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1.
Bioengineering (Basel) ; 11(2)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38391606

RESUMO

In the modern era, patients often resort to the internet for answers to their health-related concerns, and clinics face challenges to providing timely response to patient concerns. This has led to a need to investigate the capabilities of AI chatbots for ophthalmic diagnosis and triage. In this in silico study, 80 simulated patient complaints in ophthalmology with varying urgency levels and clinical descriptors were entered into both ChatGPT and Bard in a systematic 3-step submission process asking chatbots to triage, diagnose, and evaluate urgency. Three ophthalmologists graded chatbot responses. Chatbots were significantly better at ophthalmic triage than diagnosis (90.0% appropriate triage vs. 48.8% correct leading diagnosis; p < 0.001), and GPT-4 performed better than Bard for appropriate triage recommendations (96.3% vs. 83.8%; p = 0.008), grader satisfaction for patient use (81.3% vs. 55.0%; p < 0.001), and lower potential harm rates (6.3% vs. 20.0%; p = 0.010). More descriptors improved the accuracy of diagnosis for both GPT-4 and Bard. These results indicate that chatbots may not need to recognize the correct diagnosis to provide appropriate ophthalmic triage, and there is a potential utility of these tools in aiding patients or triage staff; however, they are not a replacement for professional ophthalmic evaluation or advice.

2.
Ophthalmic Plast Reconstr Surg ; 39(4): e122-e123, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36972126

RESUMO

This is a case report of a single patient who had pulsed dye laser and hybrid fractional laser treatments for facial rosacea and subsequently developed a prolonged papular reaction in and adjacent to the area of treatment, which was unresponsive to topical therapy. Biopsies of these lesions revealed necrotizing granulomas. This is a previously unreported side effect of these laser treatments and clinicians should be aware of this potential sequela.


Assuntos
Lasers de Corante , Rosácea , Humanos , Lasers de Corante/efeitos adversos , Face
3.
Telemed J E Health ; 29(9): 1349-1355, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36730708

RESUMO

Purpose: Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus (DM). Standard of care for patients with DM is an annual eye examination or retinal imaging to assess for DR, the latter of which may be completed through telemedicine approaches. One significant issue is poor-quality images that prevent adequate screening and are thus ungradable. We used artificial intelligence to enable point-of-care (at time of imaging) identification of ungradable images in a DR screening program. Methods: Nonmydriatic retinal images were gathered from patients with DM imaged during a primary care or endocrinology visit from September 1, 2017, to June 1, 2021. The Topcon TRC-NW400 retinal camera (Topcon Corp., Tokyo, Japan) was used. Images were interpreted by 5 ophthalmologists for gradeability, presence and stage of DR, and presence of non-DR pathologies. A convolutional neural network with Inception V3 network architecture was trained to assess image gradeability. Images were divided into training and test sets, and 10-fold cross-validation was performed. Results: A total of 1,377 images from 537 patients (56.1% female, median age 58) were analyzed. Ophthalmologists classified 25.9% of images as ungradable. Of gradable images, 18.6% had DR of varying degrees and 26.5% had non-DR pathology. 10 fold cross-validation produced an average area under receiver operating characteristic curve (AUC) of 0.922 (standard deviation: 0.027, range: 0.882 to 0.961). The final model exhibited similar test set performance with an AUC of 0.924. Conclusions: This model accurately assesses gradeability of nonmydriatic retinal images. It could be used for increasing the efficiency of DR screening programs by enabling point-of-care identification of poor-quality images.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Telemedicina , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Retinopatia Diabética/diagnóstico por imagem , Inteligência Artificial , Fotografação/métodos , Programas de Rastreamento/métodos , Redes Neurais de Computação
4.
Ophthalmic Epidemiol ; 30(5): 453-461, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36705505

