Outcomes of Combined Phacovitrectomy Without Corneal Suturing.

BACKGROUND: During combined phacovitrectomy, it is common practice to suture the main corneal incision to prevent intraoperative and postoperative wound leak. However, it may be possible to avoid suturing using a self-sealing corneal incision technique as in standard cataract surgery. OBJECTIVES: To evaluate the clinical outcome, safety, and complications of combined phacovitrectomy without preventive suturing. METHODS: This retrospective case series study included consecutive patients who underwent combined phacovitrectomy between January 2018 and June 2019 for mixed indications. Surgeries were performed at a tertiary university hospital. All surgeries were performed by the same two retinal surgeons. Cataract surgery was performed first, followed by insertion of trocars and vitrectomy. Corneal sutures were not planned but were used at the discretion of the surgeon. RESULTS: The cohort included 106 eyes of 102 patients. Suturing of the main corneal incision was deemed necessary in five cases (5%) because of a main incision leak or anterior chamber shallowing during trocar insertion. No other complications related to the absence of prophylactic corneal sutures were encountered during surgery or follow-up. CONCLUSIONS: Preventive corneal suturing may not be necessary in combined phacovitrectomy surgery and can be used in the few cases in which it is indicated during surgery.

3K3A-Activated Protein C Inhibits Choroidal Neovascularization Growth and Leakage and Reduces NLRP3 Inflammasome, IL-1ß, and Inflammatory Cell Accumulation in the Retina.

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-1ß, 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-1ß 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.

Optical Coherence Tomography Angiography for the Differentiation of Glaucoma from Pituitary Macroadenoma Related Optic Disc Measurements.

OBJECTIVE: To determine the potential of optical coherence tomography (OCT) and OCT angiography (OCTA) to distinguish between glaucoma and pituitary macroadenoma by optic disc appearance. METHODS: This prospective case-control study comprised 31 patients: 23 with glaucoma (18 male, 5 female) and 8 with pituitary macroadenoma and chiasmatic compression (3 male, 5 female). The corresponding mean ages were 72.8 years (range 58-90) and 60.7 years (range 43-73). All participants underwent complete ophthalmological examination, spectral domain OCT and OCTA, and visual field testing. Clinical, imaging, and visual field results were compared between the groups. RESULTS: On OCT analysis, the glaucoma group had relatively lower peripapillary retinal nerve fiber layer (RNFL) thickness (65.79 ± 15.46, 86.0 ± 11.37, respectively, P = .002) and lower rim area (1.00 ± 0.22 mm2 and 1.2 ± 0.15 mm2, respectively, P = .005). On OCTA, peripapillary vessel density was significantly lower in all quadrants in the glaucoma group. The significance of these between-group differences was maintained when patients were stratified by visual field mean deviation. CONCLUSIONS: This is the first comparative analysis of optic disc morphology between glaucoma and pituitary macroadenoma using combined OCT and OCTA. The results yielded lower peripapillary RNFL thickness, lower rim area, and lower peripapillary vessel density in the glaucoma group. These parameters may aid in the initial differentiation between these two optic neuropathies.

LASER PHOTOCOAGULATION FOR THE TREATMENT OF OPTIC NERVE HEAD PIT-RELATED MACULOPATHY IN A PATIENT WITH BILATERAL CHORIORETINAL COLOBOMA.

PURPOSE: To report a case of laser photocoagulation for the treatment of a combined coloboma and optic nerve head pit-related maculopathy in a patient with bilateral chorioretinal coloboma. METHODS: A case report. RESULTS: A 15-year-old woman, presented with the visual acuity of 20/100 in her right eye for six weeks. She was diagnosed with macular detachment secondary to optic nerve head pit in her right eye and bilateral chorioretinal coloboma. Multimodal imaging, including color photography, fluorescein angiography, and spectral-domain optical coherence tomography, was used to identify and demonstrate the location of the tract of fluid from the optic nerve head pit, isolated from the coloboma. Optical coherence tomography-guided laser photocoagulation treatment at the location of the tract resulted in complete resolution of macular fluid with visual recovery to 20/25. CONCLUSION: Our case stresses the value of correct diagnosis directing photocoagulation treatment of combined optic nerve head pit-related maculopathy in eyes with chorioretinal coloboma using multimodal imaging.

