| 1. |
- Krogh Nielsen, Marie, et al.
(författare)
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Patients with a fast progression profile in geographic atrophy have increased CD200 expression on circulating monocytes
- 2019
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Ingår i: Clinical and Experimental Ophthalmology. - : Wiley. - 1442-6404. ; 47:1, s. 69-78
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Geographic atrophy (GA) is a progressing atrophy of the neuroretina with no treatment option. Background: Age-related malfunction of retinal microglia amplifies response towards age-related tissue stress in age-related macular degeneration. Here, we investigated monocyte CD200 expression – the circulating middleman negotiating retinal microglial activity – in a poorly understood subtype of age-related macular degeneration. Design: Prospective case–control study. Participants: Forty-six patients with GA and 26 healthy controls were included. Methods: All participants were subjected to a structured interview and detailed retinal examination. Controls were recruited from patient's spouses accompanying them in the clinic to match the groups best possibly. Participants had no history of immune disorders or cancer, and did not receive any immune-modulating medication. Patients did not have any history or sign of choroidal neovascularization in either eye. Fresh drawn blood was stained with monoclonal antibodies and prepared for flow cytometry to evaluate CD200 expression in monocytes and their functional subsets. Main Outcome Measures: The percentage of CD200+ monocytes in patients and controls. Results: We found that monocytes were more CD200 positive in patients with GA compared to healthy age-matched controls. Then, we explored the potential relationship between CD200 expression and important fundus autofluorescence patterns that predict disease progression. Patients with a high risk of progression (patients with high degree of hyperautofluorescence) had distinctly increased CD200 expression compared to other patients with GA. Conclusions and Relevance: Our data reveals that abnormal monocytic CD200 expression is present in GA, and in particular among those identified as fast progressors.
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| 2. |
- Lomo, Trine, et al.
(författare)
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Three cases of Charles Bonnet Syndrome in patients with advanced glaucomatous visual field loss but preserved visual acuity
- 2021
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 99:4, s. 448-451
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe three cases of Charles Bonnet syndrome (CBS) in glaucoma patients with preserved visual acuity. Methods: Three glaucoma patients who had taken part in a recent CBS study were interviewed about their hallucinations. The patients underwent macular optical coherence tomography (OCT) of both eyes. The visual function was evaluated with visual field measurement (Humphrey visual field analyser) and visual acuity testing (Snellen scale). Results: All three patients had preserved visual acuity (≥0.5 in both eyes) and at least one eye with advanced visual field defect (Mean Deviation worse than −12.00 decibel). They all reported vivid visual hallucinations with insight into the unreal nature of the hallucinations. Conclusion: Charles Bonnet syndrome can occur in glaucoma despite preserved visual acuity. Awareness of this relation is desirable among clinicians, as it will improve communication with patients.
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| 3. |
- Niazi, Siar, et al.
(författare)
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Prevalence of Charles Bonnet syndrome in patients with age-related macular degeneration : systematic review and meta-analysis
- 2020
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 98:2, s. 121-131
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Forskningsöversikt (refereegranskat)abstract
- Age-related macular degeneration (AMD) is the most common cause of visual impairment in the developed world. A number of patients experience complex lifelike visual experiences—Charles Bonnet syndrome (CBS). In this systematic review, our aim was to provide an overview of the CBS literature in relation to AMD, to determine the prevalence of CBS in patients with AMD and to provide an overview of associated demographical and clinical aspects. We searched the literature databases PubMed/MEDLINE, EMBASE, Web of Science, the Cochrane Central, and PsycINFO on 22 March 2019 for studies evaluating the prevalence of CBS in patients with AMD. Two independent authors extracted the data and evaluated risk of bias. Studies were reviewed qualitatively in the text and quantitatively in a meta-analysis including subgroup analyses for differences between demographic and clinical factors. We identified 18 studies with data on >4303 patients with AMD. We found an overall prevalence of CBS of 15.8% (95% confidence interval: 11.0%–21.2%). When looking at consecutively recruited patients with neovascular AMD from the clinic, prevalence of CBS was 7.2% (95% confidence interval: 4.3%–10.6%). Among visitors to visual rehabilitation centres, prevalence of CBS was 31.6% (95% confidence interval: 21.7%–42.3%). Taken together, we find that CBS is rather common in patients with AMD.
