Purpose: To determine if perceived social support is relevant for depression and anxiety in patients with age-related neovascular macular degeneration.

Methods: This observational cross-sectional study involved participants diagnosed with neovascular age-related macular degeneration (nAMD) from Sweden. All participants were receiving treatment for their condition. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS), while perceived social support was measured with the Multidimensional Scale of Perceived Social Support (MSPSS). Visual acuity was evaluated using ETDRS charts, and the number of hospital episodes related to mental health visits was obtained from electronic records.

Results: Of the 179 participants included in this study, 124 (70%) were female, and the mean age was 78.6 (SD = 7.60) years. The mean acuity in the better-seeing eye was 0.26 (SD = 0.24) logMAR. The mean anxiety score was 4.97 (SD = 3.33), and the mean depression score was 4.25 (SD = 3.26). The mean social support score was 5.73 (SD = 1.29). Significant multivariate regression models were found for anxiety (p < 0.001), depression (p < 0.0001), and both combined as given by the total HADS score (p < 0.0001). Higher perceived social support was independently associated with lower anxiety and depression, while a greater number of mental health–related hospital visits was independently associated with higher anxiety and depression.

Conclusions: We found that perceived social support was indeed relevant to depression and anxiety in patients with neovascular AMD undergoing anti-VEGF therapy. As a modifiable factor, targeted interventions that enhance social connectedness may help mitigate mental health risks in this patient group.

Tick-over of C3 to fluid-phase C3(H₂O) is considered the initiator of the alternative pathway by mediating random depositing of C3b on target surfaces. This slow mechanism does not explain the specificity and rapid activation of the alternative pathway in vivo. In thromboinflammatory disorders, C3(H₂O) also exists in a bound form on activated platelets and endothelial cells. Here, we investigate this binding mechanism. C3, C3b, and C3(H₂O) were exposed to activated platelets expressing phospholipid-scrambled membranes. Native C3 demonstrated the highest binding to activated platelets compared to C3b and soluble C3(H₂O) and revealed the most efficient convertase (C3bBb) formation. The specific binding of annexin V to phospholipid-scrambled membranes, inhibited C3 binding to activated platelets, and to apoptotic PMN and endothelial cells, while properdin enhanced both binding and convertase generation. Model liposomes exposing phosphatidylserine, bound native C3 in a cholesterol-dependent manner. Neoepitopes and cryo-TEM, showed that the conformation of liposome-bound C3 resembles C3(H₂O) and quartz crystal microbalance with dissipation monitoring (QCM-D) its ability to form C3bBb convertases. Thus, native C3 transforms into C3(H₂O) by binding to phospholipid-scrambled membranes, identifying native C3 without proteolytic cleavage, as a direct recognition molecule of altered self (in this case exposure of phospholipids that are not found on the surface of native, healthy, cells) acting as a key initiator of the alternative pathway and a mediator of phagocytosis in thromboinflammatory pathologies.

Purpose: The aim of this study was to assess perceived stress levels in patients with nAMD undergoing treatment with anti-VEGF injections, and to investigate psychosocial and visual factors that can be associated with perceived stress among these patients.

Methods: We recruited 202 patients diagnosed with nAMD (mean age of 78 years) who had received three or more anti-VEGF injections and had been scheduled for further treatments. To measure perceived stress, participants completed the Perceived Stress Scale-10 (PSS10). For the associated factors, the participants also completed the National Eye Institute Visual Function Questionnaire-25 and Multidimensional Perceived Social Support. Participants completed the questionnaires at home before an upcoming treatment scheduled at the hospital. Best corrected visual acuity was measured at the hospital before the treatment. Factors associated with PSS10 scores were examined using multiple regression models.

Results: Participants with near vision impairment perceived higher stress levels than those without near vision impairment (p = 0.034). Younger age (β = -0.15, p = 0.003), better visual acuity (β = -4.20, p = 0.036), poorer perceived social support (β = -1.21, p < 0.001), and poorer self-reported visual function (β = -0.16, p < 0.001) were significantly associated with increased levels of perceived stress.

Conclusions: Our study highlighted factors potentially associated with increased perceived stress in nAMD patients undergoing anti-VEGF treatment. Self-reported visual function, in particular near-vision, and perceived social support are factors that can be addressed to reduce the levels of stress and risk of mental health disorders in this patient group.

Syfte: Syftet med denna studie var att undersöka upplevda stressnivåer hos patienter med nAMD som genomgår behandling med anti-VEGF-injektioner samt att analysera psykosociala och visuella faktorer som kan vara associerade med upplevd stress hos dessa patienter.

