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1.
Cont Lens Anterior Eye ; 47(2): 102110, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38171995

RESUMO

PURPOSE: To report the clinical signs, symptoms, and viral clearance in individuals in the United States with adenoviral conjunctivitis (Ad-Cs). METHODS: Individuals ≥ 18 years presenting within 4 days of symptoms of Ad-Cs who met eligibility criteria and tested positive with both point-of-care immunoassay antigen and quantitative polymerase chain reaction (qPCR) testing were enrolled. Patient-reported symptoms, clinician-graded signs, and qPCR viral titers were collected at baseline, days 1-2, 4 (days 3-5), 7 (days 6-10), 14 (days 11-17) and 21 (days 18-21). RESULTS: There was no detectable viral titers by the day 14 visit in 6/8 patients. By day 21, there was no detectable viral titers in the 7 participants who completed the visit; however, signs and symptoms persisted including: blurry vision (5/7), discomfort (2/7) or redness (1/7). Masked clinicians also noted conjunctival redness (4/7), follicular conjunctivitis (4/7) and bulbar edema (3/7). CONCLUSION: Many patient-reported symptoms and clinical signs persist after viral titers are no longer detectable by qPCR. Using clinical signs and symptoms to determine quarantine duration may result in patients being furloughed longer than the time that the patient is infectious.


Assuntos
Conjuntivite Viral , Conjuntivite , Humanos , Estados Unidos/epidemiologia , Conjuntivite Viral/diagnóstico , Conjuntivite Viral/epidemiologia , Carga Viral , Conjuntivite/diagnóstico , Conjuntivite/epidemiologia
2.
Nat Commun ; 15(1): 396, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195602

RESUMO

Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide. However, its molecular and cellular causes are not well understood. Elevated intraocular pressure (IOP) is a major risk factor, but many patients have normal IOP. Colocalization and Mendelian randomization analysis of >240 POAG and IOP genome-wide association study (GWAS) loci and overlapping expression and splicing quantitative trait loci (e/sQTLs) in 49 GTEx tissues and retina prioritizes causal genes for 60% of loci. These genes are enriched in pathways implicated in extracellular matrix organization, cell adhesion, and vascular development. Analysis of single-nucleus RNA-seq of glaucoma-relevant eye tissues reveals that the POAG and IOP colocalizing genes and genome-wide associations are enriched in specific cell types in the aqueous outflow pathways, retina, optic nerve head, peripapillary sclera, and choroid. This study nominates IOP-dependent and independent regulatory mechanisms, genes, and cell types that may contribute to POAG pathogenesis.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Humanos , Estudo de Associação Genômica Ampla , Glaucoma de Ângulo Aberto/genética , Regulação da Expressão Gênica , Causalidade , Glaucoma/genética
3.
Nat Commun ; 14(1): 7300, 2023 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-37949852

RESUMO

Anterior Uveitis (AU) is the inflammation of the anterior part of the eye, the iris and ciliary body and is strongly associated with HLA-B*27. We report AU exome sequencing results from eight independent cohorts consisting of 3,850 cases and 916,549 controls. We identify common genome-wide significant loci in HLA-B (OR = 3.37, p = 1.03e-196) and ERAP1 (OR = 0.86, p = 1.1e-08), and find IPMK (OR = 9.4, p = 4.42e-09) and IDO2 (OR = 3.61, p = 6.16e-08) as genome-wide significant genes based on the burden of rare coding variants. Dividing the cohort into HLA-B*27 positive and negative individuals, we find ERAP1 haplotype is strongly protective only for B*27-positive AU (OR = 0.73, p = 5.2e-10). Investigation of B*27-negative AU identifies a common signal near HLA-DPB1 (rs3117230, OR = 1.26, p = 2.7e-08), risk genes IPMK and IDO2, and several additional candidate risk genes, including ADGFR5, STXBP2, and ACHE. Taken together, we decipher the genetics underlying B*27-positive and -negative AU and identify rare and common genetic signals for both subtypes of disease.


