Danson Vasanthan Muttuvelu

Purpose: To investigate the association between accelerated biological ageing, measured by Phenotypic Age (PhenoAge) and PhenoAge Acceleration (PhenoAgeAccel), and features of early and intermediate age‐related macular degeneration (AMD) in a population‐based cohort. Methods: This cross‐sectional study used data from the National Health and Nutrition Examination Survey. Biological age was estimated using the PhenoAge algorithm, a composite of routine blood biomarkers and chronological age, and PhenoAgeAccel was defined as the residual from regression of PhenoAge on chronological age. Retinal outcomes were drusen ≥500 μm (primary outcome), drusen ≥125 μm and pigmentary abnormalities. Associations were evaluated using logistic regression adjusted for biological sex, race/ethnicity, smoking, body mass index and diabetes. Results: A total of 5322 participants were included (mean age 59.4 ± 12.4 years; 50.4% female). Drusen ≥500 μm were present in 4.1%, drusen ≥125 μm in 10.2% and pigmentary abnormalities in 5.6%. PhenoAgeAccel > + 3 years was associated with higher odds of drusen ≥500 μm (OR: 1.56, 95%CI: 1.07–2.27, p = 0.022), whereas no association was observed for <−3 years. Each 1‐year increase in PhenoAgeAccel was associated with higher odds of drusen ≥500 μm (OR: 1.02, 95%CI: 1.00–1.04, p = 0.022). PhenoAgeAccel > + 3 years was also associated with drusen ≥125 μm (OR: 1.29, 95%CI: 1.00–1.65, p = 0.049), but not with pigmentary abnormalities. Conclusion: Accelerated biological ageing was associated with increased drusen burden, but not pigmentary abnormalities, suggesting that early structural features of AMD may reflect broader systemic ageing processes.

Purpose: To investigate anterior scleral thickness (AST) as a potential anatomical biomarker for central serous chorioretinopathy (CSC) by synthesizing the evidence on differences in AST between eyes with CSC and healthy controls through a systematic review and meta‐analysis. Methods: A systematic literature search was conducted across multiple databases in January 2026. Observational studies comparing AST measured using optical coherence tomography in eyes with CSC and healthy controls were included. Data were extracted independently by two reviewers. Random‐effects meta‐analyses were performed using standardized mean differences (SMD, Cohen's d ). Risk of bias was assessed using the Agency for Healthcare Research and Quality checklist. Results: Eight studies comprising 805 individuals (454 CSC, 351 controls) were included in the qualitative synthesis, seven of which were eligible for meta‐analysis. AST was significantly higher in eyes with CSC compared with controls in all quadrants: temporal (SMD 0.57, 95% CI 0.40–0.75), nasal (SMD 0.48, 95% CI 0.25–0.71), superior (SMD 0.28, 95% CI 0.04–0.53), and inferior (SMD 0.32, 95% CI 0.08–0.57). Analysis for the temporal quadrant showed low heterogeneity. Findings were robust in sensitivity analyses, and funnel plot assessment did not reveal substantial asymmetry. Conclusion: Eyes with CSC exhibited increased AST compared with healthy controls. These findings support a potential role for scleral morphology in CSC pathophysiology.

Purpose: To examine the age distribution and characteristics of choroidal nevi in a large nationwide sample. Methods: We included all individuals who underwent fundus photography in a nationwide chain of optometry stores during a 5‐week period in 2023. Non‐mydriatic 45° or 60° digital fundus images were reviewed asynchronously by a subspecialized ocular oncologist. All images with suspected choroidal nevi, defined as a pigmented choroidal lesion of slate blue or green grey colour, were jointly re‐examined by two ocular oncologists and subsequently reviewed by a third ocular oncologist for confirmation and detailed characterization. Age, sex and geographic distribution were correlated with demographic data from the predominantly white Danish population. Results: Fundus images from 35 559 individuals aged 5–100 years (median, 54 years; interquartile range, 40–56 years) were included, representing 0.60% of the Danish population. Gradable images of both eyes were available in 31 129 participants, and at least one gradable image was available in 33 588 participants. In total, 852 nevi were identified, corresponding to a crude prevalence of 2.54% (95% CI 2.37%–2.71%). Prevalence increased during the first 5 decades of life (0%, 0.74%, 1.40%, 2.23%, 2.87%, 2.94%, 2.88%, 2.53% and 2.51% in individuals aged 80 years, respectively). Median largest basal diameter of nevi was 1.75 mm (interquartile range 1.33–2.30) and was only weakly associated with age ( R ² < 0.01; p = 0.041). According to the MOLES system, most nevi were classified as common (90.8%) or low‐risk (5.28%), with fewer graded as high‐risk (2.70%) or probable melanoma (1.17%). Conclusions: The prevalence of choroidal nevi increased throughout the first 5 decades of life. Most nevi were small and lacked risk factors for malignant transformation. This indicates that the emergence of a choroidal nevus can be expected to occur by the age of 50. If supported by longitudinal studies, these findings could inform risk‐based surveillance strategies to optimize resource allocation.

