No abstract

Purpose: To examine the contribution of anterior chamber depth (ACD), lens thickness (LT), and white-to-white (WTW) measurements to intraocular lens (IOL) power calculations using the Barrett Universal II (BUII) formula. Methods: Measurements taken with the IOLMaster 700 (Carl Zeiss, Meditec AG, Jena, Germany) swept-source biometry of 501 right eyes of 501 consecutive patients undergoing cataract extraction surgery between January 2019 and March 2020 were reviewed. IOL power was calculated using the BUII formula, first through the inclusion of all measured variables and then by using partial biometry data. For each calculation method, the IOL power targeting emmetropia was recorded and compared for the whole cohort and stratified by axial length (AL) of the measured eye. Results: The mean IOL power calculated for the entire cohort using all available parameters was 19.50 ± 5.11 diopters (D). When comparing it to the results obtained by partial biometry data, the mean absolute difference ranged from 0.05 to 0.14 D; p < 0.001. The optional variables (ACD, LT, WTW) had the least effect in long eyes (AL ≥ 26 mm; mean absolute difference ranging from 0.02 to 0.07 D; p < 0.001), while the greatest effect in short eyes (AL ≤ 22 mm; mean absolute difference from 0.10 to 0.21 D; p < 0.001). The percentage of eyes with a mean absolute IOL dioptric power difference more than 0.25 D was the highest (32.0%) among the short AL group when using AL and keratometry values only. Conclusions: Using partial biometry data, the BUII formula in small eyes (AL ≤ 22 mm) resulted in a clinically significant difference in the calculated IOL power compared to the full biometry data. In contrast, the contribution of the optional parameters to the calculated IOL power was of little clinical importance in eyes with AL longer than 22 mm.

The activated protein C (APC) ability to inhibit choroidal neovascularization (CNV) growth and leakage was recently shown in a murine model. A modified APC, 3K3A-APC, was designed to reduce anticoagulant activity while maintaining full cytoprotective properties, thus diminishing bleeding risk. We aimed to study the ability of 3K3A-APC to induce regression of CNV and evaluate vascular endothelial growth factor (VEGF) role in APC’s activities in the retina. CNV was induced by laser photocoagulation on C57BL/6J mice. APC and 3K3A-APC were injected intravitreally after verification of CNV presence. CNV volume and vascular penetration were evaluated on retinal pigmented epithelium (RPE)-choroid flatmount by fluorescein isothiocyanate (FITC)-dextran imaging. VEGF levels were measured using immunofluorescence anti-VEGF staining. We found that 3K3A-APC induced regression of pre-existing CNV. VEGF levels, measured in the CNV lesion sites, significantly decreased upon APC and 3K3A-APC treatment. Reduction in VEGF was sustained 14 days post a single APC injection. As 3K3A-APC retained APCs’ activities, we conclude that the anticoagulant properties of APC are not mandatory for APC activities in the retina and that VEGF reduction may contribute to the protective effects of APC and 3K3A-APC. Our results highlight the potential use of 3K3A-APC as a novel treatment for CNV and other ocular pathologies.

3K3A-Activated Protein C (APC) is a recombinant variant of the physiological anticoagulant APC with pleiotropic cytoprotective properties albeit without the bleeding risks. The anti-inflammatory activities of 3K3A-APC were demonstrated in multiple preclinical injury models, including various neurological disorders. We determined the ability of 3K3A-APC to inhibit ocular inflammation in a murine model of lipopolysaccharide (LPS)-induced uveitis. Leukocyte recruitment, microglia activation, NLRP3 inflammasome and IL-1β levels were assessed using flow cytometry, retinal cryosection histology, retinal flatmount immunohistochemistry and vascular imaging, with and without 3K3A-APC treatment. LPS triggered robust inflammatory cell recruitment in the posterior chamber. The 3K3A-APC treatment significantly decreased leukocyte numbers and inhibited leukocyte extravasation from blood vessels into the retinal parenchyma to a level similar to controls. Resident microglia, which underwent an inflammatory transition following LPS injection, remained quiescent in eyes treated with 3K3A-APC. An inflammation-associated increase in retinal thickness, observed in LPS-injected eyes, was diminished by 3K3A-APC treatment, suggesting its clinical relevancy. Finally, 3K3A-APC treatment inhibited inflammasome activation, determined by lower levels of NLRP3 and its downstream effector IL-1β. Our results highlight the anti-inflammatory properties of 3K3A-APC in ocular inflammation and suggest its potential use as a novel treatment for retinal diseases associated with inflammation.