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1.
Eur J Pediatr ; 183(2): 827-834, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38030929

RESUMO

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness in preterm infants. The incidence of ROP varies widely across countries, with rates as high as 30% in some regions. This study investigated the incidence, risk factors, treatment, and mortality of ROP patients in Germany. Data were extracted from the German Federal Statistical Office (Destatis) diagnosis-related group (DRG) and Institute for the Remuneration System in Hospitals (InEK) databases. Patients with a secondary diagnosis of ROP (ICD-10 code H35.1) in the first 28 days of life were included. Data were extracted for patients admitted between January 1, 2019 and December 31, 2019. The diagnoses and procedures were determined using the German version of the International Classification of Diseases (ICD-10-GM) and the German procedure coding system (OPS). The codes 5-154.xx, 5-155.xx, 8-020.xx, 5-156.9, 6-003.(c&d), 6-007.(2&8) were utilised to denote different ocular treatments. Patient Clinical Complexity Levels were extracted and used to compare ROP with non-ROP patients. A total of 1326 patients with ROP were identified. The incidence of ROP is estimated to be 17.04 per 10,000 live births. The incidence was highest in infants with birth weights less than 500 g and decreased with increasing birth weight. The most common risk factors for ROP were low birth weight, male sex, and prematurity. Of the infants with ROP, 7.2% required ocular treatment. The most common treatment was intraocular injections, followed by photocoagulation. No surgical treatment was required for any of the infants during the study period. The mortality rate for infants with ROP was 60.33 per 10,000. This is higher than the overall neonatal death rate of 24.2 per 10,000. CONCLUSIONS: This study found that the incidence of ROP in Germany is similar to that in other developed countries. The study also found that the mortality rate for infants with ROP is higher than the overall neonatal death rate. These findings highlight the importance of early detection and treatment of ROP in preterm infants. WHAT IS KNOWN: • ROP is a severe eye condition often affecting preterm infants. • Previous data are limited in scope and generalizability. WHAT IS NEW: • Based on a national database, our study found ROP incidence to be 17.04 per 10,000 new births, higher in males (17.71) than in females (16.34). • 7.2% of ROP cases required ocular treatment, inversely correlated with birth weight. • High rates of multimorbidity such as neonatal jaundice (84.69%), respiratory distress syndrome (80.84%), and apnea (78.88%) were observed.


Assuntos
Morte Perinatal , Retinopatia da Prematuridade , Lactente , Feminino , Recém-Nascido , Humanos , Masculino , Recém-Nascido Prematuro , Peso ao Nascer , Estudos de Coortes , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/epidemiologia , Retinopatia da Prematuridade/terapia , Incidência , Idade Gestacional , Fatores de Risco
2.
Artigo em Inglês | MEDLINE | ID: mdl-38466396

RESUMO

PURPOSE: This nationwide study aims to delineate the incidence and trends of rhegmatogenous retinal detachment (rRD) in Germany across 17 years (2005-2021). METHODS: We conducted a retrospective cohort study using data from the German Federal Statistics Office and the Institute for the Hospital Remuneration System (InEK). The dataset includes approximately 19 million annual inpatient admissions annually. Retinal detachment was identified through ICD-10 code H33.0. Adjusted incidence rates were estimated after excluding reoperation cases. We used R Statistical Software to calculate estimates to 2021, and Tableau for visualisation. RESULTS: From 2005 to 2021, Germany reported 332,650 rRD cases, with males consistently more affected. Adjusted incidence rose from 15.6 per 100,000 in 2005 to 24.8 in 2021. Variable annual percentage changes in incidence were noted, averaging 4.0% for males and 2.6% for females. The annual mean age of affected individuals ranged from 60.2 to 62 years, with a median age between 62 and 63, suggesting increasing diagnoses at younger ages. Hospital stays declined from 6 to 3.3 days, and higher management rates were observed in Saarland and Rhineland-Palatine. CONCLUSION: The study confirms an increasing incidence of rRD in Germany from 2005 to 2021, particularly among males. These findings call for further research to investigate the underlying causes. Collaboration among healthcare professionals, researchers, and policymakers is essential for effective management and improved visual outcomes.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38951225