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| 4. |
- Peters, Dorothea, et al.
(författare)
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Charles Bonnet Syndrome in Patients with Open-Angle Glaucoma : Prevalence and Correlation to Visual Field Loss
- 2022
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Ingår i: Ophthalmology Glaucoma. - : Elsevier BV. - 2589-4234 .- 2589-4196. ; 5:3, s. 337-344
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To determine the prevalence and characteristics of Charles Bonnet Syndrome (CBS) and its relation to visual field loss (VFL) in patients with open-angle glaucoma (OAG). Design: Prospective, cross-sectional study. Participants: Adult patients (n = 337) with manifest OAG with verified VFL and without significant macular disease or extraocular conditions known to cause visual hallucinations. Methods: Patients attending the glaucoma outpatient department of the Skåne University hospital, Malmö, Sweden, between April 1, 2018, and December 31, 2018, were consecutively evaluated for inclusion. Potentially eligible patients admitting to having complex visual hallucinations were interviewed to explore the characteristics of their hallucinatory experiences. Recent automated visual field examinations were available for all participants, and swept-source OCT was performed in participants with CBS to rule out previously undiagnosed macular pathology. The correlation between potential risk factors and CBS was evaluated with logistic regression analysis. Main Outcome Measure: Prevalence of CBS in patients with OAG. Results: Charles Bonnet Syndrome was found in 7.1% (95% confidence interval [CI], 4.7–10.6) of patients with OAG. Participants with CBS were more likely to have at least 1 eye with a visual field index (VFI) of ≤30% compared with those without CBS (71% vs. 34.2%; P = 0.001). Although the best-corrected visual acuity (BCVA) in the worse eye was significantly lower in participants with CBS (decimal equivalent of Snellen BCVA: 0.25 vs. 0.6, P = 0.003), 33% of these participants had a BCVA of ≥0.5 in the worse eye. In multivariable analysis, CBS was correlated to the VFI of the better eye (odds ratio, 0.984; 95% CI, 0.969–0.998, P = 0.030) and the BCVA of the worse-seeing eye (odds ratio, 0.210; 95% CI, 0.046–0.952, P = 0.043). Conclusions: Charles Bonnet Syndrome was not a rare condition in patients with glaucoma. Patients with a combination of advanced VFL and low BCVA had the highest risk of CBS; however, 1 of 3 patients with CBS had a BCVA of ≥0.5 in both eyes. These findings emphasize the importance of being attentive to symptoms of CBS in patients with glaucomatous VFL even when visual acuity is preserved.
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| 5. |
- Randeblad, Patrik, et al.
