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PURPOSE OF REVIEW: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious coronavirus causing the COVID-19 pandemic. Although airborne spread through infectious respiratory droplets is the primary source of transmission, recent literature has suggested the ocular surface may be able to harbor viral particles. Here, we aim to discuss how SARS-CoV-2 affects the ocular surface and updated guidance on how SARS-CoV-2 transmission should be considered in the setting of eye banking and corneal transplantation procedures. RECENT FINDINGS: SARS-CoV-2 RNA can be found on the ocular surface, which may suggest the eye as a site of viral replication. However, there is poor correlation between PCR positivity on the ocular surface and ocular symptoms. To date, although viral particles can be found on the ocular surface, use of standard antiseptic procedures during corneal tissue procurement appears to sufficiently reduce viral load. In addition, preprocedure testing may further decrease the chances of transplanting an infected cornea without significantly impacting the overall accessibility to corneal tissue by decreasing the donor pool. SUMMARY: Corneal transplantation remains a well tolerated and highly successful procedure with no evidence of viral transmission with transplantation. Although the ocular surface has the required receptors to allow for viral replication, there is no clear evidence that the eye is a site for primary viral infection.
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COVID-19/prevenção & controle , Córnea/virologia , Transplante de Córnea/normas , Bancos de Olhos , Obtenção de Tecidos e Órgãos/métodos , COVID-19/transmissão , Humanos , Guias de Prática Clínica como Assunto , SARS-CoV-2/isolamento & purificação , Doadores de Tecidos/provisão & distribuiçãoRESUMO
The capability to conditionally inactivate gene function is essential for understanding the molecular basis of development. In gene and mRNA targeting approaches, protein products can perdure, complicating genetic analysis. Current methods for selective protein degradation require drug treatment or take hours for protein removal, limiting their utility in studying rapid developmental processes in vivo. Here, we repurpose an endogenous protein degradation system to rapidly remove targeted C. elegans proteins. We show that upon expression of the E3 ubiquitin ligase substrate-recognition subunit ZIF-1, proteins tagged with the ZF1 zinc-finger domain can be quickly degraded in all somatic cell types examined with temporal and spatial control. We demonstrate that genes can be engineered to become conditional loss-of-function alleles by introducing sequences encoding the ZF1 tag into endogenous loci. Finally, we use ZF1 tagging to establish the site of cdc-42 gene function during a cell invasion event. ZF1 tagging provides a powerful new tool for the analysis of dynamic developmental events.
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Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Proteínas de Transporte/metabolismo , Regulação da Expressão Gênica/fisiologia , Engenharia Genética/métodos , Proteólise , Dedos de Zinco/genética , Animais , Western Blotting , Caenorhabditis elegans/metabolismo , Primers do DNA/genética , Fluorescência , Regulação da Expressão Gênica/genética , Processamento de Imagem Assistida por Computador , Cinética , Plasmídeos/genética , Transgenes/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Lumenogenesis of small seamless tubes occurs through intracellular membrane growth and directed vesicle fusion events. Within the Caenorhabditis elegans excretory cell, which forms seamless intracellular tubes (canals) that mediate osmoregulation, lumens grow in length and diameter when vesicles fuse with the expanding lumenal surface. Here, we show that lumenal vesicle fusion depends on the small GTPase RAL-1, which localizes to vesicles and acts through the exocyst vesicle-tethering complex. Loss of either the exocyst or RAL-1 prevents excretory canal lumen extension. Within the excretory canal and other polarized cells, the exocyst co-localizes with the PAR polarity proteins PAR-3, PAR-6 and PKC-3. Using early embryonic cells to determine the functional relationships between the exocyst and PAR proteins, we show that RAL-1 recruits the exocyst to the membrane, while PAR proteins concentrate membrane-localized exocyst proteins to a polarized domain. These findings reveal that RAL-1 and the exocyst direct the polarized vesicle fusion events required for intracellular lumenogenesis of the excretory cell, suggesting mechanistic similarities in the formation of topologically distinct multicellular and intracellular lumens.