Assuntos
Uveíte Anterior , Humanos , Uveíte Anterior/genética , Inflamação/genética , Haplótipos , Genes MHC Classe I , Antígenos HLA-B/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Aminopeptidases/genética , Antígenos de Histocompatibilidade Menor
4.
Proc Natl Acad Sci U S A ; 120(34): e2306153120, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37566633

RESUMO

Although the visual system extends through the brain, most vision loss originates from defects in the eye. Its central element is the neural retina, which senses light, processes visual signals, and transmits them to the rest of the brain through the optic nerve (ON). Surrounding the retina are numerous other structures, conventionally divided into anterior and posterior segments. Here, we used high-throughput single-nucleus RNA sequencing (snRNA-seq) to classify and characterize cells in six extraretinal components of the posterior segment: ON, optic nerve head (ONH), peripheral sclera, peripapillary sclera (PPS), choroid, and retinal pigment epithelium (RPE). Defects in each of these tissues are associated with blinding diseases-for example, glaucoma (ONH and PPS), optic neuritis (ON), retinitis pigmentosa (RPE), and age-related macular degeneration (RPE and choroid). From ~151,000 single nuclei, we identified 37 transcriptomically distinct cell types, including multiple types of astrocytes, oligodendrocytes, fibroblasts, and vascular endothelial cells. Our analyses revealed a differential distribution of many cell types among distinct structures. Together with our previous analyses of the anterior segment and retina, the data presented here complete a "Version 1" cell atlas of the human eye. We used this atlas to map the expression of >180 genes associated with the risk of developing glaucoma, which is known to involve ocular tissues in both anterior and posterior segments as well as the neural retina. Similar methods can be used to investigate numerous additional ocular diseases, many of which are currently untreatable.


Assuntos
Glaucoma , Disco Óptico , Humanos , Transcriptoma , Células Endoteliais , Glaucoma/genética , Nervo Óptico , Esclera
5.
bioRxiv ; 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37162855

RESUMO

Although the visual system extends through the brain, most vision loss originates from defects in the eye. Its central element is the neural retina, which senses light, processes visual signals, and transmits them to the rest of the brain through the optic nerve (ON). Surrounding the retina are numerous other structures, conventionally divided into anterior and posterior segments. Here we used high-throughput single nucleus RNA sequencing (snRNA-seq) to classify and characterize cells in the extraretinal components of the posterior segment: ON, optic nerve head (ONH), peripheral sclera, peripapillary sclera (PPS), choroid, and retinal pigment epithelium (RPE). Defects in each of these tissues are associated with blinding diseases - for example, glaucoma (ONH and PPS), optic neuritis (ON), retinitis pigmentosa (RPE), and age-related macular degeneration (RPE and choroid). From ∼151,000 single nuclei, we identified 37 transcriptomically distinct cell types, including multiple types of astrocytes, oligodendrocytes, fibroblasts, and vascular endothelial cells. Our analyses revealed a differential distribution of many cell types among distinct structures. Together with our previous analyses of the anterior segment and retina, the new data complete a "Version 1" cell atlas of the human eye. We used this atlas to map the expression of >180 genes associated with the risk of developing glaucoma, which is known to involve ocular tissues in both anterior and posterior segments as well as neural retina. Similar methods can be used to investigate numerous additional ocular diseases, many of which are currently untreatable.

6.
Commun Biol ; 5(1): 1051, 2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-36192519

RESUMO

Glaucoma is a leading cause of blindness. Current glaucoma medications work by lowering intraocular pressure (IOP), a risk factor for glaucoma, but most treatments do not directly target the pathological changes leading to increased IOP, which can manifest as medication resistance as disease progresses. To identify physiological modulators of IOP, we performed genome- and exome-wide association analysis in >129,000 individuals with IOP measurements and extended these findings to an analysis of glaucoma risk. We report the identification and functional characterization of rare coding variants (including loss-of-function variants) in ANGPTL7 associated with reduction in IOP and glaucoma protection. We validated the human genetics findings in mice by establishing that Angptl7 knockout mice have lower (~2 mmHg) basal IOP compared to wild-type, with a trend towards lower IOP also in heterozygotes. Conversely, increasing murine Angptl7 levels via injection into mouse eyes increases the IOP. We also show that acute Angptl7 silencing in adult mice lowers the IOP (~2-4 mmHg), reproducing the observations in knockout mice. Collectively, our data suggest that ANGPTL7 is important for IOP homeostasis and is amenable to therapeutic modulation to help maintain a healthy IOP that can prevent onset or slow the progression of glaucoma.


