Outcomes of Scleral Buckling After Failed Pneumatic Retinopexy.

Purpose: To assess the visual and anatomic outcomes of eyes that had secondary scleral buckle (SB) surgery after unsuccessful pneumatic retinopexy (PR) for rhegmatogenous retinal detachment (RRD). Methods: A retrospective study, performed over a 12-year period, comprised patients who had secondary SB procedures after failed primary PR. Clinical parameters (eg, best-corrected visual acuity [BCVA], lens status, macula status, details of RRD and subretinal fluid) were assessed at presentation, before additional procedures, and at follow-up (6 months, 1 year, and last visit). Statistical comparisons were made using Brown-Forsythe and Welch analysis-of-variance tests, with significance levels set at P < .05. Results: Fifty-four eyes with adequate follow-up were included. Forty-four (81.5%) of 54 eyes had successful retinal reattachment with secondary SB alone. The remaining eyes had subsequent pars plana vitrectomy (PPV). Patients presenting with macula-on RRD who had successful secondary SB had no statistically significant change in BCVA from baseline (mean final, 0.23 ± 0.25 logMAR [Snellen 20/34]; P = .999). There was a statistically significant improvement in BCVA in patients presenting with macula-off RRD who had successful secondary SB (mean final, 0.32 ± 0.36 logMAR [20/42]; P < .001 and mean change, -1.06 ± 0.85 logMAR). Ten patients presenting with macula-off RRD who had failed secondary SB had a significant improvement in the final BCVA (mean final, 0.22 ± 0.28 logMAR [20/33]; P = .044), despite the need for an additional PPV to achieve reattachment. Conclusions: Secondary SB remains a good option for RRD repair after unsuccessful PR and may avoid the need for PPV.

Risk of ocular adverse events with aromatase inhibitors.

PURPOSE: Aromatase inhibitors (AIs) are a class of medications used for adjuvant treatment of breast cancer. Recent case reports suggest that AIs may be associated with various ocular adverse events (AEs). This study evaluates the risk of ocular AEs in patients who take AIs. METHOD: Disproportionality analysis was performed using data from the U.S. Food and Drug Administration's Adverse Events Reporting System database from 2004 to 2022. All cases of vitreomacular traction, macular edema, retinal deposits, retinal artery occlusion, macular hole, retinal hemorrhage, uveitis, retinal tear, retinal detachment, dry eye disease, blepharitis, and optic neuropathy were searched for the 3 AIs anastrozole, letrozole, and exemestane. A search also was performed on trastuzumab as a control. Reported odds ratios (RORs) and corresponding 95% CIs were computed. RESULTS: We identified 322 ocular AEs of interest for the 3 AIs and 55 for trastuzumab. Anastrozole had the most AEs (n = 163) and was found to have strong associations with vitreomacular traction (ROR = 665; 95% CI, 352-1255), macular edema (ROR = 37; 95% CI, 25-54), retinal deposits (ROR = 11; 95% CI, 2-77), and uveitis (ROR = 6; 95% CI, 4-9). Letrozole had strong associations with retinal deposits (ROR = 8, 95% CI, 1-57) and retinal artery occlusion (ROR = 6; 95% CI, 3-11). Exemestane had a strong association with macular holes (ROR = 10; 95% CI, 3-30). CONCLUSION: Disproportionality analysis revealed an increased risk of ocular AEs with each of the AIs. This study calls for clinicians, especially oncologists and ophthalmologists, to be vigilant in patients who are on AI therapy, allowing them to provide prompt interventions to mitigate further ocular morbidities.

Assessing the feasibility, acceptability, and fidelity of a tele-retinopathy-based intervention to encourage greater attendance to diabetic retinopathy screening in immigrants living with diabetes from China and African-Caribbean countries in Ottawa, Canada: a protocol.

