Neuroretinal degeneration in a mouse model of systemic chronic immune activation observed by proteomics.

Blindness or vision loss due to neuroretinal and photoreceptor degeneration affects millions of individuals worldwide. In numerous neurodegenerative diseases, including age-related macular degeneration, dysregulated immune response-mediated retinal degeneration has been found to play a critical role in the disease pathogenesis. To better understand the pathogenic mechanisms underlying the retinal degeneration, we used a mouse model of systemic immune activation where we infected mice with lymphocytic choriomeningitis virus (LCMV) clone 13. Here, we evaluated the effects of LCMV infection and present a comprehensive discovery-based proteomic investigation using tandem mass tag (TMT) labeling and high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS). Changes in protein regulation in the posterior part of the eye, neuroretina, and RPE/choroid were compared to those in the spleen as a secondary lymphoid organ and to the kidney as a non-lymphoid but encapsulated organ at 1, 8, and 28 weeks of infection. Using bioinformatic tools, we found several proteins responsible for maintaining normal tissue homeostasis to be differentially regulated in the neuroretina and the RPE/choroid during the degenerative process. Additionally, in the organs we observed, several important protein pathways contributing to cellular homeostasis and tissue development were perturbed and associated with LCMV-mediated inflammation, promoting disease progression. Our findings suggest that the response to a systemic chronic infection differs between the neuroretina and the RPE/choroid, and the processes induced by chronic systemic infection in the RPE/choroid are not unlike those induced in non-immune-privileged organs such as the kidney and spleen. Overall, our data provide detailed insight into several molecular mechanisms of neuroretinal degeneration and highlight various novel protein pathways that further suggest that the posterior part of the eye is not an isolated immunological entity despite the existence of neuroretinal immune privilege.

Microperimetry and Structural Risk Factors on OCT in Intermediate Age-Related Macular Degeneration.

PURPOSE: To determine the relationship between structural biomarkers on OCT that increase the risk of disease progression and microperimetric retinal sensitivity in patients with intermediate age-related macular degeneration (iAMD). DESIGN: Prospective cross-sectional, observational study. PARTICIPANTS: Forty-five eyes of 23 patients with iAMD. METHODS: Patients underwent OCT and microperimetry. OCT scans were evaluated for the risk factors intraretinal hyperreflective foci (HRF), hyporeflectivity within drusenoid lesions (HRDL), subretinal drusenoid deposits, double-layer sign (DLS), and drusen volume. Microperimetric retinal sensitivity was analyzed with a 33-point grid covering the macula. With a novel method of determining what part of the retina corresponded to each microperimetry point, a Voronoi diagram was constructed, dividing the macula in cells consisting of the region nearer to each point than any other. The Voronoi diagram was superimposed on the OCT, making it possible to determine the point-to-point location of the OCT risk factors. Univariable and multivariable linear mixed-effect models were used for analysis. MAIN OUTCOME MEASURES: Association between microperimetric retinal sensitivity and OCT risk factors at individual measuring points. RESULTS: One thousand four hundred seventy-nine points of retinal sensitivity and corresponding structural area on OCT were included in this study. Retinal sensitivity was significantly decreased with presence of the OCT risk factors HRF, HRDL, DLS, and drusen volume (all P < 0.001) when analyzed with the univariable linear mixed-effect model. The multivariable model showed a significant decrease of retinal sensitivity with presence of HRF (P < 0.001), DLS (P = 0.025), and greater drusen volume (P < 0.001). CONCLUSIONS: Presence of HRF, DLS, and greater drusen volume, all of which increase the risk of disease progression, is significantly and independently associated with decreased microperimetric retinal sensitivity in patients with iAMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Lifestyle and demographic associations with 47 inflammatory and vascular stress biomarkers in 9876 blood donors.