Assuntos
Glaucoma , Pressão Intraocular , Adulto , Proteína 7 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina/genética , Animais , Cegueira , Glaucoma/tratamento farmacológico , Glaucoma/genética , Humanos , Camundongos , Camundongos Knockout
7.
Proc Natl Acad Sci U S A ; 119(29): e2200914119, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35858321

RESUMO

The anterior segment of the eye consists of the cornea, iris, ciliary body, crystalline lens, and aqueous humor outflow pathways. Together, these tissues are essential for the proper functioning of the eye. Disorders of vision have been ascribed to defects in all of them; some disorders, including glaucoma and cataract, are among the most prevalent causes of blindness in the world. To characterize the cell types that compose these tissues, we generated an anterior segment cell atlas of the human eye using high-throughput single-nucleus RNA sequencing (snRNAseq). We profiled 195,248 nuclei from nondiseased anterior segment tissues of six human donors, identifying >60 cell types. Many of these cell types were discrete, whereas others, especially in the lens and cornea, formed continua corresponding to known developmental transitions that persist in adulthood. Having profiled each tissue separately, we performed an integrated analysis of the entire anterior segment, revealing that some cell types are unique to a single structure, whereas others are shared across tissues. The integrated cell atlas was then used to investigate cell type-specific expression patterns of more than 900 human ocular disease genes identified through either Mendelian inheritance patterns or genome-wide association studies.


Assuntos
Segmento Anterior do Olho , Oftalmopatias , Adulto , Segmento Anterior do Olho/citologia , Segmento Anterior do Olho/metabolismo , Humor Aquoso/citologia , Humor Aquoso/metabolismo , Atlas como Assunto , Corpo Ciliar/citologia , Corpo Ciliar/metabolismo , Oftalmopatias/genética , Estudo de Associação Genômica Ampla , Humanos , Iris/citologia , Especificidade de Órgãos
8.
Am J Ophthalmol ; 231: 28-38, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34102153

RESUMO

PURPOSE: To evaluate the safety and efficacy of a single, in-office administration of 5% povidone-iodine (PVP-I) compared to artificial tears (AT) for adenoviral conjunctivitis (Ad-Cs). DESIGN: Double-masked pilot randomized trial. METHODS: Patients presenting with presumed adenoviral conjunctivitis were screened at 9 U.S. clinics. INCLUSION CRITERIA: ≥18 years of age, symptoms ≤4 days, and a positive AdenoPlus test. EXCLUSION CRITERIA: thyroid disease, iodine allergy, recent ocular surgery, and ocular findings inconsistent with early-stage Ad-Cs. Randomization was to a single administration of 5% PVP-I or AT in 1 eye and examinations on days 1-2, 4, 7, 14, and 21 with conjunctival swabs taken at each visit for quantitative polymerase chain reaction. Primary outcome was percent reduction from peak viral load. Secondary outcomes were improvement in clinical signs and symptoms. RESULTS: Of 56 patients randomized, 28 had detectable viral titers at baseline. Day 4 posttreatment, viral titers in the 5% PVP-I and AT groups were 2.5% ± 2.7% and 14.4% ± 10.5% of peak, respectively (P = .020). Severity of participant-reported tearing, lid swelling, and redness as well as clinician-graded mucoid discharge, bulbar redness, and bulbar edema were lower in the 5% PVP-I group than AT group on day 4 (P < .05). After day 4, viral titers and severity of signs and symptoms decreased markedly in both groups and no differences between groups were detected. CONCLUSIONS: Pilot data suggest a single, in-office administration of 5% PVP-I could reduce viral load and hasten improvement of clinical signs and symptoms in patients with Ad-Cs.


