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Human pluripotent stem cell (hPSC)-derived retinal organoids (ROs) can efficiently and reproducibly generate retinal neurons that have potential for use in cell replacement strategies [Capowski et al., Development 146, dev171686 (2019)]. The ability of these lab-grown retinal neurons to form new synaptic connections after dissociation from ROs is key to building confidence in their capacity to restore visual function. However, direct evidence of reestablishment of retinal neuron connectivity via synaptic tracing has not been reported to date. The present study employs an in vitro, rabies virus-based, monosynaptic retrograde tracing assay [Wickersham et al., Neuron 53, 639-647 (2007); Sun et al., Mol. Neurodegener. 14, 8 (2019)] to identify de novo synaptic connections among early retinal cell types following RO dissociation. A reproducible, high-throughput approach for labeling and quantifying traced retinal cell types was developed. Photoreceptors and retinal ganglion cells-the primary neurons of interest for retinal cell replacement-were the two major contributing populations among the traced presynaptic cells. This system provides a platform for assessing synaptic connections in cultured retinal neurons and sets the stage for future cell replacement studies aimed at characterizing or enhancing synaptogenesis. Used in this manner, in vitro synaptic tracing is envisioned to complement traditional preclinical animal model testing, which is limited by evolutionary incompatibilities in synaptic machinery inherent to human xenografts.
Assuntos
Células-Tronco Pluripotentes , Retina , Animais , Humanos , Espécies Reativas de Oxigênio , Retina/fisiologia , Células Ganglionares da Retina , Organoides , Diferenciação CelularRESUMO
PURPOSE: To determine whether short-latency changes in multifocal electroretinography (mfERG) observed in experimental glaucoma (EG) are secondary solely to retinal ganglion cell (RGC) loss or whether there is a separate contribution from elevated intraocular pressure (IOP). METHODS: Prior to operative procedures, a series of baseline mfERGs were recorded from six rhesus macaques using a 241-element unstretched stimulus. Animals then underwent hemiretinal endodiathermy axotomy (HEA) by placing burns along the inferior 180° of the optic nerve margin in the right eye (OD). mfERG recordings were obtained in each animal at regular intervals following for 3-4 months to allow stabilization of the HEA effects. Laser trabecular meshwork destruction (LTD) to elevate IOP was then performed; first-order kernel (K1) waveform root-mean-square (RMS) amplitudes for the short-latency segment of the mfERG wave (9-35 ms) were computed for two 7-hexagon groupings-the first located within the superior (non-axotomized) macula and the second within the inferior (axotomized) macula. Immunohistochemistry for glial fibrillary acidic protein (GFAP) was done. RESULTS: By 3 months post HEA, there was marked thinning of the inferior nerve fiber layer as measured by optical coherence tomography. Compared with baseline, no statistically significant changes in 9-35 ms K1 RMS amplitudes were evident in either the axotomized or non-axotomized portions of the macula. Following LTD, mean IOP in HEA eyes rose to 46 ± 9 compared with 20 ± 2 mmHg (SD) in the fellow control eyes. In the HEA + EG eyes, statistically significant increases in K1 RMS amplitude were present in both the axotomized inferior and non-axotomized superior portions of the OD retinas. No changes in K1 RMS amplitude were found in the fellow control eyes from baseline to HEA epoch, but there was a smaller increase from baseline to HEA + EG. Upregulation of GFAP in the Müller cells was evident in both non-axotomized and axotomized retina in eyes with elevated IOP. CONCLUSIONS: The RMS amplitudes of the short-latency mfERG K1 waveforms are not altered following axotomy but undergo marked increases following elevated IOP. This suggests that the increase in mfERG amplitude was not solely a result of RGC loss and may reflect photoreceptor and bipolar cell dysfunction and/or changes in Müller cells.