(författare)
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Charles Bonnet Syndrome Adversely Affects Vision-Related Quality of Life in Patients with Glaucoma
- 2024
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Ingår i: Ophthalmology Glaucoma. - 2589-4234. ; 7:1, s. 30-36
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the impact of Charles Bonnet syndrome (CBS) on vision-related quality of life (VRQoL) in patients with glaucoma. Design: Cross-sectional cohort study. Participants: Twenty-four patients with CBS and 42 matched controls without CBS out of 337 patients with open-angle glaucoma (OAG) with visual field (VF) loss. Methods: A matching technique was used to identify control patients with similar disease stage, best-corrected visual acuity (BCVA) and age to patients with CBS. Patients’ VRQoL was determined using the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25). Rasch-calibrated NEI VFQ-25 scores of the CBS group and the control group were compared. Uni- and multivariable regression analysis was used to evaluate the impact of different factors on VRQoL. Main Outcome Measures: Vision-related quality of life in patients with glaucoma with CBS and without CBS. Results: Vision-related quality of life scores were significantly lower in the CBS group than in the control group on both the visual functioning scale with 39 points (95% confidence interval (CI): 30–48) vs. 52 points (95% CI: 46–58) (P = 0.013) and on the socioemotional scale with 45 points (95% CI: 37–53) vs. 58 points (95% CI: 51–65) (P = 0.015). Univariable regression analysis showed that integrated visual field mean deviation (IVF-MD) (r2 = 0.334, P < 0.001), BCVA in the better eye (r2 = 0.117, P = 0.003), and the presence of CBS (r2 = 0.078, P = 0.013) were significantly correlated to VRQoL scores on the visual functioning scale. Integrated visual field mean deviation (r2 = 0.281, P < 0.001), age (r2 = 0.048, P = 0.042), and the presence of CBS (r2 = 0.076, P = 0.015) were significantly correlated to VRQoL scores on the socioemotional scale. Multivariable regression analysis showed that IVF-MD and the presence of CBS accounted for nearly 40% of the VRQoL score on the visual functioning scale (R2 = 0.393, P < 0.001) and for 34% of the VRQoL score on the socioemotional scale (R2 = 0.339, P < 0.001). Conclusions: Charles Bonnet syndrome had a significant negative association to VRQoL in patients with glaucoma. Presence of CBS should be considered when evaluating VRQoL in patients with glaucoma. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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| 6. |
- Subhi, Yousif, et al.
(författare)
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Association of CD11b + Monocytes and Anti-Vascular Endothelial Growth Factor Injections in Treatment of Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy
- 2019
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Ingår i: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 137:5, s. 515-522
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Tidskriftsartikel (refereegranskat)abstract
- Importance: CD11b + immune cells have been implicated in the formation of choroidal neovascularization in experimental studies on animals and disease-association studies on humans. However, the clinical importance of such observations remains unknown. Objective: To investigate whether the proportion of CD11b + circulating monocytes is associated with the number of anti-vascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Design, Setting, and Participants: These observational cohort studies collected data from January 1, 2010, through December 31, 2013, and from January 1, 2015, through December 31, 2018. Fresh venous blood samples were acquired for flow cytometric immune studies in patients with neovascular AMD or PCV receiving treatment with aflibercept or ranibizumab as needed for 36 months. Patients (n = 81) without immune diseases were consecutively recruited from a single center in Denmark. Exposures: Proportion of CD11b + circulating monocytes. Main Outcomes and Measures: The estimation of the number of intravitreal anti-VEGF injections given at 12, 24, and 36 months by the proportion of CD11b + circulating monocytes and the correlation between these values. The angiogenic role of CD11b + circulating monocytes was further evaluated by investigating the expression of the known proangiogenic receptor CCR2. Results: Eighty-one patients were included in the analysis (54% women; mean [SD] age, 76 [7] years). The proportion of CD11b + monocytes at baseline positively estimated the future number of anti-VEGF injections at 12 (ρ = 0.77; 95% CI, 0.35-0.93; P =.004), 24 (ρ = 0.82; 95% CI, 0.44-0.95; P =.002), and 36 (ρ = 0.78; 95% CI, 0.34-0.94; P =.005) months. This association was also found retrospectively in a larger sample of patients with neovascular AMD at 12 (ρ = 0.46; 95% CI, 0.16-0.68; P =.004), 24 (ρ = 0.49; 95% CI, 0.20-0.70; P =.002), and 36 (ρ = 0.65; 95% CI, 0.41-0.80; P <.001) months and patients with PCV at 12 (ρ = 0.27; 95% CI, -0.28 to 0.68; P =.30), 24 (ρ = 0.60; 95% CI, 0.12-0.85; P =.02), and 36 (ρ = 0.70; 95% CI, 0.27-0.90; P =.005) months, suggesting that this association is not specific to AMD but rather reflects VEGF activity in neovascularization. CD11b + monocytes highly coexpressed CCR2, an important monocytic marker of proangiogenic activity. Conclusions and Relevance: Results of this study demonstrated that the proportion of circulating CD11b + monocytes estimated and correlated with the number of anti-VEGF injections in patients with neovascular AMD and PCV. Additional longitudinal studies are needed to determine whether these findings have clinical relevance to influence treatment algorithms or provide novel targets for medical therapy..
