In developed countries, age-related macular degeneration (AMD) is the leading cause of visual impairment in the aging population. Understanding of its pathogenesis is limited and the number of patients is predicted to continue rising. AMD is classified into two main forms: dry and neovascular AMD (dAMD and nAMD, respectively). Dry AMD is the most prevalent form (80-90%) of AMD cases and has no approved treatment in Europe. Neovascular AMD (10-20% of AMD cases) is treated with frequent intravitreal injections with medicines intervening with vascular growth, but unfortunately, treatment is not curative and only a portion of patients respond to the current treatments. Increasing number of patients will create a challenge to the healthcare system and will underline the need to find either novel, more durable treatment options or ways to intervene with the disease course already in its early stages and prevent or delay disease escalation. Thus, understanding factors behind development of the disease and treatment response is important. Currently, the information on the factors influencing the progression and incidence of the disease is fragmented and does not provide sufficient tools for individualised patient care. In this study, our aim was to create a deeper understanding of factors modulating development and progression of AMD. By analysing data from nAMD patients treated in Kuopio University Hospital, we were able to identify that heavy smoking and high BMI increase the probability for earlier emergence of nAMD, while the presence of intraretinal fluid (IRF) resulted in a fast-progressing disease. We also observed a relationship between IRF and the appearance of subretinal drusenoid deposits, HRF and retinal atrophy. Thus, we observed that IRF plays a role in the escalation of the disease towards non-reversible changes in retinal anatomy. By analysing serum RNA profile of nAMD patients, we observed that the RNA profile of nAMD patients corresponds with anatomical changes observed in the retinal fluid compartments as well as atrophic changes in retinal layers. Especially, thioredoxin-related transmembrane protein 4 (TMX4) was identified as a protein whose function during AMD development should be evaluated more in detail in the future. Moreover, long-term follow-up of women living in the North Savo region revealed the role of systemic components during AMD progression and showed that people with long-term corticosteroid and immunosuppressant use have an increased risk for developing AMD. Our results highlight that further research on how systemic components behind corticosteroid and immunosuppressant use modulate AMD progression is needed. Thus, results of this study build more evidence from factors modulating AMD development and progression. Giving guidance to future analyses in a situation where comprehensive understanding from factors influencing AMD progression and development are lacking.

This systematic review and meta-analysis aimed to compare aqueous chlorhexidine (AqCHX) with povidone-iodine (PI) for ocular antisepsis in preventing post-procedural endophthalmitis (primary outcome) and to evaluate antimicrobial efficacy and patient-reported pain (secondary outcomes). A systematic search of PubMed, Embase and Web of Science was conducted on 26 November 2024 and updated on 25 June 2025. Randomised controlled trials (RCTs) and non-randomised studies (NRS) comparing AqCHX with PI for ocular antisepsis were included. Risk of bias was assessed using RoB 2 for RCTs and ROBINS-I for NRS. Meta-analyses were conducted using random-effects models. Endophthalmitis and microbiological culture positivity were reported as odds ratios (ORs), binary pain outcomes as risk ratios (RRs) and continuous pain outcomes as standardised mean differences (Hedges' g), each with 95% confidence intervals (CIs). The certainty of evidence was assessed using GRADE. Eight studies were included, comprising four RCTs and four NRS. Across three large NRS, endophthalmitis rates were low in both groups (0.024% with AqCHX vs. 0.025% with PI), with no statistically significant difference between AqCHX and PI (OR 0.80; 95% CI 0.54 to 1.19; I[2] = 0%). For microbiological culture positivity, pooled results from three RCTs and one NRS showed no significant difference between AqCHX and PI (OR 1.06; 95% CI 0.61 to 1.83; I[2] = 0%). The risk of pain or pain-related ocular symptoms was lower with AqCHX than with PI (RR 0.22; 95% CI 0.14 to 0.33; I[2] = 0%) and pain intensity also favoured AqCHX, although heterogeneity was substantial (Hedges' g = -1.83; 95% CI -2.54 to -1.13; I[2] = 77.3%). Certainty of evidence was rated as moderate across all outcomes. AqCHX showed comparable effectiveness to PI for ocular antisepsis while being associated with better tolerability. However, conclusions regarding endophthalmitis are limited by the reliance on NRS and the very low event rate, leaving uncertainty about the magnitude of any difference between treatments. Further well-designed, adequately powered studies are needed to clarify their comparative effectiveness and tolerability.