PREDICTIVE FACTORS OF SPONTANEOUS RELEASE OF VITREOMACULAR TRACTION: A Systematic Review and Meta-Analysis.

PURPOSE: To review predictive factors of spontaneous vitreomacular traction (VMT) release. METHODS: A systematic literature search was performed on Ovid MEDLINE, Embase, and Cochrane Library. Studies comparing spontaneously released VMT to persistent VMT were included. A meta-analysis was performed using a random effects model, and weighted mean difference, risk ratio (RR), and 95% confidence intervals (95% CI) were reported as appropriate. RESULTS: Of a search of 258 studies, 12 studies were included, from which 272 of 934 eyes (29%) underwent spontaneous release. Mean age was 70.0 years, 37.2% of patients were men, and mean follow-up was 22.0 months. Significant predictive factors for spontaneous release were smaller VMT diameter (n = 177; weighted mean difference = -212.48 µm, 95% CI = [-417.36, -7.60], P = 0.04), epiretinal membrane absence (n = 162; RR = 2.17, 95% CI = [1.18, 3.97], P = 0.01), and right eye involvement (n = 76; RR = 2.10, 95% CI = [1.14, 3.88], P = 0.02). Nonsignificant factors were age, initial best-corrected visual acuity, sex, ocular comorbidity, fellow-eye posterior vitreous detachment, previous intravitreal injection, and VMT classification with focal defined as ≤400 µm. Mean release time was 15.3 months (n = 212). Mean best-corrected visual acuity improved from 0.34 ± 0.21 (Snellen 20/44) to 0.20 ± 0.58 logMAR (Snellen 20/32) postrelease (n = 121). CONCLUSION: Smaller VMT diameter, epiretinal membrane absence, and right eye involvement may support spontaneous VMT release. If patients have tolerable symptoms, clinicians may consider observation in patients with these predictive factors.

Imaging Biomarkers and Their Impact on Therapeutic Decision-Making in the Management of Neovascular Age-Related Macular Degeneration.

These recommendations, produced by a group of Canadian retina experts, have been developed to assist both retina specialists and general ophthalmologists in the management of vision-threatening neovascular age-related macular degeneration (nAMD). The recommendations are based on published evidence as well as collective experience and expertise in routine clinical practice. We provide an update on practice principles for optimal patient care, focusing on identified imaging biomarkers, in particular retinal fluid, as well as current and emerging therapeutic approaches. Algorithms for delivering high-quality care and improving long-term patient outcomes are provided, with an emphasis on timely and appropriate treatment to preserve and maintain vision. In the context of nAMD, increasing macular fluid or leakage on fluorescein angiography (FA) may indicate disease activity regardless of its location. Early elimination of intraretinal fluid (IRF) is of particular relevance as it is a prognostic indicator of worse visual outcomes. Robust referral pathways for second opinion and peer-to-peer consultations must be in place for cases not responding to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy.

OUTCOMES OF VITRECTOMY IN TERSON SYNDROME: A Multicenter Canadian Perspective.

PURPOSE: To characterize the presentation of Terson syndrome, the occurrence of a vitreous hemorrhage in association with intracranial hemorrhage, and report on the outcomes of vitrectomy at two major centers in Canada. METHODS: Retrospective chart review of consecutive patients with Terson syndrome undergoing vitrectomy by retina specialists over the last 10 years. Primary outcome was the change in best-corrected visual acuity (BCVA) at 3 months from baseline. Secondary outcomes included the association between baseline BCVA and final BCVA, and the association between final BCVA and timing of surgery (early vs. later than 90 days). RESULTS: A total of 14 eyes of 11 patients were included. The mean time between observation of intraocular hemorrhage and vitrectomy was 160 days. Baseline preoperative BCVA was logarithm of the minimum angle of resolution 1.57 ± 1.03 (Snellen 20/740), which improved to logarithm of the minimum angle of resolution 0.53 ± 0.82 (Snellen 20/70) at the final postoperative follow-up, P = 0.01. Baseline BCVA was not significantly correlated with final BCVA, Spearman's rho = 0.016, P = 0.957. Final BCVA did not significantly differ between those who had surgery before 90 days compared with after 90 days, P = 0.087. CONCLUSION: Vitrectomy is safe and effective and should be considered for nonclearing vitreal bleeding due to Terson syndrome. Ocular hemorrhaging in Terson syndrome can be observed conservatively for spontaneous improvement without the risk of reduced visual potential. Ophthalmic evaluation should be considered promptly after intracranial hemorrhage.

