De novo and inherited monoallelic variants in TUBA4A cause ataxia and spasticity.

Alpha-tubulin 4A encoding gene (TUBA4A) has been associated with familial amyotrophic lateral sclerosis and frontotemporal dementia, based on identification of likely pathogenic variants in patients from distinct amyotrophic lateral sclerosis and frontotemporal dementia cohorts. By screening a multicentric French cohort of 448 unrelated probands presenting with cerebellar ataxia, we identified ultra-rare TUBA4A missense variants, all being absent from public databases and predicted pathogenic by multiple in silico tools. In addition, gene burden analyses in the 100 000 Genomes project (100KGP) showed enrichment of TUBA4A rare variants in the inherited ataxia group compared to controls [odds ratio: 57.0847 (10.2-576.7); P = 4.02 ×10-7]. Taken together, we report 12 patients presenting with spasticity and/or cerebellar ataxia and harbouring a predicted pathogenic TUBA4A missense mutation, including five confirmed de novo cases and a mutation previously reported in a large family presenting with spastic ataxia. Cultured fibroblasts from three patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organization and dynamics, providing insight of TUBA4A variants pathogenicity. Our data confirm the identification of a hereditary spastic ataxia disease gene with variable age of onset, expanding the clinical spectrum of TUBA4A associated phenotypes.

ARTIFICIAL INTELLIGENCE FOR OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY-BASED DISEASE ACTIVITY PREDICTION IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: The authors hypothesize that optical coherence tomography angiography (OCTA)-visualized vascular morphology may be a predictor of choroidal neovascularization status in age-related macular degeneration (AMD). The authors thus evaluated the use of artificial intelligence (AI) to predict different stages of AMD disease based on OCTA en face 2D projections scans. METHODS: Retrospective cross-sectional study based on collected 2D OCTA data from 310 high-resolution scans. Based on OCT B-scan fluid and clinical status, OCTA was classified as normal, dry AMD, wet AMD active, and wet AMD in remission with no signs of activity. Two human experts graded the same test set, and a consensus grading between two experts was used for the prediction of four categories. RESULTS: The AI can achieve 80.36% accuracy on a four-category grading task with 2D OCTA projections. The sensitivity of prediction by AI was 0.7857 (active), 0.7142 (remission), 0.9286 (dry AMD), and 0.9286 (normal) and the specificity was 0.9524, 0.9524, 0.9286, and 0.9524, respectively. The sensitivity of prediction by human experts was 0.4286 active choroidal neovascularization, 0.2143 remission, 0.8571 dry AMD, and 0.8571 normal with specificity of 0.7619, 0.9286, 0.7857, and 0.9762, respectively. The overall AI classification prediction was significantly better than the human (odds ratio = 1.95, P = 0.0021). CONCLUSION: These data show that choroidal neovascularization morphology can be used to predict disease activity by AI; longitudinal studies are needed to better understand the evolution of choroidal neovascularization and features that predict reactivation. Future studies will be able to evaluate the additional predicative value of OCTA on top of other imaging characteristics (i.e., fluid location on OCT B scans) to help predict response to treatment.

RETINAL STRUCTURAL CHANGES AFTER CESSATION OF PENTOSAN POLYSULFATE SODIUM.

PURPOSE: To quantify baseline and longitudinal structural changes post-cessation in patients with pentosan polysulfate sodium retinopathy. METHODS: This is a retrospective cohort study. Retinal thickness and volume of choroidal and hyperreflective retinal pigment epithelium excrescences were manually segmented from optical coherence tomography volume scans. Baseline measurements were compared against age-matched control subjects. Longitudinal measurements were performed on patients with follow-up data. RESULTS: Twenty-four eyes of 13 patients were included. At baseline, the mean total retinal thickness was lower in the pentosan polysulfate sodium retinopathy cohort than in age- and sex-matched control subjects (269.1 µ m vs. 290.2 µ m, P = 0.006). The median (range) of follow-up was 18.6 (4.1-34.7) months, with the mean last follow-up of 35.2 months after cessation. During the follow-up period, the thickness of the retina decreased significantly by 11.3 µ m (CI: 16.8, 5.8) ( P < 0.001), with an annual mean decrease of 6.70 µ m. However, the mean hyperreflective retinal pigment epithelium excrescence volume did not change significantly ( P = 0.140) over the follow-up period. CONCLUSION: After pentosan polysulfate sodium discontinuation, although retinal pigment epithelium excrescence volume do not change significantly, there continues to be a progressive long-term thinning of the retina, which continues at a rate greater than that associated with normal aging. Consequently, long-term follow-up is suggested to monitor patients with pentosan polysulfate sodium retinopathy.