Assuntos
Conjuntivite , Povidona-Iodo , Método Duplo-Cego , Glucocorticoides , Humanos , Lubrificantes Oftálmicos , Soluções Oftálmicas , Resultado do Tratamento
10.
Rev. bras. oftalmol ; 80(6): e0049, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1351859

RESUMO

ABSTRACT Objective To identify preoperative clinical characteristics of patients undergoing femtosecond laser-assisted anterior lamellar keratoplasty who failed to achieve optimal postoperative visual outcomes. Methods In this single-center, retrospective case series, patients who underwent femtosecond laser-assisted anterior lamellar keratoplasty between 2013 and 2018 were included if they required graft revision, subsequent corneal procedure, or additional postoperative visits for a femtosecond laser-assisted anterior lamellar keratoplasty-related issue. Visual outcomes assessed included best-corrected visual acuities and postoperative corneal astigmatism. Results Eight eyes of eight patients meeting the above criteria were included. Mean patient age was 64.5 years (range, 21 to 89 years). Mean included preoperative best-corrected visual acuities was one logarithm of the minimum angle of resolution (range, 0.3 logarithm of the minimum angle of resolution to counting fingers). Indications for femtosecond laser-assisted anterior lamellar keratoplasty included anterior stromal scarring due to viral keratitis (two cases), bacterial keratitis (one case), chronic epithelial defect (one case), Avellino dystrophy (one case), trauma (one case), and chronic endothelial failure (two cases). Six patients had history of prior intraocular surgeries including phacoemulsification (four cases), pars plana vitrectomy (one case), endothelial keratoplasty (two cases), and trabeculectomy (one case). Mean included best-corrected visual acuities at most recent follow-up was one logarithm of the minimum angle of resolution (range zero logarithm of the minimum angle of resolution to hand movements) representing improvement or stability in six of eight patients. Visually significant corneal astigmatism was present in four of eight patients. Post-femtosecond laser-assisted anterior lamellar keratoplasty procedures included graft repositioning, arcuate keratotomy, phacoemulsification, and regraft. Conclusion While femtosecond laser-assisted anterior lamellar keratoplasty offers a less-invasive treatment option compared to penetrating keratoplasty, intraoperative and postoperative management can be complex. Femtosecond laser-assisted anterior lamellar keratoplasty in patients with history of prior endothelial keratoplasty or ongoing ocular comorbidities should be pursued with caution.


RESUMO Objetivo Identificar as características clínicas pré-operatórias de pacientes submetidos à ceratoplastia lamelar anterior assistida por laser de femtossegundo que não alcançaram resultados visuais pós-operatórios ideais. Métodos Nesta série de casos retrospectiva em um único centro, os pacientes submetidos à ceratoplastia lamelar anterior assistida por laser de femtossegundo entre 2013 e 2018 foram incluídos se precisassem de revisão do enxerto, procedimento corneano subsequente ou visitas pós-operatórias adicionais por uma intercorrência relacionada à ceratoplastia lamelar anterior assistida por laser de femtossegundo. Os resultados visuais avaliados incluíram melhor acuidade visual corrigida e astigmatismo pós-operatório da córnea. Resultados Oito olhos de oito pacientes que atenderam aos critérios descritos foram incluídos. A idade média dos pacientes foi de 64,5 anos (variação de 21 a 89). A melhor acuidade visual corrigida pré-operatória média foi de um logaritmo do mínimo ângulo de resolução (variação de 0,3 logaritmo do mínimo ângulo de resolução para contagem de dedos). As indicações para ceratoplastia lamelar anterior assistida por laser de femtossegundo incluíram cicatriz do estroma anterior devido à ceratite viral (dois casos), ceratite bacteriana (um caso), defeito epitelial crônico (um caso), distrofia de Avellino (um caso), trauma (um caso) e insuficiência endotelial crônica (dois casos). Seis pacientes tinham história de cirurgias intraoculares anteriores, incluindo facoemulsificação (quatro casos), vitrectomia via pars plana (um caso), ceratoplastia endotelial (dois casos) e trabeculectomia (um caso). O mínimo ângulo de resolução médio no acompanhamento mais recente foi de um logaritmo do mínimo ângulo de resolução (variação de zero logaritmo do mínimo ângulo de resolução para movimentos das mãos), representando melhora ou estabilidade em seis de oito pacientes. Astigmatismo corneano visualmente significativo estava presente em quatro de oito pacientes. Os procedimentos pós-ceratoplastia lamelar anterior assistida por laser de femtossegundo incluíram reposicionamento do enxerto, ceratotomia arqueada, facoemulsificação e enxerto. Conclusão Embora a ceratoplastia lamelar anterior assistida por laser de femtossegundo ofereça uma opção de tratamento menos invasiva em comparação com a ceratoplastia penetrante, o manejo intra e pós-operatório pode ser complexo. A ceratoplastia lamelar anterior assistida por laser de femtossegundo em pacientes com história de ceratoplastia endotelial anterior ou comorbidades oculares correntes deve ser avaliada com cautela.


