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OBJECTIVE High cereal fiber and low-glycemic index (GI) diets are associated with reduced cardiovascular disease (CVD) risk in cohort studies. Clinical trial evidence on event incidence is lacking. Therefore, to make trial outcomes more directly relevant to CVD, we compared the effect on carotid plaque development in diabetes of a low-GI diet versus a whole-grain wheat-fiber diet. RESEARCH DESIGN AND METHODS The study randomized 169 men and women with well-controlled type 2 diabetes to counseling on a low GI-diet or whole-grain wheat-fiber diet for 3 years. Change in carotid vessel wall volume (VWV) (prespecified primary end point) was assessed by MRI as an indication of arterial damage. RESULTS Of 169 randomized participants, 134 completed the study. No treatment differences were seen in VWV. However, on the whole-grain wheat-fiber diet, VWV increased significantly from baseline, 23 mm3 (95% CI 4, 41; P = 0.016), but not on the low-GI diet, 8 mm3 (95% CI −10, 26; P = 0.381). The low-GI diet resulted in preservation of renal function, as estimated glomerular filtration rate, compared with the reduction following the wheat-fiber diet. HbA1c was modestly reduced over the first 9 months in the intention-to-treat analysis and extended with greater compliance to 15 months in the per-protocol analysis. CONCLUSIONS Since the low-GI diet was similar to the whole-grain wheat-fiber diet recommended for cardiovascular risk reduction, the low-GI diet may also be effective for CVD risk reduction.

Keyvan Koushan,1,2 Arshia Eshtiaghi,3 Pauline Fung,2 Alan R Berger,1,2 David R Chow1,2 1Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada; 2Toronto Retina Institute, Toronto, Ontario, Canada; 3Faculty of Medicine, University of Toronto, Toronto, Ontario, CanadaCorrespondence: Keyvan Koushan, Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto Retina Institute, Toronto, Ontario, Canada, Tel +1 416 356-4355, Email keyvan.koushan@uToronto.caPurpose: To investigate the safety and efficacy of micropulse (MP) macular laser in combination with intravitreal aflibercept for the treatment of center-involved diabetic macular edema (CI-DME).Methods: A single-blind prospective randomized controlled pilot trial was performed. In total, 30 eyes of 30 patients with CI-DME and best corrected visual acuity (BCVA) between, and including, 20/30 and 20/400 were enrolled. Enrolled eyes were randomized to 2 groups. Group 1 received intravitreal aflibercept injections (IVT-AFL) with sham laser. Group 2 received IVT-AFL with MP laser. Both groups were followed every 4 weeks for 48 weeks and retreatment was performed on pro re nata basis according to preset criteria. The main outcome measure was the average number of intravitreal injections for each group at 48 weeks. Secondary outcome measures included changes in BCVA and central macular thickness (CMT) at 24 and 48 weeks.Results: The average number of intravitreal injections at 48 weeks was similar between the groups (8.5± 3.3 in Group 1 vs 7.9± 3.6 in Group 2, p=0.61). After 48 weeks, both groups demonstrated an improvement in BCVA and CMT. However, the difference in improvement between the groups was not statistically significant (p=0.18 for BCVA and p=0.57 for CMT).Conclusion: Intravitreal injections of aflibercept led to improvements in BCVA and CMT at 24 and 48 weeks. Addition of MP laser to eyes in group 2 did not offer additional benefit in reducing treatment burden or improving CMT. Eyes that received MP laser showed a numerically greater improvement in BCVA, although this was not statistically significant.Clinicaltrials.gov Identifier: NCT03143192 March 8, 2017.Keywords: anti-VEGF, diabetic macular edema, micropulse laser, visual acuity

Purpose Suboptimal functional outcomes following rhegmatogenous retinal detachment (RRD) repair may be related to photoreceptor abnormalities including alterations of the ellipsoid zone (EZ) which may not be apparent on cross-sectional optical coherence tomography (OCT). This study assessed EZ recovery using en face OCT following RRD repair and its association with visual acuity. Design Post hoc analysis of a randomized controlled trial. Methods Patients with macula-off RRD were followed at 3, 6, 12 and 24 months post-operatively and annually thereafter. En face OCT of the EZ slab were analyzed. Hyporeflective areas were co-localized with EZ abnormalities on cross-sectional OCT B-Scans and measured by two masked graders. Primary outcome was change in area of EZ hyporeflectivity from 3 to 24 months and its association with ETDRS visual acuity recovery was also assessed. Results 271 images of 61 patients were assessed. Mean area of hyporeflectivity significantly decreased from 3 to 24 months (-2.98 (95%CI,1.82-4.13) mm2, P Conclusions En face OCT provides a novel biomarker for visualizing and quantifying EZ recovery following RRD repair that is associated with ETDRS visual acuity recovery. A steady decline in the area of EZ hyporeflectivity was observed over many years with delayed recovery in patients with longer duration of macula-off.

Purpose To assess the incidence of post-operative outer retinal folds (ORFs) in pars plana vitrectomy (PPV) vs pneumatic retinopexy (PnR) following rhegmatogenous retinal detachment (RRD) repair and to determine the association of ORFs with functional outcomes at 1 year. Design Randomized controlled trial Participants Patients with primary macula-off RRD meeting PIVOT trial criteria randomly assigned to PPV vs PnR. Methods Post-hoc analysis of the PIVOT trial. Incidence and quantitative morphological features of ORFs were assessed with en face and cross-sectional OCT at 1 month post-operatively by two masked graders. ETDRS letter score and quantitative metamorphopsia were measured at 1 year. Main Outcome Measures Proportion of patients with ORFs following PPV vs PnR at 1 month post-operatively. Secondary outcomes include the association of ORFs with visual acuity (ETDRS letter score) and metamorphopsia (M-CHARTS) at 12 months post-operatively. Results Eighty-eight of the 176 participants enrolled in PIVOT were macula-off RRD. 94.3% (83/88) of these macula-off eyes had month 1 post-operative OCT scans that were gradable, 93.2% (41/44) in the PPV group and 95.5% (42/44) in the PnR group. The incidence of ORFs formation was 34.1% (14/41) in the PPV group and 14.3% (6/42) in the PnR group (p=0.034). ETDRS letter score at 1 year was 65.7±6.6 letters in patients with ORFs versus 75.1±1.4 letters in those without ORFs (difference=9.4 letters, 95% CI=7.5-11.3, p=0.047). Among patients in the PPV group only, mean ETDRS letter score at 1 year in patients with ORFs was 62.8 ± 24.7 letters compared to 75.4 ± 9.2 letters in patients without ORF formation (difference=12.6 letters, 95% CI=0.05-24.59, p=0.04). Horizontal and vertical metamorphopsia scores were similar in patients with vs without ORFs: horizontal: 0.35 ± 0.12 versus 0.29 ± 0.07 (difference=0.06, 95% CI=0.01-0.11, p=0.69) and vertical: 0.25±0.07 versus 0.29±0.07 (difference=0.04, 95%CI=0-0.08, p=0.60) respectively. There was a negative correlation between the closest distance of the ORFs from the fovea and the vertical metamorphopsia score (r=-0.507, p=0.045). Conclusions There is a greater risk of developing ORFs following PPV compared to PnR for RRD. ORFs at 1 month are associated with significantly worse ETDRS visual acuity letter score at 1 year.

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.

