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1.
Klin Monbl Augenheilkd ; 241(8): 944-951, 2024 Aug.
Article in English, German | MEDLINE | ID: mdl-39146577

ABSTRACT

Disorders of blood coagulation can lead to manifest spontaneous bleeding and an increased risk of bleeding during surgical procedures and interventions. Pathophysiologically, a distinction can be made between defects in primary haemostasis, which lead to impaired platelet adhesion and platelet aggregation, and disorders of secondary (plasmatic) haemostasis, which are characterised by impaired fibrin formation or fibrin stabilisation. Aetiologically, a distinction can be made between rare genetically-determined hereditary defects and common acquired coagulation disorders, which may be based on different pathomechanisms. This overview is intended to provide ophthalmic surgeons with a basis for the perioperative management of patients with genetically determined coagulation disorders undergoing ophthalmic surgery. As there are no specific recommendations in this regard, the recommendations are based on the procedure for other surgical interventions, taking into account the specific bleeding risk associated with ophthalmic surgery.


Subject(s)
Blood Coagulation Disorders , Ophthalmologic Surgical Procedures , Perioperative Care , Humans , Ophthalmologic Surgical Procedures/methods , Ophthalmologic Surgical Procedures/adverse effects , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/etiology , Perioperative Care/methods , Blood Loss, Surgical/prevention & control
2.
J Clin Med ; 13(15)2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39124626

ABSTRACT

Background: To longitudinally investigate the impact of best-corrected visual acuity (BCVA), non-modifiable risk factors, modifiable habits, and disease course on the vision-related quality of life (VRQOL) of patients with central serous chorioretinopathy (CSCR). Methods: We longitudinally enrolled 109 CSCR patients and 42 non-diseased control participants from our clinic. In addition to clinical examination, the National Eye Institute Visual Function Questionnaire (NEI-VFQ-39) was employed for assessments, along with questions pertaining to various aspects of lifestyle habits. Alongside the cross-sectional analyses, the VRQOL of CSCR patients was tracked longitudinally over one year. Results: Consistent with prior studies, CSCR patients reported a lower VRQOL compared to non-diseased participants (79.3 ± 14.1 for CSCR and 92.6 ± 7.6 for CTRL; p < 0.0001), but fared better than those with other ocular conditions. No significant associations were observed between BCVA, any non-modifiable risk factors, or interventions, and VRQOL, both in cross-sectional and longitudinal contexts (cross-sectional BCVA with VRQOL: Pearson r correlation 0.173, p = 0.072). Among modifiable habits, sleep duration (p = 0.036), perceived quality of sleep rhythm (p = 0.006), hours of physical activity (p = 0.036), and the presence of non-ocular conditions (p = 0.001) were significantly correlated with VRQOL. Notably, enhanced sleep duration (+4.232 vs. -0.041 non-enhanced at 3 months, p = 0.033) and higher perceived quality of sleep rhythm (+6.248 vs. +0.094 non-higher, p = 0.009) showed a positive correlation with improved VRQOL over time. Conclusions: The study reveals that VRQOL has minimal dependence on BCVA or other clinical factors, suggesting that patient-reported outcome measures (PROMs) could serve as alternative endpoints in clinical studies for more holistic patient welfare assessment. Furthermore, the strong correlations between VRQOL and modifiable lifestyle habits indicate potential therapeutic value in targeting these areas for intervention.

