Search

Andrew C Crichton,1 Donald R Nixon,2 Susan Simonyi,3 Meetu Bhogal,3 Christopher S Sigouin,4 Marino J Discepola,5 Cindy ML Hutnik,6 Darryl C Baptiste,3 David B Yan7 On behalf of the CLEAR Study Group 1Division of Ophthalmology, University of Calgary, Calgary, AB, Canada; 2Private practice, Barrie, ON, Canada; 3Medical Affairs, Allergan Inc., Markham, ON, Canada; 4CLINWest Research, Burlington, ON, Canada; 5Department of Ophthalmology, McGill University, Montreal, QC, Canada; 6Department of Ophthalmology and Pathology, Ivey Eye Institute, London, ON, Canada; 7Department of Ophthalmology, University of Toronto, Toronto, ON, Canada Purpose: To evaluate the ocular hyperemia and intraocular pressure (IOP)-lowering efficacy of bimatoprost 0.01% in subjects with elevated IOP due to primary open-angle glaucoma (POAG) or ocular hypertension (OHT) in a real-world clinical setting. Subjects and methods: This open-label, 12-week, observational study was conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline, week 6, and week 12 using a standardized photographic 5-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes the subgroup of 268 subjects who had been previously treated with latanoprost 0.005%, bimatoprost 0.03%, travoprost 0.004%, and travoprost 0.004% with SofZia™ or nonselective beta-adrenergic receptor blockers prior to the study. Results: After 12 weeks of treatment with 0.01% bimatoprost, ocular hyperemia was graded as none-to-mild hyperemia (grades 0, +0.5, or +1) for 94.1% of subjects and as moderate-to-severe hyperemia (grades +2 or +3) for 5.9%. No statistically significant shifts in ocular hyperemia ratings were observed at week 12 for any of the prior IOP-lowering therapies except bimatoprost 0.03%, in which 20.8% of subjects experienced an improvement. The mean percentage change from baseline IOP at week 12 following the switch to bimatoprost 0.01% monotherapy ranged from –2.3%±17.3% to –26.3%±12.4%. Furthermore, the decreased mean percentage change from baseline IOP was statistically significant across all prior IOP-lowering medications, except for bimatoprost 0.03% at the 6- and 12-week visits and travoprost 0.004% at the 6-week visit. Conclusion: This observational study demonstrates that bimatoprost 0.01% was well tolerated among POAG and OHT subjects who switched from prior IOP-lowering medication. Furthermore, a switch in ocular hypertensive treatment to bimatoprost 0.01% was associated with an additional 10%–15% reduction in IOP. Keywords: glaucoma, intraocular pressure, hyperemia, bimatoprost

Donald R Nixon,1 Susan Simonyi,2 Meetu Bhogal,2 Christopher S Sigouin,3 Andrew C Crichton,4 Marino Discepola,5 Cindy ML Hutnik,6 David B Yan71Private Practice, Barrie, ON, 2Allergan Inc, Markham, ON, 3CLINWest Research, Burlington, ON, 4University of Calgary, Calgary, AB, 5McGill University, Montreal, QC, 6London Health Sciences Centre, London, ON, 7University of Toronto, Toronto, ON, CanadaBackground: This study was designed to evaluate the occurrence and severity of ocular hyperemia in subjects with elevated intraocular pressure (IOP) due to primary open angle glaucoma (POAG) or ocular hypertension (OHT) following treatment with bimatoprost 0.01% in a real-world clinical setting.Methods: This was an open-label, observational study conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% topically as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline and weeks 6 and 12 using a photographic five-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes only the subgroup of 522 subjects who were naïve to IOP-lowering medication prior to the study.Results: After 12 weeks of treatment with bimatoprost 0.01%, hyperemia was graded as none-to-mild (grades 0, +0.5, or +1) for 93.3% of subjects and as moderate-to-severe (grades +2 or +3) for 6.7%. At weeks 6 and 12, most subjects (93.2% and 93.5%) had no change in hyperemia grade from baseline. IOP was reduced by 7.4 mmHg (29.8%) at week 6 and 7.7 mmHg (30.9%) at week 12 from baseline.Conclusion: This real-world, observational study found that bimatoprost 0.01% instilled once daily reduced IOP by a mean of 30% from baseline without moderate or severe ocular hyperemia in 93% of treatment-naïve subjects with POAG or OHT.Keywords: glaucoma, intraocular pressure, hyperemia, bimatoprost