Evaluation of Retinal Arterial Occlusion and its Visual and Systemic Prognosis after Hyperbaric Oxygen Therapy.

PURPOSE: To evaluate the systemic and ocular outcomes of patients with branch retinal artery occlusion (BRAO) and central retinal artery occlusion (CRAO) after hyperbaric oxygen therapy (HBOT). METHODS: This is a single-institution study of 75 subjects diagnosed with BRAO (28, 37.3%) and CRAO (47, 62.7%) who visited the emergency department or stroke clinic. Twenty-seven (36%) subjects received HBOT on initial presentation (BRAO-14.3%, CRAO-48.9%). The primary outcome was the best corrective visual acuity (BCVA) change in non-HBOT and HBOT subjects. Secondary outcomes included subsequent development of an acute cerebrovascular accident (CVA)/stroke or neovascular glaucoma (NVG). RESULTS: Overall BCVA did not change from the initial presentation to the final timepoint (logMAR 1.5) in either the conservative management or HBOT cohorts for either BRAO subjects (non-HBOT-logMAR 0.4 vs. 0.6, p=0.658; HBOT-logMAR 0.1 vs. 0.4, p=0.207) or CRAO subjects (non-HBOT-logMAR 2.1 vs. 2.2, p=0.755; HBOT-logMAR 2.1 vs. 2.0, p=0.631). Seven (9.3%) subjects developed CVA (BRAO: non-HBOT-4.2% and HBOT-25.0%, p=0.207; CRAO: non-HBOT-16.7% and HBOT-4.3%, p=0.348) and five subjects (6.7%) developed NVG (BRAO: non-HBOT-4.2% and HBOT-0%, p=1.00; CRAO: non-HBOT-16.7% and HBOT-0%, p=0.109). CONCLUSIONS: Our findings suggest that HBOT does not significantly improve BCVA or mitigate the subsequent development of stroke and NVG in patients with RAOs.

A review of acute symptomatic seizures during awake craniotomy for tumour resection.

PURPOSE: Awake craniotomy (AC) is a procedure often performed concomitantly with direct electrical cortical stimulation (DES) and electrocorticography (ECoG) during functional brain mapping. Patients undergoing AC are at risk of acute symptomatic seizures, including intraoperative (IS) and early postoperative seizures (EPS) which can lead to higher risk of morbidity. Predicting those who are at risk of IS and EPS could alert clinicians and provide the ability to closely monitor and consider management changes in the acute setting to prevent seizures. MATERIALS AND METHODS: This is a narrative review of previous studies on IS and EPS during awake craniotomy, including a summary of studies from our center using a novel circular grid electrode. RESULTS AND CONCLUSIONS: There are a number of clinical features with variable association with a higher risk of EPS and IS. Surgeries involving the anterior and central head regions are a risk factor for IS. EPS is more likely to occur in patients with perioperative intracranial hemorrhage. Improving grid/electrode technology for ECoG can allow for better sensitivity of detecting epileptiform activity which can help to diagnose and predict perioperative seizures.

Laser-Based Therapy Approaches in the Retina: A Review of Micropulse Laser Therapy for Diabetic Retinopathy.