3.
J Clin Med ; 13(14)2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39064181

ABSTRACT

Background: This study aimed to evaluate the potential of human-machine interaction (HMI) in a deep learning software for discerning the malignancy of choroidal melanocytic lesions based on fundus photographs. Methods: The study enrolled individuals diagnosed with a choroidal melanocytic lesion at a tertiary clinic between 2011 and 2023, resulting in a cohort of 762 eligible cases. A deep learning-based assistant integrated into the software underwent training using a dataset comprising 762 color fundus photographs (CFPs) of choroidal lesions captured by various fundus cameras. The dataset was categorized into benign nevi, untreated choroidal melanomas, and irradiated choroidal melanomas. The reference standard for evaluation was established by retinal specialists using multimodal imaging. Trinary and binary models were trained, and their classification performance was evaluated on a test set consisting of 100 independent images. The discriminative performance of deep learning models was evaluated based on accuracy, recall, and specificity. Results: The final accuracy rates on the independent test set for multi-class and binary (benign vs. malignant) classification were 84.8% and 90.9%, respectively. Recall and specificity ranged from 0.85 to 0.90 and 0.91 to 0.92, respectively. The mean area under the curve (AUC) values were 0.96 and 0.99, respectively. Optimal discriminative performance was observed in binary classification with the incorporation of a single imaging modality, achieving an accuracy of 95.8%. Conclusions: The deep learning models demonstrated commendable performance in distinguishing the malignancy of choroidal lesions. The software exhibits promise for resource-efficient and cost-effective pre-stratification.

4.
Article in English | MEDLINE | ID: mdl-38842593

ABSTRACT

PURPOSE: To investigate the xenobiotic profiles of patients with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) intravitreal therapy (IVT) to identify biomarkers indicative of clinical phenotypes through advanced AI methodologies. METHODS: In this cross-sectional observational study, we analyzed 156 peripheral blood xenobiotic features in a cohort of 46 nAMD patients stratified by choroidal neovascularization (CNV) control under anti-VEGF IVT. We employed Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for measurement and leveraged an AI-driven iterative Random Forests (iRF) approach for robust pattern recognition and feature selection, aligning molecular profiles with clinical phenotypes. RESULTS: AI-augmented iRF models effectively refined the metabolite spectrum by discarding non-predictive elements. Perfluorooctanesulfonate (PFOS) and Ethyl ß-glucopyranoside were identified as significant biomarkers through this process, associated with various clinically relevant phenotypes. Unlike single metabolite classes, drug metabolites were distinctly correlated with subretinal fluid presence. CONCLUSIONS: This study underscores the enhanced capability of AI, particularly iRF, in dissecting complex metabolomic data to elucidate the xenobiotic landscape of nAMD and environmental impact on the disease. The preliminary biomarkers discovered offer promising directions for personalized treatment strategies, although further validation in broader cohorts is essential for clinical application.

5.
Invest Ophthalmol Vis Sci ; 65(4): 5, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38558091

ABSTRACT

Purpose: We aimed to determine the impact of artificial sweeteners (AS), especially saccharin, on the progression and treatment efficacy of patients with neovascular age-related macular degeneration (nAMD) under anti-vascular endothelial growth factor (anti-VEGF-A) treatment. Methods: In a cross-sectional study involving 46 patients with nAMD undergoing intravitreal anti-VEGF therapy, 6 AS metabolites were detected in peripheral blood using liquid chromatography - tandem mass spectrometry (LC-MS/MS). Disease features were statistically tested against these metabolite levels. Additionally, a murine choroidal neovascularization (CNV) model, induced by laser, was used to evaluate the effects of orally administered saccharin, assessing both imaging outcomes and gene expression patterns. Polymerase chain reaction (PCR) methods were used to evaluate functional expression of sweet taste receptors in a retinal pigment epithelium (RPE) cell line. Results: Saccharin levels in blood were significantly higher in patients with well-controlled CNV activity (P = 0.004) and those without subretinal hyper-reflective material (P = 0.015). In the murine model, saccharin-treated mice exhibited fewer leaking laser scars, lesser occurrence of bleeding, smaller fibrotic areas (P < 0.05), and a 40% decrease in mononuclear phagocyte accumulation (P = 0.06). Gene analysis indicated downregulation of inflammatory and VEGFR-1 response genes in the treated animals. Human RPE cells expressed taste receptor type 1 member 3 (TAS1R3) mRNA and reacted to saccharin stimulation with changes in mRNA expression. Conclusions: Saccharin appears to play a protective role in patients with nAMD undergoing intravitreal anti-VEGF treatment, aiding in better pathological lesion control and scar reduction. The murine study supports this observation, proposing saccharin's potential in mitigating pathological VEGFR-1-induced immune responses potentially via the RPE sensing saccharin in the blood stream.