Assuntos
Humanos , Transplante de Córnea/métodos , Córnea/cirurgia , Complicações Pós-Operatórias , Refração Ocular , Estudos Retrospectivos , Ceratoplastia Penetrante , Resultado do Tratamento , Cirurgia da Córnea a Laser/métodos , Terapia a Laser/métodos , Ceratite , Lasers
11.
Sci Rep ; 10(1): 9802, 2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32555229

RESUMO

Most irreversible blindness results from retinal disease. To advance our understanding of the etiology of blinding diseases, we used single-cell RNA-sequencing (scRNA-seq) to analyze the transcriptomes of ~85,000 cells from the fovea and peripheral retina of seven adult human donors. Utilizing computational methods, we identified 58 cell types within 6 classes: photoreceptor, horizontal, bipolar, amacrine, retinal ganglion and non-neuronal cells. Nearly all types are shared between the two retinal regions, but there are notable differences in gene expression and proportions between foveal and peripheral cohorts of shared types. We then used the human retinal atlas to map expression of 636 genes implicated as causes of or risk factors for blinding diseases. Many are expressed in striking cell class-, type-, or region-specific patterns. Finally, we compared gene expression signatures of cell types between human and the cynomolgus macaque monkey, Macaca fascicularis. We show that over 90% of human types correspond transcriptomically to those previously identified in macaque, and that expression of disease-related genes is largely conserved between the two species. These results validate the use of the macaque for modeling blinding disease, and provide a foundation for investigating molecular mechanisms underlying visual processing.


Assuntos
Fóvea Central/citologia , Retina/citologia , Animais , Atlas como Assunto , Cegueira/genética , Humanos , Macaca fascicularis , RNA-Seq , Especificidade da Espécie , Transcriptoma
12.
Proc Natl Acad Sci U S A ; 117(19): 10339-10349, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32341164

RESUMO

Increased intraocular pressure (IOP) represents a major risk factor for glaucoma, a prevalent eye disease characterized by death of retinal ganglion cells; lowering IOP is the only proven treatment strategy to delay disease progression. The main determinant of IOP is the equilibrium between production and drainage of aqueous humor, with compromised drainage generally viewed as the primary contributor to dangerous IOP elevations. Drainage occurs through two pathways in the anterior segment of the eye called conventional and uveoscleral. To gain insights into the cell types that comprise these pathways, we used high-throughput single-cell RNA sequencing (scRNAseq). From ∼24,000 single-cell transcriptomes, we identified 19 cell types with molecular markers for each and used histological methods to localize each type. We then performed similar analyses on four organisms used for experimental studies of IOP dynamics and glaucoma: cynomolgus macaque (Macaca fascicularis), rhesus macaque (Macaca mulatta), pig (Sus scrofa), and mouse (Mus musculus). Many human cell types had counterparts in these models, but differences in cell types and gene expression were evident. Finally, we identified the cell types that express genes implicated in glaucoma in all five species. Together, our results provide foundations for investigating the pathogenesis of glaucoma and for using model systems to assess mechanisms and potential interventions.


Assuntos
Humor Aquoso/metabolismo , Modelos Animais de Doenças , Olho/metabolismo , Glaucoma/patologia , Pressão Intraocular , Malha Trabecular/metabolismo , Transcriptoma , Animais , Biomarcadores/análise , Olho/citologia , Glaucoma/metabolismo , Humanos , Macaca fascicularis , Macaca mulatta , Camundongos , Especificidade da Espécie , Suínos
13.
Clin Ophthalmol ; 14: 187-195, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32158177

