Applicability of the New Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease Diagnostic Criteria in an Israeli Cohort.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare autoimmune demyelinating disorder of the central nervous system. Optic neuritis (ON) is the most common clinical manifestation of MOGAD in adults. In 2023, new MOGAD diagnostic criteria were proposed, highlighting the importance of supplemental criteria when MOG-immunoglobulin G (IgG) titers are unavailable. OBJECTIVES: To investigate the applicability of the 2023 MOGAD criteria in patients diagnosed with MOGAD and treated before the availability of MOG-IgG titers. METHODS: We conducted a retrospective chart review of patients classified as MOGAD between 2010 and 2023 at Rabin Medical Center. Patient demographics as well as clinical and imaging data were collected, including visual acuity, expanded disability status score, core demyelinating events, antibody status, and brain and optic nerve magnetic resonance imaging data. Patients fulfilling the 2023 MOGAD criteria were reported as definite MOGAD. RESULTS: Fifteen patients met the 2023 MOGAD diagnostic criteria despite lack of MOG-IgG titer. The most common supplemental criterion meeting the 2023 MOGAD criteria was optic disc edema (n=12, 80%), followed by longitudinal optic nerve involvement (53%), bilateral ON (40%), and perineural optic sheath enhancement (33%). CONCLUSIONS: All patients with a clinical diagnosis of MOG-ON in our cohort fulfilled the 2023 MOGAD criteria despite the lack of antibody titers. The 2023 MOGAD criteria can be reliably applied to Israeli cohorts, prior to availability of MOGAD IgG titers, with particular attention to additional supplemental criteria. Since the 2023 MOGAD criteria were published, MOGAD IgG titers have been added to routine testing at our facility.

The effect of pregnancy on the course of uveitis in single and multiple pregnancies.

PURPOSE: To explore the effect of pregnancy on the clinical course, outcome, and treatment in multiparous women with non-infectious uveitis. METHODS: Retrospective study of women with a history of non-infectious uveitis and pregnancies prior to and during disease course. Disease activity and severity 1-year prior pregnancy, during pregnancy, and 1-year postpartum were recorded as well as patients' and diseases' characteristics. The main outcome measures included the rate and severity of uveitis attacks and the effect on ocular complications and therapies. RESULTS: Included were 32 women (70 pregnancies, mean of 2.6 pregnancies/patient), with a mean follow-up time of 6.5 years. The most common uveitis types were anterior (31%) and pan-uveitis (31%). Flare-ups were more frequent in the year prior to pregnancy, in the first trimester, and in the postpartum period and decreased markedly during pregnancy. Women who experienced a flare-up during pregnancy had a higher rate of flare-ups in the year prior pregnancy than those who did not experience a flare-up during pregnancy (p-0.047). The rate of flare-ups 12 months' postpartum was also higher compared to women without any flare-up during pregnancy (p = 0.01). Severity of flare-ups in the postpartum period was worse in women who experienced a flare-up during pregnancy compared to women without flare-ups (p = 0.001). The severity of flare-ups was higher in the first pregnancy compared to subsequent pregnancies. CONCLUSIONS: Women who had active or non-controlled uveitis prior to pregnancy have higher disease activity and severity during pregnancy as well. The first pregnancy seems to behave differently from subsequent pregnancies, in terms of disease severity.