Subject(s)
Choroidal Neovascularization , Macular Degeneration , Humans , Mice , Animals , Vascular Endothelial Growth Factor Receptor-1 , Saccharin/therapeutic use , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Sweetening Agents , Cross-Sectional Studies , Chromatography, Liquid , Tandem Mass Spectrometry , Choroidal Neovascularization/metabolism , Macular Degeneration/metabolism , RNA, Messenger/genetics , Intravitreal Injections , Angiogenesis Inhibitors/therapeutic use
6.
J Clin Med ; 13(6)2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38542043

ABSTRACT

Background: To report on the outcome of intravitreal brolucizumab compared to aflibercept in patients with diabetic macular edema (DME). Methods: Prospective, observational, study in 35 eyes of 24 patients with a loading dose of five injections of 6 mg brolucizumab every 6 weeks (q6w, treatment-naïve eyes) or a minimum of two injections of brolucizumab q6w after the switch (recalcitrant DME eyes), followed by a treat and extend (T&E) regimen. The results were compared with 40 eyes of 31 DME patients who were treated with aflibercept. The data were obtained from the Berlin Macula Registry. The primary outcome measure was the change in best-corrected visual acuity (BCVA) at week 36. Secondary outcome measures were the change in central retinal thickness (CRT) and the treatment intervals until week 36. Results: BCVA increased significantly in treatment-naïve DME eyes treated with either brolucizumab (+0.12 logMAR, +6.4 letters, p = 0.03) or aflibercept (+0.19 logMAR, +9.5 letters, p = 0.001). In recalcitrant DME eyes, BCVA also increased significantly after switching to brolucizumab (+0.1 logMAR, +5 letters, p = 0.006) or aflibercept (+0.11 logMAR, +5.5 letters, p = 0.02). All treatment-naïve and recalcitrant DME eyes had a significant decrease in CRT after treatment with brolucizumab (p = 0.001 and p < 0.001) or aflibercept (p = 0.0002 and p = 0.03). At week 36, the mean treatment interval for brolucizumab was 11.3 weeks, while for aflibercept, it was 6.5 weeks for treatment-naïve eyes and 9.3 weeks vs. 5.3 weeks for pretreated eyes. Conclusions: In routine clinical practice, patients with treatment-naïve and recalcitrant DME showed a favorable response to brolucizumab and aflibercept therapy, with a reduced injection frequency after brolucizumab treatment.

7.
Eur J Ophthalmol ; 34(5): 1532-1540, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38263930

ABSTRACT

BACKGROUND: Central Serous Chorioretinopathy (CSCR) manifests as fluid accumulation between the neurosensory retina and the retinal pigment epithelium (RPE). Elevated levels of steroid hormones have been implicated in CSCR pathogenesis. This investigation aims to delineate the gene expression patterns of CSCR-associated risk and steroid receptors across human choroidal cell types and RPE cells to discern potential underlying mechanisms. METHODS: This study utilized a comprehensive query of transcriptomic data derived from non-pathological human choroid and RPE cells. FINDINGS: CSCR-associated genes such as PTPRB, CFH, and others are predominantly expressed in the choroidal endothelium as opposed to the RPE. The androgen receptor, encoded by the AR gene, demonstrates heightened expression in the macular endothelium compared to peripheral regions, unlike other steroid receptor genes. AR-expressing endothelial cells display an augmented responsiveness to Transforming growth factor beta (TGF-ß), indicating a propensity towards endothelial to mesenchymal transition (endMT) transcriptional profiling. INTERPRETATION: These results highlight the proclivity of CSCR to manifest primarily within the choroidal vasculature rather than the RPE, suggesting its categorization as a vascular eye disorder. This study accentuates the pivotal role of androgenic steroids, in addition to glucocorticoids. The observed linkage to TGF-ß-mediated endMT provides a potential mechanistic insight into the disease's etiology.