A randomized, double-blind, window of opportunity trial evaluating the effects of chloroquine in breast cancer patients.

PURPOSE: Chloroquine has demonstrated anti-tumor activities through autophagy inhibition and cell cycle disruption. This study aimed to assess the effect of single-agent chloroquine on breast tumor cellular proliferation in a randomized, phase II, double-blind, placebo-controlled, pre-surgical window of opportunity trial. METHODS: Patients with newly diagnosed breast cancer were randomized 2:1 to chloroquine 500 mg daily or placebo for 2- to 6-weeks prior to their breast surgery. The primary outcome was the relative change in measures of proliferation (Ki67) in primary breast cancer cells pre- and post-treatment. Adverse events and toxicity profiles were also evaluated. RESULTS: From September 2015 to December 2016, 70 patients were randomized [46 (66%) chloroquine and 24 (34%) placebo]. Ten patients who were randomized to chloroquine withdrew from study due to adverse events. Mean duration of drug intake was 15 days (range 14-29 days). There were no significant differences between the chloroquine or placebo arms with respect to either the percentage change (- 0.4 vs. - 1.2, p = 0.088) or absolute change (- 2.0% vs. - 5.2%, p = 0.066) in Ki67 index pre- and post-drug treatment. Although adverse effects were minimal and all classified as grade 1, the effects were significant enough to cause nearly 15% of patients to discontinue therapy. CONCLUSIONS: Treatment with single-agent chloroquine 500 mg daily in the preoperative setting was not associated with any significant effects on breast cancer cellular proliferation. It was, however, associated with toxicity that may affect its broader use in oncology.

Safety and Efficacy of Adeno-Associated Viral Gene Therapy in Patients With Retinal Degeneration: A Systematic Review and Meta-Analysis.

Purpose: This systematic review evaluates the safety and efficacy of ocular gene therapy using adeno-associated virus (AAV). Methods: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched systematically for controlled or non-controlled interventional gene therapy studies using key words related to retinal diseases, gene therapy, and AAV vectors. The primary outcome measure was safety, based on ocular severe adverse events (SAEs). Secondary outcome measures evaluated efficacy of the therapy based on best corrected visual acuity (BCVA) and improvements in visual sensitivity and systemic involvement following ocular delivery. Pooling was done using a DerSimonian Laird random effects model. Risk of bias was assessed using the Cochrane Risk of Bias Tool, version 1. Results: Our search identified 3548 records. Of these, 80 publications met eligibility criteria, representing 28 registered clinical trials and 5 postmarket surveillance studies involving AAV gene therapy for Leber congenital amaurosis (LCA), choroideremia, Leber hereditary optic neuropathy (LHON), age-related macular degeneration (AMD), retinitis pigmentosa (RP), X-linked retinoschisis, and achromatopsia. Overall, AAV therapy vectors were associated with a cumulative incidence of at least one SAE of 8% (95% confidence intervals [CIs] of 5% to 12%). SAEs were often associated with the surgical procedure rather than the therapeutic vector itself. Poor or inconsistent reporting of adverse events (AEs) were a limitation for the meta-analysis. The proportion of patients with any improvement in BCVA and visual sensitivity was 41% (95% CIs of 31% to 51%) and 51% (95% CIs of 31% to 70%), respectively. Systemic immune involvement was associated with a cumulative incidence of 31% (95% CI = 21% to 42%). Conclusions: AAV gene therapy vectors appear to be safe but the surgical procedure required to deliver them is associated with some risk. The large variability in efficacy can be attributed to the small number of patients treated, the heterogeneity of the population and the variability in dosage, volume, and follow-up. Translational Relevance: This systematic review will help to inform and guide future clinical trials.

