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PURPOSE: Hydroxychloroquine (HCQ) is an important medication for patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other rheumatic diseases. Although it is well-tolerated and cost-effective, the risk of HCQ retinal toxicity is of increasing concern. The aim of this study is to re-examine the HCQ retinal toxicity incidence rate, risk factors and clinical course after discontinuation. METHODS: We designed a prospective population-based cohort study in adult patients with SLE or RA, currently receiving HCQ for five or more years, who are residents of British Columbia (BC), Canada. Based on administrative data, we identified 5508 eligible participants (1346 SLE and 4162 RA). They will participate in annual or biannual retinal screening over 5 years in alignment with the recently revised American Academy of Ophthalmology guidelines. To standardise procedures for retinal screening, imaging, diagnostic criteria, severity staging and data transfer, a consensus meeting was convened in December 2019 with participation of BC retinal specialists and the research team. Agreement was attained on: use of spectral domain-optical coherence tomography as the primary objective screening modality; classification of images into categories of normal, equivocal or abnormal; and transferring the equivocal and abnormal images plus corresponding subjective test results via cloud-based server from each clinic to a reading centre. Confirmation of HCQ retinal toxicity diagnoses and severity staging will be performed by three independent and masked reviewers. The incidence of HCQ retinal toxicity will be calculated, accounting for the competing risk of death. Hazard ratios for each risk factor will be calculated for the risk of HCQ retinopathy, after adjusting for confounders. We will also estimate the risk of HCQ retinal toxicity progression over 5 years. ETHICS AND DISSEMINATION: This study has received approval from the University of British Columbia Clinical Research Ethics Board (H20-00736) and the Vancouver Coastal Health Research Institute.

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PURPOSE: To investigate the effect of anti-inflammatory therapy on selective laser trabeculoplasty (SLT) outcomes. DESIGN: Randomized, double-masked, placebo-controlled trial. PARTICIPANTS: Patients with primary open-angle or pseudo-exfoliation glaucoma. METHODS: Patients undergoing SLT were randomized to receive placebo (artificial tears), prednisolone acetate 1%, or ketorolac tromethamine 0.5% eye drops 4 times per day for 5 days commencing immediately after SLT. MAIN OUTCOME MEASURES: Change in intraocular pressure (IOP) from baseline to the 1-month post-SLT visit. RESULTS: Mean change in IOP at the 1-month primary outcome time point, as well as all other time points, was not significantly different among groups (P = 0.99). Likewise, a repeated-measures, mixed-effects model did not find significant differences in IOP outcome at the 1-month time point (P = 0.95). The IOP was reduced in all groups at the 1-month post-SLT time point and all other time points, and no significant differences were found between groups using separate unadjusted cross-sectional analyses of variance (P > 0.15 for analyses at all time points). Treatment failure rates were not different among groups (P = 0.75), and at 1 year after SLT, the percentage of patients maintaining a 20% IOP reduction ranged from 18% to 22% in the 3 study groups. CONCLUSIONS: Anti-inflammatory therapy after SLT does not seem to substantially influence the IOP-lowering effect of SLT. In this study of patients with low baseline IOP, SLT showed limited efficacy in achieving a sustained reduction in IOP.

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IMPORTANCE: Glaucoma is the second leading cause of blindness worldwide, and its insidious onset is often associated with diagnostic delay. Since glaucoma progression can often be effectively diminished when treated, identifying individuals at risk for glaucoma could potentially lead to earlier detection and prevent associated vision loss. OBJECTIVE: To quantify the diagnostic accuracy of examination findings and relevant risk factors in identifying individuals with primary open-angle glaucoma (POAG), the most common form of glaucoma in North America. DATA SOURCES: Structured Medline (January 1950-January 2013) search and a hand search of references and citations of retrieved articles yielding 57 articles from 41 studies. STUDY SELECTION: Population-based studies of high-level methods relating relevant examination findings of cup-to-disc ratio (CDR), CDR asymmetry, intraocular pressure (IOP), and demographic risk factors to the presence of POAG. RESULTS: The summary prevalence of glaucoma in the highest-quality studies was 2.6% (95% CI, 2.1%-3.1%). Among risk factors evaluated, high myopia (≥6 diopters; odds ratio [OR], 5.7; 95% CI, 3.1-11) and family history (OR, 3.3; 95% CI, 2.0-5.6) had the strongest association with glaucoma. Black race (OR, 2.9; 95% CI, 1.4-5.9) and increasing age (especially age >80 years; OR, 2.9; 95% CI, 1.9-4.3) were also associated with an increased risk. As CDR increased, the likelihood for POAG increased with a likelihood ratio (LR) of 14 (95% CI, 5.3-39) for CDR of 0.7 or greater. Increasing CDR asymmetry was also associated with an increased likelihood for POAG (CDR asymmetry ≥0.3; LR, 7.3; 95% CI, 3.3-16). No single threshold for CDR or asymmetry ruled out glaucoma. The presence of a disc hemorrhage (LR, 12; 95% CI, 2.9-48) was highly suggestive of glaucoma, but the absence of a hemorrhage was nondiagnostic (LR, 0.94; 95% CI, 0.83-0.98). At the commonly used cutoff for high IOP (≥22), the LR was 13 (95% CI, 8.2-17), while lower IOP made glaucoma less likely (LR, 0.65; 95% CI, 0.55-0.76). We found no studies of screening examinations performed by generalist physicians in a routine setting. CONCLUSIONS AND RELEVANCE: Individual findings of increased CDR, CDR asymmetry, disc hemorrhage, and elevated IOP, as well as demographic risk factors of family history, black race, and advanced age are associated with increased risk for POAG, but their absence does not effectively rule out POAG. The best available data support examination by an ophthalmologist as the most accurate way to detect glaucoma.

