Sample multiplexing for retinal single-cell RNA-sequencing.

Rare cell populations can be challenging to characterize using microfluidic single-cell RNA sequencing (scRNA-seq) platforms. Typically, the population of interest must be enriched and pooled from multiple biological specimens for efficient collection. However, these practices preclude the resolution of sample origin together with phenotypic data and are problematic in experiments in which biological or technical variation is expected to be high (e.g., disease models, genetic perturbation screens, or human samples). One solution is sample multiplexing whereby each sample is tagged with a unique sequence barcode that is resolved bioinformatically. We have established a scRNA-seq sample multiplexing pipeline for mouse retinal ganglion cells using cholesterol-modified-oligos and utilized the enhanced precision to investigate cell type distribution and transcriptomic variance across retinal samples. As single cell transcriptomics are becoming more widely used to research development and disease, sample multiplexing represents a useful method to enhance the precision of scRNA-seq analysis.

Comprehensive single-cell atlas of the mouse retina.

Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cellular heterogeneity by characterizing cell types across tissues and species. While several mouse retinal scRNA-seq datasets exist, each dataset is either limited in cell numbers or focused on specific cell classes, thereby hindering comprehensive gene expression analysis across all retina types. To fill the gap, we generated the largest retinal scRNA-seq dataset to date, comprising approximately 190,000 single cells from C57BL/6J mouse retinas, enriched for rare population cells via antibody-based magnetic cell sorting. Integrating this dataset with public datasets, we constructed the Mouse Retina Cell Atlas (MRCA) for wild-type mice, encompassing over 330,000 cells, characterizing 12 major classes and 138 cell types. The MRCA consolidates existing knowledge, identifies new cell types, and is publicly accessible via CELLxGENE, UCSC Cell Browser, and the Broad Single Cell Portal, providing a user-friendly resource for the mouse retina research community.

Longitudinal Retinal and Choroidal Image Analysis in a Set of Monozygotic Twins.

We analyzed multimodal retinal and choroidal imaging, including optical coherence tomography (OCT) and OCT angiography (OCTA), to assess differences and characterize variations in the retinal and choroidal structure and microvasculature between healthy monozygotic twins without ocular or systemic pathology over a five-year period. Retinal imaging of both subjects revealed normal age-related changes. There was up to an 11% difference in OCT and OCTA variables within the subjects, both at baseline and at five years, and there was up to an 18% difference in OCT and OCTA parameters between the subjects for both time points. Larger changes in subfoveal choroidal thickness and foveal avascular zone area were observed. Our observations suggest that the parafoveal superficial capillary plexus, choroidal vascularity index, central subfield thickness, retinal nerve fiber layer thickness, and ganglion cell-inner plexiform layer thickness may be more heavily influenced by genetic, rather than environmental, factors. In contrast, subfoveal choroidal thickness and the foveal avascular zone area may be more heavily influenced by environmental factors. The environmental impact on retinal and choroidal structure and microvasculature is increasingly important to characterize, as such imaging parameters are being explored as potential biomarkers of systemic disease. These differences, as seen in these identical twin subjects, may be important considerations in supporting the security of biometric identifiers.

Peripapillary Optical Coherence Tomography Angiography in Alzheimer's Disease, Mild Cognitive Impairment, and Normal Cognition.

OBJECTIVE: This study aimed to identify peripapillary microvascular changes in Alzheimer's disease (AD) and mild cognitive impairment (MCI). PATIENTS AND METHODS: In this prospective study, 66 eyes of 36 subjects with AD, 119 eyes of 63 with MCI, and 513 eyes of 265 controls with normal cognition were enrolled. Peripapillary capillary perfusion density (CPD), capillary flux index (CFI), and retinal nerve fiber layer (RNFL) thickness were determined. RESULTS: Average CPD differed significantly between all three groups (P = 0.001), being significantly greater in AD vs controls (0.446 ± 0.015 vs 0.439 ± 0.017, P = 0.001) and MCI vs controls (0.443 ± 0.020 vs 0.439 ± 0.017, P = 0.007) but not AD vs MCI (P = 0.69). CFI and average RNFL thickness did not significantly differ among groups (all P > 0.05). CONCLUSION: Peripapillary CPD is increased in eyes with AD or MCI compared to controls despite similar RNFL thickness. [Ophthalmic Surg Lasers Imaging Retina 2024;55:78-84.].