In this study, we systematically review and synthesize the evidence on the association between central serous chorioretinopathy (CSC) and personality types, and quantify the relationship between Type A behaviour and CSC. We systematically searched 12 literature databases on 5 October 2025 for studies in which personality types were evaluated in patients with CSC. Data extraction and risk‐of‐bias assessment followed standardized protocols. Studies were reviewed qualitatively. Random‐effects meta‐analysis was performed for the association between Type A behaviour and CSC. Twelve studies of 2176 participants (949 patients with CSC, 1227 controls) were included. Across studies, patients with CSC exhibited personality profiles marked by time urgency, competitiveness, emotional tension and maladaptive affect regulation, including higher neuroticism‐anxiety, aggression‐hostility and alexithymia scores. A significant association was found between Type A behaviour and CSC (pooled OR 3.43; 95% CI 1.94–6.07; p = 0.00002) in the four studies that evaluated this relationship. Sensitivity analysis confirmed robustness of the association. In conclusion, certain personality traits, particularly Type A behaviour, are associated with CSC. The relationship between personality and CSC appears biologically plausible given the role of stress‐related hypothalamic–pituitary–adrenal axis activation and elevated cortisol levels, both recognized in CSC pathophysiology. However, complex biopsychosocial interactions without a direct causal pathway may also be the case. Understanding psychological predispositions may contribute to a more comprehensive view of CSC risk and care. Further longitudinal and mechanistic studies are warranted.

Elevated corticosteroid levels are the strongest known risk factor for central serous chorioretinopathy ( CSC ), and previous studies have explored if alterations in systemic immunity could play a role in CSC . Here, we explored if elevated systemic C‐reactive protein ( CRP ), a marker of systemic low‐grade inflammation, is associated with CSC . We systematically searched 12 literature databases on 12 April 2025 for studies in which blood CRP is measured in both patients with CSC and a comparable control group. Studies were reviewed qualitatively. Meta‐analysis using the random‐effects model was performed on the weighted mean difference in systemic CRP levels between patients with CSC and controls. Six studies comprising 544 patients with CSC and 655 control individuals were eligible for this review. The meta‐analysis of the difference in CRP between patients with CSC and controls showed no statistically significant difference at 0.86 mg/L (95% CI : −1.03–2.75 mg/L; p = 0.37). One study reported a very high degree of association between elevated CRP and CSC , which was not reproduced in the other studies. The lack of association remained consistent in the sensitivity analyses. Current evidence does not suggest that elevated systemic CRP levels are associated with CSC . Further studies on CSC pathophysiology are warranted.

Purpose: Central serous chorioretinopathy (CSC) is a prevalent maculopathy, but epidemiological studies are few. In this study, we determined the prevalence of CSC for the first time in a Scandinavian population.Methods: This cross‐sectional study was based on nationwide opportunistic retinal examination from 79 high street chain optician stores in Denmark. Retinal imaging was made using non‐mydriatic colour fundus photography. Any abnormal result in the optometrist‐facilitated retinal examination was referred to tele‐ophthalmologic evaluation, which was performed by experienced consultant ophthalmologists who diagnosed CSC.Results: During the 4‐year study period, a total of 968 610 unique individuals underwent retinal examination, which corresponded to 16.3% of the entire population of Denmark. Of these, 113 individuals were diagnosed with CSC, which corresponded to a prevalence of 14 per 100 000. Individuals with CSC presented at a mean age of 48.2 ± 12.3 years; however, CSC was present in a large age range as both teenagers and the elderly with CSC were identified. Male biological sex was a statistically significant risk factor (odds ratio: 2.33; 95% confidence interval: 1.64–3.33, p < 0.0001). By extrapolating prevalence numbers to population statistics, we estimate that 219 females and 511 males had CSC in Denmark in December 2022.Conclusion: We identified a prevalence of 14 per 100 000, confirmed male biological sex as a significant risk factor for CSC, and found that the disease most commonly occurs among individuals aged 30–60 years. Further studies with multimodal imaging including optical coherence tomography are warranted for better accuracy.

