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PURPOSE OF REVIEW: To review the literature evaluating systemic medications for treatment of sickle cell disease (SCD) and their applications for sickle cell retinopathy. RECENT FINDINGS: Prior studies have demonstrated the efficacy of traditional systemic therapies in reducing the risk of development of sickle cell retinopathy. Since 2017, several new and promising disease-modifying therapies for sickle cell disease have been approved for clinical use, including the first genetic therapies such as exagamglogene autotemcel (exa-cel) and lovotibeglogene autotemcel (lovo-cel). These treatments have shown promising results for systemic management but are not widely utilized due to limited access and high cost. The efficacy of these therapies for the prevention of sickle cell retinopathy remains unknown and opens the door to new avenues for research. Furthermore, the role of systemic therapy for the management of hemoglobin SC (HbSC) disease, which has milder systemic effects but higher likelihood of causing retinopathy, remains poorly understood. SUMMARY: Hydroxyurea has been a mainstay of systemic management of SCD with prior work suggesting its ability to reduce the likelihood of developing retinopathy. There are several new and potentially curative systemic therapies for SCD, though their role in retinopathy prevention and management has not been studied extensively. Future studies are necessary to understand the implications of these emerging therapies for sickle cell retinopathy.
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Anemia de Células Falciformes , Enfermedad de la Hemoglobina SC , Enfermedades de la Retina , Humanos , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/genética , Enfermedad de la Hemoglobina SC/complicaciones , Enfermedad de la Hemoglobina SC/tratamiento farmacológico , Enfermedades de la Retina/tratamiento farmacológico , Enfermedades de la Retina/prevención & control , Hidroxiurea/uso terapéuticoRESUMEN
PURPOSE OF REVIEW: To review the literature evaluating the effect of cataract surgery on intraocular pressure (IOP) in patients with glaucoma. RECENT FINDINGS: Recent high-quality secondary analyses of large and primary trials continue to show IOP lowering following cataract surgery. Likewise, cataract surgery remains a key treatment for angle closure glaucoma. Some micro-invasive glaucoma surgeries (MIGS) have strong evidence to be performed at the time of cataract surgery. Data clarifying when these surgeries should be combined with cataract surgery is emerging. The mechanism underlying IOP lowering after cataract surgery remains unclear. SUMMARY: Patients who are glaucoma suspects with visually significant cataracts would benefit from cataract surgery alone. Those with mild-moderate damage on 1-2 classes of medications would most likely benefit from additional MIGS. Patients with advanced disease would benefit from cataract surgery and a choice of additional surgery, which depends on disease status and patient factors. Clear lens extraction is becoming a more accepted practice as a primary procedure for patients with angle closure and high IOP or glaucoma. The role of additional MIGS in angle closure needs further study.
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Extracción de Catarata , Catarata , Glaucoma , Cristalino , Facoemulsificación , Humanos , Presión Intraocular , Extracción de Catarata/métodos , Glaucoma/cirugía , Cristalino/cirugía , Catarata/complicaciones , Facoemulsificación/métodosRESUMEN
Studies of color perception have led to mechanistic models of how cone-opponent signals from retinal ganglion cells are integrated to generate color appearance. But it is unknown how this hypothesized integration occurs in the brain. Here we show that cone-opponent signals transmitted from retina to primary visual cortex (V1) are integrated through highly organized circuits within V1 to implement the color opponent interactions required for color appearance. Combining intrinsic signal optical imaging (ISI) and 2-photon calcium imaging (2PCI) at single cell resolution, we demonstrate cone-opponent functional domains (COFDs) that combine L/M cone-opponent and S/L + M cone-opponent signals following the rules predicted from psychophysical studies of color perception. These give rise to an orderly organization of hue preferences of the neurons within the COFDs and the generation of hue "pinwheels". Thus, spatially organized neural circuits mediate an orderly transition from cone-opponency to color appearance that begins in V1.
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Calcio , Corteza Visual Primaria , Células Fotorreceptoras Retinianas Conos/fisiología , Percepción de Color/fisiología , Retina/fisiología , Estimulación Luminosa/métodos , ColorRESUMEN
Similar to other organs, the retina relies on tightly regulated perfusion and oxygenation. Previous studies have demonstrated that retinal blood flow is affected in a variety of eye and systemic diseases, including diabetic retinopathy, age-related macular degeneration, and glaucoma. Although measurement of peripheral oxygen saturation has become a standard clinical measurement through the development of pulse oximetry, developing a noninvasive technique to measure retinal oxygen saturation has proven challenging, and retinal oximetry technology currently remains inadequate for reliable clinical use. Here, we review current strategies and approaches, as well as several newer technologies in development, and discuss the future of retinal oximetry.