BACKGROUND: The emerging use of biomarkers in research and tailored care introduces a need for information about the association between biomarkers and basic demographics and lifestyle factors revealing expectable concentrations in healthy individuals while considering general demographic differences. METHODS: A selection of 47 biomarkers, including markers of inflammation and vascular stress, were measured in plasma samples from 9876 Danish Blood Donor Study participants. Using regression models, we examined the association between biomarkers and sex, age, Body Mass Index (BMI), and smoking. RESULTS: Here we show that concentrations of inflammation and vascular stress biomarkers generally increase with higher age, BMI, and smoking. Sex-specific effects are observed for multiple biomarkers. CONCLUSION: This study provides comprehensive information on concentrations of 47 plasma biomarkers in healthy individuals. The study emphasizes that knowledge about biomarker concentrations in healthy individuals is critical for improved understanding of disease pathology and for tailored care and decision support tools.

Blood-based biomarkers are circulating molecules that can help to indicate health or disease. Biomarker levels may vary depending on demographic and lifestyle factors such as age, sex, smoking status, and body mass index. Here, we examine the effects of these demographic and lifestyle factors on levels of biomarkers related to activation of the immune system and cardiovascular stress. Measurements of 47 different proteins were performed on blood samples from nearly 10,000 healthy Danish blood donors. Measurement data were linked with questionnaire data to assess effects of lifestyle. We found that immune activation and vascular stress generally increased with age, BMI, and smoking. As these measurements are from healthy blood donors they can serve as a reference for expectable effects and inflammation levels in healthy individuals. Knowledge about the healthy state is important for understanding disease progression and optimizing care.

VEGF Inhibition Associates With Decreased Risk of Mortality in Patients With Neovascular Age-related Macular Degeneration.

Purpose: Controversy exists regarding the systemic safety of intravitreal VEGF inhibitors in the treatment of neovascular age-related macular degeneration (nAMD). We aimed to investigate the potential impact of VEGF inhibitor treatment on the risk of all-cause mortality and cardiovascular disease (CVD) among patients with nAMD. Design: A nationwide register-based cohort study with 16 years follow-up. Participants: Patients with nAMD exposed with VEGF inhibitors (n = 37 733) and unexposed individuals without nAMD (n = 1 897 073) aged ≥ 65 years residing in Denmark between January 1, 2007, and December 31, 2022. Methods: Cox proportional hazards analysis was conducted to assess the effect of intravitreal VEGF inhibitor treatment on all-cause mortality and incident CVD. Main Outcome Measures: In a predefined analysis plan we defined primary outcomes as hazard ratios (HRs) of all-cause mortality and a composite CVD endpoint in patients with nAMD treated with VEGF inhibitors compared with individuals without nAMD. The secondary outcomes encompassed analyses that explored the impact of the number of doses and the association between exposure and outcome over a specific time period. Results: Overall, 63.7% of patients with nAMD were women with an average age of 69.9 years (interquartile range 65.0-76.0 years). Patients exposed to VEGF inhibitors demonstrated a reduced risk of all-cause mortality compared with individuals without nAMD (HR, 0.79; 95% confidence interval [CI], 0.78-0.81), and an increased risk of composite CVD (HR, 1.04; 95% CI, 1.01-1.07). The decreased risk of all-cause mortality persisted, but there was no significant association between VEGF inhibitor treatment and CVD when patients with nAMD were grouped by the number of doses or considered exposed within 60 days postinjection. Conclusions: Our study revealed a decreased risk of all-cause mortality and a 4% increased risk of CVD among patients with nAMD exposed with VEGF inhibitors. The decreased risk of mortality is unlikely to be directly pathophysiologically related to VEGF inhibitor treatment. Instead, we speculate that patients undergoing VEGF inhibitor treatment are, on average, individuals in good health with adequate personal resources. Therefore, they also have a higher likelihood of overall survival. These findings strongly support the safety of VEGF inhibitor treatment in terms of all-cause mortality and CVD among patients with nAMD. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Interleukin-8 Promoter Polymorphism -251 A/T and Treatment Response in Neovascular Age-related Macular Degeneration.