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Caenorhabditis elegans/embriologia , Fusão de Membrana/fisiologia , Vesículas Secretórias/metabolismo , Proteínas ral de Ligação ao GTP/genética , Animais , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Osmorregulação/genética , Proteína Quinase C/genética , Proteína Quinase C/metabolismo , Proteínas Serina-Treonina Quinases , Interferência de RNA , RNA Interferente Pequeno , Proteínas de Transporte Vesicular/genéticaRESUMO
PURPOSE: To compare the efficacy of an intracanalicular dexamethasone intracanalicular insert (DII) to a topical prednisolone acetate 1% taper for preventing breakthrough inflammation (iritis or cystoid macular edema) during the first post-operative month (POM1) after cataract surgery DESIGN: Retrospective, non-randomized comparative interventional study METHODS: Patients received either DII or topical prednisolone acetate 1% eyedrops (control) during POM1. Exclusion criteria included history of iritis, glaucoma, intraoperative posterior capsular rupture or vitreous prolapse, immediate postoperative anterior chamber inflammation requiring treatment, or less than 1 month follow up post-operatively. Outcomes included development of breakthrough inflammation after >3 days postoperatively necessitating additional anti-inflammatory drops, cystoid macular edema, and increased intraocular pressure at POM1. RESULTS: 266 eyes of 174 patients were included in the DII group, and 258 eyes of 167 patients in the control group. Demographics, comorbidities, and baseline IOP were comparable between groups. The breakthrough inflammation rate was significantly higher in the DII group compared to control (9.0% vs 3.1%; p < .01); cystoid macular edema rates were similar between groups (4.9% vs 4.3%; pâ¯=â¯.75). There were no cases of increased IOP >10mmHg at POM1 compared to baseline in either group. CONCLUSION: After cataract surgery, DII demonstrated a higher rate of breakthrough inflammation than a standard topical steroid regimen with no significant differences in CME rate or IOP increase; however, overall, the rate of postoperative complications was low. DII can be a safe and effective alternative to topical corticosteroid therapy after cataract surgery.
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PURPOSE: To report and evaluate a multicenter series of 18 cases of severe, spontaneous IOL tilt involving the flanged intrascleral haptic fixation technique (FISHF). DESIGN: Clinical study with historical controls. METHODS: We report a cross-sectional study of 46 FISHF cases using the CT Lucia 602 IOL at a single academic center over a period of 24 weeks to determine the incidence of severe rotisserie-style rotational tilt. These rates were then compared with the same time-frame the prior year to help determine if this is a new phenomenon. Additional cases of severe tilt were solicited from another 4 academic centers. RESULTS: Among 46 FISHF cases at a single center, 5 developed severe tilt. No clear pattern in surgical technique, ocular history, or ocular anatomy was evident in these cases compared with controls, although the involved IOLs clustered within a narrow diopter range, indicative of a batch effect. In the same 24-week interval the year before, 33 FISHF cases were performed, none of which exhibited severe rotational tilt. In our multicenter dataset, 18 cases of tilt were identified. Surgeons included fellow and early-career physicians as well as surgeons with multiple years of experience with the Yamane technique. A variety of surgical approaches for FISHF were represented. In at least 8 of the cases, haptic rotation and/or dehiscence at the optic-haptic junction were documented. CONCLUSIONS: The identification of haptic rotation and dehiscence intraoperatively in several cases may reflect a new stability issue involving the optic-haptic junction.
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Migração do Implante de Lente Intraocular , Implante de Lente Intraocular , Lentes Intraoculares , Esclera , Humanos , Esclera/cirurgia , Estudos Transversais , Implante de Lente Intraocular/métodos , Feminino , Masculino , Idoso , Migração do Implante de Lente Intraocular/cirurgia , Migração do Implante de Lente Intraocular/fisiopatologia , Pessoa de Meia-Idade , Acuidade Visual/fisiologia , Idoso de 80 Anos ou mais , FacoemulsificaçãoRESUMO
INTRODUCTION: Corticosteroids (CS) have been standard immunosuppression to prevent and treat rejection. However, CS are associated with increased risk of infection, obesity, hypertension, hyperlipidemia, diabetes, and accelerated hepatitis C virus (HCV) recurrence post-orthotopic liver transplantation (OLT). This study assesses the safety and efficacy of CS-free immunosuppressive regimen in adult OLT. METHODS: A two-yr, prospective, randomized study of CS with delayed withdrawal (CS) or CS-free regimen with basiliximab, tacrolimus, and enteric-coated mycophenolate sodium (EC-MPS) was performed in 39 patients (CS=20; CS-free=19). CS group received intra-operative methylprednisolone weaned by six months. HCV patients had HCV PCR pre-OLT and 0.5, one, three, and six months post-OLT. Protocol liver biopsies were performed at OLT, 2 and 24 wk post-OLT or when indicated. RESULTS: Rejection occurred in two patients. Patient survival at one yr (100% vs. 95%), three yr (85% vs. 63%), and five yr (80% vs. 63%) post-OLT were similar between CS and CS-free group, respectively. Death-censored graft survival at one yr (100% vs. 95%), three yr (85% vs. 63%), and five yr (75% vs. 63%) were also similar. The risk of new-onset DM, hypertension, hypercholesterolemia, and weight gain was similar between groups. CONCLUSION: CS avoidance with basiliximab, calcineurin inhibitor, and EC-MPS is safe and effective as CS- containing immunosuppression in adult OLT.
