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Intraocular pressure is currently the only known reliable, modifiable risk factor for the development and progression of glaucoma. Other risk factors for glaucoma include increasing age, myopia, decreased central corneal thickness, and low corneal hysteresis (CH) measurements. Photoablative keratorefractive surgery including laser assisted in situ keratomileusis (LASIK) has become a common way to treat refractive error, with over 25 million procedures performed in the United States alone. Though myopic LASIK has been associated with a decrease in CH measurements, relatively little is known about the risk of LASIK on glaucoma onset and progression. Here we present an observational study of 4 consecutive relatively young and otherwise healthy glaucoma patients with a history of myopic LASIK who showed progression of paracentral visual field deficits at intraocular pressures of 12 mm Hg or less while being carefully monitored. Therefore, these patients required lower targets of intraocular pressure, in the single-digit range, to slow or halt progression. In this cohort, the average corneal hysteresis was more than 2 standard deviations below normal values. This series suggests that additional study into the association of LASIK and glaucoma is warranted, including the potential risk contribution of diminished CH. These studies may be particularly relevant as patients who underwent LASIK procedures in the early 2000s may now be at increased risk of glaucoma due to the risk factor of age.
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Progressão da Doença , Pressão Intraocular , Ceratomileuse Assistida por Excimer Laser In Situ , Miopia , Tonometria Ocular , Campos Visuais , Humanos , Ceratomileuse Assistida por Excimer Laser In Situ/efeitos adversos , Pressão Intraocular/fisiologia , Campos Visuais/fisiologia , Miopia/cirurgia , Miopia/fisiopatologia , Masculino , Feminino , Adulto , Córnea/fisiopatologia , Transtornos da Visão/fisiopatologia , Transtornos da Visão/etiologia , Transtornos da Visão/diagnóstico , Testes de Campo Visual , Pessoa de Meia-Idade , Acuidade Visual/fisiologia , Fatores de Risco , Lasers de Excimer/uso terapêutico , Adulto JovemRESUMO
PURPOSE: To determine whether corneal backscatter, pachymetric indices, and ectasia indices derived from Scheimpflug tomography can identify Fuchs endothelial corneal dystrophy (FECD) corneas with abnormal tomography, the relationships between these parameters and tomographic edema in FECD, and if these parameters help predict improvement in central corneal thickness (CCT) after Descemet membrane endothelial keratoplasty (DMEK). METHODS: Tomography maps of 132 eyes of 80 subjects with FECD were analyzed to determine how backscatter, pachymetric, and ectasia parameters compared with the instrument's normative database and if any predicted tomographic edema. Tomography maps from a separate group undergoing DMEK were split into derivation (48 eyes of 39 subjects) and validation (45 eyes of 41 subjects) subgroups to derive a predictive model of improvement in CCT after DMEK. Backscatter, pachymetric, and ectasia parameters were incorporated to determine if the model could be enhanced. RESULTS: Among all ectasia, pachymetric, and backscatter parameters, at best only 65% of FECD corneas with definite tomographic edema could be identified based on the instrument's normative database. Among all parameters individually, the highest sensitivity for detecting tomographic edema was 77%. Anterior and mid-corneal backscatter featured in a model predicting improvement in CCT after DMEK with high performance in derivation (R2 = 0.79; 95% confidence interval, 0.65-0.87) and validation (R2 = 0.72; 95% confidence interval, 0.52-0.83) subgroups. CONCLUSIONS: The Scheimpflug camera software program could not reliably detect abnormal tomography in FECD from corneal backscatter, pachymetric indices, or ectasia indices. Corneal backscatter contributes to, but does not enhance, a predictive model of improvement in CCT after DMEK.
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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.
