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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.

Introduction: We have recently shown that defects in interdigitation and ellipsoid zones (IZ and EZ) can predict response to anti-VEGF therapy in a small group of treatment-naïve diabetic macular edema (DME) patients. The aim of the current study is to further evaluate this association in a larger study group of patients over a longer follow-up time. Methods: Thirty eyes of 30 treatment-naïve DME patients were analyzed in this retrospective study. The integrity of foveal IZ and EZ was evaluated using OCT at the diagnosis of DME and following anti-VEGF injections. The defect size was correlated with best-corrected visual acuity (BCVA) and central macular thickness (CMT). Results: The mean patients' age at baseline was 63.0±10.0 years. Patients underwent 3.9±2.9 anti-VEGF injections for a mean of 9.1±4.8 months. Following treatment, the mean Snellen visual acuity improved from 20/52 to 20/44 (p=0.05), CMT decreased from 432.5±141.4 m to 375.2±121.4 µm (p=0.05) and IZ/EZ defect size decreased from 259.83±375.94 µm to 65.34±143.97 µm (p=0.001). In patients with no IZ/EZ defects at baseline the mean Snellen visual acuity was better when compared to those with IZ/EZ defects (20/36 vs. 20/70, p=0.031). The number of eyes with IZ/EZ defects decreased from 17 (57%) at baseline to 6 (20%) at end of follow-up (p<0.01). BCVA gain correlated with IZ/EZ defect size reduction (r=0.41, p=0.02) but not with improvement in CMT (r=0.28, p=0.121). Conclusions: IZ/EZ defect size correlated not only with baseline BCVA, but also predicted the change in BCVA after anti-VEGF treatment. Possible future automatic measurement of IZ/EZ defect size might prove helpful for evaluation of treatment response.

Background: Dacryocystorhinostomy is used to treat nasolacrimal duct obstruction when conservative measures fail. It may be performed via an external or endoscopic-endonasal approach. The aim of this study was to compare the outcomes of patients with nasolacrimal duct obstruction treated with simultaneous bilateral or unilateral dacryocystorhinostomy. Methods: The database of a tertiary medical center was retrospectively reviewed for all patients treated for nasolacrimal duct obstruction in 2012–2017. The study sample was divided into six groups by surgery type and approach: adults (>18 years) – external or endoscopic-endonasal sequential unilateral or simultaneous bilateral dacryocystorhinostomy (four subgroups); children (18 years) – endoscopic-endonasal unilateral or simultaneous bilateral dacryocystorhinostomy (two subgroups). Data were collected on patient age and sex, surgery and anesthesia type and duration, and complications. Results: The cohort included 95 adults and 27 children who underwent 111 and 41 surgical procedures, respectively. Among the adults, the durations of anesthesia and surgery were significantly longer in the external bilateral dacryocystorhinostomy group than the others, but no such differences were found between simultaneous bilateral endonasal dacryocystorhinostomy and unilateral dacryocystorhinostomy by either approach. Among the children, there was no significant between-group difference in surgery duration. In neither age population was bilateral endoscopic surgery associated with an excess of intraoperative or postoperative complications of hemorrhage, infection, and epiphora. Conclusion: The lack of intergroup differences in clinical, surgical, and outcome parameters suggests that in cases of bilateral nasolacrimal duct obstruction in adults and children, simultaneous bilateral endoscopic-endonasal dacryocystorhinostomy may yield excellent therapeutic results.

3K3A-Activated Protein C (APC) is a recombinant variant of the physiological anticoagulant APC with cytoprotective properties and reduced bleeding risks. We studied the potential use of 3K3A-APC as a multi-target therapeutic option for choroidal neovascularization (CNV), a common cause of vision loss in age-related macular degeneration. CNV was induced by laser photocoagulation in a murine model, and 3K3A-APC was intravitreally injected. The impact of 3K3A-APC treatment on myeloid and microglia cell activation and recruitment and on NLRP3 inflammasome, IL-1β, and VEGF levels was assessed using cryosection, retinal flat-mount immunohistochemistry and vascular imaging. Additionally, we evaluated the use of fluorescein angiography as a surrogate marker for in vivo evaluation of the efficacy of 3K3A-APC treatment against leaking CNV lesions. Our results demonstrated that 3K3A-APC treatment significantly reduced the accumulation and activation of myeloid cells and microglia in the CNV area and decreased the NLRP3 and IL-1β levels at the CNV site and the surrounding retina. Furthermore, 3K3A-APC treatment resulted in leakage regression and CNV growth suppression. These findings indicate that the anti-inflammatory activities of 3K3A-APC contribute to CNV inhibition. Our study suggests the potential use of 3K3A-APC as a novel multi-target treatment for CNV.

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