RESUMO

PURPOSE: To characterize the visual outcomes and the treatment course of patients with exudative age-related macular degeneration (AMD) based on ocular hypotensive use. DESIGN: A matched retrospective cohort study of patients enrolled in Kaiser Permanente Southern California health plan was conducted. Patients taking ocular hypotensives were identified using pharmacy dispensing data and were matched to controls to compare visual acuity, number of anti-VEGF injections, and conversation to secondary anti-VEGF agents in the first year of treatment. Subgroup analysis was performed based on the number of ocular hypotensive agents (0, 1, 2 or 3+ agents) and drug class (aqueous suppressants and prostaglandin analogs). RESULTS: A total of 234 patients patients were examined. Baseline and final visual acuity did not significantly differ between drop users and controls, including on subgroup analysis. The average number of anti-VEGF injections did not differ between drop users and controls (6.1 vs 6.2, p=0.97), nor did the percentage of patients who were switched to a second-line anti-VEGF agent (23.9% vs 17.9%, p=0.26). Subgroup analysis did not reveal significant differences in the number of anti-VEGF injections and the percentage of patients switched to secondary agents, with patients receiving 6 ±1 injections across regardless of the number or class of ocular hypotensive agents used. CONCLUSION: Patients with concurrent glaucoma and exudative AMD have similar visual outcomes and treatment courses compared to those not taking ocular hypotensives. Although aqueous suppressants have been suggested to prolong anti-VEGF residence time, patients using these agents did not demonstrate visual benefit or a reduced injection burden in this series.

15.
Klin Monbl Augenheilkd ; 237(2): 133-139, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-32040976

RESUMO

Glaucoma is a neurodegenerative disease that leads to irreversible blindness over time. Its defining feature is the loss of retinal ganglion cells (RGCs) in the eye and their axons in the optic nerve. Increased intraocular pressure (IOP) is a major risk factor for the development of glaucoma, but is neither necessary nor sufficient for the disease and its progression; this motivates research and development of new strategies for the detection and treatment of glaucoma that focus on neuroprotection - protection of RGCs from dying. In addition, for diagnosis and treatment by reducing IOP, new approaches have been developed in recent years. This article reviews current theories of pathophysiological mechanisms underlying glaucoma and recent research - with a focus on neuroprotection and current preclinical and clinical studies to improve the diagnosis and treatment of glaucoma.


Assuntos
Glaucoma , Doenças Neurodegenerativas , Humanos , Pressão Intraocular , Neuroproteção , Nervo Óptico , Células Ganglionares da Retina
18.
Ophthalmol Retina ; 3(1): 61-72, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30929817

RESUMO

PURPOSE: To describe the characteristics and outcomes of endogenous endophthalmitis. DESIGN: Retrospective case series. PARTICIPANTS: Patients with endogenous endophthalmitis. METHODS: A retrospective chart review of patients diagnosed with endogenous endophthalmitis between September 1, 2006, and November 1, 2014. MAIN OUTCOME MEASURES: Clinical findings, treatments, microbial results, visual outcomes, and secondary ocular sequelae. RESULTS: Sixty-three patients (68 eyes) were diagnosed with endogenous endophthalmitis. Ocular symptoms were the first manifestation of disease in 76% of patients. Fungal and bacterial endophthalmitis were seen in 37% (n = 25) and 43% (n = 29) of eyes, respectively. In 47% of eyes (n = 32), the disease was associated with intravenous drug use. Eighteen percent of eyes (n = 12) underwent an initial pars plana vitrectomy (PPV) with intravitreal antibiotics, none of which required a secondary intervention for acute infection. Four percent of eyes (n = 3) received only systemic treatment. Seventy-eight percent of eyes (n = 53) underwent initial bedside aspirate with intravitreal injection of antibiotics (tap-and-injection), of which 55% (n = 29) required a secondary PPV. Of eyes that underwent secondary PPV after initially negative culture results from the tap-and-injection, 52% demonstrated positive culture results at the time of secondary PPV (n = 11/21) despite all but 1 having received appropriate antimicrobial coverage initially. Fifty-four percent of eyes (n = 37) experienced secondary ocular sequelae. Eyes that received initial tap-and-injection had statistically nonsignificant better average initial vision, but worse average vision at each follow-up interval, compared to PPV while being less likely to gain 2 lines or more of vision at every follow-up interval except 6 months, with the difference reaching statistical significance at 1 week (odds ratio = 0.014; P = 0.037). Eyes that underwent initial tap-and-injection were statistically significantly more likely to require a secondary PPV (55% vs. 0%; P = 0.0006) and had fewer positive microbial results (19% vs. 67%) than those that underwent initial PPV (P = 0.002). CONCLUSIONS: Most eyes that received initial tap-and-injection eventually underwent a secondary PPV. Initial PPV may have an important role in management because it was associated with better diagnostic yield and a trend toward better visual outcomes.


