, present gonioscopic photographs, and explore mechanisms of disease that may account for this association., Patients and Methods: We describe a 35-week-old girl with previously diagnosed CHARGE syndrome who presented with corneal edema, buphthalmos, and elevated intraocular pressure in the left eye. She was subsequently diagnosed with congenital glaucoma and started on topical and oral therapy., Results: Examination under anesthesia confirmed the above findings as well as bilateral abnormal angles with an anterior iris insertion at the level of the posterior trabecular meshwork, prominent iris vasculature and stromal strands, and nonvisible scleral spur and ciliary body bands. Trabeculotomy and trabeculectomy were performed in the left eye with a poor outcome. CHARGE syndrome is a complex neurocristopathy, and we propose that the abnormal angle findings and associated asymmetric glaucoma in our patient share a common mechanism of neural crest cell dysfunction., Conclusions: CHARGE syndrome can be associated with congenital glaucoma and we emphasize the importance of a thorough ophthalmic examination to detect glaucoma with surgical management as deemed appropriate.

Background: New glaucoma diagnostic technologies are penetrating clinical care and are changing rapidly. Having a systematic review of these technologies will help clinicians and decision makers and help identify gaps that need to be addressed. This systematic review studied five glaucoma technologies compared to the gold standard of white on white perimetry for glaucoma detection., Methods: OVID(®) interface: MEDLINE(®) (In-Process & Other Non-Indexed Citations), EMBASE(®), BIOSIS Previews(®), CINAHL(®), PubMed, and the Cochrane Library were searched. A gray literature search was also performed. A technical expert panel, information specialists, systematic review method experts and biostatisticians were used. A PRISMA flow diagram was created and a random effect meta-analysis was performed., Results: A total of 2,474 articles were screened. The greatest accuracy was found with frequency doubling technology (FDT) (diagnostic odds ratio (DOR): 57.7) followed by blue on yellow perimetry (DOR: 46.7), optical coherence tomography (OCT) (DOR: 41.8), GDx (DOR: 32.4) and Heidelberg retina tomography (HRT) (DOR: 17.8). Of greatest concern is that tests for heterogeneity were all above 50%, indicating that cutoffs used in these newer technologies were all very varied and not uniform across studies., Conclusions: Glaucoma content experts need to establish uniform cutoffs for these newer technologies, so that studies that compare these technologies can be interpreted more uniformly. Nevertheless, synthesized data at this time demonstrate that amongst the newest technologies, OCT has the highest glaucoma diagnostic accuracy followed by GDx and then HRT.

Objective: Wet labs are an important part of ophthalmology residency training in order to develop intraocular surgical proficiency. The purpose of this study was to compare the effectiveness of formalin versus microwave treatment to produce porcine cadaveric cataracts., Design: This study was a comparative observational study at a single centre., Methods: Cataracts were created through the injection of 0.1 mL of 100% ethanol into the anterior chamber followed by the infiltration of 0.1 mL of 37% formalin using a short 30-gauge needle into the lens by introduction through the pars plana. The comparison group investigated porcine eyes treated with a microwave for 5-13 seconds using a 700 W power setting. Two observers used a validated nuclear opalescence and corneal clarity scale to independently grade the treated eyes., Results: In total, 70 eyes were treated with either formalin or by microwave. The formalin eyes had an average lens opacity score of 0.04 ± 0.03 and 1.91 ± 01.10 pre- and post-treatment (p < 0.001). Microwaved eyes had an average pretreatment lens opacity of score 0.10 ± 0.31, which increased to 2.86 ± 0.1.08 post-treatment (p < 0.001). Post-treatment lens opacity was significantly greater in microwave eyes than in formalin-treated eyes (p = 0.003). Pretreatment corneal clarity was 3.65 ± 0.73 in the formalin group, and 3.70 ± 0.93 in the microwave group. After treatment, there was a significant reduction in corneal clarity within the formalin (3.01 ± 1.04, p = 0.0012) and microwave groups (3.03 ± 1.07, p < 0.001)., Conclusions: Porcine eye models provide a realistic way to simulate cataracts and so residents can practice the basics of cataract surgery. Both microwave and formalin-based treatments are able to opacify the porcine lens with acceptable reductions in corneal clarity., (Copyright © 2016 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.