Metod: Vi rekryterade 202 patienter med diagnosen nAMD (medelålder 78 år) som hade fått tre eller fler anti-VEGF-injektioner och som var planerade för fortsatt behandling. För att mäta upplevd stress fyllde deltagarna i frågeformuläret Perceived Stress Scale-10 (PSS10). För att bedöma relaterade faktorer fyllde deltagarna även i National Eye Institute Visual Function Questionnaire-25 och Multidimensional Perceived Social Support. Deltagarna besvarade frågeformulären i hemmet inför ett kommande behandlingsbesök på sjukhuset. Bästa korrigerade synskärpa mättes på sjukhuset före behandlingen. Faktorer associerade med PSS10-poäng analyserades med multipla regressionsmodeller.

Resultat: Deltagare med närseendeförsämring upplevde högre stressnivåer än de utan närseendeförsämring (p = 0,034). Yngre ålder (β = -0,15, p = 0,003), bättre synskärpa (β = -4,20, p = 0,036), sämre upplevt socialt stöd (β = -1,21, p < 0,001) och sämre självrapporterad synfunktion (β = -0,16, p < 0,001) var signifikant associerade med högre nivåer av upplevd stress.

Slutsats: Vår studie belyser faktorer som potentiellt är associerade med ökad upplevd stress hos patienter med nAMD som får anti-VEGF-behandling. Självrapporterad synfunktion, särskilt närseende, samt upplevt socialt stöd är faktorer som kan adresseras för att minska stressnivåer och risken för psykisk ohälsa i denna patientgrupp.

** machine translated not reviewed by a human **

Objectivo: O objectivo deste estudo foi avaliar os níveis de stress percebido em doentes com DMRI neovascular (nAMD) a receber tratamento com injecções de anti-VEGF, e investigar factores psicossociais e visuais que possam estar associados ao stress percebido entre estes doentes.

Métodos: Foram recrutados 202 doentes diagnosticados com nAMD (idade média de 78 anos), que tinham recebido três ou mais injecções de anti-VEGF e tinham tratamentos subsequentes agendados. Para medir o stress percebido, os participantes preencheram o questionário Perceived Stress Scale-10 (PSS10). Para análise dos factores associados, os participantes também preencheram o questionário National Eye Institute Visual Function Questionnaire-25 e a Escala Multidimensional de Suporte Social Percebido. Os questionários foram preenchidos em casa antes da consulta hospitalar programada para tratamento. A melhor acuidade visual corrigida foi medida no hospital antes do tratamento. Os factores associados aos resultados do PSS10 foram analisados utilizando modelos de regressão múltipla.

Resultados: Os participantes com défice de visão ao perto perceberam níveis de stress mais elevados do que aqueles sem défice de visão ao perto (p = 0,034). Idade mais jovem (β = -0,15, p = 0,003), melhor acuidade visual (β = -4,20, p = 0,036), menor suporte social percebido (β = -1,21, p < 0,001) e pior função visual auto-relatada (β = -0,16, p < 0,001) estiveram significativamente associados a níveis mais elevados de stress percebido.

Conclusões: O nosso estudo destacou factores potencialmente associados ao aumento do stress percebido em doentes com nAMD em tratamento com anti-VEGF. A função visual auto-relatada, particularmente a visão ao perto, e o suporte social percebido são factores que podem ser abordados para reduzir os níveis de stress e o risco de perturbações de saúde mental neste grupo de doentes.

** machine translated not reviewed by a human **

Purpose: To determine predictors of success and failure events during treatment of neovascular AMD (nAMD) using real-world data.

Methods: We analysed data from one eye of 54 patients treated for nAMD, diagnosed up to 36 months from the date of participation and loading phase completed. Exclusion criteria: missing pre-treatment optical coherence tomography (OCT) scan or visual acuity (VA). Longitudinal morphological measures were obtained from the central 1mm of macular cube scans using the artificial intelligence (AI) based software RetinAI OCT Segmentation in Discovery (Ikerian AG). Measurements performed: intraretinal fluid (IRF), sub-retinal fluid (SRF), posterior epithelial detachment all in nanolitres, and retinal thickness in micrometres. VA and OCT scans were available from the treatment visits; plasma cytokines were measured at the time of participation in the current study. Definition of events – success: IRF+SRF reduced 50% or more, VA improved 5 letters or both; failure: IRF+SRF reduced by less than 50%, VA reduced 5 letters, or both. The reference for comparisons were pre-treatment OCT and VA measures. Time-to-event was modulated using Cox regression, that provides the hazard ratio of the event (HR).

Results: The mean age of the participants was 78.04 years (SD=7.69), 75% females, baseline VA mean=59.6 letters (SD=13.7). The median time for the first treatment success event was 125 days (IQR=108-199), 73% of the eyes experienced a treatment success event during follow-up. Higher levels of cytokine MCP-1 had a negative association, HR=0.92 (CI=0.84-1.00, p=0.046), and start VA less than 70 letters had a (marginally sig.) positive association, HR=2.52 (CI=0.98-6.44, p=0.057) with success events. The median time for the first treatment failure event was 196 days (IQR=122-405), 47% of the eyes experienced a failure event during the follow-up. Higher levels of cytokine MCP-1 had a positive association, HR=1.16 (CI=1.03-1.31, p=0.018), and start VA less than 70 letters had a negative association, HR=0.18 (CI=0.05-0.53, p=0.007) with failure events.

