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Microglia are resident central nervous system macrophages and the first responders to neural injury. Until recently, microglia have been studied only in animal models with exogenous or transgenic labeling. While these studies provided a wealth of information on the delicate balance between neuroprotection and neurotoxicity within which these cells operate, extrapolation to human immune function has remained an open question. Here we examine key characteristics of retinal macrophage cells in live human eyes, both healthy and diseased, with the unique capabilities of our adaptive optics-optical coherence tomography approach and owing to their propitious location above the inner limiting membrane (ILM), allowing direct visualization of cells. Our findings indicate that human ILM macrophage cells may be distributed distinctly, age differently, and have different dynamic characteristics than microglia in other animals. For example, we observed a macular pattern that was sparse centrally and peaked peripherally in healthy human eyes. Moreover, human ILM macrophage density decreased with age (â¼2% of cells per year). Our results in glaucomatous eyes also indicate that ILM macrophage cells appear to play an early and regionally specific role of nerve fiber layer phagocytosis in areas of active disease. While we investigate ILM macrophage cells distinct from the larger sample of overall retinal microglia, the ability to visualize macrophage cells without fluorescent labeling in the live human eye represents an important advance for both ophthalmology and neuroscience, which may lead to novel disease biomarkers and new avenues of exploration in disease progression.
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Macrófagos/metabolismo , Imagen Molecular , Imagen Óptica , Retina/metabolismo , Retina/patología , Biomarcadores , Susceptibilidad a Enfermedades , Glaucoma/diagnóstico , Glaucoma/etiología , Glaucoma/metabolismo , Humanos , Macrófagos/inmunología , Mácula Lútea/metabolismo , Microglía/inmunología , Microglía/metabolismo , Microglía/patología , Imagen Molecular/métodos , Neuroprotección , Imagen Óptica/métodos , Retina/diagnóstico por imagen , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: To evaluate the association between postoperative intraocular pressure (IOP) reduction and phacoemulsification parameters in patients who underwent both conventional phacoemulsification surgery (CPS) and femtosecond laser-assisted cataract surgery (FLACS). METHODS: This was a prospective multicenter comparative study that enrolled 90 participants who underwent cataract surgery at the University of Maryland Medical System and the Wilmer Eye Institute. Patients underwent FLACS in one eye and CPS in the fellow eye. IOP was measured prior to surgery and monitored through six months postoperatively. Demographic, clinical, biometric, and intraoperative variables including cumulative dissipated energy (CDE), aspiration time, and phacoemulsification time were analyzed for any significant association with postoperative IOP. Postoperative IOP reduction was the primary outcome variable. A secondary goal of the study was to determine differences in postoperative IOP reduction between CPS and FLACS cohorts. RESULTS: In total, 157 non-glaucomatous eyes were included. Using multivariable analysis, we found preoperative IOP to be consistently associated with postoperative IOP reduction in the entire cohort. At the 6-month follow-up visit, there was a 12.4% reduction in IOP (-2.2 ± 3.4 mm Hg) seen, with no statistically significant difference between FLACS and CPS (12.3% ± 19.4% vs 12.5% ± 19.3%, respectively, p = 0.32). FLACS reduced the CDE required for phacoemulsification (6.6 ± 4.4%-seconds vs 8.6 ± 6.9%-seconds, respectively, p < 0.05). CDE was a predictor of IOP response at 6 months, but subgroup analysis revealed that this trend was driven by seven eyes requiring high CDE, and for the majority of eyes, CDE did not influence the size of the decrease. The seven eyes experiencing highest CDE were less likely to show IOP reduction at 6 months. CONCLUSION: Both FLACS and CPS resulted in similar and significant IOP reductions through 6 months after surgery. Preoperative IOP was significantly associated with IOP reduction, and CDE generally did not influence the size of the decrease.