PURPOSE To evaluate the ectopic inner foveal layer (EIFL) staging scheme as a visual prognostic factor for patients undergoing epiretinal membrane (ERM) surgery. METHODS Retrospective study of 88 pseudophakic patients with diagnosis of idiopathic ERM who underwent ERM surgery with a minimum follow-up of 12 months. Preoperative and postoperative EIFL staging was correlated with the final best-corrected visual acuity (BCVA). As a secondary outcome, evaluation of the proportion of patients achieving final best-corrected visual acuity ≥20/40 in each stage was assessed. RESULTS Based on the EIFL staging scheme, of 88 pseudophakic eyes analyzed, 24 (27.4%) were diagnosed as Stage 2 ERM, 45 (51.1%) as Stage 3 ERM, and 19 (21.5%) as Stage 4 ERM preoperatively. At the final follow-up visit, 70.8% of eyes with Stage 2 showed an improvement in EIFL staging scheme, while 68% of eyes in Stage 3 and 4 remained the same. The final best-corrected visual acuity significantly improved with all EIFL stages (P = Stage 3 > Stage 4 P < 0.001). Final best-corrected visual acuity ≥20/40 was reached in 91.7% of eyes with Stage 2, 42.3% with Stage 3, and 5.2% with Stage 4. CONCLUSION The EIFL staging scheme is an easy, fast, and reproducible method to evaluate visual prognosis with ERM surgery. Surgery on Stage 2 ERM results in significantly better visual outcomes and a greater chance of reversibility in anatomical changes.

PurposeTo assess the incidence of persistent subfoveal fluid (PSFF) in pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV) following rhegmatogenous retinal detachment (RRD) repair and to determine its association with functional outcomes.MethodsPosthoc analysis of the PIVOT randomised trial. Eyes with gradable en face and cross-sectional spectral-domain optical coherence tomography (SD-OCT) scans at 1–2 months postoperatively were included. Primary outcome was the proportion of patients with PSFF following PnR versus PPV at 1–2 months postoperatively. Secondary outcomes included association of PSFF with Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at 3, 6 and 12 months and metamorphopsia score (MCHARTs) at 12 months.ResultsOf 176 participants enrolled in PIVOT, 158 (89.8%) had gradable SD-OCT scans. Intergrader agreement was 0.870 (Cohen’s kappa). The incidence of PSFF was 16% (13/81) following PnR and 10.4% (8/77) following PPV (p=0.298; OR=1.65, 95% CI 0.64 to 4.23). Median ETDRS score at 3 months postoperatively between eyes with and without PSFF was 71 (IQR=58–78) and 78 (IQR=70–84), respectively (difference=7 letters, p=0.037), with no significant difference at subsequent 6-month and 12-month visits. Median metamorphopsia scores in patients with versus without PSFF were: horizontal: 0.1 (IQR=0–0.3) vs 0 (IQR=0–0.2) (difference=0.1, p=0.228) and vertical: 0.25 (IQR=0–0.4) vs 0 (IQR=0–0.2) (difference=0.25, p=0.148), respectively.ConclusionsThere was no significant difference in the incidence of PSFF in eyes undergoing PnR versus PPV for RRD. The presence of PSFF at 1–2 months postoperatively was associated with worse ETDRS letter score at 3 months, but there was no difference at 1 year.Trial registration numberNCT01639209.

To determine the association of aqueous humor cytokine concentrations with long-term treatment response to anti-vascular endothelial growth factor (VEGF) agents in diabetic macular edema (DME).Retrospective case series.Pooled data of aqueous humor cytokine concentrations collected at baseline and 2-month follow-up (2 injections) for treatment-naïve eyes with center-involving DME previously enrolled in a prospective study were reviewed. Subjects receiving intravitreal anti-VEGF injections outside of study protocol as per standard of care were classified into Responders versus Nonresponders based on qualitative assessment of optical coherence tomography for persistence of DME at longitudinal follow-up visits.Of the 41 eyes, 85% were classified as Responders with a significant decline in baseline central subfield thickness and macular volume (P values.001), and 15% were identified as Nonresponders to anti-VEGF therapy over 51.4 ± 18.7 months of follow-up. No significant difference in baseline aqueous humor VEGF concentration was noted, while at the 2-month follow-up the Nonresponder group had a significantly higher VEGF concentration compared with the Responder group (451.5 ± 690.9 pg/mL vs 113.7 ± 211.4 pg/mL; P = .02). The Responder group also demonstrated a significant decline from baseline to 2-month follow-up in concentration of intercellular adhesion molecule-1 (P.001), interleukin-10 (P = .041), monocyte chemotactic protein-1 (P = .046), placental growth factor (P = .027), and transforming growth factor-β2 (P = .017).Aqueous humor cytokine concentrations serve as an early biomarker for long-term response to anti-VEGF therapy and may enable more effective treatment regimens that improve anatomical outcomes in eyes with DME.

Purpose: This study assesses the frequency of projection artifacts in optical coherence tomography angiography (OCTA) en face images and compares images before and after applying a 3-dimensional projection artifact removal (3D-PAR) algorithm. Methods: This is a single-center, retrospective study that included consecutive patients with any underlying diagnosis who had OCTA obtained from January to March 2017. Patients with various retinal diseases and also healthy eyes were included. All participants underwent imaging with a scan area of 3 mm × 3 mm. The 4 default en face slabs were analyzed: superficial capillary plexus (SCP), deep capillary plexus (DCP), outer retina (OR), and choriocapillaris (CC). Images were qualitatively analyzed before and after 3D-PAR by 2 independent graders. Results: None of the SCP images had projection artifact before or after 3D-PAR. Scans of the DCP presented projection artifact in 96.5% of the cases. After 3D-PAR, 14.7% had a complete improvement of projection artifact, 56.5% had a partial improvement, 14.1% were worse, and 14.7% presented no change. In the OR, 2.9% had projection artifact, with a complete improvement after 3D-PAR in 40%, partial improvement in 20%, and no change in 40%. Projection artifact was initially present in 97.6% of the images in the CC. After 3D-PAR, there was a complete improvement in 72.9%, partial improvement in 26.5%, and no change in 0.6%. Choroidal neovascularization (CNV) was detected in 29 eyes (17.1%), and 3D-PAR improved detection of CNV in 12 cases (41.4%). Conclusions: OCTA with 3D-PAR technology minimizes the appearance of projection artifacts in the DCP and CC slabs.

Purpose: Recent publications have reported that the deep capillary plexus (DCP) area of the foveal avascular zone (FAZ) is significantly larger in eyes following pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD) repair when compared with controls. To the best of the authors’ knowledge, there have been no publications on the evaluation of the macular microvasculature using optical coherence tomography angiography (OCTA) in post–pneumatic retinopexy (PnR) eyes. Therefore, the purpose of this study was to investigate FAZ-area changes following PnR. Methods: This retrospective cohort included 19 patients with macula-off RRD who underwent PnR repair. Each patient’s fellow eye was used as a control. The FAZ area in the superficial capillary plexus and DCP was investigated with OCTA and the areas were measured by 2 masked graders. Results: Both superficial (PnR: 0.22 [0.16-0.35] vs control: 0.24 [0.18-0.34] mm2; P = .715) and deep (PnR: 0.56 [0.51-0.76] vs control: 0.7 [0.59-0.89] mm2; P = .105) FAZ areas were not significantly different between eyes. Conclusions: Our results suggest that the lack of FAZ-area enlargement after PnR repair may indicate that there is less ischemic damage to the retinal capillary plexus in the fovea when compared with that described in the literature for PPV. The PIVOT trial demonstrated that PnR is associated with superior visual acuity and less metamorphopsia when compared with PPV at 1 year. The results of the current study may provide insight into the potential advantages of PnR. Further studies are needed to elucidate how the macular microvasculature is affected after RRD and to clarify how the FAZ area changes following PnR and PPV.