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Purpose: Trabeculectomy surgery is a commonly performed procedure for treatment of glaucoma. While the goal is to lower intraocular pressure, over-filtration may cause hypotony with ocular structural changes and vision loss. Observations: A 53-year-old woman with primary open-angle glaucoma was referred to our service for further evaluation. The patient previously underwent trabeculectomy 9 years prior and was found to have a cataract and hypotony maculopathy in the right eye. Treatment options included cataract surgery alone, bleb revision alone, or combined cataract extraction and bleb revision. Biometry revealed corneal astigmatism in the right eye, and significant disparity in axial length between the two eyes. Since the axial length and corneal astigmatic changes were presumed to be at least partially reversible, measurements from the non-operative left eye influenced the lens selection for the hypotonous right eye. The patient underwent combined phacoemulsification and bleb revision. While IOP increased and hypotony was partly reversed, there was hyperopic and astigmatic refractive surprise after surgery.The patient subsequently underwent intraocular lens exchange using biometric values of the previously hypotonous eye and met the target post-operative refractive goal. Conclusions and importance: This case demonstrates changes to the axial length and ocular structure following longstanding hypotony maculopathy may be permanent, even after restoration of normotensive intraocular pressure.
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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.
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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/cirurgiaRESUMO
PURPOSE: The goal of this study was to determine changes in best-corrected visual acuity (BCVA), refractive error, and central corneal thickness (CCT) during the first decade after Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: Outcomes of all consecutive eyes undergoing DSAEK for Fuchs endothelial corneal dystrophy (FECD) were reviewed; eyes with untreatable comorbidities before DSAEK were excluded. DSAEK was performed through a temporal incision and all eyes were pseudophakic postoperatively. Changes in BCVA, manifest spherical equivalent, manifest cylinder (vector analysis), and CCT were assessed by using generalized estimating equation models. RESULTS: BCVA improved between 6 months (0.18 ± 0.12 logarithm of the minimum angle of resolution (logMAR); Snellen equivalent, 20/30) and 5 years (0.10 ± 0.10 logMAR; 20/25; n = 74, P < 0.001) and then remained stable at 10 years (0.09 ± 0.10 logMAR, n = 48, P = 0.22). There was a myopic shift of -0.20 ± 0.51 D between 6 months and 5 years (n = 65, P = 0.002) that remained stable at 10 years (-0.09 ± 0.44 D; 20/25; n = 34, P = 0.33). Manifest cylinder drifted with-the-rule between 6 months and 5 years (n = 65, P < 0.001) and between 5 and 10 years (n = 34, P < 0.001). CCT was stable between 6 months (672 ± 57 µm) and 5 years (677 ± 55 µm, n = 67, P = 0.47), but increased at 10 years (702 ± 60 µm, n = 39, P = 0.001). CONCLUSIONS: Excellent BCVA can be achieved during the first decade after DSAEK for FECD, although improvement seems to plateau after 5 years. Changes in manifest refractive error were not clinically significant. The gradual increase in CCT was consistent with longer-term changes found after other types of keratoplasty.
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Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Distrofia Endotelial de Fuchs , Erros de Refração , Humanos , Distrofia Endotelial de Fuchs/cirurgia , Endotélio Corneano , Acuidade Visual , Lâmina Limitante Posterior/cirurgia , Estudos RetrospectivosRESUMO
PURPOSE: The aim of this study was to describe the indications and outcomes of flap amputation after laser in situ keratomileusis (LASIK) at a referral-based institution. METHODS: In this retrospective consecutive case series, medical records of patients who underwent LASIK flap amputation at Mayo Clinic, Rochester, MN, between January 1, 1998, and January 31, 2023, were reviewed. RESULTS: Fifteen eyes (15 patients) underwent flap amputation during the study period. The median age was 45 years (range, 25-71 years), and 8 patients (53%) were men. The median uncorrected visual acuity before flap amputation was 20/200 (range 20/40-hand motions). Indications for flap amputation included epithelial ingrowth (n = 6, 40%), infectious keratitis (n = 6, 40%), diffuse lamellar keratitis (n = 1, 7%), vegetative foreign body (n = 1, 7%), and astigmatism from fixed flap striae (n = 1, 7%). The median duration of follow-up was 8 months (range 1-234 months). Subsequent corneal interventions included chelation of calcific band keratopathy (n = 1, 7%), lamellar keratoplasty (n = 1, 7%), penetrating keratoplasty (n = 2, 18%), keratoprosthesis (n = 1, 7%), and rigid contact lens wear (n = 4, 27%). The final median best visual acuity was 20/25 (range 20/20-20/200). Compared with noninfectious indications for flap amputation, eyes with infectious indications had worse baseline median uncorrected visual acuity (hand motions vs. 20/63, P < 0.001), were more likely to undergo major corneal surgical intervention (50% vs. 11%), and had worse final median best visual acuity (20/50 vs. 20/20, P = 0.018). CONCLUSIONS: LASIK flap amputation is sometimes necessary to control threatening corneal diseases. Excellent visual outcomes were achieved in most cases, albeit with additional intervention or rigid contact lens wear.
