RetINal Toxicity And HydroxyChloroquine Therapy (INTACT): protocol for a prospective population-based cohort study.

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.

Evaluating Signs of Microangiopathy Secondary to Diabetes in Different Areas of the Retina with Swept Source OCTA.

Purpose: The purpose of this study was to compare perfusion parameters of the parafovea with scans outside the parafovea to find an area most susceptible to changes secondary to diabetic retinopathy (DR). Methods: Patients with different DR severity levels as well as controls were included in this cross-sectional clinical trial. Seven standardized 3 × 3 mm areas were recorded with Swept Source Optical Coherence Tomography Angiography: one centered on the fovea, three were temporal to the fovea, and three nasally to the optic disc. The capillary perfusion density (PD) of the superficial capillary complex (SCC) and deep capillary complex (DCC) as well as the fractal dimension (FD) were generated. Statistical analyses were done with R software. Results: One hundred ninety-two eyes (33 controls, 51 no-DR, 41 mild DR, 37 moderate/severe DR, and 30 proliferative DR), of which 105 patients with diabetes and 25 healthy controls were included (59 ± 15 years; 62 women). Mean PD of the DCC was significantly less in patients without DR (parafovea = 0.48 ± 0.03; temporal = 0.48 ± 0.02; and nasal = 0.48 ± 0.03) compared to controls (parafovea = 0.49 ± 0.02; temporal = 0.50 ± 0.02; and nasal = 0.50 ± 0.03). With increasing DR severity, PD and FD of the SCC and DCC further decreased. Conclusions: Capillary perfusion of the retina is affected early by diabetes. PD of the DCC was significantly reduced in patients with diabetes who did not have any clinical signs of DR. The capillary network outside the parafovea was more susceptible to capillary perfusion deficits compared to the capillaries close to the fovea. Trial Registration: clinicaltrial.gov, NCT03765112, https://clinicaltrials.gov/ct2/show/NCT03765112?term=NCT03765112&rank=1.

A comparison of robotic and manual surgery for internal limiting membrane peeling.

PURPOSE: To compare the Preceyes Surgical Robotic System (Eindhoven, Netherlands) to manual internal limiting membrane (ILM) peeling using the Eyesi surgical simulator (VRmagic, Mannheim, Germany) as the operative platform. METHODS: A comparative study was carried out with surgeons initially performing ILM peeling manually and then with the robot. Twenty-three vitreoretinal surgeons agreed to participate and all consented to the use of their surgical data from the Eyesi surgical simulator. Surgeons were given a 5-min demonstration of the devices and were allowed to practice for 10 min before attempting the membrane peel. Initially, the peel was performed manually and afterwards, this was repeated using the robot-controlled forceps. Surgical simulator outcome measures were compared between approaches. RESULTS: The average time required for the procedure was 5 min for the manual approach and 9 min with the robot (paired t test, p = 0.002). Intraocular instrument movement was reduced by half with the robot. On average 344 mm was required to complete the ILM peeling with the robot compared with 600 mm using the manual approach (paired t test, p = 0.002). There were fewer macular retinal hemorrhages with the robot: 53 with manual surgery, 32 with the robot (Mann-Whitney U test, p = 0.035). Retinal injuries were eliminated with the robot. CONCLUSIONS: Intraocular robotic surgery is still in its infancy and validation work is needed to understand the potential benefits and limitations of emerging technologies. Safety enhancements over current techniques may be possible and could lead to the broader adoption of robotic intraocular surgery in the future.

One-year effectiveness study of intravitreous bevacizumab in neovascular age-related macular degeneration: a population-based retrospective cohort study.