Serum chromogranin A is the most useful general and prognostic tumour marker available for neuroendocrine tumour (NET) patients. The role of other tumour markers is less clear. In order to determine the diagnostic and prognostic value of serum alpha-fetoprotein (AFP) and human chorionic gonadotrophin-beta (hCGbeta) in NETs, a database containing biochemical, histological, and survival data on 360 NET patients was constructed. This data was statistically assessed, using Statistical Package for the Social Sciences, to determine the utility of commonly measured tumour markers with particular emphasis on AFP and hCGbeta. Alpha-fetoprotein and hCGbeta were raised in 9.5 and 12.3% of patients respectively and jointly raised in 9.1% of patients in whom it was measured. Alpha-fetoprotein levels associated strongly and positively with tumour grade, serum CgA and hCGbeta levels, and worse survival. Human chorionic gonadotrophin-beta levels also associated strongly and positively with serum CgA and AFP levels, and worsening survival. Alpha-fetoprotein and hCGbeta are elevated in high-grade NETs, with a rapidly progressive course and poorer survival. They also correlate with chromogranin-A, which is known to be a marker of tumour burden and to have prognostic value. Thus AFP and hCGbeta are clinically important in NETs and when elevated are poor prognostic markers. [ABSTRACT FROM AUTHOR]

We investigated the effects of a protein kinase A (PKA) inhibitor, H-89 { N-[2-(p-bromocinnamylamino)ethyl]-5-iso-quinolinesulphonamide}, on Ca2+ regulation in Fura-2-loaded ferret myocytes. H-89 (10 µmol/l) decreased the amplitude of the Fura-2 transient to 28.2±4.3% ( P<0.001) of control and prolonged its duration, characterized by a decrease in the rate of decline of Ca2+ to diastolic levels: t1/2 increased from 311±35 ms to 547±43 ms ( P<0.001, n=7). Reduced Ca2+ uptake by the sarcoplasmic reticulum (SR) in the presence of H-89 was also indicated by a decrease in the SR Ca2+ content, as assessed with caffeine. The apparent slowing of the SR Ca2+-ATPase was not caused by changes in phosphorylation of phospholamban (PLB). However, Ca2+ uptake in microsomal vesicles prepared from canine hearts and fast-twitch rat skeletal muscle (which lacks PLB) was decreased by 34.1 and 46.8% ( n=3), respectively, suggesting that H-89 has a direct inhibitory effect on the SR Ca2+-ATPase. In electrophysiological experiments, 5.0 µmol/l H-89 decreased the L-type Ca2+ current ( ICa) by 39.5% ( n=6) and slowed the upstroke of the action potential and, in some cases, caused loss of excitability without changes in the resting membrane potential. In summary, data show that [Ca2+ ]i regulation, and hence contraction, is sustained by PKA-mediated phosphorylation, even in the absence of β-agonists. However, the use of H-89 as a tool to study the role of this signalling pathway is limited by the non-specific effects of H-89 on the SR Ca2+-ATPase. [ABSTRACT FROM AUTHOR]