Intravenous administration of Penicillin results in therapeutic intravitreal levels in chronic postoperative endophthalmitis.

IMPORTANCE: The role of systemic antibiotics in the treatment of bacterial endophthalmitis remains controversial. While penicillin is a highly effective antibiotic against bacteria that frequently cause endophthalmitis, the ability of systemically administered Penicillin G to penetrate into the vitreous at adequate therapeutic concentrations has not been studied. Its role in the treatment of endophthalmitis, particularly for bacteria for which it is the antibiotic of choice, therefore remains unknown. OBJECTIVE: We sought to determine whether intravenous administration of Penicillin G leads to adequate therapeutic concentrations in the vitreous for the treatment of bacterial endophthalmitis. DESIGN AND SETTING: This study was conducted in an ambulatory setting, at the Ottawa Hospital Eye Institute, a university-affiliated tertiary care center, where a 77-year old gentleman with chronic post-cataract surgery Actinomyces neuii endophathalmitis was treated with intravenous Penicillin G (4 × 106 units every 4 h) and intravitreal ampicillin (5000µg/0.1 m1). MAIN OUTCOMES AND MEASURES: Intravitreal concentration of Penicillin G and ampicillin were obtained at the time of intraocular lens removal, measured by high-performance liquid chromatography. RESULTS: The intravitreal concentration of penicillin and ampicillin was 3.5µg/ml and 0.3µg/ml, respectively. Both the concentration of penicillin and ampicillin were within the level of detection of their respective assays (penicillin 0.06-5µg/ml, ampicillin 0.12-2.5µg/ml). CONCLUSION AND RELEVANCE: This study shows that intravenous Penicillin G administered every four-hours allows for adequate intravitreal concentrations of penicillin. Future studies are required to determine if the results of this study translate into improved clinical outcomes.

Effects of Internal Limiting Membrane Peel for Idiopathic Epiretinal Membrane Surgery: A Systematic Review of Randomized Controlled Trials.

PURPOSE: The purpose of this study was to compare functional and anatomical outcomes after epiretinal membrane (ERM) peeling with internal limiting membrane (ERM/ILM) peeling and without for the treatment of idiopathic ERM. DESIGN: Systematic review and meta-analysis. METHODS: A comprehensive search of Cochrane CENTRAL, MEDLINE Ovid, and Embase Ovid for randomized controlled trials comparing ERM/ILM with ERM was performed. Two independent reviewers selected papers and extracted data. Methodological quality was assessed using the Cochrane Risk of Bias (RobVis) tool. Data was analyzed using RevMan 5.3. Quality of body of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Seven studies reporting 387 eyes overall were included. A total of 207 eyes (53%) received ERM/ILM. A total of 180 (47%) received ERM. Post-operative visual acuities (logMAR) were not significantly different between ERM/ILM and ERM, with a mean difference (MD) of 0.02 (95% confidence interval [CI]: -0.04 to 0.09; P = .45; I2= 42%; n = 101) at 1 month; 0.03 (95% CI: -0.01 to 0.06; P = .11, I2 = 15%; n = 299; High Certainty of Evidence) at 3 months; 0.01 (95% CI: -0.03 to 0.04; P = .72; I2 = 21%; n = 317; High Certainty of Evidence) at 6 months; and 0.01 (95% CI: -0.02 to 0.04; P = .49; I2 = 39%; n = 234) at 12 months post-operatively. ERM/ILM was significantly associated with lower ERM recurrence at 6-12 months with a relative risk of 0.16 (95% CI: 0.04-0.64; P = .01; I2 = 0%; n = 155; Moderate certainty of evidence) and an increased central macular thickness (micrometers) at 12 months with an MD of 20.53 (95% CI: 4.96-36.09; P = .01; I2 = 12%; n = 234). CONCLUSIONS: ERM/ILM and ERM result in similar visual acuity despite subtle differences in anatomical outcomes (central macular thickness). ERM/ILM is associated with a significantly lower rate of ERM recurrence at 6-12 months post-operatively and should be considered where recurrence prevention is the treatment priority.