OBJECTIVE: To assess effectiveness of intravitreous bevacizumab in a cohort of patients with neovascular age-related macular degeneration (nAMD) in British Columbia, Canada. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with new-onset AMD who completed 1 year of bevacizumab treatment. METHODS: A cohort of 4507 patients with nAMD (5174 eyes) aged 50 years and older treated on an as-needed basis with bevacizumab was followed from June 1, 2010, to May 31, 2014, and then evaluated after completing a follow-up treatment at 1 year. Descriptive statistics were used to characterize eyes treated with bevacizumab. Multivariable regression models were used to quantify visual acuity (VA) changes over time, adjusting for baseline prognostic variables. RESULTS: On average, patients received 8.6 injections (SD 2.4) per eye during the year of treatment. There was an average gain of 5.2 letters over the 1-year study period. Among eyes treated with bevacizumab, improvement in VA was greater for eyes with poorer baseline VA and for eyes receiving more injections. The odds ratio for VA at 1 year was 9.35 (95% CI 6.00-14.6) for eyes with VA 20/50-20/80 versus 20/20-20/40 and increased to 74.5 (95% CI 47.7-116.4) for eyes 20/400 or worse versus 20/20-20/40. CONCLUSION: Intravitreous bevacizumab is effective in treating nAMD, especially for eyes with poor baseline VA. Gains in VA were greatest by month 3 and were generally maintained thereafter.

One-Year Effectiveness Study of Intravitreous Ranibizumab in Wet (Neovascular) Age-Related Macular Degeneration: A Meta-Analysis.

PURPOSE: The clinical efficacy of ranibizumab has been examined by a large number of prospective and retrospective studies to date. This meta-analysis was conducted to summarize the current body of evidence on visual acuity (VA) changes with use of ranibizumab in the treatment of wet (neovascular) age-related macular degeneration (wAMD). METHODS: A literature review of multiple electronic databases (EMBASE, MEDLINE, MedMEME) was conducted to find randomized controlled trials (RCTs) and observational studies that reported changes in VA while patients with wAMD were on ranibizumab. Study factors analyzed were baseline patient characteristics, study type, sample size, and 12-month change in VA. Data were pooled in a meta-analysis with VA change as the main outcome. Data were then stratified by study design and a meta-regression was conducted to assess 12-month VA change against baseline VA and age. RESULTS: A total of 42 studies were included for analysis. An overall increase of 5.58 letters (95% confidence interval [CI]: 4.42-6.75; p heterogeneity, < 0.001) was shown with use of ranibizumab compared to baseline. Improvements in VA were larger for RCTs, at 7.71 letters (95% CI: 6.66-8.76; p heterogeneity, 0.013), compared to observational studies, at 4.85 letters (95% CI: 3.32-6.38; p heterogeneity, < 0.001). The meta-regression showed a significant decrease in effect size between baseline VA and 12-month VA change. CONCLUSION: This meta-analysis suggests visual improvements at 12 months of 0.5-mg ranibizumab use in patients with wAMD. A higher gain in VA was observed when pooling results from RCTs compared to those in observational studies.

ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR PROLIFERATIVE DIABETIC RETINOPATHY: A Systematic Review and Meta-Analysis.

PURPOSE: To systematically review and perform meta-analysis on the available randomized controlled trial data for anti-vascular endothelial growth factor (anti-VEGF) agents in the management of proliferative diabetic retinopathy and its complications. METHODS: The authors identified randomized controlled trials using anti-VEGF agents, either as stand-alone therapy or combined with other interventions, in the management of proliferative diabetic retinopathy. The primary outcome measures were change in best-corrected visual acuity and (in the context of vitrectomy) duration of surgery and postoperative vitreous hemorrhage. Secondary outcomes were change in central retinal thickness and (in the context of vitrectomy) intraoperative variables suggestive of complex surgery (retinal breaks, intraoperative bleeding, and endodiathermy applications). The quality of evidence for all outcomes was appraised using the GRADE criteria. RESULTS: Twenty-two studies involving 1,397 subjects met the criteria for inclusion in this study. One study compared intravitreal ranibizumab with saline, one compared intravitreal pegaptanib to pan-retinal photocoagulation (PRP), one compared intravitreal bevacizumab to PRP, 3 compared combined intravitreal ranibizumab/PRP to PRP, 5 compared combined intravitreal bevacizumab/PRP to PRP alone, and 11 compared combined intravitreal bevacizumab/PPV to PPV alone. When used in conjunction with PRP, there is a high-quality evidence to suggest that intravitreal ranibizumab is associated with superior visual acuity and central retinal thickness outcomes at 3 months to 4 months. In the context of PPV, there is moderate quality evidence to suggest that preoperative intravitreal bevacizumab results in a significant reduction in the duration of surgery, fewer retinal breaks, less intraoperative bleeding, and fewer endodiathermy applications. Although there is evidence to suggest occurrence of early postoperative vitreous hemorrhage is reduced, the quality of evidence in support of this finding is low. CONCLUSION: The use of anti-VEGF agents before PRP results in superior functional and structural outcomes at 3 months to 4 months. The use of anti-VEGF agents before PPV results in decreased duration of surgery, fewer breaks, and less intra-operative bleeding. Although there is evidence for a decreased incidence of early postoperative vitreous hemorrhage, the quality of evidence is low. The available data therefore support the use of anti-VEGF agents as adjuncts to PRP and PPV in patients with complicated proliferative diabetic retinopathy primarily as a means of facilitating, and potentially minimizing the iatrogenic damage resulting from, these procedures.