PURPOSE: This review aims to elucidate the mechanisms and clinical utility of subthreshold micropulse laser (SML) therapy in the context of retinal care. Subthreshold or "nondestructive" laser therapy encompasses treatment modalities that induce minimal or no harm to retinal or choroidal tissue and leave no visible sings post-application, while achieving clinical efficacy. METHODS: A comprehensive review of literature sourced from databases including PubMed, Medline, Embase, Cochrane, and Web of Science was conducted, focusing on articles published before February 2024, and discussing the contemporary use of SML therapy in treating diabetic retinopathy (DR). RESULTS: The review presents evidence from scientific literature supporting SML therapy as a viable therapeutic approach for management of DR. Across numerous studies, SML therapy has demonstrated safety and additional therapeutic efficacy without causing damage to underlying retinal tissue. CONCLUSION: Subthreshold laser treatment emerges as a safe strategy for addressing DR. Numerous studies have shown its additional efficacy to anti-VEGF pharmacotherapy, which is the currently approved monotherapy for complications of DR. Ongoing research and clinical investigations aim to further elucidate the mechanisms and optimize the therapeutic advantages of this technology.

REFINING THE RETINAL PHENOTYPE OF PATIENTS WITH SUSPECTED PENTOSAN POLYSULFATE SODIUM RETINOPATHY.

PURPOSE: To refine the retinal phenotypes of suspected pentosan polysulfate sodium toxicity using ultra-widefield imaging. METHODS: Patients with complete dosing profiles who visited the ophthalmology department and with ultra-widefield and optical coherence tomography imaging records were identified using electronic health records at a large academic center. Retinal toxicity was initially identified using previously published imaging criteria, while grading was categorized using both previously reported and new classification systems. RESULTS: One hundred and four patients were included in this study. Twenty-six (25%) were identified as having toxicity from PPS. The mean duration of exposure and cumulative dose between the retinopathy group (162.7 months, 1,803.2 g) were longer and higher compared with the nonretinopathy group (69.7 months, 972.6 g) (both P < 0.001). There was variability of extramacular phenotype in the retinopathy group, with four eyes having only peripapillary involvement and six eyes having far peripheral extension. CONCLUSION: Retinal toxicity in the setting of prolonged exposure and increased cumulative dosing from PPS therapy produces phenotypic variability. Providers should be aware of the extramacular component of toxicity when screening patients. Understanding the different retinal phenotypes may prevent continued exposure and reduce the risk of vision-threatening foveal-involving disease.

PENTOSAN POLYSULFATE SODIUM (ELMIRON) MACULOPATHY: A Genetic Perspective.

PURPOSE: To assess genetic associations for pentosan polysufate sodium maculopathy. METHODS: Genetic testing for inherited retinal dystrophy genes using exome testing and for 14 age-related macular degeneration-associated single nucleotide polymorphisms (SNPs) using panel testing were performed. In addition, full-field electroretinograms (ffERG) were obtained to identify any cone-rod dystrophy. RESULTS: Eleven of 15 patients were women, with a mean age of 69 (range 46-85). Inherited retinal dystrophy exome testing in five patients revealed six pathogenic variants, but failed to confirm inherited retinal dystrophy in any patient genetically. FfERG performed in 12 patients demonstrated only nonspecific a- and b-wave abnormalities in 11 cases and was normal in one case. For age-related macular degeneration single nucleotide polymorphisms, CFH rs3766405 ( P = 0.003) and CETP ( P = 0.027) were found to be statistically significantly associated with pentosan polysulfate maculopathy phenotype compared with the control population. CONCLUSION: Pentosan polysulfate maculopathy is not associated with Mendelian inherited retinal dystrophy genes. However, several age-related macular degeneration risk alleles were identified to be associated with maculopathy compared with their frequency in the normal population. This suggests a role for genes in disease pathology, particularly the alternative complement pathway. These findings would benefit from further investigation to understand the risk of developing maculopathy in taking pentosan polysulfate.

DIRECT MACULAR HOLE MANIPULATION RESULTS IN HIGH SUCCESS RATE IN SECONDARY MACULAR HOLE REPAIR.

