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1.
Mayo Clin Proc Digit Health ; 2(1): 119-128, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38577703

RESUMO

Objective: To determine the appropriateness of ophthalmology recommendations from an online chat-based artificial intelligence model to ophthalmology questions. Patients and Methods: Cross-sectional qualitative study from April 1, 2023, to April 30, 2023. A total of 192 questions were generated spanning all ophthalmic subspecialties. Each question was posed to a large language model (LLM) 3 times. The responses were graded by appropriate subspecialists as appropriate, inappropriate, or unreliable in 2 grading contexts. The first grading context was if the information was presented on a patient information site. The second was an LLM-generated draft response to patient queries sent by the electronic medical record (EMR). Appropriate was defined as accurate and specific enough to serve as a surrogate for physician-approved information. Main outcome measure was percentage of appropriate responses per subspecialty. Results: For patient information site-related questions, the LLM provided an overall average of 79% appropriate responses. Variable rates of average appropriateness were observed across ophthalmic subspecialties for patient information site information ranging from 56% to 100%: cataract or refractive (92%), cornea (56%), glaucoma (72%), neuro-ophthalmology (67%), oculoplastic or orbital surgery (80%), ocular oncology (100%), pediatrics (89%), vitreoretinal diseases (86%), and uveitis (65%). For draft responses to patient questions via EMR, the LLM provided an overall average of 74% appropriate responses and varied by subspecialty: cataract or refractive (85%), cornea (54%), glaucoma (77%), neuro-ophthalmology (63%), oculoplastic or orbital surgery (62%), ocular oncology (90%), pediatrics (94%), vitreoretinal diseases (88%), and uveitis (55%). Stratifying grades across health information categories (disease and condition, risk and prevention, surgery-related, and treatment and management) showed notable but insignificant variations, with disease and condition often rated highest (72% and 69%) for appropriateness and surgery-related (55% and 51%) lowest, in both contexts. Conclusion: This LLM reported mostly appropriate responses across multiple ophthalmology subspecialties in the context of both patient information sites and EMR-related responses to patient questions. Current LLM offerings require optimization and improvement before widespread clinical use.

2.
Cornea ; 43(4): 425-431, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37506362

RESUMO

PURPOSE: The aim of this study was to report the outcomes of graft fixation using interrupted, full-thickness sutures on graft detachment after Descemet stripping endothelial keratoplasty (DSEK). METHODS: All DSEK procedures performed at Mayo Clinic, Rochester, MN, from 2015 through 2022 were retrospectively reviewed. Risk factors for graft detachment were defined as previous incisional glaucoma surgery, previous penetrating keratoplasty, or absence of the normal lens-capsule barrier. Cases were categorized into sutured, high-risk grafts; unsutured, high-risk grafts; and unsutured, low-risk grafts. The primary outcome was graft detachment, and secondary outcomes were early graft failure and graft clarity at 12 months after surgery. RESULTS: Demographics between the high-risk groups were similar for sex and age at the time of surgery. Graft detachment occurred in 4 of 97 sutured, high-risk eyes (4.1%) and 24 of 119 unsutured high-risk eyes (20.2%) ( P = 0.002). In comparison, graft detachment occurred in 18 of 181 unsutured low-risk eyes (9.9%). The incidence of early graft failure was 2.1%, 5.0%, and 3.3% and late graft failure by 12 months was 9.8%, 12.8%, and 4.2%, respectively. CONCLUSIONS: In eyes with high-risk factors for graft detachment, suture fixation of the graft in DSEK decreased graft detachment to a rate at least as low as that in low-risk eyes.


Assuntos
Doenças da Córnea , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Humanos , Estudos Retrospectivos , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Lâmina Limitante Posterior/cirurgia , Ceratoplastia Penetrante/métodos , Suturas , Sobrevivência de Enxerto , Doenças da Córnea/cirurgia , Endotélio Corneano/cirurgia
3.
Cornea ; 42(5): 549-556, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35543582

RESUMO

PURPOSE: The goal of this study was to compare outcomes of Descemet stripping endothelial keratoplasty (DSEK) in eyes with glaucoma and abnormal anatomy to eyes with Fuchs endothelial corneal dystrophy (FECD). METHODS: In a retrospective interventional series of all cases of DSEK between April 1, 2006, and November 30, 2015, recipient diagnosis, preoperative glaucoma status, concurrent surgical procedures, and graft outcomes were recorded. Graft survival, risk of rejection, and subsequent glaucoma surgery were estimated by using Kaplan-Meier analysis with risk factors determined by proportional hazard models. RESULTS: Of 703 DSEKs in 666 eyes (509 subjects), the main recipient diagnoses were FECD (n = 496), pseudophakic corneal edema (n = 112), and failed graft (n = 83). Glaucoma was present in 150 cases before DSEK. Overall graft survival was 85%, 75%, and 71% at 5, 10, and 12 years, respectively, and for FECD without glaucoma was 95%, 89%, and 87% at 5, 10, and 12 years, respectively. Independent risk factors for graft failure included recipient diagnoses of pseudophakic corneal edema (HR = 8.3, P < 0.001), failed graft (HR = 6.4, P < 0.001), and preoperative medical glaucoma (HR = 7.1, P < 0.001) or surgical glaucoma (HR = 12.3, P < 0.001). Preoperative glaucoma treated by previous surgery resulted in graft survival of 28% at 10 years. Preoperative glaucoma was associated with an increased risk of graft rejection (HR = 6.8, P < 0.001) and subsequent glaucoma surgery (HR > 17.4, P < 0.001). CONCLUSIONS: Preoperative glaucoma increases the risk of graft failure, graft rejection, and needing subsequent glaucoma surgery in the first decade after DSEK. With previous glaucoma surgery, DSEK graft survival was more favorable compared with published reports of Descemet membrane endothelial keratoplasty.