Purpose: Interleukin-8 (IL-8) is a potent pro-angiogenic and pro-inflammatory chemokine, suggested to hold a role in neovascular age-related macular degeneration (nAMD). Our aim is to study the association of the single-nucleotide polymorphism -251 A/T (rs4073) in the IL-8 promoter region with the treatment response to intravitreal anti-vascular endothelial growth factor (VEGF) injections in nAMD. Patients and Methods: This is a prospective study of treatment-naïve patients with nAMD. Treatment response after a loading dose of three intravitreal anti-VEGF injections was defined as functional response based on change in visual acuity, and morphological response based on change in central retinal thickness (CRT) and intraretinal fluid on optical coherence tomography. Morphological response was categorized in good, partial, and poor responders. Blood DNA was analyzed for -251 A/T genotype. Results: The IL-8 promoter polymorphism -251 A/T was not significantly associated to functional treatment response (P=0.09). No significant association was found between genotype and morphological treatment response (P=0.799). Older age was significantly associated to good morphological responders compared to partial and poor responders (P=0.014). Conclusion: The IL-8 polymorphism -251 A/T is not associated to morphological nor functional treatment response to intravitreal anti-VEGF injections in patients with nAMD.

Chemokine Receptor Profile of T Cells and Progression Rate of Geographic Atrophy Secondary to Age-related Macular Degeneration.

Purpose: Geographic atrophy (GA) secondary to age-related macular degeneration is a progressive retinal degenerative disease. Systemic chemokine receptors and known risk-associated single-nucleotide polymorphisms have been associated with GA pathogenesis. Because halting progression is pivotal for patients, we investigated the association of candidate chemokine receptors and progression rate (PR) of atrophic lesions in patients with GA. Methods: This prospective observational study conducted at a single center included 85 patients with GA and 45 healthy controls. Patients were followed up after 13 months on average. Serial fundus autofluorescence images were used to determine the PR of atrophic lesions. The proportion of chemokine receptors on peripheral lymphocytes were determined by flow cytometric analysis. Results: Patients with GA had a lower proportion of CCR6 on CD8+T cells compared to healthy controls. Importantly, the proportion of CCR6 on CD4+T cells was lower in patients with fast GA progression compared to patients with slow progression of disease, suggesting that dysregulation of CCR6 could be involved in progression of GA. We also found that GA patients had a markedly higher percentage of CCR5 on CD4+ and CD8+T cells compared to healthy controls. After stratification according to ARMS2 polymorphism, we found a significantly lower level of CCR5 on CD8+T cells among patients with high-risk genotypes compared with patients with the low-risk genotype. Conclusions: Our study finds that chemokine receptors are dysregulated in patients with GA and that CCR6 might be involved in GA progression, making it a potential target for intervention.

Splenic monocytes drive pathogenic subretinal inflammation in age-related macular degeneration.

Age-related macular degeneration (AMD) is invariably associated with the chronic accumulation of activated mononuclear phagocytes in the subretinal space. The mononuclear phagocytes are composed of microglial cells but also of monocyte-derived cells, which promote photoreceptor degeneration and choroidal neovascularization. Infiltrating blood monocytes can originate directly from bone marrow, but also from a splenic reservoir, where bone marrow monocytes develop into angiotensin II receptor (ATR1)+ splenic monocytes. The involvement of splenic monocytes in neurodegenerative diseases such as AMD is not well understood. Using acute inflammatory and well-phenotyped AMD models, we demonstrate that angiotensin II mobilizes ATR1+ splenic monocytes, which we show are defined by a transcriptional signature using single-cell RNA sequencing and differ functionally from bone marrow monocytes. Splenic monocytes participate in the chorio-retinal infiltration and their inhibition by ATR1 antagonist and splenectomy reduces the subretinal mononuclear phagocyte accumulation and pathological choroidal neovascularization formation. In aged AMD-risk ApoE2-expressing mice, a chronic AMD model, ATR1 antagonist and splenectomy also inhibit the chronic retinal inflammation and associated cone degeneration that characterizes these mice. Our observation of elevated levels of plasma angiotensin II in AMD patients, suggests that similar events take place in clinical disease and argue for the therapeutic potential of ATR1 antagonists to inhibit splenic monocytes for the treatment of blinding AMD.

Exudative Progression of Treatment-Naïve Nonexudative Macular Neovascularization in Age-Related Macular Degeneration: A Systematic Review With Meta-Analyses.