To assess the incidence of postoperative outer retinal folds (ORFs) after pars plana vitrectomy (PPV) vs. pneumatic retinopexy (PnR) for rhegmatogenous retinal detachment (RRD) repair and to determine the association of ORFs with functional outcomes at 1 year.Randomized controlled trial.Patients with primary macula-off RRD meeting the Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized (PIVOT) trial criteria who were randomly assigned to undergo PPV or PnR.Post hoc analysis of the PIVOT trial. The incidence and quantitative morphologic features of ORFs were assessed using en face and cross-sectional OCT at 1 month postoperatively by 2 masked graders. The ETDRS letter score was measured and quantitative assessment of metamorphopsia was performed at 1 year.Proportion of patients with ORFs at 1 month postoperatively among those who underwent PPV versus PnR. The secondary outcomes included the association of ORFs with visual acuity (ETDRS letter score) and metamorphopsia via metamorphopsia charts at 12 months postoperatively.Of 176 participants enrolled in PIVOT, 88 were macula-off RRDs. Of them, 94.3% (83 of 88) underwent postoperative OCT scans that were gradable at month 1, 93.2% (41 of 44) in the PPV group and 95.5% (42 of 44) in the PnR group. The incidence of ORF formation was 34.1% (14 of 41) in the PPV group and 14.3% (6 of 42) in the PnR group (P = 0.034). The ETDRS letter score at 1 year was 65.7 ± 6.6 letters in patients with ORFs vs. 75.1 ± 1.4 letters in those without ORFs (difference = 9.4 letters, 95% confidence interval [CI] = 7.5-11.3, P = 0.047). Among patients in the PPV group alone, the mean ETDRS letter score at 1 year in patients with ORFs was 62.8 ± 24.7 letters, compared with 75.4 ± 9.2 letters in patients without ORF formation (difference = 12.6 letters, 95% CI = 0.05-24.59, P = 0.04). Horizontal and vertical metamorphopsia scores were similar in patients with and without ORFs: horizontal, 0.35 ± 0.12 vs. 0.29 ± 0.07 (difference = 0.06, 95% CI = 0.01-0.11, P = 0.69); vertical, 0.25 ± 0.07 vs. 0.29 ± 0.07 (difference = 0.04, 95% CI = 0-0.08, P = 0.60). There was a negative correlation between the closest distance of an ORF from the fovea and vertical metamorphopsia score (r = -0.507, P = 0.045).There is greater risk of developing ORFs after PPV compared to PnR for primary RRD. Outer retinal folds at 1 month are associated with significantly worse ETDRS visual acuity letter scores at 1 year.

Background: There is an unmet need for treatment options for generalised myasthenia gravis that are effective, targeted, well tolerated, and can be used in a broad population of patients. We aimed to assess the safety and efficacy of efgartigimod (ARGX-113), a human IgG1 antibody Fc fragment engineered to reduce pathogenic IgG autoantibody levels, in patients with generalised myasthenia gravis. Methods: ADAPT was a randomised, double-blind, placebo-controlled, phase 3 trial done at 56 neuromuscular academic and community centres in 15 countries in North America, Europe, and Japan. Patients aged at least 18 years with generalised myasthenia gravis were eligible to participate in the study, regardless of anti-acetylcholine receptor antibody status, if they had a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 5 (>50% non-ocular), and were on a stable dose of at least one treatment for generalised myasthenia gravis. Patients were randomly assigned by interactive response technology (1:1) to efgartigimod (10 mg/kg) or matching placebo, administered as four infusions per cycle (one infusion per week), repeated as needed depending on clinical response no sooner than 8 weeks after initiation of the previous cycle. Patients, investigators, and clinical site staff were all masked to treatment allocation. The primary endpoint was proportion of acetylcholine receptor antibody-positive patients who were MG-ADL responders (≥2-point MG-ADL improvement sustained for ≥4 weeks) in the first treatment cycle. The primary analysis was done in the modified intention-to-treat population of all acetylcholine receptor antibody-positive patients who had a valid baseline MG-ADL assessment and at least one post-baseline MG-ADL assessment. The safety analysis included all randomly assigned patients who received at least one dose or part dose of efgartigimod or placebo. This trial is registered at ClinicalTrials.gov (NCT03669588); an open-label extension is ongoing (ADAPT+, NCT03770403). Findings: Between Sept 5, 2018, and Nov 26, 2019, 167 patients (84 in the efgartigimod group and 83 in the placebo group) were enrolled, randomly assigned, and treated. 129 (77%) were acetylcholine receptor antibody-positive. Of these patients, more of those in the efgartigimod group were MG-ADL responders (44 [68%] of 65) in cycle 1 than in the placebo group (19 [30%] of 64), with an odds ratio of 4·95 (95% CI 2·21–11·53, p

Retinopathy of prematurity (ROP), previously known as retrolental fibroplasia, was first described by Terry in 1942 (1). It is a vasoproliferative disorder that is a leading cause of childhood blindness in the United States, causing 550 new cases of infant blindness each year (2). It occurs principally in premature infants treated with high concentrations of oxygen. There are two phases of ROP: (i) an acute phase in which normal vasculogenesis is interrupted, and (ii) a chronic phase in which vascular membranes proliferate into thevitreous. This proliferation can lead to retinal detachment, scarring of the macula, and significant visual loss (3).This article summarizes the incidence, pathophysiology, and classification of ROP. Current protocols for evaluating and treating ROP, as well as long-term sequelae, are also described.

Importance Although rhegmatogenous retinal detachment (RRD) repair techniques have high anatomical reattachment rates, there may be differences in various aspects of postoperative vision-related quality of life (VRQoL). Objective To explore the differences in various aspects of VRQoL between pneumatic retinopexy (PnR) and pars plana vitrectomy (PPV) following RRD repair. Design, Setting, and Participants Post hoc exploratory analysis of the the Pneumatic Retinopexy vs Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes randomized clinical trial conducted between August 2012 and May 2017 at St Michael’s Hospital, Toronto, Ontario, Canada. Patients with RRD with a single break or multiple breaks within 1 clock hour of detached retina in the superior 8 clock hours of the retina with any number, location, and size of retinal breaks or lattice degeneration in attached retina. Main Outcomes and Measures Differences in the 25-Item National Eye Institute Visual Function Questionnaire 12 subscale scores between the PnR and PPV groups at 6 months following RRD repair. Results A total of 160 patients were included in this analysis, with 81 patients (92%) and 79 patients (90%) in the PnR and PPV groups, respectively. The PnR group consisted of 32% women with a mean (SD) age of 60.9 (9.3) years, while the PPV group consisted of 38% women with a mean (SD) age of 60.3 (7.6) years. For the 152 patients with 6-month follow-up (75 patients in PnR [85%] and 77 patients in PPV [88%]), there was evidence for an association of PnR with superior vision-related functioning compared with PPV for several subscales. There were no differences between groups at 1 year. After adjusting for age, sex, baseline macular status, visual acuity in the nonstudy eye, and lens status, patients who underwent PnR had higher scores for distance activities (mean [SD] PnR, 88.7 [13.4]; PPV, 82.8 [17.1]; adjusted difference, 6.5; 95% CI, 1.6-11.4;P = .01), mental health (mean [SD] PnR, 84.3 [17.4]; PPV, 78.7 [21.1]; adjusted difference, 6.7; 95% CI, 0.4-13;P = .04), dependency (mean [SD] PnR, 96.1 [10.1]; PPV, 91.1 [18.6]; adjusted difference, 5.7; 95% CI, 0.6-10.8;P = .03), and peripheral vision (mean [SD] PnR, 91.6 [16.2]; PPV, 81.2 [24.4]; adjusted difference, 10.8; 95% CI, 4.3-17.4;P = .001) at 6 months. Conclusions and Relevance These findings demonstrate that patients undergoing PnR for RRD report higher mental health scores and superior vision-related functioning scores in several subscales of the 25-Item National Eye Institute Visual Function Questionnaire during the first 6 months postoperatively compared with PPV. Trial Registration ClinicalTrials.gov Identifier:NCT01639209.