Assuntos
Glaucoma , Células Ganglionares da Retina , Animais , Células Ganglionares da Retina/fisiologia , Eletrorretinografia/métodos , Axotomia , Macaca mulatta/fisiologia , Glaucoma/diagnóstico , Retina , Pressão IntraocularRESUMO
SIGNIFICANCE: We assessed the number of referrals for low vision (LV) services to determine if establishing an LV program at a large academic medical center impacted referral rates. Visual acuity (VA), referral outcome, location, and specialty were examined as factors that could impact referrals. PURPOSE: This study aimed to identify gaps in the referral process to LV services. METHODS: Electronic medical records of patients were reviewed to ascertain the referral rate among those who qualified for services, both before (2014 to 2016) and after (2017 to 2019) the establishment of an LV program. The medical records were further subdivided into two categories based on VA in the better-seeing eye: 20/70 to 20/200 and 20/200 to worse vision. RESULTS: A total of 2014 patient records with VA qualifying for LV services were reviewed. The proportion of patients who had a VA of 20/70 to 20/200 inclusive in their better eye was 91.7%. A majority (89.8%) of patients with VA of 20/70 to 20/200 and 74.4% of patients with VA worse than 20/200 were never referred. Before establishing an LV program, only 2.2% of patients with VA of 20/70 to 20/200 were referred for services on their first visit, which improved to 8% after the program was established (odds ratio [OR], 3.88; 95% confidence interval [CI], 2.37 to 6.33; P < .001). Also, before the program's establishment, 12.5% of patients with VA worse than 20/200 were referred on their first visit, which increased to 31.9% after the program's establishment (OR, 3.29; 95% CI, 1.50 to 7.19; P = .002). Patients with VA worse than 20/200 were more likely to be referred (before: OR, 6.34 [95% CI, 3.03 to 13.28; P < .001]; after: OR, 5.38 [95% CI, 3.09 to 9.37; P < .001]). Our data also showed that 10.3% of patients in this study declined referral to LV services. CONCLUSIONS: Referral rates to LV services are low among patients who qualify. The establishment of an LV program at the medical center significantly increased referral rates. However, more improvement is necessary to connect patients to LV services.
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Baixa Visão , Humanos , Baixa Visão/diagnóstico , Baixa Visão/epidemiologia , Baixa Visão/terapia , Encaminhamento e Consulta , Acuidade VisualRESUMO
AIMS: There are limited studies on dipeptidyl-peptidase 4 inhibitor (DPP-4i), sodium glucose cotransporter 2 inhibitor (SGLT2-i), and glucagon-like peptide 1 (GLP-1) receptor agonist use and occurrence of diabetic macular edema (DME). The objective of this study was to determine the association between DPP-4i, SGLT2-i, and GLP-1 receptor agonist use and occurrence of DME. METHODS: Proportional hazard models were used to evaluate the change in hazard of developing DME associated with DPP-4i, SGLT2-i, or GLP-1 receptor agonist use. Models accounted for age at DR diagnosis, DR severity (proliferative vs non-proliferative stage), time-weighted average of HbA1c level, sex, and self-reported race/ethnicity. A p-value ≤ 0.05 was considered statistically significant. RESULTS: The hazard ratio of developing DME after diagnosis of DR was 1.2 (CI = 0.75 to 1.99; p = 0.43) for DPP-4i use, 0.93 (CI = 0.54 to 1.61; p = 0.81) for GLP-1 receptor agonist use, 0.82 (CI = 0.20 to 3.34; p = 0.78) for SGLT2-i use, 1.1 (CI = 0.75 to 1.59; p = 0.66) for any one medication use, 1.1 (CI = 0.62 to 2.09; p = 0.68) and for any two or more medications use. CONCLUSIONS: We did not find an association between DPP-4i, SGLT2-i, or GLP-1 receptor agonist use and increased hazard of development of DME among patients with DR.
Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Inibidores da Dipeptidil Peptidase IV , Receptor do Peptídeo Semelhante ao Glucagon 1 , Edema Macular , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Retinopatia Diabética/epidemiologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Masculino , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Pessoa de Meia-Idade , Idoso , Edema Macular/epidemiologia , Edema Macular/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Estudos de CoortesRESUMO
INTRODUCTION: The coronavirus pandemic created large shifts in utilization of hospital resources, patient presentations, and delivery of medical care. OBJECTIVES: This retrospective study evaluated the ocular emergencies at a tertiary-care academic hospital in Wisconsin during the COVID-19-related "Safer at Home" order. METHODS: Ophthalmology consultations performed March 23 through May 26, 2020, were compared to the same time period in the 4 preceding years and the subsequent year. Billing codes were obtained to evaluate the diagnoses and procedures performed during this time frame. RESULTS: In 2020, 155 consultations were performed (42 emergency department, 113 inpatient), compared to a mean of 214 over the 5 other study years. The incidence rate ratio (IRR) of total consultations in 2020 was 0.72 (P ≤ 0.001) compared to previous years. Significantly fewer emergency department consultations were performed (IRR 0.62, P ≤ 0.001), while inpatient consultations were similar (IRR 0.88, P = 0.119). The most common diagnosis across all study years was fracture of the skull/orbit with injury to the eye/orbit. In 2020, 13% of consultations led to a procedure, compared to a total of 16% in the other years (IRR 0.59, P = 0.018). CONCLUSIONS: This study demonstrated a 28% reduction in ophthalmology consultations at a major university hospital in Wisconsin during the COVID-19-related "Safer at Home" order, though the number of consultations leading to surgery were stable. This suggests that while patients with less acute needs may have deferred care, those requiring urgent surgery still presented to the emergency department. These data may help hospitals appropriately allocate eye care resources during future public health emergencies.