The optic nerve gray crescent can be of clinical significance if unrecognized during assessment for glaucoma. It has a characteristic appearance of a slate gray area of pigmentation within the disc margins and commonly appears along the inferotemporal or temporal neuroretinal rim areas. This type of disc rim pigmentation can create the impression of neuroretinal rim thinning, and thus lead to the misdiagnosis of glaucoma or "glaucoma suspect" with attendant implications for overtreatment or unnecessary close monitoring of such patients. The gray crescent is more common in African Americans than whites (prevalence rate 27% vs 7%) and is bilateral in at least 58% of cases. It has been reported in association with Kjer optic atrophy type 1. Suggested causes of the gray crescent include an accumulation of melanocytes, or retinal pigment epithelium cells partially located in the optic nerve head region if Bruch's membrane extends internal to the peripapillary scleral ring. Other causes of pigmentation that may resemble gray crescent are conus pigmentosus and variations of peripapillary atrophy. When a gray crescent is present, clinicians should endeavour to identify the true anatomical disc margins via the scleral lip and, if necessary, evaluate the patient further with imaging and visual field studies., (Copyright © 2014 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background: To compare access time and cycle time between an "in-house" teleglaucoma program and in-person glaucoma consultation., Patients and Methods: This was a prospective comparative study of 71 patients seen through the teleglaucoma program (eligible patients were glaucoma suspects or early-stage open-angle glaucoma) and 63 patients seen via a traditional in-person exam with a physician present. Access time was calculated as the time from the patient being referred to the date of a booked visit for either a teleglaucoma or in-person exam. Cycle time was defined as the time from registration until departure during the visit to the hospital; it was calculated for the subset of patients from each study group who completed activity logs on the day of their visit., Results: The mean access time was significantly shorter for patients seen through teleglaucoma compared with in-person exam: 45±22 days (range, 13-121 days) (n=68) versus 88±47 days (range, 27-214 days) (n=63), respectively (p<0.0001). The cycle time was also reduced for patients seen through teleglaucoma, compared with in-person assessment: 78±20 min (range, 40-130 min) (n=39) versus 115±44 min (range, 51-216 min) (n=39), respectively (p<0.001). The mean percentage time spent in the waiting room was also significantly reduced for patients seen through teleglaucoma versus in-person assessments: 19±13% versus 41±24% (n=39), respectively (p<0.01)., Conclusions: Teleglaucoma improves access to care and is a more efficient way of managing glaucoma suspects and patients with early-stage glaucoma compared with in-person assessment.

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.)

Objective: To describe ocular phenotypic features in Chinese families with primary angle closure (PAC)., Design: Prospective cohort study., Participants: 428 individuals of 103 eligible families., Methods: Probands identified in clinic and their relatives were examined. Measurements included intraocular pressure, anterior chamber depth, lens thickness, axial length, and gonioscopic features related to the anterior chamber angle. Electroretinogram (ERG) testing for dark and light adaptation on both eyes of each individual examined was also obtained., Results: There were 144 PAC affected patients (33.7%), 60 suspects (14%), and 224 unaffected individuals (52.3%). There were more than 2 affected members in 51 families (49.5%). Compared with unaffected individuals, affected individuals were more likely to be female, have shallower peripheral and central anterior chamber depths, narrower angles, thicker lenses, and shorter axial lengths (p<0.001). Affected patients and suspects had similar axial lengths (p>0.05). Compared with unaffected individuals, affected and suspect individuals showed ERG adaptation abnormalities (p<0.05). Of 45 unaffected individuals with mean axial length ≤ 22.00 mm (10.51%), 20 individuals (4.67%) showed ERG adaptation abnormalities similar to affected patients and suspects (p> 0.05)., Conclusions: Patients with PAC were significantly more likely to be female, have shorter axial length, and have thicker lenses compared with unaffected individuals. PAC suspects showed similar axial lengths to affected individuals. ERG abnormalities mainly occurred in affected patients and suspects, but also occurred in unaffected individuals with short axial length., (Copyright © 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