Comprehensive single-cell atlas of the mouse retina.

Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cellular heterogeneity at the single-cell resolution by classifying and characterizing cell types in multiple tissues and species. While several mouse retinal scRNA-seq reference datasets have been published, each dataset either has a relatively small number of cells or is focused on specific cell classes, and thus is suboptimal for assessing gene expression patterns across all retina types at the same time. To establish a unified and comprehensive reference for the mouse retina, we first generated the largest retinal scRNA-seq dataset to date, comprising approximately 190,000 single cells from C57BL/6J mouse whole retinas. This dataset was generated through the targeted enrichment of rare population cells via antibody-based magnetic cell sorting. By integrating this new dataset with public datasets, we conducted an integrated analysis to construct the Mouse Retina Cell Atlas (MRCA) for wild-type mice, which encompasses over 330,000 single cells. The MRCA characterizes 12 major classes and 138 cell types. It captured consensus cell type characterization from public datasets and identified additional new cell types. To facilitate the public use of the MRCA, we have deposited it in CELLxGENE, UCSC Cell Browser, and the Broad Single Cell Portal for visualization and gene expression exploration. The comprehensive MRCA serves as an easy-to-use, one-stop data resource for the mouse retina communities.

Differences in Retinal and Choroidal Microvasculature and Structure in Dementia With Lewy Bodies Compared With Normal Cognition.

Purpose: To evaluate the retinal and choroidal microvasculature and structure in individuals with dementia with Lewy bodies (DLB) compared with controls with normal cognition using optical coherence tomography (OCT) and OCT angiography (OCTA). Methods: An institutional review board-approved cross-sectional comparison of patients with DLB and cognitively normal controls was performed. The Cirrus HD-OCT 5000 with AngioPlex (Carl Zeiss Meditec) was used to obtain OCT and OCTA images. Results: Thirty-four eyes of 18 patients with DLB and 85 eyes of 48 cognitively normal patients were analyzed. The average capillary perfusion density (CPD) was higher in the DLB group than in the control group (P = .005). The average capillary flux index (CFI) and ganglion cell inner-plexiform layer (GC-IPL) thickness were lower in the DLB group than in the control group (P = .016 and P = .040, respectively). Conclusions: Patients with DLB had an increased peripapillary CPD, decreased peripapillary CFI, and attenuated GC-IPL thickness compared with those with normal cognition.

Ultra-Widefield Imaging of the Retinal Macrovasculature in Parkinson Disease Versus Controls With Normal Cognition Using Alpha-Shapes Analysis.

Purpose: To investigate retinal vascular characteristics using ultra-widefield (UWF) scanning laser ophthalmoscopy in Parkinson disease (PD). Methods: Individuals with an expert-confirmed clinical diagnosis of PD and controls with normal cognition without PD underwent Optos California UWF imaging. Patients with diabetes, uncontrolled hypertension, glaucoma, dementia, other movement disorders, or known retinal or optic nerve pathology were excluded. Images were analyzed using Vasculature Assessment and Measurement Platform for Images of the Retina (VAMPIRE-UWF) software, which describes retinal vessel width gradient and tortuosity, provides vascular network fractal dimensions, and conducts alpha-shape analysis to further characterize vascular morphology (complexity, Opαmin; spread, OpA). Results: In the PD cohort, 53 eyes of 38 subjects were assessed; in the control cohort, 51 eyes of 33 subjects were assessed. Eyes with PD had more tortuous retinal arteries in the superotemporal quadrant (P = 0.043). In eyes with PD, alpha-shape analysis revealed decreased OpA, indicating less retinal vasculature spread compared to controls (P = 0.032). Opαmin was decreased in PD (P = 0.044), suggesting increased vascular network complexity. No differences were observed in fractal dimension in any region of interest. Conclusions: This pilot study suggests that retinal vasculature assessment on UWF images using alpha-shape analysis reveals differences in retinal vascular network spread and complexity in PD and may be a more sensitive metric compared to fractal dimension. Translational Relevance: Retinal vasculature assessment using these novel methods may be useful in understanding ocular manifestations of PD and the development of retinal biomarkers.