Assuntos
Edema da Córnea , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Distrofia Endotelial de Fuchs , Glaucoma , Humanos , Estudos Retrospectivos , Edema da Córnea/cirurgia , Sobrevivência de Enxerto , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Rejeição de Enxerto/diagnóstico , Glaucoma/cirurgia , Distrofia Endotelial de Fuchs/cirurgia , Seguimentos
4.
Cornea ; 41(9): 1088-1093, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35588167

RESUMO

PURPOSE: The purpose of this study is to quantify cancer risk in patients with Fuchs endothelial corneal dystrophy (FECD). METHODS: Using the 2014 to 2016 Medicare Limited 5% Data Sets-Carrier Line File, US Medicare fee-for-service beneficiaries (aged 65 years or older) with FECD and cancer were identified through International Classification of Diseases , ninth and 10th Revision diagnostic codes from January 1, 2014, to December 31, 2016. The main outcome measures were odds ratios (ORs) of cancer at various anatomic locations in patients with versus without FECD. RESULTS: Of the 1,462,740 Medicare beneficiaries, 15,534 patients (1.1%) had an International Classification of Disease code for FECD. Compared with US Medicare beneficiaries without FECD, patients with FECD were at increased risk for the following malignancies: breast [OR: 1.32; 95% confidence interval (CI): 1.22-1.43; P < 0.001], cutaneous basal cell (OR: 1.42; 95% CI: 1.35-1.49; P < 0.001), cutaneous melanoma (OR: 1.20; 95% CI: 1.03-1.40; P = 0.02), cutaneous squamous cell (OR: 1.45; 95% CI: 1.38-1.53; P < 0.001), ovarian (OR: 1.84; 95% CI: 1.48-2.30; P < 0.001), and thyroid (OR: 1.32; 95% CI: 1.04-1.68; P = 0.02). By contrast, FECD cases were at lower odds of having lung (OR: 0.81; 95% CI: 0.71-0.93; P = 0.003) and prostate cancer diagnoses (OR: 0.88; 95% CI: 0.81-0.96; P = 0.002). CONCLUSIONS: Patients with FECD aged 65 years or older may be at increased risk for cancer at several anatomic locations. Follow-up studies are needed to further explore the association of FECD and malignancy, elucidate potential disease mechanisms, and identify genetic and/or environmental risk factors.


Assuntos
Distrofia Endotelial de Fuchs , Melanoma , Neoplasias Cutâneas , Idoso , Endotélio Corneano/patologia , Seguimentos , Distrofia Endotelial de Fuchs/diagnóstico , Humanos , Masculino , Medicare , Melanoma/patologia , Neoplasias Cutâneas/patologia , Estados Unidos/epidemiologia
5.
Am J Ophthalmol Case Rep ; 26: 101533, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35479520

RESUMO

Purpose: Describe a case of intraocular plasmacytoma in a patient with multiple myeloma successfully treated with photon irradiation. Observations: A 61-year-old man with a history of relapsing/refractory multiple myeloma and left frontal bone plasmacytoma treated with monthly belantamab mafodotin salvage chemotherapy developed bilateral treatment-related corneal keratopathy. An iris mass was incidentally noted in the right eye during a follow-up examination. The mass was amelanotic with diffuse intrinsic vasculature involving the pupillary margin from 1:30 to 10:30. Fundus examination showed an irregularly shaped amelanotic superotemporal scleral lesion in the right eye and two smaller amelanotic scleral lesions in the left eye. Given known systemic multiple myeloma and history of left frontal bone plasmacytoma, a presumed diagnosis of iris and scleral plasmacytoma was made. Due to rapid progression of the iris plasmacytoma despite systemic chemotherapy, the patient was treated with 20 Gy photon irradiation to the anterior and posterior segments of both eyes. One month after photon irradiation, there was complete regression of the iris plasmacytoma, and the scleral lesions in both eyes also appeared to be regressing despite systemic progression of multiple myeloma. Conclusions and importance: Intraocular plasmacytoma is rare and can occur in isolation but typically occurs as a manifestation of systemic multiple myeloma. Intraocular plasmacytoma can be successfully treated with photon irradiation in patients with multiple myeloma who progress on systemic chemotherapy.

