Multimodal imaging of experimental choroidal neovascularization.

AIM: To compare choroidal neovascularization (CNV) lesion measurements obtained by in vivo imaging modalities, with whole mount histological preparations stained with isolectin GS-IB4, using a murine laser-induced CNV model. METHODS: B6N.Cg-Tg(Csf1r-EGFP)1Hume/J heterozygous adult mice were subjected to laser-induced CNV and were monitored by fluorescein angiography (FA), multicolor (MC) fundus imaging and optical coherence tomography angiography (OCTA) at day 14 after CNV induction. Choroidal-retinal pigment epithelium (RPE) whole mounts were prepared at the end of the experiment and were stained with isolectin GS-IB4. CNV areas were measured in all different imaging modalities at day 14 after CNV from three independent raters and were compared to choroidal-RPE whole mounts. Intraclass correlation coefficient (ICC) type 2 (2-way random model) and its 95% confidence intervals (CI) were calculated to measure the correlation between different raters' measurements. Spearman's rank correlation coefficient (Spearman's r) was calculated for the comparison between FA, MC and OCTA data and histology data. RESULTS: FA (early and late) and MC correlates well with the CNV measurements ex vivo with FA having slightly better correlation than MC (FA early Spearman's r=0.7642, FA late Spearman's r=0.7097, and MC Spearman's r=0.7418), while the interobserver reliability was good for both techniques (FA early ICC=0.976, FA late ICC=0.964, and MC ICC=0.846). In contrast, OCTA showed a poor correlation with ex vivo measurements (Spearman's r=0.05716) and high variability between different raters (ICC=0.603). CONCLUSION: This study suggests that FA and MC imaging could be used for the evaluation of CNV areas in vivo while caution must be taken and comparison studies should be performed when OCTA is employed as a CNV monitoring tool in small rodents.

Occurrence and outcome of firework-related ocular injuries in Switzerland: A descriptive retrospective study.

BACKGROUND: Firework-related ocular injuries (FWROI) are a major cause of preventable visual impairment. This study aimed to analyze the occurrence and outcome of FWROI in Switzerland. METHODS: This retrospective multicenter study included patients with FWROI from seven centers in Switzerland from January 2009 to August 2020. Demographic information, type of injuries, medical and surgical treatments, the best corrected visual acuity (BCVA) at baseline and end of follow-up, occurrence and type of secondary complications, and duration of hospitalization were analyzed. RESULTS: A total of 105 patients (119 eyes) with a mean age of 27.1 ± 15.9 years were included in the study (71.4% male patients; 29.5% underage). Most injuries occurred around New Year's Eve (32.4%) and the Swiss national holiday on 1 August (60.9%). The most common anterior segment findings were conjunctival or corneal foreign bodies (58%), whereas Berlin's edema was the most common posterior segment finding (11.4%). Globe ruptures were found in four patients. The mean BCVA in all patients at first presentation was 0.4 ± 0.8 logMAR and improved to 0.3 ± 0.8 logMAR at last follow-up. A primary surgical intervention was performed in 48 eyes (40.3%). Hospitalization directly after the trauma was necessary for 18 patients for a mean of 5.8 ± 4.1 days, and a total of 4.9 ± 7.6 follow-up visits were needed. CONCLUSION: This study provides the first data on FWROI in Switzerland, which are helpful for further preventive and educational programs and comparisons with other countries.

Effect of Inhibition of Colony-Stimulating Factor 1 Receptor on Choroidal Neovascularization in Mice.

Neovascular age-related macular degeneration is one of the leading causes of blindness. Microglia and macrophages play a critical role in choroidal neovascularization (CNV) and may, therefore, be potential targets to modulate the disease course. This study evaluated the effect of the colony-stimulating factor-1 receptor inhibitor PLX5622 on experimental laser-induced CNV. A 98% reduction of retinal microglia cells was observed in the retina 1 week after initiation of PLX5622 treatment, preventing accumulation of macrophages within the laser site and leading to a reduction of leukocytes within the choroid after CNV induction. Mice treated with PLX5622 had a significantly faster decrease of the CNV lesion size, as revealed by in vivo imaging and immunohistochemistry from day 3 to day 14 compared with untreated mice. Several inflammatory modulators, such as chemokine (C-C motif) ligand 9, granulocyte-macrophage colony-stimulating factor, soluble tumor necrosis factor receptor-I, IL-1α, and matrix metallopeptidase-2, were elevated in the acute phase of the disease when microglia were ablated with PLX5622, whereas other cytokines (eg, interferon-γ, IL-4, and IL-10) were reduced. Our results suggest that colony-stimulating factor-1 receptor inhibition may be a novel therapeutic target in patients with neovascular age-related macular degeneration.

One-Year Results of Using a Treat-and-Extend Regimen without a Loading Phase with Anti-VEGF Agents in Patients with Treatment-Naive Diabetic Macular Edema.

PURPOSE: To evaluate real-life outcomes in treatment-naive patients with diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (VEGF) agents using a treat-and-extend regimen without a fixed loading phase. METHODS: Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) measured using optical coherence tomography at baseline and after 1 year of treatment, intervals and number of injections were analyzed. Subgroup analysis was performed to compare anatomical and functional outcomes between patients receiving ranibizumab or aflibercept. RESULTS: Seventy-five eyes of 61 patients met the inclusion criteria and had follow-up for 1 year. Baseline BCVA and CRT were 68.1 ± 13.2 letters and 424 ± 135 µm, retrospectively. After 1 year, there was a significant mean gain in BCVA of +5.8 ± 7.4 letters (paired t test: p < 0.0001) and a significant decrease in mean CRT of -117 ± 134 µm (paired t test: p < 0.0001). The mean number of anti-VEGF injections was 10.0 ± 1.6 (range 6-12). The mean maximum interval between injections was 8.5 ± 2.9 weeks (range 4-14) and the mean interval 6.0 ± 1.2 weeks (range 4.1-8.9). 96% of eyes could be extended after a mean of 5.3 injections and 17% of patients could be extended before reaching a formal loading dose of 3 injections. Subgroup analysis did not reveal any differences in outcomes between patients treated with ranibizumab or aflibercept. Subretinal fluid at baseline was associated with better BCVA gain after 1 year (stepwise forward regression analysis, p = 0.003). CONCLUSION: Our results suggest that not all patients with DME require a fixed loading phase when initiating anti-VEGF treatment. Finding anatomical predictors to identify this subgroup of patients would help to reduce treatment burden and optimize clinical outcomes.