BACKGROUND: Diabetic retinopathy is a leading cause of preventable blindness in Canada. Clinical guidelines recommend annual diabetic retinopathy screening for people living with diabetes to reduce the risk and progression of vision loss. However, many Canadians with diabetes do not attend screening. Screening rates are even lower in immigrants to Canada including people from China, Africa, and the Caribbean, and these groups are also at higher risk of developing diabetes complications. We aim to assess the feasibility, acceptability, and fidelity of a co-developed, linguistically and culturally tailored tele-retinopathy screening intervention for Mandarin-speaking immigrants from China and French-speaking immigrants from African-Caribbean countries living with diabetes in Ottawa, Canada, and identify how many from each population group attend screening during the pilot period. METHODS: We will work with our health system and patient partners to conduct a 6-month feasibility pilot of a tele-retinopathy screening intervention in a Community Health Centre in Ottawa. We anticipate recruiting 50-150 patients and 5-10 health care providers involved in delivering the intervention for the pilot. Acceptability will be assessed via a Theoretical Framework of Acceptability-informed survey with patients and health care providers. To assess feasibility, we will use a Theoretical Domains Framework-informed interview guide and to assess fidelity, and we will use a survey informed by the National Institutes of Health framework from the perspective of health care providers. We will also collect patient demographics (i.e., age, gender, ethnicity, health insurance status, and immigration information), screening outcomes (i.e., patients with retinopathy identified, patients requiring specialist care), patient costs, and other intervention-related variables such as preferred language. Survey data will be descriptively analyzed and qualitative data will undergo content analysis. DISCUSSION: This feasibility pilot study will capture how many people living with diabetes from each group attend the diabetic retinopathy screening, costs, and implementation processes for the tele-retinopathy screening intervention. The study will indicate the practicability and suitability of the intervention in increasing screening attendance in the target population groups. The study results will inform a patient-randomized trial, provide evidence to conduct an economic evaluation of the intervention, and optimize the community-based intervention.

Learning from small data: Classifying sex from retinal images via deep learning.

Deep learning (DL) techniques have seen tremendous interest in medical imaging, particularly in the use of convolutional neural networks (CNNs) for the development of automated diagnostic tools. The facility of its non-invasive acquisition makes retinal fundus imaging particularly amenable to such automated approaches. Recent work in the analysis of fundus images using CNNs relies on access to massive datasets for training and validation, composed of hundreds of thousands of images. However, data residency and data privacy restrictions stymie the applicability of this approach in medical settings where patient confidentiality is a mandate. Here, we showcase results for the performance of DL on small datasets to classify patient sex from fundus images-a trait thought not to be present or quantifiable in fundus images until recently. Specifically, we fine-tune a Resnet-152 model whose last layer has been modified to a fully-connected layer for binary classification. We carried out several experiments to assess performance in the small dataset context using one private (DOVS) and one public (ODIR) data source. Our models, developed using approximately 2500 fundus images, achieved test AUC scores of up to 0.72 (95% CI: [0.67, 0.77]). This corresponds to a mere 25% decrease in performance despite a nearly 1000-fold decrease in the dataset size compared to prior results in the literature. Our results show that binary classification, even with a hard task such as sex categorization from retinal fundus images, is possible with very small datasets. Our domain adaptation results show that models trained with one distribution of images may generalize well to an independent external source, as in the case of models trained on DOVS and tested on ODIR. Our results also show that eliminating poor quality images may hamper training of the CNN due to reducing the already small dataset size even further. Nevertheless, using high quality images may be an important factor as evidenced by superior generalizability of results in the domain adaptation experiments. Finally, our work shows that ensembling is an important tool in maximizing performance of deep CNNs in the context of small development datasets.

The co-development of a linguistic and culturally tailored tele-retinopathy screening intervention for immigrants living with diabetes from China and African-Caribbean countries in Ottawa, Canada.