A significant proportion of glaucoma patients present late, particularly in the developing world, and unfortunately, in an advanced stage of the disease. They are at imminent danger of losing remaining vision, and may also be afflicted with various socioeconomic and health challenges. The encounter with such a patient is typically characterized by anxiety/fear and sometimes hopelessness from the patient's perspective. The physician may also feel that they are in a difficult position managing the patient's disease. When dealing with such cases, we suggest a holistic, individualized approach taking into account the 'biopsychosociospiritual' (BPSS) profile of each patient. The BPSS model takes into account relevant ocular as well as systemic biology (factors such as the mechanism of glaucoma, level of intraocular pressure [IOP], rate of progression, life expectancy, general health), psychological considerations (e.g., fear, depression), socio-economic factors and spiritual/cultural values and beliefs before being able to decide with the patient and their care partner(s) what treatment goals should be and how they can best be approached. Treatment for advanced glaucoma can be highly effective, and patients and their care partners should be informed that aggressive IOP lowering to the low teens or even single digits offers the best chance of protecting remaining vision. This can be achieved safely and effectively in most cases with trabeculectomy (including an antimetabolite), and in some cases with medical and/or laser therapy. Vision rehabilitation and psychosocial support should also be considered in order to optimize remaining vision, replace fear with hope as appropriate, and thus improve the overall quality of life.

Teleglaucoma is the application of telemedicine for glaucoma. We review and present the current literature on teleglaucoma; present our experience with teleglaucoma programs in Alberta, Canada and Western Australia; and discuss the challenges and opportunities in this emerging field. Teleglaucoma is a novel area that was first explored a little over a decade ago and early studies highlighted the technical challenges of delivering glaucoma care remotely. Advanced technologies have since emerged that show great promise in providing access to underserviced populations. Additionally, these technologies can improve the efficiency of healthcare systems burdened with an increasing number of patients with glaucoma, and a limited supply of ophthalmologists. Additional benefits of teleglaucoma systems include e-learning and e-research. Further work is needed to fully validate and study the cost and comparative effectiveness of this approach relative to traditional models of healthcare.

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 assess patient preference for diabetic retinopathy (DR) screening with teleophthalmology or face-to-face ophthalmologist evaluation in Nairobi, Kenya., Materials and Methods: Fifty seven diabetic patients from a one-stop multidisciplinary diabetic clinic (consisting of a diabetologist, nurse educator, foot specialist, nutritionist, ophthalmologist, and neurologist) in Nairobi, Kenya were included if they had undergone both a teleophthalmology (stereoscopic digital retinal photographs graded by an ophthalmologist remotely) and a traditional clinical screening exam (face to face examination). A structured questionnaire with a 5-point Likert scale was developed in both English and Swahili. The questionnaire was administered over the telephone. Ten questions were used to compare patient experience and preferences between teleophthalmology and a traditional clinical examination for DR. A mean score >3.25 on the Likert scale was considered favourable., Results: Successfully telephone contact was possible for 26 (58% male, 42% females) of the 57 patients. The mean ages of the male and female patients were 52.4 and 46.5 years respectively. Patients were satisfied with their teleophthalmology examination (mean 4.15 ± 0.97). Patients preferred the teleophthalmology option for future screenings (mean 3.42 ± 1.52). This preference was driven primarily by convenience, reduced examination time, and being able to visualize their own retina., Conclusion: In this study, diabetic patients preferred a teleophthalmology based screening over a traditional ophthalmologist-based screening. The use of teleophthalmology in Africa warrants further study and has the potential to become the screening model of choice. Cost effectiveness in comparison to an ophthalmologist-based screening also requires evaluation.