Infantile Refsum disease in a young adult: case presentation and brief review.

PURPOSE: To review and describe findings, pathophysiology, and management of infantile Refsum disease in a young adult, and to compare with those of classic Refsum Disease. METHODS: Retrospective chart and digital photography review. RESULTS: A 25-year-old woman with a diagnosis of infantile Refsum disease presented with progressively decreasing vision. Findings included a noncorpuscular pigmentary degeneration of both fundi, optic nerve head drusen, attenuated retinal vasculature, cataract, myopia, and esotropia. She was treated with a low phytanic acid diet, resulting in improved metabolic values on laboratory testing. CONCLUSION: Infantile Refsum disease has clinical features and a pathophysiology distinct from classic Refsum disease, despite occasionally presenting for examination later in life. Ophthalmic and systemic distinctions between the two are important to consider for the ophthalmologist, who may be involved in the initial diagnosis of the patient.

The effects of intravitreal bevacizumab on patients with macular edema secondary to branch retinal vein occlusion.

OBJECTIVE: To evaluate the effect of intravitreal bevacizumab on visual acuity (VA) and central retinal thickness (CRT) in patients with macular edema (ME) secondary to branch retinal vein occlusion (BRVO). DESIGN: Retrospective review. PARTICIPANTS: The study included 42 patients with ME secondary to BRVO who received intravitreal injections of bevacizumab in 2 referral-based retinal practices in Vancouver, B.C., between November 2005 and July 2006. METHODS: We performed a retrospective review of consecutive patients with ME secondary to BRVO. All of the patients in this study had nonischemic BRVOs. Patients were all treated with at least 1 bevacizumab injection and were seen at 6- to 8-week intervals for VA testing. Most of the patients also underwent optical coherence tomography (OCT) 2 months and 6 months after treatment. VA and OCT measurements at each follow-up time point were compared with the baseline values. RESULTS: A total of 42 eyes from 42 patients with ME secondary to BRVO were reviewed. The mean VA improved from 20/280 at baseline to 20/180 at first follow-up session (p < 0.04; average follow-up = 42 days) and remained at a similar level, 20/170, through the eighth follow-up session (p < 0.04; average follow-up = 356). The CRT was reduced from a mean of 451 microm (388-512 microm) at baseline to 358 microm (298-418 microm) at 2 months (p < 0.02) and to 400 microm (335-465 microm) at 6 months postinjection (p < 0.068). CONCLUSIONS: We found a significant improvement in VA and CRT in patients with ME secondary to BRVO after intravitreal bevacizumab injection(s). No complications or serious side effects were observed. Intravitreal bevacizumab appears to have an emerging role as either a primary or an adjuvant treatment modality in the setting of ME secondary to BRVO.

Correctable visual impairment and its impact on quality of life in a marginalized Canadian neighbourhood.

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.