Subject(s)
Central Serous Chorioretinopathy , Choroid , Gene Expression Profiling , Receptors, Androgen , Retinal Pigment Epithelium , Humans , Central Serous Chorioretinopathy/genetics , Central Serous Chorioretinopathy/metabolism , Central Serous Chorioretinopathy/diagnosis , Choroid/blood supply , Choroid/metabolism , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Retinal Pigment Epithelium/metabolism , Retinal Pigment Epithelium/pathology , Transcriptome , Gene Expression Regulation , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta/genetics , Endothelium, Vascular/metabolism
8.
Int J Mol Sci ; 24(12)2023 Jun 19.
Article in English | MEDLINE | ID: mdl-37373474

ABSTRACT

There is early evidence of extraocular systemic signals effecting function and morphology in neovascular age-related macular degeneration (nAMD). The prospective, cross-sectional BIOMAC study is an explorative investigation of peripheral blood proteome profiles and matched clinical features to uncover systemic determinacy in nAMD under anti-vascular endothelial growth factor intravitreal therapy (anti-VEGF IVT). It includes 46 nAMD patients stratified by the level of disease control under ongoing anti-VEGF treatment. Proteomic profiles in peripheral blood samples of every patient were detected with LC-MS/MS mass spectrometry. The patients underwent extensive clinical examination with a focus on macular function and morphology. In silico analysis includes unbiased dimensionality reduction and clustering, a subsequent annotation of clinical features, and non-linear models for recognition of underlying patterns. The model assessment was performed using leave-one-out cross validation. The findings provide an exploratory demonstration of the link between systemic proteomic signals and macular disease pattern using and validating non-linear classification models. Three main results were obtained: (1) Proteome-based clustering identifies two distinct patient subclusters with the smaller one (n = 10) exhibiting a strong signature for oxidative stress response. Matching the relevant meta-features on the individual patient's level identifies pulmonary dysfunction as an underlying health condition in these patients. (2) We identify biomarkers for nAMD disease features with Aldolase C as a putative factor associated with superior disease control under ongoing anti-VEGF treatment. (3) Apart from this, isolated protein markers are only weakly correlated with nAMD disease expression. In contrast, applying a non-linear classification model identifies complex molecular patterns hidden in a high number of proteomic dimensions determining macular disease expression. In conclusion, so far unconsidered systemic signals in the peripheral blood proteome contribute to the clinically observed phenotype of nAMD, which should be examined in future translational research on AMD.


Subject(s)
Angiogenesis Inhibitors , Macular Degeneration , Humans , Angiogenesis Inhibitors/therapeutic use , Ranibizumab/therapeutic use , Vascular Endothelial Growth Factor A/metabolism , Proteome , Prospective Studies , Chromatography, Liquid , Cross-Sectional Studies , Proteomics , Tandem Mass Spectrometry , Macular Degeneration/drug therapy , Phenotype
9.
J Vitreoretin Dis ; 7(1): 8-15, 2023.
Article in English | MEDLINE | ID: mdl-37008402

ABSTRACT

Purpose: To compare intravitreal nesvacumab (anti-angiopoietin-2) + aflibercept vs intravitreal aflibercept injection (IAI) in neovascular age-related macular degeneration (nAMD). Methods: Eyes were randomized (1:2:3) to nesvacumab 3 mg + aflibercept 2 mg (LD combo), nesvacumab 6 mg + aflibercept 2 mg (HD combo), or IAI 2 mg at baseline, week 4, and week 8. The LD combo was continued every 8 weeks (q8w). At week 12, the HD combo was re-randomized to q8w or every 12 weeks (q12w) and IAI was re-randomized to q8w, q12w, or HD combo q8w through week 32. Results: The study comprised 365 eyes. At week 12, the mean best-corrected visual acuity (BCVA) gains from baseline were similar in the LD combo group, HD combo group, and IAI group (5.2 letters, 5.6 letters, and 5.4 letters, respectively); the mean central subfield thickness (CST) reductions were similar (182.2 µm, 200.0 µm, and 178.6 µm, respectively). The mean changes in BCVA and CST through week 36 were similar across groups. At week 12, complete retinal fluid resolution was observed in 49.1% (LD combo), 50.8% (HD combo), and 43.6% (IAI) of eyes; the proportions with a CST of 300 µm or less were similar across groups. Numerical trends at week 32 toward complete retinal fluid resolution with combination treatment were not maintained at week 36. Serious ocular adverse events were infrequent and comparable across groups. Conclusions: In nAMD, nesvacumab + aflibercept showed no additional BCVA or CST benefit over IAI monotherapy.

