Diabetic Disease of the Eye in Canada: Consensus Statements from a Retina Specialist Working Group.

Despite advances in systemic care, diabetic disease of the eye (DDE) remains the leading cause of blindness worldwide. There is a critical gap of up-to-date, evidence-based guidance for ophthalmologists in Canada that includes evidence from recent randomized controlled trials. Previous guidance has not always given special consideration to applying treatments and managing DDE in the context of the healthcare system. This consensus statement aims to assist practitioners in the field by providing a spectrum of acceptable opinions on DDE treatment and management from recognized experts in the field. In compiling evidence and generating consensus, a working group of retinal specialists in Canada addressed clinical questions surrounding the four themes of disease, patient, management, and collaboration. The working group reviewed literature representing the highest level of evidence on DDE and shared their opinions on topics surrounding the epidemiology and pathophysiology of diabetic retinopathy and diabetic macular edema; diagnosis and monitoring; considerations around diabetes medication use; strategic considerations for management given systemic comorbidities, ocular comorbidities, and pregnancy; treatment goals and modalities for diabetic macular edema, non-proliferative and proliferative diabetic retinopathy, and retinal detachment; and interdisciplinary collaboration. Ultimately, this work highlighted that the retinal examination in DDE not only informs the treating ophthalmologist but can serve as a global index for disease progression across many tissues of the body. It highlighted further that DDE can be treated regardless of diabetic control, that a systemic approach to patient care will result in the best health outcomes, and prevention of visual complications requires a multidisciplinary management approach. Ophthalmologists must tailor their clinical approach to the needs and circumstances of individual patients and work within the realities of their healthcare setting.

Early Canadian Real-World Experience with Brolucizumab in Anti-Vascular Endothelial Growth Factor-Experienced Patients with Neovascular Age-Related Macular Degeneration: A Retrospective Chart Review.

Purpose: To assess early real-world outcomes with brolucizumab in Canadian patients with neovascular age-related macular degeneration (nAMD) for which they previously received ≥1 anti-vascular endothelial growth factor (anti-VEGF) agent(s). Patients and Methods: This multisite, real-world, retrospective chart review included data from a consecutive sample of 73 patients who received brolucizumab for nAMD after treatment with ≥1 other anti-VEGF agents. The principal reasons for switching to brolucizumab were to extend the treatment interval (51.6% of patients) and to treat persistent macular fluid (34.2%). The primary outcomes were best-corrected visual acuity (BCVA) and the incidence rates of intraocular inflammation (IOI), retinal vasculitis (RV), and retinal vascular occlusion (RVO). Secondary outcomes included central retinal thickness (CRT), injection interval, and presence of intraretinal and subretinal fluid (IRF and SRF). All parameters were measured at baseline until the last treatment visit between April 27, 2020, and August 31, 2021. Results: Over a mean follow-up of 28 weeks, a nonsignificant mean improvement in BCVA was identified (4.3 [standard deviation (SD) 8.3] letters; P=0.057), with 47.9% experiencing a gain of ≥5 letters. IOI was detected in 3 patients (4.1%), one of whom also developed RV and RVO (1.4%), which is consistent with existing brolucizumab data. Significant reductions were observed in mean CRT (-36.6 µm [SD 56.1 µm]; P=0.0002) and presence of any macular fluid (56.1% [SD 5.6%]; P<0.001), IRF (66.6% [SD 6.3%]; P<0.001), and SRF (62.7% [SD 6.3%]; P<0.001). The mean injection interval increased significantly by 2.1 weeks (SD 2.7; P<0.001). Conclusion: In the first real-world Canadian analysis, brolucizumab was associated with improvements in functional outcomes in treatment-experienced patients, consistent with other real-world studies. The incidence of IOI, RV, and RVO were in line with the post hoc safety analysis of HAWK and HARRIER data.

Paediatric vision screening in the primary care setting in Ontario.