PURPOSE: To systematically review and report the rate of exudative progression over time in patients with nonexudative macular neovascularization (MNV) in age-related macular degeneration (AMD). DESIGN: Systematic review with prevalence meta-analyses and individual participant meta-analysis. METHODS: We searched 10 literature databases on March 26, 2023, for studies of consecutive patients with treatment-naïve nonexudative MNV in AMD. The primary outcome of interest was time from diagnosis to exudative progression. We conducted meta-analyses on the prevalence of exudative progression at 1 and 2 years. Where possible, we extracted individual participant data from studies and conducted an individual participant meta-analysis and explored the exudative progression using a time-to-event curve. RESULTS: We identified 16 eligible studies with a total of 384 eyes with nonexudative MNV. Exudative progression had occurred in 20.9% (95% CI 13.1%-29.8%) of eyes at 1 year and in 30.7% (95% CI 21.8%-40.4%) at 2 years. Similar results were observed in the individual participant meta-analysis, showing exudative progression in 18.9% (95% CI 13.5%-26.3%) of eyes at 1 year and 31.3% (95% CI 24.2%-40.0%) at 2 years. Risk factors for a fast exudative progression were the presence of subretinal lipid globules, large MNV areas, rapid MNV growth, growth in pigment epithelium detachment height and width, appearance of a branching pattern, and development of a hyporeflective halo around the MNV. CONCLUSIONS: Nonexudative MNVs in AMD are at high risk of exudative progression. Recognition of these lesions may allow for better individualized follow-up regimens in which closer monitoring may facilitate earlier diagnosis of exudative progression.

Complement factor H Y402H polymorphism results in diminishing CD4+ T cells and increasing C-reactive protein in plasma.

Age-related macular degeneration (AMD) is a common cause of visual loss among the elderly. Genetic variants in the gene encoding complement factor H (CFH) have been identified as an AMD susceptibility gene, however, the mechanistic link is debated. Here, we investigated the link between the CFH Y402H genotype and low-grade inflammation. We recruited 153 healthy individuals, 84 participants with dry stages of AMD, and 148 participants with neovascular AMD. All participants were subjected to detailed retinal examination, and interview regarding comorbidities and lifestyle. Blood samples were analyzed for level of C-Reactive Protein (CRP), white blood cell differential count, and stained with fluorescent antibodies to differentiate CD4+ and CD8+ T cells. CFH Y402H genotyping was performed using an allele-specific polymerase chain reaction genotyping assay. Splenocytes from young and aged wild type and Cfh null mutant C57BL/6J mice were examined for CD4+ and CD8+ T cells. Healthy individuals with the CFH Y402H at-risk polymorphism HH had higher levels of CRP and lower proportions of CD4+ T cells compared to persons with the YH or YY polymorphism (P = 0.037, Chi-square). Healthy individuals with the HH polymorphism displayed lower proportions of CD4+ T cells with ageing (P < 0.01, one-way ANOVA), whereas both young and aged Cfh null mutant mice displayed lower proportions of CD4+ T cells (P < 0.001 and P < 0.05; unpaired t test). Participants with dry AMD and the HH polymorphism had similarly lower proportions of CD4+ T cells (P = 0.024, one-way ANOVA), but no difference in CRP-levels. In the neovascular stage of AMD, there was no difference in proportion of CD4+ cells or CRP levels according to genotype. The risk-associated CFH genotype is associated with an age-related decrease in proportion of CD4+ T cells and increased levels of CRP in healthy individuals. This indicates that decreased complement regulation results in extensive changes in innate and adaptive immune compartments that precede development of AMD.

Age-related macular degeneration.

This review investigates age-related macular degeneration (AMD) which is a degenerative retinal disease. The pathogenesis of the disease is unknown, but tobacco smoking is a significant risk factor for the development of the disease. The wet form of AMD can be treated by intraocular injection of an antibody that binds vascular endothelial growth factor (VEGF) which is involved in the disease process. The introduction of anti-VEGF treatment is a major reason why blindness secondary to wet AMD is now negligible. The demographic development can be expected to increase the demand for treatment of AMD considerably in the future.