The aim of the teleglaucoma service at the University of Alberta is to improve access for people in northern Alberta who have early-stage glaucoma or who are at risk for glaucoma. Two types of teleglaucoma service are offered: remote and in-house. A standardized approach is used to capture patient information (structured histories, examinations and fundus photographs) which is then sent to a tertiary care centre for grading and recommendations. Only one grader reads and makes management recommendations for each case. Reports are sent electronically. A total of 195 cases have been graded through the remote service since 2008. A total of 62 cases have been graded through the in-house service since 2011. The average reporting time for consultations in the in-house service was 7 days, and it was also 7 days for the remote service. We believe that the use of teleglaucoma can improve the way that patients are diagnosed and managed, both in industrialized and developing countries. Teleglaucoma is currently being used as a screening tool at the Aga Khan University Hospital in Nairobi with mobile units equipped with a fundus camera and a visual field machine.

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.)

A 3-year-old monocular boy with a history of congenital glaucoma and aqueous shunt implantation presented with periorbital swelling, erythema, and purulent discharge in his seeing right eye. Examination revealed an extensive hypopyon. Computed tomography (CT) showed right-sided proptosis, and a displaced aqueous shunt device deep in the orbit. Significant purulent fluid was encountered when the device was removed; vitreous and orbital cultures revealed Streptococcus pneumoniae. The patient received intravitreal, topical, intravenous, and oral antibiotics as well as intraocular tissue plasminogen activator and topical steroid. Orbital and intraocular inflammation decreased significantly but he developed a cataract, further complicated by a retinal detachment.

Aim: To examine the age- and gender-specific prevalent and 5-year incident risk of developing exfoliation syndrome (XFS)., Methods and Participants: In a population-based random sample of citizens 50 years and older, 1045 persons had baseline examination in 1996; 846 of the 958 survivors (88.2%) had a follow-up examination in 2001. Following maximum dilatation of pupils, a diagnosis of exfoliation was established on slit-lamp examination. An extensive questionnaire was administered at baseline and follow-up. Prevalent and incident risk was then calculated using a multivariate analysis., Results: The following variables were found to correlate significantly with prevalence risk of XFS at baseline: age, female gender, increased iris pigmentation, moderate use of alcohol and self-reported asthma. We also found that, compared with those who consumed dietary fibre-rich vegetables, green or yellow vegetables, and fruit less than once a month in their 20s and 40s, those consuming the same food items once or twice every 2 weeks were found to be less likely to have XFS. The same applied to those consuming dietary fibre rich once or twice every 2 weeks in their 40s and 60s., Conclusion: Food items that are possibly surrogates for antioxidative effect may correlate with decreased risk of XFS and increased iris pigmentation may correlate with increased risk. Given the large number of comparisons, these findings require validation through additional clinical studies. Increased age and female gender increase the likelihood of XFS.

Purpose: To review the technique and early outcomes of endoscopic goniotomy (EG) in children with opaque corneas and primary congenital glaucoma (PCG) or developmental glaucoma with ocular or systemic anomalies (DG)., Methods: EG was performed for approximately 300 degrees of the angle through temporal and superonasal corneal incisions. We retrospectively reviewed consecutive cases from 2003 to 2007. Primary outcome was intraocular pressure (IOP) change from baseline to last postoperative visit. Success was defined as IOP < or=21 mm Hg with or without medication but no further surgical intervention., Results: Fourteen eyes of 8 patients (4 PCG, 4 DG) were included. Mean age at surgery was 3.88+/-3.72 months. The reduction in IOP from baseline to the last follow-up visit was -16.7+/-16.7 mm Hg. Success was achieved in 6 of the 16 eyes (Total=43%, PCG=50%, DG=30%). Corneal diameter and axial length remained stable in all eyes. Two patients with DG needed additional surgery after 8 to 9 months. Complications included cataract and zonular dialysis both in 2 patients with aniridia., Conclusions: This pilot study indicates that EG shows reasonable potential for IOP control in congenital glaucoma. The safety and efficacy of EG needs to be further studied with a larger sample size and comparison to other angle surgery techniques.

