ABSTRACT
Purpose: The purpose of this study was to investigate the presence of sex-steroid receptors in human choroidal tissue across different ages and sex, aiming to better understand the pronounced sex difference in central serous chorioretinopathy (CSC) occurrence. Methods: Paraffin-embedded enucleated eyes of 14 premenopausal women, 15 postmenopausal women, 10 young men (<45 years), and 10 older men (>60 years) were used. A clinically certified immunostaining was performed to detect the presence of the androgen receptor (AR), progesterone receptor (PR; isoform A and B), and estrogen receptor (ERα). The stained slides were scored in a blinded manner for positive endothelial cells and stromal cells in consecutive sections of the same choroidal region. Results: Our analysis revealed the presence of AR, PR, and ERα in endothelial cells and stromal cells of choroidal tissue. The mean proportion of AR-positive endothelial cells was higher in young men (46% ± 0.15) compared to aged-matched women (29% ± 0.12; P < 0.05, 95% confidence interval [CI]). Premenopausal women showed markedly lower mean proportion of ERα (5% ± 0.02) and PR-positive endothelial cells (2% ± 0.01) compared to postmenopausal women (15% ± 0.07 and 19% ± 0.13; both P < 0.05, 95% CI), young men (13% ± 0.04 and 21% ± 0.10; both P < 0.05, 95% CI), and older men (18% ± 0.09 and 27% ± 0.14; both P < 0.05, 95% CI). Mean PR-positive stromal cells were also less present in premenopausal women (12% ± 0.07) than in other groups. Conclusions: The number of sex-steroid receptors in the choroidal tissue differs between men and women across different ages, which aligns with the prevalence patterns of CSC in men and postmenopausal women.
Subject(s)
Central Serous Chorioretinopathy , Choroid , Receptors, Androgen , Receptors, Progesterone , Humans , Female , Male , Choroid/metabolism , Choroid/pathology , Middle Aged , Adult , Central Serous Chorioretinopathy/metabolism , Central Serous Chorioretinopathy/epidemiology , Central Serous Chorioretinopathy/diagnosis , Receptors, Progesterone/metabolism , Receptors, Androgen/metabolism , Aged , Sex Factors , Prevalence , Estrogen Receptor alpha/metabolismABSTRACT
Lactate and ATP formation by aerobic glycolysis, the Warburg effect, is considered a hallmark of cancer. During angiogenesis in non-cancerous tissue, proliferating stalk endothelial cells (ECs) also produce lactate and ATP by aerobic glycolysis. In fact, all proliferating cells, both non-cancer and cancer cells, need lactate for the biosynthesis of building blocks for cell growth and tissue expansion. Moreover, both non-proliferating cancer stem cells in tumors and leader tip ECs during angiogenesis rely on glycolysis for pyruvate production, which is used for ATP synthesis in mitochondria through oxidative phosphorylation (OXPHOS). Therefore, aerobic glycolysis is not a specific hallmark of cancer but rather a hallmark of proliferating cells and limits its utility in cancer therapy. However, local treatment of angiogenic eye conditions with inhibitors of glycolysis may be a safe therapeutic option that warrants experimental investigation. Most types of cells in the eye such as photoreceptors and pericytes use OXPHOS for ATP production, whereas proliferating angiogenic stalk ECs rely on glycolysis for lactate and ATP production. (J Histochem Cytochem XX.XXX-XXX, XXXX).