The Effect of COVID-19 on Israeli Ophthalmology Departments: Directors' Perspectives.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic presented a major medical management challenge to ophthalmology departments throughout Israel. OBJECTIVES: To examine the managerial challenges, actions taken, and insights of directors of ophthalmology departments in Israel during the COVID-19 pandemic. METHODS: We conducted a cross sectional survey of directors of ophthalmology departments during the COVID-19 pandemic while the Israeli population was quarantined. RESULTS: All 21 directors answered the survey. The majority of the COVID-19 admissions were located in the center of Israel (53%) and Jerusalem (30%). E-communication took a central role in coping with the pandemic with 80% of the directors satisfied with this form of communication; 75% reported a reduction in clinical and surgery volume of at least 25%, and 40% reported reallocations of manpower. Most of the medical staff used gloves, a face shield, disposable robe, and a mask with no uniformity across departments. Cross satisfaction was noted regarding a hospital's ability to equip the departments. Lack of preparation for post-pandemic era was reported by all directors, but one (95%). Directors sought guidelines and uniformity regarding outpatient referral to the hospital (p = 0.035). CONCLUSIONS: Guidelines via safe digital platforms aid in management decisions and uniformity across departments. Advanced preparation is needed to prevent adverse clinical outcomes and to maintain treatment continuum. Our results can be used to guide and help improve the preparedness of ophthalmology departments during COVID-19 and for future pandemics.

Posterior synechia formation after phacovitrectomy - Predicting factors and the role of short-acting mydriatics.

PURPOSE: To evaluate the influence of topical short-acting mydriatics on the formation of posterior synechia after phacovitrectomy surgery of pars plana vitrectomy and phacoemulsification with intraocular lens implantation. METHODS: A prospective randomised controlled trial. Fifty-seven adult (>18 years old) patients (57 eyes) who underwent phacovitrectomy surgery at a single tertiary hospital, were randomly divided into two groups. The control group (29 eyes) received standard postoperative treatment (topical antibiotics and steroids). The study group (28 eyes) received short-acting mydriatics together with standard therapy. Patients were followed until 24 months after surgery. The primary outcome measure was the formation of posterior synechia during the follow-up period. RESULTS: A total of 7 patients developed posterior synechia during the follow-up period (12%), 3 in the study group (11%) and 4 in the control group (14%). There was no statistical difference between the groups. Significant associations for the development of posterior synechia were surgery for retinal detachment, longer surgery duration (>93 min) and the use of tamponade, in particular silicone oil. CONCLUSIONS: The use of topical short-acting mydriatic drops after phacovitrectomy surgery, in addition to standard post-operative treatment, did not reduce the formation of posterior synechia. However, we identified several factors that may influence or act as predictors for the development of posterior synechia: surgery for retinal detachment, using silicone oil tamponade and a longer surgery duration. Our findings may aid in the standardisation of post-phacovitrectomy surgery treatment and define potential at-risk patients who should be monitored more closely.

Machine Learning-Based Identification of Risk Factors of Keratoconus Progression Using Raw Corneal Tomography Data.

PURPOSE: The purpose of this study was to identify early indicators of keratoconus progression in Pentacam data using machine learning (ML) techniques. METHODS: A retrospective Pentacam tabular data set was created by retrieving 11,760 tomography tests performed in patients with keratoconus. Data for eyes labeled unstable based on their referral for cross-linking were differentiated from data for eyes labeled stable and not referred for follow-up procedures. A boosted decision tree was trained on the final data set using a cross-validation method. RESULTS: The final labeled data set included 1218 tomography tests. Training a ML model on a single test for each eye did not accurately predict disease progression, as indicated by the mean receiver-operating characteristic area under the curve of 0.59 ± 0.1, with precision of 0.27, recall of 0.3, and F1 score of 0.28. Training on serial tests for each eye included 819 tomography scans and yielded good prognostic abilities: a receiver-operating characteristic area under the curve of 0.75 ± 0.07, precision of 0.32, recall of 0.67, and F1 score of 0.43. In addition, 4 of the 55 Pentacam raw data parameters predominantly used the algorithm decision: age, central keratoconus index, Rs B, and D10 mm pachy. CONCLUSIONS: This study revealed specific dominant parameters attributing to the classification of stability, which are not routinely assessed in determining progression in common practice. Using ML techniques, keratoconus deterioration was evaluated algorithmically with training on multiple tests, yet was not predicted by a single tomography test. Hence, our study highlights novel factors to the current consideration of cross-linking referral and may serve as a supportive tool for clinicians.

Application of the international criteria for optic neuritis in the Acute Optic Neuritis Network.