6.
Cornea ; 41(2): 243-248, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35037906

RESUMO

ABSTRACT: The Rho kinase inhibitor netarsudil is a recently approved therapeutic option for the management of increased intraocular pressure in the United States. Although phase 3 clinical trials noted corneal changes related to the medication-namely, nonvisually-significant corneal verticillata-descriptions of a unique form of cystic epithelial edema began to surface as netarsudil (and its sister drug ripasudil, approved in Japan) gained widespread use. This series adds 3 new cases and reviews the current literature on this unique side effect.


Assuntos
Benzoatos/efeitos adversos , Edema da Córnea/induzido quimicamente , Epitélio Corneano/patologia , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/tratamento farmacológico , beta-Alanina/análogos & derivados , Quinases Associadas a rho/antagonistas & inibidores , Benzoatos/uso terapêutico , Edema da Córnea/diagnóstico , Epitélio Corneano/efeitos dos fármacos , Humanos , Hipertensão Ocular/enzimologia , Hipertensão Ocular/fisiopatologia , Estudos Retrospectivos , beta-Alanina/efeitos adversos , beta-Alanina/uso terapêutico
7.
Invest Ophthalmol Vis Sci ; 62(1): 17, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33444430

RESUMO

Purpose: To characterize inheritance, penetrance, and trinucleotide repeat expansion stability in Fuchs endothelial corneal dystrophy (FECD). Methods: One thousand unrelated and related subjects with and without FECD were prospectively recruited. CTG18.1 repeat length (CTG18.1L) was determined via short tandem repeat assay and Southern blotting of leukocyte DNA. Multivariable logistic regression and generalized estimating equation models were employed. Results: There were 546 unrelated FECD cases (67.6% female; 70 ± 10 years) and 235 controls (63.8% female; 73 ± 8 years; all ≥ 50 years). CTG18.1 expansion (CTG18.1exp+) was observed in 424 (77.7%) cases and 18 (7.7%) controls (P = 2.48 × 10-44). CTG18.1 expansion was associated with FECD severity (P = 5.62 × 10-7). The family arm of the study included 331 members from 112 FECD-affected families; 87 families were CTG18.1exp+. Autosomal dominant inheritance with variable expression of FECD was observed, regardless of expansion status. FECD penetrance of CTG18.1 expansion increased with age, ranging from 44.4% in the youngest (19-46 years) to 86.2% in the oldest (64-91 years) age quartiles. Among 62 parent-offspring transmissions of CTG18.1exp+, 48 (77.4%) had a change in CTG18.1L ≤ 10 repeats, and eight (12.9%) were ≥50 repeats, including five large expansions (∼1000-2000 repeats) that contracted. Among 44 offspring who did not inherit the CTG18.1exp+ allele, eight (18.2%) exhibited FECD. Conclusions: CTG18.1 expansion was highly associated with FECD but demonstrated incomplete penetrance. CTG18.1L instability occurred in a minority of parent-offspring transmissions, with large expansions exhibiting contraction. The observation of FECD without CTG18.1 expansion among family members in CTG18.1exp+ families highlights the complexity of the relationship between the FECD phenotype and CTG18.1 expansion.


Assuntos
Distrofia Endotelial de Fuchs/genética , Fator de Transcrição 4/genética , Expansão das Repetições de Trinucleotídeos/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Southern Blotting , DNA/genética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Padrões de Herança , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Linhagem , Penetrância , Reação em Cadeia da Polimerase , Polimorfismo Genético , Estudos Prospectivos , Adulto Jovem
8.
Am J Ophthalmol ; 222: 157-165, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32818451

RESUMO

PURPOSE: To determine if there is an increased incidence rate of post-cataract surgery (pcs) anterior ischemic optic neuropathy (AION) compared to spontaneous AION (sAION). DESIGN: Retrospective, population-based cohort. METHODS: Patients diagnosed with AION from January 1, 1990, through December 31, 2016, while residing in Olmsted County, Minnesota. Patients with cataract surgery preceding AION were included in the pcsAION cohort defined in 2 ways: AION within 2 months and AION within 1 year of cataract surgery. The incidence rates of pcsAION and sAION were compared using Poisson regression models. RESULTS: During the study period, 102 residents developed AION. The median age was 65 years (range, 40-90 years), 44 (43.1%) were female. Twenty of 102 (19.6%) patients had previous cataract surgery, of which 2 and 9 developed AION within 2 months and 1 year of surgery, respectively. The annual incidence rate of pcsAION within 2 months of surgery (8.6 per 100,000) was not significantly greater than the annual incidence rate of sAION (6.9 per 100,000; P = .78). However, the annual incidence rate of pcsAION within 1 year of surgery (38.9 per 100,000) was significantly higher than the incidence rate of sAION (6.5 per 100,000; P < .001). CONCLUSION: The incidence of AION is increased in the first year after cataract surgery, but not in the early (i.e., 2 months) postoperative period.