RESUMO

PURPOSE: To investigate prevalence of diabetes (DM), diabetic retinopathy (DR), and areas with highest rates of undetected DR. To quantify and map locations of disparities as they relate to poverty and minority populations. METHODS: Retrospective cohort study from large regional health data repository (HealthLNK). Geographic Information System (GIS) analysis mapped rates of DM and DR in Chicago area ZIP Codes. RESULTS: Of 1,086,921 adults who met the inclusion criteria, 143,790 with DM were identified. ZIP Codes with higher poverty rates were correlated with higher prevalence of DM and DR (Pearson's correlation coefficient 0.614, p < .05, 0.333, p < .05). Poverty was negatively correlated with likelihood of DR diagnosis (-0.638, p < .05). Relative risks of DM and DR were calculated in each ZIP Code and compared to actual rates. 36 high-risk ZIP Codes had both high-risk of DM and low DR detection. In high-risk ZIP Codes 85.4% of households self-identified as ethnic minority and 33.0% were below the Federal Poverty Level (FPL). Both percentages were significantly higher than the Chicago average of 50.5% minority and 19.9% below FPL (p < .05). 67 ideal ZIP Codes had both low risk of DM and high DR detection. In ideal ZIP Codes 32.6% of households self-identified as minority, and 10.2% were below the FPL (p < .05). CONCLUSIONS: A health care disparity exists with regards to DM and DR. High-risk ZIP Codes are associated with higher poverty and higher minority population, and they are highly concentrated in just 17% of the ZIP codes in the Chicago area.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Adulto , Humanos , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Disparidades em Assistência à Saúde , Estudos Retrospectivos , Etnicidade , Grupos Minoritários , Diabetes Mellitus/epidemiologia
5.
Ocul Oncol Pathol ; 8(2): 141-147, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35959156

RESUMO

Introduction: When indicated, intraoperative use of frozen sections may assist in determining the surgical course or appropriate processing of surgical specimens. Knowing the accuracy of a preliminary frozen section diagnosis is important. The purpose of this study is to determine the rate of correlation between frozen and permanent histopathologic diagnoses of adult orbital lesions, analyze characteristics of discordant cases, and examine the effects of discordance on surgical decision-making. Methods: A 15-year retrospective chart review was conducted at a tertiary care center of all adult patients with orbital lesions for which frozen section and corresponding permanent section tissue diagnoses were obtained. Results: Sixty-five orbital surgeries were performed with a total of 89 frozen sections sampled. In 63 surgeries (96.9%), at least 1 frozen section diagnosis matched the final permanent section diagnosis. Overall, frozen section diagnosis corresponded with permanent section diagnosis in 81 of 89 (91.0%) specimens. Of the 8 (9.0%) specimens from 5 unique patients that did not correlate, the final diagnoses on permanent sections were amyloidosis (5), margin-positive infiltrating breast carcinoma (2), and lymphoid hyperplasia (1). The discrepancy between frozen and permanent sections did not alter care in any patient. Conclusion: Frozen section diagnoses correlate with permanent histopathologic tissue diagnosis in adult orbital biopsies in greater than 90% of cases. Among non-correlated specimens, amyloidosis was the most common diagnosis. Although rare, orbital amyloid disorders may be considered in the differential diagnosis of cases of orbital biopsies with nonspecific findings on a frozen section.

6.
Med Clin North Am ; 105(3): 397-407, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33926637

RESUMO

Incidence of cataract, diabetic retinopathy, macular degeneration, and glaucoma will significantly increase by 2050. Visual impairment can increase morbidity and mortality in nonocular disease. There are different patterns of vision loss in cataract, diabetic retinopathy, age-related macular degeneration, and glaucoma. Internists and medical subspecialists play an important role in prevention, detection, and early treatment of eye disease. Awareness of screening guidelines for eye disease as well as a basic ocular history and simple penlight examination can decrease incidence of vision loss and its impact. Visual impairment places a significant financial burden on society.