Subject(s)
Adenosine Triphosphate , Neoplasms , Neovascularization, Pathologic , Humans , Adenosine Triphosphate/metabolism , Adenosine Triphosphate/biosynthesis , Neoplasms/metabolism , Neoplasms/pathology , Neoplasms/blood supply , Neoplasms/drug therapy , Animals , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Glycolysis , Eye Diseases/metabolism , Eye Diseases/pathology , Oxidative PhosphorylationABSTRACT
An ongoing global shortage of verteporfin (Visudyne®) limits the treatment possibilities for several chorioretinal diseases, including central serous chorioretinopathy, choroidal hemangioma, and polypoidal choroidal vasculopathy. Verteporfin is required to perform photodynamic therapy in these ocular diseases. Therefore, the current situation has a substantial impact on eye care worldwide. The worldwide supply of verteporfin appears to be manufactured by a single factory, which is situated in the United States. The distribution of verteporfin is done by different companies for different regions of the world. Official communication on the shortage by the responsible companies has been scarce and over the past years several promises with regards to resolution of the shortage have not been fulfilled. The delivery of new batches of verteporfin is at irregular intervals, unpredictable, and may not be fairly balanced between different regions or countries in the world. To ensure a fair distribution of available verteporfin within a country, several measures can be taken. In the Netherlands, a national committee, consisting of ophthalmologists, is in place to arrange this. On the European level, the European Union and European Medicine Agency have plans to monitor medicine shortages more closely and to intervene if necessary. With a more intensified monitoring and regulation of medicine supplies, future impending shortages may be prevented. Remarkably, the amount of medicine shortages is increasing, having a significant and sometimes irreversible impact on patient care. Thus, efforts should be undertaken to minimize the consequences and, whenever possible, to prevent future medicine shortages.
ABSTRACT
PURPOSE: Choroidal vascular hyperpermeability (CVH) on indocyanine green angiography (ICGA) is a hallmark feature of central serous chorioretinopathy (CSC). We identified three distinct CVH phenotypes in CSC: uni-focal indistinct signs of choroidal hyperpermeability (uni-FISH) with one focal area of CVH, multiple areas of focal CVH (multi-FISH), and diffuse hyperpermeability covering most of the posterior pole (DISH). This report investigates the distribution of these phenotypes and their association with signs of disease chronicity. METHODS: The CERTAIN study is a monocentric, retrospective study on consecutive CSC patients referred to a large tertiary referral centre that underwent ultra-widefield (UWF) and 55° ICGA. Two independent graders assessed CVH patterns based on mid- to late-phase UWF and 55° ICGA with a third grader acting as referee. RESULTS: Of the 167 eyes of 91 patients included in this study, 43 (26%) showed uni-FISH, 87 (52%) multi-FISH, and 34 (20%) showed DISH based on UWF ICGA. Median age (40 vs. 45 vs. 57; p < 0.001) and logMAR visual acuity (0 vs. 0 vs. 0.1, p < 0.001) differed significantly in-between groups, as did the occurrence of cystoid retinal degeneration (PCRD; 0% vs. 1% vs. 18%, p < 0.001) or diffuse atrophic RPE alterations (DARA; 0% vs. 17% vs. 29%, p < 0.001). The same was true when grading was based on 55° ICGA. CONCLUSIONS: The CVH patterns of uni-FISH, multi-FISH, and DISH are typical of CSC. These patterns correlate with established signs of CSC chronicity. Their predictive role in treatment response and prognosis remains to be evaluated.
Subject(s)
Central Serous Chorioretinopathy , Choroid , Fluorescein Angiography , Tomography, Optical Coherence , Visual Acuity , Humans , Central Serous Chorioretinopathy/diagnosis , Central Serous Chorioretinopathy/physiopathology , Female , Male , Fluorescein Angiography/methods , Retrospective Studies , Middle Aged , Adult , Choroid/blood supply , Choroid/pathology , Choroid/diagnostic imaging , Visual Acuity/physiology , Tomography, Optical Coherence/methods , Capillary Permeability/physiology , Fundus Oculi , Severity of Illness Index , Indocyanine Green/administration & dosage , Coloring Agents/administration & dosage , Aged , Follow-Up StudiesABSTRACT
Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid leakage and it is often associated with reduced vision-related quality of life. In CSC, the leakage of subretinal fluid through defects in the retinal pigment epithelial layer's outer blood-retina barrier appears to occur secondary to choroidal abnormalities and dysfunction. The treatment of CSC is currently the subject of controversy, although recent data obtained from several large randomized controlled trials provide a wealth of new information that can be used to establish a treatment algorithm. Here, we provide a comprehensive overview of our current understanding regarding the pathogenesis of CSC, current therapeutic strategies, and an evidence-based treatment guideline for CSC. In acute CSC, treatment can often be deferred for up to 3-4 months after diagnosis; however, early treatment with either half-dose or half-fluence photodynamic therapy (PDT) with the photosensitive dye verteporfin may be beneficial in selected cases. In chronic CSC, half-dose or half-fluence PDT, which targets the abnormal choroid, should be considered the preferred treatment. If PDT is unavailable, chronic CSC with focal, non-central leakage on angiography may be treated using conventional laser photocoagulation. CSC with concurrent macular neovascularization should be treated with half-dose/half-fluence PDT and/or intravitreal injections of an anti-vascular endothelial growth factor compound. Given the current shortage of verteporfin and the paucity of evidence supporting the efficacy of other treatment options, future studies-ideally, well-designed randomized controlled trials-are needed in order to evaluate new treatment options for CSC.