Assuntos
Extração de Catarata/efeitos adversos , Disco Óptico/patologia , Neuropatia Óptica Isquêmica/diagnóstico , Vigilância da População , Complicações Pós-Operatórias , Acuidade Visual , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neuropatia Óptica Isquêmica/epidemiologia , Neuropatia Óptica Isquêmica/etiologia , Estudos Retrospectivos , Estados Unidos/epidemiologia
9.
Ophthalmology ; 127(3): 315-323, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31685256

RESUMO

PURPOSE: To determine if Scheimpflug tomography pachymetry map and posterior elevation map patterns, central corneal thickness (CCT), and corneal backscatter can predict the prognosis of Fuchs endothelial corneal dystrophy (FECD). DESIGN: Cross-sectional study with follow-up of outcomes. PARTICIPANTS: Ninety-six eyes (56 subjects) with a range of severity of FECD. METHODS: Corneas were graded by cornea specialists according to the area and confluence of guttae and the presence of clinically definite edema. Masked and randomized Scheimpflug imaging pachymetry map and posterior elevation map patterns were assessed by 1 observer for loss of regular isopachs, displacement of the thinnest point of the cornea, and the presence of posterior surface depression. The prognosis of eyes over a 5-year (median) follow-up period was determined based on FECD progression (new onset of clinically definite edema or ≥5% increase in CCT) or intervention by endothelial keratoplasty. Cumulative probabilities of progression and intervention were estimated from survival analyses, with risk factors determined by using Cox proportional hazards models. MAIN OUTCOME MEASURES: Pachymetry map and posterior elevation map patterns, corneal backscatter, and CCT (ultrasonic pachymetry). RESULTS: In univariate analyses, loss of regular isopachs (hazard ratio [HR], 18.00) displacement of the thinnest point (HR, 11.53), focal posterior surface depression (HR, 10.21), and anterior corneal backscatter (HR, 1.22, per 1-grayscale unit increment), were risk factors for progression or intervention (P < 0.001), whereas CCT (HR, 1.30, per 25-µm increment) was not (P = 0.15). In multivariate analyses, loss of regular isopachs (HR, 11.57; P < 0.001) and displacement of the thinnest point (HR, 5.61; P = 0.02) were independent and clinically important risk factors for progression and intervention. The 5-year cumulative risk of disease progression and intervention was 7%, 48%, and 89% when none, 1 or 2, and all 3 pachymetry map and posterior elevation map parameters were present, respectively (P <0.001). The 4-year cumulative risk of disease progression and intervention after uncomplicated cataract surgery was 0%, 50%, and 75% when none, 1 or 2, and all 3 pachymetry map and posterior elevation map parameters were present, respectively (P < 0.001). CONCLUSIONS: Three Scheimpflug tomography pachymetry map and posterior elevation map patterns can predict FECD prognosis independent of CCT. The risk of FECD progression and intervention, including after uncomplicated cataract surgery, increases according to the number of parameters present.


Assuntos
Técnicas de Diagnóstico Oftalmológico/estatística & dados numéricos , Distrofia Endotelial de Fuchs/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Paquimetria Corneana/métodos , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Tomografia Computadorizada por Raios X/métodos
10.
Invest Ophthalmol Vis Sci ; 60(10): 3636-3643, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31469403

RESUMO

Purpose: CTG trinucleotide repeat (TNR) expansion in an intron of the TCF4 gene is the most common genetic variant associated with Fuchs' endothelial corneal dystrophy (FECD). Although several mechanisms have been implicated in the disease process, their exact pathophysiologic importance is unclear. To understand events leading from TCF4 TNR expansion to disease phenotype, we characterized splicing, gene expression, and exon sequence changes in a rare cohort of patients with TNR expansions but no phenotypic FECD (RE+/FECD-). Methods: Corneal endothelium and blood were collected from patients undergoing endothelial keratoplasty for non-FECD corneal edema. Total RNA was isolated from corneal endothelial tissue (n = 3) and used for RNASeq. Gene splicing and expression was assessed by Mixture of Isoforms (MISO) and MAP-RSeq software. Genomic DNA was isolated from blood mononuclear cells and used for whole genome exome sequencing. Base calling was performed using Illumina's Real-Time Analysis. Results: Three genes (MBNL1, KIF13A, AKAP13) that were previously identified as misspliced in patients with a CTG TNR expansion and FECD disease (RE+/FECD+) were found normally spliced in RE+/FECD- samples. Gene expression differences in pathways associated with the innate immune response, cell signaling (e.g., TGFß, WNT), and cell senescence markers were also identified between RE+/FECD- and RE+/FECD+ groups. No consistent genetic variants were identified in RE+/FECD- patient exomes. Conclusions: Identification of novel splicing patterns and differential gene expression in RE+/FECD- samples provides new insights and more relevant gene targets that may be protective against FECD disease in vulnerable patients with TCF4 CTG TNR expansions.