Objective To assess the clinical findings and microbiology investigations in patients with suspected infectious posterior segment uveitis (PSU). Design Retrospective case study. Methods Between January and December 2014, medical records of 270 patients with PSU were reviewed. Baseline ocular examination, presumed and final diagnoses, microbiology investigations from aqueous or vitreous fluid, and peripheral blood were reviewed. Results Infectious PSU was suspected in 28 patients among 270 PSU cases (10.4%, 28/270), and 11 cases were of infectious origin (4.1%, 11/270). Six patients were immunocompromised: 5 patients in the confirmed infectious PSU group (45.5%, 5/11) and 1 in the confirmed noninfectious group (5.9%, 1/17; p = 0.002). Initial visual acuity was 1.8 ± 0.35 logMAR and 0.9 ± 0.23 logMAR for patients with confirmed infectious and noninfectious PSU, respectively (p = 0.04). Anterior chamber reaction was worse in patients with confirmed infectious PSU (1.8 ± 0.49) than confirmed noninfectious cases (0.5 ± 0.1; p = 0.003). The frequency of chorioretinitis among patients with confirmed infectious and noninfectious PSU is 54.5% (6/11) and 11.8% (2/17; p = 0.03), respectively. Onset of confirmed infectious uveitis was more acute (≤6 weeks in duration) than noninfectious cases (p = 0.0015). Among the 11 patients with positive blood culture or serology, 6 had anterior and vitreous chamber fluid analysis. The rate of positive cultures and PCR is 16.7% (1/6) for aqueous humour and 50% (3/6) for vitreous samples. Conclusions Clinical features more suggestive of infectious PSU include immunosuppression, worse initial visual acuity, acute onset, worse anterior chamber reaction, and chorioretinitis. Further studies are needed to enhance the diagnostic yields of aqueous and vitreous fluid analyses.

INTRODUCTION Amyotrophic lateral sclerosis (ALS) patients benefit from multidisciplinary care in an ALS clinic. We studied whether multidisciplinary care of ALS patients using the store and forward method of telemedicine was feasible and acceptable to patients and providers. METHODS ALS patients seen in the University of Florida (UF) Jacksonville ALS clinic were eligible for our study. A trained telemedicine nurse performed and recorded a multidisciplinary assessment of the patient in their home. Clinic team members reviewed the assessments and provided recommendations, and the clinic director discussed the plan with the patient via videoconference. Patient and provider satisfaction was evaluated using surveys. RESULTS Eighteen patients completed a total of 27 telemedicine visits. Patient satisfaction was excellent and provider satisfaction was very good. DISCUSSION The store and forward method of telemedicine is an acceptable alternative to live telemedicine for the multidisciplinary care of ALS patients. This method of care may improve access to multidisciplinary care for this patient population. Muscle Nerve 59:34-39, 2019.

Background Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. Methods We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229. Findings Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56·6 [SEM 4·5] vs 68·3 [4·5]; rank-based treatment difference -11·7, 95% CI -24·3 to 0·96; p=0·0698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy. Interpretation The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed. Funding Alexion Pharmaceuticals.

Objective To assess how polypoidal choroidal vasculopathy (PCV) is recognized and treated, and to assess whether treatment outcomes are different between Chinese and Caucasian Canadian patients with age-related macular degeneration (AMD). Design Retrospective chart review. Participants 154 eyes from 135 Chinese patients and 2291 eyes from 1792 Caucasian patients who were newly diagnosed with either AMD or PCV and had more than 1 year of follow-up were included. Methods All newly diagnosed AMD patients presenting to the Retina Service of 3 Toronto University Hospitals, between March 25, 2008, to September 30, 2014, were reviewed. Results 10/154 eyes (6.5%) in Chinese Canadians and 16/2291 eyes (0.7%) in Caucasian Canadians were diagnosed as having PCV. Indocyanine green angiography (ICGA) was used to diagnose PCV in 20% of Chinese Canadians and 8.8% of Caucasian Canadians. Clinical practices with a larger percentage of Chinese patients were more likely to diagnose PCV in both Chinese ( p = 0.004) and Caucasian patients ( p = 0.03), were more likely to use photodynamic therapy (PDT) ( p p Conclusion Our study has shown that PCV is under-recognized in a Canadian population, and ICGA is underutilized. In clinical practices with a greater portion of Chinese patients, PCV is more often recognized and PDT is used more liberally.

Purpose: To investigate the differences in surgical maneuvers between vitreoretinal fellows and experienced vitreoretinal surgeons (attendings) when performing internal limiting membrane (ILM) peel during macular hole (MH) surgery and repair. Methods: Prospective case series. Macular hole surgeries performed by fellows and attendings at St Michael’s Hospital (Toronto, Canada) were recorded during a 12-month period. Evaluation of recordings was masked. Total peel time (TPL) in seconds, total movement attempts initiating and extending ILM flaps, intrasurgical complications, and surgical efficiency (ratio of approaches leading to case progression to total approaches) were quantified. Results: A total of 145 surgeries were evaluated; 44 met inclusion and exclusion criteria. Of the 44 cases, 25 were performed by fellows and 19 by attendings. Mean TPL was shorter for attendings (336 vs 506 seconds, P = .0032). Attendings had a lower average total movement attempts (32.2 vs 43.2, P = .045) and average flap initiation attempts (16.1 vs 23.3, P = .042). Surgical efficiency was better for attendings (45% vs 37% of approaches led to case progression, P = .038). There was no significant difference between groups in total flap extension attempts or intrasurgical complications. Conclusions: Compared to fellows, attendings peel ILM in MH surgery faster, more efficiently with a lower number of flap initiation attempts and total movements.

Optic disc pit is a rare congenital anomaly of the optic nerve. Retinal detachment is a common complication with poor outcomes. Many surgical alternatives have been described for the treatment of this condition, producing variable results. Herein, the authors describe four cases of optic disc pit-associated macular detachment managed with pars plana vitrectomy, fluid-air exchange, drainage of subretinal fluid through the optic disc pit, temporal peripapillary laser, and application of Evicel fibrin sealant (human) (Ethicon, Bridgewater, NJ) over the optic disc head. Case 1 showed stable visual acuity and improvement of subretinal fluid. Cases 2 and 3 showed visual acuity and subretinal fluid improvements. At the 1-week follow-up visit, Case 4 showed almost total subretinal fluid absorption. The sealant invariably disappeared between 1 and 2 weeks and was tolerated by all patients. This case series suggests that Evicel fibrin sealant may be considered as an adjunctive option in the surgical treatment of optic disc pit-associated maculopathy. [ Ophthalmic Surg Lasers Imaging Retina. 2017;48:358–363.]