Subject(s)
Central Serous Chorioretinopathy , Photochemotherapy , Central Serous Chorioretinopathy/therapy , Central Serous Chorioretinopathy/diagnosis , Humans , Photochemotherapy/methods , Evidence-Based Medicine , Practice Guidelines as Topic , Photosensitizing Agents/therapeutic use , Fluorescein Angiography , Angiogenesis Inhibitors/therapeutic use , Laser Coagulation/methodsABSTRACT
PURPOSE: Choroidal venous overload was recently suggested to be a pathogenetic factor in central serous chorioretinopathy (CSC). Manifestations of venous overload on ultrawidefield indocyanine green angiography (UWF ICGA) include asymmetric arterial choroidal filling (AACF), enlarged choroidal vessels ("pachyvessels"), and asymmetric venous drainage (AVD) leading to choroidal intervortex venous anastomoses (CVAs) accompanied by choroidal vascular hyperpermeability (CVH). The purpose of the current study is to assess the presence of these signs of venous overload in a large cohort of CSC patients. DESIGN: Monocentric retrospective cohort study. PARTICIPANTS: Consecutive CSC patients seen at a large tertiary referral center. METHODS: For the CERTAIN study, patients underwent a standardized imaging protocol including UWF ICGA. Features of choroidal venous overload were graded for each eye individually by 2 independent graders and, in case of disagreement, by a third grader. MAIN OUTCOME MEASURES: Presence of AAFC, pachyvessels, AVD, CVA, and CVH. RESULTS: In total, 178 eyes of 91 patients were included in this study. Mean patient age was 47.6 (± 12.0) years and 75 patients (82%) were male. The 116 eyes (65%) that showed subretinal fluid were considered affected (bilateral disease in 29 patients). In affected eyes, AACF was present in 62 eyes (85% of gradable eyes), pachyvessels in 102 eyes (88%), AVD in 81 eyes (74%), CVA in 107 eyes (94%), and CVH in 100% of affected eyes. For fellow eyes, prevalence of pachyvessels (94%), AVD (67%), and CVA (90%) was similar to affected eyes, whereas CVH was present in 85% of fellow eyes. Intergrader agreement was excellent for CVH (94%), and 74%-82% for all other criteria. Patients with pachyvessels and AVD in 1 eye were more likely to also show the same characteristic in the fellow eye (odds ratios 22.2 and 9.9, P < 0.01). CONCLUSIONS: Signs of venous overload are seen in the vast majority of CSC patients, both in affected and unaffected eyes. Although pachyvessels, AVD, and CVA are observed frequently, CVH was observed in all affected eyes, showed excellent intergrader reliability, and is diagnostic for CSC. This supports the concept of choroidal venous overload as a major factor in CSC pathogenesis. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Subject(s)
Central Serous Chorioretinopathy , Humans , Male , Adult , Middle Aged , Female , Central Serous Chorioretinopathy/diagnosis , Indocyanine Green/pharmacology , Retrospective Studies , Reproducibility of Results , Fluorescein Angiography/methods , Tomography, Optical Coherence/methods , Choroid/pathologyABSTRACT
Vascular endothelial growth factor (VEGF)-A induces endothelial hyperpermeability, but the molecular pathways remain incompletely understood. Endothelial nitric oxide synthase (eNOS) regulates acute effects of VEGF-A on permeability of endothelial cells (ECs), but it remains unknown whether and how eNOS regulates late effects of VEGF-A-induced hyperpermeability. Here we show that VEGF-A induces hyperpermeability via eNOS-dependent and eNOS-independent mechanisms at 2 days after VEGF-A stimulation. Silencing of expression of the eNOS gene (NOS3) reduced VEGF-A-induced permeability for dextran (70 kDa) and 766 Da-tracer in human dermal microvascular ECs (HDMVECs), but not in human retinal microvascular ECs (HRECs) and human umbilical vein ECs (HUVECs). However, silencing of NOS3 expression in HRECs increased permeability to dextran, BSA and 766 Da-tracer in the absence of VEGF-A stimulation, suggesting a barrier-protective function of eNOS. We also investigated how silencing of NOS3 expression regulates the expression of permeability-related transcripts, and found that NOS3 silencing downregulates the expression of PLVAP, a molecule associated with trans-endothelial transport via caveolae, in HDMVECs and HUVECs, but not in HRECs. Our findings underscore the complexity of VEGF-A-induced permeability pathways in ECs and the role of eNOS therein, and demonstrate that different pathways are activated depending on the EC phenotype.