11.
Graefes Arch Clin Exp Ophthalmol ; 261(6): 1681-1690, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36633668

ABSTRACT

PURPOSE: Bevacizumab, ranibizumab, and aflibercept are commonly used to treat neovascular age-related macular degeneration (nAMD). The results of various interventional, mostly randomized head-to-head studies, indicate statistical non-inferiority of these three drugs. The results of these studies are often interpreted as the three drugs being freely interchangeable, resulting in some health systems to pressure ophthalmologists to preferentially use the less expensive bevacizumab. This study analyzes switching from aflibercept or ranibizumab to bevacizumab and back under real-world conditions in order to investigate the assumption of interchangeability of the drugs. METHODS: Treatment data of IVT patients with diagnosed nAMD were extracted from the clinical Berlin Macular Registry database. Patients who underwent a drug switch from aflibercept or ranibizumab to bevacizumab were subject of this study. Statistical comparisons were pre-planned for best corrected visual acuity, central retinal thickness, macular volume, and length of injection interval. Additional endpoints were analyzed descriptively. RESULTS: Mean visual acuity decreased from 0.57 ± 0.05 under aflibercept/ranibizumab to 0.68 ± 0.06 logMAR after the switch (P = 0.001; N = 63). CRT increased from 308 ± 11 µm to 336 ± 16 µm (P = 0.011; N = 63). About half of the subjects were switched back: visual acuity increased from 0.69 ± 0.08 logMAR to 0.58 ± 0.09 logMAR (N = 26). CRT decreased from 396 ± 28 to 337 ± 20 µm (N = 28). CONCLUSION: The data provides real-world evidence that there is loss of visual acuity and an increase in retinal edema after switching to bevacizumab. Thus, the assumption of free interchangeability cannot be confirmed in this cohort.


Subject(s)
Macular Degeneration , Ranibizumab , Humans , Bevacizumab , Angiogenesis Inhibitors , Vascular Endothelial Growth Factor A , Berlin , Receptors, Vascular Endothelial Growth Factor , Registries , Macular Degeneration/drug therapy , Recombinant Fusion Proteins/therapeutic use , Intravitreal Injections , Treatment Outcome
12.
Ophthalmol Retina ; 7(3): 266-274, 2023 03.
Article in English | MEDLINE | ID: mdl-36087876

ABSTRACT

OBJECTIVE: To investigate the oncologic and functional outcomes of a large cohort of patients with a favorable stage of circumscribed and diffuse iris melanoma who underwent primary proton treatment and the risk factors related to initial tumor characteristics and the treatment field architecture. DESIGN: Retrospective, single-center, case study. PARTICIPANTS: We reviewed 225 patients with iris melanoma who were consecutively treated with proton beam therapy at our institution between 1998 and 2020. METHODS: We performed Kaplan-Meier time-to-event analyses and multivariate Cox proportional hazard analyses to identify the impacts of tumor characteristics and target volumes on oncologic and functional outcomes. MAIN OUTCOME MEASURES: We measured local tumor control, eye preservation rates, metastasis-free survival, cataract and glaucoma-directed surgery, intraocular pressure, and changes in visual acuity. RESULTS: Of the 192 patients with tumors confined to the iris (T1a-c) who underwent proton therapy as primary treatment, a total of 166 patients (mean age, 58.4 years; 88 women) with a minimum follow-up of 6 months were included. Multifocal or diffuse tumor spread was present in 77 (46.4%) patients. The median follow-up time was 54.0 (interquartile range, 27.4-91.8 months) months. Local recurrence occurred in 2 patients (1.2%) with circumscribed iris melanoma. Enucleation was a rare event (n = 5, 3%) and no patient developed metastatic disease. A large-treatment field (full aperture, involving > 10 clock hours) was identified as a risk factor for the development of secondary glaucoma (hazard ratio [HR], 6.3; P < 0.001) and subsequent surgical interventions (HR, 10.85; P < 0.001). The large-treatment field group showed a significant decline in visual acuity (logarithm of the minimum angle of resolution > 0.3; log-rank P < 0.0001), which was associated with secondary glaucoma (HR, 3.40; P = 0.002). CONCLUSIONS: Proton therapy provides an effective, noninvasive treatment option for patients with a favorable stage of iris melanoma. Irradiation of the anterior segment for up to 10 clock hours is associated with a low risk of the development of secondary glaucoma and vision loss. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.