Health care systems in many developing countries are rapidly evolving to respond to urbanization and shifting epidemiological profiles, creating an environment favorable for subspecialty development. The struggle for developing nations to train and retain highly skilled clinicians within academic institutions has highlighted the need for creative approaches to subspecialty education in these regions. The "Sandwich fellowship" is an educational model in which a fellow completes rotations at an academic institution in the developed world as well as in his or her home environment. An important component of the model is the expansion of institutional capacity at the fellow's home institution to create an enabling environment to practice newly acquired skills. The fellowship provides experience in diverse geographic and cultural contexts under the guidance of a preceptor from an institution in the developed world who teaches in both settings. Preceptors are given opportunities to continue professional growth and gain from exposure to pathology not commonly seen at home. Successful pilots of a Sandwich fellowship took place in ophthalmology and orthopedic surgery at the University of Ottawa in 2007-2008 and required funding from multiple sources with bilateral institutional support. Emphasis was also placed on teaching, leadership, management, and research so the fellows could return home and lead the development of their subspecialty areas. Early contact between administrations enables the model to serve as a gateway to a long-term partnership between developed world academic establishments and developing world institutions. Such a relationship yields a mutually beneficial exchange of knowledge and skills. Beneficiaries include the hospitals, their staff, and patients at both institutions.

Purpose: To examine the 5-year incidence of pseudoexfoliation (PEX) and monitor changes in related ophthalmologic variables., Design: Population-based, prospective cohort study., Methods: A random sample from the Reykjavik Population Census for persons 50 years and older was used. At baseline 1,045 participants were examined for signs of PEX including peripheral band and/or central shield of exfoliative material on the anterior lens capsule. Five years later, 846 (88.2%) of survivors returned for a follow-up visit., Results: The 5-year incidence of PEX was 3.5% in right eyes only, and 5.2% in either eye. Age increased the risk of 5-year incidence by 5% when looking at 10-year age groups (P = .02); the incidence was higher in female subjects (P = .05) than in male. A total of 27% of clinically asymmetric cases converted to clinically bilateral disease over 5 years. Intraocular pressure increased in the group that developed PEX during the 5 years, but the size of the optic cup increased most in eyes that already had PEX at baseline., Conclusion: This incidence study from Iceland confirms findings from previous prevalence studies that PEX is increasingly common with older age in this population. Earliest changes related to PEX may be subtle and difficult to detect, which may lead to some misclassification. Further study is needed to identify clinical features that can reliably detect patients at risk for developing PEX.

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: This study aims to characterize the reflective properties of some commonly used intraocular lenses (IOLs) in vitro, with a particular focus on lens haptics., Methods: Six different types of IOLs, representative of silicone, acrylic, and polymethyl methacrylate (PMMA), single, multipiece, and multifocal were imaged using high-resolution ultrasound biomicroscopy (UBM)., Results: Reflectivity patterns were distinct to the material that was being imaged irrespective of whether the part being imaged was the haptic or optic. Acrylic haptics demonstrated a single "tram-track" reduplication echo, whereas PMMA haptics showed multiple reverberation echoes off the posterior surface. The optics of various PMMA and acrylic lenses demonstrated a reflectivity pattern similar to the respective haptics made of the same material. Silicone optics displayed clear delineation with no reverberation. Both acrylic and silicone material was relatively less reflective when compared with PMMA., Interpretation: With UBM imaging, the haptics of acrylic and PMMA IOLs demonstrate unique reflective patterns, depending on the material being studied. Prior knowledge of what the lens haptics and optics look like in vitro provides information that may assist in identifying and localizing misplaced intraocular lenses in vivo.