RESUMO

INTRODUCTION: Magnetic intraocular foreign bodies can be removed with magnetized disposable forceps. Aim of this study is to compare the forceps magnetizability of different size, form and manufacturer. METHODS: The forceps were magnetized using an established procedure. The inducible magnetic flux density was measured at the tip of the forceps. The mass that can be lifted with the magnetized forceps was then tested using steel balls in BSS solution. The weight of the metal parts of the forceps was measured. RESULTS: The magnetic flux density that could be induced, the weight of the steel balls that could be lifted and the mass of stainless steel used in the forceps were as follows: Alcon end-grasping 23G: 7.12 mT, 87.43 mg, 1191 mg; Alcon end-grasping 25G: 6.43 mT, 87.43 mg, 1189 mg; Alcon serrated: 4.39 mT, 63.78 mg, 1284 mg; Alcon serrated 23G: 3.62 mT, 13.74 mg, 1200 mg; Alcon serrated 25G: 2.4 mT, 13.74 mg, 1195 mg; DORC end-grasping 23G: 5.52 mT, 32.54 mg, 153 mg; Synergetics end-grasping 23G: 4.35 mT, 16.37 mg, 193 mg; Vitreq BV end-grasping 23G: 2.65 mT, none, 88 mg. DISCUSSION: The magnetizability of a disposable microforceps seems to depend on the mass of steel at the tip of the forceps. The structure of the iron lattice could have an even greater influence. Not every disposable forceps can be sufficiently magnetized for this technique.

4.
Ophthalmologica ; 247(2): 85-94, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38142686

RESUMO

INTRODUCTION: The aim of this study was to describe differences in the vitreomacular interface (VMI) in idiopathic epiretinal membrane (ERM) foveoschisis compared to macular pseudohole (MPH) and lamellar macular hole (LMH). METHODS: We analysed surgically excised epiretinal material and internal limiting membrane (ILM) specimens obtained from 16 eyes of 16 patients with ERM foveoschisis (6 eyes), MPH (5 eyes), and LMH (5 eyes) during standard pars plana vitrectomy (PPV) with membrane peeling. The three entities were classified according to the newly introduced optical coherence tomography (OCT) terminology. Transmission electron microscopy (TEM) was used to describe the ultrastructural features. RESULTS: We found fibrocellular epiretinal tissues in all samples analysed. However, the cell and collagen composition of the VMI differed between groups. Eyes with ERM foveoschisis were characterized by a higher number of cells, multilayered membranes, and thick strands of vitreous collagen embedding the major cell types of myofibroblasts compared to MPH. Eyes with MPH also showed a predominance of myofibroblasts, but these were located directly on the ILM with no collagen between the cells and the ILM. Eyes with LMH showed a thick, multilayered epiretinal proliferation consisting mainly of non-tractional glial cells, corresponding to hypodense epiretinal proliferation on OCT. Eyes with ERM foveoschisis and MPH were more likely to have incomplete PVD compared to LMH in terms of posterior hyaloid status. DISCUSSION/CONCLUSION: Tractional ERMs in eyes with ERM foveoschisis and MPH differ in their ultrastructure. The main difference is in the amount and topographical distribution of vitreous collagen. However, the epiretinal cell types are predominantly myofibroblasts in both entities. This highlights the importance of distinguishing ERM foveoschisis from both MPH and LMH in terms of pathogenesis and surgical peeling procedures.


Assuntos
Membrana Epirretiniana , Microscopia Eletrônica de Transmissão , Retinosquise , Tomografia de Coerência Óptica , Vitrectomia , Humanos , Membrana Epirretiniana/diagnóstico , Membrana Epirretiniana/cirurgia , Tomografia de Coerência Óptica/métodos , Retinosquise/diagnóstico , Feminino , Masculino , Idoso , Vitrectomia/métodos , Pessoa de Meia-Idade , Membrana Basal/ultraestrutura , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Corpo Vítreo/ultraestrutura , Corpo Vítreo/patologia
5.
Graefes Arch Clin Exp Ophthalmol ; 261(7): 1933-1940, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36680612

RESUMO

PURPOSE: The following is a comparative analysis on the treatment outcomes of corneal perforations using amniotic membrane transplantation (AMT) or penetrating keratoplasty (PK). METHODS: This monocentric retrospective study was performed at the Department of Ophthalmology, University Hospital Ulm, Germany. A total of 78 eyes of 78 patients were included. Thirty-nine eyes received an AMT, and 39 patients were treated with a PK. Primary outcome was recurrence of perforation. Secondary outcomes were patient mortality and visual acuity. RESULTS: No statistically significant difference was observed with regard to a recurrence of perforation between the two groups (26% in AMT vs 23% in PK, p > 0.99). The time of recurrences was within the first two years and did not differ statistically (p = 0.97). In addition, a proportional hazards model with cox regression regarding recurrent perforation showed no significant differences (p = 0.5). After AMT, 41% and after KP, 28% of the patients died during follow-up (p = 0.2), respectively. The Charlson Comorbidity Index (p < 0.0001) and the age at the time of surgery (p = 0.0002) were statistically significantly higher in those who were deceased. A mean follow-up of 485 ± 517 days was recorded. CONCLUSION: Both surgical methods show good results and no statistically significant difference regarding recurrent perforation rate. About a third of the patients died during the follow-up period. The decision regarding the appropriate method should therefore be based on a combination of all factors.