Assuntos
Oftalmopatias/diagnóstico , Oftalmopatias/terapia , Oftalmopatias/complicações , Oftalmopatias/prevenção & controle , Humanos , Medicina Interna , Programas de Rastreamento/normas , Guias de Prática Clínica como Assunto , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologia , Transtornos da Visão/prevenção & controle , Transtornos da Visão/terapia
7.
Med Clin North Am ; 105(3): xvii-xviii, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33926649
8.
Telemed J E Health ; 26(10): 1252-1256, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32083513

RESUMO

Purpose: To study the rates and severity of diabetic retinopathy (DR), rates of nondiabetic ocular disease, and rates of referral to eye care providers in the context of nonmydriatic retinal screening performed in primary care and endocrinology clinics. Materials and Methods: This study is a retrospective chart review of patients who had nonmydriatic retinal imaging in the primary care setting. Presence and severity of DR as well as detection of nondiabetic ocular diseases were analyzed. Referral rates for different types of pathology were determined. Results: A total of 324 patients were imaged and 294 (90.7%) had gradable images. Mild DR was found in at least one eye of 71 (24.1%) patients, moderate in 20 (6.8%), severe in 3 (1.0%), and proliferative DR in 2 (0.6%). Macular edema was found in 13 (4.4%) patients. Nondiabetic ocular diseases were suspected in 106 (36.1%) patients. The most prevalent findings included glaucoma suspect (10.9%), age-related macular degeneration suspect (8.8%), and hypertensive retinopathy (5.4%). Seventy (23.8%) patients were referred to an eye care provider for DR, 66 (22.4%) were referred for nondiabetic eye disease, and 21 (7.1%) were referred for both. Conclusion: One-third of patients were found to have some degree of DR. Suspected nondiabetic disease or other pathologies were found in one-third of the study population. Referral for examination by an eye care provider was recommended for approximately half of the patients.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Doenças Retinianas , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Técnicas de Diagnóstico Oftalmológico , Humanos , Incidência , Programas de Rastreamento , Fotografação , Atenção Primária à Saúde , Estudos Retrospectivos
9.
Ophthalmic Plast Reconstr Surg ; 35(5): e116-e118, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31365512

RESUMO

This is the first case of histopathologically proven blastomycosis involving the lacrimal gland. A 51-year-old woman with a history of disseminated blastomycosis involving her lungs and skin, on oral itraconazole, presented with 3 days of right upper eyelid swelling, erythema, and pain concerning for recurrent dacryoadenitis. MRI showed enlargement of the right lacrimal gland with a cystic lesion at the anterior aspect of the gland with a radiographic differential diagnosis of abscess versus cyst. After no improvement with intravenous antibiotics, orbitotomy with lacrimal gland biopsy and incision and drainage of the cystic lesion were performed. Culture and pathology of the drained fluid demonstrated an abscess with both viable and nonviable broad-based budding yeast consistent with partially treated blastomycosis. The patient's symptoms improved after the surgery and continued itraconazole therapy.


Assuntos
Blastomicose/complicações , Dacriocistite/microbiologia , Cistos/microbiologia , Feminino , Humanos , Pessoa de Meia-Idade
10.
Cornea ; 36(5): 628-630, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28181930

RESUMO

PURPOSE: To report a case of recurrent conjunctival myofibrosarcoma treated with wide surgical excision, cryotherapy, and triple sequential applications of episcleral brachytherapy. METHODS: A single case of recurrent conjunctival myofibrosarcoma. RESULTS: A 54-year-old man with a history of a renal transplant presented with a recurrent conjunctival tumor. Histopathologic diagnosis was established through immunohistochemistry. In total, 3 iodine radiation episcleral plaques were used over a period of 49 weeks. After cicatricial ectropion repair and cataract surgery, visual acuity was 20/20 at 4.5-year follow-up without evidence of recurrence or radiation retinopathy. CONCLUSIONS: Myofibrosarcoma is a rare mesenchymal tumor that can present as ocular surface tumor. Final histopathologic diagnosis can be challenging, and immunohistochemistry is important for evaluation. Myofibrosarcoma should be considered in the clinical differential diagnosis of atypical ocular surface lesions and the histopathologic differential diagnosis of ocular spindle neoplasms.


