C-reactive protein-complement factor H axis as a biomarker of activity in early and intermediate age-related macular degeneration.

Purpose: To determine and compare the serum levels of complement Factor H (FH), monomeric C-Reactive Protein (mCRP) and pentameric C-Reactive protein (pCRP) in patients with age-related macular degeneration (AMD) and to correlate them with clinical, structural and functional parameters. Methods: Cross-sectional observational study. One hundred thirty-nine individuals (88 patients and 51 healthy controls) from two referral centers were included and classified into three groups: early or intermediate AMD (n=33), advanced AMD (n=55), and age and sex matched healthy controls (n=51). Serum levels of FH, mCRP, and pCRP were determined and correlated with clinical and imaging parameters. Results: Patients with intermediate AMD presented FH levels significantly lower than controls [186.5 (72.1-931.8) µg/mL vs 415.2 (106.1-1962.2) µg/mL; p=0.039] and FH levels <200 µg/mL were associated with the presence of drusen and pigmentary changes in the fundoscopy (p=0.002). While no differences were observed in pCRP and mCRP levels, and mCRP was only detected in less than 15% of the included participants, women had a significantly higher detection rate of mCRP than men (21.0% vs. 3.8%, p=0.045). In addition, the ratio mCRP/FH (log) was significantly lower in the control group compared to intermediate AMD (p=0.031). Visual acuity (p<0.001), macular volume (p<0.001), and foveal thickness (p=0.034) were significantly lower in the advanced AMD group, and choroidal thickness was significantly lower in advanced AMD compared to early/intermediate AMD (p=0.023). Conclusion: Intermediate AMD was associated in our cohort with decreased serum FH levels together with increased serum mCRP/FH ratio. All these objective serum biomarkers may suggest an underlying systemic inflammatory process in early/intermediate AMD patients.

Artificial intelligence-based fluid quantification and associated visual outcomes in a real-world, multicentre neovascular age-related macular degeneration national database.

AIM: To explore associations between artificial intelligence (AI)-based fluid compartment quantifications and 12 months visual outcomes in OCT images from a real-world, multicentre, national cohort of naïve neovascular age-related macular degeneration (nAMD) treated eyes. METHODS: Demographics, visual acuity (VA), drug and number of injections data were collected using a validated web-based tool. Fluid compartment quantifications including intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED) in the fovea (1 mm), parafovea (3 mm) and perifovea (6 mm) were measured in nanoliters (nL) using a validated AI-tool. RESULTS: 452 naïve nAMD eyes presented a mean VA gain of +5.5 letters with a median of 7 injections over 12 months. Baseline foveal IRF associated poorer baseline (44.7 vs 63.4 letters) and final VA (52.1 vs 69.1), SRF better final VA (67.1 vs 59.0) and greater VA gains (+7.1 vs +1.9), and PED poorer baseline (48.8 vs 57.3) and final VA (55.1 vs 64.1). Predicted VA gains were greater for foveal SRF (+6.2 vs +0.6), parafoveal SRF (+6.9 vs +1.3), perifoveal SRF (+6.2 vs -0.1) and parafoveal IRF (+7.4 vs +3.6, all p<0.05). Fluid dynamics analysis revealed the greatest relative volume reduction for foveal SRF (-16.4 nL, -86.8%), followed by IRF (-17.2 nL, -84.7%) and PED (-19.1 nL, -28.6%). Subgroup analysis showed greater reductions in eyes with higher number of injections. CONCLUSION: This real-world study describes an AI-based analysis of fluid dynamics and defines baseline OCT-based patient profiles that associate 12-month visual outcomes in a large cohort of treated naïve nAMD eyes nationwide.

Macular Neovascularization Type Influence on Anti-VEGF Intravitreal Therapy Outcomes in Age-Related Macular Degeneration.