Assuntos
Doenças da Córnea , Perfuração da Córnea , Transplante de Córnea , Humanos , Ceratoplastia Penetrante , Perfuração da Córnea/diagnóstico , Perfuração da Córnea/cirurgia , Âmnio/transplante , Estudos Retrospectivos , Resultado do Tratamento , Transplante de Córnea/métodos , Doenças da Córnea/diagnóstico , Doenças da Córnea/cirurgia
6.
Retina ; 43(8): 1393-1398, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37155957

RESUMO

PURPOSE: To verify whether disposable microforceps can be magnetized to atraumatically attract and then grasp intraocular foreign bodies. An effective magnetization protocol was developed. The clinical relevance was tested, and a first practical application was performed. METHODS: The magnetic flux density (MFD) of a bar magnet and an electromagnet was measured. Steel screws were used to determine the magnetization protocol. Disposable microforceps was magnetized, MFD generated at the tip was measured, and the weight that can be lifted was tested. Foreign body removal with such forceps was performed. RESULTS: The electromagnet MFD was much higher than the bar magnet. The most effective magnetization protocol was to pass the screw from the end along the shaft and back over the electromagnet. Magnetized microforceps had a 7.12 mT change in MFD at the tip. Steel balls up to 87 mg could be lifted in buffered saline solution. In clinical use, the intraocular foreign body could be attracted and grasped safely. CONCLUSION: Disposable microforceps can be easily and inexpensively magnetized. The achievable MFD is clinically relevant to attract typical intraocular foreign bodies. An electromagnet is best suited for this purpose. With such prepared forceps, foreign bodies can be attracted atraumatically and grasped securely.


Assuntos
Corpos Estranhos no Olho , Instrumentos Cirúrgicos , Humanos , Corpos Estranhos no Olho/cirurgia , Relevância Clínica
7.
Retina ; 43(10): 1773-1779, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37315515

RESUMO

PURPOSE: To describe presence and distribution of pores of the inner limiting membrane (ILM) in eyes with vitreomaculopathies. METHODS: Inner limiting membrane specimens were harvested from 117 eyes of 117 patients during vitrectomy with membrane peeling from eyes with vitreomacular traction syndrome, idiopathic and secondary epiretinal gliosis, and idiopathic full-thickness macular hole. All specimens were processed as flat-mounts for immunocytochemistry and examined by phase-contrast, interference, and fluorescence microscopy. Demographic and clinical data were correlated. RESULTS: Inner limiting membrane pores were found in all vitreomaculopathies. They were identified in 47 (40.2%) of 117 eyes being most evident with antilaminin. In eyes with full-thickness macular hole >400 µ m, pores were seen in more than half of all eyes. They occur as numerous and uniformly distributed defects of the flat-mounted ILM with a mean diameter of 9.5 ± 2.4 µ m. Edges of ILM pores are round with an irregular contour and no specific cellular pattern. Pores were distinguished from retinal vessel thinning and iatrogenic artefacts. CONCLUSION: Contrary to previous reports, ILM pores are a common finding in vitreomaculopathies easily visible with antilaminin staining. Further studies are needed to clarify whether their presence correlates with differences in disease progression or imaging before and after vitrectomy with ILM peeling.


Assuntos
Membrana Epirretiniana , Degeneração Retiniana , Perfurações Retinianas , Humanos , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/cirurgia , Perfurações Retinianas/complicações , Membrana Epirretiniana/diagnóstico , Membrana Epirretiniana/cirurgia , Membrana Epirretiniana/complicações , Retina , Vitrectomia/métodos , Coloração e Rotulagem , Degeneração Retiniana/cirurgia , Membrana Basal/cirurgia , Estudos Retrospectivos , Tomografia de Coerência Óptica
8.
PLoS Genet ; 16(9): e1008934, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32870927

RESUMO

Significant association signals from genome-wide association studies (GWAS) point to genomic regions of interest. However, for most loci the causative genetic variant remains undefined. Determining expression quantitative trait loci (eQTL) in a disease relevant tissue is an excellent approach to zoom in on disease- or trait-associated association signals and hitherto on relevant disease mechanisms. To this end, we explored regulation of gene expression in healthy retina (n = 311) and generated the largest cis-eQTL data set available to date. Genotype- and RNA-Seq data underwent rigorous quality control protocols before FastQTL was applied to assess the influence of genetic markers on local (cis) gene expression. Our analysis identified 403,151 significant eQTL variants (eVariants) that regulate 3,007 genes (eGenes) (Q-Value < 0.05). A conditional analysis revealed 744 independent secondary eQTL signals for 598 of the 3,007 eGenes. Interestingly, 99,165 (24.71%) of all unique eVariants regulate the expression of more than one eGene. Filtering the dataset for eVariants regulating three or more eGenes revealed 96 potential regulatory clusters. Of these, 31 harbour 130 genes which are partially regulated by the same genetic signal. To correlate eQTL and association signals, GWAS data from twelve complex eye diseases or traits were included and resulted in identification of 80 eGenes with potential association. Remarkably, expression of 10 genes is regulated by eVariants associated with multiple eye diseases or traits. In conclusion, we generated a unique catalogue of gene expression regulation in healthy retinal tissue and applied this resource to identify potentially pleiotropic effects in highly prevalent human eye diseases. Our study provides an excellent basis to further explore mechanisms of various retinal disease etiologies.