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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.
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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 , SeguimentosRESUMO
Purpose: To develop a model to predict corneal improvement after Descemet membrane endothelial keratoplasty (DMEK) for Fuchs endothelial corneal dystrophy (FECD) from Scheimpflug tomography. Design: Cross-sectional study. Participants: Forty-eight eyes (derivation group) and 45 eyes (validation group) with a range of severity of FECD undergoing DMEK. Methods: Scheimpflug images were obtained before and after DMEK. Before DMEK, pachymetry map and posterior elevation map patterns were quantified by a special image analysis program measuring tomographic features of edema (loss of regular isopachs, displacement of the thinnest point of the cornea, posterior surface depression). Image-derived novel parameters were combined with instrument-derived parameters, and the relative influences of parameters associated with the change in central corneal thickness (CCT) after DMEK in the derivation group were determined by using a gradient boosting machine learning model. The parameters with highest relative influence were then fit in a linear regression model. The derived model was applied to the validation group. Correlations and agreement were assessed between predicted and observed changes in CCT. Main Outcome Measures: Predictive power (R 2) and mean difference between predicted and observed change in CCT. Results: The gradient boosting machine model identified 4 novel parameters of isopach circularity and eccentricity and 1 instrument-derived parameter (posterior surface radius); preoperative CCT was a poor predictor. In the derivation group, the model strongly predicted the change in CCT after DMEK (R 2 = 0.80; 95% confidence interval [CI], 0.71-0.89) and the mean difference between predicted and observed change was, by definition, 0 µm. When the same 5 parameters were fit to the validation group, the model performed very highly (R 2 = 0.89; 95% CI, 0.84-0.94). When the coefficient estimates from the derivation model were used to predict the change in CCT in the validation group, the predictive power was also high (R 2 = 0.78; 95% CI, 0.68-0.88), and the mean difference was 4 µm (predicted minus observed). Conclusions: Scheimpflug tomography maps of corneas with FECD can predict the improvement in CCT after DMEK, independent of preoperative corneal thickness measurement. The model could be applied in clinical practice or for clinical research of FECD.
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PURPOSE: Oleander is a poisonous plant with extensively documented systemic side effects; however, oleander's ophthalmic side effects have not been detailed in the literature. We report a case of oleander-associated keratitis with subsequent corneal edema and anterior uveitis. METHODS: This is a case report and review of relevant literature. RESULTS: A 58-year-old woman presented with large corneal epithelial defect after being struck in the eye with an oleander leaf. Despite treatment with topical moxifloxacin, she developed severe corneal edema and anterior uveitis. A diagnosis of oleander-associated ocular inflammation with secondary corneal edema was made, given the temporal relationship, and treatment was initiated with topical prednisolone and cyclopentolate. However, the corneal edema and inflammation continued to progress until oral prednisone and topical difluprednate were initiated. Visual acuity, anterior uveitis, and corneal edema significantly improved with aggressive immunomodulation. Follow-up at 1 month confirmed complete recovery of symptoms, corneal edema and anterior uveitis. CONCLUSIONS: Severe corneal edema and anterior uveitis can be associated with oleander exposure. Aggressive treatment with oral and topical steroids may be required without persistent sequelae at the 5-month follow-up. Ophthalmologists should consider this inflammatory reaction if patients experience ocular exposure to oleander.