PURPOSE: To investigate closure rates and functional outcomes of surgery for refractory and recurrent macular holes (MHs) in a real-world setting. METHODS: Retrospective review of secondary MH surgeries. RESULTS: A total of 72 eyes from 72 patients were included. Eyes had a mean of 1.51 surgeries before inclusion into this study with a mean MH size of 762 µ m and a mean baseline logarithm of the minimum angle of resolution best-corrected visual acuity of 1.11 (∼20/260 Snellen). Closure rates were 89.3% for tissue transplantation, 77.3% for internal limiting membrane (ILM) flaps, 92.9% for MH manipulation, and 12.5% for repeat ILM peeling ( P < 0.05). Best-corrected visual acuity changes in logarithm of the minimum angle of resolution from baseline to postoperative month six were +0.29 for ILM peeling alone (15 Early Treatment Diabetic Retinopathy Study letters worse), -0.39 for MH manipulation (20 Early Treatment Diabetic Retinopathy Study letters improved), -0.23 for tissue transplantation (13 Early Treatment Diabetic Retinopathy Study letters improved), and -0.2 for ILM flaps (10 Early Treatment Diabetic Retinopathy Study letters improved; P < 0.05). CONCLUSION: Secondary MH closure is possible using various surgical techniques with acceptable anatomical closure rates. Repeat ILM peeling is associated with the lowest closure rates and poorest functional results. To distinguish between techniques would require a large sample size of approximately 750 eyes.

Inner Retinal Thickness and Vasculature in Patients with Reticular Pseudodrusen.

INTRODUCTION: The aim of this study was to investigate retinal layer thickness and vessel density differences between patients with reticular pseudodrusen (RPD) and intermediate dry age-related macular degeneration (iAMD). METHODS: Participants included in the study were patients diagnosed by retinal specialists with RPD, iAMD, and both RPD and iAMD at our academic referral center, seen from May 2021 until February 2022. The central 3 mm retinal thickness was measured using spectral-domain optical coherence tomography (Heidelberg Spectralis HRA+OCT System; Heidelberg Engineering, Heidelberg, Germany). Individual retinal thickness measurements were obtained from the innermost layer (nerve fiber layer) until the outermost layer (retinal pigment epithelium [RPE]). Each thickness measurement was subdivided into nine Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. For the vessel density, OCT angiography from the Heidelberg Spectralis System was measured using proprietary third-party software (AngioTool; National Institutes of Health, National Cancer Institute, Bethesda, MD). Clinical and demographic characteristics were compared across the three groups (iAMD, RPD, iAMD and RPD) and analyzed with necessary adjustments. Linear mixed-effects models with necessary corrections were employed to compare continuous eye-level measurements between our three groups as well as in pairwise fashion using the R statistical programming software (R version 4.2.1). RESULTS: A total of 25 eyes of 17 patients with RPD, 20 eyes of 15 patients with iAMD, and 14 eyes of 9 patients with both iAMD and RPD were analyzed. Retinal thickness analysis identified that the superior inner (p = 0.028) and superior outer (p = 0.027) maculas of eyes with both iAMD and RPD were significantly thinner than those with iAMD alone. In eyes with RPD, the superior inner and superior outer RPE (p = 0.011 and p = 0.05, respectively), outer plexiform layer (p = 0.003 and p = 0.013, respectively), and inner nuclear layer (p = 0.034 and p = 0, respectively) were noted to be thinner compared to eyes with iAMD alone. In addition, the macular deep capillary plexus vessel density was significantly reduced in eyes with RPD compared to eyes with iAMD (p = 0.017). CONCLUSION: Patients with RPD had inner retinal structural as well as vascular changes compared to iAMD patients. Inner retinal vascular attenuation should be investigated further to see if there is a causal association with retinal thinning.

Efficacy and accuracy of artificial intelligence to overlay multimodal images from different optical instruments in patients with retinitis pigmentosa.