Conclusions: Most eyes experienced at least one treatment success event, close to half experienced a treatment failure event during the follow-up time. Chemokine MCP-1 was consistently associated with both types of events. Further work is warranted to confirm the robustness of the current findings.

Human transferrin receptor 1 (TfR) is essential for cellular iron homeostasis by internalizing the iron carrier proteins transferrin and ferritin. It is also an entry point for various pathogens, such as South American hemorrhagic fever caused by arenaviruses and the malaria parasite Plasmodium vivax, which utilize TfR to gain access to cells. The receptor is additionally upregulated in many aggressive cancers and at the blood-brain barrier. Altogether, the TfR is a highly relevant target for many medical applications, and novel protein-interacting partners are sought after. A protein design strategy was explored here to develop a small protein that can be used for drug delivery across cell membranes, to investigate blood-brain barrier crossing, study endocytosis, or to block pathogen access to the apical domain. A computationally docked library of small protein scaffolds to the TfR apical domain, the native binding site of the Machupo arenavirus, was a starting point for the design and optimization. The best variants were expressed in a yeast surface display system and assessed for interaction with TfR by flow cytometry. One protein variant, which initially showed a low binding signal, was further optimized by directed evolution to bind to the target receptor at nanomolar concentration. The evolved construct, tagged with the enhanced green fluorescent protein (eGFP) and bacterially expressed, showed uptake similar to that of FITC-coupled transferrin in a cell-based assay. The designed protein can be utilized as a tool to target cell entry via TfR for drug delivery applications or as a foundation for developing antiviral therapeutics against arenaviruses.

Aims/Purpose: To compare the perceived social support in patients with retinal diseases living in Sweden or in Portugal.

Methods: Participants from Sweden were patients diagnosed with neovascular age-related macular degeneration (nAMD). Participants from Portugal were patients diagnosed with AMD or diabetic retinopathy. Participants completed the Swedish or Portuguese version of the Multidimensional Perceived Social Support (MSPSS) scale. Visual acuity was measured using an ETDRS scale.

Results: The final sample was formed of 269 patients comprising two groups, one group with 198 from Sweden and a second group with 71 from Portugal. The median age was 77 years (IQR = 11) and the median visual acuity was 0.22 logMAR (IQR = 0.44). There was no statistically significant difference in age nor in acuity between the groups. The Swedish group had higher proportion of women (67%) compared to the Portuguese (52%). For the MSPSS there was a higher median score of 6.08 (IQR = 1.60) in the Swedish group compared with the median of 5.33 (IQR = 0.75) in the Portuguese group (p < 0.001). The Swedish group reported higher scores in the family (p < 0.001) and significant other (p < 0.001) subscales compared to the Portuguese.

Conclusions: Patients with retinal diseases from Sweden perceived better social support than patients from Portugal. Better perceived social support is expected to improve coping and adherence to treatments among patients with eye diseases. This aspect seems open for improvement in the Portuguese group.

A late stage of several retinal disorders is retinal detachment, a complication that results in rapid photoreceptor degeneration and synaptic damage. The porcine retina is a favorable in vitro model for studies of the degenerative processes that follow retinal detachment. Photoreceptor degeneration and synaptic injuries develop rapidly in the cultured porcine retina and correlate with resident microglial cell transition into a reactive phenotype. In this in vitro study, we used retinas cultured for five days and analyzed reactive CD11b and Iba1 immunoreactive microglia that localized close to/within the synaptic outer plexiform layer (OPL) and in the outer nuclear layer (ONL). A subpopulation of the CD11b and Iba1immunoreactive microglia also expressed CD68 immunoreactivity on lysosomal membranes or as a diffuse cytoplasmic stain. Some CD68 immunoreactive microglia were juxtaposed to L/M-opsin immunoreactive cone photoreceptors in the ONL. CD11b and Iba immunoelectron microscopy further suggests the presence of a dark microglial phenotype in the degenerating cultured porcine retina. For immunoelectron microscopy, nickel-enhanced diaminobenzidine (DAB) staining resulted in clearly distinguished reaction products in the cytosol of dark microglia.

Introduction: Our aim was to assess vision-related activity difficulties (visual ability) among patients with neovascular AMD using a Swedish version of the Massof ActivityInventory (MAI).