OBJECTIVES: Early intervention is critical to prevent treatable causes of vision loss in children. The objectives of the current study are: (1) to assess how well primary care physicians in Ontario follow the vision screening guidelines for children as recommended by the Canadian Paediatric Society and the Rourke Baby Record and (2) to identify barriers to vision screening in the primary care setting. DESIGN: Cross-sectional survey. METHODS: A 19-question survey was mailed out to 1000 randomly selected family physicians (family MDs), 1000 general practitioners (GPs) and 1000 paediatricians in Ontario as listed in the 2013 Canadian Medical Directory. RESULTS: A total of 719 completed surveys were included in the analysis (449 from family MDs/GPs and 270 from paediatricians). Vision screening was reported to be performed by 65% of family MDs/GPs and 52% of general paediatricians at every well child visit. While red reflex was reported to be checked by 94% of all physicians in children under 3, it was only performed by 25% of respondents for children over 3. Thirty seven percent of all physicians reported never performing a visual acuity test in any age group. When asked about the obstacles preventing them from performing vision screening, lack of training (family MDs/GPs: 50%, paediatricians: 42%), time constraints (family MDs/GPs: 42%; paediatricians: 40%) and inadequate reimbursement (family MDs/GPs: 17%; paediatricians: 15%) were the most commonly cited reasons. CONCLUSIONS: Strategies to improve vision screening are necessary given that early intervention is crucial to prevent treatable causes of vision loss in children.

Sterol uptake and sterol biosynthesis act coordinately to mediate antifungal resistance in Candida glabrata under azole and hypoxic stress.

Pathogenic fungi, including Candida glabrata, develop strategies to grow and survive both in vitro and in vivo under azole stress. However, the mechanisms by which yeast cells counteract the inhibitory effects of azoles are not completely understood. In the current study, it was demonstrated that the expression of the ergosterol biosynthetic genes ERG2, ERG3, ERG4, ERG10, and ERG11 was significantly upregulated in C. glabrata following fluconazole treatment. Inhibiting ergosterol biosynthesis using fluconazole also increased the expression of the sterol influx transporter AUS1 and the sterol metabolism regulators SUT1 and UPC2 in fungal cells. The microarray study quantified 35 genes with elevated mRNA levels, including AUS1, TIR3, UPC2, and 8 ERG genes, in a C. glabrata mutant strain lacking ERG1, indicating that sterol importing activity is increased to compensate for defective sterol biosynthesis in cells. Bioinformatic analyses further revealed that those differentially expressed genes were involved in multiple cellular processes and biological functions, such as sterol biosynthesis, lipid localization, and sterol transport. Finally, to assess whether sterol uptake affects yeast susceptibility to azoles, we generated a C. glabrata aus1∆ mutant strain. It was shown that loss of Aus1p in C. glabrata sensitized the pathogen to azoles and enhanced the efficacy of drug exposure under low oxygen tension. In contrast, the presence of exogenous cholesterol or ergosterol in medium rendered the C. glabrata AUS1 wild­type strain highly resistant to fluconazole and voriconazole, suggesting that the sterol importing mechanism is augmented when ergosterol biosynthesis is suppressed in the cell, thus allowing C. glabrata to survive under azole pressure. On the basis of these results, it was concluded that sterol uptake and sterol biosynthesis may act coordinately and collaboratively to sustain growth and to mediate antifungal resistance in C. glabrata through dynamic gene expression in response to azole stress and environmental challenges.

Barriers to electronic medical record implementation: a comparison between ophthalmology and other surgical specialties in Canada.