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Corticosteroides , Rejeição de Enxerto/prevenção & controle , Terapia de Imunossupressão/mortalidade , Imunossupressores/uso terapêutico , Hepatopatias/cirurgia , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Basiliximab , Feminino , Seguimentos , Rejeição de Enxerto/mortalidade , Humanos , Hepatopatias/mortalidade , Transplante de Fígado , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Estudos Prospectivos , Proteínas Recombinantes de Fusão/uso terapêutico , Taxa de Sobrevida , Tacrolimo/uso terapêutico , Adulto JovemRESUMO
Caenorhabditis elegans provides a simplified, in vivo model system in which to study adherens junctions (AJs) and their role in morphogenesis. The core AJ components-HMR-1/E-cadherin, HMP-2/ß-catenin and HMP-1/α-catenin-were initially identified through genetic screens for mutants with body axis elongation defects. In early embryos, AJ proteins are found at sites of contact between blastomeres, and in epithelial cells AJ proteins localize to the multifaceted apical junction (CeAJ)-a single structure that combines the adhesive and barrier functions of vertebrate adherens and tight junctions. The apically localized polarity proteins PAR-3 and PAR-6 mediate formation and maturation of junctions, while the basolaterally localized regulator LET-413/Scribble ensures that junctions remain apically positioned. AJs promote robust adhesion between epithelial cells and provide mechanical resistance for the physical strains of morphogenesis. However, in contrast to vertebrates, C. elegans AJ proteins are not essential for general cell adhesion or for epithelial cell polarization. A combination of conserved and novel proteins localizes to the CeAJ and works together with AJ proteins to mediate adhesion.
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Junções Aderentes/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/embriologia , Embrião não Mamífero/citologia , Regulação da Expressão Gênica no Desenvolvimento , Morfogênese , Animais , Caenorhabditis elegans/metabolismo , Embrião não Mamífero/metabolismoRESUMO
Progressive corneal opacification can result from multiple etiologies, including corneal dystrophies or systemic and genetic diseases. We describe a novel syndrome featuring progressive epithelial and anterior stromal opacification in a brother and sister and their mildly affected father, with all three family members having sensorineural hearing loss and two also with tracheomalacia/laryngomalacia. All carried a 1.2 Mb deletion at chromosome 13q12.11, with no other noteworthy co-segregating variants identified on clinical exome or chromosomal microarray. RNAseq analysis from an affected corneal epithelial sample from the proband's brother revealed downregulation of XPO4, IFT88, ZDHHC20, LATS2, SAP18, and EEF1AKMT1 within the microdeletion interval, with no notable effect on the expression of nearby genes. Pathway analysis showed upregulation of collagen metabolism and extracellular matrix (ECM) formation/maintenance, with no significantly down-regulated pathways. Analysis of overlapping deletions/variants demonstrated that deleterious variants in XPO4 were found in patients with laryngomalacia and sensorineural hearing loss, with the latter phenotype also being a feature of variants in the partially overlapping DFNB1 locus, yet none of these had reported corneal phenotypes. Together, these data define a novel microdeletion-associated syndromic progressive corneal opacification and suggest that a combination of genes within the microdeletion may contribute to ECM dysregulation leading to pathogenesis.
