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BACKGROUND: The influence of Vitreomacular Interface Abnormalities (VMIA) such as Epiretinal Membrane (ERM) and/or vitreomacular traction (VMT) on the response of patients with Centre Involving Diabetic Macular Edema (CIDME) to standard of care Anti-VEGF medications is under-researched. The aims of this study were: 1) To determine the incidence of VMIA at baseline and 12 months amongst treatment naive patients commencing anti-VEGF treatment 2) To compare the response to Anti-VEGF medications at 3 monthly intervals for 12 months in a large cohort of patients with and without VMIA on their baseline OCT scan. Response was determined in terms of: number of injections, central macular thickness and visual acuity. METHODS: A retrospective case notes review of treatment naïve patients with newly diagnosed CIDME. Included patients had been commenced on intravitreal Anti-VEGF injections (ranibizumab or aflibercept) at a single centre. Inclusion criteria were: treatment naïve DME patients with a CMT of 400µ or more receiving anti-VEGF treatment with at least 12 months follow up and in whom macular OCT scans and visual acuity (VA) measurements were available within two weeks of baseline, 3, 6, 9 and 12 months. Exclusion criteria included: previous intravitreal therapy, previous vitrectomy, cataract surgery during the follow-up period, concurrent eye conditions affecting vision or CMT. RESULTS: 119 eyes met the inclusion criteria and underwent analysis. Groups were comparable in their baseline demographics. Baseline CMT measurements were comparable at baseline (417µ and 430µ in the No-VMIA and VMIA groups respectively) and improved to approximately 300µ in both groups. From 6 months CMT continued to improve in the no-VMIA while progressively deteriorating in the VMIA group. Change in CMT was statistically different at 12 months between the 2 groups (108µ and 79µ, p= 0.04). There was a mean of 7 injections after 12 months. CONCLUSION: Our study has shown a 46% incidence of VMIA amongst patients newly diagnosed with centre involving DME undergoing treatment with anti-VEGF injections. We have also demonstrated a significant difference in CMT and VA response to anti-VEGF treatment in patients with and without VMIA. Initial response was similar between the 2 groups up until 6 months. From 6 to 12 months significant differences in treatment response emerged. Differences in clinical response between patients with and without VMIA may help guide further prospective controlled studies and optimise treatment strategies.
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PURPOSE: To analyze the outcomes of revision surgery for idiopathic full-thickness macular holes that have failed to close after primary surgery, and also to assess factors predicting success and to review the relative effect of adjunctive surgical techniques. METHODS: A multicenter retrospective study. Anatomical closure rates and visual acuity change between pre and postrevision surgery were assessed. Hole size, age, symptom duration, surgical interval, and reduced hole size were analyzed as predictive factors for success. Effectiveness of adjunctive surgical techniques was reviewed. RESULTS: Seventy-seven eyes were included in the study. Anatomical closure was achieved in 71% (55/77) cases. There was a median gain of 11 Early Treatment of Diabetic Retinopathy Score letters in all holes and 14 letters in closed holes. Full-thickness macular holes that increased in size by more than 10% following primary surgery had a closure rate of 50% compared with 80% in holes that reduced by 10% or stayed the same (P = 0.015). Increasing hole size is associated with a modest reduction in odds of closure (odds ratio = 0.99; P = 0.04). Surgical interval <2 months is not associated with better outcomes compared with >2 months (P = 0.14). CONCLUSION: Revision surgery for full-thickness macular holes that have failed to close after primary surgery is associated with high closure rates and significant visual gains.
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Macula Lutea/diagnóstico por imagem , Perfurações Retinianas/reabilitação , Acuidade Visual , Vitrectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação/métodos , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Introduction: Calcification of hydrophilic intraocular lenses (IOL) is a rare complication following cataract surgery. Secondary calcification is described as due to host factors or changes in the IOL environment and uveitis, proliferative diabetic retinopathy and sequelae of ocular surgery are recognised potentiators. The impact of systemic connective tissue disease on IOL opacification is yet to described. Purpose: To describe the clinical presentation and management of a young patient, with a rare subtype of Ehlers-Danlos syndrome, who presented with secondary IOL calcification 14 years after primary IOL insertion. Observations: Floret-like lesions were observed on the IOL surface. Positive staining for calcification was observed with Alizarin red and von Kossa method on laboratory analysis. Conclusions and importance: Patients with systemic connective tissue disease, such as a subtype of Ehlers-Danlos, may present with secondary IOL calcification many years after primary lens insertion. This poses an additional consideration when implanting IOLs in these patients.Good visual acuity can be achieved with IOL exchange.