OBJECTIVE: In the present study, the barriers limiting widespread adoption of electronic medical records (EMRs) among Canadian ophthalmologists were evaluated in comparison with physicians from other surgical specialities. The published literature regarding EMR use in ophthalmic practice was also reviewed. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 1199 Canadian surgeons participating in the 2014 National Physician Survey (NPS). METHODS: Data regarding speciality surgeons' adoption of EMR programs were extracted from the 2014 NPS, a nationwide survey of practicing physicians in Canada. The data were entered into a spreadsheet, and basic statistical analyses, including χ2 analyses, were performed to compare the responses of ophthalmologists to other surgeons. RESULTS: Compared with other surgeons, ophthalmologists surveyed were significantly more likely to identify the following barriers to EMR adoption: "no suitable product for my practice" (p = 0.01), "too costly" (p = 0.0006), "too time consuming" (p < 0.0001), and "planning to retire soon" (p = 0.001). No statistically detectable differences were found between ophthalmologists and other surgeons for the following barriers: privacy concerns, reliability concerns, and lack of training. CONCLUSIONS: The barriers that limit increased EMR adoption among Canadian ophthalmologists are different from those of other surgeons. This may be attributed to unique features of the field, including heavy reliance on hand-drawn figures in documentation, high patient volume, and the high costs associated with independent practice. Given the well-established benefits of EMR technology, consideration should be given to implementing strategies to mitigate these barriers. Additional research may help determine which specific improvements can be made to increase the use of EMR systems by ophthalmologists.

CENTRAL SEROUS CHORIORETINOPATHY IN POSTMENOPAUSAL WOMEN RECEIVING EXOGENOUS TESTOSTERONE.

PURPOSE: Central serous chorioretinopathy (CSR) is a serous detachment of the neurosensory retina commonly associated with male sex, Type-A personality and corticosteroid use. Exogenous administration of androgens and development of CSR in men has been reported. Only one case of CSR in a postmenopausal woman receiving exogenous androgen therapy has been reported. The authors describe three cases of chronic CSR in postmenopausal women receiving exogenous testosterone therapy. METHODS: Diagnosis was based on characteristic clinical, fluorescein angiographic, and optical coherence tomography findings. The three women were being treated with exogenous testosterone and progesterone therapy for symptoms of menopause and libido loss. RESULTS: Average age at presentation was 54.7 years (53-56 years), average duration of exogenous androgen use was 61 months (36-87 months), with average 19.7-month follow-up. Resolution of symptoms seemed correlated with cessation of androgen use despite treatment with oscillatory photodynamic therapy and intravitreal pharmacotherapy with antivascular endothelial growth factor agents. CONCLUSION: Exogenous testosterone is increasingly prescribed for menopausal symptoms and libido loss. Treatment with oscillatory photodynamic therapy, supplemental bevacizumab intravitreal pharmacotherapy, and cessation of exogenous androgen therapy was successful in three cases of chronic, therapy-resistant CSR. Ophthalmologists should inquire about androgen usage in patients who present with CSR, especially in the setting of therapy resistance.

Effect of Geography on the Analysis of Coccidioidomycosis-Associated Deaths, United States.

Because coccidioidomycosis death rates vary by region, we reanalyzed coccidioidomycosis-associated mortality in the United States by race/ethnicity, then limited analysis to Arizona and California. Coccidioidomycosis-associated deaths were shown to increase among African-Americans but decrease among Native Americans and Hispanics. Separately, in a Native American cohort, diabetes co-varied with coccidioidomycosis-associated death.

Trends in subspecialty training by Canadian ophthalmology graduates.

OBJECTIVE: To evaluate the trends in subspecialty fellowship training by Canadian ophthalmology graduates over the last 25 years. DESIGN: Cross-sectional study. PARTICIPANTS: Canadian-funded, Royal College-certified graduates from 1990 to 2014 who completed a full residency in an English-language Canadian ophthalmology postgraduate training program. METHODS: Data were obtained by contacting all 11 English-language ophthalmology residency programs across Canada for demographic and fellowship information regarding their graduates. Society web sites were then used to corroborate and complement the data set, including those of the Canadian Ophthalmology Society, American Academy of Ophthalmology, and Provincial Colleges of Physicians and Surgeons. Data were organized by demographic variables, and analysis was performed using SPSS v22.0. RESULTS: Of the 528 graduates from 1990 to 2014, 63.5% pursued fellowship training. Males and females were equally likely to undertake fellowship training. The proportion of graduates obtaining fellowship training did not change significantly during this 25-year period. The most popular subspecialty choices were vitreoretinal surgery (24.5%), glaucoma (16.7%), and anterior segment (16.7%). Significantly more males than females pursued vitreoretinal surgery and oculoplastics fellowships (p = 0.001, χ(2) test), whereas females were more likely to train in a paediatric ophthalmology and strabismus fellowship (p = 0.001, χ(2) test). CONCLUSIONS: The majority of ophthalmology graduates from English-language residency programs pursue subspecialty fellowship training. An understanding of trends in fellowship training may be helpful for both workforce planning and career decision making.