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Perda Auditiva Neurossensorial , Laringomalácia , Masculino , Feminino , Humanos , Perda Auditiva Neurossensorial/genética , Síndrome , Irmãos , Análise em Microsséries , Proteínas Serina-Treonina Quinases , Proteínas Supressoras de TumorRESUMO
Purpose: To develop a method for accurate automated real-time identification of instruments in cataract surgery videos. Methods: Cataract surgery videos were collected at University of Michigan's Kellogg Eye Center between 2020 and 2021. Videos were annotated for the presence of instruments to aid in the development, validation, and testing of machine learning (ML) models for multiclass, multilabel instrument identification. Results: A new cataract surgery database, BigCat, was assembled, containing 190 videos with over 3.9 million annotated frames, the largest reported cataract surgery annotation database to date. Using a dense convolutional neural network (CNN) and a recursive averaging method, we were able to achieve a test F1 score of 0.9528 and test area under the receiver operator characteristic curve of 0.9985 for surgical instrument identification. These prove to be state-of-the-art results compared to previous works, while also only using a fraction of the model parameters of the previous architectures. Conclusions: Accurate automated surgical instrument identification is possible with lightweight CNNs and large datasets. Increasingly complex model architecture is not necessary to retain a well-performing model. Recurrent neural network architectures add additional complexity to a model and are unnecessary to attain state-of-the-art performance. Translational Relevance: Instrument identification in the operative field can be used for further applications such as evaluating surgical trainee skill level and developing early warning detection systems for use during surgery.
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Extração de Catarata , Catarata , Oftalmologia , Catarata/diagnóstico , Humanos , Aprendizado de Máquina , Redes Neurais de ComputaçãoRESUMO
Autoimmune and autoinflammatory diseases cause morbidity in multiple organ systems including the ocular anterior segment. Genetic disorders of the innate and adaptive immune system present an avenue to study more common inflammatory disorders and host-pathogen interactions. Many of these Mendelian disorders have ophthalmic manifestations. In this review, we highlight the ophthalmic and molecular features of disorders of the innate immune system. A comprehensive literature review was performed using PubMed and the Online Mendelian Inheritance in Man databases spanning 1973-2020 with a focus on three specific categories of genetic disorders: RIG-I-like receptors and downstream signaling, inflammasomes, and RNA processing disorders. Tissue expression, clinical associations, and animal and functional studies were reviewed for each of these genes. These genes have broad roles in cellular physiology and may be implicated in more common conditions with interferon upregulation including systemic lupus erythematosus and type 1 diabetes. This review contributes to our understanding of rare inherited conditions with ocular involvement and has implications for further characterizing the effect of perturbations in integral molecular pathways.
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PURPOSE: Studies have identified a wide range of ocular signs and symptoms in coronavirus disease 2019 (COVID-19) patients; however, these studies were often conducted outside of the United States. We aim to investigate the ocular manifestations of hospitalized COVID-19 patients at a tertiary care medical center in the United States. PATIENTS AND METHODS: A retrospective, cross-sectional study was conducted on individuals aged 18 and over who were hospitalized for COVID-19 between March 10, 2020 and April 13, 2020. The electronic health record was reviewed for all patients, and a follow-up phone survey was conducted on patients who were discharged home. Data on patient history, physical exam, laboratory results, and hospital disposition were collected and analyzed. RESULTS: A total of 400 patients were included. The mean patient age was 61.7 years (SD 15.5) and 233 (58.3%) were males. Ocular signs and symptoms were noted in 38 (9.5%) patients. The most common ocular abnormality was conjunctival injection, followed by vision changes and ocular irritation. Among the 38 patients, 30 (79.0%) developed ocular involvement prior to day 30 of onset of their COVID symptoms. Univariate analysis showed that age, gender, ocular history, fever, mechanical ventilation, and increasing inflammatory markers were not significantly associated with the presence or development of ocular symptoms. CONCLUSION: In this study, 9.5% of hospitalized COVID-19 patients exhibited ocular signs and symptoms. Factors associated with severe systemic COVID-19 disease were not associated with developing ocular abnormalities. The rate of ocular manifestations of COVID-19 should not be ignored, and thus physicians should routinely evaluate for ocular involvement in hospitalized COVID-19 patients.