Assuntos
Retina/metabolismo , Retina/fisiologia , Doenças Retinianas/genética , Autopsia , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Estudo de Associação Genômica Ampla/métodos , Genômica/métodos , Genótipo , Voluntários Saudáveis , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética
9.
Klin Monbl Augenheilkd ; 240(9): 1046-1051, 2023 Sep.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-37353213

RESUMO

There have been marked increases in the numbers of patients with retinal detachments at individual centres in recent years and this is supported by the subjective impression of many experts. We therefore surveyed the literature on changes in the incidence of retinal detachments worldwide. This revealed quite significant methodological differences between the studies, so that it was difficult to achieve a conclusive comparison of the development of the incidence of retinal detachment. Despite these limitations, all data from recent studies suggest an increase in the number of retinal detachments. The incidence of retinal detachment in the western world currently seems to be more than 20 cases per 100,000 person-years, which is significantly higher than described in earlier decades. It can be assumed that an increase in the number of individuals with myopia, a demographic increase in patients of the typical age group for retinal detachment and an increasing number of cataract surgeries, especially in younger patients, are responsible for the rising incidence of retinal detachment.


Assuntos
Saúde Global , Descolamento Retiniano , Humanos , Alemanha/epidemiologia , Saúde Global/estatística & dados numéricos , Hospitais Universitários , Incidência , Ambulatório Hospitalar , Descolamento Retiniano/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso
10.
Exp Eye Res ; 216: 108945, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35038456

RESUMO

The VEGF-A-induced functional impairment of the barrier formed by retinal endothelial cells (REC) can be prevented and even - at least temporarily - reverted by trapping the growth factor in a complex with a VEGF-binding protein or by inhibiting the activity of the VEGF receptor 2 (VEGFR2). In an approach to emulate the clinically relevant situation of constant exposure to effectors, we investigated (1) whether prolonged exposure to VEGF-A165 for up to six days results in a different type of disturbance of the barrier formed by immortalized bovine REC (iBREC) and (2) whether alterations of the barrier induced by VEGF-A165 can indeed be sustainably reverted by subsequent treatment with the VEGF-A-binding proteins ranibizumab or brolucizumab. As a measure of barrier integrity, the cell index (CI) of iBREC cultivated on gold electrodes was monitored continuously. CI values declined shortly after addition of the growth factor and then remained low for more than six days over which considerable amounts of both extra- and intracellular VEGF-A were measured. Interestingly, the specific VEGFR2 inhibitor nintedanib normalized the lowered CI when added to iBREC pre-treated with VEGF-A165 for one day, but failed to do so when cells had been exposed to the growth factor for six days. Expression of the tight junction (TJ) protein claudin-5 was unchanged early after addition of VEGF-A165 but higher after prolonged treatment, whereas decreased amounts of the TJ-protein claudin-1 remained low, and increased expression of the plasmalemma vesicle-associated protein (PLVAP) remained high during further exposure. After two days, the characteristic even plasma membrane stainings of claudin-1 or claudin-5 appeared weaker or disordered, respectively. After six days the subcellular localization of claudin-5 was similar to that of control cells again, but claudin-1 remained relocated from the plasma membrane. To counteract these effects of VEGF-A165, brolucizumab or ranibizumab was added after one day, resulting in recovery of the then lowered CI to normal values within a few hours. However, despite the VEGF antagonist being present, the CI declined again two days later to values that were just slightly higher than without VEGF inhibition during further assessment for several days. At this stage, neither the supernatants nor whole cell extracts from iBREC treated with VEGF-A165 and its antagonists contained significant amounts of free VEGF-A. Treatment of VEGF-A165-challenged iBREC with ranibizumab or brolucizumab normalized expression of claudin-1 and claudin-5, but not completely that of PLVAP. Interestingly, the characteristic VEGF-A165-induced relocalization of claudin-1 from the plasma membrane was reverted within one day by any of the VEGF antagonists, but reappeared despite their presence after further exposure for several days. Taken together, barrier dysfunction induced by VEGF-A165 results from deregulated para- and transcellular flow but the precise nature or magnitude of underlying changes on a molecular level clearly depend on the time of exposure, evolving into a stage of VEGF-A165-independent barrier impairment. These findings also provide a plausible explanation for resistance to treatment with VEGF-A antagonists frequently observed in clinical practice.