OBJECTIVE: The first international consensus criteria for optic neuritis (ICON) were published in 2022. We applied these criteria to a prospective, global observational study of acute optic neuritis (ON). METHODS: We included 160 patients with a first-ever acute ON suggestive of a demyelinating CNS disease from the Acute Optic Neuritis Network (ACON). We applied the 2022 ICON to all participants and subsequently adjusted the ICON by replacing a missing relative afferent pupillary defect (RAPD) or dyschromatopsia if magnetic resonance imaging pathology of the optical nerve plus optical coherence tomography abnormalities or certain biomarkers are present. RESULTS: According to the 2022 ICON, 80 (50%) patients were classified as definite ON, 12 (7%) patients were classified as possible ON, and 68 (43%) as not ON (NON). The main reasons for classification as NON were absent RAPD (52 patients, 76%) or dyschromatopsia (49 patients, 72%). Distribution of underlying ON etiologies was as follows: 78 (49%) patients had a single isolated ON, 41 (26%) patients were diagnosed with multiple sclerosis, 25 (16%) patients with myelin oligodendrocyte glycoprotein antibody-associated disease, and 15 (9%) with neuromyelitis optica spectrum disorder. The application of the adjusted ON criteria yielded a higher proportion of patients classified as ON (126 patients, 79%). INTERPRETATION: According to the 2022 ICON, almost half of the included patients in ACON did not fulfill the requirements for classification of definite or possible ON, particularly due to missing RAPD and dyschromatopsia. Thorough RAPD examination and formal color vision testing are critical to the application of the 2022 ICON.

Academic benchmark of highly influential ophthalmologists listed in the ophthalmology power list.

OBJECTIVE: To review the academic benchmark of highly influential ophthalmologists listed in the ophthalmology '2020 Power List'. METHODS: In this cross-sectional study, the academic profiles, achievements, and bibliometric profiles of all ophthalmologists listed in the 'Power List of 2020', regarded as the most influential figures in ophthalmology today, were analysed. RESULTS: Ninety-five ophthalmologists were studied, after excluding 10 non-ophthalmologist figures that are also listed. Their mean age is 63 ± 11.7 years, with a strong male predominance (84.2%, n = 80 males, P < 0.001). All have a medical doctorate degree, and 31% (n = 29) have a Philosophy Doctor (PhD) degree. Fifty-three percent (n = 51) are graduates of medical schools in the United States (US). However, non-US ophthalmologists have a higher percentage of PhD degrees (41%, 18/44) vs. US ophthalmologists (22%, 11/51, P = 0.069), and also a longer duration of post-residency training (5.8 ± 3.1 vs. 1.8 ± 0.9 years, P < 0.001). The most common subspecialty was cataract and anterior segment surgery (42%, n = 40). The mean and standard deviation of the total number of papers published by ophthalmologists were 307.4 ± 226.3, with a mean citation record of 11,835.7 ± 13,330.5, and a mean h-index of 46.9 ± 27.9. CONCLUSIONS: The ophthalmologists listed on the 'Power List of 2020' are leaders with high accomplishments and an established interest in research evidenced by a high record of publications and an exceptional bibliometric profile. The list contains more US figures with a gender disparity, demonstrating a greater difficulty for international ophthalmologists, especially women, in achieving this high level of recognition.

ABCD progression display for keratoconus progression: a sensitivity-specificity study.