Patient perspectives and barriers in the treatment of neovascular age-related macular degeneration in Denmark: a qualitative study.

OBJECTIVES: This qualitative study aims to identify patient-reported barriers to treatment for neovascular age-related macular degeneration (nAMD) and investigate their impact on quality of life. DESIGN: Using a qualitative explorative design. SETTING: Semi-structured individual or dyadic interviews were conducted with patients and their relatives. PARTICIPANTS: Twenty-one patients completed the interview, with four of them having a relative present. INTERVENTIONS: Gadamer's hermeneutics guided the epistemological approach, and maximum variation sampling was employed to capture diverse patient experiences. An advisory board consisting of patients, relatives and ophthalmologists ensured the relevance of the study. Thematic analysis was conducted using NVivo software. PRIMARY AND SECONDARY OUTCOME MEASURES: To investigate patient-reported barriers to the recommended treatment for nAMD and impact on quality of life. RESULTS: The study included 21 patients with nAMD, with a median age of 79 years. Five themes emerged: (1) good compliance with intravitreal treatment, (2) the dual role of relatives, (3) treatment commute, (4) hospital barriers, (5) preventive health literacy. CONCLUSION: This study highlights the resilience and adherence of patients with nAMD in Denmark to their treatment despite various barriers. While the therapy may have negative effects on their well-being, patients do not opt out of treatment. These findings underscore the importance of personalised treatment plans that provide, for example, convenient access to care and clear future agreements at the hospital. By adopting more patient-centred approaches, healthcare providers can enhance patient satisfaction and improve treatment adherence, ultimately leading to better patient outcomes and quality of life.

Geographic atrophy - Signs, symptoms, and quality of life.

Geographic atrophy (GA) is a prevalent cause of vision loss among elderly and is associated with a significant loss of function. We reviewed the current literature to assess the effect of GA on patients' daily lives and well-being. We record and organize the signs, symptoms, and impacts that are important in life with GA. Further, we examined the impact of GA on vision-related quality of life. The main complaint among patients was difficulties regarding daily tasks, especially reading and other near activities. However, a large proportion of patients also reported fear, frustration, and anxiety as salient symptoms with large impact. Many patients do not have adequate information about their condition as well as the prognosis. The most commonly used measure of patient-reported outcome measure (PROM) is the National Eye Institute Visual Function Questionnaire (VFQ), that reflects the severity of impact on 12 subscales, from where near activities, general vision, mental health, and role difficulties had the lowest scores. Longitudinal studies of GA and the impact of low-vision rehabilitation efforts on health-related quality of life are sparse but suggest a significant improvement on several items. PROM is included in clinical trials, and so far, no drug has shown to improve the functional outcome in terms of PROM.

Use of optical coherence tomography angiography for the diagnosis of age-related macular degeneration.

INTRODUCTION: Age-related macular degeneration (AMD) causes approximately 9% of all blindness worldwide. The introduction of optical coherence tomography angiography (OCT-A) has revealed a potential for non-invasive diagnosis of neovascular AMD (nAMD), but has yet to be proven an accurate method for nAMD diagnosis. The purpose of this study was to map the clinical use of OCT-A in nAMD diagnosis and to investigate the agreement between two consultants in diagnosing nAMD. METHODS: A survey was administered to assess Danish ophthalmologists in nAMD diagnostic modalities. Furthermore, a prospective observational cohort study was conducted in which two consultants graded Triton and Heidelberg OCT-A in patients with suspected nAMD. RESULTS: A total of 21 ophthalmologists completed the survey. OCT-A combined with structural OCT was the first choice for the majority (81%), whereas dye-based ophthalmic angiography was used when in doubt of the diagnosis. OCT-A was used to guide treatment decisions in 64% of patients. Some ophthalmologists (48%) had no formal OCT-A training. In the second part of the study, an agreement was recorded between the two consultants in 86% of the cases with Triton OCT-A and 66% with Heidelberg OCT-A. CONCLUSIONS: OCT-A with structural OCT has become a primary diagnostic method of nAMD, but national guidelines are lacking. Future implementation of new diagnostic technology of nAMD should include trial-based guidelines and physician training. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Systemic virus infection results in CD8 T cell recruitment to the retina in the absence of local virus infection.