Importance Pneumatic retinopexy (PnR) is associated with superior visual acuity and reduced vertical metamorphopsia compared with pars plana vitrectomy (PPV) for primary rhegmatogenous retinal detachment (RRD). It is important to determine postoperative photoreceptor integrity with both surgical techniques. Objective To compare photoreceptor integrity on spectral domain-optical coherence tomography (SD-OCT) between PnR and PPV at 12 months postoperatively. Design, setting, and participants Post hoc analysis of the Pneumatic Retinopexy Versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) conducted between August 2012 and May 2017 at St Michael's Hospital, Toronto, Ontario, Canada. Primary RRDs with specific criteria were included. Data were analyzed between April and August 2020. Intervention Randomization to PnR vs PPV stratified by macular status. Main outcomes and measures Difference in proportion of patients with discontinuity of the ellipsoid zone (EZ) and external limiting membrane (ELM) between groups assessed independently by 2 masked graders at an external masked image reading center. Results A total of 150 participants completed the 12-month follow-up visit. A total of 145 patients (72 PPV and 73 PnR) had gradable spectral-domain optical coherence tomography at 12 months. Analysis of the central 3-mm (foveal) scans found that 24% (n = 17 of 72) vs 7% (n = 5 of 73) displayed EZ discontinuity (difference, 17%; odds ratio [OR], 4.204; 95% CI, 1.458-12.116; P = .005) and 20% (n = 14 of 71) vs 6% (n = 4 of 73) displayed ELM discontinuity (difference, 14%; OR, 4.237; 95% CI, 1.321-13.587; P = .01) in the PPV and PnR groups, respectively. Analysis of the 6-mm (foveal and nonfoveal) scans revealed that EZ and ELM discontinuity was greater in the PPV vs PnR groups (EZ, 32% [n = 23 of 72] vs 11% [n = 8 of 73]; difference, 21%; OR, 3.814; 95% CI, 1.573-9.249; P = .002; ELM, 32% [n = 23 of 71] vs 18% [n = 13 of 73]; difference, 14%; OR, 2.211; 95% CI, 1.015-4.819; P = .04). Conclusions and relevance Discontinuity of the EZ and ELM was more common at 12 months postoperatively following PPV vs PnR for RRD repair. The findings of this post hoc analysis suggest that less discontinuity of the EZ and ELM may provide an anatomic basis for the previously reported superior functional outcomes with PnR, although the analysis does not prove a cause-and-effect relationship. Trial registration ClinicalTrials.gov Identifier: NCT01639209.

Optical coherence tomography angiography (OCTA) is a novel imaging modality that incorporates blood motion contrast to create angiograms of the retinal vasculature in a noninvasive manner, without the use of dye. It is a safe procedure and can be repeated as frequently as desired. The use of OCTA for delineation of choroidal neovascular membranes, for the study of microvascular abnormalities in diabetic patients, to assess nonperfused areas in retinal occlusions and vascular changes in macular telangiectasia are some of the potential OCTA applications. However, it is not free of drawbacks. Major limitations include the small field of view and its great sensitivity to movement. As a result, it is prone to motion artifacts, leading to poor-quality images. The scope of the body literature regarding this new modality rapidly increases as we learn how to better use this technology. Our objective is to point overall aspects of OCTA, including its limitations and review some of its initial reports on chorioretinal diseases.

PURPOSE To identify favorable ocriplasmin candidates from a cohort of idiopathic full thickness macular hole surgery patients. METHODS The records of patients with full thickness macular hole who underwent pars plana vitrectomy surgery between 2011 and 2015 were reviewed. Clinical data collected included patient demographics, pre- and post-operative Snellen visual acuity, optical coherence tomography findings, and lens status. The authors defined "favorable" ocriplasmin candidates as patients with focal vitreomacular traction, no epiretinal membrane, and hole size ≤400 μm. The authors further categorized "optimal" candidates as age ≤65, phakic, no epiretinal membrane, with focal vitreomacular traction, and hole size ≤400 μm. RESULTS The records of 238 patients were assessed; 30.7% were male while mean age was 68.6 ± 8.3 years. The mean logMAR acuity was 1.2 (Snellen 20/317) preoperatively and 0.90 (Snellen 20/159) postoperatively. Optical coherence tomography findings indicated that 46.5% of the macular holes studied were less than ≤400 μm in size, 14.8% had an epiretinal membrane, and 25.3% had vitreomacular traction. A total of 17.7% of study patients were found to be favorable candidates, whereas 3.8% were optimal ocriplasmin candidates. CONCLUSION Only a minority of full thickness macular hole surgical candidates in this cohort would be considered favorable ocriplasmin candidates.

Purpose: To report the first case of gold shunt surgery for treatment of silicone oil–induced refractory glaucoma in a tertiary care academic center, with 5-year follow-up. Design: The study design is a case report. Participants: The participant was a patient who underwent gold shunt surgery. Methods: Institutional Research Ethics Board approval for the study was obtained. A diabetic patient was referred for refractory glaucoma with a history of proliferative diabetic retinal detachment, and surgery with silicone oil. She was uncontrolled on maximal medical therapy and following informed consent, gold shunt surgery was performed. Ocular outcomes and number of medications were reviewed over a 5-year period. Results: Following uncomplicated surgery, intraocular pressure was reduced from 41 to 14 mm Hg, and the number of medications was reduced from 4 to 1. Glaucomatous optic neuropathy remained stable. Conclusions: Gold shunt surgery in this challenging case of silicone oil refractory glaucoma provided long-term intraocular pressure control and reduced need for medication over a 5-year period.

Objective To assess the rate of visual impairment and quantify the unmet eye care needs within Toronto's homeless youth community. Design Prospective and cross sectional. Participants Ninety randomly selected homeless youth aged 16–24 years. Methods From each of 9 participating homeless youth shelters and drop-in centres in Toronto, 10 English-speaking youths between ages 16 and 24 were randomly recruited. Information regarding sociodemographics, medical history, subjective visual acuity, and access to eye care was collected. Comprehensive visual screening and undilated direct fundoscopy were also performed. Results The median age of participants was 21 years (interquartile range=19–23 years), and 62.2% were male. Most participants were homeless for less than 5 years (90%) and earning less than $500 monthly (57.8%). Despite 51.1% of participants having previously owned corrective lenses, only 20% of participants currently owned them when assessed/at study time. When analyzing the better-seeing eye, presenting visual acuity was 20/50 or worse in 18.9% (95% CI 10.8%–27.0%) of participants. Pinhole occlusion decreased the number to 2.2% (95% CI 0%–5.3%). The most common cause of visual impairment was uncorrected refractive error. Ocular pathology was observed in 8 participants. Compared to adults, youth have similar functional visual impairment (adults 24.0%, youth 18.9%) but less impairment uncorrectable by pinhole occlusion (adults 11.0%, youth 2.2%) and are less dissatisfied with their vision (adults 70.0%, youths 36.7%). Although a higher proportion of homeless youths have visited an eye specialist in the past year (adults 14.0%; youths 17.8%), neither group is visiting as frequently as the Canadian average (41%) ( p Conclusions Homeless youth have a high prevalence of visual impairment, even when living within a system of universal health insurance. Ongoing vision-screening programs, readily accessible free eye clinics, and particularly low-cost glasses may help address this need.