Subject(s)
Glaucoma , Iris Neoplasms , Melanoma , Proton Therapy , Humans , Female , Middle Aged , Proton Therapy/adverse effects , Retrospective Studies , Melanoma/complications , Iris/pathology
15.
BMJ Open ; 12(6): e058266, 2022 06 15.
Article in English | MEDLINE | ID: mdl-35705348

ABSTRACT

OBJECTIVES: In order to better understand the continued barriers to the provision of vascular endothelial inhibitor therapy, this study aims to investigate patients' experiences with neovascular age-related macular degeneration (nvAMD) in Germany during the injection process and how they deal with it. DESIGN AND PARTICIPANTS: This analysis is part of the qualitative arm of a wider mixed-methods study. We recruited participants all over Germany via ophthalmologists, eye clinics, general practitioners, care bases and support groups between June 2018 and December 2020 and selected a subsample of study participants with nvAMD who were either undergoing or had previously undergone vascular endothelial growth factor inhibitor therapy. We conducted narrative, semistructured, face-to-face interviews at the participants' homes, which were audio-recorded. The interviews were thematically analysed. RESULTS: Twenty-two participants were included in this analysis. Experiencing neovascular macular degeneration was dominated by the injection experience. Study participants perceived the treatment with vascular endothelial inhibitor injections as uncomfortable, and they described undergoing varying levels of anxiety during the whole injection process. After some years of receiving multiple injections, the pain and not experiencing any positive effects made participants with significant vision loss want to discontinue therapy. Furthermore, they narrated negative injection experiences in association with their interactions with medical staff and doctors. CONCLUSION: Although time in the medical setting is limited, efficient and good doctor-patient relationships seem crucial for satisfying care experiences. A respectful and humane relationship may be one key to achieving treatment adherence.


Subject(s)
Intravitreal Injections , Macular Degeneration , Wet Macular Degeneration , Angiogenesis Inhibitors/therapeutic use , Germany , Humans , Intravitreal Injections/psychology , Macular Degeneration/drug therapy , Macular Degeneration/psychology , Qualitative Research , Ranibizumab , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/therapeutic use , Wet Macular Degeneration/drug therapy , Wet Macular Degeneration/psychology
16.
J Ophthalmol ; 2022: 2659714, 2022.
Article in English | MEDLINE | ID: mdl-35369000

ABSTRACT

Background: To report on the short-term outcome of intravitreal brolucizumab in patients with neovascular age-related macular degeneration (nAMD). Methods: This is a prospective, interventional, monocentric study on 10 eyes of 10 patients with a treatment-naïve neovascular AMD. Patients were treated according to the HAWK and HARRIER trials. After loading with 3 monthly injections, eyes received an injection 12 weeks after the upload (q12w) or were adjusted to an 8 week interval (q8w), if disease activity was present 8 weeks after the upload. Main outcome measures were the change in central retinal thickness (CRT) assessed by spectral domain optical coherence tomography (SD-OCT), the change in macular neovascularization (MNV) size on optical coherence tomography angiography (OCTA), and the change in best corrected visual acuity (BCVA) 8 and 12 weeks after the upload. We further assessed clinical parameters that predict the treatment response at baseline based on the need of q8w or q12w injections after the upload. Results: CRT decreased significantly from 461.7 ± 82.9 µm to 343.6 ± 74.3 µm (p=0.004) 12 weeks after the upload. The MNV size decreased significantly from 0.85 ± 1.1 to 0.75 ± 1.2 mm2 (p=0.022). BCVA improved from 0.67 ± 0.4 to 0.55 ± 0.4logMAR but without statistical significance. MNV size in eyes on q12w was considerably smaller compared to that in eyes on q8w (0.54 ± 0.7 mm2 vs. 1.98 ± 2.4 mm2). The percentage of eyes without any persistent fluid was 70% (7/10 eyes). Conclusions: Brolucizumab appears to be a valuable tool for the management of patients with nAMD. Furthermore, MNV size at baseline might serve as an early predictor of treatment response.