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COVID-19 , Emergências , Humanos , Wisconsin/epidemiologia , Estudos Retrospectivos , COVID-19/epidemiologia , Encaminhamento e ConsultaRESUMO
OBJECTIVE: Assess refractive outcomes following uveitic cataract surgery and identify factors associated with deviations from the target refractive goal. METHODS: A multicenter retrospective chart review was performed for 216 subjects with uveitis undergoing cataract surgery. Prediction error was calculated and tested for association with demographic and clinical characteristics using single variable and multiple regression analysis. RESULTS: 39.8% of eyes deviated from the intended refractive target by at least 0.5 diopters (D). The mean prediction error was 0.56 ± 0.67 D. Younger age (p = 0.042), preoperative inflammatory corneal findings (keratic precipitates and/or band keratopathy) (p = 0.0004), and poorer postoperative visual acuity (p = 0.0054) were associated with a deviation from the intended refractive target by at least 1 D. CONCLUSIONS: A higher percentage of eyes undergoing uveitic cataract surgery deviated from the intended refractive target when compared to reported refractive outcomes in normal subjects. Younger age, preoperative inflammatory corneal sequelae, and poorer postoperative visual acuity were associated with this outcome.
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AIM: To determine whether macular retinal nerve fibre layer (mRNFL) and ganglion cell-inner plexiform layer (GC-IPL) thicknesses vary by ethnicity after accounting for total retinal thickness. METHODS: We included healthy participants from the UK Biobank cohort who underwent macula-centred spectral domain-optical coherence tomography scans. mRNFL and GC-IPL thicknesses were determined for groups from different self-reported ethnic backgrounds. Multivariable regression models adjusting for covariables including age, gender, ethnicity and refractive error were built, with and without adjusting for total retinal thickness. RESULTS: 20237 participants were analysed. Prior to accounting for total retinal thickness, mRNFL thickness was on average 0.9 µm (-1.2, -0.6; p<0.001) lower among Asians and 1.5 µm (-2.3, -0.6; p<0.001) lower among black participants compared with white participants. Prior to accounting for total retinal thickness, the average GC-IPL thickness was 1.9 µm (-2.5, -1.4; p<0.001) lower among Asians compared with white participants, and 2.4 µm (-3.9, -1.0; p=0.001) lower among black participants compared with white participants. After accounting for total retinal thickness, the layer thicknesses were not significantly different among ethnic groups. When considered as a proportion of total retinal thickness, mRNFL thickness was ~0.1 and GC-IPL thickness was ~0.2 across age, gender and ethnic groups. CONCLUSIONS: The previously reported ethnic differences in layer thickness among groups are likely driven by differences in total retinal thickness. Our results suggest using layer thickness ratio (retinal layer thicknesses/total retinal thickness) rather than absolute thickness values when comparing retinal layer thicknesses across groups.
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Macula Lutea , Fibras Nervosas , Humanos , Fibras Nervosas/fisiologia , Células Ganglionares da Retina/fisiologia , Tomografia de Coerência Óptica/métodos , Retina/diagnóstico por imagemAssuntos
Atenção à Saúde/estatística & dados numéricos , Complicações do Diabetes/diagnóstico , Retinopatia Diabética/diagnóstico , Oftalmopatias/diagnóstico , Programas de Rastreamento/estatística & dados numéricos , Adulto , Idoso , Bases de Dados Factuais , Diabetes Mellitus , Oftalmopatias/etiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , WisconsinRESUMO
Many surveys contain sets of questions (e.g., batteries), in which the same phrase, such as a reference period or a set of response categories, applies across the set. When formatting questions for interviewer administration, question writers often enclose these repeated phrases in parentheses to signal that interviewers have the option of reading the phrase. Little research, however, examines what impact this practice has on data quality. We explore whether the presence and use of parenthetical statements is associated with indicators of processing problems for both interviewers and respondents, including the interviewer's ability to read the question exactly as worded, and the respondent's ability to answer the question without displaying problems answering (e.g., expressing uncertainty). Data are from questions about physical and mental health from 355 digitally recorded, transcribed, and interaction-coded telephone interviews. We implement a mixed-effects model with crossed random effects and nested and crossed fixed effects. The models also control for some respondent and interviewer characteristics. Findings indicate respondents are less likely to exhibit a problem when parentheticals are read, but reading the parentheticals increase the odds (marginally significant) that interviewers will make a reading error.