BACKGROUND: Retinitis pigmentosa (RP) represents a group of progressive, genetically heterogenous blinding diseases. Recently, relationships between measures of retinal function and structure are needed to help identify outcome measures or biomarkers for clinical trials. The ability to align retinal multimodal images, taken on different platforms, will allow better understanding of this relationship. We investigate the efficacy of artificial intelligence (AI) in overlaying different multimodal retinal images in RP patients. METHODS: We overlayed infrared images from microperimetry on near-infra-red images from scanning laser ophthalmoscope and spectral domain optical coherence tomography in RP patients using manual alignment and AI. The AI adopted a two-step framework and was trained on a separate dataset. Manual alignment was performed using in-house software that allowed labelling of six key points located at vessel bifurcations. Manual overlay was considered successful if the distance between same key points on the overlayed images was ≤1/2°. RESULTS: Fifty-seven eyes of 32 patients were included in the analysis. AI was significantly more accurate and successful in aligning images compared to manual alignment as confirmed by linear mixed-effects modelling (p < 0.001). A receiver operating characteristic analysis, used to compute the area under the curve of the AI (0.991) and manual (0.835) Dice coefficients in relation to their respective 'truth' values, found AI significantly more accurate in the overlay (p < 0.001). CONCLUSION: AI was significantly more accurate than manual alignment in overlaying multimodal retinal imaging in RP patients and showed the potential to use AI algorithms for future multimodal clinical and research applications.

Echocardiographic Assessment of Prosthetic Valves.

Prosthetic valves are increasingly encountered in clinical practice. A grasp of the intricacies of the assessment and management of prosthetic valves is thus a crucial skillset for the practicing cardiologist. Echocardiography is the imaging modality of choice for the anatomic and functional evaluation of prosthetic valve. This document reviews the general features of prosthetic valves, echocardiographic identification of normally functioning and dysfunctional prosthetic valves as well as echocardiographic diagnosis of specific prosthetic valvular abnormalities.

Comparison of multicolor scanning laser imaging and color fundus photography in evaluating vessel whitening in branch retinal vein occlusion.

INTRODUCTION: Few studies have explored Multicolor™ imaging (MCI) in evaluating retinal vascular diseases, particularly branch retinal vein occlusion (BRVO). This study aimed to compare the identification of retinal vessel whitening in BRVO using MCI by scanning confocal laser versus conventional white flash color fundus photography (CFP). METHODS: Paired images of consecutive patients diagnosed with BRVO who underwent same-day MCI and CFP were reviewed. Visualization of vessel whitening on MCI and CFP was graded and scored using a scale by two masked graders. A longitudinal analysis of the vessel grading score was performed to evaluate the vessel whitening detection by MCI. A correlation analysis was conducted between vessel whitening on MCI and the measured area of retinal ischemia on fluorescein angiography to evaluate the MCI performance. RESULTS: Forty-four eyes of 41 patients (mean age 69±14 years; 61% female) were analyzed. MCI demonstrated superior vessel whitening visibility score than CFP (p<0.001). Longitudinal analysis showed no significant changes in vessel whitening visibility scores over a mean follow-up time of 430 ± 648 days (p=0.655). There was a significantly positive correlation between the grading score of vessels whitening by MCI and the area of ischemia by fluorescein angiography (r2=0.15; p=0.036). CONCLUSION: MCI appears to provide a superior detection of whitening BRVO compared to CFP, serving as a rapid and non-invasive correlate of retinal ischemia.

Effect of Early vs Standard Approach to Tracheostomy on Functional Outcome at 6 Months Among Patients With Severe Stroke Receiving Mechanical Ventilation: The SETPOINT2 Randomized Clinical Trial.