Subject(s)
Nitric Oxide Synthase Type III , Vascular Endothelial Growth Factor A , Humans , Caveolae/metabolism , Cells, Cultured , Dextrans , Human Umbilical Vein Endothelial Cells/metabolism , Nitric Oxide Synthase Type III/genetics , Nitric Oxide Synthase Type III/metabolism , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/pharmacologyABSTRACT
PURPOSE: We performed a multicenter, retrospective study on patients with bilateral chronic central serous chorioretinopathy (cCSC) who received single-session bilateral reduced-settings photodynamic therapy (ssbPDT) and assessed anatomical (resolution of subretinal fluid [SRF]) and functional (best-corrected visual acuity [BCVA]) outcomes and safety. METHODS: Patients who underwent ssbPDT between 01/01/2011 and 30/09/2022 were included. The resolution of SRF at first, second, and final follow-up was assessed on optical coherence tomography (OCT), and BCVA measurements were collected at these visits. When fovea-involving ssbPDT was performed, ellipsoid zone (EZ) and external limiting membrane (ELM) integrity was graded before and after treatment. RESULTS: Fifty-five patients were included in this study. Sixty-two of hundred and eight eyes (56%) showed a complete resolution of SRF at the first follow-up, which increased to 73/110 (66%) at the final follow-up. The mean logMAR BCVA improved by -0.047 ( P = 0.02) over follow-up. EZ integrity increased from 14/21 (67%) to 24/30 (80%) while ELM integrity increased from 22/30 (73%) to 29/30 (97%). CONCLUSION: Patients with cCSC with bilateral SRF at baseline showed significant anatomical and functional improvements after ssbPDT, both at short-term and long-term follow-up. No relevant adverse events were noted.
Subject(s)
Central Serous Chorioretinopathy , Photochemotherapy , Porphyrins , Humans , Central Serous Chorioretinopathy/drug therapy , Photosensitizing Agents/therapeutic use , Verteporfin/therapeutic use , Retrospective Studies , Porphyrins/therapeutic use , Photochemotherapy/methods , Tomography, Optical Coherence/methods , Chronic Disease , Fluorescein AngiographyABSTRACT
Sickle cell retinopathy (SCR) is a complication of sickle cell disease (SCD). Proliferative SCR (PSCR) can lead to severe visual impairment due to vitreous hemorrhage or retinal detachment. Knowledge of risk factors for progression and complications of SCR is limited. The aim of this study is to describe the natural history of SCR and to identify risk factors for progressive SCR and development of PSCR. We retrospectively analyzed disease progression in 129 patients with SCD with a median follow-up period of 11 years (interquartile range, 8.5-12). Patients were divided in 2 groups. The genotypes hemoglobin SS (HbSS), HbSß0-thalassemia, and HbSß+-thalassemia were grouped together (n = 83; 64.3%), whereas patients with HbSC (n = 46; 35.7%) were grouped separately. Progression of SCR was observed in 28.7% (37 of 129) of patients. Older age (adjusted odds ratio [aOR], 1.073; 95% confidence interval [CI], 1.024-1.125; P = .003), HbSC genotype (aOR, 25.472; 95% CI, 3.788-171.285; P ≤ 0.001), and lower HbF (aOR, 0.786; 95% CI, 0.623-0.993; P = .043) were associated with PSCR at end of follow-up. Lack of any SCR at end of follow-up was associated with female sex (aOR, 2.555; 95% CI, 1.101-5.931; P = .029), HbSS/HbSß0/HbSß+ genotype (aOR, 3.733; 95% CI, 1.131-12.321; P = .031), and higher HbF levels (aOR, 1.119; 95% CI, 1.007-1.243; P = .037). Differentiated strategies for screening and follow-up of SCR could be considered for patients at low or high risk.