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Extracción de Catarata , Catarata , Terapia por Láser , Facoemulsificación , Humanos , Facoemulsificación/métodos , Presión Intraocular , Estudios Prospectivos , Terapia por Láser/métodos , Agudeza Visual , Extracción de Catarata/métodos , Rayos LáserRESUMEN
OBJECTIVE: To identify corneal structure differences on quantitative high-frequency ultrasound biomicroscopy (UBM) among subjects with congenital glaucoma compared with controls. METHODS: This prospective case-control study evaluated 180 UBM images from 44 eyes of 30 subjects (18 control and 12 glaucoma, mean age 5.2±8.0 years, range 0.2-25.8 years) enrolled in the Pediatric Anterior Segment Imaging and Innovation Study (PASIIS). ImageJ was used to quantify a comprehensive set of corneal structures according to 21 quantitative parameters. Statistical analysis compared corneal measurements in glaucoma subtypes and age-matched controls with significance testing and mixed effects models. RESULTS: Significant differences between congenital glaucoma cases and controls were identified in 16 of 21 measured parameters including angle-to-angle, central and peripheral corneal thicknesses, scleral integrated pixel density, anterior corneal radius of curvature, and posterior corneal radius of curvature. Eight parameters differed significantly between primary congenital glaucoma and glaucoma following congenital cataract surgery. CONCLUSION: Multiple measurable corneal structural differences exist between congenital glaucoma and control eyes, and between primary and secondary congenital glaucoma, including but not limited to corneal width and thickness. The structural differences can be quantified from UBM image analysis. Further studies are needed to determine whether corneal features associated with glaucoma can be used to diagnose or monitor progression of congenital glaucoma.
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Glaucoma , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Córnea/diagnóstico por imagen , Glaucoma/diagnóstico , Humanos , Lactante , Microscopía Acústica , Esclerótica , Adulto JovenRESUMEN
Congenital cataracts (CC) are responsible for approximately one-tenth of childhood blindness cases globally. Here, we report an African American family with a recessively inherited form of CC. The proband demonstrated decreased visual acuity and bilateral cataracts, with nuclear and cortical cataracts in the right and left eye, respectively. Exome sequencing revealed a novel homozygous variant (c.563A > G; p.(Asn188Ser)) in GJA3, which was predicted to be pathogenic by structural analysis. Dominantly inherited variants in GJA3 are known to cause numerous types of cataracts in various populations. Our study represents the second case of recessive GJA3 allele, and the first report in African Americans. These results validate GJA3 as a bona fide gene for recessively inherited CC in humans.
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Catarata/congénito , Catarata/genética , Conexinas/química , Conexinas/genética , Mutación Missense/genética , Secuencia de Aminoácidos , Secuencia de Bases , Niño , Femenino , Homocigoto , Humanos , Dominios ProteicosRESUMEN
PURPOSE: To develop an artificial intelligence (AI) dashboard for monitoring glaucomatous functional loss. DESIGN: Retrospective, cross-sectional, longitudinal cohort study. PARTICIPANTS: Of 31 591 visual fields (VFs) on 8077 subjects, 13 231 VFs from the most recent visit of each patient were included to develop the AI dashboard. Longitudinal VFs from 287 eyes with glaucoma were used to validate the models. METHOD: We entered VF data from the most recent visit of glaucomatous and nonglaucomatous patients into a "pipeline" that included principal component analysis (PCA), manifold learning, and unsupervised clustering to identify eyes with similar global, hemifield, and local patterns of VF loss. We visualized the results on a map, which we refer to as an "AI-enabled glaucoma dashboard." We used density-based clustering and the VF decomposition method called "archetypal analysis" to annotate the dashboard. Finally, we used 2 separate benchmark datasets-one representing "likely nonprogression" and the other representing "likely progression"-to validate the dashboard and assess its ability to portray functional change over time in glaucoma. MAIN OUTCOME MEASURES: The severity and extent of functional loss and characteristic patterns of VF loss in patients with glaucoma. RESULTS: After building the dashboard, we identified 32 nonoverlapping clusters. Each cluster on the dashboard corresponded to a particular global functional severity, an extent of VF loss into different hemifields, and characteristic local patterns of VF loss. By using 2 independent benchmark datasets and a definition of stability as trajectories not passing through over 2 clusters in a left or downward direction, the specificity for detecting "likely nonprogression" was 94% and the sensitivity for detecting "likely progression" was 77%. CONCLUSIONS: The AI-enabled glaucoma dashboard, developed using a large VF dataset containing a broad spectrum of visual deficit types, has the potential to provide clinicians with a user-friendly tool for determination of the severity of glaucomatous vision deficit, the spatial extent of the damage, and a means for monitoring the disease progression.