Identifying gaps in patient access to diabetic screening eye examinations in Ontario: a provincially representative cross-sectional study.

OBJECTIVE: Diabetes is the leading cause of acquired blindness in Canadians under the age of 50 years, and diabetic retinopathy affects an estimated 500 000 Canadians. Early identification of retinopathy with screening eye examinations allows for secondary prevention. To understand the need for resource allotment in diabetic screening, we undertook a cross-sectional study of key demographics and geographics of screened and unscreened patients in Ontario. METHODS: Ontario Health Insurance Plan (OHIP) records were derived from physician and optometry billing, matched with patients aged >19 years with prevalent diabetes between 2011 and 2013. Data were cross-correlated with demographic covariates, including age, sex, income quintile, immigrant status, as well as geographic covariates such as rurality and patient Local Health Integration Network (LHIN). RESULTS: Of almost 1 146 000 patients included in the analysis, approximately 406 000 were unscreened. Of note, this included 234 000 adults aged 40-64 years. Approximately 818 000 patients with diabetes lived in large cities, and 301 000 (37%) were unscreened. When the City of Toronto was analyzed as an urban area with the highest density of unscreened prevalence, autocorrelation between the percentage of eye examinations among patients with diabetes aged >40 years and low-income revealed that large areas of Toronto Central correlated for low examination rates and low income. The majority (13/22) of Community Health Centres are present in these areas. CONCLUSIONS: Large cross-sectional population statistics for diabetes prevalence and ophthalmic examinations provides a geographic and socioeconomic profile for populations of middle-aged adults in large urban areas at risk for developing diabetic retinopathy and who might benefit from interventions to improve the rates of screening eye examinations.

Trends in Canadian ophthalmology residency match outcomes.

BACKGROUND: To date, there exists no formal assessment of the competitiveness of the residency match for Canadian ophthalmology programs. The primary objective of this study was to use Canadian Resident Matching Service (CaRMS) data to describe trends in the number of positions, number of applicants and level of competition for the Canadian ophthalmology match. METHODS: The number of positions and the number of applicants for each ophthalmology program were received from CaRMS for each cycle of the match from 2006-2017. The level of competition was calculated by dividing total number of applicants by the total number of positions in any given year. RESULTS: The level of competition was consistently high with a median number of 2.0 applicants per anglophone Canadian Medical Graduate (CMG) position, 2.6 applicants per francophone CMG position and 32.5 applicants per International Medical Graduate (IMG) position. Over the study period, the level of competition decreased for francophone CMG and IMG positions and did not change for anglophone CMG positions. CONCLUSION: Consistently there are a greater number of applicants than positions for Canadian ophthalmology residency programs and therefore CMG applicants should be encouraged to apply to more than one discipline. The trends in the number of residency positions can be used to update supply projections for ophthalmologists and guide human resource planning.

CONTEXTE: À ce jour, il n'existe aucune évaluation officielle de la compétitivité du jumelage des résidents pour les programmes canadiens d'ophtalmologie. L'objectif principal de cette étude était d'utiliser les données du Service canadien de jumelage des résidents (CaRMS) pour décrire les tendances dans le nombre de postes, le nombre de candidats et le niveau de compétitivité pour le jumelage canadien en ophtalmologie. MÉTHODES: Le nombre de postes et le nombre de candidats pour chaque programme d'ophtalmologie ont été reçus du CaRMS pour chaque cycle du jumelage de 2006 à 2017. Le niveau de compétitivité a été calculé en divisant le nombre total de candidats par le nombre total de postes pour chaque année. RÉSULTATS: Le niveau de compétitivité était constamment élevé avec un nombre médian de 2,0 candidats par poste pour les diplômés canadiens en médecine (DCM) anglophones, 2,6 candidats par poste pour les DCM francophones et 32,5 candidats par poste pour les dipl00F4més internationaux en médecine (DIM). Au cours de la période de l'étude, le niveau de compétitivité a diminué pour les postes pour les DCM et DIM francophones et est demeuré inchangé pour les postes pour les DCM anglophones. CONCLUSIONS: On retrouve constamment un plus grand nombre de candidats que de postes pour les programmes canadiens de résidence en ophtalmologie et, par conséquent, les candidats DCM doivent être encouragés à postuler dans plus d'une discipline. Les tendances dans le nombre de postes de résidence peuvent être utilisées pour mettre à jour les prévisions de postes pour les ophtalmologistes et guider la planification des ressources humaines.