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OBJECTIVE: To compare adverse intraocular pressure (IOP) spikes in patients receiving intravitreal triamcinolone acetonide (IVTA) in 2 cohorts: (i) patients who underwent a topical prednisolone acetate trial (PAT) without incurring a short-term IOP rise, and (ii) control patients who did not undergo a PAT. DESIGN: Retrospective cohort study. PARTICIPANTS: Charts of all patients who underwent any intravitreal injection during the study period were reviewed (n = 1150). METHODS: Patients in the PAT group received a 6-week course of prednisolone acetate 1% 4 times per day and had an IOP that did not rise above 25 mm Hg or above 8 mm Hg over the IOP in the contralateral eye. Patients undergoing a PAT and having a short-term IOP rise were not studied. Control patients did not receive a PAT. All patients received 12-20 mg of IVTA. Patients were followed for a minimum of 6 weeks and follow-up lasted for 1 year or until intraocular surgery or another IVTA injection was performed. RESULTS: There were 97 patients in the PAT cohort and 75 control patients. Patients in the PAT cohort had a lower proportional rise between maximum IOP and baseline (43%) compared with controls (64%) (p = 0.035). Patients in the PAT group also had a lower risk of incurring a 40% (p = 0.05), 60% (p = 0.018), and 100% (p = 0.045) increase in maximum IOP (vs baseline) compared with controls and were less likely to require glaucoma filtration surgery (p = 0.035). CONCLUSIONS: Patients undergoing a PAT who did not have a subsequent short-term IOP rise had a lower risk of severe IOP spikes after IVTA compared with those patients receiving IVTA but not having undergone a PAT.

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OBJECTIVE: To determine the incidence and characteristics of acute intraocular inflammation after intravitreal bevacizumab injections from a tertiary care retinal practice. DESIGN: Retrospective cohort study. PARTICIPANTS: A consecutive series of patients who had received bevacizumab injections performed by a single surgeon. METHODS: We reviewed the records of all patients with severe anterior chamber inflammation and (or) vitritis after bevacizumab injections. RESULTS: A total of 693 bevacizumab injections were performed on 193 eyes of 173 patients between June 2006 and March 2008. There were a total of 9 cases of acute intraocular inflammation for an incidence of 1.30% (95% CI: 0.69%-2.47%). All patients had a worse visual acuity at the end of follow-up than on injection day. The mean loss of vision was 6.1 lines of Snellen visual acuity; one patient developed inflammation-induced glaucoma which required surgical intervention. CONCLUSIONS: Intravitreal injection of bevacizumab is associated with a low but significant risk of acute intraocular inflammation and may result in significant visual loss.

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PURPOSE OF REVIEW: To compare health-related quality of life (HRQoL) in American vs. Canadian populations suffering from retinal diseases. RECENT FINDINGS: A search of Medline was conducted according to a strategy that combined the MeSH heading 'retinal diseases' with either of 'quality of life' as a MeSH or 'utility' as a keyword. We included studies of American or Canadian patients using any of the National Eye Institute 25-item visual functioning questionnaire (NEI-VFQ-25), visual function index (VF-14), short form health survey (SF-36), or utility to assess HRQoL. A total of 22 studies with American patients and five with Canadian patients were found. There was no significant HRQoL difference found between the American and Canadian patients for any of the HRQoL instruments (P = 0.14-0.80); however, for all instruments mean HRQoL correlated positively with mean visual acuity in the better-seeing eye (P < 0.001). SUMMARY: On the basis of a review of the currently published literature, we were unable to detect significant differences in HRQoL between American and Canadian patients. Further research into the topic is necessary.