OBJECTIVE: To evaluate the sensitivity and specificity of the ABCD progression display for keratoconus progression. METHODS: Data was collected from patients that underwent at least two Pentacam assessments 6 months apart. Sensitivity and specificity were calculated for the ABCD progression display. Progression was defined by criterion 1: change in two ABCD parameters above 80% confidence interval (CI) or criterion 2: change in one ABCD parameter above 95%CI. Receiver operating characteristic analysis compared the area under the curve (AUC) of all ABCD parameter combinations. RESULTS: Thirty eyes were evaluated over a median time of 10.3 months. Progression by criterion 1 resulted in a sensitivity of 61.9% and specificity of 88.9%. Progression by criterion 2 resulted in higher sensitivity (80.9%) and specificity (100%). Pairwise comparisons of the ROC curves show that the AUC achieved by criterion 2 was significantly higher than criterion 1 (0.905 vs. 0.754, p = 0.0332). Evaluation of all ABCD combinations with a significant change of 80% or 95% CI did not show superiority over criterion 1 or 2 regarding progression detection. The D parameter had a very low AUC (0.5-0.556). CONCLUSIONS: The ABCD progression display can assess keratoconus progression with high sensitivity and specificity, thus assisting the patients' decision-making process. The D parameter did not contribute to the sensitivity or specificity of this classification.

The initial rate of tumour response to vismodegib treatment, can predict a complete response outcome for periocular LA-BCC.

PURPOSE: To establish a model to predict treatment outcome of periocular locally advanced basal cell carcinoma (POLA BCC) based on initial response to treatment with vismodegib (ErivedgeTM), a sonic hedgehog inhibitor. DESIGN: Subgroup analysis of data from the STEVIE study database. METHODS: Analysis of medical history, treatment protocol, and treatment outcome of POLA BCC tumours in a STEVIE study population of 244 POLA BCC patients treated with ≥1 dose of vismodegib. RESULTS: A predictive model for complete response (CR) was established based on the initial treatment response. A cutoff value of 20% reduction in tumour size at 3 months of treatment identified the patients with a high probability (82.76%) to achieve CR. A second cutoff value of 67.7% reduction in tumour size at 6 months of treatment improved the prediction to a 95.42% probability of a CR outcome. CONCLUSIONS: A treatment model was constructed based on the prediction of a CR outcome and the initial response to vismodegib treatment at 3 and 6 months. The study result provide significant new insights can facilitate decision-making on treatment management according to tumour response in patients with POLA BCC.

Primary cemiplimab treatment for orbital squamous cell carcinoma is effective and may alleviate the need for orbital exenteration.

PURPOSE: To evaluate the effectiveness of cemiplimab, a Programmed-cell-death-1(PD-1) protein inhibitor, for the treatment of cutaneous periocular-locally-advanced squamous-cell-carcinoma (POLA-SCC) with orbital-invasion. METHODS: Multicentre real-world retrospective study. Demographic and clinical data were collected and analysed for patients with biopsy-proven POLA-SCC(AJCC-T4) with orbital-invasion who were treated with cemiplimab at one of four tertiary medical centres in 2019-2022. RESULTS: The cohort included 13 patients, 8 males and 5 females, of median age 76 years (IQR65-86). The median duration of treatment was 5.0months (IQR3.5-10.5) and the median follow-up time, 15.0 months (IQR10.5-30). The overall response rate was 69.2%. Complete response was documented in seven patients (53.8%), partial response in two (15.4%), stable disease in one (7.7%), and progressive disease in two (15.4%); in one patient (7.7%), response was not evaluable. Six complete responders (46.1% of the cohort) received no further treatment and did not have a recurrence during an average follow-up of 6.14 (±6.9) months from treatment cessation. None of the patients underwent orbital-exenteration. The majority of adverse events were mild (grade-1), except for a moderate increase in creatinine level (grade-2), severe bullous dermatitis (grade-3), and myocarditis (grade-5) in one patient each. Four patients (30.7%) died during the follow-up period, all of whom had an Eastern-Cooperative-Oncology-Group score of 4 at presentation. CONCLUSIONS: To our knowledge, this is the largest study to date on cemiplimab therapy for cutaneous POLA-SCC with orbital-invasion. Treatment was shown to be effective, with an overall response rate of 69.2%. Cemiplimab holds promise for the treatment of patients with tumours invading the orbit as it may alleviate the need for orbital exenteration.

Prognostic factors for visual acuity improvement after treatment of submacular hemorrhage secondary to exudative age-related macular degeneration.