Unsuspected and misdiagnosed posterior uveal melanoma following enucleation and evisceration in Ottawa-Gatineau.

OBJECTIVE: There is a gap in the recent literature on the topic of clinically misdiagnosed and unsuspected posterior uveal melanomas (PUM) with a calculation of the frequency of these events for a specific geographical area. As the only ophthalmic pathology laboratory in our region, we determined the rate of these outcomes over a 16-year period. METHODS: We retrospectively reviewed 2558 consecutive ophthalmic pathologic specimens in the Ottawa-Gatineau region, of which 334 were eviscerations and 227 were enucleations. We calculated the frequency of clinically misdiagnosed PUM and of clinically unsuspected PUM. We also determined the rate of uveal melanoma undergoing enucleation. RESULTS: From 100 diagnoses of PUM, 2 (2.0%) cases were clinically unsuspected and 2 (2.0%) cases were clinically misdiagnosed. The rate of uveal melanoma undergoing enucleation was 5.6 cases per 1 000 000 of population per annum. From 2009 to 2012, the incidence of this event was 3.8 cases per 1 000 000 per annum, which was lower than the previous three 4-year increments. CONCLUSIONS: We present the first and only single-centred, population-based data on the rates of unsuspected PUM and of clinical misdiagnosis of PUM in the era of modern diagnostic imaging. Our rate of clinical misdiagnosis is within the range of recent reports of this event. Unsuspected PUM occurred at a rate substantially lower than previously published. The incidence of uveal melanoma undergoing enucleation has decreased despite an increase in population, which reflects a shift in management from enucleation to radiation therapy.

Flashes and floaters: a survey of Canadian ophthalmology residents' practice patterns.

BACKGROUND: Residents are often the first point of contact in assessing patients who present with "flashes and floaters" in the emergency ophthalmology clinic. Most often, these symptoms are attributed to a posterior vitreous detachment (PVD), which may be associated with a retinal tear in up to 14% of cases. A proper peripheral retinal exam is, thus, imperative, and techniques other than scleral depression may not be sufficient. We conducted a cross-sectional survey of Canadian ophthalmology residents-in-training to understand the current resident practice patterns for examination of the peripheral retina. METHODS: Anonymous electronic survey of all Canadian ophthalmology residents (postgraduate years 2-5). RESULTS: On average, residents (n = 47) perform a peripheral retinal examination 5 to 7 times per day in the emergency clinic and on call. Reported techniques for assessing the peripheral retina include scleral depression with indirect ophthalmoscopy alone (45.7%), scleral depression combined with the 3-mirror (15.2%) or panretinal lens (10.9%), or each of these techniques alone (23.9% and 4.3%, respectively). The major factors deterring resident use of scleral depression include history of recent trauma (47.5%), patient discomfort (16.3%), personal discomfort (16.3%), or lack of time (13.8%). CONCLUSIONS: Although scleral depression is the recommended standard of care for assessment of flashes and floaters, residents in training may routinely use alternative techniques as a result of extrinsic and intrinsic factors.

Test characteristics of point-of-care ultrasonography for the diagnosis of acute posterior ocular pathology.