BACKGROUND: Diabetic retinopathy is a sight-threatening ocular complication of diabetes. Screening is an effective way to reduce severe complications, but screening attendance rates are often low, particularly for newcomers and immigrants to Canada and people from cultural and linguistic minority groups. Building on previous work, in partnership with patient and health system stakeholders, we co-developed a linguistically and culturally tailored tele-retinopathy screening intervention for people living with diabetes who recently immigrated to Canada from either China or African-Caribbean countries. METHODS: Following an environmental scan of diabetes eye care pathways in Ottawa, we conducted co-development workshops using a nominal group technique to create and prioritize personas of individuals requiring screening and identify barriers to screening that each persona may face. Next, we used the Theoretical Domains Framework to categorize the barriers/enablers and then mapped these categories to potential evidence-informed behaviour change techniques. Finally with these techniques in mind, participants prioritized strategies and channels of delivery, developed intervention content, and clarified actions required by different actors to overcome anticipated intervention delivery barriers. RESULTS: We carried out iterative co-development workshops with Mandarin and French-speaking individuals living with diabetes (i.e., patients in the community) who immigrated to Canada from China and African-Caribbean countries (n = 13), patient partners (n = 7), and health system partners (n = 6) recruited from community health centres in Ottawa. Patients in the community co-development workshops were conducted in Mandarin or French. Together, we prioritized five barriers to attending diabetic retinopathy screening: language (TDF Domains: skills, social influences), retinopathy familiarity (knowledge, beliefs about consequences), physician barriers regarding communication for screening (social influences), lack of publicity about screening (knowledge, environmental context and resources), and fitting screening around other activities (environmental context and resources). The resulting intervention included the following behaviour change techniques to address prioritized local barriers: information about health consequence, providing instructions on how to attend screening, prompts/cues, adding objects to the environment, social support, and restructuring the social environment. Operationalized delivery channels incorporated language support, pre-booking screening and sending reminders, social support via social media and community champions, and providing using flyers and videos as delivery channels. CONCLUSION: Working with intervention users and stakeholders, we co-developed a culturally and linguistically relevant tele-retinopathy intervention to address barriers to attending diabetic retinopathy screening and increase uptake among two under-served groups.

Risk of Ocular Adverse Events With Taxane-Based Chemotherapy.

Importance: Taxane-based chemotherapy agents, such as docetaxel and paclitaxel, are used for treating a wide range of cancers. Although much has been published on adverse events related to taxanes, data on ocular outcomes with these very important drugs are scant. Objective: To quantify the risk of 3 mutually exclusive ocular adverse events of epiphora, cystoid macular edema (CME), and optic neuropathy with taxane-based chemotherapy agents by undertaking a large pharmacoepidemiologic study. Design, Setting, and Participants: This retrospective cohort study design used a private health-claims database from the US that captures health information of more than 150 million enrollees. The study team created a cohort of new users of women with cancer who were taking taxane-based chemotherapy (docetaxel or paclitaxel) and new users of tamoxifen as controls. Study members were observed to the first incidence of each of the 3 mutually exclusive outcomes. An analysis of taxane-only users was also undertaken. Exposure: Tamoxifen (unexposed) and taxanes (ie, paclitaxel and docetaxel) as the exposed. Main Outcomes and Measures: First diagnosis of (1) epiphora, (2) cystoid macular edema (CME), or (3) optic neuropathy ascertained using International Statistical Classification of Diseases and Related Health Problems, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. Results: Among the 18 219 users in the epiphora analysis and optic neuropathy analysis, there were 1824 taxane users (paclitaxel and docetaxel) (age, mean [SD], 62.1 [12.7] years) and 16 395 tamoxifen users (age, mean [SD], 54.6 [12.8] years), respectively. The crude hazard ratio (HR) for epiphora was 5.55 (95% CI, 2.99-10.29) and adjusted HR was 5.15 (95% CI, 2.79-9.54). For optic neuropathy, the crude HR was 4.43 (95% CI, 1.10-17.82) and the adjusted HR was 4.44 (95% CI, 1.04-18.87). Among the 18 433 users in the CME analysis, there were 1909 taxane users (paclitaxel and docetaxel) (age, mean [SD], 62.5 years) and 16 524 tamoxifen users (age, mean [SD], 54.6 years). The crude HR for CME comparing taxane users with tamoxifen users was 1.37 (95% CI, 0.72-2.60) and adjusted HR was 1.33 (95% CI, 0.70-2.53). The HRs for epiphora and CME in the taxane cohort during the time of exposure compared with the period prior to use of the drugs were 2.86 (95% CI, 1.11-7.39) and 2.27 (95% CI, 0.68-7.54), respectively. Conclusions and Relevance: In a cohort of women who were using taxane chemotherapy agents, there was an association with elevated risk for epiphora, CME, and optic neuropathy. Ophthalmologists and oncologists should be aware of these adverse events in women with breast cancer who receive these drugs.