PURPOSE: To recognize prognostic factors for better final visual acuity (VA) in patients presenting with submacular hemorrhage (SMH) secondary to exudative age-related macular degeneration. METHODS: This retrospective study included patients who presented to a tertiary ophthalmology department between 2012 and 2019 with SMH and were treated by pars plana vitrectomy (PPV) or injection of tissue plasminogen activator (tPA) with pneumatic displacement. Baseline characteristics included demographic data, VA and optical coherence tomography (OCT) characteristics of the SMH. Patients were divided into groups by improvement of at least 2 lines in BCVA (best corrected visual acuity), and by having a final BCVA better than 20/200. RESULTS: Forty-three eyes of 43 patients were included. Mean age was 86.72 ± 7.18. Prognostic factors for final VA better than 20/200 included better VA at presentation (1.25 vs 1.90 logMAR, p < 0.001), smaller area of SMH in the infra-red image (19.47 mm2 vs 38.45 mm2, p = 0.024), and lower height of SMH as measured by OCT (713.5 µm vs 962.5 µm, p = 0.03). Third of the patients improved in ≥2 lines from presentation, all in the group of the pneumatic and TPA displacement. CONCLUSION: Smaller SMHs with good VA at presentation have a better chance for improvement and result in a better final VA. These patients may benefit the most from pneumatic displacement of the SMH with intravitreal tPA and gas.

Visual acuity outcome in patients with subretinal hemorrhage - office procedure vs. surgical treatment.

PURPOSE: To evaluate the effects of intravitreal injection of tissue plasminogen activator (tPA) and gas vs. pars plana vitrectomy (PPV) surgery as first-line treatment for subretinal hemorrhage. METHODS: Retrospective study of 107 adults treated for subretinal hemorrhage at a tertiary hospital during 2008-2019; 51 received injection of tPA and gas and 56 underwent PPV. RESULTS: No between-group differences were found in age and sex, medical history, use of anticoagulants or antiplatelets, history of ocular surgeries, and previous use of intravitreal anti-VEGF. Overall follow-up time was longer in the PPV group (median 4.9 vs 3.28 years, p = 0.005). The hemorrhage was displaced in a similar percentage of patients in the tPA-and-gas group (n = 40, 78.4%) and the PPV group (n = 45, 80.4%) (p = 0.816). Approximately 80% of patients in the tPA-and-gas group were able to forgo PPV surgery. Visual acuity (in LogMAR) was similar in the two groups prior to the diagnosis of subretinal hemorrhage but better in the tPA-and-gas group at the end of follow-up (p < 0.001). CONCLUSION: Injection of gas and tPA can be done immediately following diagnosis of subretinal hemorrhage as an office procedure. Visual acuity outcome is good, with a high rate of blood displacement. About 20% of patients might require additional PPV as secondary intervention.

Vismodegib improves quality of life in patients with periocular locally advanced basal cell carcinoma: subgroup analysis, STEVIE trial.

OBJECTIVES: To evaluate the effect of locally advanced periocular basal cell carcinoma (POLA-BCC) on health-related quality of life (HRQoL) and the benefit of vismodegib treatment among participants in the Safety Events in Vismodegib (STEVIE) trial between 2011 and 2017. METHODS: The STEVIE trial was conducted in patients with BCC (all anatomic locations) who were treated with vismodegib in 28-day cycles. Patients completed the Skindex-16, a validated questionnaire for the analysis symptoms, emotions, and functioning, at baseline, on day 1 of cycle 2, on day 1 of cycle 7, and at the end-of-study visit. For the present study, data mining techniques were used to construct an ophthalmic database of the STEVIE study. Skindex-16 scores were compared among patients with POLA-BCC between baseline and follow-up and between patients with POLA-BCC and patients with locally advanced BCC on other sites of the head and face (controls). RESULTS: The cohort included 169 patients with POLA-BCC and 428 patients with non-periocular head BCC. Patients with POLA-BCC had a significantly worse overall functioning score at baseline than controls (p = 0.038) and a lower score specifically in activities of daily living (p = 0.001). At the last follow-up, patients with POLA-BCC showed significant improvement in scores for functioning (100%), symptoms (100%), and emotions (75%) relative to baseline. CONCLUSIONS: Secondary analysis of the results of the STEVIE trial showed that the HRQoL of patients with POLA-BCC is significantly impaired and can be greatly improved with vismodegib treatment.