Exploiting Human Resource Requirements to Infer Human Movement Patterns for Use in Modelling Disease Transmission Systems: An Example from Eastern Province, Zambia.

In this research, an agent-based model (ABM) was developed to generate human movement routes between homes and water resources in a rural setting, given commonly available geospatial datasets on population distribution, land cover and landscape resources. ABMs are an object-oriented computational approach to modelling a system, focusing on the interactions of autonomous agents, and aiming to assess the impact of these agents and their interactions on the system as a whole. An A* pathfinding algorithm was implemented to produce walking routes, given data on the terrain in the area. A* is an extension of Dijkstra's algorithm with an enhanced time performance through the use of heuristics. In this example, it was possible to impute daily activity movement patterns to the water resource for all villages in a 75 km long study transect across the Luangwa Valley, Zambia, and the simulated human movements were statistically similar to empirical observations on travel times to the water resource (Chi-squared, 95% confidence interval). This indicates that it is possible to produce realistic data regarding human movements without costly measurement as is commonly achieved, for example, through GPS, or retrospective or real-time diaries. The approach is transferable between different geographical locations, and the product can be useful in providing an insight into human movement patterns, and therefore has use in many human exposure-related applications, specifically epidemiological research in rural areas, where spatial heterogeneity in the disease landscape, and space-time proximity of individuals, can play a crucial role in disease spread.

Evaluating the safety of air travel for patients with scleral buckles and small volumes of intraocular gas.

AIM: To evaluate the effect of scleral buckling on intraocular pressure (IOP) change during atmospheric decompression for eyes with small volumes of intravitreal gas. METHODS: 12 eyes of 12 patients, including 6 with and 6 without scleral buckles, were evaluated in a hypobaric chamber simulating air travel approximately 1 month post pars plana vitrectomy with 15% C3F8 gas fluid exchange. The chamber was decompressed with an ascent rate of 300 feet/min to a peak altitude of 8000 feet. After 15 min of cruising, descent was undertaken at 300 feet/min. IOP was measured at baseline and then every 5 min using slit-lamp mounted Goldmann applanation tonometry. The data were entered onto a spreadsheet and comparative statistics were done. RESULTS: During ascent, IOP steadily rose from an average of 13±3 mm Hg to a peak of 26±9 mm Hg at 8000 feet. Patients with scleral buckles had significantly lower peak IOPs compared with those without buckles (20±5 mm Hg vs 32±8 mm Hg, p=0.013, t test) representing lower absolute increases in IOP (7±1 mm Hg vs 19±7 mm Hg, p=0.001, t test) and lower percentage increases in IOP from baseline (62±25% vs 140±40%, respectively). CONCLUSIONS: Eyes with small volumes of intravitreal gas demonstrate significant IOP changes during atmospheric decompression in simulated flight. The presence of a scleral buckle significantly limits the magnitude of IOP change, suggesting that such patients can likely tolerate typical air travel without undue risk of dangerous IOP elevation.

Central serous chorioretinopathy: update on pathophysiology and treatment.

Recent technological advances--new pathophysiological insights, new imaging techniques for diagnosis and management, and new treatments--have led to an improved understanding of central serous chorioretinopathy (CSC). The primary role of the choroid has become more widely accepted with widespread use of indocyanine green angiography. Optical coherence tomography (OCT), and particularly enhanced depth imaging OCT, demonstrate a thickened and engorged choroid. Adaptive optics, fundus autofluorescence, multifocal electroretinography, microperimetry, and contrast sensitivity testing reveal that patients with even a mild course suffer previously undetected anatomic and functional loss. Although focal laser and photodynamic therapy are the current standard of care for persistent subretinal fluid in CSC, they are not appropriate in all cases, and the optimal timing of intervention remains unclear.