During recent years, evidence has emerged that immune privileged sites such as the CNS and the retina may be more integrated in the systemic response to infection than was previously believed. In line with this, it was recently shown that a systemic acute virus infection leads to infiltration of CD8 T cells in the brains of immunocompetent mice. In this study, we extend these findings to the neurological tissue of the eye, namely the retina. We show that an acute systemic virus infection in mice leads to a transient CD8 T cell infiltration in the retina that is not directed by virus infection inside the retina. CD8 T cells were found throughout the retinal tissue, and had a high expression of CXCR6 and CXCR3, as also reported for tissue residing CD8 T cells in the lung and liver. We also show that the pigment epithelium lining the retina expresses CXCL16 (the ligand for CXCR6) similar to epithelial cells of the lung. Thus, our results suggest that the retina undergoes immune surveillance during a systemic infection, and that this surveillance appears to be directed by mechanisms similar to those described for non-privileged tissues.

Heart-Rate Variability Correlates to Choroidal Thickness in Central Serous Chorioretinopathy.

Purpose: Patients with central serous chorioretinopathy (CSC) have previously been shown to have a lower heart rate variability (HRV), implying a lower vagal tone. Vagal tone alters mineralocorticoids, which in turn affect the thickness of the choroid. Since increased choroidal thickness is characteristic of CSC, we wanted to investigate its correlation with HRV. Patients and Methods: In this case-control study, 21 acute CSC patients and 31 healthy controls were included. Diagnosis was confirmed by optical coherence tomography (OCT) and retinal examination. HRV was evaluated following accepted standards. Outcome measures were chosen beforehand as follows: Standard deviation of N-N intervals (SDNN), root mean square of successive differences (RMSDD), low frequency/high frequency ratio (LF/HF ratio), and standard deviation ratio from commonly used Poincare plot (SD2/SD1 ratio). Choroidal thickness was measured using OCT directly under the foveola. Results: Patients and healthy controls did not differ in health and medical characteristics in addition to CSC disease. Choroidal thickness was greatest in patients with CSC (mean±SD: 342±80 µm) compared to controls (235±60 µm, p<0.0001). A correlation was observed between LF/HF ratio and choroidal thickness in patients with CSC (Pearson correlation 0.63, p=0.02), where the CSC group had a lower LF/HF ratio (Median 2.39 ms2, IQR: 1.2-4.34 ms2) compared to controls (Median 1.2 ms2, IQR: 0.9-2.4 ms2, p=0.06) and SD2/SD1 ratio (CSC 0.59±0.2 vs controls 0.74±0.3, p=0.06). Conclusion: We found a correlation between the thickness of the choroid and the HRV-measured LF/HF ratio in patients with CSC and showed a borderline significant reduction in HRV measurements in patients with CSC. The data imply that vagal alterations exist in patients with CSC. Due to the low n, this should be considered as a pilot study. Further studies are warranted to elucidate mechanisms and validate findings.

Predictive value of retinal oximetry, optical coherence tomography angiography and microperimetry in patients with treatment-naïve branch retinal vein occlusion.

Vascular endothelial growth factor inhibitors have substantially improved the visual outcomes in patients with macular edema (ME) caused by branch retinal vein occlusion (BRVO), but treatment outcomes are highly variable and early prediction of expected clinical outcome would be important for individualized treatment.As non-invasive metabolic, structural and functional retinal markers might act as early predictors of clinical outcomes, we performed a 12-month, prospective study aimed to evaluate if baseline retinal oximetry, optical coherence tomography angiography (OCT-A) or microperimetry were able to predict need of treatment, structural or functional outcome in patients with ME caused by treatment-näive BRVO.We evaluated 41 eyes of 41 patients with a mean age of 69.6 years and 56% females. We found a strong tendency towards a higher retinal arteriolar oxygen saturation in patients without a need of additional aflibercept treatment after the loading phase (99.8% vs. 92.3%, adjusted odds ratio 0.80 (95% confidence interval 0.64-1.00), adjusted p = 0.058), but otherwise, retinal oximetry, OCT-A or microperimetry were not able to predict need of treatment, structural nor functional outcomes. (Trial registration: clinicaltrials.gov, S-20,170,084. Registered 24 August 2014, https://clinicaltrials.gov/ct2/show/NCT03651011 ).