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Retinopatía Diabética , Vasos Retinianos , Humanos , Oximetría , Oxígeno , Retina/diagnóstico por imagen , Vasos Retinianos/diagnóstico por imagenRESUMEN
BACKGROUND: Cardiovascular disease is the leading cause of mortality and disability worldwide. A noninvasive test that can detect underlying cardiovascular disease has the potential to identify patients at risk prior to the occurrence of adverse cardiovascular events. We sought to determine whether an easily observed imaging finding indicative of retinal ischemia, which we term 'retinal ischemic perivascular lesions' (RIPLs), could serve as a biomarker for cardiovascular disease. METHODS: We reviewed optical coherence tomography (OCT) scans of individuals, with no underlying retinal pathology, obtained at UC San Diego Health from July 2014 to July 2019. We identified 84 patients with documented cardiovascular disease and 76 healthy controls. OCT scans were assessed for evidence of RIPLs. In addition, the 10-year atherosclerotic cardiovascular disease (ASCVD) risk calculator was used to risk-stratify the subjects into four different categories. FINDINGS: Patients with documented cardiovascular disease had higher number of RIPLs compared to healthy controls (2.8 vs 0.8, p < 0.001). After adjusting for age, sex, smoking history, systolic blood pressure and triglycerides, cholesterol and hemoglobin A1C levels, each RIPL was associated with an odds ratio of having cardiovascular disease of 1·60 (1.09-2>37). The number of RIPLs in individuals with intermediate and high 10-year ASCVD risk scores was higher than in those with low ASCVD risk scores (1.7 vs 0.64, p = 0.02 and 2.9 vs 0.64, p 0.002, respectively). INTERPRETATION: The presence of RIPLs, which are anatomical markers of prior retinal ischemic infarcts, is suggestive of coexisting cardiovascular disease. RIPLs detection, obtained from routine retinal scans, may thus provide an additional biomarker to identify patients at risk of developing adverse cardiovascular events. FUNDING: None.
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PURPOSE: The global COVID-19 pandemic has resulted in a renewed focus on the importance of personal protective equipment (PPE) and other interventions to decrease spread of infectious diseases. Although several ophthalmology organizations have released guidance on appropriate PPE for surgical procedures and ophthalmology clinics, there is limited experimental evidence that demonstrates the efficacy of various interventions that have been suggested. In this study, we evaluated high-risk aspects of the slit-lamp exam and the effect of various PPE interventions, specifically the use of a surgical mask and a slit-lamp shield. DESIGN: Experimental simulation study. METHODS: This was a single-center study in a patient simulation population. This study examined the presence of particles in the air near or on a slit-lamp, a simulated slit-lamp examiner, or a simulated patient using a fluorescent surrogate of respiratory droplets. RESULTS: Simulated coughing without a mask or slit-lamp shield resulted in widespread dispersion of fluorescent droplets during the model slit-lamp examination. Coughing with a mask resulted in the most significant decrease in droplets; however, particles still escaped from the top of the mask. Coughing with the slit-lamp shield alone blocked most of forward particle dispersion; however, significant distributions of respiratory droplets were found on the slit-lamp joystick and table. Coughing with both a mask and slit-lamp shield resulted in the least dispersion to the simulated examiner and the simulated patient. Scanning electron microscopy demonstrated particle sizes of 3-100 µm. CONCLUSIONS: Masking had the greatest effect in limiting spread of respiratory droplets, whereas slit-lamp shields and gloves also contributed to limiting exposure to droplets from SARS-CoV-2 during slit-lamp examination.