Assuntos
Proteínas de Ancoragem à Quinase A/genética , Processamento Alternativo , Endotélio Corneano/metabolismo , Distrofia Endotelial de Fuchs/genética , Regulação da Expressão Gênica/fisiologia , Cinesinas/genética , Antígenos de Histocompatibilidade Menor/genética , Proteínas Proto-Oncogênicas/genética , Proteínas de Ligação a RNA/genética , Fator de Transcrição 4/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Genótipo , Humanos , Masculino , Expansão das Repetições de Trinucleotídeos/genética , Sequenciamento do Exoma
12.
Ophthalmology ; 126(2): 195-204, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30153944

RESUMO

PURPOSE: To determine if Scheimpflug tomography can identify subclinical corneal edema in Fuchs endothelial corneal dystrophy (FECD), and to recommend a new classification of FECD for clinical practice and research. DESIGN: Cross-sectional study with follow-up of outcomes. PARTICIPANTS: Ninety-three eyes from 57 subjects with a range of severity of FECD and 74 eyes from 40 subjects with normal corneas. METHODS: Corneas were clinically assessed for FECD and corneal edema by using slit-lamp biomicroscopy, and categorized as having clinically definite edema (obvious visible edema), being suspicious for subclinical edema (possible corneal thickening without obvious edema on slit-lamp examination), or not having edema (no clinical suspicion of edema). Tomographic pachymetry and elevation maps derived from Scheimpflug images were evaluated by 3 masked observers for specific features believed to be consistent with corneal edema. FECD clinical disease course and outcomes were reviewed from the time of Scheimpflug image acquisition to the last available follow-up. MAIN OUTCOME MEASURES: Presence of tomographic features: (1) loss of parallel isopachs, (2) displacement of the thinnest point of the cornea, and (3) focal posterior corneal surface depression. Clinical outcomes included the change in central corneal thickness (CCT) and vision after endothelial keratoplasty (EK). RESULTS: The 3 specific tomographic features were all present in all FECD corneas with clinically definite edema (n = 15), in ≥81% of FECD corneas suspicious for subclinical edema (n = 16), in ≤42% of FECD corneas deemed not to have edema (n = 62), and in ≤5% of normal corneas (n = 74). Corneas suspicious for subclinical edema that subsequently underwent EK (n = 9) all had at least 2 of the tomographic features present before EK, and improvement in vision, CCT, and tomographic features after EK confirmed the presence of subclinical edema preoperatively. CONCLUSIONS: Subclinical corneal edema in FECD can be detected by Scheimpflug tomography. We recommend classifying FECD corneas as having clinically definite edema (based on slit-lamp examination), subclinical edema (based on tomographic features without clinically definite edema), or no edema (no tomographic or slit-lamp features of edema). This classification is independent of CCT and should be considered when evaluating FECD eyes for cataract surgery or EK.


Assuntos
Córnea/patologia , Edema da Córnea/diagnóstico , Distrofia Endotelial de Fuchs/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Edema da Córnea/classificação , Paquimetria Corneana , Estudos Transversais , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Diagnóstico por Imagem/métodos , Feminino , Distrofia Endotelial de Fuchs/classificação , Distrofia Endotelial de Fuchs/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Microscopia com Lâmpada de Fenda , Tomografia/métodos , Acuidade Visual/fisiologia
14.
Invest Ophthalmol Vis Sci ; 59(5): 1888-1896, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29677349

RESUMO

Purpose: The strongest genetic association with Fuchs' endothelial corneal dystrophy (FECD) is the presence of an intronic (CTG·CAG)n trinucleotide repeat (TNR) expansion in the transcription factor 4 (TCF4) gene. Repeat-associated non-ATG (RAN) translation, an unconventional protein translation mechanism that does not require an initiating ATG, has been described in many TNR expansion diseases, including myotonic dystrophy type 1 (DM1). Given the similarities between DM1 and FECD, we wished to determine whether RAN translation occurs in FECD. Methods: Antibodies against peptides in the C-terminus of putative RAN translation products from TCF4 were raised and validated by Western blotting and immunofluorescence (IF). CTG·CAG repeats of various lengths in the context of the TCF4 gene were cloned in frame with a 3× FLAG tag and transfected in human cells. IF with antipeptide and anti-FLAG antibodies, as well as cytotoxicity and cell proliferation assays, were performed in these transfected cells. Corneal endothelium derived from patients with FECD was probed with validated antibodies by IF. Results: CTG·CAG repeats in the context of the TCF4 gene are transcribed and translated via non-ATG initiation in transfected cells and confer toxicity to an immortalized corneal endothelial cell line. An antipeptide antibody raised against the C-terminus of the TCF4 poly-cysteine frame recognized RAN translation products by IF in cells transfected with CTG·CAG repeats and in FECD corneal endothelium. Conclusions: Expanded CTG·CAG repeats in the context of the third intron of TCF4 are transcribed and translated via non-ATG initiation, providing evidence for RAN translation in corneal endothelium of patients with FECD.