Obesity is associated with myelin oligodendrocyte glycoprotein antibody-associated disease in acute optic neuritis.

Optic neuritis (ON) is a frequent presentation at onset of multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). The pathophysiology underlying these diseases, especially MOGAD, is still being elucidated. While obesity has been reported to potentially be a risk factor for MS, this has not been explored in NMOSD or MOGAD. We aimed to investigate a possible association between obesity (body mass index [BMI] > 30 kg/m2) in patients with MOGAD, aquaporin 4-IgG positive NMOSD (AQP4-IgG+ NMOSD) or MS. In this multicenter non-interventional retrospective study, data was collected from patients with a first ever demyelinating attack of ON subsequently diagnosed with MOGAD (n = 44), AQP4-IgG+ NMOSD (n = 49) or MS (n = 90) between 2005 and 2020. The following data was collected: age, sex, ethnicity, BMI (documented before corticosteroid treatment), and the ON etiology after diagnostic work-up. A mixed model analysis was performed to assess the potential of obesity or BMI to predict MOGAD-ON, and to distinguish MOGAD-ON from AQP4-IgG+ NMOSD-ON and MS-ON. Main outcome measures included BMI in patients with acute ON and subsequent diagnosis of MOGAD, AQP4-IgG+ NMOSD or MS. A higher BMI was significantly associated with a diagnosis of MOGAD-ON (p < 0.001); in MOGAD patients the mean BMI was 31.6 kg/m2 (standard deviation (SD) 7.2), while the mean BMI was 24.7 kg/m2 (SD 5.3) in AQP4-IgG+ NMOSD patients, and 26.9 kg/m2 (SD 6.2) in MS patients. Mixed-effects multinomial logistic regression, adjusted for age and sex, with obesity as a binary variable, revealed that obesity was associated with a higher odds ratio (OR) of a subsequent MOGAD diagnosis (OR 5.466, 95% CI [2.039, 14.650], p = 0.001) in contradistinction with AQP4-IgG+ NMOSD. This study suggests an association between obesity and MOGAD. Our findings require further exploration, but could have significant pathophysiologic implications if confirmed in larger prospective studies.

Academic background, professional experience, and research achievements of United States academic ophthalmology leadership.

PURPOSE: To characterize the academic background, professional experience, and scholarly achievements of United States (US) academic ophthalmologists serving in leadership positions. METHODS: This is a cross-sectional study. An online search of publicly available resources was conducted for demographics, background, research productivity, and academic appointments of academic ophthalmologists in leadership positions: chairperson (CP), vice chair (VC), service director (SD), and program director (PD). RESULTS: Five hundred and fifty-one academic ophthalmologists in leadership positions were analyzed. A male predominance was found in all positions, ranging from 86% male CPs to 68% of SDs. Eighty-nine percent were graduates of US medical schools, and 97% completed their residency in a US ophthalmology program. Harvard Medical School and The Johns Hopkins University School of Medicine and their affiliated programs were the most frequently attended by leaders. The most common subspecialties among leaders were surgical retina (21%), cornea (18%), and glaucoma (16%). Overall, 18% of leaders are endowed professors, 34% are full professors, 25% are associate professors, and 20% are assistant professors. Overall, 28% of department leaders were residents and 16% were fellows in their current program. Chairpersons, followed by their vice, are the most academically proficient leaders within their departments, having the largest number of publications and h, hc, hm, and AWCR bibliometric indices. CONCLUSIONS: Ophthalmology leaders in all positions are highly accomplished with an established interest in research. Typically, CPs and their VCs have a longer duration of professional experience with a greater research output and a superior median academic appointment. Gender discrepancies within leadership positions are evident.