Assuntos
Braquiterapia/métodos , Neoplasias da Túnica Conjuntiva/radioterapia , Miofibroma/radioterapia , Sarcoma/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
11.
Ophthalmol Ther ; 6(1): 123-131, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27885590

RESUMO

INTRODUCTION: The Affordable Care Act (ACA) has expanded health coverage for thousands of Illinois residents. Expanded coverage, however, does not guarantee appropriate health care. Diabetes and its ocular complications serve as an example of how providers in underserved urban areas may not be able to keep up with new demand for labor- and technology-intensive health care unless changes in reimbursement policies are instituted. METHODS: A retrospective cohort study was conducted using medical encounter information from the Chicago HealthLNK Data Repository (HDR), an assembly of non-duplicated and de-identified patient medical records. We used a method of estimating the geographic distribution of undiagnosed diabetic retinopathy in the city of Chicago to illustrate the magnitude of potentially preventable eye disease. All rates were calculated for all ZIP Codes within Chicago (Cook County), and statistical differences between observed and geographically adjusted expected rates (p < 0.10, p < 0.05, p < 0.01) were highlighted as underserved areas. RESULTS: This analysis included 150,661 patients with diabetes identified from a total of nearly two million patients in Chicago. High rates of undetected diabetic retinopathy were found in low-income and minority areas. Within these areas, 37% of the identified diabetics were uninsured, with rates ranging widely from 20% to 68.6%. Among those with insurance, 32.8% were covered by Medicare and only 10% by Medicaid. Most patients with untreated diabetic retinopathy were found to reside in areas where primary health care is provided through Federally Qualified Health Centers. CONCLUSIONS: With 150,661 diabetics identified in the city of Chicago, and this number continuing to rise each year, a manpower approach with ophthalmologist screening for diabetic retinopathy is not realistic. The ability to identify the growing number of diabetic patients with retinopathy in low-income areas will likely require the adoption of cost-effective screening technologies that are currently not funded by Medicare and Medicaid.

12.
JMIR Med Inform ; 4(2): e14, 2016 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-27146002

RESUMO

BACKGROUND: Visual acuity is the primary measure used in ophthalmology to determine how well a patient can see. Visual acuity for a single eye may be recorded in multiple ways for a single patient visit (eg, Snellen vs. Jäger units vs. font print size), and be recorded for either distance or near vision. Capturing the best documented visual acuity (BDVA) of each eye in an individual patient visit is an important step for making electronic ophthalmology clinical notes useful in research. OBJECTIVE: Currently, there is limited methodology for capturing BDVA in an efficient and accurate manner from electronic health record (EHR) notes. We developed an algorithm to detect BDVA for right and left eyes from defined fields within electronic ophthalmology clinical notes. METHODS: We designed an algorithm to detect the BDVA from defined fields within 295,218 ophthalmology clinical notes with visual acuity data present. About 5668 unique responses were identified and an algorithm was developed to map all of the unique responses to a structured list of Snellen visual acuities. RESULTS: Visual acuity was captured from a total of 295,218 ophthalmology clinical notes during the study dates. The algorithm identified all visual acuities in the defined visual acuity section for each eye and returned a single BDVA for each eye. A clinician chart review of 100 random patient notes showed a 99% accuracy detecting BDVA from these records and 1% observed error. CONCLUSIONS: Our algorithm successfully captures best documented Snellen distance visual acuity from ophthalmology clinical notes and transforms a variety of inputs into a structured Snellen equivalent list. Our work, to the best of our knowledge, represents the first attempt at capturing visual acuity accurately from large numbers of electronic ophthalmology notes. Use of this algorithm can benefit research groups interested in assessing visual acuity for patient centered outcome. All codes used for this study are currently available, and will be made available online at https://phekb.org.