Methods: Participants were diagnosed with neovascular age-related macular degeneration (nAMD) and receiving treatment for the disease in a hospital in Sweden. Participants completed the Swedish version of the MAI questionnaire, best corrected distance and near visual acuity (VA) were measured. MAI is formed of 50 goals (items) and can be used to measure the overall or specific visual ability in 4 functional domains: reading, mobility, visual motor function, and visual information processing. Charlson comorbidity index weighted by age was computed.

Results: There was a total of 196 participants (mean age=78.5 years, SD=7.67, 66% female), 67 with vision impairment defined as distance VA in the better eye 0.32 logMAR or worse. Among the visually impaired, median VA was 0.53 logMAR (IQR=0.22). The median Charlson comorbidity index weighted by age was 4, range 0 to 15. After excluding participants with VA better than 0.32 logMAR, 12 items were excluded from the final Rasch analysis due to poor fitting. The mean visual ability for the visually impaired participants was 1.64 logits (SD= 1.55). The most difficult item was "sew and needlework"and the less difficult was "eat meals", items removed included, for example, "fishing"or "do electrical work". Visual ability was correlated with distance VA (p=0.043), near VA (p=0.01) and Charlson comorbidity index (p=0.026).

Discussion: The results revealed that the MAI produces reliable measures of visual ability among patients with nAMD and can be used for vision rehabilitation outcomes. Some items in the Swedish version of the MAI seem redundant for patients with nAMD. Shorter instruments are always preferrable, and we will investigate further the possibility of an item reduction for this target group.

Platelet activation and the complement system are mutually dependent. Here, we investigated the effects of storage time on complement activation and platelet function in routinely produced platelet concentrates. The platelet concentrates (n = 10) were stored at 22 degrees C for seven days and assessed daily for complement and platelet activation markers. Additionally, platelet function was analyzed in terms of their responsiveness to protease-activated receptor-1 (PAR-1) and thromboxane A2 receptor (TXA(2)R) activation and their capacity to adhere to collagen. Complement activation increased over the storage period for all analyzed markers, including the C1rs/C1-INH complex (fold change (FC) = 1.9; p < 0.001), MASP-1/C1-INH complex (FC = 2.0; p < 0.001), C4c (FC = 1.8, p < 0.001), C3bc (FC = 4.0; p < 0.01), and soluble C5b-9 (FC = 1.7, p < 0.001). Furthermore, the levels of soluble platelet activation markers increased in the concentrates over the seven-day period, including neutrophil-activating peptide-2 (FC = 2.5; p < 0.0001), transforming growth factor beta 1 (FC = 1.9; p < 0.001) and platelet factor 4 (FC = 2.1; p < 0.0001). The ability of platelets to respond to activation, as measured by surface expression of CD62P and CD63, decreased by 19% and 24% (p < 0.05) for PAR-1 and 69-72% (p < 0.05) for TXA(2)R activation, respectively, on Day 7 compared to Day 1. The extent of platelet binding to collagen was not significantly impaired during storage. In conclusion, we demonstrated that complement activation increased during the storage of platelets, and this correlated with increased platelet activation and a reduced ability of the platelets to respond to, primarily, TXA(2)R activation.

Aims/Purpose: The aim of this study was to assess vision-related activity difficulties among patients with neovascular AMD using a Swedish version of the mass of activity inventory (MAI). Methods: Participants were patients diagnosed with neovascular AMD receiving treatment for the disease in a hospital in southeast Sweden. Participants completed the Swedish version of the MAI questionnaire. MAI can be used to measure the overall visual ability and visual ability in 4 functional domains: reading, mobility, visual motor function and visual information processing. Best corrected distance and near visual acuity (VA) were also measured. Results: Among the 196 participants (mean age=78.5 years, SD=7.67, 66% female) the median VA in the better seeing eye was 0.18 logMAR (IQR=?0.34), and in the worse eye was 0.54 logMAR (IQR=0.98). The median visual ability for all participants was 1.92 logits (IQR=2.69). There was a significant negative correlation between distance VA in the better eye and visual ability (rho=0.4025, p<0.01). Using ROC curves, we tested the capacity of the MAI to detect cases of any vision impairment (VA worse than 0.3 logMAR in the better seeing eye), the area under the curve (AUC) was 0.717 (95% CI=0.643 - 0.791 p<0.001). When we tested for detection of moderate vision impairment (VA worse than 0.5 logMAR in the better seeing eye) the AUC was 0.738 (95% CI=0.648 - 0.829 p?<0.001). Conclusions: The results indicate that the Swedish version of the MAI produce measures of visual ability that are consistent with clinical measures among patients with nAMD. The Swedish version of the MAI can be used as outcome measure in interventions for people with nAMD.

References

1. Macedo, A.F. et al. Predictors of problems reported on the EQ-5D-3L dimensions among people with impaired vision in northern Portugal. Health Qual Life Outcomes 2022; 20: 132.