Importance: Many patients with severe stroke have impaired airway protective reflexes, resulting in prolonged invasive mechanical ventilation. Objective: To test whether early vs standard tracheostomy improved functional outcome among patients with stroke receiving mechanical ventilation. Design, Setting, and Participants: In this randomized clinical trial, 382 patients with severe acute ischemic or hemorrhagic stroke receiving invasive ventilation were randomly assigned (1:1) to early tracheostomy (≤5 days of intubation) or ongoing ventilator weaning with standard tracheostomy if needed from day 10. Patients were randomized between July 28, 2015, and January 24, 2020, at 26 US and German neurocritical care centers. The final date of follow-up was August 9, 2020. Interventions: Patients were assigned to an early tracheostomy strategy (n = 188) or to a standard tracheostomy (control group) strategy (n = 194). Main Outcomes and Measures: The primary outcome was functional outcome at 6 months, based on the modified Rankin Scale score (range, 0 [best] to 6 [worst]) dichotomized to a score of 0 (no disability) to 4 (moderately severe disability) vs 5 (severe disability) or 6 (death). Results: Among 382 patients randomized (median age, 59 years; 49.8% women), 366 (95.8%) completed the trial with available follow-up data on the primary outcome (177 patients [94.1%] in the early group; 189 patients [97.4%] in the standard group). A tracheostomy (predominantly percutaneously) was performed in 95.2% of the early tracheostomy group in a median of 4 days after intubation (IQR, 3-4 days) and in 67% of the control group in a median of 11 days after intubation (IQR, 10-12 days). The proportion without severe disability (modified Rankin Scale score, 0-4) at 6 months was not significantly different in the early tracheostomy vs the control group (43.5% vs 47.1%; difference, -3.6% [95% CI, -14.3% to 7.2%]; adjusted odds ratio, 0.93 [95% CI, 0.60-1.42]; P = .73). Of the serious adverse events, 5.0% (6 of 121 reported events) in the early tracheostomy group vs 3.4% (4 of 118 reported events) were related to tracheostomy. Conclusions and Relevance: Among patients with severe stroke receiving mechanical ventilation, a strategy of early tracheostomy, compared with a standard approach to tracheostomy, did not significantly improve the rate of survival without severe disability at 6 months. However, the wide confidence intervals around the effect estimate may include a clinically important difference, so a clinically relevant benefit or harm from a strategy of early tracheostomy cannot be excluded. Trial Registration: ClinicalTrials.gov Identifier: NCT02377167.

NIH funding trends for neurosurgeon-scientists from 1993-2017: Biomedical workforce implications for neurooncology.

INTRODUCTION: Neurosurgeons represent 0.5% of all physicians and currently face a high burden of disease. Physician-scientists are essential to advance the mission of National Academies of Science (NAS) and National Institutes of Health (NIH) through discovery and bench to bedside translation. We investigated trends in NIH neurosurgeon-scientist funding over time as an indicator of physician-scientist workforce training. METHODS: We used NIH Research Portfolio Online Reporting Tools (RePORTER) to extract grants to neurosurgery departments and neurosurgeons from 1993 to 2017. Manual extraction of each individual grant awardee was conducted. RESULTS: After adjusting for U.S. inflation (base year: 1993), NIH funding to neurosurgery departments increased yearly (P < 0.00001). However, neurosurgeon-scientists received significantly less NIH funding compared to scientists (including basic scientists and research only neurosurgeons) (P = 0.09). The ratio of neurosurgeon-scientists to scientists receiving grants was significantly reduced (P = 0.002). Interestingly, the percentage of oncology-related neurosurgery grants significantly increased throughout the study period (P = 0.002). The average number of grants per neurosurgeon-scientists showed an upward trend (P < 0.001); however, the average number of grants for early-career neurosurgeon-scientists, showed a significant downward trend (P = 0.05). CONCLUSION: Over the past 23 years, despite the overall increasing trends in the number of NIH grants awarded to neurosurgery departments overall, the proportion of neurosurgeon-scientists that were awarded NIH grants compared to scientists demonstrates a declining trend. This observed shift is disproportionate in the number of NIH grants awarded to senior level compared to early-career neurosurgeon-scientists, with more funding allocated towards neurosurgical-oncology-related grants.

Influence of vitrectomy on the progression of dry age-related macular degeneration.