Risk of Ocular Adverse Events Associated With Use of Phosphodiesterase 5 Inhibitors in Men in the US.

Importance: A number of case reports and small epidemiologic studies have quantified the risk of ocular adverse events associated with the use of phosphodiesterase type 5 inhibitors (PDE5Is). However, results have been conflicting, and epidemiologic data on the risk of serous retinal detachment (SRD) and retinal vascular occlusion (RVO) are not available. Objective: To quantify the risk of SRD, RVO, and ischemic optic neuropathy (ION) associated with the use of PDE5Is. Design, Setting, and Participants: This cohort study with a nested case-control analysis was performed using data obtained from the PharMetrics Plus database (IQVIA) from January 1, 2006, to December 31, 2020. Cohort members were followed up until the first diagnosis of SRD, RVO, or ION or termination of insurance coverage. For each case, 4 controls were matched by age and time of study entry using density-based sampling. Risk for regular users of PDE5Is was compared with that for nonusers, adjusting for potential confounding variables. Cases with diagnoses of SRD, RVO, and ION in the year before the cohort were excluded. Main Outcomes and Measures: First diagnosis of SRD, RVO, or ION identified by International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Adjusted incidence rate ratios (IRRs) with 95% CIs were calculated using conditional logistic regression, controlling for hypertension, coronary artery disease, smoking, and diabetes (for all 3 outcomes) as well as sleep apnea for the ION outcome. Results: The cohort consisted of 213 033 men receiving PDE5Is, including sildenafil, tadalafil, vardenafil, and avanafil. The case-control analysis included a total of 1146 cases of SRD (278), RVO (628), and ION (240) and 4584 controls, and the mean (SD) age in both groups was 64.6 (13.3) years. Patients with SRD, RVO, and ION were more likely to have hypertension, diabetes, coronary artery disease, and sleep apnea. The adjusted IRR for the composite end points of any of the 3 outcomes was 1.85 (95% CI, 1.41-2.42; incidence, 15.5 cases per 10 000 person-years). The adjusted IRR for SRD, RVO, and ION as individual outcomes was 2.58 (95% CI, 1.55-4.30; incidence, 3.8 cases per 10 000 person-years), 1.44 (95% CI, 0.98-2.12; incidence, 8.5 cases per 10 000 person-years), and 2.02 (95% CI, 1.14-3.58; incidence, 3.2 cases per 10 000 person-years), respectively. Conclusions and Relevance: Findings of this cohort study suggest that regular users of PDE5Is might have an increased risk for SRD, RVO, and ION. Regular users of PDE5Is need to be cognizant of ocular adverse events associated with these drugs and alert their physicians if they experience any visual deficits.

Risk of maculopathy with pentosan polysulfate sodium use.

AIMS: Recent epidemiologic studies have examined the risk of maculopathy with pentosan polysulfate sodium (PPS), a drug indicated for the treatment of interstitial cystitis. However, results have been contradictory. Thus, we quantified the risk of maculopathy with PPS with a focus on risk with duration of use. METHODS: We used a new user, retrospective cohort study with an active comparator. We created a cohort of mutually exclusive 6221 PPS users and 89 744 amitriptyline users, a tricyclic antidepressant also used for the treatment of pain secondary to interstitial cystitis. Subjects were selected from the PharMetrics Plus database (IQVIA, Durham, NC) from 2006 to 2020. Cohort members were followed to the first event of the study outcome (maculopathy) or end of enrolment. A Cox regression model was constructed to adjust for potential confounders. RESULTS: The mean follow-up was 3.0 years for PPS users and amitriptyline users. The adjusted hazard ratio (HR) for maculopathy in PPS users was 2.64 (95% confidence interval [CI]: 1.90-3.68). The HR for the sensitivity analysis that combined maculopathy and age-related macular degeneration (AMD) was 1.38 (95% CI: 1.16-1.65). A cumulative duration-response pattern was observed, with use greater than 3 years having a 9.5-fold risk of maculopathy (HR = 9.56, 95% CI: 3.60-25.37) compared to a 2.3-fold risk of maculopathy with use for 1 year or less (HR = 2.27, 95% CI: 1.50-3.43). The number needed to harm for the first 4 years of use was 250. CONCLUSIONS: The results of this study suggest an increased risk of maculopathy with PPS use, particularly with longer duration of use.