Background/aims To identify predictive markers for the outcomes of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD). Methods AURA was a retrospective, observational, multicentre study that monitored the 2-year outcomes following intravitreal ranibizumab treatment in patients with nAMD. Using stepwise regression analysis, we evaluated the association between visual acuity outcomes, baseline characteristics and resource utilisation in order to determine which variables are significantly linked to outcomes in AURA. We also examined the relationship between visual acuity outcomes and number of injections received. Results Analyses were performed using data from year 1 (n=1695) and year 2 completers (n=1184). Logistic analysis showed that baseline visual acuity score, age at start of therapy, number of ophthalmoscopies and optical coherence tomography (OCT) (combined) and number of injections (ranibizumab) were significant (p7 injections (in 1 year) or >14 injections (over 2 years) gained more letters and demonstrated greater vision maintenance (loss of

IMPORTANCE: Retinal displacement following rhegmatogenous retinal detachment repair may have consequences for visual function. It is important to know whether surgical technique is associated with risk of displacement. OBJECTIVE: To compare retinal displacement following rhegmatogenous retinal detachment repair with pneumatic retinopexy (PR) vs pars plana vitrectomy (PPV). INTERVENTIONS OR EXPOSURES: Fundus autofluorescence images were assessed by graders masked to surgical technique. DESIGN, SETTING, AND PARTICIPANTS: A multicenter retrospective consecutive case series in Canada and the UK. A total of 238 patients (238 eyes) with rhegmatogenous retinal detachments treated with PR or PPV who underwent fundus autofluorescence imaging from November 11, 2017, to March 22, 2019, were included. MAIN OUTCOMES AND MEASURES: Proportion of patients with retinal displacement detected by retinal vessel printings on fundus autofluorescence imaging in PR vs PPV. RESULTS: Of the 238 patients included in the study, 144 were men (60.5%) and 94 were women (39.5%); mean (SD) age was 62.0 (11.0) years. Of the 238 eyes included in this study, 114 underwent PR (47.9%) and 124 underwent PPV (52.1%) as the final procedure to achieve reattachment. Median time from surgical procedure to fundus autofluorescence imaging was 3 months (interquartile range, 1-5 months). Baseline characteristics in both groups were similar. The proportion of eyes with retinal vessel printing on fundus autofluorescence was 7.0% for PR (8 of 114) and 44.4% for PPV (55 of 124) (37.4% difference; 95% CI, 27.4%-47.3%; P

Purpose The optimal surgery to repair rhegmatogenous retinal detachment (RRD) is unknown. The purpose of this trial was to compare outcomes of pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV) for the management of primary RRD. Design Prospective, randomized controlled trial. Participants Patients with RRD demonstrating a single retinal break or a group of breaks in detached retina within 1 clock hour above the 8- and 4-o’clock meridians, with any number, location and size of retinal breaks or lattice degeneration in attached retina. Methods Patients were randomized to undergo either PnR or PPV. Macula-on and macula-off patients were assigned to intervention group by stratified randomization and were treated within 24 and 72 hours, respectively. Main Outcome Measures The primary outcome was 1-year Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA). Important secondary outcomes were subjective visual function (25-item National Eye Institute Visual Function Questionnaire), metamorphopsia score (M-CHARTS), and primary anatomic success. Results One hundred seventy-six patients were recruited between August 2012 and May 2016. ETDRS VA after PnR exceeded that after PPV by 4.9 letters at 12 months (79.9±10.4 letters vs. 75.0±15.2 letters; P = 0.024). Mean ETDRS VA also was superior for the PnR group compared with the PPV group at 3 months (78.4±12.3 letters vs. 68.5±17.8 letters) and 6 months (79.2±11.1 letters vs. 68.6±17.2 letters). Composite 25-item National Eye Institute Visual Function Questionnaire scores were superior for PnR at 3 and 6 months. Vertical metamorphopsia scores were superior for the PnR group compared with the PPV group at 12 months (0.14±0.29 vs. 0.28±0.42; P = 0.026). Primary anatomic success at 12 months was achieved by 80.8% of patients undergoing PnR versus 93.2% undergoing PPV (P = 0.045), with 98.7% and 98.6%, respectively, achieving secondary anatomic success. Sixty-five percent of phakic patients in the PPV arm underwent cataract surgery in the study eye before 12 months versus 16% in the PnR group (P Conclusions Pneumatic retinopexy should be considered the first line treatment for RRD in patients fulfilling Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) recruitment criteria. Pneumatic retinopexy offers superior VA, less vertical metamorphopsia, and reduced morbidity when compared with PPV.

Objective To examine the spectrum and sensitivity patterns of bacterial isolates derived from all culture-positive aqueous and vitreous samples submitted for culture and sensitivity analysis at our institution over a 10-year period. Design Retrospective cohort study. Participants A total of 368 culture-positive aqueous and vitreous samples from 265 patients were reviewed. Methods Over a decade extending from January 2000 through December 2009, all culture-positive aqueous and vitreous specimens at our institution were identified. Isolated bacterial pathogens and their in vitro antibiotic sensitivities were analyzed. Results Approximately 86.4% of patients had positive cultures for either staphylococci ( Staphylococcus aureus and coagulase-negative staphylococci [CNS]) or streptococci. Gram-negative bacteria were isolated in only 9.8% of patients. From 2000 to 2004, 81.2% and 55.9% of CNS isolates were sensitive to ciprofloxacin and cefazolin, respectively, compared with 41.2% and 23.5% of isolates in the last 5 years. Over the study period, ceftazidime retained 100% efficacy against the gram-negative isolates tested. Vancomycin was 99.6% effective against the gram-positive isolates tested. Conclusions The microbiology of pathogens in endophthalmitis is evolving, with an increase in streptococcal isolates and a decrease in CNS. The apparent lack of efficacy of conventionally used antibiotics and the emergence of increasingly resistant strains of bacteria may have significant implications in the management of bacterial endophthalmitis.

Amyotrophic lateral sclerosis (ALS) patients benefit from multidisciplinary care in an ALS clinic. We studied whether multidisciplinary care of ALS patients using the store and forward method of telemedicine was feasible and acceptable to patients and providers.ALS patients seen in the University of Florida (UF) Jacksonville ALS clinic were eligible for our study. A trained telemedicine nurse performed and recorded a multidisciplinary assessment of the patient in their home. Clinic team members reviewed the assessments and provided recommendations, and the clinic director discussed the plan with the patient via videoconference. Patient and provider satisfaction was evaluated using surveys.Eighteen patients completed a total of 27 telemedicine visits. Patient satisfaction was excellent and provider satisfaction was very good.The store and forward method of telemedicine is an acceptable alternative to live telemedicine for the multidisciplinary care of ALS patients. This method of care may improve access to multidisciplinary care for this patient population. Muscle Nerve 59:34-39, 2019.

To report the anatomical and visual outcomes of patients with thick submacular hemorrhage (SMH) treated with pars plana vitrectomy (PPV), subretinal tissue plasminogen activator (t-PA), and pneumatic displacement.Single-centre, retrospective case series.A total of 99 eyes of 99 consecutive patients with thick SMH secondary to any underlying etiology treated with PPV with subretinal t-PA and pneumatic displacement by 6 vitreoretinal surgeons at St. Michael's Hospital, Toronto, between July 2004 and August 2016.All medical records and colour fundus photographs were reviewed for data collection. Blood displacement was evaluated at follow-up visits and classified as complete, partial, or none. Main outcome measures included blood displacement at final follow-up, postoperative Snellen best-corrected visual acuities (BCVA), and complication and recurrence rates.Patients had a mean age of 77.7 ± 12.3 years and were followed up for an average of 18.4 ± 22.3 months. Wet age-related macular degeneration was the most common etiology associated with thick SMH (80.8%). Complete blood displacement was observed by final follow-up in 85.9% of the cases, partial displacement in 12.1%, and none in 2.0%. Mean logMAR BCVA improved from 2.03 ± 0.81 (Snellen 20/2143) at baseline to 1.80 ± 1.00 (Snellen 20/1262; p = 0.009) at final follow-up, and baseline BCVA was a significant predictor of final BCVA (p0.001). Early postoperative complications included vitreous hemorrhage in 13 eyes and rhegmatogenous retinal detachment in 8. Recurrent SMH was observed in 12 cases.Vitrectomy with subretinal t-PA and pneumatic displacement seems to be an effective treatment for SMH in terms of blood displacement and visual outcomes.