Use of lipid-lowering agents for the prevention of age-related macular degeneration: a meta-analysis of observational studies.

PURPOSE: To examine the effect of lipid-lowering agents in the development of age-related macular degeneration (AMD) through the techniques of meta-analysis. METHODS: Case-control and cohort studies presenting relative risks and 95% confidence intervals were identified through a literature review. Inclusion was limited to studies where both the exposure of interest (lipid-lowering agents) and outcome (AMD) were explicitly defined. Pooled estimates were computed using the random effects model. To quantify heterogeneity we calculated the proportion of total variance of between study variance using the Ri statistic. The Q statistic for heterogeneity was also calculated. RESULTS: Eight studies were identified. The pooled relative risk (RR) for all studies was 0.74 (95% CI, 0.55-1.00). When only those studies examining the use of statins were pooled (n=7), the RR was 0.70 (95% CI, 0.48-1.03). Using the Ri statistic, the heterogeneity between studies was found to be 0.85 for all studies and 0.89 for studies examining statins. CONCLUSION: Lipid-lowering agents, including statins, do not appear to lower the risk of developing AMD, although clinically significant effects cannot be excluded. The use of these agents in the prevention of AMD cannot be recommended until well designed prospective studies with long follow up have demonstrated a benefit.

Sensitivity and specificity of the optos optomap for detecting peripheral retinal lesions.

PURPOSE: To compare the sensitivity and specificity of the Optomap Panoramic200 wide-field confocal scanning laser imaging system for detecting peripheral retinal lesions. METHODS: Optomap images were obtained in patients with known retinal pathology. Two masked retinal specialists evaluated Optomap images to identify lesions requiring referral to a retinal specialist. Their performance was compared to gold standard examination with scleral indentation performed by a retinal specialist. Sensitivity was calculated overall and again for lesions that were found on clinical examination to require treatment. These sensitivities were calculated separately for lesions posterior and anterior to the equator. Specificity was calculated from fellow eyes that were found to have no pathology on clinical examination. RESULTS: For retinal lesions posterior to the equator, sensitivity was 74% (95% confidence interval [95% CI] 61%-87%) overall for all lesions and 76% (95% CI 59%-93%) for lesions requiring treatment. For anterior lesions, sensitivity was 45% (95% CI 28%-62%) overall and 36% (95% CI 14%-58%) for treatable lesions. Specificity was 85% (95% CI 63%-100%). CONCLUSIONS: The Optomap showed high specificity and moderate sensitivity for lesions posterior to the equator and low sensitivity for lesions anterior to the equator.

Risk factors for posterior vitreous detachment: a case-control study.

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.

Comparison of photodynamic therapy and transpupillary thermotherapy for subfoveal choroidal neovascularization due to age-related macular degeneration.

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.

Socioeconomic status and clinical features of patients undergoing photodynamic therapy or transpupillary thermotherapy for subfoveal choroidal neovascularization due to age-related macular degeneration.

BACKGROUND: The purpose of this study was to compare baseline clinical and socioeconomic features of patients undergoing self-funded photodynamic therapy (PDT) or government-funded subthreshold transpupillary thermotherapy (TTT) with a diode laser for subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). METHODS: Between July 2000 and August 2001, 115 patients with subfoveal choroidal neovascularization secondary to AMD were offered PDT as an initial intervention. If individuals believed that they could not afford or did not want PDT, then TTT was offered. In masked fashion, leakage pattern and lesion size were determined retrospectively from pretreatment angiograms. Baseline visual acuity was determined with autorefraction and subsequent Snellen testing. The mean income of each treatment group was estimated from the average sex-specific income for each subject's postal code, based on the 1996 Canadian census data. The average education level for each subject's postal code was also determined. RESULTS: The patients who were not willing to pay for PDT had significantly worse macular disease before treatment (larger lesions and poorer visual acuity) and a significantly lower mean income than the patients who were willing to pay for PDT. INTERPRETATION: The severity of exudative choroidal neovascularization appears to be associated with lower socioeconomic status.