Assuntos
Células Endoteliais/efeitos dos fármacos , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/farmacologia , Vasos Retinianos/citologia , Junções Íntimas/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/farmacologia , Inibidores da Angiogênese/uso terapêutico , Animais , Anticorpos Monoclonais Humanizados/uso terapêutico , Transporte Biológico , Western Blotting , Bovinos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Claudina-1/metabolismo , Claudina-5/metabolismo , Eletroforese em Gel de Poliacrilamida , Células Endoteliais/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Ranibizumab/uso terapêutico
11.
Graefes Arch Clin Exp Ophthalmol ; 260(3): 873-884, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34729639

RESUMO

PURPOSE: To describe characteristics of the vitreomacular interface (VMI) in traumatic macular holes (TMH) compared to idiopathic macular holes (IMH) using immunofluorescence and electron microscopy, and to correlate with clinical data. METHODS: For immunocytochemical and ultrastructural analyses, premacular tissue with internal limiting membrane (ILM) and epiretinal membrane (ERM) was harvested during vitrectomy from 5 eyes with TMH and 5 eyes with IMH. All specimens were processed as flat mounts for phase-contrast microscopy, interference and fluorescence microscopy, and transmission electron microscopy (TEM). Primary antibodies were used against microglial and macroglial cells. Clinical data was retrospectively evaluated. RESULTS: Surgically excised premacular tissue of eyes with TMH showed a less pronounced positive immunoreactivity for anti-glutamine synthetase, anti-vimentin and anti-IBA1 compared to eyes with IMH. Cell nuclei staining of the flat-mounted specimens as well as TEM presented a lower cell count in eyes with TMH compared to IMH. All detected cells were found on the vitreal side of the ILM. No collagen fibrils were seen in specimens of TMH. According to patients' age, intraoperative data as well as spectral-domain optical coherence tomography (SD-OCT) analysis revealed an attached posterior vitreous in the majority of TMH cases (60%), whereas all eyes with IMH presented posterior vitreous detachment. CONCLUSION: The vitreomacular interface in TMH and IMH shows significant differences. In TMH, glial cells are a rare finding on the vitreal side of the ILM.


Assuntos
Membrana Epirretiniana , Perfurações Retinianas , Membrana Basal/metabolismo , Membrana Epirretiniana/diagnóstico , Membrana Epirretiniana/metabolismo , Membrana Epirretiniana/cirurgia , Humanos , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/metabolismo , Perfurações Retinianas/cirurgia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Vitrectomia/métodos
12.
Retina ; 42(7): 1392-1398, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35321998

RESUMO

PURPOSE: The aim of our prospective off-label, interventional clinical trial was to evaluate the efficacy and safety of the fluocinolone-loop-anchoring technique over two years in eyes with iris-lens diaphragm disruption and pseudophakic cystoid macular edema. METHODS: In 10 eyes, scleral fixation of fluocinolone implant was performed. Main outcome measures were the development of best-corrected visual acuity (BCVA), central retinal thickness over 24 months, and general safety of the procedure. RESULTS: A significant improvement to 0.57 ± 0.38 log MAR (Snellen 20/80) (range 0-1.30) was observed (P = 0.003) at 1 month. Further improvement to 0.45 ± 036 log MAR (Snellen 20/60) was observed until month 18 (P = 0.081). Mean central retinal thickness decreased by 22% from 601.6 ± 235.5 µm to 449.1 ± 128.9 µm at 1 month. In one patient, the implant has to be removed at Month 7 because of elevated intraocular pressure and one patient after globe rupture had a retinal redetachment at Month 4. CONCLUSION: In this study, we showed that the treatment of recalcitrant pseudophakic cystoid macular edema with scleral fixated fluocinolone implant in eyes with disruption of the iris-lens diaphragm provides good anatomical and functional results with a reasonable safety profile over 24 months in eyes where pseudophakic cystoid macular edema is otherwise difficult to treat and often left untreated.