13.
Taiwan J Ophthalmol ; 6(1): 26-31, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29018706

RESUMO

BACKGROUND/PURPOSE: Orbital fractures are a common facial fracture managed by multiple surgical specialties. Methods: A retrospective review of the electronic medical records of patients (age, 18-85 years) presenting to Northwestern Memorial Hospital and Northwestern Medical Faculty Foundation in Chicago, IL, USA with International Classification of Diseases, Ninth Revision codes for facial fractures or CPT (Current Procedural Terminology) codes for orbital fracture repair. RESULTS: A review of the electronic medical records identified 504 individual incidents of orbital fractures with available imaging for review. The most common location for an orbital fracture was a floor fracture (48.0%) followed by a medial wall fracture (25.2%). Left-sided orbital fractures were statistically significantly more common than right-sided orbital fractures (99% confidence interval). Orbital fractures were more prevalent in younger age groups. The mean patient age was 39.3 years. The most common cause of all orbital fractures was assault followed by falls. However, falls were the most common cause of orbital fractures in women and in patients aged 50 years and older. Evaluation by an ophthalmologist occurred in 62.8% of orbital fracture patients, and evaluation by a team comprising the facial trauma service (Otolaryngology, Plastic Surgery, and Oral and Maxillofacial Surgery) occurred in 81.9% of orbital fracture patients. CONCLUSION: Assault was the largest cause of all orbital fractures, and occurred most commonly in young males. Assaulted patients were more likely to have left-sided fractures compared to nonassaulted patients. In patients aged 50 years and older, falls were the most common cause of orbital fractures.

14.
PLoS One ; 10(9): e0138366, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26379276

RESUMO

Retinoblastoma is the most common intraocular tumor in children. Current management includes broad-based treatments such as chemotherapy, enucleation, laser therapy, or cryotherapy. However, therapies that target specific pathways important for retinoblastoma progression could provide valuable alternatives for treatment. MicroRNAs are short, noncoding RNA transcripts that can regulate the expression of target genes, and their aberrant expression often facilitates disease. The identification of post-transcriptional events that occur after the initiating genetic lesions could further define the rapidly aggressive growth displayed by retinoblastoma tumors. In this study, we used two phenotypically different retinoblastoma cell lines to elucidate the roles of miRNA-31 and miRNA-200a in tumor proliferation. Our approach confirmed that miRNAs-31 and -200a expression is significantly reduced in human retinoblastomas. Moreover, overexpression of these two miRNAs restricts the expansion of a highly proliferative cell line (Y79), but does not restrict the growth rate of a less aggressive cell line (Weri1). Gene expression profiling of miRNA-31 and/or miRNA-200a-overexpressing cells identified differentially expressed mRNAs associated with the divergent response of the two cell lines. This work has the potential to enhance the development of targeted therapeutic approaches for retinoblastoma and improve the efficacy of treatment.


Assuntos
Proliferação de Células/genética , MicroRNAs/genética , Neoplasias da Retina/genética , Retinoblastoma/genética , Linhagem Celular Tumoral , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Humanos
15.
Ocul Oncol Pathol ; 2(1): 48-50, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27171204

RESUMO

We report a case of an unsuspected ganglioneuroma of the choroid in a patient with neurofibromatosis type 1. A 5-year-old girl presented from an outside institution with right proptosis and glaucoma since birth. Magnetic resonance imaging was obtained and showed a cavernous sinus mass extending into the right orbit and multiple orbital lesions. Additionally, increased signal in the posterior globe of the right eye was noted, but its etiology was unclear at the time. She was lost to follow-up for 3 years and later returned with a blind painful eye. Enucleation was performed, and histopathology was significant for diffuse choroidal ganglioneuroma and advanced glaucoma. We report the atypical history, examination findings, and histopathology to support the diagnosis.