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| 7. |
- Subhi, Yousif, et al.
(författare)
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CD11b and CD200 on circulating monocytes differentiate two angiographic subtypes of polypoidal choroidal vasculopathy
- 2017
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404. ; 58:12, s. 5242-5250
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate surface expression of CD11b and CD200 on circulating monocytes in patients with polypoidal choroidal vasculopathy (PCV). Methods: This was a prospective case-control study of patients with PCV (n = 27), age-matched healthy controls (n = 27), and patients with neovascular AMD (n = 49). All participants underwent a comprehensive ocular examination. Fluorescein and indocyanine green angiography were performed in patients suspected of neovascular AMD or PCV. Polypoidal choroidal vasculopathy was angiographically categorized into those with a strong presence of a branching vascular network (BVN) (type 1) or with a faint/no clear presence of a BVN (type 2). Fresh venous blood was stained with fluorescent antibodies for flow cytometric analyses. We compared the percentages of CD11b+, CD200+, and CD11b+CD200+monocytes between groups of diagnosis and between different angiographic subtypes of PCV. Results: Overall, CD11b+monocytes were both increased in patients with PCV and neovascular AMD. CD200+and CD11b+CD200+monocytes were increased in patients with neovascular AMD. An age-related increase in CD11b+CD200+monocytes was absent in patients with PCV and neovascular AMD. Patients with PCV type 1 had significantly higher CD11b+, CD200+, and CD11b+CD200+monocytes, whereas patients with PCV type 2 had levels similar to that in healthy controls. Conclusions: We found that PCV is immunologically heterogeneous with significant differences between angiographic subtypes. Increased CD11b+and CD200+monocytes in those with a strong presence of BVN indicate that BVN development may be associated with retinal injury and a VEGF-mediated process that is either reflected or propelled by systemic changes in monocytes.
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| 8. |
- Subhi, Yousif, et al.
(författare)
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Plasma markers of chronic low-grade inflammation in polypoidal choroidal vasculopathy and neovascular age-related macular degeneration
- 2019
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X. ; 97:1, s. 99-106
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Ageing is the strongest predictor of neovascular age-related macular degeneration (AMD), where neuroinflammation is known to play a major role. Less is known about polypoidal choroidal vasculopathy (PCV), which is an important differential diagnosis to neovascular AMD. Here, we report plasma markers of inflammation with age (inflammaging) in patients with PCV, patients with neovascular AMD and a healthy age-matched control group. Methods: We isolated plasma from fresh venous blood obtained from participants (n = 90) with either PCV, neovascular AMD, or healthy maculae. Interleukin(IL)-1β, IL-6, IL-8, IL-10 and tumour necrosis factor receptor 2 (TNF-R2) were measured using U-PLEX Human Assays. Routine plasma C-reactive protein (CRP) was measured using Dimension Vista 1500. Results: Patients with PCV had plasma levels of IL-1β, IL-6, IL-8, IL-10 and TNF-R2 similar to that in healthy controls. Patients with neovascular AMD had significantly higher plasma IL-1β, IL-6 and IL-10 than healthy controls, whereas no significant differences were observed for plasma IL-8 and TNF-R2. Differences between plasma IL-1β, IL-6 and IL-10 possessed a positive but weak ability in discriminating neovascular AMD from PCV. Both patients with PCV and patients with neovascular AMD had significantly higher levels of routine plasma CRP. Conclusion: Patients with PCV differ from patients with neovascular AMD in terms of plasma inflammaging profile. Apart from increased CRP, no signs of inflammaging were observed in patients with PCV. In patients with neovascular AMD, we find a specific angiogenesis-twisted inflammaging profile.