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Edema da Córnea , Ceratite , Nerium , Uveíte Anterior , Edema da Córnea/etiologia , Ciclopentolato/uso terapêutico , Feminino , Humanos , Inflamação , Ceratite/diagnóstico , Ceratite/tratamento farmacológico , Ceratite/etiologia , Pessoa de Meia-Idade , Moxifloxacina/uso terapêutico , Prednisolona/uso terapêutico , Prednisona/uso terapêutico , Uveíte Anterior/diagnóstico , Uveíte Anterior/tratamento farmacológico , Uveíte Anterior/etiologiaRESUMO
Belantamab mafodotin (BLMF) is a B-cell maturation antigen-directed antibody-drug conjugate, recently approved for advanced multiple myeloma (MM). The impact of BLMF-induced ocular toxicity on patient outcomes is unknown. We studied a cohort of 38 consecutively seen patients treated with BLMF outside of trials. Of those, 75% experienced ocular toxicity, with 69% developing keratopathy. Among patients requiring ocular toxicity-related permanent BLMF discontinuation (14%) or dose reduction (11%), 70% had progression of MM within a median of 3 months (95% confidence interval: 0.2-not reached) following BLMF interruption or dose reduction. Ocular toxicity is a major deterrent to the continuous use of BLMF in routine clinical practice. Measures to successfully prevent and mitigate ocular toxicity should be developed to achieve the full potential of this agent.
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Imunoconjugados , Mieloma Múltiplo , Anticorpos Monoclonais Humanizados , Antígeno de Maturação de Linfócitos B , Humanos , Imunoconjugados/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Neuropatia Óptica TóxicaRESUMO
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.
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PURPOSE: To assess vision in pseudophakic eyes with Fuchs' endothelial corneal dystrophy (FECD) before the onset of clinically detectable corneal edema. DESIGN: Cross-sectional study. METHODS: Sixty-one otherwise healthy pseudophakic eyes of 38 subjects with FECD (without clinically detectable edema) and 17 otherwise healthy pseudophakic eyes of 9 subjects with normal corneas. Subjects underwent clinical examination to determine the morphologic distribution of guttae (severity grading). Standardized best-corrected high-contract and low-contrast (photopic and mesopic) visual acuity (HCVA, LCVA) and straylight were measured. Scheimpflug tomography posterior elevation and pachymetry maps were interpreted for 3 tomographic features of subclinical edema: loss of regular isopachs, displacement of the thinnest point of the cornea, and presence of posterior surface depression. RESULTS: In FECD without tomographic features of edema (ie, normal tomography patterns), HCVA, LCVA, and straylight did not differ from that of eyes with normal corneas (P ≥ .09); these eyes encompassed the full range of severity grading of guttae. In FECD with all 3 tomographic features of edema, the same parameters were worse compared with eyes with normal corneas (P ≤ .02). In FECD with 1 or 2 tomographic abnormalities, mesopic LCVA (P = .04) and straylight (P = .003) were worse compared with eyes with normal corneas. CONCLUSIONS: Impairment of vision was associated with the presence of tomographic edema in eyes with FECD. When tomography patterns were normal in FECD (ie, guttae were present without tomographic edema), visual acuity and straylight were normal, and therefore corneal surgical intervention would not typically be indicated to improve vision.