Subject(s)
Anemia, Sickle Cell , Retinal Diseases , Thalassemia , Humans , Adult , Female , Follow-Up Studies , Retrospective Studies , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/diagnosis , Hemoglobin, Sickle , Thalassemia/complications , Retinal Diseases/etiology , Retinal Diseases/complicationsABSTRACT
PURPOSE: A retrospective study was performed with data from the prospective randomized controlled trials, PLACE and SPECTRA, assessing the risk of foveal atrophy and the likelihood of structural and functional improvement on optical coherence tomography, after foveal half-dose photodynamic therapy in chronic central serous chorioretinopathy. METHODS: A total of 57 chronic central serous chorioretinopathy patients received a single half-dose photodynamic therapy with a treatment spot that included the fovea. Optical coherence tomography scans and fundus autofluorescence images were analyzed for structural improvement and possible atrophy development, at baseline and at several visits after treatment. Main outcome measures were integrity of the external limiting membrane and ellipsoid zone on optical coherence tomography and hypoautofluorescence on fundus autofluorescence. RESULTS: The subfoveal external limiting membrane was graded as continuous in 21 of 57 of patients (36.8%) at baseline, and the subfoveal ellipsoid zone was graded as continuous in 5 of 57 patients (8.8%) at first visit, which improved to 50 of 51 (98.0%) and 32 out of 51 (62.7%) at the final visit at 2 years, respectively (both P < 0.001). Hypoautofluorescent changes on fundus autofluorescence were present in 25 of 55 patients (45.5%) at baseline and in 23 of 51 patients (45.1%) at the final visit ( P = 0.480). CONCLUSION: In patients with chronic central serous chorioretinopathy who received a single, foveal, half-dose photodynamic therapy, a significant improvement in structure and function was seen at the final follow-up. None of the patients developed foveal atrophy.
Subject(s)
Central Serous Chorioretinopathy , Photochemotherapy , Porphyrins , Humans , Central Serous Chorioretinopathy/drug therapy , Photosensitizing Agents/therapeutic use , Verteporfin/therapeutic use , Retrospective Studies , Prospective Studies , Porphyrins/therapeutic use , Fluorescein Angiography , Photochemotherapy/methods , Chronic Disease , Tomography, Optical Coherence , Randomized Controlled Trials as TopicABSTRACT
PURPOSE: Comparing anatomic and functional efficacy and safety of primary treatment with either half-dose photodynamic therapy (PDT) or oral eplerenone, or crossover treatment in chronic central serous chorioretinopathy patients. METHODS: After the SPECTRA trial baseline visit, patients were randomized to either half-dose PDT or eplerenone and received crossover treatment if persistent subretinal fluid (SRF) on optical coherence tomography (OCT) was present at first follow-up (at 3 months). Presence of SRF and best-corrected visual acuity (BCVA) was evaluated at 12 months. RESULTS: Out of the 90 patients evaluated at 12 months, complete SRF resolution was present on OCT in 43/48 (89.6%) of patients who were primarily randomized to half-dose PDT and in 37/42 (88.1%) who were primarily randomized to eplerenone. Out of the 42 patients that were primarily randomized to eplerenone, 35 received crossover treatment with half-dose PDT. The BCVA improved significantly more at 12 months in patients who had received primary half-dose PDT as compared to the primary eplerenone group (p = 0.030). CONCLUSIONS: Twelve months after baseline visit, most patients treated with half-dose PDT (either primary or crossover treatment) still had complete SRF resolution. The long-term BCVA in patients who receive primary half-dose PDT is better than in patients in whom PDT is delayed due to initial eplerenone treatment with persistent SRF.