Characterizing differences in retinal and choroidal microvasculature and structure in individuals with Huntington's Disease compared to healthy controls: A cross-sectional prospective study.

OBJECTIVE: To characterize retinal and choroidal microvascular and structural changes in patients who are gene positive for mutant huntingtin protein (mHtt) with symptoms of Huntington's Disease (HD). METHODS: This study is a cross-sectional comparison of patients who are gene positive for mHtt and exhibit symptoms of HD, either motor manifest or prodromal (HD group), and cognitively normal individuals without a family history of HD (control group). HD patients were diagnosed by Duke movement disorder neurologists based on the Unified Huntington's Disease Rating Scale (UHDRS). Fovea and optic nerve centered OCT and OCTA images were captured using Zeiss Cirrus HD-5000 with AngioPlex. Outcome metrics included central subfield thickness (CST), peripapillary retinal nerve fiber layer (pRNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, and choroidal vascularity index (CVI) on OCT, and foveal avascular zone (FAZ) area, vessel density (VD), perfusion density (PD), capillary perfusion density (CPD), and capillary flux index (CFI) on OCTA. Generalized estimating equation (GEE) models were used to account for inter-eye correlation. RESULTS: Forty-four eyes of 23 patients in the HD group and 77 eyes of 39 patients in the control group were analyzed. Average GCIPL thickness and FAZ area were decreased in the HD group compared to controls (p = 0.001, p < 0.001). No other imaging metrics were significantly different between groups. CONCLUSIONS: Patients in the HD group had decreased GCIPL thickness and smaller FAZ area, highlighting the potential use of retinal biomarkers in detecting neurodegenerative changes in HD.

Autoimmune-Related Retinopathy Presenting As Plaquenil Toxicity in Patients With Systemic Lupus Erythematosus.

Purpose: To report 3 cases of autoimmune retinopathy (AIR) in patients with systemic lupus erythematosus (SLE) to explore the association between these conditions and highlight additional clinical consideration of AIR in patients presenting with atypical retinopathy in the context of hydroxychloroquine use. Methods: The medical and clinical follow-up records of 3 clinical cases were reviewed. The eligibility criteria were the absence of other retinopathy or systemic autoimmune diseases. Results: All patients had a long-standing diagnosis of SLE and had been taking hydroxychloroquine at a dose exceeding the American Academy of Ophthalmology recommendations. All 3 patients had extensive retinal degeneration atypical in appearance for drug toxicity alone. Examination, imaging, electroretinograms, and autoantibody assays eventually led to the diagnosis of AIR. Conclusions: Further study of the AIR and SLE may reveal an association between these conditions. In patients with SLE presenting with retinal degeneration, AIR may be underdiagnosed.

Intrasession Repeatability of OCT Angiography Parameters in Neurodegenerative Disease.