Assuntos
Distrofia Endotelial de Fuchs/genética , Biossíntese de Proteínas , Fator de Transcrição 4/genética , Expansão das Repetições de Trinucleotídeos/genética , Western Blotting , Proliferação de Células , Células Cultivadas , Endotélio Corneano/metabolismo , Fibroblastos/metabolismo , Técnica Indireta de Fluorescência para Anticorpo , Expressão Gênica/fisiologia , Humanos , Íntrons , Reação em Cadeia da Polimerase em Tempo Real , Transfecção
15.
Cornea ; 35(3): 402-4, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26764883

RESUMO

PURPOSE: To describe the first-documented case of histoplasma scleritis in an immunocompetent patient. METHODS: Medical and pathological records of the patient described were reviewed. RESULTS: A 77-year-old immunocompetent man presented with necrotizing scleritis. Biopsy was consistent with histoplasma species, and culture results confirmed a causative agent of Histoplasma capsulatum. The patient required a long course of treatment, which included topical voriconazole and amphotericin, oral itraconazole and voriconazole, intravenous amphotericin, and periocular voriconazole and amphotericin. After 8 months of treatment, the patient's scleritis resolved, and he maintained good visual acuity. CONCLUSIONS: To our knowledge, this is the second report of histoplasma scleritis in the literature and the first report in an immunocompetent patient.


Assuntos
Infecções Oculares Fúngicas/microbiologia , Histoplasma/isolamento & purificação , Histoplasmose/complicações , Esclerite/microbiologia , Idoso , Antifúngicos/uso terapêutico , Humanos , Masculino , Resultado do Tratamento
16.
Ophthalmology ; 123(1): 154-60, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26481820

RESUMO

PURPOSE: To determine 5-year outcomes of Descemet stripping endothelial keratoplasty (DSEK) for Fuchs' endothelial corneal dystrophy (FECD). DESIGN: Prospective cohort study. PARTICIPANTS: Fifty-two eyes of 45 subjects with FECD undergoing primary DSEK. METHODS: Subjects were examined before and at fixed intervals through 60 months after DSEK. At each visit, graft survival was determined by slit-lamp examination; best spectacle-corrected visual acuity (BSCVA) was measured using the electronic Early Treatment Diabetic Retinopathy Study (ETDRS) protocol; total anterior corneal higher-order aberrations (HOAs) were derived from corneal topography; and corneal backscatter, corneal thickness, and endothelial cell density were measured from confocal microscopy images. Corneal thickness also was measured by ultrasonic pachymetry. Changes after DSEK were analyzed using generalized estimating equation models. MAIN OUTCOME MEASURES: Best-corrected visual acuity, HOAs, endothelial cell loss, corneal thickness, and corneal backscatter. RESULTS: Complete 60-month follow-up was possible in 34 eyes. Mean BSCVA±standard deviation improved from 0.45±0.19 logarithm of the minimum angle of resolution (logMAR) (Snellen equivalent, 20/56) before DSEK to 0.09±0.13 logMAR (Snellen equivalent, 20/25) at 5 years (P < 0.001). Between 1 and 5 years, BSCVA improved by 0.06 logMAR (or 3 ETDRS letters; 95% confidence interval, 0.05-0.07 logMAR) per year (P < 0.001), and 56% of eyes were 0.1 logMAR (20/25) or better at 5 years. Graft thickness (approximately 155 µm) and corneal thickness (approximately 700 µm) did not change after surgery. Anterior corneal HOAs and backscatter decreased between 1 and 5 years (P ≤ 0.002). Six grafts failed, of which 4 were primary (iatrogenic); mean endothelial cell loss±standard deviation was 55±15% at 5 years. CONCLUSIONS: Between 1 and 5 years after DSEK, BSCVA continues to improve such that at 5 years, more than half of eyes see better than 20/25 with a mean total corneal thickness of 700 µm. Improvement in vision is accompanied by continued reduction in corneal haze and aberrations, suggesting ongoing remodeling of the cornea after restoration of endothelial function.


Assuntos
Córnea/patologia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Distrofia Endotelial de Fuchs/cirurgia , Acuidade Visual , Adulto , Idoso , Idoso de 80 Anos ou mais , Córnea/cirurgia , Feminino , Seguimentos , Distrofia Endotelial de Fuchs/diagnóstico , Distrofia Endotelial de Fuchs/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
17.
Ophthalmology ; 121(12): 2325-33, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25156138