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CONTEXT: Acute onset of monocular floaters and/or flashes represents a common presentation to primary care physicians, and the most likely diagnosis is posterior vitreous detachment (PVD). A significant proportion of patients with acute PVD develop an associated retinal tear that can lead to retinal detachment and permanent vision loss if left untreated. OBJECTIVE: To quantify the association between relevant clinical variables and risk of retinal tear in patients presenting with acute-onset floaters and/or flashes and PVD. DATA SOURCES: Structured MEDLINE (January 1950-September 2009) and EMBASE (January 1980-September 2009) searches and a hand search of references and citations of retrieved articles yielded 17 relevant studies. STUDY SELECTION: Studies of high-level methods that related elements of the history or physical examination in patients presenting with floaters and/or flashes and PVD to the likelihood of retinal tear. RESULTS: For patients with acute onset of floaters and/or flashes who are self-referred or referred to an ophthalmologist, the prevalence of retinal tear is 14% (95% confidence interval [CI], 12%-16%). Subjective visual reduction is the most important symptom associated with retinal tear (likelihood ratio [LR], 5.0; 95% CI, 3.1-8.1). Vitreous hemorrhage on slitlamp biomicroscopy is the best-studied finding with the narrowest positive LR for retinal tear (summary LR, 10; 95% CI, 5.1-20). Absence of vitreous pigment during this examination is the best-studied finding with the narrowest negative LR (summary LR, 0.23; 95% CI, 0.12-0.43). Patients initially diagnosed as having uncomplicated PVD have a 3.4% chance of a retinal tear within 6 weeks. The risk increases with new onset of at least 10 floaters (summary LR, 8.1-36) or subjective visual reduction (summary LR, 2.3-17) during this period. CONCLUSIONS: Primary care physicians should evaluate patients with acute-onset floaters and/or flashes due to suspected PVD, or patients with known PVD and a change in symptoms, for high-risk features of retinal tear and detachment. Physicians should always assess these patients' visual acuity. Patients at increased risk should be triaged for urgent ophthalmologic assessment.

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OBJECTIVE: To study the impact of visual impairment due to either underlying ocular pathology or easily correctable refractive error on vision-related functioning and quality of life (QOL) in Vancouver's downtown eastside (VDES). DESIGN: Cross-sectional study. PARTICIPANTS: Two hundred consecutive patients seeking general medical care at the Vancouver Native Health Society (VNHS) medical clinic were included. METHODS: An ocular examination was performed and a standardized history and QOL information were obtained for each participant. Effective visual impairment was classified based on patients' current refractive means. Pathological visual impairment was classified based on patients' best-corrected visual acuity (VA). Vision-related functioning was quantified using the Daily Tasks Dependent on Vision (DTDV) questionnaire. Health-related QOL was assessed using the 12-Item Short Form Health Survey (SF-12). RESULTS: Two hundred patients participated; they suffered, on average, 6.2 comorbid conditions. Sixty-two patients (31%) were effectively visually impaired and, of these, 14 patients (7%) were effectively blind. Ten patients (5%) had pathological eye disease to explain their visual impairment. The remaining 52 visually impaired patients (26%) had VA that normalized with correction. Difficulty with the tasks described in the DTDV questions was significantly correlated with effective visual impairment. Patients with effective visual impairment had lower Physical Composite Scores on the SF-12 in multivariate analyses. CONCLUSIONS: We have demonstrated a very high rate of visual impairment in a low socioeconomic population that is associated with decreased vision-dependent functioning and decreased overall physical health status. Public health efforts need to be directed toward improving easily correctable refractive error.