STB5 is a negative regulator of azole resistance in Candida glabrata.

The opportunistic yeast pathogen Candida glabrata is recognized for its ability to acquire resistance during prolonged treatment with azole antifungals (J. E. Bennett, K. Izumikawa, and K. A. Marr. Antimicrob. Agents Chemother. 48:1773-1777, 2004). Resistance to azoles is largely mediated by the transcription factor PDR1, resulting in the upregulation of ATP-binding cassette (ABC) transporter proteins and drug efflux. Studies in the related yeast Saccharomyces cerevisiae have shown that Pdr1p forms a heterodimer with another transcription factor, Stb5p. In C. glabrata, the open reading frame (ORF) designated CAGL0I02552g has 38.8% amino acid identity with STB5 (YHR178w) and shares an N-terminal Zn(2)Cys(6) binuclear cluster domain and a fungus-specific transcriptional factor domain, prompting us to test for homologous function and a possible role in azole resistance. Complementation of a Δyhr178w (Δstb5) mutant with CAGL0I02552g resolved the increased sensitivity to cold, hydrogen peroxide, and caffeine of the mutant, for which reason we designated CAGl0I02552g CgSTB5. Overexpression of CgSTB5 in C. glabrata repressed azole resistance, whereas deletion of CgSTB5 caused a modest increase in resistance. Expression analysis found that CgSTB5 shares many transcriptional targets with CgPDR1 but, unlike the latter, is a negative regulator of pleiotropic drug resistance, including the ABC transporter genes CDR1, PDH1, and YOR1.

Pneumothorax, an underappreciated complication with an airway exchange catheter.

While airway exchange catheters (AEC) are designed to safely maintain a secure airway and sometimes allow for ventilation while exchanging an endotracheal tube or performing a trial tracheal extubation, their use is sometimes associated with devastating complications. Pneumothorax is an underappreciated complication with AECs that can occur even in the absence of high pressure ventilation with quick clinical deterioration. The development of a pneumothorax can be difficult to distinguish from other potential causes of clinical deterioration and the clinician should maintain a high level of suspicion for quick diagnosis and treatment. Here we report a case of tension pneumothorax leading to cardiovascular collapse that occurred very suddenly with the introduction of an AEC. This pneumothorax presented in an atypical manner by all monitors available except for blood pressure monitoring. Therefore this case highlights the need for strong clinical suspicion of pneumothorax with the use of AECs.

A comparison of hand- and foot-activated surgical tools in simulated ophthalmic surgery.

OBJECTIVE: To compare the performance characteristics of hand-activated surgical tools with those of foot-activated surgical tools using a virtual-reality simulator of intraocular surgery. DESIGN: Prospective, unmasked, interventional cohort study. PARTICIPANTS: Eighteen ophthalmology residents at the University of Toronto. METHODS: The EYESi ophthalmic surgery simulator was used for the study. The surgical tool evaluated was a simulation of intraocular forceps activated by either a handpiece or a foot pedal. Each resident completed 2 modules-a dexterity module and a capsulorrhexis/cataract module. Each module was completed 4 times, alternating between the hand-activated forceps and the foot-activated forceps. An overall score was calculated for each task on the basis of the efficiency and accuracy of completion of the task, with 100 representing a perfect score. Overall scores were compared between hand and foot control for both modules. RESULTS: For the dexterity module, there was no significant difference in the overall scores between the 2 groups (91 ± 6 and 93 ± 6 for the foot- and hand-activated forceps groups, respectively; p > 0.05, t test). For the capsulorrhexis module, overall scores were also similar for both groups, the scores being 50 ± 21 and 53 ± 16 for the foot- and hand-activated forceps groups, respectively (p > 0.05, t test). An exit survey of the study's participants revealed that subjects did not have a preference for the hand or foot modality of the forceps tool, with 10 preferring the hand-activated forceps tool and 8 preferring the foot-activated tool. CONCLUSIONS: During simulated intraocular surgery, foot- and hand-activated surgical tools appear to have similar performance characteristics and are equally well received by residents.