PURPOSE: To demonstrate whether pars plana vitrectomy (PPV) changes the progression of dry age-related macular degeneration (AMD) by assessing longitudinal changes in drusen volume over follow-up. METHODS: Dry AMD patients who had undergone unilateral PPV for symptomatic vitreomacular disorders were evaluated for the progression of disease by spectral domain-optical coherence tomography (SD-OCT) features including drusen volume, development of geographic atrophy, or choroidal neovascularization during follow-up. Drusen volume was manually calculated using an image processing software (ImageJ, NIH) on raster SD-OCT scans. Mean change in drusen volume of surgery eyes was compared with values of the fellow eyes of the same subjects (control group). RESULTS: Among 183 eyes with both vitreoretinal disorder and dry AMD, 48 eyes of 24 patients met the inclusion criteria and were included. The mean drusen volume change during a mean of 25.49 ± 23.35 months of follow-up (range: 6.00-86.87 months) was 4.236.899 ± 20.488.913 µm3 in the study eye and 7.796.357 ± 34.798.519 µm3 in the fellow eye (p = 0.297). Best-corrected visual acuity (BCVA) significantly increased from 0.40 ± 0.18 logMAR (≈ 20/50 Snellen equivalent) to 0.32 ± 0.31 (≈ 20/41 Snellen equivalent) after surgery (p = 0.012) in the study group while BCVA remained stable in the control group (0.19 ± 0.34 logMAR [≈ 20/30 Snellen equivalent] at baseline and 0.20 ± 0.31 logMAR [≈ 20/31 Snellen equivalent], p = 0.432). Choroidal neovascularization developed in 1 vitrectomized eye (4.54%) and in 1 eye (4.54%) from the control group during follow-up. CONCLUSION: Vitrectomy did not seem to worsen dry AMD progression; even more visual acuity may improve despite a slight increase in drusen volume following surgery.

Higher Risk for Reintervention in Patients after Stenting for Radiation-Induced Internal Carotid Artery Stenosis: A Single-Center Analysis and Systematic Review.

BACKGROUND: This study aimed to review short- and long-term outcomes of all carotid artery stenting (CAS) in patients with radiation-induced (RI) internal carotid artery (ICA) stenosis compared with patients with atherosclerotic stenosis (AS). METHODS: We performed a single-center, multisite case-control study of transfemoral carotid artery intervention in patients stented for RI or AS. Cases of stented RI carotid arteries were identified using a CAS database covering January 2000 to December 2019. These patients were randomly matched 2:1 with stented patients because of AS by age, sex, and year of CAS. A conditional logistic regression model was performed to estimate the odds of reintervention in the RI group. Finally, a systematic review was performed to assess the outcomes of RI stenosis treated with CAS. RESULTS: There were 120 CAS in 113 patients because of RI ICA stenosis. Eighty-nine patients (78.8%) were male, and 68 patients (60.2%) were symptomatic. The reasons for radiation included most commonly treatment for diverse malignancies of the head and neck in 109 patients (96.5%). The mean radiation dose was 58.9 ± 15.6 Gy, and the time from radiation to CAS was 175.3 ± 140.4 months. Symptoms included 31 transient ischemic attacks (TIAs), 21 strokes (7 acute and 14 subacute), and 17 amaurosis fugax. The mean National Institutes of Health Stroke Scale in acute strokes was 8.7 ± 11.2. In asymptomatic patients, the indication for CAS was high-grade stenosis determined by duplex ultrasound. All CAS were successfully completed. Reinterventions were more frequent in the RI ICA stenosis cohort compared with the AS cohort (10.1% vs. 1.4%). Reinterventions occurred in 14 vessels, and causes for reintervention were restenosis in 12 followed by TIA/stroke in two vessels. On conditional regression modeling, patients with RI ICA stenosis were at a higher risk for reintervention (odds ratio = 7.1, 95% confidence interval = 2.1-32.8; P = 0.004). The mean follow-up was 33.7 ± 36.9 months, and the mortality across groups was no different (P = 0.12). CONCLUSIONS: In our single-center, multisite cohort study, patients who underwent CAS for RI ICA stenosis experienced a higher rate of restenosis and a higher number of reinterventions compared with CAS for AS. Although CAS is safe and effective for this RI ICA stenosis cohort, further data are needed to reduce the risk of restenosis, and close patient surveillance is warranted. In our systematic review, CAS was considered an excellent alternative option for the treatment of patients with RI ICA stenosis. However, careful patient selection is warranted because of the increased risk of restenosis on long-term follow-up.