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.

The effect of stiffened diabetic red blood cells on wall shear stress in a reconstructed 3D microaneurysm.

Blood flow within the vasculature of the retina has been found to influence the progression of diabetic retinopathy. In this research cell resolved blood flow simulations are used to study the pulsatile flow of whole blood through a segmented retinal microaneurysm. Images were collected using adaptive optics optical coherence tomography of the retina of a patient with diabetic retinopathy, and a sidewall (sacciform) microaneurysm was segmented from the volumetric data. The original microaneurysm neck width was varied to produce two additional aneurysm geometries in order to probe the influence of neck width on the transport of red blood cells and platelets into the aneurysm. Red blood cell membrane stiffness was also increased to resolve the impact of rigid red blood cells, as a result of diabetes, in blood flow. Wall shear stress and wall shear stress gradients were calculated throughout the aneurysm domains, and the quantification of the influence of the red blood cells is presented. Average wall shear stress and wall shear stress gradients increased due to the increase of red blood cell membrane stiffness. Stiffened red blood cells were also found to induce higher local wall shear stress and wall shear stress gradients as they passed through the leading and draining parental vessels. Stiffened red blood cells were found to penetrate the aneurysm sac more than healthy red blood cells, as well as decreasing the margination of platelets to the vessel walls of the parental vessel, which caused a decrease in platelet penetration into the aneurysm sac.

A review of robotic surgical training: establishing a curriculum and credentialing process in ophthalmology.

Ophthalmic surgery requires a highly dexterous and precise surgical approach to work within the small confines of the eye, and the use of robotics offers numerous potential advantages to current surgical techniques. However, there is a lag in the development of a comprehensive training and credentialing system for robotic eye surgery, and certification of robotic skills proficiency relies heavily on industry leadership. We conducted a literature review on the curricular elements of established robotics training programs as well as privileging guidelines from various institutions to outline key components in training and credentialing robotic surgeons for ophthalmic surgeries. Based on our literature review and informal discussions between the authors and other robotic ophthalmic experts, we recommend that the overall training framework for robotic ophthalmic trainees proceeds in a stepwise, competency-based manner from didactic learning, to simulation exercises, to finally operative experiences. Nontechnical skills such as device troubleshooting and interprofessional teamwork should also be formally taught and evaluated. In addition, we have developed an assessment tool based on validated global rating scales for surgical skills that may be used to monitor the progress of trainees. Finally, we propose a graduating model for granting privileges to robotic surgeons. Further work will need to be undertaken to assess the feasibility, efficacy and integrity of the training curriculum and credentialing practices for robotic ophthalmic surgery.

Ensemble Deep Learning for Diabetic Retinopathy Detection Using Optical Coherence Tomography Angiography.

Purpose: To evaluate the role of ensemble learning techniques with deep learning in classifying diabetic retinopathy (DR) in optical coherence tomography angiography (OCTA) images and their corresponding co-registered structural images. Methods: A total of 463 volumes from 380 eyes were acquired using the 3 × 3-mm OCTA protocol on the Zeiss Plex Elite system. Enface images of the superficial and deep capillary plexus were exported from both the optical coherence tomography and OCTA data. Component neural networks were constructed using single data-types and fine-tuned using VGG19, ResNet50, and DenseNet architectures pretrained on ImageNet weights. These networks were then ensembled using majority soft voting and stacking techniques. Results were compared with a classifier using manually engineered features. Class activation maps (CAMs) were created using the original CAM algorithm and Grad-CAM. Results: The networks trained with the VGG19 architecture outperformed the networks trained on deeper architectures. Ensemble networks constructed using the four fine-tuned VGG19 architectures achieved accuracies of 0.92 and 0.90 for the majority soft voting and stacking methods respectively. Both ensemble methods outperformed the highest single data-type network and the network trained on hand-crafted features. Grad-CAM was shown to more accurately highlight areas of disease. Conclusions: Ensemble learning increases the predictive accuracy of CNNs for classifying referable DR on OCTA datasets. Translational Relevance: Because the diagnostic accuracy of OCTA images is shown to be greater than the manually extracted features currently used in the literature, the proposed methods may be beneficial toward developing clinically valuable solutions for DR diagnoses.