Assuntos
Edema Macular , Fluocinolona Acetonida/análogos & derivados , Humanos , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Estudos Prospectivos , Pirimidinas , Estudos Retrospectivos , Esclera/cirurgia
13.
BMC Ophthalmol ; 22(1): 138, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35337287

RESUMO

PURPOSE: Choroidal neovascularizations (CNV) are partially stabilized through a coverage of pericytes leading to a partial anti-VEGF resistence. Drugs licensed for neovascular AMD (nAMD) do not take this mechanical and growth factor-driven CNV stability into account. The purpose of this work was to see if inhibiting the mammalian target of rapamycin (mTOR) may successfully block angiogenic cellular pathways in primary human retinal pericytes in an in vitro model of nAMD. METHODS: The mTOR inhibitor rapamycin was used to treat human retinal pericytes (HRP) at doses ranging from 0.005 to 15 g/ml. A modified metabolism-based XTT-Assay was used to assess toxicity and anti-proliferative effects. A scratch wound experiment showed the effects on migration. On Cultrex basement membrane gels, the influence of rapamycin on the development of endothelial cell capillary-like structures by human umbilical vein vascular endothelial cells (HUVEC) in the absence and presence of pericytes was investigated. RESULTS: Rapamycin showed no signs of toxicity within its range of solubility. The drug showed dose dependent anti-proliferative activity and inhibited migration into the scratch wound. Endothelial cell tube formation in a HUVEC monoculture was effectively inhibited at 45%. A co-culture of HUVEC with pericytes on Cultrex induced endothelial tube stabilization but was disrupted by the addition of rapamycin leading to degradation of 94% of the tubes. CONCLUSIONS: Rapamycin allows for an efficient modulation of aspects of angiogenesis in pericytes via mTOR-modulation in vitro. Further studies are needed to elucidate whether rapamycin may have an impact on CNV in nAMD in vivo.


Assuntos
Neovascularização de Coroide , Degeneração Macular Exsudativa , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Células Endoteliais/metabolismo , Humanos , Pericitos/metabolismo , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/farmacologia , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológico
14.
Ophthalmologica ; 245(4): 315-322, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35344964

RESUMO

INTRODUCTION: This post hoc analysis applies a fixed dosing stratification approach to patient-level brolucizumab data from the phase III HAWK and HARRIER trials to determine the proportion of patients who would have been assigned to fixed dosing regimens with treatment intervals of 8, 12, or 16 weeks (q8w, q12w, or q16w) based on the presence/absence of disease activity (DA) following the loading phase. The analysis also simulates central subfield thickness (CSFT) data to estimate the anatomical outcomes if the patients had been thus assigned. Of note, the limitations of this analysis include the post hoc nature of the work and the inability to directly compare HAWK and HARRIER with TENAYA and LUCERNE due to the differences in design. DESIGN: This study was a post hoc modelling analysis of patient-level data. METHODS: Using patient-level data from HAWK and HARRIER, patients (n = 730) were allocated to a fixed q16w, q12w, or q8w regimen based on assessment of DA at weeks 16 and 20. Two definitions of DA were used: DA 1, based on a phase II study of faricimab, and DA 2, a definition derived from common clinical consideration including visual acuity and anatomical changes. CSFT simulations were performed using a pharmacokinetic/pharmacodynamic model describing CSFT response to anti-VEGF treatment. Outcome measures were modelled patient allocation to fixed regimens and mean CSFT reduction. RESULTS: Using DA definitions 1 and 2, respectively, 78% and 76% of patients in the brolucizumab arm were allocated to a greater than or equal to q12w regimen, and 56% and 52% were allocated to a q16w regimen. Mean reduction in CSFT was similar between the two study drugs with both DA definition assumptions. CONCLUSIONS: This analysis demonstrates the potential durability of action and effectiveness of brolucizumab.


Assuntos
Degeneração Macular Exsudativa , Humanos , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados , Injeções Intravítreas , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológico
15.
Graefes Arch Clin Exp Ophthalmol ; 259(5): 1289-1296, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33386963

RESUMO

PURPOSE: Long total waiting times (TWT) experienced by patients during a clinic visit have a significant adverse effect on patient's satisfaction. Our aim was to use big data simulations of a patient scheduling calendar and its effect on TWT in a general ophthalmology clinic. Based on the simulation, we implemented changes to the calendar and verified their effect on TWT in clinical practice. DESIGN AND METHODS: For this retrospective simulation study, we generated a discrete event simulation (DES) model based on clinical timepoints of 4.401 visits to our clinic. All data points were exported from our clinical warehouse for further processing. If not available from the electronic health record, manual time measurements of the process were used. Various patient scheduling models were simulated and evaluated based on their reduction of TWT. The most promising model was implemented into clinical practice in 2017. RESULTS: During validation of our simulation model, we achieved a high agreement of mean TWT between the real data (229 ± 100 min) and the corresponding simulated data (225 ± 112 min). This indicates a high quality of the simulation model. Following the simulations, a patient scheduling calendar was introduced, which, compared with the old calendar, provided block intervals and extended time windows for patients. The simulated TWT of this model was 153 min. After implementation in clinical practice, TWT per patient in our general ophthalmology clinic has been reduced from 229 ± 100 to 183 ± 89 min. CONCLUSION: By implementing a big data simulation model, we have achieved a cost-neutral reduction of the mean TWT by 21%. Big data simulation enables users to evaluate variations to an existing system before implementation into clinical practice. Various models for improving patient flow or reducing capacity loads can be evaluated cost-effectively.