Subject(s)
Central Serous Chorioretinopathy , Photochemotherapy , Humans , Eplerenone/therapeutic use , Central Serous Chorioretinopathy/diagnosis , Central Serous Chorioretinopathy/drug therapy , Photosensitizing Agents/therapeutic use , Follow-Up Studies , Photochemotherapy/methods , Visual Acuity , Chronic Disease , Tomography, Optical Coherence/methods , Fluorescein Angiography/methods , Treatment OutcomeABSTRACT
Extracellular signalling proteins interact in networks rather than in isolation. In this context we investigated vitreous protein levels, including placental growth factor (PlGF), angiopoietin-2 (ANG2) and vascular endothelial growth factor (VEGF), in patients with proliferative diabetic retinopathy (PDR) with variable disease severities, and after anti-VEGF pre-treatment. Vitreous samples of 112 consecutive patients undergoing vitrectomy for PDR and of 52 non-diabetic patients with macular holes as controls were studied. A subset of the PDR patients were treated with either aflibercept (AFB, n = 25) or bevacizumab (BVZ)/ranibizumab (RZB) (n = 13), before surgery. Antibody-based analysis of 35 proteins (growth factors and cytokines) showed a significant increase in expression levels of 27 proteins in PDR patients as compared to controls. In network analysis of co-regulated proteins, a strong correlation in expression levels between VEGF, PlGF, MCP1 and ANG2 was found, mostly clustered around ANG2. In the AFB treatment group, concentrations of several proteins were decreased, including VEGFR1, whereas interleukin 6 and 8 were increased as compared to untreated PDR patients. The observed differences in vitreous protein levels between the different treatments and untreated PDR patients may underlie differences in clinical outcomes in patients with PDR.
Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Humans , Female , Bevacizumab/pharmacology , Bevacizumab/therapeutic use , Diabetic Retinopathy/drug therapy , Vascular Endothelial Growth Factor A , Placenta Growth FactorABSTRACT
The purpose of this study was to provide an estimate of the number of current and future patients with polypoidal choroidal vasculopathy (PCV) in Europe. We systematically searched 11 literature databases on 18 May 2022 for studies on the prevalence of PCV among a consecutive and representative group of patients with suspected neovascular age-related macular degeneration (AMD). Prevalence of PCV in patients with suspected neovascular AMD was summarized and included in a prevalence meta-analysis. We then used current population data and population forecasts by Eurostat and the Office for National Statistics to determine current and future number of patients with neovascular AMD in Europe. Then, we calculated the number of patients with PCV with our calculated estimate of the prevalence of PCV among Europeans suspected with neovascular AMD. A total of five eligible studies were identified which included a total of 1359 patients. All these studies used the gold standard of indocyanine green angiography as a routine part of their diagnostic approach. Among patients undergoing detailed retinal examination for suspected neovascular AMD, our meta-analysis calculated the prevalence of PCV to be 8.3% (95% confidence interval: 6.8-9.8%). Our population estimates find that a total of 217,404 patients with PCV exist in Europe in the year 2022, which constitutes 0.04% of the entire population of Europe. This number is estimated to increase to 287,517 patients in the year 2040. Our estimates are important for different healthcare stakeholders, especially when planning and allocating expensive resources.
ABSTRACT
Endothelial cells (ECs) form a precisely regulated polarized monolayer in capillary walls. Vascular endothelial growth factor-A (VEGF-A) induces endothelial hyperpermeability, and VEGF-A applied to the basolateral side, but not the apical side, has been shown to be a strong barrier disruptor in blood-retinal barrier ECs. We show here that VEGF-A presented to the basolateral side of human umbilical vein ECs (HUVECs) induces higher permeability than apical stimulation, which is similar to results obtained with bovine retinal ECs. We investigated with immunocytochemistry and confocal imaging the distribution of VEGF receptor-2 (VEGFR2) and neuropilin-2 (NRP2) in perinuclear apical and basolateral membrane domains. Orthogonal z-sections of cultured HUVECs were obtained, and the fluorescence intensity at the apical and basolateral membrane compartments was measured. We found that VEGFR2 and NRP2 are evenly distributed throughout perinuclear apical and basolateral membrane compartments in unstimulated HUVECs grown on Transwell inserts, whereas basolateral VEGF-A stimulation induces a shift toward basolateral VEGFR2 and NRP2 localization. When HUVECs were grown on coverslips, the distribution of VEGFR2 and NRP2 across the perinuclear apical and basolateral membrane domains was different. Our findings demonstrate that HUVECs dynamically regulate VEGFR2 and NRP2 localization on membrane microdomains, depending on growth conditions and the polarity of VEGF-A stimulation.