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Acute acquired comitant esotropia (AACE) is a rare form of esotropia in the older pediatric population. Although the workup for pediatric AACE varies, patients often do not undergo lab testing and imaging, because the overwhelming majority of cases are idiopathic. We describe AACE as the presenting manifestation of multiple sclerosis in a pediatric patient. His only other finding was a horizontal jerk nystagmus isolated to end gaze. Magnetic resonance imaging revealed extensive demyelinating lesions, with a small thalamic lesion possibly accounting for his esotropia. Our case underscores the need for extensive diagnostic workup for any ophthalmic or neurologic findings or symptoms accompanying AACE.
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Esotropia , Esclerose Múltipla , Doença Aguda , Criança , Esotropia/diagnóstico , Esotropia/etiologia , Humanos , Imageamento por Ressonância Magnética , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico , Estudos RetrospectivosRESUMO
BACKGROUND/AIMS: To determine the rate of endophthalmitis and assess risk factors for development of endophthalmitis following open globe injury (OGI). METHODS: A retrospective chart review of all patients treated for OGI at the University of Michigan from January 2000 to July 2017 was conducted. Exclusion criteria included intravitreal injection or intraocular surgery in the 30 days prior to injury or less than 30 days of follow-up. A total of 586 out of 993 open globe injuries were included in the study. The main outcome measure was the rate of endophthalmitis. RESULTS: In this study, 25/586 eyes (4.3%) had endophthalmitis. Of these, 12/25 eyes (48.0%) presented with endophthalmitis and 13/25 eyes (52.0%) developed endophthalmitis after globe closure. Multivariate analysis identified time to globe repair (OR 4.5, CI 1.9-10.7, p = 0.0008), zone I injury (OR 3.6, CI 1.1-11.0, p = 0.0282), and need for additional surgery (OR 5.5, CI 1.5-19.7, p = 0.0092) as factors associated with increased risk of developing endophthalmitis. Subconjunctival antibiotic injection at the time of globe closure (OR 0.3, CI 0.1-0.7, p = 0.0036) was associated with decreased risk of developing endophthalmitis. CONCLUSION: Prompt globe closure and subconjunctival antibiotics may reduce the risk of endophthalmitis in OGI. Furthermore, our practice of a one-time dose of systemic prophylactic antibiotics, and intravitreal antibiotics if intraocular foreign body (IOFB) removal is delayed, was not found to increase the rate of endophthalmitis.
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Precise temporal and spatial regulation of gene expression during Drosophila oogenesis is essential for patterning the anterior-posterior and dorsal-ventral body axes. Establishment of the anterior-posterior axis requires posterior localization and translational control of both oskar and nanos mRNAs. Establishment of the dorsal-ventral axis depends on the precise restriction of gurken mRNA and protein to the dorsal-anterior corner of the oocyte. We have previously shown that Glorund, the Drosophila hnRNP F/H homolog, contributes to anterior-posterior axis patterning by regulating translation of nanos mRNA, through a direct interaction with its 3' untranslated region. To investigate the pleiotropy of the glorund mutant phenotype, which includes dorsal-ventral and nuclear morphology defects, we searched for proteins that interact with Glorund. Here we show that Glorund is part of a complex containing the hnRNP protein Hrp48 and the splicing factor Half-pint and plays a role both in mRNA localization and nurse cell chromosome organization, probably by regulating alternative splicing of ovarian tumor. We propose that Glorund is a component of multiple protein complexes and functions both as a translational repressor and splicing regulator for anterior-posterior and dorsal-ventral patterning.