Introduction This study reports our experiences with systematic retinal screening in Denmark through optometrists with access to tele-ophthalmological services before, during, and after the COVID-19 pandemic. Methods We evaluated an optometrist-based retinal screening system with a referral option for tele-ophthalmological service by a consultant ophthalmologist within the time period of August 1, 2018 to September 30, 2023. The optometrist collected patient history, refraction, best-corrected visual acuity, intraocular pressure, basic slit-lamp examination, 4-in-1 visual field report, and retinal imaging using color fundus 45° photography. Tele-ophthalmological services were provided by consultant ophthalmologists. Within pre-defined periods of pre-COVID-19, COVID-19, and post-COVID-19, we evaluated the rate of referrals to the tele-ophthalmological service, diagnoses made, and referrals to the public healthcare system. Results A total of 1,142,028 unique individuals, which corresponded to 19.1% of the entire population of Denmark, underwent screening by the optometrists; 50,612 (4.4%) of these individuals were referred to the tele-ophthalmological examination by consultant ophthalmologists. A referral for further ophthalmic examination, either at hospital or at an ophthalmic practice, was made for 10,300 individuals (20.4% of those referred for tele-ophthalmology, corresponding to 0.9% of the population screened). The referral rate from the screening to the tele-ophthalmological service increased from before COVID-19 (3.4%) to during COVID-19 (4.3%) and further after COVID-19 (6.4%). This increase coincided with an increasing prevalence of conditions seen in the tele-ophthalmological service. Conclusion During a period of 5 years, 19.1% of the entire population of Denmark underwent retinal screening. This provided an adjunctive health service during a period of severe strain on the public healthcare system, while limiting the number of excessive referrals to the public healthcare system. Temporal trends illustrated an increased pattern of use of a large-scale tele-ophthalmological system.

Purpose: The management of blepharitis continues to challenge clinicians due to the poorly understood aetiology of the condition. We recently identified the family of intracellular plakin proteins as essential driving forces underlying anterior blepharitis. A large‐scale protein analysis was used to study if a topical dexamethasone/tobramycin solution could be used to reverse the expression of plakin proteins.Methods: Tear film samples from treatment naïve patients with anterior blepharitis (n = 15) were collected with Schirmer filtration paper. A subgroup of the patients (n = 10) received treatment with a dexamethasone/tobramycin 1 + 3 mg/mL ophthalmic suspension (Tobradex^®) for 3 weeks and collection of tear film samples was repeated. The samples were analysed with label‐free quantification nano liquid chromatography–tandem mass spectrometry requiring quantification in at least 70% of the samples in each group. Proteins were considered differentially expressed if p < 0.05.Results: Following Tobradex^® intervention, 27 proteins were upregulated while 61 proteins were downregulated. Regulated proteins after Tobradex^® treatment were involved in intermediate filament cytoskeleton organization including downregulation of the plakin proteins envoplakin, epiplakin and periplakin. Plectin, a protein of the plakin family, remained unchanged after Tobradex^® therapy. Tobradex^® treatment resulted in the regulation of proteins involved in translation including a cluster of downregulated ribosomal proteins. Tobradex^® intervention was associated with the regulation of proteins involved in fructose metabolism and glycolytic processes including fructose‐1.6‐bisphosphatase 1, fructose‐bisphosphate aldolases A and B, pyruvate kinase PKM and transketolase. Ig lambda chain V‐I region, prominin‐1, and protein Niban were upregulated after Tobradex^® treatment.Conclusions: Tobradex treatment reversed the expression of plakin proteins in anterior blepharitis. Topical solutions which inhibit the expression of plakin proteins may have the potential to restore the ocular surface integrity in anterior blepharitis and should be explored further.

Meibomian gland dysfunction (MGD) is a highly prevalent condition and the most common cause of evaporative dry eye disease. Studying the proteome of MGD can result in important advances in the management of the condition. Here, we collected tear film samples from treatment naïve patients with MGD (n = 10) and age-matched controls (n = 11) with Schirmer filtration paper. The samples were analyzed with label-free quantification nano liquid chromatography—tandem mass spectrometry. The proteins were considered differentially expressed if p < 0.05. A total of 88 proteins were significantly regulated. The largest change was observed in cystatin-SN, which was downregulated in MGD and correlated negatively with tear meniscus height. The downregulation of cystatin-SN was confirmed with targeted mass spectrometry by single reaction monitoring (SRM). Eighteen immunoglobulin components involved in B cell activation, phagocytosis, and complement activation were downregulated in MGD including Ig alpha-1 chain C region, immunoglobulin J chain, immunoglobulin heavy variable 3–15, and Ig mu chain C region. The changes in cystatin-SN and immunoglobulin chains are likely to result from the inflammatory changes related to tear film evaporation, and future studies may assess their association with the meibum quality.