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Inteligencia Artificial , Glaucoma/diagnóstico , Monitoreo Fisiológico , Enfermedades del Nervio Óptico/diagnóstico , Trastornos de la Visión/diagnóstico , Campos Visuales/fisiología , Adulto , Anciano , Estudios Transversales , Reacciones Falso Negativas , Femenino , Glaucoma/fisiopatología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedades del Nervio Óptico/fisiopatología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad , Trastornos de la Visión/fisiopatología , Agudeza Visual/fisiologíaRESUMEN
PURPOSE: To determine the agreement of 6 established visual field (VF) progression algorithms in a large dataset of VFs from multiple institutions and to determine predictors of discordance among these algorithms. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: Visual fields from 5 major eye care institutions in the United States were analyzed, including a subset of eyes with at least 5 Swedish interactive threshold algorithm standard 24-2 VFs that met our reliability criteria. Of a total of 831 240 VFs, a subset of 90 713 VFs from 13 156 eyes of 8499 patients met the inclusion criteria. METHODS: Six commonly used VF progression algorithms (mean deviation [MD] slope, VF index slope, Advanced Glaucoma Intervention Study, Collaborative Initial Glaucoma Treatment Study, pointwise linear regression, and permutation of pointwise linear regression) were applied to this cohort, and each eye was determined to be stable or progressing using each measure. Agreement between individual algorithms was tested using Cohen's κ coefficient. Bivariate and multivariate analyses were used to determine predictors of discordance (3 algorithms progressing and 3 algorithms stable). MAIN OUTCOME MEASURES: Agreement and discordance between algorithms. RESULTS: Individual algorithms showed poor to moderate agreement with each other when compared directly (κ range, 0.12-0.52). Based on at least 4 algorithms, 11.7% of eyes progressed. Major predictors of discordance or lack of agreement among algorithms were more depressed initial MD (P < 0.01) and older age at first available VF (P < 0.01). A greater number of VFs (P < 0.01), more years of follow-up (P < 0.01), and eye care institution (P = 0.03) also were associated with discordance. CONCLUSIONS: This extremely large comparative series demonstrated that existing algorithms have limited agreement and that agreement varies with clinical parameters, including institution. These issues underscore the challenges to the clinical use and application of progression algorithms and of applying big-data results to individual practices.
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Algoritmos , Trastornos de la Visión/diagnóstico , Campos Visuales/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Conjuntos de Datos como Asunto , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Presión Intraocular/fisiología , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Trastornos de la Visión/fisiopatología , Pruebas del Campo Visual/métodos , Adulto JovenRESUMEN
OBJECTIVES: Ocular surface disease frequently coexists with glaucoma and may be initiated or exacerbated by topical glaucoma medications. We performed a review of current literature to assess the prevalence, causes, and treatment of ocular surface disease in glaucoma patients, specifically those on topical therapy. METHODS: A Pubmed database search was conducted. A total of 720 articles published from 1972 to 2018 were found in relation with ocular surface disease, glaucoma, and glaucoma medications. Of these, 102 articles were included in this analysis. We included primary and empirical studies for patients on topical glaucoma medications. Exclusion criteria included case reports, non-English studies, and articles unrelated to the primary subject of this review. RESULTS: Ocular surface disease among normal and glaucomatous eyes was evaluated based on diagnostic testing including clinical examination and questionnaires to determine visual function and quality of life. Glaucoma medications can be associated with toxicities to the ocular surface, most often due to the nature of the preservative included in the medication; however, the incidence of toxicity can be mitigated by the use of preservative free medications, decreased preservative medications, or treatment of dry eye disease. Treatment of glaucoma with laser trabeculoplasty or minimally invasive glaucoma surgeries that spare the conjunctiva and the cornea may avoid or decrease reliance on topical glaucoma medications, potentially avoiding the initiation or progression of ocular surface disease. CONCLUSIONS: Recognition and treatment of ocular surface disease in glaucoma patients may improve patient quality of life and medication adherence. This may ultimately improve glaucoma treatment outcomes.