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BACKGROUND: To evaluate the cost-effectiveness of anterior uveitis investigation by Canadian ophthalmologists and to assess the role of implementing national clinical guidelines for such investigation. METHODS: Based on data extracted from the Canadian National Uveitis Survey (CNUS, 2007 version), the cost of investigating a patient with anterior uveitis, according to current practice patterns of Canadian ophthalmologists, was determined and grouped across 4 clinical scenarios: (i) nongranulomatous anterior uveitis in an adult, (ii) granulomatous anterior uveitis in an adult, (iii) granulomatous anterior uveitis with suspected sarcoidosis in an adult or a child, and (iv) nongranulomatous anterior uveitis in a child. Similarly, the cost of investigating a patient with anterior uveitis as per published evidence-based guidelines was determined and compared with the current practice pattern using a cost-minimization model, sensitivity analyses, and Monte Carlo simulations. RESULTS: Ophthalmologists were found to consistently order more tests than recommended by evidence-based guidelines, across each of the scenarios studied (p < 0.05). Overall, complete blood count, erythrocyte sedimentation rate, C-reactive protein, antinuclear antibody, and rheumatoid factor were the most commonly ordered extraneous tests that were not included in the evidence-based guidelines for the routine investigation of anterior uveitis. Also, there were significant differences in the cost of investigating a patient with anterior uveitis when compared with those predicted by adhering to evidence-based clinical practice guidelines. Cost minimization and sensitivity analyses revealed that published guidelines imparted cost savings when compared with current practice patterns across the 4 clinical scenarios studied (p < 0.01). The maximum additional cost was associated with investigating nongranulomatous anterior uveitis in an adult, where a minimal additional cost of $75 per patient was spent. For granulomatous anterior uveitis in an adult, the additional cost was approximately $40, whereas the additional cost for investigating an adult or a child with suspected sarcoidosis was $36. Only $11 of additional cost was spent in the workup of a child with nongranulomatous anterior uveitis. When applied to the Canadian population, adherence to the Clinical Practice Guidelines recommended by the CNUS may result in cost savings of $600,000 per year to the Canadian health care system. INTERPRETATION: Adherence to the evidence-based Clinical Practice Guidelines recommended by the CNUS may result in significant cost savings, with virtually no loss of sensitivity in the routine investigation of anterior uveitis in Canada.

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PURPOSE: To report the overall incidence of endophthalmitis associated with office based intravitreal injections of bevacizumab and ranibizumab. METHODS: This is a retrospective, consecutive, multicenter case series involving four large clinical sites. Included were all patients receiving at least one injection of intravitreal bevacizumab or intravitreal ranibizumab. Follow-up after each injection was at least 4 weeks. RESULTS: A total of 12,585 injections of intravitreal bevacizumab and 14,320 injections of intravitreal ranibizumab were given during the study period. Infectious endophthalmitis developed in three patients after administration of bevacizumab and in three patients after administration of ranibizumab. Four of these patients were culture positive. Rates of endophthalmitis were 0.02% and 0.02%, respectively, with an overall rate of 0.02%. CONCLUSION: The rate of endophthalmitis associated with intravitreal bevacizumab and ranibizumab is low, with an incidence of approximately 1 in 4,500 injections.

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PURPOSE: To evaluate the efficacy of prophylactic administration of the topical nonsteroidal antiinflammatory drug (NSAID) ketorolac tromethamine 0.5% on acute (within 4 weeks of surgery) cystoid macular edema (CME) and total macular volume (TMV) in patients having phacoemulsification cataract surgery. SETTING: Department of Ophthalmology, Queen's University, Hotel Dieu Hospital, Kingston, Ontario, Canada. METHODS: This open-label nonmasked randomized (random number assignment) study comprised 106 eyes of 98 patients. Exclusion criteria included hypersensitivity to the NSAID drug class, aspirin/NSAID-induced asthma, and pregnancy in the third trimester. Ketorolac tromethamine 0.5% was administered starting 2 days before surgery and for 29 days after surgery for a total of 31 days. The outcome measure was macular swelling, which was quantified by the optical coherence tomography. RESULTS: At 1 month, there was a statistically significant difference in TMV between the control group (0.4420 mm3) and the ketorolac group (0.2392 mm3), with the ketorolac group having 45.8% less macular swelling (P = .009). Multiple linear regression with backward selection indicated a 44.3% (P = .013) and 46.1% (P = .030) reduction in macular swelling in the ketorolac group at 1 week and 1 month, respectively. CONCLUSION: Used prophylactically after cataract surgery, ketorolac 0.5% was efficacious in decreasing postoperative macular edema.