CHOROIDAL IMAGING BIOMARKERS TO PREDICT HIGHLY RESPONSIVE AND RESISTANT CASES TREATED WITH STANDARDIZED ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR REGIMEN IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To determine structural predictors of treatment response in neovascular age-related macular degeneration analyzing optical coherence tomography (OCT)-related biomarkers. METHODS: A retrospective review of patients undergoing treatment for neovascular age-related macular degeneration at a tertiary institute was performed at presentation. High-intensity regimen included eyes on long-term anti-vascular endothelial growth factor treatment with the inability to extend beyond a month without a relapse and needed double the dose of medication (n = 25). Low-intensity regimen had eyes that went into long-term remission after at least three injections and remained dry for more than a year until the last visit (n = 20). Multimodal imaging including fluorescein angiogram, OCT, and comprehensive ocular evaluation were done. Choroidal vascularity index, total choroidal area, luminal area, subfoveal choroidal thickness, choriocapillaris thickness and Haller and Sattler layer thickness were analyzed for statistical significance. RESULTS: The groups had no significant difference at baseline in age, gender, incidence of reticular pseudodrusen, polypoidal choroidal vasculopathy feature on OCT, type of choroidal neovascular membrane, and geographic atrophy. Multinomial logistic regression revealed that thicker subfoveal choroidal thickness and larger total choroidal area were the significant predictors of poor response to anti-vascular endothelial growth factor treatment (E = 0.02; P = 0.02; E = 1.82; P = 0.0075). CONCLUSION: Thicker subfoveal choroidal thickness and higher total choroidal area are useful variables to predict a poor treatment response.

REPLACEMENT OF LIDOCAINE GEL WITH TOPICAL PROPARACAINE ANESTHESIA FOR ROUTINE INTRAVITREAL INJECTIONS: A Comparative Study.

PURPOSE: Lidocaine gel was suggested to be highly effective in providing anesthesia for intravitreal injections but adverse effects include a possibility of making sterilization of the conjunctiva difficult. Hence, we wished to determine the effect of using 0.5% proparacaine drops alone over the use of 3.5% lidocaine hydrochloride gel anesthesia during office-based intravitreal injections. METHODOLOGY: This was a case-control study in patients who came routinely to the clinic for antivascular endothelial growth factor injections. Eyes were treated with one of two anesthesia modalities. A total of 216 injections in 120 patients were reviewed. One group (N = 107) underwent anesthesia with 0.5% proparacaine drops, and the control group (N = 109) received 3.5% lidocaine gel. The pain perceived after injection was graded using the numerical rating scale, and score was immediately recorded by the "masked" injecting physician. RESULTS: The mean pain score (±SD) for the proparacaine-only group versus gel group was 1.97 (±1.17) versus 1.76 (±0.92), P value = 0.3174. There was no statistical difference between the 2 groups. CONCLUSION: 3.5% lidocaine gel is not superior to 0.5% proparacaine drops as patients attained good pain control and excellent rates of overall satisfaction with proparacaine drops alone.

PHASE 2 STUDY OF THE SAFETY AND EFFICACY OF BRIMONIDINE DRUG DELIVERY SYSTEM (BRIMO DDS) GENERATION 1 IN PATIENTS WITH GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the safety and efficacy of Brimonidine Drug Delivery System (Brimo DDS), a biodegradable intravitreal implant, in the treatment of geographic atrophy (GA) secondary to age-related macular degeneration. METHODS: Phase 2, randomized, multicenter, double-masked, 24-month study. Study eyes were treated (Day 1; Month 6 retreatment) with Brimo DDS 132 µg (n = 49), Brimo DDS 264 µg (n = 41), or sham procedure (n = 23). The primary timepoint for efficacy analysis was Month 12. RESULTS: Mean GA area growth at Month 12 was 1.78 mm2, 1.59 mm2, and 2.19 mm2 in the Brimo DDS 132 µg, 264 µg, and sham groups, respectively. Geographic atrophy area growth was consistently smaller with Brimo DDS 132 and 264 µg than sham; between-group differences were significant (P ≤ 0.032) at Month 3. In patients with baseline lesion area ≥6 mm2 (two-thirds of patients), GA lesion area and effective radius growth was reduced with Brimo DDS 132 and 264 µg at Month 12 (P ≤ 0.050 vs. sham). Treatment-related adverse events were usually injection procedure-related. CONCLUSION: Brimo DDS demonstrated a favorable safety profile and reduced GA lesion area growth at Month 3. Lesion growth at Month 12 was reduced in patients with baseline GA lesion area ≥6 mm2. The results support Phase 3 development.