Subject(s)
Neuropilin-2 , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism , Animals , Cattle , Cell Membrane/metabolism , Cells, Cultured , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Neuropilin-2/metabolism , Retina/metabolismABSTRACT
The Swiss Ophthalmic Image Network (SOIN) is part of the Swiss Personalized Health Network (SPHN). SOIN contains a collaborative, clinical research environment, MI Data Lab, which allows privacy-preserving, data-driven, research. Personalized care of chronic ocular disease, based on Machine Learning (ML) and medical imaging, can dramatically improve quality of life and reduce the burden on health and social care systems. MI Data Lab allows research partners to consolidate their data in a space where doctors and data scientists cooperate to design novel ML algorithms, on curated datasets. To date, we have created several algorithms to detect ocular biomarkers automatically, and applied such tools to 100k+ retinal images. MI Data Lab enables the development of predictive models, the extraction novel traits to be explored in terms of -omic associations, treatment outcome, and priors for disease progression.
Subject(s)
Ophthalmology , Data Collection , Humans , Informed Consent , Privacy , Quality of LifeABSTRACT
PURPOSE: To compare the efficacy and safety of crossover treatment to half-dose photodynamic therapy (PDT) and eplerenone treatment after the failure of primary treatment in patients with chronic central serous chorioretinopathy (cCSC). DESIGN: Multicenter crossover clinical trial. SUBJECTS: At 3 months after the baseline visit of the SPECTRA (Half-Dose Photodynamic Therapy Versus Eplerenone: Treatment Trial for Chronic Central Serous Chorioretinopathy) randomized controlled trial, either half-dose PDT or eplerenone treatment was evaluated for each patient, and patients who still demonstrated subretinal fluid (SRF) were included in the current study, the SPECS (Central Serous Chorioretinopathy Treated with Half-Dose PDT or Eplerenone Crossover Study) trial. METHODS: At the baseline visits for the current SPECS trial, crossover treatment was performed for patients who still demonstrated SRF. These patients received either half-dose PDT or oral eplerenone for 12 weeks. Both anatomic and functional parameters were evaluated 3 months after crossover treatment. MAIN OUTCOME MEASURES: Complete resolution of SRF on OCT. RESULTS: Forty-nine patients were included in the SPECS trial (38 received primary eplerenone treatment; 11 received half-dose PDT). At 3 months after crossover treatment, 32 of 37 (86.5%) in the crossover to half-dose PDT group and 2 of 9 (22.2%) in the crossover to eplerenone group had complete SRF resolution (P = 0.030). The mean foveal sensitivity increased significantly more in the crossover to half-dose PDT group (mean, +3.08 dB) compared with the crossover to eplerenone group (mean, -0.27 dB; P = 0.009). CONCLUSIONS: Patients with cCSC with the persistence of SRF after primary eplerenone treatment can benefit from half-dose PDT, which can induce a relatively fast and complete SRF resolution, along with an improvement in foveal sensitivity.