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COVID-19/transmisión , Transmisión de Enfermedad Infecciosa/prevención & control , Simulación de Paciente , Equipo de Protección Personal , Impresión Tridimensional , SARS-CoV-2 , Microscopía con Lámpara de Hendidura/métodos , COVID-19/epidemiología , Humanos , PandemiasRESUMEN
Various breathing and cough simulators have been used to model respiratory droplet dispersion and viral droplets, in particular for SARS-CoV-2 modeling. However, limited data are available comparing these cough simulations to physiological breathing and coughing. In this study, three different cough simulators (Teleflex Mucosal Atomization Device Nasal (MAD Nasal), a spray gun, and GloGermTM MIST) that have been used in the literature were studied to assess their physiologic relevance. Droplet size, velocity, dispersion, and force generated by the simulators were measured. Droplet size was measured with scanning electron microscopy (SEM). Slow-motion videography was used to 3D reconstruct and measure the velocity of each simulated cough. A force-sensitive resistor was used to measure the force of each simulated cough. The average size of droplets from each cough simulator was 176 to 220 µm. MAD Nasal, the spray gun, and GloGermTM MIST traveled 0.38 m, 0.89 m, and 1.62 m respectively. The average velocities for the MAD Nasal, spray gun, and GloGermTM MIST were 1.57 m/s, 2.60 m/s, and 9.27 m/s respectively, and all yielded a force of <0.5 Newtons. GloGermTM MIST and the spray gun most closely resemble physiological coughs and breathing respectively. In conclusion, none of the simulators tested accurately modeled all physiologic characteristics (droplet size, 3-D dispersion velocity, and force) of a cough, while there were various strengths and weaknesses of each method. One should take this into account when performing simulations with these devices.
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Previous studies support the textbook model that shape and color are extracted by distinct neurons in primate primary visual cortex (V1). However, rigorous testing of this model requires sampling a larger stimulus space than previously possible. We used stable GCaMP6f expression and two-photon calcium imaging to probe a very large spatial and chromatic visual stimulus space and map functional microarchitecture of thousands of neurons with single-cell resolution. Notable proportions of V1 neurons strongly preferred equiluminant color over achromatic stimuli and were also orientation selective, indicating that orientation and color in V1 are mutually processed by overlapping circuits. Single neurons could precisely and unambiguously code for both color and orientation. Further analyses revealed systematic spatial relationships between color tuning, orientation selectivity, and cytochrome oxidase histology.
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Percepción de Color/fisiología , Orientación/fisiología , Conducta Espacial/fisiología , Corteza Visual/fisiología , Animales , Complejo IV de Transporte de Electrones/metabolismo , Femenino , Macaca fascicularis , Neuroimagen , Neuronas , Corteza Visual/ultraestructuraRESUMEN
PURPOSE: To describe a standardized flood-illuminated adaptive optics (AO) imaging protocol suitable for the clinical setting and to assess sampling methods for measuring cone density. METHODS: Cone density was calculated following three measurement protocols: 50 × 50-µm sampling window values every 0.5° along the horizontal and vertical meridians (fixed-interval method), the mean density of expanding 0.5°-wide arcuate areas in the nasal, temporal, superior, and inferior quadrants (arcuate mean method), and the peak cone density of a 50 × 50-µm sampling window within expanding arcuate areas near the meridian (peak density method). Repeated imaging was performed in nine subjects to determine intersession repeatability of cone density. RESULTS: Cone density montages could be created for 67 of the 74 subjects. Image quality was determined to be adequate for automated cone counting for 35 (52%) of the 67 subjects. We found that cone density varied with different sampling methods and regions tested. In the nasal and temporal quadrants, peak density most closely resembled histological data, whereas the arcuate mean and fixed-interval methods tended to underestimate the density compared with histological data. However, in the inferior and superior quadrants, arcuate mean and fixed-interval methods most closely matched histological data, whereas the peak density method overestimated cone density compared with histological data. Intersession repeatability testing showed that repeatability was greatest when sampling by arcuate mean and lowest when sampling by fixed interval. CONCLUSIONS: We show that different methods of sampling can significantly affect cone density measurements. Therefore, care must be taken when interpreting cone density results, even in a normal population.