Purpose: To identify areas of consensus among experts on the performance of endothelial keratoplasty by using a modified Delphi approach, to help create a framework for novice surgeons to adopt these procedures., Methods: Thirty-one international experts in endothelial keratoplasty participated. Two rounds of electronic survey were followed by a hybrid, virtual meeting. Consensus was set at 75%, and results with agreement between 70% and 75% were deemed as achieving near consensus., Results: A consensus was reached for 98 statements covering the preoperative, intraoperative, and postoperative aspects of Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping endothelial keratoplasty/Descemet stripping automated endothelial keratoplasty. Four statements achieved near consensus, and consensus could not be achieved for 11 statements. For DMEK, the panel supported a peel technique to prepare tissue for endothelium out DMEK, implanted via an injector and supported by a near full air/gas fill as a baseline procedure onto which more advanced techniques can be built. DMEK tissue should be marked to ensure correct orientation. An inferior peripheral iridotomy should be used to prevent pupil block when a near full air/gas fill in used in endothelial keratoplasty (EK). Descemet stripping automated endothelial keratoplasty was considered preferable to Descemet stripping endothelial keratoplasty where access to microkeratome preparation was available., Conclusions: The Delphi process allowed areas of consensus on the performance of EK to be established by a group of international experts. The statements generated are a helpful framework for novice surgeons learning EK. Further research is needed to help determine what specific tomographic features indicate EK, when guttae are considered visually significant and how to approach combined aphakia and endothelial dysfunction., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To investigate patient understanding of, and attitudes to, premium (toric, extended depth of focus/multifocal) intraocular lenses (premIOLs) in public health sector patients undergoing cataract surgery (CS) in the UK., Methods: A 12 question survey with Likert scale questions was designed, to assess patient attitudes to post-operative spectacle dependence, refractive target and desirability of spectacle independence whilst considering possible complications of dysphotopsias and need for premIOL exchange/adjustment., Results: 360 surveys were collected. CS had not been performed in 66.5%. Separate spectacles were worn for reading and distance in 28.8%, 19.2% had varifocals, 11.2% bifocals, 22.9% reading glasses only and 1.6% computer glasses only. Contact lenses were not worn in 95.7%. Only 41.6% were drivers. Most patients (85.8%) did not mind wearing glasses after CS, with 78.9% preferring reading glasses, compared with 29.7% preferring distance glasses. Most patients (75.3%) were not familiar with premIOLs, with 58.9% not willing to consider them in the context of a 2% risk of debilitating dysphotopsia and 54.2% rejecting a 5% risk of second surgery., Conclusions: There is a lack of awareness of premIOLs in public health sector (NHS) patients in the UK, suggesting limitations in the "fully informed" consent process for CS. Most NHS CS patients are currently willing to wear spectacles after CS, especially reading glasses. There is reluctance in such patients to consider premIOLs on a background of small risks of debilitating dysphotopsias and increased risks of a second operation., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: To compare productivity of National Health Service cataract lists performing unilateral cataract (UC) surgery vs Immediate Sequential Bilateral Cataract Surgery (ISBCS)., Methods: Five 4-hour lists with ISBCS cases and five with UC were observed using time and motion studies (TMS). Individual tasks and timings of each staff member in theatre was recorded by two observers. All operations were performed by consultant surgeons under local anaesthesia (LA)., Results: Median number of eyes operated per 4-hour list was 8 (range 6-8) in the ISBCS group and 5 (5-7) in the UC group (p = 0.028). Mean total theatre time (defined as time between the entry of the first patient and the exit of the last patient from theatre) was 177.12 (SD 73.62) minutes in the ISBCS group and 139.16 (SD 47.73) minutes in the UC group (p = 0.36). Mean time to complete two consecutive unilateral cataract surgery operations was 48.71 minutes compared to 42.23 minutes for a single ISBCS case (13.30% time saved). Based on our collected TMS data, a possible 5 consecutive ISBCS cases and 1 UC (total 11 cataract surgeries) could be performed during a four-hour theatre session, with a theatre utilisation quotient of 97.20%, contrasting to nine consecutive UC, with a theatre utilisation quotient of 90.40%., Discussion: Performing consecutive ISBCS cases under LA on routine cataract surgery lists can increase surgical efficiency. TMS are a useful way to investigate surgical productivity and test theoretical models for efficiency improvements., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: Studies of predominantly White participants show that cryolipolysis reduces subcutaneous fat in the arms and inner thighs, but none have specifically tested for similar outcomes in participants of Chinese descent., Objectives: This study assessed the safety and effectiveness of cryolipolysis treatment for noninvasive subcutaneous fat reduction of arms and inner thighs in participants of Chinese descent to assess equivalence to results seen in a prior study of White participants., Methods: Replicating a similar study design, participants of first- or second-generation Chinese descent underwent cryolipolysis treatment of arms and/or inner thighs. Effectiveness was assessed using pretreatment and posttreatment photographic review by blinded, independent experts, investigator-assessed caliper measurements, and participant satisfaction 12 weeks posttreatment. Safety was assessed throughout., Results: Among 50 enrolled participants, 48 completed the study. The majority of participants (97.9%) were female, with a mean age of 36.0 years and mean BMI of 24.16 kg/m 2 (range 19.3-29.9 kg/m 2 ). Overall, 76.4% and 70.0% of pretreatment photographs of arms and pairs of inner thighs, respectively, were correctly identified by at least 2 of 3 reviewers. The mean reduction from baseline in caliper-measured fat thickness was 6.5 mm for arms and 6.6 mm for inner thighs, and the majority of participants (>60%) were satisfied with the treatment. No adverse events were reported., Conclusions: Cryolipolysis is a well-tolerated, effective means of noninvasive fat reduction of arms and inner thighs in participants of Chinese descent. The results from this study show similar effectiveness and safety in Chinese participants compared with White participants treated in a prior study., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Aesthetic Society.)