Purpose: To assess the intrasession repeatability of macular OCT angiography (OCTA) parameters in Alzheimer's disease (AD), mild cognitive impairment (MCI), Parkinson's disease (PD), and normal cognition (NC). Design: Cross sectional study. Subjects: Patients with a clinical diagnosis of AD, PD, MCI, or NC were imaged. Images with poor quality and of those with diabetes mellitus, glaucoma, or vitreoretinal disease were excluded from analysis. Methods Intervention or Testing: All participants were imaged using the Zeiss Cirrus HD-5000 with AngioPlex (Carl Zeiss Meditec, Software Version 11.0.0.29946) and repeat OCTA images were obtained for both eyes. Perfusion density (PFD), vessel density (VD), and Foveal avascular zone (FAZ) area were measured from 3 × 3 mm and 6 × 6 mm OCTA images centered on the fovea using an ETDRS grid overlay. Main Outcome Measures: Intraclass correlation coefficients were used to quantify repeatability of PFD, VD, and FAZ area measurements obtained from imaging. Results: 3 × 3 mm scans of 22 AD, 40 MCI, 21 PD, and 26 NC participants and 6 × 6 mm scans of 29 AD, 44 MCI, 29 PD, and 30 NC participants were analyzed. Repeatability values ranged from 0.64 (0.49-0.82) for 6 × 6 mm PFD in AD participants to 0.87 (0.67-0.92) for 3 × 3 mm PFD in AD participants. No significant differences were observed in repeatability between NC participants and those with neurodegenerative disease. Conclusions: Overall, similar OCTA repeatability was observed between NC participants and those with neurodegeneration. Regardless of diagnostic group, macular OCTA metrics demonstrated moderate to good repeatability. Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

Retinal Vascular Changes in Alzheimer's Dementia and Mild Cognitive Impairment: A Pilot Study Using Ultra-Widefield Imaging.

Purpose: Retinal microvascular abnormalities measured on retinal images are a potential source of prognostic biomarkers of vascular changes in the neurodegenerating brain. We assessed the presence of these abnormalities in Alzheimer's dementia and mild cognitive impairment (MCI) using ultra-widefield (UWF) retinal imaging. Methods: UWF images from 103 participants (28 with Alzheimer's dementia, 30 with MCI, and 45 with normal cognition) underwent analysis to quantify measures of retinal vascular branching complexity, width, and tortuosity. Results: Participants with Alzheimer's dementia displayed increased vessel branching in the midperipheral retina and increased arteriolar thinning. Participants with MCI displayed increased rates of arteriolar and venular thinning and a trend for decreased vessel branching. Conclusions: Statistically significant differences in the retinal vasculature in peripheral regions of the retina were observed among the distinct cognitive stages. However, larger studies are required to establish the clinical importance of our findings. UWF imaging may be a promising modality to assess a larger view of the retinal vasculature to uncover retinal changes in Alzheimer's disease. Translational Relevance: This pilot work reports an investigation into which retinal vasculature measurements may be useful surrogate measures of cognitive decline, as well as technical developments (e.g., measurement standardization), that are first required to establish their recommended use and translational potential.

Longitudinal Analysis of Retinal Microvascular and Choroidal Imaging Parameters in Parkinson's Disease Compared with Controls.

Purpose: To quantify rate of change of retinal microvascular and choroidal structural parameters in subjects with Parkinson's disease (PD) compared with controls using OCT and OCT angiography (OCTA). Design: Prospective longitudinal study. Participants: Seventy-four eyes of 40 participants with PD and 149 eyes of 78 control individuals from the Eye Multimodal Imaging in Neurodegenerative Disease database. Methods: Subjects underwent OCT and OCTA imaging at 2 time points approximately 12 months apart. Main Outcome Measures: Imaging parameters included central subfield thickness, ganglion cell-inner plexiform layer (GC-IPL) thickness, peripapillary retinal nerve fiber layer thickness, choroidal vascularity index, superficial capillary plexus perfusion density (PFD), vessel density (VD), and foveal avascular zone area. Results: Participants with PD had greater rate of yearly decrease in GC-IPL (PD = -0.403µm, control = + 0.128 µm; P = 0.01), greater yearly decline in PFD in the 3 × 3 mm ETDRS circle (PD = -0.016, control = + 0.002; P < 0.001) and ring (PD = -0.016, control = + 0.002; P < 0.001); 6 × 6 mm ETDRS circle (PD = -0.021, control = 0.00; P = 0.001), and outer ring (PD = -0.022, control = 0.00; P = 0.001). Participants with PD had greater rate of yearly decline in VD in 3 × 3 mm circle (PD = -0.939/mm, control = + 0.006/mm; P < 0.001) and ring (PD = -0.942/mm, control = + 0.013/mm; P < 0.001); 6 × 6 mm circle (PD = -0.72/mm, control = -0.054/mm; P = 0.006), and outer ring (PD = -0.746/mm, control = -0.054/mm; P = 0.005). When stratified by PD severity based on Hoehn and Yahr stage, faster rates of decline were seen in Hoehn and Yahr stages 3 to 4 in the 3 × 3 mm circle PFD and VD as well as 3 × 3 mm ring VD. Conclusions: Individuals with PD experience more rapid loss of retinal microvasculature quantified on OCTA and more rapid thinning of the GC-IPL than controls. There may be more rapid loss in patients with greater disease severity. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Design and Fabrication of a Fiber Bragg Grating Shape Sensor for Shape Reconstruction of a Continuum Manipulator.