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Antihipertensivos/efectos adversos , Síndromes de Ojo Seco/inducido químicamente , Glaucoma/tratamiento farmacológico , Antihipertensivos/administración & dosificación , Conjuntiva/patología , Córnea/patología , Síndromes de Ojo Seco/diagnóstico , Humanos , Soluciones OftálmicasRESUMEN
PURPOSE: In this novel study, we demonstrate a standardized imaging and measurement protocol of anterior segment (AS) structures with reliability analysis using ultrasound biomicroscopy (UBM) and ImageJ software. METHODS: Ten pediatric and young adult patients undergoing examination under anesthesia for AS pathology were imaged using UBM. Four trained observers analyzed 20 images using ImageJ. Forty-five structural parameters were measured. Those that relied on the trabecular-iris angle (TIA) as a reference landmark were labeled TIA-dependent (TD) and all others were labeled non-TIA dependent (NTD). Intra-observer repeatability (IOR) and inter-observer agreement (IOA) of measurements were determined using coefficient of variation (CV) and intra-class correlation (ICC) followed by assessment of Bland-Altman plots (BAP) for each pair of observers, respectively. RESULTS: For NTD parameters, non-ciliary body (CB) related measurements showed CV range 0.60-16.22% and ICC range 0.84-0.89, whereas CB-related parameters showed CV range 2.86-23.40% and ICC range 0.29-0.92. For TD parameters, parameters < 2 degrees removed from reference showed CV range 0.02-5.40% and ICC range 0.89-1.00, whereas parameters > 1 degree removed showed CV range 0.63-27.44% and ICC range 0.22-1.00. No systematic proportional bias was detected by BAPs. CONCLUSIONS: Preplaced landmarks yielded good IOR and IOA in quantitative assessment of AS structures that were NTD and non-CB-related or less removed from the reference. CB-related NTD measurements varied greatly in IOR and IOA, indicating protocol modifications or CB qualitative assessments needed to improve accuracy. Variability in TD measurements increased the further removed from the reference, which supports implementation of a reliable reference landmark to minimize variation.
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Cámara Anterior/diagnóstico por imagen , Catarata/diagnóstico por imagen , Glaucoma/diagnóstico por imagen , Microscopía Acústica , Adolescente , Adulto , Puntos Anatómicos de Referencia , Catarata/congénito , Niño , Preescolar , Femenino , Glaucoma/congénito , Humanos , Interpretación de Imagen Asistida por Computador , Lactante , Recién Nacido , Masculino , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
PURPOSE: To compare the amount of phacoemulsification ultrasound energy used between eyes undergoing femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification. METHODS: One eye of consecutive patients undergoing routine non-complicated phacoemulsification from January 2014 to December of 2015 was included in the analysis. FLACS was performed using the Alcon LenSx. Linear regression was used for analysis with type of surgery (FLACS versus conventional phacoemulsification) as the exposure and cumulative dispersed energy (CDE) as the outcome variable. Age, surgeon, eye side, and eye sequence (first versus second eye) were covariates. RESULTS: A total of 1159 surgeries met inclusion criteria. The average age of the cohort was 70.6 (SD 8.6) years, 590 cases (51%) were performed by surgeon 1, and 582 cases (50%) were right eyes. Overall, FLACS resulted in significantly lower CDE as compared to conventional phacoemulsification (ß = 0.89, 95% CI 0.83, 0.95). When stratified by eye side and surgeon, FLACS performed on left eyes operated on by surgeon 1 resulted in lower CDE as compared to conventional phacoemulsification (ß = 0.76, 95% CI 0.66, 0.87), but not for right eyes operated on by surgeon 1 (ß = 0.92, 95% CI 0.79, 1.07) or for eyes operated on by surgeons 2 or 3. CONCLUSIONS: The use of FLACS on the Alcon LenSx platform results in a small decrease in phacoemulsification energy as compared to conventional phacoemulsification in certain cases. Further study assessing optimal laser settings and surgical technique is necessary.