Descemet membrane endothelial keratoplasty (DMEK) is a partial-thickness corneal transplantation procedure that involves selective transplantation of the Descemet membrane and endothelium. DMEK offers significant advantages over other keratoplasty techniques, such as faster visual rehabilitation, better final visual acuity due to minimal optical interface effects, lower risk of allograft rejection, and less long-term dependence on topical steroids. Despite all its advantages, DMEK has been found to be more challenging than other corneal transplantation techniques, and its steep learning curve appears to be an obstacle to its widespread use and adoption by corneal surgeons worldwide. DMEK surgical training laboratories (wet labs) provide a window of opportunity for surgeons to learn, prepare, manipulate, and deliver these grafts in a risk-free environment. Wet labs are a significant learning tool, especially for those institutions that have limited tissue availability in their local centers. We provide a step-by-step guide for preparing DMEK grafts using different techniques on human and nonhuman models with instructional videos. This article should eventually help the trainees and the educators understand the requirements for performing DMEK and conducting a DMEK wet lab and develop their skills and interests from a wide variety of available techniques., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate corneal astigmatic outcomes of femtosecond laser-assisted arcuate keratotomies (FAKs) combined with femtosecond-laser assisted cataract surgery (FLACS) over 12mo follow-up., Methods: Totally 145 patients with bilateral cataracts and no ocular co-morbidities were recruited to a single-centre, single-masked, prospective randomized controlled trial (RCT) comparing two monofocal hydrophobic acrylic intraocular lenses. Eyes with corneal astigmatism (CA) of >0.8 dioptres (D) received unpaired, unopened, surface penetrating FAKs at the time of FLACS. Visual acuity, subjective refraction and Scheimpflug tomography were recorded at 1, 6, and 12mo. Alpins vectoral analyses were performed., Results: Fifty-one patients (61 eyes), mean age 68.2±9.6y [standard deviation (SD)], received FAKs. Sixty eyes were available for analysis, except at 12mo when 59 attended. There were no complications due to FAKs. Mean pre-operative CA was 1.13±0.20 D. There was a reduction of astigmatism at all post-operative visits (residual CA 1mo: 0.85±0.42 D, P =0.0001; 6mo: 0.86±0.35 D, P =0001; and 12mo: 0.90±0.39, P =0.0001). Alpins indices remained stable over 12mo. Overall, the cohort was under-corrected at all time points. At 12mo, 61% of eyes were within ±15 degrees of pre-operative astigmatic meridian., Conclusion: Unpaired unopened penetrating FAKs combined with on-axis phacoemulsification are safe but minimally effective. CA is largely under-corrected in this cohort using an existing unmodified nomogram. The effect of arcuate keratotomies on CA remained stable over 12mo., (International Journal of Ophthalmology Press.)

Background: PREDICT was a Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA treatment for chronic migraine (CM). We descriptively assess health resource utilization, work productivity, and acute medication use., Methods: OnabotulinumtoxinA (155-195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Participants completed a 4-item health resource utilization questionnaire and 6-item Work Productivity and Activity Impairment Questionnaire: Specific Health Problem V2.0. Acute medication use was recorded in daily headache diaries. Treatment-emergent adverse events were recorded throughout the study., Results: A total of 197 participants were enrolled, and 184 received ≥1 treatment with onabotulinumtoxinA and were included in the analysis. Between baseline and the final visit, there were decreases in the percentage of participants who reported headache-related healthcare professional visit(s) (96.2% to 76.8%) and those who received headache-related diagnostic testing (37.5% to 9.9%). Reductions from baseline were also observed in the mean number of headache-related visits to an emergency room/urgent care clinic (2.5 to 1.4) and median headache-related hospital admissions (4.0 to 1.0). OnabotulinumtoxinA improved work productivity and reduced the mean (standard deviation) number of hours missed from work over a 7-day period (6.1 [9.7] to 3.0 [6.8]). Mean (standard deviation) acute medication use decreased from baseline (15.2 [7.6] to 9.1 [6.5] days). No new safety signals were identified., Conclusions: Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA treatment for CM in the Canadian population reduces health resource utilization and acute medication use and improves workplace productivity, supporting the long-term benefits of using onabotulinumtoxinA for CM.