Assuntos
Oftalmologia , Instituições de Assistência Ambulatorial , Agendamento de Consultas , Big Data , Humanos , Estudos Retrospectivos
16.
Graefes Arch Clin Exp Ophthalmol ; 259(12): 3655-3664, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34216254

RESUMO

PURPOSE: As the number of intravitreal injections (IVI) increases annually, this study aimed to assess the anatomical and functional outcomes following rhegmatogenous retinal detachment (RRD) surgery for IVI-associated RRD (IVARD). METHODS: All non-vitrectomized eyes developing IVARD since 2007 in two European vitreoretinal centers (Department of Ophthalmology, LMU Munich, Germany, and Eye Clinic Luigi Sacco, University of Milan, Milan, Italy) were included. Main outcomes were primary and secondary retinal attachment rate after surgery, rate of proliferative vitreoretinopathy (PVR), and final functional result. Ten years of incidence rates per injection were calculated for one center. RESULTS: Fifty-two eyes of 52 patients comprised the study. Primary anatomic success rate was 83% (n = 43) and secondary 96% (n = 50). PVR was observed in all uveitic eyes (n = 3), in eyes with postoperative cystoid macular edema (n = 2), and in 8 of 9 eyes that received the dexamethasone implant (DEX). Age, number of prior injections, duration of symptoms, or time between last IVI and RRD did not show any statistically significant differences with regard to presence of PVR or not. Mean BCVA improved in 28 cases, remained stable in 16 cases, and worsened in 8 cases. The RRD incidence rate was statistically significant higher for DEX and ocriplasmin compared with that for anti-VEGF agents. CONCLUSION: The anatomical result after one surgical intervention seems acceptable, but the final visual outcome remains rather poor, because of the underlying macular disease. In our population, injection with DEX is associated with higher IVARD rate, presence and development of PVR, and recurrent RRD in comparison with anti-VEGF agents.


Assuntos
Descolamento Retiniano , Humanos , Injeções Intravítreas , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/epidemiologia , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Acuidade Visual , Vitrectomia
17.
BMC Ophthalmol ; 21(1): 4, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402147

RESUMO

BACKGROUND: To study the enlargement rate of primary geographic atrophy (GA) before and after diagnosis of a secondary choroidal neovascularization (CNV) treated with anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Five hundred twenty-two consecutive eyes with primary GA were screened for the development of a complicating secondary CNV. Geographic atrophy was measured on blue autofluorescence (BAF) by two readers and calculated into mean growth rate before and after CNV diagnosis. RESULTS: Ten eyes of six patients were included in the study (six study eyes with GA complicated by CNV, four GA only partner eyes). Follow-up was 1.42 ± 0.48 years before and 3.64 ± 2.73 years after CNV. There was no significant difference between mean growth rate before and after CNV (1.58 ± 0.99 vs. 1.39 ± 0.65 mm2/year; p = 0.44) or between study and partner eyes (p = 0.86). Over a mean time of 3.64 ± 2.73 years, a mean of 8.3 ± 2.8 anti-VEGF injections were given. No correlation between the amount of anti-VEGF injections and change in growth rate could be observed (r = 0.58; p = 0.23). CONCLUSION: In this pilot study, primary GA enlargement did not seem to be influenced by a secondary CNV. No association between the intensity of anti-VEGF treatment and changes in atrophy enlargement rates were found. Further studies with larger sample sizes are warranted.


Assuntos
Neovascularização de Coroide , Atrofia Geográfica , Inibidores da Angiogênese , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/etiologia , Angiofluoresceinografia , Atrofia Geográfica/induzido quimicamente , Atrofia Geográfica/diagnóstico , Atrofia Geográfica/tratamento farmacológico , Humanos , Injeções Intravítreas , Projetos Piloto , Ranibizumab/uso terapêutico , Tomografia de Coerência Óptica
18.
Klin Monbl Augenheilkd ; 238(8): 868-874, 2021 Aug.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-33853190