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Edema da Córnea , Distrofia Endotelial de Fuchs , Córnea , Edema da Córnea/diagnóstico , Paquimetria Corneana/métodos , Estudos Transversais , Endotélio Corneano , Distrofia Endotelial de Fuchs/complicações , Distrofia Endotelial de Fuchs/diagnóstico , Humanos , Visão OcularRESUMO
OBJECTIVE: To determine the root causes of patient safety events in a high-volume intravitreal injection clinic and to assess the effect of interventions to reduce the rate of events. DESIGN: Quality improvement study. SUBJECTS: All cases of intravitreal injection in a designated injection clinic between January 1, 2016, and December 31, 2019. METHODS: The injection clinic model involved an injecting physician, who usually differed from a prescribing physician. The procedural injection area was also physically separate from the retina outpatient clinic. A root cause analysis was used to determine the factors that contributed to possible patient safety events in an institutional quality improvement project. Specific interventions were implemented to address each specific root cause. The rates of patient safety events (never events and near misses), whether associated with patient harm or not, were compared before and after the intervention. MAIN OUTCOME MEASURES: Frequency (%) of patient-safety-related intravitreal injection events before (January 1, 2016, to December 31, 2018) and after (January 1, 2019, to December 31, 2019) intervention. RESULTS: The root cause analysis included complex treatment plans that could be difficult to interpret, insufficient time to adequately review the designated treatment plans, and the risk of human error given the pace and volume of scheduled injections. Quality improvement strategies included revising the standardized treatment plan documentation template, scheduling block time for injecting physicians to review treatment plans within 24 hours of the injection clinic, and requiring agreement between dual, independent, site, and medication verifications of the treatment plan by the injecting physician and an allied health coordinator before site marking. The rate of events was 0.1% (28 in 27 400, or 9.3 events per year) before intervention and decreased to 0.01% (1 in 9375, or 1 event per year) after intervention (P = 0.01). Most events were classified as near misses, and there were no instances of patient harm. CONCLUSIONS: A high level of patient safety can be achieved in a complex, high-volume intravitreal injection practice by recognizing potential safety issues and root causes and implementing relevant quality improvements. Although most events were near misses and no patients were harmed, reducing near misses can reduce the likelihood of harm associated with never events.
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Erros Médicos , Segurança do Paciente , Instituições de Assistência Ambulatorial , Humanos , Injeções IntravítreasAssuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Neoplasias da Túnica Conjuntiva/diagnóstico por imagem , Fluorofotometria/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Neoplasias da Túnica Conjuntiva/patologia , Neoplasias da Túnica Conjuntiva/terapia , Crioterapia , Fluoresceína/administração & dosagem , Corantes Fluorescentes/administração & dosagem , Humanos , Masculino , Mitomicina/administração & dosagem , Recidiva Local de Neoplasia/patologia , Procedimentos Cirúrgicos OftalmológicosRESUMO
Expansion of CTG trinucleotide repeats (TNR) in the transcription factor 4 (TCF4) gene is highly associated with Fuchs Endothelial Corneal Dystrophy (FECD). Due to limitations in the availability of DNA from diseased corneal endothelium, sizing of CTG repeats in FECD patients has typically been determined using DNA samples isolated from peripheral blood leukocytes. However, it is non-feasible to extract enough DNA from surgically isolated FECD corneal endothelial tissue to determine repeat length based on current technology. To circumvent this issue, total RNA was isolated from FECD corneal endothelium and sequenced using long-read sequencing. Southern blotting of DNA samples isolated from primary cultures of corneal endothelium from these same affected individuals was also assessed. Both long read sequencing and Southern blot analysis showed significantly longer CTG TNR expansion (>1000 repeats) in the corneal endothelium from FECD patients than those characterized in leukocytes from the same individuals (<90 repeats). Our findings suggest that the TCF4 CTG repeat expansions in the FECD corneal endothelium are much longer than those found in leukocytes.