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Proteínas de Drosophila/metabolismo , Drosophila/fisiologia , Ribonucleoproteínas Nucleares Heterogêneas Grupo F-H/metabolismo , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador alfa/metabolismo , Processamento Alternativo , Animais , Padronização Corporal/fisiologia , Cromossomos/metabolismo , Drosophila/embriologia , Proteínas de Drosophila/genética , Embrião não Mamífero/fisiologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo F-H/genética , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Mutação , Oócitos/fisiologia , Oogênese/fisiologia , Ligação Proteica , RNA Mensageiro/genética , Fator de Crescimento Transformador alfa/genética , Regiões não TraduzidasRESUMO
PURPOSE: To report a case of an adult who developed toxic shock syndrome following COVID-19 infection. OBSERVATIONS: A 28-year-old female tested positive for COVID-19. 19 days later, she developed a fever, rash and a burning sensation in both eyes. Her examination revealed mild ocular inflammation with bilateral eyelid and conjunctival involvement. Skin biopsy favored a diagnosis of toxic shock syndrome. She was initiated on corticosteroid eye drops and her ocular symptoms resolved three days later. CONCLUSION AND IMPORTANCE: Toxic shock syndrome is almost always associated with conjunctival inflammation. To our knowledge, this is the first report of an adult patient with toxic shock syndrome following COVID-19 infection. The association between toxic shock syndrome and COVID-19 is unclear; however, patients should be vigilant for symptoms as toxic shock syndrome can progress rapidly and cause multi-organ failure.
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Epithelial cells form intercellular junctions to strengthen cell-cell adhesion and limit diffusion, allowing epithelia to function as dynamic tissues and barriers separating internal and external environments. Junctions form as epithelial cells differentiate; clusters of junction proteins first concentrate apically, then mature into continuous junctional belts that encircle and connect each cell. In mammals and Drosophila, atypical protein kinase C (aPKC) is required for junction maturation, although how it contributes to this process is poorly understood. A role for the Caenorhabditis elegans aPKC homolog PKC-3 in junction formation has not been described previously. Here, we show that PKC-3 is essential for junction maturation as epithelia first differentiate. Using a temperature-sensitive allele of pkc-3 that causes junction breaks in the spermatheca and leads to sterility, we identify intragenic and extragenic suppressors that render pkc-3 mutants fertile. Intragenic suppressors include an unanticipated stop-to-stop mutation in the pkc-3 gene, providing evidence for the importance of stop codon identity in gene activity. One extragenic pkc-3 suppressor is a loss-of-function allele of the lethal(2) giant larvae homolog lgl-1, which antagonizes aPKC within epithelia of Drosophila and mammals, but was not known previously to function in C. elegans epithelia. Finally, two extragenic suppressors are loss-of-function alleles of sups-1-a previously uncharacterized gene. We show that SUPS-1 is an apical extracellular matrix protein expressed in epidermal cells, suggesting that it nonautonomously regulates junction formation in the spermatheca. These findings establish a foundation for dissecting the role of PKC-3 and interacting genes in epithelial junction maturation.
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Junções Aderentes/metabolismo , Células Epiteliais/metabolismo , Proteína Quinase C/metabolismo , Supressão Genética , Animais , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Polaridade Celular , Células Epiteliais/citologia , Mutação , Proteína Quinase C/genéticaRESUMO
PURPOSE: To assess whether publication of Comparison of Age-related macular degeneration Treatment Trial (CATT) results and introduction of aflibercept to the marketplace affected intravitreal bevacizumab and ranibizumab utilization. DESIGN: Retrospective analysis of treatment patterns. METHODS: We calculated weekly bevacizumab and ranibizumab utilization during 3 timeframes: (1) before CATT publication, (2) between CATT publication (April 28, 2011) and assignment of a unique aflibercept billing code (January 1, 2013), and (3) afterward for 164,188 Medicare beneficiaries with neovascular macular degeneration receiving ≥1 anti-vascular endothelial growth factor injection(s) from January 1, 2008 to December 31, 2014. We identified ophthalmologists who predominantly (≥80%) administered bevacizumab or ranibizumab and evaluated changes in preferences over the 3 periods. We replicated analyses on 881,381 commercially insured beneficiaries. RESULTS: Among 317 ophthalmologists administering predominantly ranibizumab to Medicare beneficiaries pre-CATT, 221 (69.7%) reduced ranibizumab use post-CATT, whereas 96 (30.3%) continued using ranibizumab ≥80% of the time. Findings were reversed among 1041 ophthalmologists who predominantly administered bevacizumab pre-CATT-777 (74.6%) continued bevacizumab-predominant use while 264 (25.4%) reduced bevacizumab use post-CATT. Among the 145 ophthalmologists who predominantly administered ranibizumab before aflibercept's availability, 77 (53.1%) reduced ranibizumab utilization and 68 (46.9%) continued using ranibizumab ≥80% of the time after aflibercept became available. Corresponding numbers among the 909 ophthalmologists who predominantly administered bevacizumab pre-aflibercept were 381 (41.9%) reducing and 528 (58.1%) continuing bevacizumab-predominant use. Similar results were observed for commercially insured patients. CONCLUSIONS: Many ophthalmologists who favored ranibizumab switched to bevacizumab after CATT publication, while most who favored bevacizumab before CATT publication continued favoring it afterward. Aflibercept's introduction had little impact on preferences for ranibizumab or bevacizumab.