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.

Application of optical coherence tomography angiography in diabetic retinopathy: a comprehensive review.

Optical coherence tomography angiography (OCTA) is a noninvasive method that enables visualization of blood flow within retinal vessels down to the size of capillaries by detecting motion contrast from moving blood cells. OCTA provides a fast and safe procedure to assess retinal microvasculature with higher contrast and resolution than conventional fluorescence angiography. The different capillary plexuses are displayed separately and their perfusion density can be quantified. Imaging capabilities such as these have led to an emerging field of clinical application for OCTA in vascular diseases such as diabetic retinopathy (DR). Evaluation of parameters such as parafoveal capillary perfusion density could be a biomarker for disease diagnosis and progression. Typical microvascular changes in DR such as capillary nonperfusion, microaneurysms, intraretinal microvascular abnormalities, and neovascularization can be reliably detected in optical coherence tomography angiograms, characterized in detail and attributed to the different capillary plexuses. Monitoring of these lesions in vivo gives potential novel insight into the pathophysiology in DR. The aim of this article is to summarize the potential applications/utility of OCTA in DR reported in the literature.

Ozurdex for refractory macular edema secondary to diabetes, vein occlusion, uveitis and pseudophakia.

OBJECTIVE: To analyze the functional and morphological effects of the intravitreal dexamethasone implant (Ozurdex, Allergan) on patients with macular edema secondary to retinal vein occlusion (RVO), diabetic retinopathy (DME), posterior noninfectious uveitis (NIU), or pseudophakic Irvine-Gass syndrome (IGS). METHODS: 144 charts were retrospectively reviewed; 100 eyes met inclusion criteria for analysis: at least one intravitreal dexamethasone implant injection, refractory to antivascular endothelial growth factor, and had ≥6 months of follow-up postinsertion. The primary outcome was the efficacy of the dexamethasone implant in reducing macular edema as measured by reduction in central retinal thickness (CRT). Secondary outcomes included visual acuity (VA), duration of treatment efficacy (measured by time to next treatment), and safety. The Wilcoxon signed-rank test was used to compare values from baseline, and Kaplan-Meier survival curves were used to analyze time to retreatment. RESULTS: There were 28 patients with RVO, 30 with DME, 24 with posterior NIU, and 18 with IGS. VA improved from baseline to month 6 in all groups, but was not statistically significant. CRT improved in all 4 groups, and was statistically significant for DME (p = 0.008) and NIU (p = 0.05). At 3 months, 34 patients (41.5%) required retreatment; by month 6, 46 patients (56.1%) required retreatment. There was a large variation between the groups in number of patients requiring intraocular pressure (IOP)-lowering medications. Two patients needed IOP-lowering surgery. One patient developed endophthalmitis. CONCLUSION: The use of intravitreal dexamethasone implants in patients with refractory retinal diseases is well tolerated and results in consistently improved anatomic outcomes, but the positive anatomic outcomes are not necessarily correlated to improvements in visual function. Patients who are treated earlier in the disease process will had better outcomes. This patient population were refractory to treatment and, therefore, have less-predictable functional outcomes.

Ocular adverse events with immune checkpoint inhibitors.