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DNA/genética , Endotélio Corneano/patologia , Distrofia Endotelial de Fuchs/patologia , Leucócitos/patologia , Fator de Transcrição 4/genética , Expansão das Repetições de Trinucleotídeos , Idoso , Idoso de 80 Anos ou mais , Southern Blotting , Criança , DNA/análise , Endotélio Corneano/metabolismo , Feminino , Distrofia Endotelial de Fuchs/epidemiologia , Distrofia Endotelial de Fuchs/genética , Predisposição Genética para Doença , Genótipo , Humanos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
Primary cultures of human corneal endothelial cells (HCECs) are an important model system for studying the pathophysiology of corneal endothelium. The purpose of this study was to identify and validate an optimal primary culture model of normal and Fuchs endothelial corneal dystrophy (FECD) endothelial cells by comparing cell morphology and marker expression under different media conditions to in vivo donor tissues. Primary and immortalized HCECs, isolated from normal and FECD donors, were cultured in proliferation media (Joyce, M4, Bartakova) alone or sequentially with maturation media (F99, Stabilization 1, M5). CD56, CD73 and CD166 expressions were quantified in confluent and matured cell lines by flow cytometry. HCECs that were allowed to proliferate in Joyce's medium followed by maturation in low-mitogen containing media yielded cells with similar morphology to corneal endothelial tissues. Elevated expression of CD56 and CD166 and low expression of CD73 correlated with regular, hexagonal-like HCEC morphology. CD56:CD73 > 2.5 was most consistent with normal HCEC morphology and mimicked corneal endothelial tissue. Immortalization of normal HCECs by hTERT transduction showed morphology and CD56:CD73 ratios similar to parental cell lines. HCECs established from FECD donors showed reduced CD56:CD73 ratios compared to normal HCECs which coincided with reduced uniformity and regularity of cell monolayers. Overall, a dual media system with Joyce's medium for proliferation and a low-mitogen media for maturation, provided normal cultures with regular, hexagonal-like cell morphologies consistent with corneal endothelial cells in vivo. CD56:CD73 expression ratio >2.5 was predictive of in vivo-like cellular morphology.
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Técnicas de Cultura de Células , Células Endoteliais/patologia , Distrofia Endotelial de Fuchs/patologia , Proliferação de Células , Meios de Cultura , Endotélio Corneano , HumanosAssuntos
Ado-Trastuzumab Emtansina/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma Ductal de Mama/tratamento farmacológico , Doenças da Córnea , Técnicas de Diagnóstico Oftalmológico , Maitansina/efeitos adversos , Mesotelioma Maligno/tratamento farmacológico , Mieloma Múltiplo/tratamento farmacológico , Ado-Trastuzumab Emtansina/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Doenças da Córnea/induzido quimicamente , Doenças da Córnea/diagnóstico , Doenças da Córnea/fisiopatologia , Monitoramento de Medicamentos/métodos , Epitélio Corneano/efeitos dos fármacos , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/efeitos adversos , Maitansina/administração & dosagem , Fotofobia/diagnóstico , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologiaRESUMO
PURPOSE: To quantify changes in manifest refractive error and mean keratometric power (Km) at 1 month and ≥12 months after Salzmann nodule excision. SETTING: Cornea service at Mayo Clinic, Rochester, MN. DESIGN: Retrospective consecutive case series. METHODS: Changes in manifest refractive error (spherical equivalent), Km, and corrected distance visual acuity (CDVA) were compared for 73 eyes of 58 patients who underwent Salzmann nodule excision. Eyes with ocular comorbidities were excluded. Comparisons between preoperative and postoperative measurements were made by using generalized estimating equation models. RESULTS: Mean patient age was 66 years, and 53 patients (91%) were female. Spherical equivalent manifest refractive error was -0.27 ± 2.66 diopters (D) before nodule excision and became more myopic (-1.10 ± 2.78 D) at 1 month after nodule excision (n = 69, P < .001) with no change at 12 months (n = 14, P = .13). A myopic shift ≥0.5 D occurred in 65% of eyes and ≥1.0 D in 36% of eyes. Km increased from 42.7 ± 2.11 D before nodule excision to 44.2 ± 1.82 D at 1 month after excision (n = 49, P < .001). CDVA improved from 0.18 ± 0.15 logMAR (Snellen equivalent 20/30) before nodule excision to 0.05 ± 0.09 logMAR (20/22, n = 69, P < .001) at 1 month after excision with no change at 12 months (n = 14, P = .73). CONCLUSIONS: In addition to known changes in cylinder, Salzmann nodule excision is associated with a myopic shift in most eyes caused by corneal steepening. Patients should be counseled about the likelihood of refractive changes, and cataract surgery should be deferred until refractive stability is achieved.