RESUMO

PURPOSE: Corneas with advanced Fuchs' endothelial dystrophy that require endothelial keratoplasty manifest anterior corneal structural and cellular abnormalities that have been associated with visual deficits before and after endothelial keratoplasty. In this study, we determined the onset of these abnormalities in the course of the disease. DESIGN: Cross-sectional study. PARTICIPANTS: Sixty-three eyes (39 subjects) with a range of severity of Fuchs' dystrophy and 25 eyes (13 subjects) with normal corneas. METHODS: All corneas were examined using slit-lamp biomicroscopy, ultrasonic pachymetry, and confocal microscopy. The clinical grade of Fuchs' dystrophy was assessed according to the presence and extent of guttae and clinically evident edema and was categorized as mild (grades 1 and 2), moderate (grades 3 and 4), or advanced (grades 5 and 6). Normal corneas were devoid of any central guttae (grade 0). Corneal backscatter (haze) was measured from the confocal image light intensity profile. Stromal cell density and number and the presence of abnormal subepithelial cells were determined from confocal images. Comparisons between groups were made by using generalized estimating equation models. MAIN OUTCOME MEASURES: Anterior corneal backscatter, stromal cell density and number, presence of subepithelial cells, and central corneal thickness. RESULTS: Anterior corneal backscatter was 18% to 67% higher in eyes with moderate and advanced Fuchs' dystrophy compared with normal eyes (P ≤ 0.003); a similar trend was noted in mild Fuchs' dystrophy eyes compared with normal eyes (P = 0.08). Stromal cell density and the absolute number of stromal cells in the anterior 10% of the stroma were approximately 20% and 27% lower, respectively, in Fuchs' dystrophy (regardless of severity) compared with normal (P < 0.001). Abnormal subepithelial cells were visible in 9%, 19%, and 30% of corneas with mild, moderate, and advanced Fuchs' dystrophy, respectively. Only corneas with advanced Fuchs' dystrophy were thicker than normal (P < 0.001). CONCLUSIONS: Anterior corneal cellular and structural abnormalities begin early in the course of Fuchs' dystrophy, before the onset of clinically evident edema. The chronicity of these changes can explain their incomplete resolution after endothelial keratoplasty, and understanding the onset of these may help to determine the optimal time to intervene to achieve best outcomes.


Assuntos
Córnea/patologia , Distrofia Endotelial de Fuchs/patologia , Idoso , Idoso de 80 Anos ou mais , Substância Própria/patologia , Estudos Transversais , Endotélio Corneano/patologia , Células Epiteliais/patologia , Feminino , Humanos , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Células Estromais/patologia
18.
Ophthalmology ; 119(8): 1522-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22480739

RESUMO

PURPOSE: To determine the change in anterior corneal high-order aberrations (HOAs) after Descemet's stripping endothelial keratoplasty (DSEK) for Fuchs' dystrophy, and to compare the HOAs with those of age-matched controls. DESIGN: Prospective cohort and cross-sectional study. PARTICIPANTS AND CONTROLS: Forty-eight eyes with Fuchs' dystrophy were examined before and after DSEK, and were compared with 52 eyes of age-matched controls with normal corneas. METHODS: Corneas of patients with Fuchs' dystrophy were examined prospectively before and at intervals through 2 years after DSEK. Wavefront errors from the anterior corneal surface were derived from corneal topograms and were expressed as Zernike polynomials through the sixth order. Best-corrected visual acuity (BCVA) was measured by the electronic Early Treatment of Diabetic Retinopathy Study protocol, and subepithelial haze was measured from the brightness of confocal images. Total HOAs were compared before and after DSEK, and with those of age-matched controls, by using generalized estimating equation models. Relationships between HOAs, BCVA, subepithelial haze, and recipient age were determined. MAIN OUTCOME MEASURES: Anterior corneal HOAs, BCVA, and subepithelial haze (backscattered light). RESULTS: In Fuchs' dystrophy before DSEK, total HOAs (4 mm optical zone) from the anterior corneal surface (0.29±0.13 µm) were higher than those of controls (0.17±0.08 µm; P<0.001). At 2 years after DSEK, total HOAs (0.26±0.13 µm) did not differ from preoperative aberrations (P = 0.99), and remained higher than in controls (P<0.001). At 2 years, total HOAs were correlated with BCVA (r = 0.59; P<0.001; n = 27), with subepithelial haze (r = 0.41; P = 0.01; n = 25), and with recipient age (r = 0.59; P<0.001; n = 27). CONCLUSIONS: Anterior corneal HOAs are higher in Fuchs' dystrophy than in controls, and remain higher through 2 years after DSEK. The aberrated anterior surface might be related to anterior corneal ultrastructural changes and haze formation in Fuchs' dystrophy, and should not be ignored as a source of decreased visual acuity after DSEK.