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Importance: There are reported benefits from vitrectomy for diabetic macular edema (DME); however, data precede anti-vascular endothelial growth therapy (VEGF) therapy, supporting a need to assess the current role of vitrectomy. Objective: To determine rates of recruitment and efficacy outcomes of vitrectomy plus internal limiting membrane (ILM) peeling adjunctive to treat-and-extend (T&E) anti-VEGF injections for diabetic macular edema (DME). Design, Setting, and Participants: This was a single-masked, multicenter randomized clinical trial at 21 sites in the United Kingdom from June 2018 to January 2021, evaluating single eyes of treatment-naive patients with symptomatic vision loss from DME for less than 1 year. Inclusion criteria were best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter score greater than 35 (approximate Snellen equivalent, 20/200 or better) and central subfield thickness (CST) greater than 350 µm after 3 monthly intravitreal injections of ranibizumab or aflibercept. Data analysis was performed in July 2023. Interventions: Patients were randomized 1:1 into vitrectomy plus standard care or standard care alone and further stratified into groups with vs without vitreomacular interface abnormality. Both groups received a T&E anti-VEGF injection regimen with aflibercept, 2 mg, or ranibizumab, 0.5 mg. The vitrectomy group additionally underwent pars plana vitrectomy with epiretinal membrane or ILM peel within 1 month of randomization. Main Outcomes and Measures: Rate of recruitment and distance BCVA. Secondary outcome measures were CST, change in BCVA and CST, number of injections, rate of completed follow-up, and withdrawal rate. Results: Over 32 months, 47 of a planned 100 patients were enrolled; 42 (89%; mean [SD] age, 63 [11] years; 26 [62%] male) completed 12-month follow-up visits. Baseline characteristics appeared comparable between the control (n = 23; mean [SD] age, 66 [10] years) and vitrectomy (n = 24; mean [SD] age, 62 [12] years) groups. No difference in 12-month BCVA was noted between groups, with a 12-month median (IQR) BCVA letter score of 73 (65-77) letters (Snellen equivalent, 20/40) in the control group vs 77 (67-81) letters (Snellen equivalent, 20/32) in the vitrectomy group (difference, 4 letters; 95% CI, -8 to 2; P = .24). There was no difference in BCVA change from baseline (median [IQR], -1 [-3 to 2] letters for the control group vs -2 [-8 to 2] letters for the vitrectomy group; difference, 1 letter; 95% CI, -5 to 7; P = .85). No difference was found in CST changes (median [IQR], -94 [-122 to 9] µm for the control group vs -32 [-48 to 25] µm for the vitrectomy group; difference, 62 µm; 95% CI, -110 to 11; P = .11). Conclusions and Relevance: Enrollment goals could not be attained. However, with 47 participants, evidence did not support a clinical benefit of vitrectomy plus ILM peeling as an adjunct to a T&E regimen of anti-VEGF therapy for DME. Trial Registration: isrctn.org Identifier: ISRCTN59902040.
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PTEN promoter hypermethylation is nearly universal and PTEN copy number loss occurs in ~25% of fusion-negative rhabdomyosarcoma (FN-RMS). Here we show Pten deletion in a mouse model of FN-RMS results in less differentiated tumors more closely resembling human embryonal RMS. PTEN loss activated the PI3K pathway but did not increase mTOR activity. In wild-type tumors, PTEN was expressed in the nucleus suggesting loss of nuclear PTEN functions could account for these phenotypes. Pten deleted tumors had increased expression of transcription factors important in neural and skeletal muscle development including Dbx1 and Pax7. Pax7 deletion completely rescued the effects of Pten loss. Strikingly, these Pten;Pax7 deleted tumors were no longer FN-RMS but displayed smooth muscle differentiation similar to leiomyosarcoma. These data highlight how Pten loss in FN-RMS is connected to a PAX7 lineage-specific transcriptional output that creates a dependency or synthetic essentiality on the transcription factor PAX7 to maintain tumor identity.
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Fator de Transcrição PAX7/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Rabdomiossarcoma/metabolismo , Rabdomiossarcoma/patologia , Animais , Cruzamento , Diferenciação Celular , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Humanos , Integrases/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos Knockout , Desenvolvimento Muscular , PTEN Fosfo-Hidrolase/deficiência , Fosfoproteínas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Rabdomiossarcoma/genéticaRESUMO
Purpose: To determine the association between training-load (TL) factors, baseline characteristics, and new injury and/or pain (IP) risk in an endurance sporting population (ESP). Methods: Ninety-five ESP participants from running, triathlon, swimming, cycling, and rowing disciplines initially completed a questionnaire capturing baseline characteristics. TL and IP data were submitted weekly over a 52-wk study period. Cumulative TL factors, acute:chronic workload ratios, and exponentially weighted moving averages were calculated. A shared frailty model was used to explore time to new IP and association to TL factors and baseline characteristics. Results: 92.6% of the ESP completed all 52 wk of TL and IP data. The following factors were associated with the lowest risk of a new IP episode: (a) a low to moderate 7-d lag exponentially weighted moving averages (0.8-1.3: hazard ratio [HR] = 1.21; 95% confidence interval [CI], 1.01-1.44; P = .04); (b) a low to moderate 7-d lag weekly TL (1200-1700 AU: HR = 1.38; 95% CI, 1.15-1.65; P < .001); (c) a moderate to high 14-d lag 4-weekly cumulative TL (5200-8000 AU: HR = 0.33; 95% CI, 0.21-0.50; P < .001); and (d) a low number of previous IP episodes in the preceding 12 mo (1 previous IP episode: HR = 1.11; 95% CI, 1.04-1.17; P = .04). Conclusions: To minimize new IP risk, an ESP should avoid high spikes in acute TL while maintaining moderate to high chronic TLs. A history of previous IP should be considered when prescribing TLs. The demonstration of a lag between a TL factor and its impact on new IP risk may have important implications for future ESP TL analysis.
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Traumatismos em Atletas/prevenção & controle , Dor/prevenção & controle , Condicionamento Físico Humano , Carga de Trabalho , Adulto , Atletas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resistência Física , Estudos Prospectivos , Fatores de RiscoAssuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Descolamento Retiniano , Humanos , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/terapia , Acuidade Visual , Angiofluoresceinografia , Tomografia de Coerência ÓpticaRESUMO
It is difficult to assess countries' relative success in addressing issues of public health because countries are subject to very different background conditions. To address this problem we offer a model-based approach for assessing health system performance. Specifically, an index of public health is regressed against a vector of variables intended to capture economic, educational, cultural, geographic, and epidemiological endowments. The residual from this model is regarded as a plausible measure of public health performance at the national level. We argue that a model-based approach to performance is informative for policymakers and academics as it focuses attention on those aspects of a country's health profile that are not constrained by structural factors. This sharpens comparisons across countries and through time, and also allows one to evaluate the degree to which health systems have lived up to their potential.