PURPOSE: To evaluate the influence of macular neovascularization (MNV) lesion type on 12-month clinical outcomes in treatment-naive eyes with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF drugs nationwide. DESIGN: Multicenter national nAMD database observational study. SUBJECTS: One thousand six hundred six treatment-naive nAMD eyes (1330 patients) undergoing anti-VEGF therapy for 12 months nationwide. METHODS: Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution letters, number of injections and visits were was collected using a validated web-based tool. Neovascular lesion phenotype was classified as type 1 (T1, n = 711), type 2 (T2, n = 505), type 3 (T3, n = 315), and aneurysmal type 1 (A-T1, n = 75), according to the new proposed consensus classification. MAIN OUTCOME MEASURES: Mean VA change at 12 months, final VA at 12 months, number of injections, time to lesion inactivation. RESULTS: A total of 1606 treatment-naive nAMD eyes (1330 patients) received a median of 7 injections over 12 months. Mean (± standard deviation) baseline VA was significantly lower for T2 (49.4 ± 23.5 letters) compared with T1 (57.8 ± 20.8) and T3 (58.2 ± 19.4) (both P < 0.05) lesions. Mean VA change at 12 months was significantly greater for A-T1 (+9.5 letters) compared with T3 (+3.1 letters, P < 0.05). Patients with T3 lesions had fewer active visits (24.9%) than those with other lesion types (T1, 30.5%; T2, 32.6%; A-T1, 27.5%; all P < 0.05). Aflibercept was the most used drug in A-T1 lesions (70.1%) and ranibizumab in T1 (40.7%), T2 (57.7%), and T3 (47.6%) lesions. CONCLUSIONS: This study highlights the relevance of MNV type on clinical outcomes in nAMD and reports significant differences in baseline VA, VA change, and lesion activity at 12 months. This report provides data about lesion-specific clinical features, which may guide the management of nAMD cases and potentially support personalized clinical decision making for these patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Ocular related emergencies in Spain during the COVID-19 pandemic, a multicenter study.

PURPOSE: To evaluate ophthalmological emergencies (OE) during the COVID-19 pandemic comparing them with the same period of the previous year. METHODS: Retrospective observational study of all OE visits in four tertiary hospitals in Spain comparing data from March 16th to April 30th, 2020 (COVID-19 period) and the same period of 2019 (pre-COVID-19 period). Severity of the conditions was assessed following Channa et al. publication. Data on demographics, diagnosis and treatments were collected from Electronic Medical Records. RESULTS: During lockdown, OE significantly declined by 75.18%, from 7,730 registered in the pre-COVID-19 period to 1,928 attended during the COVID-19 period (p < 0.001). In 2019, 23.86% of visits were classified as emergent, 59.50% as non-emergent, and 16.65% could not be determined. In 2020, the percentage of emergent visits increased up to 29.77%, non-emergent visits significantly decreased to 52.92% (p < 0.001), and 17.31% of the visits were classified as "could not determine". During the pandemic, people aged between 45 and 65 years old represented the largest attending group (37.89%), compared to 2019, where patients over 65 years were the majority (39.80%). In 2019, most frequent diagnosis was unspecified acute conjunctivitis (11.59%), followed by vitreous degeneration (6.47%), and punctate keratitis (5.86%). During the COVID-19 period, vitreous degeneration was the first cause for consultation (9.28%), followed by unspecified acute conjunctivitis (5.63%) and punctate keratitis (5.85%). CONCLUSIONS: OE visits dropped significantly during the pandemic in Spain (75.18%), although more than half were classified as non-urgent conditions, indicating a lack of understanding of the really emergent ocular pathologies among population.

XEN45 real-life evaluation: Survival analysis with bleb needling and major revision outcomes.

PURPOSE: To evaluate real-life outcomes of XEN45 stent surgery including bleb needling (BN) and surgical bleb revision (SBR). METHODS: Retrospective analysis of all XEN45 gel stents implanted in a tertiary glaucoma center with a minimum follow-up of 6 months. The main outcomes were intraocular pressure (IOP), the number of glaucoma medications, postoperative maneuvers like BN, and subsequent SBR. Success was defined as IOP ⩽ 18 and 20% reduction (criterion A), ⩽15 and 25% reduction (criterion B), and ⩽12 mmHg and 30% reduction (criterion C) reached with (qualified) or without (complete) medications at the last visit. Complete failure was defined as additional glaucoma surgery, loss of light perception, or sight-threatening complications. Multivariable Cox regression and Kaplan-Meier survival estimates tests were performed. RESULTS: Fifty-eight eyes with either stand-alone or combined Phaco-XEN surgery were included. Complete success by the different definitions was 50.0% (95% confidence interval, 5.8%-84.5%) (A), 50.0% (5.8%-84.5%) (B), and 25% (0.9%-66.5%) (C) whereas qualified success was 38.3% (1.6%-80.1%), 31.7% (2.0%-71.4%), and 0%, respectively, at the 24-months visit. 30% of cases underwent BN with 5-Fluorouracil, and SBR was performed in 17.5% of eyes. Low IOP levels at 1-month and early BN were significantly associated with success. The highest chance of failure was achieved in the combined Phaco-XEN group undergoing SBR. CONCLUSIONS: In our real-life setting, the first month IOP was associated with greater success rates. Although BN obtained improved IOP values, SBR was associated with a greater bleb survival in the stand-alone XEN group. Both BN and SBR had poor outcomes in the combined Phaco-XEN group.