Vision-related quality of life is selectively affected by comorbidities in patients with geographic atrophy.

BACKGROUND: The atrophic late stage of age-related macular degeneration (AMD) is termed geographic atrophy (GA), and affects visual acuity (VA) as well as quality of life (QoL). Previous studies have found that best-corrected VA (BCVA), the standard vision assessment often underrepresents functional deficits. Therefore, the purpose of this study was to evaluate the correlation between atrophic lesion size, VA and QoL measured with the National Eye Institute Visual Function Questionnaire (VFQ-39) in a Danish population. Moreover, we wanted to evaluate the correlation between comorbidities, behavioural factors, and QoL. METHODS: This was prospective clinical study of 51 patients with GA in one or both eyes, of these 45 patients had bilateral GA. Patients were consecutively included between April 2021 and February 2022. All patients filled in the VFQ-39 questionnaire except the subscales "ocular pain" and "peripheral vision." Lesion size was measured from fundus autoflourescense images, and BCVA was assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. RESULTS: We found an overall low score in each VFQ-39 subscale scores reflected by GA. Lesion size and VA were both significantly associated with all VFQ-39 subscale scores except for "general health." VA showed a larger effect on QoL than lesion size. Chronic obstructive pulmonary disease (COPD) was associated with a lower score in the subscale score "general health" but none of the other subscale scores were affected. Cardiovascular disease (CVD) was associated with a lower BCVA as well as in QoL reflected in the subscale scores "poor general vision," "near activities," and "dependency" of VFQ-39. CONCLUSION: Both atrophic lesion size and visual acuity affects QoL in Danish patients with GA, who reports an overall poor QoL. CVD seems to have a negative effect on disease, as well as in VFQ-39 in several subscales, whereas COPD did not affect disease severity or vision-related subscales in VFQ-39.

Serum levels of IL-4, IL-13 and IL-33 in patients with age-related macular degeneration and myeloproliferative neoplasms.

Immune responses play a key role in the pathogenesis and progression of myeloproliferative neoplasms (MPN) and age-related macular degeneration (AMD). Recent studies suggested using MPNs as a "Human Inflammation Model" of drusen development and previous results showed interleukin-4 (IL-4) dysregulation in MPN and AMD. IL-4, IL-13 and IL-33 are all cytokines involved in the type 2 inflammatory response. This study investigated the cytokine levels of IL-4, IL-13 and IL-33 in serum of MPN and AMD patients. This cross-sectional study included 35 patients with MPN with drusen (MPNd) and 27 with MPN and normal retinas (MPNn), 28 patients with intermediate AMD (iAMD) and 29 with neovascular AMD (nAMD). With immunoassays, we quantified and compared levels of IL-4, IL-13 and IL-33 in serum between the groups. The study was conducted at Zealand University Hospital, Roskilde, Denmark, between July 2018 and November 2020. The serum levels of IL-4 were significantly higher in the MPNd group than in the MPNn group (p = 0.003). In regard to IL-33, the difference between MPNd and MPNn was not significant (p = 0.069), however, when subdivided into subgroups, a significant difference was found between polycythemia vera patients with drusen and those without drusen (p = 0.005). We found no IL-13 difference between the MPNd and MPNn groups. Our data didn't show any significant IL-4 or IL-13 serum level difference between the MPNd and iAMD groups but in regard to IL-33, data recorded a significant serum level difference between the two groups. There was no statistically significant difference between the MPNn, iAMD and nAMD groups in levels of IL-4, IL-13 and IL-33. These findings suggested that the serum levels of IL-4 and IL-33 might play a role in drusen development in MPN patients. The results might represent the type 2 inflammatory arm of the disease. The findings support the association between chronic inflammation and drusen.