Assuntos
Aberrações de Frente de Onda da Córnea/etiologia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Distrofia Endotelial de Fuchs/cirurgia , Complicações Pós-Operatórias , Adulto , Idoso , Idoso de 80 Anos ou mais , Topografia da Córnea , Aberrações de Frente de Onda da Córnea/fisiopatologia , Estudos Transversais , Endotélio Corneano/fisiopatologia , Endotélio Corneano/transplante , Feminino , Distrofia Endotelial de Fuchs/fisiopatologia , Ofuscação , Humanos , Luz , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Espalhamento de Radiação , Acuidade Visual/fisiologia
19.
Arch Ophthalmol ; 130(7): 868-74, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22410629

RESUMO

OBJECTIVE: To quantify corneal light scatter and its relationship to vision after Descemet stripping with endothelial keratoplasty (DSEK). METHODS: Eyes with Fuchs corneal dystrophy were examined before and 1, 3, 6, 12, and 24 months after DSEK. Outcome measures were high- and low-contrast visual acuity, contrast sensitivity, and forward light scatter. Corneal reflectivity (backscatter), expressed in scatter units (SU), was quantified using in vivo confocal microscopy. RESULTS: Comparing 49 study eyes with 35 normal eyes, the mean (SD) corneal subepithelial layer was more reflective than normal before (2325 [613] vs 1208 [287] SU, P<.001) and through 24 months after DSEK (1760 [432] SU, P<.001). Interface reflectivity remained higher than in normal stroma through 24 months (1228 [287] vs 827 [188] SU, P<.001). At 1 year, forward light scatter correlated with subepithelial reflectivity (r=0.28, P=.01) but not interface reflectivity. Recipient age was correlated with improvement in subepithelial reflectivity at 12 months (r=­0.41, P=.01, 34 eyes) and 24 months (r=­0.36, P=.02, 26 eyes) after DSEK, and the improvement of subepithelial haze in eyes of participants aged 62 years or younger was correlated with improvement in forward light scatter at 12 months (r=0.52, P=.008) and 24 months (r=0.62, P=.004). CONCLUSIONS: In Fuchs corneal dystrophy, the corneal subepithelial region is a more important source of forward light scatter than the DSEK interface. Subepithelial haze improves more in younger patients and is associated with improvement in forward light scatter. CLINICAL RELEVANCE: Visual function after DSEK is affected by residual haze in the anterior host cornea more so than the surgical interface. Haze, which likely is experienced as glare disability, improves after surgical intervention but improves more in younger patients.


Assuntos
Opacidade da Córnea/diagnóstico , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Distrofia Endotelial de Fuchs/cirurgia , Microscopia Confocal , Complicações Pós-Operatórias , Adulto , Idoso , Idoso de 80 Anos ou mais , Sensibilidades de Contraste/fisiologia , Opacidade da Córnea/fisiopatologia , Seguimentos , Distrofia Endotelial de Fuchs/fisiopatologia , Humanos , Luz , Pessoa de Meia-Idade , Estudos Prospectivos , Espalhamento de Radiação , Acuidade Visual/fisiologia , Adulto Jovem
20.
Ophthalmology ; 119(2): 213-20, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21925736

RESUMO

PURPOSE: To evaluate the prevalence of musculoskeletal disorders among eye care physicians compared with family medicine physicians. DESIGN: Case control study. PARTICIPANTS AND CONTROLS: Ophthalmologists and optometrists at the University of Iowa and Mayo Clinic (participants) and family medicine physicians at the University of Iowa and Mayo Clinic (controls). METHODS: An electronic survey was e-mailed to all subjects. MAIN OUTCOME MEASURES: The prevalence of musculoskeletal symptoms between eye care providers and family medicine physicians (control group). RESULTS: One hundred eight-six surveys were completed by 94 eye care physicians and 92 family medicine physicians with a response rate of 99% and 80%, respectively. There were no significant differences between the 2 groups with regard to mean age, gender, body mass index, years with current employer, or years in practice. Eye care providers, compared with their family medicine colleagues, reported a higher prevalence of neck (46% vs 21%; P<0.01), hand/wrist pain (17% vs 7%; P = 0.03), and lower back pain (26% vs 9%; P<0.01). A greater proportion of eye care physicians classified their job as a high-strain job (high demand, low control; 31% vs 20%) and a lower proportion classified their job as an active job (high demand, high control; 24% vs 47%; p = 0.01). Several job factors reported by eye care providers to contribute to musculoskeletal symptoms included performing the same task repeatedly, working in awkward/cramped positions, working in the same position for long periods, and bending/twisting the back (all P<0.01). CONCLUSIONS: In this survey, the study group, composed of ophthalmologists and optometrists, had a higher prevalence of neck, hand/wrist, and lower back pain compared with family medicine physicians; repetitive tasks, prolonged or awkward/cramped positions, and bending/twisting were contributory factors. Given the ramifications of these findings, future efforts should concentrate on modifications to the eye care providers' work environment to prevent or alleviate musculoskeletal disorders and their personal and socioeconomic burden.


Assuntos
Doenças Musculoesqueléticas/epidemiologia , Doenças Profissionais/epidemiologia , Oftalmologia/estatística & dados numéricos , Optometria/estatística & dados numéricos , Médicos de Família/estatística & dados numéricos , Centros Médicos Acadêmicos , Adulto , Escolha da Profissão , Estudos Transversais , Transtornos Traumáticos Cumulativos/epidemiologia , Ergonomia , Feminino , Inquéritos Epidemiológicos , Humanos , Iowa/epidemiologia , Masculino , Médicos/estatística & dados numéricos , Postura , Prevalência , Estresse Psicológico , Inquéritos e Questionários
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