Here we describe a new, non-human, ex-vivo model (goat eye model) for training surgeons in DMEK surgeons. In a wet lab setting, goat eyes were used to obtain a pseudo-DMEK graft of 8 mm from the goat lens capsule that was injected into another goat eye with the same maneuvers described for human DMEK. The DMEK pseudo-graft can be easily prepared, stained, loaded, injected, and unfolded into the goat eye model reproducing the similar maneuvers used for DMEK in a human eye, except for the descemetorhexis, which cannot be performed. The pseudo-DMEK graft behaves similar to human DMEK graft and useful for surgeons to experience and understand steps of DMEK early in learning curve. The concept of a non-human ex-vivo eye model is simple and reproducible and obviates the need for human tissue and the issues of poor visibility in stored corneal tissue., Competing Interests: None

Abstract: Descemet membrane (DM) endothelial keratoplasty is considered the gold standard for treating corneal endothelial decompensation and is a true like-for-like replacement. Not all causes of endothelial dysfunction are global, with conditions such as viral endotheliitis affecting discrete populations of endothelial cells. In this study, endothelial grafts matching the area of dysfunction were produced to preserve healthy host cells and limit the immunological burden of new grafts. We have termed this modified DM endothelial keratoplasty procedure DM endothelial patching., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Emerging monoclonal antibody therapies are assuming greater importance in the management of severe and refractory forms of immunity-driven and oncological disorders. However, some have been found to induce adverse ocular events (AOEs) leading to discontinuation of treatment or additional multidisciplinary management. We present the current knowledge concerning AOEs associated with 3 monoclonal antibody therapies: dupilumab, tralokinumab, and belantamab mafodotin. We examine the manifestations of their AOEs, proposed pathophysiological mechanisms, and current treatment recommendations. We identified and reviewed all studies for dupilumab, tralokinumab, and belantamab mafodotin using the keywords "dupilumab," "tralokinumab," "belantamab mafodotin," "conjunctivitis," and "keratopathy" from January 2016 to November 2021. Conjunctivitis was the most frequently reported AOE in patients with atopic dermatitis receiving dupilumab or tralokinumab. Mild cases were managed with warm compresses for associated meibomian gland dysfunction, artificial tears, and antihistamine/mast cell stabilizer eye drops. In more severe cases, additional anti-inflammatory therapy, with corticosteroid eye drops or ointments, or topical calcineurin inhibitors-such as tacrolimus or ciclosporin-were required. Patients with resistant or refractory multiple myeloma treated with belantamab mafodotin often developed keratopathy, which could necessitate contact lens fitting, or for cycles of belantamab mafodotin to be delayed., Competing Interests: S. J. Robbie has received consultancy fees from Sanofi Genzyme. A. E. Pink has acted as investigator, speaker, advisor or received educational or research support from Lilly, Pfizer, Sanofi, Abbvie, Leo, Novartis, Almirall, Boehringer, Amgen, UCB. BMS, La-Roche Posay, Janssen. David O'Brart holds noncommercial research grants with Rayner Ltd. and Johnson and Johnson Inc. He is a consultant for Sparca Inc. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background/objectives: During the COVID-19, elective cataract surgery (CS) was significantly curtailed. We investigated whether consequent reduction of micro-surgical skills practice might lead to higher operative complications., Methods: Single-centre, electronic note review of consecutive patients undergoing CS during three periods: 1 st February 2019 to 13 th January 2020 (P1) prior to pandemic; 3rd June 2020 to 11th January 2021 after 1 st lockdown (P2); and 25 th January to 30 th July 2021 (P3) after/during second lockdown., Results: 2276 operations occurred during P1, 999 during P2, 846 during P3. During P1, posterior capsular rupture (PCR) rate was 1.67%, similar to P2 (1.30%, p = 0.54), but lower than P3 (3.55%, p = 0.002). There was no difference in PCR risk percentage scores between routine and PCR cases during P1 (1.90% vs 2.03%, p = 0.83), P2 (2% vs 2.18%, p = 0.18), or P3 (1.87% vs. 2.71%, p = 0.08). During P2 and P3, there was a higher rate of cystoid macular oedema (CMO) compared with P1 (4.9% and 6.86% vs. 1.93%, p = 0.0001), with no differences in proportion of diabetics or cases with CMO in combination with PCR. There was no difference in surgeons grade experiencing PCR., Conclusions: In P3 following 9 months of curtailed elective CS, PCR rates were increased across all surgeon grades, occurring in cases with similar risk percentage scores. CMO rates were increased during COVID and not related to proportion of diabetics or increased PCR rates. The reduction in elective CS during the pandemic was associated with more complications, perhaps due to attenuation of microsurgical skills., (© 2022. The Author(s).)