Purpose: To evaluate clinical aspects of patients with the diagnosis of plateau iris (PI) or pseudoplateau iris (PPI) made by ultrasound biomicroscopy (UBM) in order to determine if there are any clinical factors that can help differentiate between these two entities., Method: A retrospective cohort of consecutive UBM patients with the diagnosis of PI or PPI. The diagnosis of PI was based on an anteriorly positioned ciliary body that abutted the peripheral iris, a narrow (<10 degrees) or closed angle for at least 180 degrees, and the anterior portion of the iris positioned anterior to scleral spur. The diagnosis of PPI was similar to plateau except that large or a cluster of small cysts had to be present in the iridociliary sulcus., Results: There were a total of 76 patients (29% male), 21 with PPI and 55 with PI. Patients with PPI were more likely to be male (p = 0.005), slightly younger (51.5 (SD 10.7) vs 57.9 (10.2) p = 0.0190), have a "bumpy" peripheral iris appearance (p = 0.003), have greater trabecular meshwork pigmentation (2.0 (0.7) vs 1.3 (0.6) p = 0.004) and have fewer clock hours of gonioscopic angle closure versus plateau iris patients (5.1 (4.3) vs 9.2 (4.2) p = 0.0009). Spherical equivalent was not significantly different between groups (0.50D (1.69) PPI vs 1.33D (2.42) PI; p = 0.187)., Conclusions: In patients being referred to a UBM clinic for evaluation of angle-closure mechanism, younger males with a bumpy peripheral iris have a higher likelihood of having a diagnosis of pseudoplateau iris. However, clinical factors do not appear to discriminate well between PPI and PI. UBM is extremely helpful in confirming underlying mechanism and guiding therapy.

Primary open angle glaucoma is a chronic optic neuropathy often requiring lifelong treatment. Patient compliance, adherence and persistence with therapy play a vital role in improved outcomes by reducing morbidity and the economic consequences that are associated with disease progression. A literature review including searches of The Cochrane Library, MEDLINE, PubMed, conference proceedings, and bibliographies of identified articles reveals the enormous public health burden in various populations due to the impact of glaucoma associated visual impairment on the overall quality of life eg, fear of blindness, inability to work in certain occupations, driving restrictions, motor vehicle accidents, falls, and general health status. Providing specific definitions for the frequently misunderstood terms "compliance, persistence and adherence" with reference to medication use is central not only for monitoring patients' drug dosing histories and clinical outcomes but also for subsequent research. In this review article, a summary of the advantages/disadvantages including cost-effectiveness of various medical approaches to glaucoma treatment, techniques employed for measuring patient compliance and actual patient preferences for therapy are outlined. We conclude by identifying the key barriers to ongoing treatment and suggest some best practices to enhance compliance and persistence.

Case Report: Four years after trabeculectomy, a patient developed unilateral tearing and presented with an ipsilateral conjunctival filtering bleb that had dissected into the cornea. The corneal portion of the bleb was excised for symptomatic relief. Histopathological examination disclosed dissection of the conjunctival filtering bleb into the cornea between Bowman's layer and the corneal epithelium. The internal portion of the bleb consisted of loose stromal tissue lacking any internal epithelial lining., Comments: A conjunctival bleb dissecting into the cornea is a well-described late complication of trabeculectomy; however, its pathophysiology remains controversial. The subepithelial dissection plane in this specimen supports the concept that the conjunctival filtering bleb may dissect into, as well as "overhang", the limbal cornea.