OBJECTIVES: The objective of this study was to determine the test characteristics of point-of-care ultrasonography (POCUS) for the diagnosis of retinal tear (RT), retinal detachment (RD), posterior vitreous detachment (PVD), and vitreous hemorrhage (VH). DESIGN: A prospective observation study on a convenience sample of patients presenting to a tertiary care emergency general ophthalmology clinic was performed. PARTICIPANTS: Adult patients with acute flashes/floaters or new visual field defects were included (n = 62). METHODS: POCUS was performed by a study sonographer and compared with a retina specialist examination without sonography imaging. Sonographers were masked to clinical information. Follow-up was performed by a 6-week health records review. The primary outcome was the diagnosis of RD/RT, PVD, and VH. Analyses included descriptive statistics and test characteristics. RESULTS: A total of 62 patients with a mean age of 60.8 years were enrolled; 62.9% were female. The mean time to scan required was 7.4 minutes. There was no change in diagnosis at 6 weeks. The sensitivities and specificities, respectively, are as follows: any pathology (n = 60) 88.3% (95% CI 86.8%-89.9%) and 50% (95% CI 2.7%-97.3%); RD (n = 6) 100% (95% CI 53.9%-100%) and 67.9% (95% CI 62.9%-67.9%); RD/RT (n = 23) 47.8% (95% CI 30.8%-62.2%) and 82.1% (95% CI 72.0%-90.6%); PVD (n = 47) 80.9% (95% CI 74.7%-88.0%) and 33.3% (95% CI 14.0%-55.7%); and VH (n = 14) 43.0% (95% CI 21.4%-58.0%) and 93.8% (95% CI 87.5%-98.2%). CONCLUSIONS: Ocular POCUS detected all RDs but has limited use for the diagnosis of RTs. Patients with suspected acute ocular posterior pathology should be referred to ophthalmology independent of ocular POCUS.

Controlled release of bevacizumab through nanospheres for extended treatment of age-related macular degeneration.

Bevacizumab (Avastin(®)) has been used by ophthalmologists in many countries as an off-label drug for the treatment of wet age-related macular degeneration (AMD). Due to its short half-life necessitating frequent intravitreal injection, a method for sustained delivery is in need. We demonstrated that bevacizumab could be released in a sustained fashion over 90 days from nano- and microspheres fabricated from poly(DL-lactide-co-glycolide) and poly(ethylene glycol)-b-poly(D,L-lactic acid), respectively. The drug release rate could be adjusted by alteration of the drug/polymer ratio. The use of such nano- and microspheres as bevacizumab delivery vehicles may improve the treatment of wet AMD.

Restoration of vision after surgical removal of an intraocular needlefish jaw.

PURPOSE: To describe the case of a globe-penetrating intraocular needlefish injury. METHODS: Clinicopathologic case report. RESULTS: A 38-year-old man had a globe-penetrating injury while swimming without eye protection in the Caribbean Sea. The foreign body was impaled in the nasal retina. After surgical removal, retinal repair, and subsequent cataract surgery, the best-corrected visual acuity was 20/20 in the affected eye. Histopathologic examination of the foreign body was consistent with a needlefish jaw. CONCLUSION: This is the first reported case of a successful visual outcome after the surgical removal of an intraocular needlefish jaw. Furthermore, we advise that ophthalmologists should be recommending eye protection to people swimming in waters endemic to this dangerous fish.

The novel use of bevacizumab and photodynamic therapy in the treatment of best disease.

PURPOSE: To report on the novel use of bevacizumab (Avastin) in combination with photodynamic therapy (PDT) for the treatment of Best disease with choroidal neovascularization. METHODS: A 17-year-old girl with Best disease, choroidal neovascularization, and subretinal hemorrhage in the right eye was treated with bevacizumab and PDT. RESULTS: The use of bevacizumab and PDT was associated with a change in vision from counting fingers to 20/25 and was well tolerated by the patient. CONCLUSION: The use of bevacizumab and PDT in the management of Best disease seems to be a very effective method of treatment showing improvement in visual acuity.This is the first case to be reported in the literature of bevacizumab in combination with PDT for the treatment of choroidal neovascularization in Best disease.