Objectives: The aim of the present study was to explore self-interest, kin altruism and non-kin altruism reasons that influence people to vaccinate against COVID-19., Study Design: This was a cross-sectional study using a fully repeated measures design., Methods: Participants (N = 178) answered questions on perceived threat and likelihood of infection, vaccination status and opinion on mandatory vaccination. Participants also rated a set of statements that asked how likely these would influence them and others to vaccinate against COVID-19. Statements reflected self-interest, kin altruism or non-kin altruism., Results: Just more than half of the sample (50.8%) reported the likelihood of infection as somewhat or extremely likely, and almost three-fourths (74.2%) reported that COVID-19 posed a minor or moderate threat to their physical health. Almost three-fourths (74.3%) of the sample were vaccinated, with just more than half (56.2%) in favour of mandatory vaccination. A 2 (self/other) × 3 (self-interest/kin altruism/non-kin altruism) fully repeated measures analysis of variance showed that kin-altruistic reasons were rated most highly, regardless of whether this was regarding oneself or others. Participants rated others as having greater self-interest reasons for vaccination compared with oneself, whereas non-kin altruism reasons for vaccination were rated higher for oneself, compared with others., Conclusion: Highlighting the benefits of vaccination for close relatives and vulnerable others in the population would be a useful strategy for government to use when urging the public to vaccinate against COVID-19., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The purpose of this study was to report a novel surgical technique for altering donor Descemet membrane endothelial keratoplasty (DMEK) curvature to match host posterior stroma in a patient with advanced keratoconus (KC) and endothelial decompensation., Methods: We report a 56-year-old man with Fuch endothelial dystrophy and KC, who underwent DMEK due to endothelial decompensation. A triangular area of graft detachment centered on the apex of cones persisted after repeat gas tamponade. A radial incision from the graft edge to the apex was used to allow overlapping of the graft, thereby increasing the grafts curvature., Results: The use of a radial incision in the Descemet membrane (DM) graft was made to allow the graft overlap and adapt to the new shape. By matching the donor curvature to that of the hosts posterior curvature, full adhesion of the graft was achieved with the use of a short-acting air bubble by 1 week after the procedure., Conclusions: The mismatch in the curvature of the DM graft and the host posterior corneal surface, in cases with KC or very steep corneas, should be taken into consideration because it can lead to redundancy folds. These can result in atypical, conical detachments, distinct from the typical peripheral detachments seem commonly in DMEK. A single radial incision in the DM graft combined with air tamponade is a feasible treatment option in cases where DMEK fails to attach because of apparent curvature mismatch between the donor and host., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The PREDICT study assessed real-world, long-term health-related quality of life in adults with chronic migraine (CM) receiving onabotulinumtoxinA., Methods: Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA for CM. OnabotulinumtoxinA (155-195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Primary endpoint: mean change in Migraine-Specific Quality of Life Questionnaire (MSQ) at treatment 4 (Tx4) versus baseline. Secondary endpoints: mean change in MSQ at final visit versus baseline, and headache days., Results: 184 participants (average age 45 years; 84.8% female; 94.6% Caucasian) received ≥1 onabotulinumtoxinA treatment; 150 participants completed 4 treatments (1 year) and 123 completed all 7 treatment cycles (2 years). Mean (SD) onabotulinumtoxinA dose per treatment cycle was 171 (18) U and treatment interval was 13.2 (1.8) weeks. Baseline mean (SD) 20.9 (6.7) headache days/month decreased (Tx1: -3.5 [6.3]; Tx4: -6.5 [6.6]; p < 0.0001 versus baseline). Mean (SD) increased from baseline in MSQ at Tx4 (restrictive: 21.5 [24.3], preventive: 19.5 [24.7], emotional: 22.9 [32.9]) and the final visit (restrictive: 21.3 [23.0], preventive: 19.2 [23.7], emotional: 27.4 [30.7]), exceeding minimal important differences (all p < 0.0001). Seventy-seven (41.8%) participants reported 168 treatment-emergent adverse events (TEAEs); 38 TEAEs (12.0%) were considered treatment-related. Four (2.2%) participants reported six serious TEAEs; none were considered treatment-related. No new safety signals were identified., Conclusions: Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA for CM in Canada improved MSQ scores and reduced headache frequency and severity, adding to the body of evidence on the long-term safety and effectiveness of onabotulinumtoxinA for CM.