Assuntos
Antibacterianos/administração & dosagem , Endoftalmite/diagnóstico , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Fúngicas/diagnóstico , Centros de Atenção Terciária/estatística & dados numéricos , Vitrectomia/métodos , Corpo Vítreo/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bactérias/isolamento & purificação , Endoftalmite/microbiologia , Endoftalmite/terapia , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/terapia , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/terapia , Feminino , Seguimentos , Fungos/isolamento & purificação , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Acuidade Visual , Corpo Vítreo/microbiologia , Adulto Jovem
19.
Cell ; 176(5): 1222-1237.e22, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30712875

RESUMO

High-acuity vision in primates, including humans, is mediated by a small central retinal region called the fovea. As more accessible organisms lack a fovea, its specialized function and its dysfunction in ocular diseases remain poorly understood. We used 165,000 single-cell RNA-seq profiles to generate comprehensive cellular taxonomies of macaque fovea and peripheral retina. More than 80% of >60 cell types match between the two regions but exhibit substantial differences in proportions and gene expression, some of which we relate to functional differences. Comparison of macaque retinal types with those of mice reveals that interneuron types are tightly conserved. In contrast, projection neuron types and programs diverge, despite exhibiting conserved transcription factor codes. Key macaque types are conserved in humans, allowing mapping of cell-type and region-specific expression of >190 genes associated with 7 human retinal diseases. Our work provides a framework for comparative single-cell analysis across tissue regions and species.


Assuntos
Fóvea Central/fisiologia , Primatas/fisiologia , Retina/fisiologia , Idoso , Animais , Callithrix , Feminino , Humanos , Macaca , Masculino , Retina/anatomia & histologia , Células Ganglionares da Retina/metabolismo
20.
Am J Ophthalmol ; 199: 94-100, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30339795

RESUMO

PURPOSE: To ascertain the incidence of unexpected management changes at the postoperative week 1 visit in asymptomatic patients who have had an uncomplicated cataract surgery and a routine postoperative day 1 examination. DESIGN: Retrospective observational study. METHODS: A retrospective chart review was conducted of all cases of cataract extraction by phacoemulsification with intraocular lens insertion performed by the Comprehensive Ophthalmology Service at Massachusetts Eye and Ear between January 1, 2014 and December 31, 2014. The preoperative consultation, operative report, and postoperative day 1 and week 1 (postoperative days 5-14) visits were reviewed. Cases with intraoperative complications, as well as clinical findings at postoperative day 1 requiring close follow-up, were excluded. The main outcome measure was incidence of unexpected management changes at the postoperative week 1 visit after cataract surgery, defined as an unanticipated change in postoperative drops, additional procedures, or urgent referral to a specialty service. RESULTS: Overall, 1938 surgical cases of 1471 patients were reviewed, and 1510 cases (77.9%) underwent uncomplicated phacoemulsification with intraocular lens implantation with a routine postoperative day 1 examination. Of these 1510 cases, 238 (15.8%) reported symptoms at the postoperative week 1 visit, including flashes, floaters, redness, pain, or decreased vision, which warranted an examination. In total, 1272 cases were asymptomatic, and only 11 of these cases (0.9%) had an unexpected management change at postoperative week 1. Eight of 11 patients were asymptomatic steroid responders requiring alteration of their postoperative drops. Two of these patients had an intraocular pressure >30 mm Hg. CONCLUSIONS: Unexpected management changes at the postoperative week 1 timepoint after cataract surgery are rare in asymptomatic patients who have had uncomplicated cataract surgery and a routine postoperative day 1 examination. Limited data are available to outline an optimal postoperative regimen after cataract surgery. The results of this study suggest that postoperative week 1 examinations could potentially be performed on an as-needed basis in the appropriate subgroup of patients after cataract surgery.


Assuntos
Implante de Lente Intraocular/métodos , Assistência Perioperatória/métodos , Facoemulsificação/métodos , Complicações Pós-Operatórias/epidemiologia , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Feminino , Humanos , Incidência , Inflamação/tratamento farmacológico , Inflamação/etiologia , Pressão Intraocular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/etiologia , Complicações Pós-Operatórias/tratamento farmacológico , Período Pós-Operatório , Estudos Retrospectivos
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