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| 9. |
- Subhi, Yousif, et al.
(författare)
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Polypoidal Choroidal Vasculopathy Associate With Diminished Regulatory T Cells That Are Polarized Into a T Helper 2-Like Phenotype
- 2019
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 60:7, s. 2583-2590
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate possible roles of T helper (Th) cells, regulatory T cells (Tregs), and the recently mapped Th-like Tregs in patients with polypoidal choroidal vasculopathy (PCV). Methods: In this prospective case-control study, we obtained fresh venous blood from patients with PCV (n = 24), age-matched healthy controls (n = 32), and patients with neovascular AMD (n = 45). All participants underwent a comprehensive ocular examination including fluorescein and indocyanine green angiography for where retinal disease was suspected. Using flow cytometry, we identified Th subsets, Tregs, and Th-like Tregs. Plasma samples were stored at -80°C to investigate plasma cytokines of interest. Results: Compared to healthy controls, patients with PCV had lower percentages of Tregs (8.7% ± 2.8% vs. 7.3% ± 1.7%, P = 0.027), which were significantly more Th2-like polarized (42.6% ± 13.3% vs. 50.5% ± 13.0%, P = 0.029). These changes differed from that observed in neovascular AMD, which compared to healthy controls had fewer Th1/Th17 cells (3.6% ± 2.7% vs. 2.4% ± 2.5%, P = 0.049), comparable Treg levels, and no distinct polarization of Th-like Tregs. Because of these findings, we measured plasma IL-4 and IL-33 levels. Plasma IL-33 in patients with PCV (median 0.30 pg/mL) was twice as high compared to healthy controls (median 0.16 pg/mL; P = 0.037). Conclusions: PCV associate with diminished Tregs that are polarized more into a Th2-like phenotype. This is correlated to IL-33 levels, which we also find increased in patients with PCV. Our findings suggest a possible role for Th2-like Tregs and IL-33 in PCV.
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| 10. |
- Subhi, Yousif, et al.
(författare)
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Prevalence of Charles Bonnet syndrome in patients with glaucoma : a systematic review with meta-analyses
- 2021
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 99:2, s. 128-133
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Forskningsöversikt (refereegranskat)abstract
- Glaucoma is a widespread sight-threatening condition often only recognized when very pronounced. It is initially characterized by peripheral visual field losses, while advanced stages also affect the central vision. Some of these patients may experience visual hallucinations, the Charles Bonnet syndrome (CBS). In this systematic review and meta-analysis, we provide an overview of the literature dealing with the prevalence of CBS in patients with glaucoma. We searched the databases PubMed/MEDLINE, Embase, Web of Science, the Cochrane Central and PsycInfo on 22 March 2020. Eight studies (n = 827 patients) were identified and included for a qualitative and quantitative analysis. No studies included a representative sample of patients with only glaucoma. In patients with glaucoma in different stages and with ocular comorbidities, prevalence of CBS was 2.8% (CI95%: 0.7–6.1%). Among patients with glaucoma where all had bilateral low visual acuity, prevalence of CBS was 13.5% (CI95%: 8.4–19.6%). In patients with glaucoma who visited vision rehabilitation clinics, presumably due to an extensive vision impairment, prevalence of CBS was 20.1% (CI95%: 16.8–23.6%). Risk factors of CBS besides low vision were high age, female gender, reduced contrast sensitivity and not living alone. Taken together, we find that CBS may not be rare in patients with advanced glaucoma with and without ocular comorbidities. However, limitations of the current literature should be highlighted and careful approach towards conclusions is important. More studies are needed to better understand the prevalence and risk factors among different populations of patients with glaucoma.
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