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Terapia por Láser/métodos , Facoemulsificación/métodos , Agudeza Visual , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Prospectivos , Resultado del Tratamiento , Ondas UltrasónicasRESUMEN
The purpose of the study was to determine the independent predictors of long-term intraocular pressure (IOP) reduction after cataract surgery with phacoemulsification. This is a retrospective review of uncomplicated cataract surgeries from 2006 to 2008 at the Baltimore VA Medical Center with longitudinal follow-up. Demographic, clinical, biometric, and intraoperative variables including phacoemulsification parameters were recorded. Univariate and multivariate linear regression were used to analyze the relationship between these variables and postoperative IOP, which was the outcome variable. Analysis was performed in 115 eyes of 115 patients who underwent uncomplicated phacoemulsification during the study period. There was an average postoperative IOP reduction through 12, 24, and 36 months of -1.7 ± 3.1, -1.5 ± 3.8, and -1.3 ± 2.6 mmHg, respectively. Higher preoperative IOP (P < 0.001), a more anterior relative lens position (P < 0.05), and longer phaco time (P < 0.05) were significantly associated with greater postoperative decrease in IOP using univariate analysis. Using multivariate analysis, preoperative IOP (P < 0.001), and phaco time (P = 0.038) were associated with greater postoperative IOP reduction through 24 months. Phaco time is independently associated with IOP reduction after adjusting for age and preoperative IOP. Higher preoperative IOP is associated with a greater IOP-lowering effect after phacoemulsification.
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Catarata/complicaciones , Presión Intraocular/fisiología , Facoemulsificación , Anciano , Anciano de 80 o más Años , Cámara Anterior/patología , Longitud Axial del Ojo , Catarata/fisiopatología , Femenino , Humanos , Cristalino/patología , Masculino , Persona de Mediana Edad , Tempo Operativo , Análisis de Regresión , Estudios Retrospectivos , Factores de RiesgoAsunto(s)
Velocidad del Flujo Sanguíneo/fisiología , Membrana Eritrocítica/fisiología , Angiografía con Fluoresceína , Flujo Sanguíneo Regional/fisiología , Esclerótica/irrigación sanguínea , Anciano de 80 o más Años , Colorantes/administración & dosificación , Femenino , Humanos , Verde de Indocianina/administración & dosificación , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: To determine the frequency, clinical characteristics, and visual outcomes of patients who present with high or normal intraocular pressure (IOP) and open globe injuries. DESIGN: Retrospective chart review. SETTING: University of Maryland Medical Center, a level 1 trauma center. PATIENT OR STUDY POPULATION: All cases of open globe injury presenting to The University of Maryland Medical Center from July 2005 to January 2014. OBSERVATION: Demographics, initial physical examination, computed tomography findings, IOP of the affected and unaffected eyes, and follow-up evaluations. MAIN OUTCOME MEASURES: (1) IOP 10 mm Hg or greater and (2) visual acuity. RESULTS: Of 132 eyes presenting with open globe injury, IOP was recorded in 38 (28%). Mean IOP for the affected and unaffected eyes was 14±10.3 mm Hg and 16.6±4.1 mm Hg, respectively. Twenty-three (59.4%) eyes had IOP greater than 10 mm Hg. Six eyes (16.2%) had IOP greater than 21 mm Hg. Using bivariate analysis, IOP greater than 10 mm Hg was associated with posterior open globe injury (P=0.01), posterior hemorrhage (P=0.04), and intraconal retrobulbar hemorrhage (P=0.05). Adjusting for age, sex, and race, IOP greater than 10 mm Hg was associated with the presence of posterior open globe injury on clinical examination (P=0.04). Higher presenting IOP was found to predict light perception or worse vision (P=0.01). Multivariate analysis showed that poor presenting vision was the best predictor of poor final vision (P<0.01). CONCLUSIONS: High IOP does not exclude open globe injury. It is a frequent finding in patients with open globe injuries and may be associated with posterior injury and poor visual prognosis.