RESUMO

BACKGROUND: Evaluation of the three currently most common techniques for intraocular lens (IOL) sclera fixation: (1) Prolene suture with Hoffman sclera pocket (2) four-point GoreTex suture technique (3) sutureless flanged intrascleral IOL fixation with double-needle ("Yamane") technique. MATERIAL AND METHODS: Retrospective, clinical case series (chart review) at the Department of Ophthalmology, Ludwig-Maximilians-University (LMU), Munich, Germany. Enrolled in the study were 51 patients with 55 eyes. Best-corrected visual acuity (BCVA); manifest refraction (OR); corneal tomography (central corneal thickness, CCT); biometry; central macular thickness (CMT) by optical coherence tomography (OCT); intraocular pressure (IOP); and IOL type and IOL power were recorded and compared prior to and 3 - 12 months post IOL sclera fixation surgery. Pre- and postsurgery difference analysis was performed by Wilcoxon rank sum testing (z). RESULTS: Intrascleral fixation by GoreTex suture was performed in 14 (25.5%) eyes, by Prolene suture in 19 (34.5%,) and by Yamane technique in 22 (40.0%) eyes. Within the 3 - 12 months follow-up post scleral fixation, a total of 2 (14.3%) eyes from the GoreTex, 3 (15.8%) from the Prolene and 1 (4.5%) eye from the Yamane group required refixation. Pre- and post-surgery analysis revealed a statistically significant difference in the total patient population BCVA (exact Wilcoxon test: z = - 3.202; p = 0.001; n = 55) and the Yamane subgroup (exact Wilcoxon test: z = - 2.068; p = 0.001; n = 22). The GoreTex (n = 14) and Prolene (n = 19) subgroups revealed no statistically significant differences versus preoperative baseline. Across groups, there was no statistically significant difference in IOP, CMT, and CCT. No retinal complications were observed, neither intraoperatively nor during follow-up. CONCLUSION: The volume of IOL revision surgery is increasing. Often, the only option left for visual rehabilitation is scleral IOL fixation. All three scleral fixation techniques studied demonstrated a good safety profile with no statistically significant impact on IOP, CMT, CCT, but with a notable revision rate. Visual rehabilitation to preoperative baseline levels (GoreTex [n = 14] and Prolene [n = 19]) and a statistically significant increase in visual acuity (total cohort [n = 55] and Yamane [n = 22]) seems possible. Unlike iris fixation, scleral fixation is surgically more complex and the surgeon must master a steeper learning curve.


Assuntos
Lentes Intraoculares , Esclera , Humanos , Implante de Lente Intraocular , Estudos Retrospectivos , Esclera/diagnóstico por imagem , Esclera/cirurgia , Acuidade Visual
19.
Graefes Arch Clin Exp Ophthalmol ; 258(10): 2151-2161, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32583283

RESUMO

INTRODUCTION: Persisting macular holes (PMH) after surgical release of any epiretinal traction of the vitreous and adjacent membrane may rely on secondary firm adhesions between the retracted retina and adjacent retinal pigment epithelium. Secondary application of subretinal (SR)-fluid may release these adhesions followed by an anatomical closure. METHODS: Twelve surgeons applied in a consecutive case series SR-fluid in 41 eyes with PMH and reported retrospectively their initial surgical, anatomical and functional experience with this approach. RESULTS: The mean duration of the MH prior to SR-fluid application was 17 months (6-96 months). The mean age of the patients at the time of surgery was 72 years (54-88). The mean preoperative aperture diameter of the opening was 1212 µm (239-4344 µm), base diameter 649 µm (SD 320 µm). The mean preoperative BCVA prior to surgery was 0.1 (0.01-0.3). All patients (41/41) complained about reduced BCVA and a significant central scotoma (negative scotoma) in their central field of vision. The secondary closure rate for our PMH was 85.36% (35 out of 41 eyes) at 6 weeks after surgery. The postoperative BCVA improved to 0.22 (0.02-0.5). The application of SR-fluid was not associated with major intraoperative adverse effects. CONCLUSION: Remaining SR-adhesions may inhibit PMH closure. Their release by application of SR-fluid will lead to a fast and immediate anatomical closure in many cases without serious adverse events.


Assuntos
Perfurações Retinianas , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/cirurgia , Estudos Retrospectivos , Líquido Sub-Retiniano/diagnóstico por imagem , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual , Vitrectomia
20.
Klin Monbl Augenheilkd ; 237(12): 1420-1428, 2020 Dec.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-33285587

RESUMO

Due to their widespread use among the population and their wide range of functions and sensors, smartphones are suitable for data collection for medical purposes. App-supported input masks, patient diaries, and patient information systems, mobile access to the patient file as well as telemedical services will continue to find their way into our field of expertise in the future. In addition, the use of smartphone sensors (GPS and motion sensors, touch display, microphone) and coupling possibilities with biosensors (for example with Continuous Glucose Monitoring [CGM] systems), advanced camera technology, the possibility of regular and appointment independent checking of the visual system (visual acuity/contrast vision) as well as real-time data transfer offer interesting possibilities for patient treatment and clinical research. The present review deals with the current status and future perspectives of smartphone-based data collection and possible applications in ophthalmology.


Assuntos
Oftalmologia , Smartphone , Glicemia , Automonitorização da Glicemia , Coleta de Dados , Humanos
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