Continuum dexterous manipulators (CDMs) are suitable for performing tasks in a constrained environment due to their high dexterity and maneuverability. Despite the inherent advantages of CDMs in minimally invasive surgery, real-time control of CDMs' shape during nonconstant curvature bending is still challenging. This study presents a novel approach for the design and fabrication of a large deflection fiber Bragg grating (FBG) shape sensor embedded within the lumens inside the walls of a CDM with a large instrument channel. The shape sensor consisted of two fibers, each with three FBG nodes. A shape-sensing model was introduced to reconstruct the centerline of the CDM based on FBG wavelengths. Different experiments, including shape sensor tests and CDM shape reconstruction tests, were conducted to assess the overall accuracy of the shape-sensing. The FBG sensor evaluation results revealed the linear curvature-wavelength relationship with the large curvature detection of 0.045 mm and a high wavelength shift of up to 5.50 nm at a 90° bending angle in both the bending directions. The CDM's shape reconstruction experiments in a free environment demonstrated the shape-tracking accuracy of 0.216 ± 0.126 mm for positive/negative deflections. Also, the CDM shape reconstruction error for three cases of bending with obstacles was observed to be 0.436 ± 0.370 mm for the proximal case, 0.485 ± 0.418 mm for the middle case, and 0.312 ± 0.261 mm for the distal case. This study indicates the adequate performance of the FBG sensor and the effectiveness of the model for tracking the shape of the large-deflection CDM with nonconstant-curvature bending for minimally invasive orthopedic applications.

ASSESSMENT OF RETINAL MICROVASCULAR ALTERATIONS IN INDIVIDUALS WITH AMNESTIC AND NONAMNESTIC MILD COGNITIVE IMPAIRMENT USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To assess retinal microvascular alterations in individuals with amnestic mild cognitive impairment (MCI) and nonamnestic MCI. METHODS: One hundred twelve eyes of 59 amnestic MCI participants, 32 eyes of 17 nonamnestic MCI participants, and 111 eyes of 56 controls with normal cognition were included. Optical coherence tomography angiography vessel density and perfusion density in the Early Treatment Diabetic Retinopathy Study 3-mm circle and ring were assessed. Retinal thickness parameters including retinal nerve fiber layer thickness, ganglion cell-inner plexiform layer thickness, central subfield thickness, and subfoveal choroidal thickness were also analyzed. Multivariable generalized estimating equations were used for statistical analysis. RESULTS: Perfusion density in the 3-mm inner ring was significantly lower in amnestic MCI patients when compared with nonamnestic MCI participants (0.29 ± 0.03 vs. 0.34 ± 0.09, P = 0.025) and controls with normal cognition (0.29 ± 0.03 vs. 0.39 ± 0.02, P < 0.001), after adjustment for age and sex as covariates. Vessel density, retinal nerve fiber layer thickness, ganglion cell-inner plexiform layer thickness, central subfield thickness, and subfoveal choroidal thickness did not differ among or between diagnostic groups. CONCLUSION: Perfusion density was significantly reduced in individuals with amnestic MCI, compared with those with nonamnestic MCI and controls with normal cognition.