Purpose: To examine the age and sex-specific prevalence of pseudoexfoliation syndrome (PEX) and its relationship with some ophthalmological variables., Methods: We carried out a population-based study using a random sample taken from the national population census for citizens of Reykjavik, aged > or = 50 years. A total of 1045 individuals participated in all parts of the study. Pseudoexfoliation was established by slit-lamp examination with a maximally dilated pupil carried out by two experienced ophthalmologists, who were masked to one another's results except in cases of disagreement where they had to reach a consensus., Results: In all, 108 (10.7%) persons were found to have PEX in at least one eye. Prevalence increased from 2.5% in those aged 50-59 years to 40.6% in those aged > or = 80 years. Women were more frequently affected than men (12.3% versus 8.7%). This difference remained statistically significant after controlling for the effect of age (p < 0.001). Eyes with PEX were found to have higher intraocular pressure (IOP) than eyes without PEX (p < 0.05). However, PEX was not found to be related to central corneal thickness, anterior chamber depth, lens thickness, nuclear lens opacifications or optic disc morphology in a multivariate model., Conclusions: Pseudoexfoliation is an age-related phenomenon commonly found in Iceland. It is more commonly found in women than in men and is associated with elevated IOP.

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.

Aim: To determine the long term intraocular pressure (IOP) response to phacoemulsification in patients with and without exfoliation syndrome (XFS)., Methods: Prospective, multicentre, cohort study with the following inclusion criteria: age over 50 years, open iridocorneal angle, and cataract. Two groups were enrolled: those with XFS and those without. The main outcome was mean IOP reduction 2 years after phacoemulsification cataract extraction (PCE). Univariate and multivariate analyses were performed., Results: 183 patients were enrolled, 71 with and 112 without XFS. There were 29 patients with glaucoma in both groups. Mean baseline IOP was higher in XFS compared to control eyes (17.60 (SD 3.23) mm Hg v 16.08 (3.18) mm Hg, p = 0.002). Overall IOP reduction was significantly greater in the XFS group at the 2 year time point (-1.85 mm Hg v -0.62 mm Hg in the controls (p = 0.0037)). Multivariate analysis demonstrated that the IOP lowering effect in the XFS group may be related to irrigation volume at the time of surgery. In the subgroup analyses IOP lowering was significantly greater in the XFS and XFG patients than in controls without glaucoma, and POAG controls, respectively. The percentage of patients with a postoperative IOP spike was similar and relatively high in both XFS and control groups (34% v 25%; p = 0.54)., Conclusion: IOP decreases more in patients with XFS following PCE compared to control eyes without XFS. This effect is more pronounced in glaucoma patients and persists for at least 2 years.

Background: To determine the efficacy and safety of trabeculectomy with mitomycin-C (trabMMC) compared with that of single-site phacotrabeculectomy with mitomycin-C (phacotrabMMC) in glaucoma patients at increased risk for filtering surgery failure., Methods: Eighty-five consecutive eyes that underwent trabMMC and 105 consecutive eyes that underwent phacotrabMMC were retrospectively compared up to 2 years postoperatively with respect to intraocular pressure (IOP), number of glaucoma medications, and surgical complication rates. The primary outcome was the difference in the cumulative proportion of patients meeting the target IOP range at 2 years. Secondary outcomes included mean postoperative IOP, mean IOP drop from baseline, mean number of glaucoma medications, and surgical complication rates., Results: Baseline characteristics were similar in the 2 groups and most patients had advanced glaucoma with a similar upper limit of the target IOP range (15.5 +/- 2.6 mm Hg for trabMMC vs. 15.3 +/- 2.1 mm Hg for phacotrabMMC, p = 0.56). Loss to follow-up was significant in both groups (almost 50% over 2 years). A statistically similar proportion of patients achieved their target IOP range at 1 and 2 years in both groups: the cumulative success rate at 2 years was 29.04% and 22.91% (p = 0.44) without add-on glaucoma therapy, 25.38% and 25.22% (p = 0.60) with the use of up to 2 glaucoma medications, and 30.01% and 25.17% (p = 0.81) with the use of any number of glaucoma medications, in the trabMMC and phacotrabMMC groups, respectively. Mean postoperative IOP was also similar between the 2 groups at almost all follow-up times up to 2 years (13.56 +/- 4.92 mm Hg in trabMMC vs. 13.98 +/- 4.74 mm Hg in phacotrabMMC at 2 years, p = 0.67). The mean IOP drop from baseline was significantly greater in the trabMMC group throughout the study period (-10.87 +/- 8.33 mm Hg in trabMMC vs. -6.15 +/- 7.01 mm Hg in phacotrabMMC at 2 years, p = 0.003); however, baseline IOP was also higher in the trabMMC group (26.1 mm Hg vs. 20.3 mm Hg, p < 0.0001). Serious postoperative complication rates were similarly low between the 2 groups., Interpretation: TrabMMC and phacotrabMMC may be equally safe and effective in bringing IOP to within an acceptable target range over 2 years in advanced glaucoma patients at increased risk for filtering surgery failure, although trabMMC appears to be associated with greater IOP lowering from baseline.