17.
Retina ; 42(6): 1111-1120, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35234673

ABSTRACT

PURPOSE: The purpose of this study was to compare intravitreal nesvacumab (anti-angiopoietin 2) plus aflibercept with intravitreal aflibercept injection (IAI) in diabetic macular edema. METHODS: The eyes (n = 302) were randomized (1:2:3) to nesvacumab 3 mg + aflibercept 2 mg (LD combo), nesvacumab 6 mg + aflibercept 2 mg (HD combo), or IAI 2 mg at baseline, Weeks 4 and 8. LD combo continued every 8 weeks (q8w). HD combo was rerandomized at Week 12 to q8w or every 12 weeks (q12w); IAI to q8w, q12w, or HD combo q8w through Week 32. RESULTS: Week 12 best-corrected visual acuity gains for LD and HD combo versus IAI were 6.8, 8.5, and 8.8 letters; Week 36 changes were similar. Central subfield retinal thickness reductions at Week 12 were -169.4, -184.0, and -174.6 µm (nominal P = 0.0183, HD combo vs. IAI); Week 36 reductions for LD combo and HD combo q8w and q12w versus IAI were -210.4, -223.4, and -193.7 versus -61.9 µm (nominal P < 0.05). At Week 12, 13.3% and 21.3% versus 15.2% had ≥2-step Diabetic Retinopathy Severity Scale improvement (LD and HD combos vs. IAI) and 59.6% and 66.3% versus 53.7% had complete foveal center fluid resolution. Safety was comparable across groups. CONCLUSION: Nesvacumab + aflibercept demonstrated no additional visual benefit over IAI. Anatomic improvements with HD combo may warrant further investigation.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Macular Edema , Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal/therapeutic use , Diabetic Retinopathy/complications , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/drug therapy , Double-Blind Method , Humans , Intravitreal Injections , Macular Edema/diagnosis , Macular Edema/drug therapy , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Vascular Endothelial Growth Factor A , Visual Acuity
18.
Retina ; 42(2): 236-243, 2022 02 01.
Article in English | MEDLINE | ID: mdl-35050927

ABSTRACT

PURPOSE: Retinal manifestations have been described in COVID-19 patients, but it is unknown whether SARS-CoV-2, the causal agent in COVID-19, can directly infect posterior ocular tissues. Here, we investigate SARS-CoV-2 host factor gene expression levels and their distribution across retinal and choroidal cell types. METHODS: Query of single-cell RNA sequencing data from human retina and choroid. RESULTS: We find no relevant expression of two key genes involved in SARS-CoV-2 entry, ACE2 and TMPRSS2, in retinal cell types. By contrast, scarce expression levels could be detected in choroidal vascular cells. CONCLUSION: Given the current understanding of viral host cell entry, these findings suggest a low vulnerability of the posterior eye segment to SARS-CoV-2 with a potential weak spot in the vasculature, which could play a putative causative role in ocular lesions in COVID-19 patients. This may qualify the vasculature of the human posterior eye segment as an in vivo biomarker for life-threatening vascular occlusions in COVID-19 patients.