Descemet Membrane Endothelial Keratoplasty Outcomes between Young and Old Graft Recipients.

Purpose: To evaluated Descemet's membrane endothelial keratoplasty (DMEK) outcomes in young and old graft recipients.Materials and Methods: Data of 164 surgeries with a median age of 76 years (interquartile range 14 years) undergoing DMEK surgery between 2016 and 2018 was reviewed. Complications, graft survival, and visual acuity gain were compared between subjects in the 25th percentile (young recipients; aged 70 years and less, n = 21) and 75th percentile (old recipients; aged 85 years and over, n = 27) over the 2-year follow-up.Results: Young recipients had a lower rate of pre-operative glaucoma (14.3% vs. 51.9%, p = .014) and pseudophakic bullous keratopathy (9.5% vs. 59.3%, p < .001), and a higher rate of Fuchs endothelial dystrophy (57.1% vs. 14.8%, p = .002) and combined cataract extraction at the time of DMEK surgery (52.4% vs. 7.4%, p = .001) when compared to old recipients. Complications (primary graft failure, pupillary block, cystoid macular edema or infectious keratitis) were independent of graft recipient age. Descemet's membrane detachment requiring re-bubbling was observed more often in young compared to the old recipients (42.9% vs. 14.8%, p = .049). Visual acuity gain between the groups remained comparable up to 1-year, whereas at 2-years old recipients showed significantly declined visual acuity gains compared to the young recipients (0.14 ± 0.68 vs. 0.74 ± 0.49, p = .012). Graft recipients aged over 85 years had a considerably higher graft failure rate over the 24-months (40.7% vs. 4.8%, p = .006) and shorter graft survival time (p = .002; log-rank) when compared to the recipients aged under 70 years. After adjusting for potential confounders such as Fuchs endothelial dystrophy, pseudophakic bullous keratopathy and glaucoma, the recipients aged over 85 remained at higher risk for graft failure (HR = 17.278, 95% CI = 1.787-167.1, p = .014).Conclusions: In aged DMEK recipients, regardless of the low incidence of early postoperative complications, the rate of postoperative graft failure was significantly higher and graft survival shorter than in younger recipients.

Postirradiation Capsular Contracture in Implant-Based Breast Reconstruction: Management and Outcome.

BACKGROUND: Implant-based breast reconstruction is commonly avoided in the setting of radiation therapy, mainly because of risks of capsular contracture. Nevertheless, as breast reconstruction is becoming more available, more patients undergo both implant-based breast reconstruction and radiotherapy. The dilemma is how to manage capsular contracture if it does occur. The goal of this study was to examine the outcome of patients with implant-based breast reconstruction who developed postirradiation capsular contracture and were treated with capsulotomy or capsulectomy, with or without fat grafting. METHODS: The authors reviewed charts of patients who developed capsular contracture following alloplastic breast reconstruction followed by radiation therapy, between 2008 and 2018. The surgical treatment methods for capsular contracture were evaluated along with their outcomes. A follow-up of at least 1 year was required. RESULTS: Forty-eight breasts with postirradiation capsular contracture underwent surgical implant exchange with capsular release, of which 15 had combined fat grafting and 33 did not. Overall, 35 breasts (72.9 percent) showed long-term resolution of capsular contracture; 24 underwent a single procedure and 11 required an additional fat grafting procedure. Some patients [six breasts (12.5 percent)] were offered a consecutive round of fat grafting, and some [seven breasts (14.5 percent)] were offered autologous reconstruction because of lack of improvement. Fat grafting increased the success rate by more than 30 percent when it was initially and consecutively used. CONCLUSIONS: Postirradiation capsular contracture may be treated successfully by secondary procedures, sustaining implant-based breast reconstruction in over 70 percent of breasts. Fat grafting may elevate resolution rates even further, to 86 percent. Larger prospective studies are required to validate these findings. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Risk factors for an atherothrombotic event in patients with diabetic macular edema treated with intravitreal injections of bevacizumab.