Contains fulltext : 153434.pdf (Publisher’s version ) (Open Access) BACKGROUND/AIMS: Real-life anti-vascular endothelial growth factor (VEGF) therapy use in patients with wet age-related macular degeneration (wAMD) was assessed in a retrospective, observational study in Canada, France, Germany, Ireland, Italy, the Netherlands, UK and Venezuela. METHODS: Medical records of patients with wAMD, who started ranibizumab treatment between 1 January 2009 and 31 August 2009, were evaluated. Data were collected until the end of treatment and/or monitoring or until 31 August 2011. RESULTS: 2227 patients who received >/=1 anti-VEGF injection with a baseline visual acuity assessment and >/=1 postbaseline visual acuity assessment for the treated eye were evaluated. Visual acuity improved until about day 120; thereafter, visual acuity gains were not maintained. Mean change in visual acuity score from baseline to years 1 and 2 was +2.4 and +0.6 letters, respectively. Patients received a mean of 5.0 and 2.2 injections in the first and second year, respectively. There were substantial differences in visual outcomes and injection frequency between countries. More frequent visits and injections were associated with greater improvements in visual acuity. CONCLUSIONS: In clinical practice, fewer injections are administered than in clinical trials. Anti-VEGF treatment resulted in an initial improvement in visual acuity; however, this was not maintained over time. TRIAL REGISTRATION NUMBER: NCT01447043.

ABSTRACT: Human toxic peripheral neuropathies (TxPN) due to occupational chemical exposure are relatively rare compared with medically related peripheral neuropathies. They are however difficult to diagnose due to their clinical and electrophysiologic similarity to nontoxic peripheral neuropathy. Understanding the cardinal tenets of neurotoxicology, as it applies to TxPN, helps differentiate between the toxic and nontoxic peripheral neuropathy. These tenets include: strong dose–response relationship, consistency of clinical response, proximity of symptoms to exposure, correlation between severity of neuropathy and degree of exposure, and improvement of PNS signs and symptoms follows cessation of exposure. A thorough clinical and occupational history is essential in identifying the possibility of a TxPN.

There have been many advances in vitreoretinal surgery since Machemer introduced the concept of pars plana vitrectomy, in 1971. Of particular interest are the changes in the vitrectomy cutters, their fluidics interaction, the wide-angle viewing systems and the evolution of endoillumination through the past decade and notably in the last few years. The indications of 27-gauge surgery have expanded, including more complex cases. Cut rates of up to 16,000 cuts per minute are already available. New probe designs and pump technology have allowed duty cycle performances of near 100% and improved flow control. The smaller vitrectomy diameter can be positioned between narrow spaces, allowing membrane dissection and serving as a multifunctional instrument. Enhanced endoillumination safety can be achieved by changing the light source, adding light filters, increasing the working distance and understanding the potential interactions between light and vital dyes commonly used to stain the retina. Wide-angle viewing systems (contact, non-contact or a combination of both) provide a panoramic view of the retina. Non-contact systems are assistant-independent, while contact systems may be associated with better image resolution. This review will cover some current aspects on vitrectomy procedures, mainly assessing vitrectomy cutters, as well as the importance of endoillumination and the use of wide-angle viewing systems. Electronic supplementary material The online version of this article (doi:10.1186/s40942-016-0052-9) contains supplementary material, which is available to authorized users.

To determine whether aqueous cytokine levels correlate with disease severity in diabetic macular edema.A prospective cross-sectional study of 49 adults with diabetes mellitus, centre-involving diabetic macular edema and central subfield macular thickness ≥310 μm on spectral domain optical coherence tomography. Clinical examination and aqueous sampling were carried out before an initial injection of ranibizumab. Multiplex immunoassay of sample was carried out for vascular endothelial growth factor, placental growth factor, transforming growth factor beta, intercellular adhesion molecule-1, interleukin (IL)-2, IL-3, IL-6, IL-8, IL-10, IL-17, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, and epidermal growth factor. Multivariate robust regression models were constructed, and adjusted for age, lens status, or severity of retinopathy, and size of foveal avascular zone.Spectral domain optical coherence tomography macular volume was an excellent measure of disease severity, correlating strongly with central subfield macular thickness (P0.001), best-corrected Snellen visual acuity (P0.001), and baseline diabetic retinopathy severity (P = 0.01). Elevated aqueous intercellular adhesion molecule-1 correlated with greater macular volume (P = 0.002). No aqueous cytokine, including VEGF, correlated with central subfield macular thickness. There was an association between IL-10 levels and best-corrected Snellen visual acuity (P = 0.03).Aqueous intercellular adhesion molecule-1 correlates with disease severity as measured by macular volume on spectral domain optical coherence tomography, and IL-10 is associated with BCVA. Intercellular adhesion molecule-1 may be a clinically useful biomarker for diabetic macular edema severity.

Objective: AURA was an observational study that monitored visual acuity outcomes following ranibizumab use in neovascular age-related macular degeneration patients over 2 years. The aim of this analysis was to identify factors that were predictive of visual acuity outcomes in AURA. Methods: The correlation between the baseline characteristics, the use of resources and the visual acuity outcomes in AURA was explored using principal component analysis (PCA) and partial least-squares-discriminant analysis (PLS-DA). The response variables analysed were mean change in visual acuity over 2 years (analysed via PCA) and no decline in visual acuity at 2 years compared with baseline (analysed via PLS-DA). Results: The AURA dataset comprised 2,227 patients and 132 variables. Using PCA and PLS-DA, we found that the number of ranibizumab injections, clinic and monitoring visits, number of optical coherence tomography scans and ophthalmoscopies correlated with a change in visual acuity at Years 1 and 2, and are therefore key drivers of treatment success. Conclusion: This is a novel approach to graphically explore relationships between multiple correlated covariates and outcomes in real-life ophthalmology studies. It identified a number of variables that are positively linked with treatment outcomes.

PURPOSE To evaluate the visual acuity results of monthly ranibizumab injections compared with a variable-dosing schedule for the treatment of neovascular age-related macular degeneration. METHODS A retrospective study that compared two cohorts of consecutive patients. All patients were treatment naive, with baseline visual acuity of 20/400 or better, and completed 12 months of therapy. In the first group all patients received monthly injections. In the other group, after 3 monthly loading doses, a variable-dosing schedule was used, based on a monthly clinical assessment and optical coherence tomography. RESULTS Fifty-six consecutive patients (60 eyes) were included. At 12 months the median number of injections were 12 and 8, respectively, and the mean change in Snellen visual acuity was an improvement of 0.27 logarithm of the minimum angle of resolution in the monthly treated group versus 0.21 logarithm of the minimum angle of resolution improvement in the variable-dosing group (P = 0.53). In the monthly treated group 96.8% of eyes lost