Following corneal transplantation, there is an initial, rapid decline in corneal endothelial cells (CECs) following surgery. Direct imaging of post-transplantation endothelial cells is only possible weeks after surgery and with a limited field of view. We have developed a labelling approach using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DIR) dye solution, that enables tracking of labelled CECs in vivo for at least 1 month. Initial in vitro optimization, with assessments of dye concentration on fluorescence, cellular toxicity and cell migration, performed in propagated primary CECs. Subsequently, in vivo evaluation of cellular labelling was assessed within a rabbit wound healing model. Finally, real-time visualization of human cadaver donor tissue incubated in DIR transplanted into rabbits was achieved using a clinical confocal microscope. Results revealed detectable fluorescence increased with concentration to a plateau of 100 µg/ml, with no toxicity of CECs at any concentration evaluated. DIR-labelled CECs were detectable in vivo up to 1 month, and transplanted labelled donor graft could be visualized and were trackable in vivo. Acute endothelial rejection in 1 rabbit was evidenced by detectable DIR positive cells within the anterior chamber. DIR imaging allowed for detailed imaging of the transplanted human corneal endothelium, and enabled non-invasive observation of the corneal endothelial morphology following transplantation., (© 2022. The Author(s).)

Introduction: Symptoms of cervical dystonia (CD) can vary in severity and cause significant pain. OnabotulinumtoxinA is an approved treatment for CD. This study assessed health-related quality of life (HRQoL) in patients with CD who received multiple onabotulinumtoxinA treatments., Methods: This prospective, observational standard-of-care study was conducted at multiple neurology centers in Québec, Canada. Patients reported the health impact of CD using the Cervical Dystonia Impact Profile (CDIP)-58, before and after up to eight onabotulinumtoxinA treatments. Other measures included the Cervical Dystonia Severity Rating Scale by physician, employment status using the Work Productivity Questionnaire and pain using the Pain Numeric Rating Scale (PNRS). Adverse events (AEs) were recorded., Results: Sixty-two patients were enrolled (safety population, n = 61; modified efficacy population, n = 58). Participants were mostly females who were employed; most (79.3%) had torticollis. In all, 21/62 patients (33.9%) discontinued the study. At the final visit, there was a statistically significant (p < 0.001) improvement in all eight CDIP-58 subscales, particularly head and neck symptoms (-31.0) and psychosocial functioning (-28.2). Employment increased from baseline (55%) to the end of the study (64%), and there was improvement in work productivity. There was a significant (p < 0.0001) reduction in pain measured by the PNRS, from -0.5 post-treatment 1 to -2.4 at end of study. AEs (neck pain, muscular weakness, dysphagia, nausea) were consistent with onabotulinumtoxinA use., Conclusion: These real-world data indicate that after repeated, long-term use, onabotulinumtoxinA continues to be a safe and effective treatment for CD, improving HRQoL and work productivity.

Corneal transplantation is the most commonly performed human tissue transplantation procedure worldwide. Because of the large number of transplants, corneal graft failure has become one of the most common indications for corneal transplantation. The relatively recently developed lamellar transplant techniques have brought about specific potential complications leading to graft failure that may require different approaches to repeat transplantation other than penetrating keratoplasty. On the other hand, these new lamellar techniques also provide novel ways of rescuing failed penetrating grafts, with potential advantages over successive penetrating keratoplasties, such as reduced intraoperative risks and faster visual rehabilitation. We summarize the incidence and risk factors of graft failure for penetrating and lamellar (stromal and endothelial) corneal transplants and discuss the various surgical alternatives currently available to rescue such failed grafts, with a focus on the reported outcomes and limitations., (Copyright © 2020 Elsevier Inc. All rights reserved.)