Nephronectin-integrin α8 signaling is required for proper migration of periocular neural crest cells during chick corneal development.

During development, cells aggregate at tissue boundaries to form normal tissue architecture of organs. However, how cells are segregated into tissue precursors remains largely unknown. Cornea development is a perfect example of this process whereby neural crest cells aggregate in the periocular region prior to their migration and differentiation into corneal cells. Our recent RNA-seq analysis identified upregulation of nephronectin (Npnt) transcripts during early stages of corneal development where its function has not been investigated. We found that Npnt mRNA and protein are expressed by various ocular tissues, including the migratory periocular neural crest (pNC), which also express the integrin alpha 8 (Itgα8) receptor. Knockdown of either Npnt or Itgα8 attenuated cornea development, whereas overexpression of Npnt resulted in cornea thickening. Moreover, overexpression of Npnt variants lacking RGD-binding sites did not affect corneal thickness. Neither the knockdown nor augmentation of Npnt caused significant changes in cell proliferation, suggesting that Npnt directs pNC migration into the cornea. In vitro analyses showed that Npnt promotes pNC migration from explanted periocular mesenchyme, which requires Itgα8, focal adhesion kinase, and Rho kinase. Combined, these data suggest that Npnt augments cell migration into the presumptive cornea extracellular matrix by functioning as a substrate for Itgα8-positive pNC cells.

Longitudinal Analysis of the Retina and Choroid in Cognitively Normal Individuals at Higher Genetic Risk of Alzheimer Disease.

PURPOSE: To assess the baseline differences and longitudinal rate of change in retinal and choroidal imaging parameters between apolipoprotein ε4 (APOE ε4) carriers and noncarriers with normal cognition. DESIGN: Prospective study. SUBJECTS: Four hundred thirteen eyes of 218 individuals with normal cognition aged ≥ 55 years with known APOE status (98 APOE ε4 carriers and 120 noncarriers). The exclusion criteria included diabetes mellitus, uncontrolled hypertension, glaucoma, and vitreoretinal or neurodegenerative disease. METHODS: OCT and OCT angiography (OCTA) were performed at baseline and 2 years (Zeiss Cirrus HD-OCT 5000 with AngioPlex; Zeiss Meditec). The groups were compared using sex- and age-adjusted generalized estimating equations. MAIN OUTCOME MEASURES: OCT parameters: retinal nerve fiber layer thickness, macular ganglion cell-inner plexiform layer thickness, central subfield thickness (CST), and choroidal vascularity index. OCT angiography parameters: foveal avascular zone area, perfusion density (PD), vessel density, peripapillary capillary PD (CPD), and capillary flux index (CFI). The rate of change per year was calculated. RESULTS: At the baseline, the APOE ε4 carriers had lower CST (P = 0.018), PD in the 6-mm ETDRS circle (P = 0.049), and temporal CFI (P = 0.047). Seventy-one APOE ε4 carriers and 78 noncarriers returned at 2 years; at follow-up, the 6-mm ETDRS circle (P = 0.05) and outer ring (P = 0.049) showed lower PD in the APOE ε4 carriers, with no differences in the rates of change between the groups (all P > 0.05). CONCLUSIONS: There was exploratory evidence of differences in the CST, PD, and peripapillary CFI between the APOE ε4 carriers and noncarriers with normal cognition. Larger and longer-term studies may help further elucidate the potential prognostic value of these findings.

Fluoroscopic Navigation for a Surgical Robotic System Including a Continuum Manipulator.