Subject(s)
Central Serous Chorioretinopathy , Photochemotherapy , Central Serous Chorioretinopathy/diagnosis , Central Serous Chorioretinopathy/drug therapy , Chronic Disease , Cross-Over Studies , Eplerenone/therapeutic use , Fluorescein Angiography , Humans , Photosensitizing Agents/therapeutic use , Tomography, Optical Coherence , Verteporfin/therapeutic use , Visual AcuityABSTRACT
INTRODUCTION: Since July 2021, a worldwide shortage of verteporfin (Visudyne®) occurred: an essential medicine required for photodynamic therapy (PDT). PDT with verteporfin has a broad range of indications in ophthalmology, including chronic central serous chorioretinopathy, polypoidal choroidal vasculopathy and choroidal haemangioma. For these disorders, PDT is either the first-choice treatment or regarded as a major treatment option. MATERIALS AND METHODS: A questionnaire was sent to key opinion leaders in the field of medical retina throughout the world, to assess the role of PDT in their country and the effects of the shortage of verteporfin. In addition, information on the application of alternative treatments during shortage of verteporfin was obtained, to further assess the impact of the shortage. RESULTS: Our questionnaire indicated that the shortage of verteporfin had a major impact on ophthalmic care worldwide and was regarded to be a serious problem by most of our respondents. However, even though there is ample evidence to support the use of PDT in several chorioretinal diseases, we found notable differences in its use in normal patient care throughout the world. Various alternative management strategies were noted during the verteporfin shortage, including lowering the dose of verteporfin per patient, the use of alternative treatment strategies and the use of a centralized system for allocating the remaining ampoules of verteporfin in some countries. CONCLUSION: The shortage of verteporfin has had a large effect on the care of ophthalmic patients across the world and may have resulted in significant and irreversible vision loss. Mitigation strategies should be developed in consultation with all stakeholders to avoid future medication shortages of verteporfin and other unique ophthalmic medications. These strategies may include mandatory stock keeping, compulsory licensing to an alternative manufacturer or incentivizing the development of competition, for example through novel public-private partnerships.
Subject(s)
Central Serous Chorioretinopathy , Choroidal Neovascularization , Photochemotherapy , Porphyrins , Central Serous Chorioretinopathy/drug therapy , Choroidal Neovascularization/drug therapy , Fluorescein Angiography , Humans , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Porphyrins/therapeutic use , Treatment Outcome , Verteporfin/therapeutic useABSTRACT
The pachychoroid disease spectrum (PDS) includes several chorioretinal diseases that share specific choroidal abnormalities. Although their pathophysiological basis is poorly understood, diseases that are part of the PDS have been hypothesized to be the result of venous congestion. Within the PDS, central serous chorioretinopathy is the most common condition associated with vision loss, due to an accumulation of subretinal fluid in the macula. Central serous chorioretinopathy is characterized by distinct risk factors, most notably a high prevalence in males and exposure to corticosteroids. Interestingly, sex differences and corticosteroids are also strongly associated with specific types of arteriovenous anastomoses in the human body, including dural arteriovenous fistula and surgically created arteriovenous shunts. In this manuscript, we assess the potential of such arteriovenous anastomoses in the choroid as a causal mechanism of the PDS. We propose how this may provide a novel unifying concept on the pathophysiological basis of the PDS, and present cases in which this mechanism may play a role.
Subject(s)
Central Serous Chorioretinopathy , Choroid Diseases , Female , Humans , Male , Central Serous Chorioretinopathy/diagnosis , Central Serous Chorioretinopathy/etiology , Fluorescein Angiography , Arteriovenous Anastomosis , Tomography, Optical Coherence , Choroid/pathology , Choroid Diseases/diagnosis , Choroid Diseases/etiologyABSTRACT
An increasing number of artificial intelligence (AI) systems are being proposed in ophthalmology, motivated by the variety and amount of clinical and imaging data, as well as their potential benefits at the different stages of patient care. Despite achieving close or even superior performance to that of experts, there is a critical gap between development and integration of AI systems in ophthalmic practice. This work focuses on the importance of trustworthy AI to close that gap. We identify the main aspects or challenges that need to be considered along the AI design pipeline so as to generate systems that meet the requirements to be deemed trustworthy, including those concerning accuracy, resiliency, reliability, safety, and accountability. We elaborate on mechanisms and considerations to address those aspects or challenges, and define the roles and responsibilities of the different stakeholders involved in AI for ophthalmic care, i.e., AI developers, reading centers, healthcare providers, healthcare institutions, ophthalmological societies and working groups or committees, patients, regulatory bodies, and payers. Generating trustworthy AI is not a responsibility of a sole stakeholder. There is an impending necessity for a collaborative approach where the different stakeholders are represented along the AI design pipeline, from the definition of the intended use to post-market surveillance after regulatory approval. This work contributes to establish such multi-stakeholder interaction and the main action points to be taken so that the potential benefits of AI reach real-world ophthalmic settings.