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Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
IMPORTANCE: A unique pigmentary maculopathy was recently described in 6 patients with long-term exposure to pentosan polysulfate sodium (PPS), a long-standing oral therapy for interstitial cystitis. OBJECTIVE: To characterize the exposure characteristics and clinical manifestations of PPS-associated maculopathy. DESIGN, SETTING, AND PARTICIPANTS: In this multi-institutional case series, medical records of patients who exhibited the characteristic maculopathy in the setting of prior PPS exposure were retrospectively reviewed. Data were collected from August 1, 2012, to October 1, 2018, and data were analyzed from October 2018 to January 2019. MAIN OUTCOMES AND MEASURES: Drug exposure, visual acuity, and retinal imaging characteristics. RESULTS: Of the 35 included patients (70 eyes), 34 (97%) were female, and the median (range) age was 60 (37-79) years. The median (range) duration of PPS intake was 15 (3-22) years, and the median (range) cumulative exposure was 1.61 (0.44-4.31) kg. The leading visual symptoms were metamorphopsia, blurred vision, and prolonged dark adaptation. Median (range) logMAR visual acuity of all eyes was 0.10 (-0.12 to 1.18). Fundus examination often revealed hyperpigmented macular spots (34 of 64 eyes [53%]) with interspersed pale-yellow deposits, although less commonly in eyes that exhibited retinal pigment epithelial atrophy (6 of 26 eyes [23%]; P < .001). Optical coherence tomography showed foci of retinal pigment epithelium elevation or thickening associated with hyperreflectance on near-infrared reflectance imaging. Fundus autofluorescence imaging typically revealed a symmetric, confluent pattern of hyperautofluorescent and hypoautofluorescent spots that involved the fovea in all eyes and extended to the retinal periphery in 24 eyes (36%). Longitudinal evaluation demonstrated dynamic changes in pigmentary abnormalities. CONCLUSIONS AND RELEVANCE: These findings suggest that PPS-associated maculopathy is a vision-threatening condition that can manifest in the setting of long-term exposure to the drug. Multimodal imaging posits a distinctive clinical phenotype, characterized in this cohort by dynamic alterations within the retinal pigment epithelium and at the retinal pigment epithelium-photoreceptor interface. Ongoing work might explore causality and direct screening guidelines.
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Importance: Immune checkpoint inhibitors, including antiprogrammed cell death protein-1 (anti-PD-1) and antiprogrammed cell death ligand-1 (anti-PD-L1) monoclonal antibodies, have recently been introduced as a promising new immunotherapy for solid cancers. The adverse effects typically include inflammation of the skin, endocrine, and gastrointestinal systems. Objective: To describe 3 patients who developed uveal effusion after initiating anti-PD-1 and anti-PD-L1 monoclonal antibody therapy. Design, Setting, and Participants: This case series was conducted in a university-based ocular oncology practice. The participants were a 68-year-old African American man with metastatic adenocarcinoma of the lung and 2 white men, aged 52 years and 85 years, with metastatic cutaneous melanoma; all were taking anti-PD-1 and anti-PD-L1 monoclonal antibody therapy. Main Outcomes and Measures: Ocular findings of 3 patients. Results: We identified 3 patients who developed uveal effusion within 1 to 2 months after initiating anti-PD-1 and anti-PD-L1 monoclonal antibody therapy. Uveal effusion resolved completely in 6 to 12 weeks after discontinuation of systemic therapy in 2 patients and persisted in 1 patient who continued the therapy. Conclusions and Relevance: Uveal effusion should be considered in patients taking anti-PD-1 and/or PD-L1 monoclonal antibody therapy. Because of the role of the PD-1 pathway in the inhibition of self-reactive T cells, PD-1 inhibition might lead to inflammation because of immune-related adverse effects.