Purpose The aim of the study was to determine whether subconjunctival anesthesia is effective at reducing pain associated with laser retinopexy. Design This was a single-center, prospective, patient-masked, randomized, controlled trial. Participants In the primary study group, 65 patients were recruited. Thirty-two patients (32 eyes) received anesthetic injection, and 33 patients (33 eyes) received the sham injection. The crossover study group consisted of 28 patients (56 eyes). Methods Between February 2008 and April 2008, all patients who were consecutively booked to undergo panretinal photocoagulation (PRP) or peripheral laser retinopexy (PLR) were invited to participate in the study. Patients were randomized to receive subconjunctival lidocaine injection or a sham injection before their intended laser retinal treatment. These patients were defined as our primary study group. Patients who required a second laser treatment received the opposite injection in a masked fashion before laser retinal treatment. These patients were defined as our crossover group. Patients in both the primary study group and the crossover group were masked to the treatment given. After the laser treatment, patients completed a pain questionnaire. Main Outcome Measures The primary outcome was incidence of pain. The secondary outcome was severity of pain. Results Primary study group: In the anesthetic treatment group, 19 patients (59%) experienced pain compared with 32 patients (97%) in the sham treatment group ( P P =0.55). Crossover study group: In the anesthetic treatment group, 12 patients (43%) experienced pain compared with 28 patients (100%) in the sham treatment group ( P Conclusions Subconjunctival 2% lidocaine significantly reduces the incidence of pain in patients who receive PRP or PLR. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

IMPORTANCE: Variability in response to anti–vascular endothelial growth factor (VEGF) treatment in diabetic macular edema (DME) remains a significant clinical challenge. Biomarkers could help anticipate responses to anti-VEGF therapy. OBJECTIVES: To investigate aqueous humor cytokine level changes in response to intravitreal ranibizumab therapy for the management of DME, and to determine the association between baseline aqueous levels and anatomic response. DESIGN, SETTING, AND PARTICIPANTS: In this prospective multicenter cohort study, 49 participants with diabetes mellitus complicated by center-involving DME, with a central subfield thickness of 310 μm or greater on spectral-domain optical coherence tomography (SD-OCT), were recruited from December 22, 2011, to June 13, 2013 and statistical analysis were performed from March 1, 2017, to June 1, 2017. A total of 48 participants proceeded to follow-up. INTERVENTIONS: Participants received monthly injections of ranibizumab, 0.5 mg, for 3 months. Aqueous fluid for cytokine analysis was obtained at baseline and repeated at the 2-month visit. Multiplex immunoassay was carried out in duplicate for VEGF, placental growth factor, transforming growth factor beta 2, intercellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), IL-8, IL-10, vascular intercellular adhesion molecule, and monocyte chemoattractant protein 1. MAIN OUTCOMES AND MEASURES: Baseline and 2-month change in aqueous cytokine levels, 3-month change in SD-OCT central subfield thickness and macular volume (MV), and the statistical association between baseline aqueous cytokine levels and these measures of anatomic response to ranibizumab in center-involving DME. RESULTS: Among the 48 participants, the mean (SD) age was 61.9 (7.1) years and 36 participants (75.0%) were men. The following cytokines were lower at month 2 vs baseline: ICAM-1 (median change, −190.88; interquartile range [IQR], −634.20 to −26.54; P

Introduction The aim of this study was to assess the impact of baseline characteristics on visual outcome of patients with diabetic macular edema and compare the results of clinical trials with different patient populations. Methods A model was created with patient-level data from the RESPOND/RESTORE trials to estimate the impact of baseline characteristics on increases in best-corrected visual acuity (BCVA) with anti-vascular endothelial growth factor therapies, measured by letters gained on the Early Treatment Diabetic Retinopathy Study scale from baseline to month 12. Mean BCVA gains with ranibizumab 0.5 mg pro re nata or laser photocoagulation monotherapy were predicted, assuming baseline characteristics equivalent to those in the VIVID-DME/VISTA-DME trials. These results were compared with the gain with aflibercept 2.0 mg every 8 weeks in VIVID-DME/VISTA-DME. Sensitivity analyses assessed outcome robustness. Results Baseline BCVA and central retinal thickness differed significantly between trials. In unadjusted data, patients in RESPOND/RESTORE receiving ranibizumab gained an additional 6.6 letters [95% confidence interval (CI): 4.5–8.7] compared with patients receiving laser monotherapy. After adjusting data to assume baseline characteristics equivalent to VIVID-DME/VISTA-DME, patients receiving ranibizumab were predicted to gain an additional 9.9 letters (95% CI: 7.3–12.4) compared with those receiving laser monotherapy. These results were similar (0.1-letter difference in favor of aflibercept; 95% CI: −2.9 to 3.2; P = 0.94) to the gain in BCVA in patients receiving aflibercept in VIVID-DME/VISTA-DME compared with those receiving laser monotherapy (10.0 letters, 95% CI: 8.3–11.7). Conclusion After adjusting for baseline characteristics, the difference in letters gained between patients receiving ranibizumab versus aflibercept was non-significant across trials, highlighting the importance of adjusting for baseline characteristics in future comparisons. Funding Novartis Pharma AG. Electronic supplementary material The online version of this article (doi:10.1007/s12325-016-0310-0) contains supplementary material, which is available to authorized users.

The chronic autoimmune neuropathies are a diverse group of disorders, whose diagnosis and classification is based on the clinical presentations and results of ancillary tests. In chronic inflammatory demyelinating polyneuropathy, controlled therapeutic trials demonstrated efficacy for intravenous gamma-globulins, corticosteroids, and plasmaphereis. In multifocal motor neuropathy, intravenous gamma-globulins have been shown to be effective. In the other immune-mediated neuropathies, there are no reported controlled therapeutic trials, but efficacy has been reported for some treatments in non-controlled trials on case studies. Choice of therapy in individual cases is based on reported efficacy, as well as severity, progression, coexisting illness, predisposition to developing complications, and potential drug interactions.

Background: The availability of new therapeutic approaches, particularly intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies, has prompted significant changes to the established treatment paradigms for retinal vein occlusion (RVO). Better visual outcomes and significantly lower rates of adverse events have been noted in multiple large randomized clinical trials and have led to a new standard of care for this sight-threatening condition. Objective: To develop an expert consensus for the management of RVO and associated complications in the context of recent clinical evidence. Methods: The development of a Canadian expert consensus for optimal treatment began with a review of clinical evidence, daily practice, and existing treatment guidelines and algorithms. The expert clinicians (11 Canadian retina specialists) met on February 1, 2014, in Toronto to discuss their findings and to propose strategies for consensus. Results: The result of this expert panel is a consensus proposal for Canadian ophthalmologists and retina specialists treating patients presenting with RVO. Treatment algorithms specific to branch and central RVO (BRVO and CRVO) were also developed. Conclusions: The consensus provides guidelines to aid clinicians in managing RVO and associated complications in their daily practice. In summary, laser remains the therapy of choice when neovascularization secondary to RVO is detected. Adjunctive anti-VEGF could be considered in managing neovascularization secondary to RVO in cases of vitreous hemorrhage. Intravitreal anti-VEGF should be considered for symptomatic visual loss associated with center-involving macular edema on optical coherence tomography. Patients with BRVO and a suboptimal response to anti-VEGF could be treated with grid laser, and those with CRVO and an inadequate response to anti-VEGF may be candidates for intravitreal steroids.

We compared the frequencies and types of motor conduction abnormalities found in peroneal and tibial nerves of patients with either L5/S1 radiculopathies (n = 47) or axonal polyneuropathies (n = 49). In axonal neuropathies, compound muscle action potentials (CMAPs) were more likely to be either unobtainable or, if present, of low amplitude, prolonged in distal latency or both. F responses were more often absent, impersistent, or prolonged in minimal latency. In contrast, CMAPs in lumbosacral radiculopathies were more likely to be normal in both amplitude and distal latency. The most frequent F-response abnormality in radiculopathies was a prolonged maximum-minimum latency range rather than abnormalities of minimal latency or persistence. Logistic regression analysis demonstrated that different patterns of motor conduction abnormalities result from lumbosacral radiculopathy and distal axonopathies. The model was able to correctly classify disease state in 76% of subjects with a sensitivity of 74% and specificity of 80%.