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Iluminación/métodos , Mácula Lútea/fisiología , Oftalmoscopía/métodos , Fenómenos Ópticos , Células Fotorreceptoras Retinianas Conos/citología , Adolescente , Adulto , Anciano , Recuento de Células , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fotograbar/métodos , Reproducibilidad de los Resultados , Células Fotorreceptoras Retinianas Conos/fisiología , Campos Visuales/fisiología , Adulto JovenRESUMEN
BACKGROUND: Adaptive optics scanning light ophthalmoscopy (AOSLO) enables direct visualisation of the cone mosaic, with metrics such as cone density and cell spacing used to assess the integrity or health of the mosaic. Here we examined the interobserver and inter-instrument reliability of cone density measurements. METHODS: For the interobserver reliability study, 30 subjects with no vision-limiting pathology were imaged. Three image sequences were acquired at a single parafoveal location and aligned to ensure that the three images were from the same retinal location. Ten observers used a semiautomated algorithm to identify the cones in each image, and this was repeated three times for each image. To assess inter-instrument reliability, 20 subjects were imaged at eight parafoveal locations on one AOSLO, followed by the same set of locations on the second AOSLO. A single observer manually aligned the pairs of images and used the semiautomated algorithm to identify the cones in each image. RESULTS: Based on a factorial study design model and a variance components model, the interobserver study's largest contribution to variability was the subject (95.72%) while the observer's contribution was only 1.03%. For the inter-instrument study, an average cone density intraclass correlation coefficient (ICC) of between 0.931 and 0.975 was calculated. CONCLUSIONS: With the AOSLOs used here, reliable cone density measurements can be obtained between observers and between instruments. Additional work is needed to determine how these results vary with differences in image quality.
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Fóvea Central/citología , Oftalmoscopios/normas , Oftalmoscopía/métodos , Células Fotorreceptoras Retinianas Conos/citología , Adulto , Recuento de Células , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Reconocimiento de Normas Patrones Automatizadas/métodos , Reproducibilidad de los Resultados , Enfermedades de la Retina/diagnóstico , Adulto JovenRESUMEN
The aim of this study was to assess the feasibility of using a commercially available high-resolution adaptive optics (AO) camera to image the cone mosaic in Japanese macaques (Macaca fuscata) with dominantly inherited drusen. The macaques examined develop drusen closely resembling those seen in humans with age-related macular degeneration (AMD). For each animal, we acquired and processed images from the AO camera, montaged the results into a composite image, applied custom cone-counting software to detect individual cone photoreceptors, and created a cone density map of the macular region. We conclude that flood-illuminated AO provides a promising method of visualizing the cone mosaic in nonhuman primates. Future studies will quantify the longitudinal change in the cone mosaic and its relationship to the severity of drusen in these animals.
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Modelos Animales de Enfermedad , Fondo de Ojo , Macaca , Degeneración Macular/patología , Drusas del Disco Óptico/patología , Células Fotorreceptoras Retinianas Conos/citología , Animales , Longitud Axial del Ojo/patología , Recuento de Células/instrumentación , Recuento de Células/métodos , Procesamiento de Imagen Asistido por Computador/instrumentación , Procesamiento de Imagen Asistido por Computador/métodos , Neoplasias Basocelulares , Oftalmoscopía/métodosRESUMEN
PURPOSE: We characterize the in vivo changes over time in the retinal structure of wild-type mice alongside two lines of mice deficient in the ß-subunit of phosphodiesterase (rd1 and rd10 mice) using spectral domain optical coherence tomography (SD-OCT). METHODS: SD-OCT images were obtained using the Bioptigen spectral domain ophthalmic imaging system (SDOIS). Wild-type C57BL/6J, rd1 and rd10 mice ranging in age from P14 to P206 were sedated with 1% isoflurane. Horizontal and vertical linear scans through the optic nerve, and annular scans around the optic nerve were obtained. RESULTS: SD-OCT imaging of wild-type mice demonstrated visibility of the inner segment/outer segment (IS/OS) junction, external limiting membrane (ELM), outer nuclear layer (ONL), and outer plexiform layer (OPL). At P14, most rd10 mice exhibited normal SD-OCT profiles, but some displayed changes in the IS/OS junction. At the same time point, rd1 mice had severe outer retinal degeneration. In rd10 mice, imaging revealed loss of the IS/OS junction by P18, hyperreflective changes in the ONL at P20, hyperreflective vitreous opacities, and shallow separation of the neural retina from the RPE. Retinal separations were not observed in rd1 mice. Segmentation analysis in wild-type mice demonstrated relatively little variability between animals, while in rd10 and rd1 mice there was a steady decline in outer retinal thickness. Histologic studies demonstrated correlation of retinal features with those seen on SD-OCT scans. Segmentation analysis provides a quantitative and reproducible method for measuring in vivo retinal changes in mice. CONCLUSIONS: SD-OCT provides a non-invasive method of following long-term retinal changes in mice in vivo. Although rd10 and rd1 mice have mutations in the same gene, they demonstrate significantly different features on SD-OCT.