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BACKGROUND: This study examines the changes in short-term intraocular pressure (IOP) in patients receiving intravitreally administered bevacizumab. A prospective series of consecutive patients undergoing injection of intravitreal bevacizumab was investigated. METHODS: All patients received bevacizumab (0.05 cc) injected intravitreally in a standard fashion. IOP was measured at baseline, 2, 5, and 30 minutes after injection by 1 of 2 observers using Goldman applanation tonometry. An intraobserver study was done to assess agreement in IOP measurements. RESULTS: We accrued 104 patients with a mean age of 76 years: 58% were female, and 42% were male. Most patients (85%) were being treated for neovascular age-related macular degeneration. The mean IOP values at baseline, 2, 5, and 30 minutes after injection were 14.0 (95% confidence interval [CI] 13.4-14.7) mm Hg, 36.1 (95% CI 33.5-38.6) mm Hg, 25.7 (95% CI 23.8-27.5) mm Hg, and 15.5 (95% CI 12.4-16.51) mm Hg, respectively. Three patients (2.9%) had an IOP of 25 mm Hg or higher at 30 minutes. IOP normalized within 2 hours without medical therapy in 2 of these patients, and 1 patient required a 1-week course of glaucoma medication. Regression analysis showed a trend towards phakic patients having higher IOP at 30 minutes (odds ratio = 3.2; p = 0.089). INTERPRETATION: Intravitreal injection of bevacizumab is safe with respect to short-term IOP changes, as almost all patients' IOP returned to a safe range (<25 mm Hg) within 30 minutes. Elevated IOP at 30 minutes after injection does occur, rarely, thus clinicians should consider checking IOP after injection as a precaution. Transient extreme IOP elevations occur in a significant percentage of patients, but the consequences of these events are unknown.

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PURPOSE: To identify possible risk factors for the development of posterior vitreous detachment (PVD). DESIGN: Retrospective case-control study. METHODS: A total of 138 cases with PVD and 114 age-matched controls were accrued from two different sites. Demographic, medical, ocular, and lifestyle data were obtained through chart review, questionnaires, and clinical examination. A 108-item semiquantitative food frequency questionnaire was also used to estimate macro- and micronutrient intake. Univariate and multivariate regression analyses were employed to identify variables significantly associated with the main outcome measure of PVD. Subgroup analysis of gender-specific variables was performed. RESULTS: Among all patients, multivariate regression analysis demonstrated female gender (odds ratio [OR] = 2.01, P = .016), myopic refraction (OR = 4.32, P < .0005), and higher intake of vitamin B6 (OR = 2.61, P = .001) to be associated with PVD after controlling for age. In the subgroup analysis of women, menopause (OR = 18.2, P < .0005), myopic refraction (OR = 3.42, P = .01), and higher intake of vitamin B6 (OR = 3.92, P = .005) were associated with PVD. Specifically, there was a significant association between vitamin B6 and PVD amongst premenopausal women but not amongst postmenopausal women. CONCLUSIONS: An association between PVD and menopause has not been documented previously. We suspect that high estrogen levels seen in premenopausal women may be protective against PVD and that hormonal changes associated with menopause may lead to changes in the vitreous, predisposing to PVD. Higher levels of intake of vitamin B6 were also associated with the development of PVD in premenopausal women possibly through an anti-estrogen effect. These findings should be investigated further with prospective studies.

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PURPOSE OF REVIEW: The purpose of this review is to summarize the recent and noteworthy utility studies and cost-utility analyses in the area of retina/vitreous during the period January 2004 to January 2006. RECENT FINDINGS: This review considers the cost-effectiveness of treatments for wet age-related macular degeneration, dry age-related macular degeneration, telemedicine in diabetic retinopathy, and utilities and patients with age-related macular degeneration and diabetic retinopathy. SUMMARY: Utilities are being used increasingly to measure health-related quality of life. Cost-utility analyses are becoming more readily available for comparing the incremental cost-effectiveness of different ophthalmic interventions.

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BACKGROUND: The purpose of this study was to compare photodynamic therapy (PDT) against subthreshold transpupillary thermotherapy (TTT) with a diode laser for subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). METHODS: Patients with subfoveal choroidal neovascularization secondary to AMD were offered PDT as an initial intervention. If they declined PDT, then TTT was offered. RESULTS: We evaluated and followed 115 consecutive patients for an average of 1 year. The primary outcome measure was visual acuity, but the interventions were also compared on the basis of lesion size and angiographically determined lesion activity. Baseline comparisons between the 2 treatment groups showed significant differences in pretreatment visual acuity, lesion size, and lesion composition. Univariate analysis of outcomes demonstrated equivalence between the treatment groups in final lesion size, angiographic activity, and visual acuity. Multivariate analysis also demonstrated equivalence between the treatment groups in final visual acuity while controlling for age, pretreatment visual acuity, and lesion category. Predominantly classic lesions were associated with poorer visual outcomes. INTERPRETATION: The PDT and TTT groups were equivalent in terms of all outcome parameters evaluated.

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