AIM: To identify risk factors for an atherothrombotic event (ATE) among patients who were treated for diabetic macular edema (DME) with intravitreal bevacizumab injections. METHODS: This retrospective study enrolled all consecutive patients with DME who were treated by intravitreal bevacizumab from 2009 through 2016 in a single center. They were divided into one group treated by bevacizumab and subsequently had an ATE and a second group also treated by bevacizumab and did not have an ATE. RESULTS: A total of 455 patients with DME were enrolled. Seventy-two of the patients had an ATE. A multivariate model adjusted for age, gender, smoking, body mass index, hemoglobin A1c (HbA1c), duration of diabetes, creatinine, and blood pressure revealed an increased risk for ATE in the patients with diabetic duration of more than 13y, a systolic blood pressure over 153.5 mm Hg at first treatment, or having been treated by more than 4 intravitreal bevacizumab injections. Additionally, patients that had an ATE within 3mo from the last intravitreal treatment underwent more bevacizumab injections (5.2±3.4 vs 3.07±1.86; P<0.001). CONCLUSION: The risk factors for an ATE identified in this study are systolic blood pressure >153.5 mm Hg, a history of diabetic mellitus for more than 13y, and treatment with more than 4 intravitreal bevacizumab injections. These factors need to be borne in mind when bevacizumab is being considered in the management of patients with DME.

Outcomes of Vismodegib for Periocular Locally Advanced Basal Cell Carcinoma From an Open-label Trial.

Importance: The outcomes of vismodegib treatment in a relatively large cohort of study participants with periocular locally advanced basal cell carcinoma (POLA-BCC) may guide physicians when considering this treatment. Objective: To report the outcomes of vismodegib treatment in patients with POLA-BCC in the Safety Events in Vismodegib (STEVIE) study. Design, Setting, and Participants: This post hoc subgroup analysis from the STEVIE single-arm, multicenter, open-label cohort study screened all 1215 participants for ocular or periocular involvement and identified 244 participants with POLA-BCC or metastatic BCC. Data for the first STEVIE trial were collected from 167 treatment locations in 36 countries from June 30, 2011, to June 14, 2017. This post hoc analysis was performed from April 1 to August 31, 2019. Main Outcomes and Measures: Response to treatment and adverse events. Results: Ocular or periocular involvement was found in 244 of 1215 STEVIE participants (20.1%), who constituted the analytic sample. The median age of the study participants was 72.0 (interquartile range [IQR], 60.0-82.0]) years, and they included 143 men (58.6%). Locally advanced BCC was diagnosed in 238 of the 244 participants (97.5%) and metastatic BCC, in 6 (2.5%). The median duration of exposure to vismodegib was 40.0 (IQR, 20.0-78.0) weeks, specifically 39.7 (IQR, 19.9-76.0) weeks for POLA-BCC and 92.4 (IQR, 53.2-163.0) weeks for metastatic BCC. Sixty-nine participants (28.3%) sustained serious adverse events (alopecia, muscle spasms, dysgeusia, weight loss, decreased appetite, asthenia, ageusia, nausea, fatigue, and diarrhea). Two hundred thirty-two study participants (95.1%) sustained more than 1 adverse effect. The overall mean (SD) number of drug-related adverse effects per study participant by first adverse event, regardless of the severity, was 5.48 (3.84). Discontinuation of vismodegib treatment owing to an adverse event was recorded in 58 participants (23.8%). During the study, 22 participants (9.0%) died, 70 (28.7%) achieved complete response, and 94 (38.5%) achieved partial response. Conclusions and Relevance: Vismodegib was well tolerated by the study participants with POLA-BCC. The safety of vismodegib treatment according to the STEVIE trial findings is consistent with that reported in previous studies. These data may be helpful when considering vismodegib for patients with POLA-BCC.