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Perforación Corneal/diagnóstico , Lesiones Oculares Penetrantes/diagnóstico , Presión Intraocular/fisiología , Segmento Posterior del Ojo/lesiones , Adulto , Anciano , Femenino , Hemorragia/complicaciones , Hemorragia/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Fracturas Orbitales , Pronóstico , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Centros Traumatológicos , Resultado del Tratamiento , Agudeza Visual/fisiologíaRESUMEN
We assessed parental attitudes towards congenital cardiovascular malformations in their children in a cross-sectional study in Egypt. Parents face many problems related to concerns about their child's prognosis, but these associations with parental stress have never been evaluated in Egypt or examined in relation to religiosity in a predominantly Muslim society. Accordingly, we conducted interviews in Cairo with mothers of 99 sequential infants born with conotruncal heart malformations (cases) and 65 mothers of age-matched controls. The survey assessed healthcare access and usage, knowledge of congenital cardiovascular malformations, religiosity, the Locus of Control Scale, and the Parenting Stress Index. Results showed that 45% of the mothers of cases had correct knowledge about their child's diagnosis; 85% were satisfied with the clinical care; and 79% reported that the cost of care was burdensome. Compared with parents of cases, parents of controls were more likely to report stress overall and all its subscales. Regarding belief about locus of control over health, God as a determining factor was given the highest endorsement. Mothers in the congenital cardiovascular malformations group reported a higher level of parental locus of control than did those in the control group. The correlations between stress and locus of control were stronger in the control than in the case group. Religiosity was related neither to stress nor to locus of control. Future studies can explore the roles that personal, familial, and societal factors play in exacerbating or reducing stress levels among parents of sick children, particularly in developing countries where economic pressures are acute.
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Conocimientos, Actitudes y Práctica en Salud , Cardiopatías Congénitas/diagnóstico , Madres/psicología , Responsabilidad Parental/psicología , Estrés Psicológico/epidemiología , Adulto , Estudios de Casos y Controles , Estudios Transversales , Egipto , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Escalas de Valoración Psiquiátrica , Religión , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Impaired retinal blood flow is associated with ocular diseases such as glaucoma, macular degeneration, and diabetic retinopathy. Among several ocular imaging techniques developed to measure retinal blood flow both invasively and non-invasively, adaptive optics (AO)-enabled scanning laser ophthalmoscopy (AO-SLO) resolves individual red blood cells and provides a high resolution with which to measure flow across retinal microvasculature. However, cross-validation of flow measures remains a challenge owing to instrument and patient-specific variability in each imaging technique. Hence, there is a critical need for a well-controlled clinical flow phantom for standardization and to establish blood-flow measures as clinical biomarkers for early diagnosis. Here, we present the design and validation of a simple, compact, portable, linear flow phantom based on a direct current motor and a conveyor-belt system that provides linear velocity tuning within the retinal microvasculature range (0.5-7 mm/s). The model was evaluated using a sensitive AO-SLO line-scan technique, which showed a <6% standard deviation from the true velocity. Further, a clinical SLO instrument showed a linear correlation with the phantom's true velocity (r2 > 0.997). This model has great potential to calibrate, evaluate, and improve the accuracy of existing clinical imaging systems for retinal blood flow and aid in the diagnosis of ocular diseases with abnormal blood flow.
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Impaired retinal blood flow (RBF) autoregulation plays a key role in the development and progression of several ocular diseases, including glaucoma and diabetic retinopathy. Clinically, reproducible RBF quantitation could significantly improve early diagnosis and disease management. Several non-invasive techniques have been developed but are limited for retinal microvasculature flow measurements due to their low signal-to-noise ratio and poor lateral resolution. In this study, we demonstrate reproducible vessel caliber and retinal blood flow velocity measurements in healthy human volunteers using a high-resolution (spatial and temporal) multimodal adaptive optics system with scanning laser ophthalmoscopy and optical coherence tomography.
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The measurement of retinal blood flow (RBF) in capillaries can provide a powerful biomarker for the early diagnosis and treatment of ocular diseases. However, no single modality can determine capillary flowrates with high precision. Combining erythrocyte-mediated angiography (EMA) with optical coherence tomography angiography (OCTA) has the potential to achieve this goal, as EMA can measure the absolute RBF of retinal microvasculature and OCTA can provide the structural images of capillaries. However, multimodal retinal image registration between these two modalities remains largely unexplored. To fill this gap, we establish MEMO, the first public multimodal EMA and OCTA retinal image dataset. A unique challenge in multimodal retinal image registration between these modalities is the relatively large difference in vessel density (VD). To address this challenge, we propose a segmentation-based deep-learning framework (VDD-Reg), which provides robust results despite differences in vessel density. VDD-Reg consists of a vessel segmentation module and a registration module. To train the vessel segmentation module, we further designed a two-stage semi-supervised learning framework (LVD-Seg) combining supervised and unsupervised losses. We demonstrate that VDD-Reg outperforms existing methods quantitatively and qualitatively for cases of both small VD differences (using the CF-FA dataset) and large VD differences (using our MEMO dataset). Moreover, VDD-Reg requires as few as three annotated vessel segmentation masks to maintain its accuracy, demonstrating its feasibility.