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.

Aim: To establish the epidemiology of the grey crescent in a white population within the age range most susceptible to glaucoma., Methods: Bruce Shields was first to use this term to describe a localised, physiological pigmentation of the optic nerve neuroretinal rim tissue that is distinct from peripapillary pigmentation. An experienced glaucomatologist (KFD) evaluated stereofundus photographs of the participants of the Reykjavik Eye Study (RES)-a random sample from the national population census including people 50 years and older. 1012 right eyes could be evaluated for grey crescent., Results: The prevalence of grey crescent in the right eyes was 22.0% (95% CI 10 to 25). It was more commonly found in women (27.0%: 95% CI 23 to 30) than in men (17.0%: 95% CI 14 to 21), and was most often located temporally (36.9%), 360 degrees (15.9%), or nasally (15.4%). The spherical equivalent was +1.30 dioptres (D) for those with and +0.80 D for those without grey crescent (p = 0.002), respectively. Vertical optic disc diameters were 0.203 v 0.195 units (p<0.001). There was no difference in the prevalence of grey crescent in glaucomatous or non-glaucomatous eyes (OR = 1.05, 95% CI 0.49 to 2.26). The prevalence of a grey crescent was inversely related to the prevalence of peripapillary atrophy (p = 0.001)., Conclusions: The grey crescent needs to be recognised as a physiological variant in order to avoid falsely labelling eyes as having glaucomatous optic nerve damage.

Purpose: Mutations of the homeodomain protein PITX2 produce Axenfeld-Rieger (AR) malformations of the anterior chamber, an autosomal dominant disorder accompanied by a 50% risk of glaucoma. Twenty-nine mutations of PITX2 have been described, with a mutational prevalence estimated between 10% and 60% in AR. In the current study, the possible role of altered PITX2 gene dosage in the etiology of AR was investigated. Gross gene deletions and duplications should alter PITX2 activity analogously to hypomorphic and hypermorphic mutations, respectively., Methods: Sixty-four patients with AR, iridogoniodysgenesis (IGD), iris hypoplasia (IH), or anterior segment dysgenesis (ASD) were screened for PITX2 mutations by sequencing. PITX2 gene dosage was concurrently examined in these patients by real-time quantitative PCR. Microsatellite markers were used to map 4q25 microdeletions at a contig scale, as well as for haplotype analysis in an extended AR kindred. An additional 27 patients with other assorted ocular phenotypes were evaluated by similar methods, amounting to a total of 91 cases analyzed., Results: Three novel mutations of PITX2 (4.7%) were identified among 64 patients with AR, IGD, IH, or ASD. Deletions of PITX2 were as frequent as mutations in our sample. Chromosome 4q25 microdeletions were physically mapped relative to several microsatellite markers in each patient. Cosegregation of AR and a PITX2 deletion was demonstrated in an extended kindred., Conclusions: Point mutations and gross deletions of PITX2 appear to produce an equivalent haploinsufficiency phenotype. Quantitative PCR is an efficient means of detecting causative PITX2 deletions in patients with AR and may increase the detection rate at this locus.