PURPOSE: To quantify the risk of ocular adverse events with immune checkpoint inhibitors (ICIs) as reported to the Food and Drug Administration (FDA). METHODS: Disproportionality analysis using data from U.S. FDA's Adverse Events Reporting System (FAERS) database 2003 to 2018. Data from pharmaceutical manufacturers, healthcare providers, consumers in the U.S., and post-marketing clinical trial reports from U.S. and non-U.S. studies. All cases of uveitis, dry eye syndrome, ocular myasthenia and eye inflammation with use of the following ICIs: atezolizumab, avelumab, cemiplimab, durvalumab, ipilimumab, nivolumab and pembrolizumab. Reported odds ratios (RORs) and corresponding 95% confidence intervals (CIs) were computed for all drugs as a group or as individual agents. RESULTS: We identified 113 ocular adverse events for all ICIs of interest including uveitis, dry eye, ocular myasthenia and eye inflammation. Nivolumab had the highest number of adverse events (N = 68) associated with use of the ICI. Nivolumab had the highest association with ocular myasthenia [ROR = 22.82, 95% CI (7.18-72.50)] followed by pembrolizumab [ROR = 20.17, 95% CI (2.80-145.20)]. Among all ICIs approved in North America, atezolizumab had the highest association with eye inflammation [ROR = 18.89, 95% CI (6.07-58.81)] and ipilmumab had the highest association with uveitis [ROR = 10.54, 95% CI (7.30-15.22)]. CONCLUSION: The results of this disproportionality analysis suggest use of ICIs is associated with an increase risk for ocular adverse reactions. Future epidemiologic studies are needed to better quantify these adverse events.

Evaluation of ophthalmology clerkships across teaching sites at the University of British Columbia.

OBJECTIVE: Clerkship at the University of British Columbia (UBC) Medical School encompasses a variety of models: traditional rotation-based clerkship; distributed rotation-based clerkship at sites across the province; and a longitudinal integrated community clerkship. The purpose of this study was to: (i) Evaluate the undergraduate ophthalmology clerkship experience at UBC to compare outcomes and experiences across the various sites and models; and (ii) Apply educational theories to evaluation outcomes in order to improve curriculum design for clerkship programs. DESIGN: Cross-sectional evaluation of the ophthalmology clerkship program at UBC. METHODS: Using a logic model, we identified inputs, activities, and outputs of the ophthalmology clerkship experience at each site at UBC. Site directors and administrators were contacted for information regarding program curriculum and delivery, and outcomes were described using written exam and clinical assessment scores as well as student and instructor feedback (questionnaires with narrative responses). RESULTS: Site directors and administrators from all clerkship sites participated in the study. Clerkship experiences across all sites (rotation-based and integrated community clerkship) were found to be unique in contexts and clinical activities. There were no significant differences noted between outcomes in the rotation-based sites. CONCLUSION: Clerkship experiences can be delivered in various contexts and through varied clinical settings, yet provide an equivalent student learning experience. As longitudinal and distributed clerkship models gain traction in medical education around the world, there are lessons for undergraduate medical education both in ophthalmology and in other areas.

One year effectiveness study of intravitreal aflibercept in neovascular age-related macular degeneration: a meta-analysis.

The current body of evidence on the efficacy and safety of aflibercept for age-related macular degeneration (AMD) is steadily growing as large clinical trials and observational studies are continually completed. Our aim was to analyse 1-year visual acuity (VA) outcomes in response to aflibercept therapy and identify factors affecting treatment response using evidence generated from a pooled analysis of current studies. A literature review of multiple electronic databases (EMBASE, MEDLINE, MedMEME) revealed 12 studies meeting inclusion and exclusion criteria for statistical analysis. Treatment posology, baseline patient characteristics, study type, sample size and 12-month change in VA were pooled in a meta-analysis with VA change as the main outcome. Data were then stratified by study design and posology in subgroup analyses. A meta-regression was conducted to regress 12-month VA change against posology, baseline VA and age. Users of aflibercept experienced an overall increase of 7.37 letters (95% confidence interval: 6.27-8.48, p heterogeneity: <0.001) in VA at 12 months of follow-up. In subgroup analyses, mean VA change was higher for randomized control trials and cohorts following regular posology (>7 injections/year) compared to observational studies and irregular posology. The meta-regression showed larger VA gains with regular posology compared to an irregular posology, and decreased effect size as age increased. This meta-analysis strongly suggests improved VA outcomes at 12 months in patients with wet AMD for 2.0 mg aflibercept, comparable to but slightly lower than landmark trials. Increased injection frequency and younger age demonstrates a trend with improved outcomes.