16.
Ophthalmic Plast Reconstr Surg ; 30(6): e155-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24801255

RESUMO

A 46-year-old man presented with an unusual papillary eyelid lesion in which histopathological study revealed a cutaneous xanthogranuloma. The clinical appearance was distinctively different from juvenile xanthogranuloma. There was no evidence of an infiltrative and orbital process consistent with adult orbital xanthogranulomatous disease. The histopathologic examination of the lesion revealed well-differentiated histiocytes with foamy cytoplasm. Immunohistochemistry stains were positive for CD163 and Factor XIIIa and negative for CD34, CD1A, CD117, and S100. The final histopathologic diagnosis was cutaneous xanthogranuloma.


Assuntos
Doenças Palpebrais/diagnóstico , Granuloma/diagnóstico , Xantomatose/diagnóstico , Antígenos CD/metabolismo , Biomarcadores/metabolismo , Doenças Palpebrais/metabolismo , Doenças Palpebrais/cirurgia , Granuloma/metabolismo , Granuloma/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Oftalmológicos , Xantomatose/metabolismo , Xantomatose/cirurgia
18.
Biochem Biophys Res Commun ; 440(4): 599-603, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-24120948

RESUMO

Retinoblastoma is the most common pediatric cancer of the eye. Currently, the chemotherapeutic treatments for retinoblastoma are broad-based drugs such as vincristine, carboplatin, or etoposide. However, therapies targeted directly to aberrant signaling pathways may provide more effective therapy for this disease. The purpose of our study is to illustrate the relationship between the expressions of miRs-449a and -449b to retinoblastoma proliferation and apoptosis. We are the first to confirm an inhibitory effect of miR-449a and -449b in retinoblastoma by demonstrating significantly impaired proliferation and increased apoptosis of tumor cells when these miRNAs are overexpressed. This study suggests that these miRNAs could serve as viable therapeutic targets for retinoblastoma treatment.


Assuntos
MicroRNAs/biossíntese , Retinoblastoma/metabolismo , Linhagem Celular Tumoral , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Terapia de Alvo Molecular , Retinoblastoma/tratamento farmacológico , Retinoblastoma/patologia
19.
JAMA Ophthalmol ; 131(9): 1187-97, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23887202

RESUMO

IMPORTANCE: Given the infrequent occurrence of hydroxychloroquine toxic effects, few data are available about the presenting features and long-term follow-up of patients with hydroxychloroquine retinopathy, making it difficult to surmise the clinical course of patients after cessation of drug treatment. OBJECTIVE: To report functional and structural findings of hydroxychloroquine retinal toxic effects after drug therapy discontinuation. DESIGN: A retrospective medical record review was performed to identify patients taking hydroxychloroquine who were screened for toxic effects from January 1, 2009, through August 31, 2012, in the eye centers of Northwestern University and the University of Southern California. SETTING: Northwestern University Sorrel Rosin Eye Center, Chicago, Illinois, and the Doheny Eye Institute at the University of Southern California, Los Angeles. PARTICIPANTS: Seven consecutive patients diagnosed as having hydroxychloroquine retinal toxic effects. MAIN OUTCOME AND MEASURE: Retinal toxic effects. RESULTS: Seven patients (1 man and 6 women) with a mean age of 55.9 years (age range, 25-74 years) developed retinal toxic effects after using hydroxychloroquine for a mean of 10.4 years (range, 3-19 years). Fundus examination revealed macular pigmentary changes in all 7 patients, corresponding to abnormal fundus autofluorescence (FAF). On spectral domain optical coherence tomography, there was outer retinal foveal resistance (preservation of the external limiting membrane and the photoreceptor layer) in 6 patients. After drug therapy discontinuation, 5 patients experienced outer retinal regeneration (3 subfoveally and 2 parafoveally), with associated functional visual improvement on static perimetry in 2 patients. Over time, FAF remained stable in 3 patients, whereas the remaining patients had a pattern of hypoautofluorescence that replaced areas of initial hyperautofluorescence (2 patients) and enlargement of the total area of abnormal FAF (2 patients). CONCLUSIONS AND RELEVANCE: Preservation of the external limiting membrane carries a positive prognostic value in hydroxychloroquine toxic effects because it may be associated with regeneration of the photoreceptor layer and with potential functional visual improvement on static perimetry. The patterns of abnormal FAF persist despite cessation of the medication, with enlargement of the total area of abnormal FAF being the hallmark of severe toxic effects. Relative foveal resistance in hydroxychloroquine toxic effects was supported by this case series. These findings emphasize the importance of early detection and the need for correlating clinical observations with multimodal imaging, particularly FAF and spectral domain optical coherence tomography.