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Objective: To characterize the effect of netarsudil 0.02% on episcleral blood flow in treatment-naive glaucoma suspect or ocular hypertension subjects. Design: Prospective, unmasked, single-arm cohort study. Participants: Ten treatment-naive patients with a diagnosis of glaucoma suspect or ocular hypertension. Methods: Erythrocyte-mediated angiography (EMA) was used to measure episcleral erythrocyte velocity, vessel diameter, and blood flow at baseline before treatment, 1 hour after drop instillation (T1), 1 to 2 weeks after daily netarsudil 0.02% drop use (T2), and 1 hour after drop instillation at the 1-to-2-week time point (T3). Intraocular pressure (IOP) and blood pressure were measured at each visit. Main Outcome Measures: Change in episcleral venous erythrocyte velocity, diameter, and blood flow between time points analyzed using generalized estimating equation models. Results: Of the 18 eligible study eyes of 10 enrolled treatment-naive subjects, baseline IOP was 16.8 ± 3.6 mmHg (mean ± standard deviation), which significantly decreased to 13.9 ± 4.2 mmHg at T1, 12.6 ± 4.1 mmHg at T2, and 11.8 ± 4.7 mmHg at T3 (P < 0.05 at each time point compared with baseline). Episcleral vessels averaged 61.3 ± 5.3 µm in diameter at baseline which increased significantly at all posttreatment time points (78.0 ± 6.6, 74.0 ± 5.2, 76.9 ± 6.9 µm, respectively; mean ± standard deviation, P < 0.05 for each time point). Episcleral venous flowrates were 0.40 ± 0.22 uL/minute (mean ± standard deviation) at baseline, which increased significantly to 0.69 ± 0.45 uL/min at T1 (P = 0.01), did not significantly differ at T2 (0.38 ± 0.30 uL/minute), and increased significantly to 0.54 ± 0.32 uL/minute at T3 (P < 0.05 compared with baseline and T2). Conclusions: Netarsudil causes episcleral venous dilation at all time points and resulting increases in episcleral venous flowrates 1 hour after drop instillation. Increased episcleral venous flow, associated with decreased episcleral venous pressure, may result in lowered IOP. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Photoreceptors (PRs) and retinal pigment epithelial (RPE) cells form a functional unit called the PR-RPE complex. The PR-RPE complex plays a critical role in maintaining retinal homeostasis and function, and the quantification of its structure and topographical arrangement across the macula are important for understanding the etiology, mechanisms, and progression of many retinal diseases. However, the three-dimensional cellular morphology of the PR-RPE complex in living human eyes has not been completely described due to limitations in imaging techniques. We used the cellular resolution and depth-sectioning capabilities of a custom, high-speed Fourier domain mode-locked laser-based adaptive optics-optical coherence tomography (FDML-AO-OCT) platform to characterize human PR-RPE complex topography across the temporal macula from eleven healthy volunteers. With the aid of a deep learning algorithm, key metrics were extracted from the PR-RPE complex of averaged AO-OCT volumes including PR and RPE cell density, PR outer segment length (OSL), and PR/RPE ratio. We found a tight grouping among our cohort for PR density, with a mean (±SD) value of 53,329 (±8106) cells/mm2 at 1° decreasing to 8669 (±737) cells/mm2 at 12°. We observed a power function relationship between eccentricity and both PR density and PR/RPE ratio. We found similar variability in our RPE density measures, with a mean value of 7335 (±681) cells/mm2 at 1° decreasing to 5547 (±356) cells/mm2 at 12°, exhibiting a linear relationship with a negative slope of -123 cells/mm2 per degree. OSL monotonically decreased from 33.3 (±2.4) µm at 1° to 18.0 (±1.8) µm at 12°, following a second-order polynomial relationship. PR/RPE ratio decreased from 7.3 (±0.9) µm at 1° to 1.5 (±0.1) µm at 12°. The normative data from this investigation will help lay a foundation for future studies of retinal pathology.