We present an image-based navigation solution for a surgical robotic system with a Continuum Manipulator (CM). Our navigation system uses only fluoroscopic images from a mobile C-arm to estimate the CM shape and pose with respect to the bone anatomy. The CM pose and shape estimation is achieved using image intensity-based 2D/3D registration. A learning-based framework is used to automatically detect the CM in X-ray images, identifying landmark features that are used to initialize and regularize image registration. We also propose a modified hand-eye calibration method that numerically optimizes the hand-eye matrix during image registration. The proposed navigation system for CM positioning was tested in simulation and cadaveric studies. In simulation, the proposed registration achieved a mean error of 1.10±0.72 mm between the CM tip and a target entry point on the femur. In cadaveric experiments, the mean CM tip position error was 2.86±0.80 mm after registration and repositioning of the CM. The results suggest that our proposed fluoroscopic navigation is feasible to guide the CM in orthopedic applications.

Fluoroscopy-Guided Robotic System for Transforaminal Lumbar Epidural Injections.

We present an autonomous robotic spine needle injection system using fluoroscopic image-based navigation. Our system includes patient-specific planning, intra-operative image-based 2D/3D registration and navigation, and automatic robot-guided needle injection. We performed intensive simulation studies to validate the registration accuracy. We achieved a mean spine vertebrae registration error of 0.8 ± 0.3 mm, 0.9 ± 0.7 degrees, mean injection device registration error of 0.2 ± 0.6 mm, 1.2 ± 1.3 degrees, in translation and rotation, respectively. We then conducted cadaveric studies comparing our system to an experienced clinician's free-hand injections. We achieved a mean needle tip translational error of 5.1 ± 2.4 mm and needle orientation error of 3.6 ± 1.9 degrees for robotic injections, compared to 7.6 ± 2.8 mm and 9.9 ± 4.7 degrees for clinician's free-hand injections, respectively. During injections, all needle tips were placed within the defined safety zones for this application. The results suggest the feasibility of using our image-guided robotic injection system for spinal orthopedic applications.

Characteristics of Branch Retinal Vein Occlusion in African American Patients.

BACKGROUND AND OBJECTIVES: To describe the presentation, management, and clinical outcomes of branch retinal vein occlusion (BRVO) in African American patients compared to patients of other racial or ethnic backgrounds. PATIENTS AND METHODS: This retrospective cohort study included eyes diagnosed with BRVO and macular edema at a tertiary referral center. Presenting features, treatment, and outcomes were compared based on racial or ethnic backgrounds. RESULTS: The study included 285 eyes: 21.8% African American, 78.2% other. African American patients were more likely to have comorbid diabetes (P = .012), open-angle glaucoma (P < .001), and to present with subretinal fluid (P = .049); multivariate analysis showed race and ethnicity alone may not fully explain presenting subretinal fluid (odds ratio = 2.807; 95% CI, 0.997 to 7.903; P = .051). There was no difference in other comparisons of clinical outcomes or treatment burden, including visual acuity, duration, or treatment method. CONCLUSIONS: Despite significant differences at presentation, the management and outcomes of BRVO did not differ significantly between African American patients and patients of other racial and ethnic backgrounds. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:492-497.].

An Active Steering Hand-held Robotic System for Minimally Invasive Orthopaedic Surgery Using a Continuum Manipulator.

This paper presents the development and experimental evaluation of an active steering hand-held robotic system for milling and curved drilling in minimally invasive orthopaedic interventions. The system comprises a cable-driven continuum dexterous manipulator (CDM), an actuation unit with a handpiece, and a flexible, rotary cutting tool. Compared to conventional rigid drills, the proposed system enhances dexterity and reach in confined spaces in surgery, while providing direct control to the surgeon with sufficient stability while cutting/milling hard tissue. Of note, for cases that require precise motion, the system is able to be mounted on a positioning robot for additional controllability. A proportional-derivative (PD) controller for regulating drive cable tension is proposed for the stable steering of the CDM during cutting operations. The robotic system is characterized and tested with various tool rotational speeds and cable tensions, demonstrating successful cutting of three-dimensional and curvilinear tool paths in simulated cancellous bone and bone phantom. Material removal rates (MRRs) of up to 571 mm3/s are achieved for stable cutting, demonstrating great improvement over previous related works.