Assuntos
Antirreumáticos/efeitos adversos , Hidroxicloroquina/efeitos adversos , Imagem Multimodal , Retina/patologia , Doenças Retinianas/diagnóstico , Suspensão de Tratamento , Adulto , Idoso , Artrite Reumatoide/tratamento farmacológico , Progressão da Doença , Feminino , Angiofluoresceinografia , Seguimentos , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Retina/efeitos dos fármacos , Retina/fisiopatologia , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/fisiopatologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Testes de Campo Visual , Campos Visuais/fisiologia
20.
Proc Natl Acad Sci U S A ; 109(35): 14030-4, 2012 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-22891326

RESUMO

Notch plays a critical role in the transition from proliferation to differentiation in the epidermis and corneal epithelium. Furthermore, aberrant Notch signaling is a feature of diseases like psoriasis, eczema, nonmelanoma skin cancer, and melanoma where differentiation and proliferation are impaired. Whereas much is known about the downstream events following Notch signaling, factors responsible for negatively regulating Notch receptor signaling after ligand activation are incompletely understood. Notch can undergo hydroxylation by factor-inhibiting hypoxia-inducible factor 1 (FIH-1); however, the biological significance of this phenomenon is unclear. Here we show that FIH-1 expression is up-regulated in diseased epidermis and corneal epithelium. Elevating FIH-1 levels in primary human epidermal keratinocytes (HEKs) and human corneal epithelial keratinocytes (HCEKs) impairs differentiation in submerged cultures and in a "three-dimensional" organotypic raft model of human epidermis, in part, via a coordinate decrease in Notch signaling. Knockdown of FIH-1 enhances keratinocyte differentiation. Loss of FIH-1 in vivo increased Notch activity in the limbal epithelium, resulting in a more differentiated phenotype. microRNA-31 (miR-31) is an endogenous negative regulator of FIH-1 expression that results in keratinocyte differentiation, mediated by Notch activation. Ectopically expressing miR-31 in an undifferentiated corneal epithelial cell line promotes differentiation and recapitulates a corneal epithelium in a three-dimensional raft culture model. Our results define a previously unknown mechanism for keratinocyte fate decisions where Notch signaling potential is, in part, controlled through a miR-31/FIH-1 nexus.


Assuntos
Queratinócitos/citologia , Queratinócitos/fisiologia , MicroRNAs/metabolismo , Oxigenases de Função Mista/metabolismo , Psoríase/metabolismo , Proteínas Repressoras/metabolismo , Animais , Diferenciação Celular/fisiologia , Linhagem Celular Transformada , Células Epidérmicas , Epiderme/fisiologia , Células Epiteliais/citologia , Células Epiteliais/fisiologia , Epitélio Corneano/citologia , Epitélio Corneano/fisiologia , Feminino , Humanos , Camundongos , Camundongos Transgênicos , Oxigenases de Função Mista/genética , Técnicas de Cultura de Órgãos , Fenótipo , Psoríase/genética , Psoríase/patologia , Receptores Notch/metabolismo , Proteínas Repressoras/genética , Transdução de Sinais/fisiologia
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