Subject(s)
COVID-19/epidemiology , Eye Infections, Viral/virology , Gene Expression Regulation, Viral , Posterior Eye Segment/virology , SARS-CoV-2 , Serine Endopeptidases/genetics , Virus Internalization , COVID-19/virology , Eye Infections, Viral/epidemiology , Eye Infections, Viral/pathology , Humans , Posterior Eye Segment/pathology , RNA, Viral/genetics , Retinal Ganglion Cells/pathology , Retinal Ganglion Cells/virology , Serine Endopeptidases/biosynthesis
19.
Ophthalmologe ; 118(12): 1287-1300, 2021 Dec.
Article in German | MEDLINE | ID: mdl-34279712

ABSTRACT

Several eye diseases requiring surgical intervention occur predominantly in elderly. Therefore, there is a significant co-incidence with systemic co-morbidities, which often do require anti-coagulation. There are several approaches to influence hemostasis pharmacologically. The number of options has increased substantially due to introduction of new drugs. This article provides an overview on the option range and gives insight, why this is of importance from the perspective of internal medicine. In addition, the basic principles of adjusting the therapy is being reviewed. Furthermore, the pharmacological inhibition of hemostasis in the context of eye surgery is being discussed. Available literature is analyzed to understand the necessity to interrupt or change the anti-coagulation for eye surgery.


Subject(s)
Platelet Aggregation Inhibitors , Platelet Aggregation , Aged , Anticoagulants , Blood Coagulation , Hemostasis , Humans , Platelet Aggregation Inhibitors/adverse effects
20.
J Diabetes Res ; 2021: 8820216, 2021.
Article in English | MEDLINE | ID: mdl-33937416

ABSTRACT

PURPOSE: Diabetic macular edema (DME) is the most common cause of blindness in the working-age population. Spectral-domain optical coherence tomography (SD-OCT) allows detection and monitoring of the edema and a detailed analysis of the retinal structure. Hyperreflective foci (HF) are small, circumscribed lesions on OCT, and their origin is yet to be determined. Our study was aimed to shed light on HF pathophysiology, by analyzing their number and location in DME patients at baseline and after therapy. METHODS: A prospective, observational study on 59 eyes of 51 DME patients who were treated with antivascular endothelial growth factor (VEGF) therapy (VEGF group, n = 40 eyes) or dexamethasone implant (DEX group, n = 19). HF and hard exudates (HE) were discriminated by their appearance on fundus photographs and their size on OCT. Quantity and location of HF and HE were analyzed at baseline and after therapy. RESULTS: DME decreased in 75% of patients in the VEGF (455.5 µm vs. 380.8 µm, p = 0.02) and in 95% of patients in the DEX group (471.6 µm vs. 381.9 µm, p = 0.007). The number of foci decreased in 62.5% of patients after anti-VEGF (130.6 vs. 111.1, p = 0.07) and in 68% of patients after dexamethasone injection ((123.4 vs. 94.9, p = 0.02) 5.1). A subgroup of 15% of eyes, all treated with anti-VEGF, showed accumulation of larger HF in outer retinal layers to visible HE during DME resolution, whereas smaller HF, found in all retinal layers, remained unchanged. There was a trend towards a dynamic shift of the foci from inner to outer retinal layers. CONCLUSION: The dynamic rearrangement of the small HF and their slightly greater reduction after anti-inflammatory therapy suggest inflammatory cells as their origin, whereas larger HF in the outer retinal layers correspond to microexudates. Furthermore, we found a more favourable outcome in patients with HF after treatment with dexamethasone implants compared to anti-VEGF agents.


Subject(s)
Angiogenesis Inhibitors/administration & dosage , Dexamethasone/administration & dosage , Diabetic Retinopathy/drug therapy , Glucocorticoids/administration & dosage , Macular Edema/drug therapy , Tomography, Optical Coherence , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Aged , Angiogenesis Inhibitors/adverse effects , Dexamethasone/adverse effects , Diabetic Retinopathy/diagnostic imaging , Diabetic Retinopathy/metabolism , Drug Implants , Female , Glucocorticoids/adverse effects , Humans , Intravitreal Injections , Macular Edema/diagnostic imaging , Macular Edema/metabolism , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Time Factors , Treatment Outcome , Vascular Endothelial Growth Factor A/metabolism
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