3K3A-Activated Protein C Prevents Microglia Activation, Inhibits NLRP3 Inflammasome and Limits Ocular Inflammation.

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-1ß 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-1ß. 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.

Simultaneous bilateral or sequential DCR? What to choose?

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.

Outcomes of Combined Scleral Buckling Plus Pneumatic Retinopexy Vs. Scleral Buckling for Primary Rhegmatogenous Retinal Detachment.

PURPOSE: To evaluate the outcomes and complications of scleral buckle surgery alone or combined with pneumatic retinopexy (pneumatic buckle) for the treatment of primary rhegmatogenous retinal detachment. DESIGN: Retrospective chart review. PARTICIPANTS: Two hundred thirteen patients with rhegmatogenous retinal detachment of whom 101 underwent primary scleral buckle surgery at Rabin Medical Center in 2005-2015 (SB group) and 112 underwent pneumatic buckle surgery at Royal Alexandra Hospital in 2013-2015 (PB group). METHODS: All patients were followed for ≥12 months. Data on clinical and surgical parameters, outcome, and complications were collected from the medical files. MAIN OUTCOME MEASURES: Best corrected visual acuity and anatomical outcomes. RESULTS: At 12 months, average best corrected visual acuity was 0.3 logMar in the SB group and 0.42 logMar in the PB group (P < 0.05). Rates of anatomical reattachment were high and similar in the two groups (99% and 97%, respectively, P = 0.623). The SB group had a higher percentage of patients requiring additional laser applications (21% vs. 7%; P < 0.01) and buckle readjustment surgery (6% vs. 0; P = 0.01), and the PB group had a higher percentage of patients who required postoperative pars plana vitrectomy (30% vs. 17%; P = 0.03). CONCLUSION: Scleral buckle surgery alone is efficient for the treatment of rhegmatogenous retinal detachment. Its combination with pneumatic retinopexy usually has no significant added value in terms of anatomical reattachment rate. Outcomes of Pneumatic buckling vs Scleral Buckling for RRD.

Activated Protein C (APC) and 3K3A-APC-Induced Regression of Choroidal Neovascularization (CNV) Is Accompanied by Vascular Endothelial Growth Factor (VEGF) Reduction.

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.

High Agreement between Barrett Universal II Calculations with and without Utilization of Optional Biometry Parameters.

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.

Interdigitation and Ellipsoid Zones Disruption Correlate with Visual Outcomes among Treatment-Naive Patients with Diabetic Macular Edema.

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-naive 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-naive DME patients were analyzed in this retrospective study. The integrity of foveal IZ and EZ was evaluated using optical coherence tomography 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 (VA) improved from 20/52 to 20/44 (p = 0.05), CMT decreased from 432.5 ± 141.4 µm 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 VA 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 the evaluation of treatment response.

Activated protein C induces suppression and regression of choroidal neovascularization- A murine model.

Activated protein C (APC) exerts diverse cell signaling pathways which results in multiple distinct cytoprotective actions. These include anti-apoptotic and anti-inflammatory activities and stabilization of endothelial and epithelial barriers. We studied the ability of APC to inhibit the leakage and the growth of newly formed as well as pre-existing choroidal neovascularization (CNV) and examined the ability of APC to stabilize the Retinal Pigmented Epithelium (RPE). We explored the contribution of Tie2 receptor to the protective effects of APC. CNV was induced by laser photocoagulation in C57BL/6J mice. APC was injected intravitreally immediately or 7 days after CNV induction. Neovascularization was evaluated on RPE-choroidal flatmounts using FITC-dextran perfusion and CD31 immunofluorescence. CNV leakage was measured by fluorescein angiography (FA). The ability of APC to stabilize the RPE barrier was evaluated in-vitro by dextran permeability and zonula occludens 1 (ZO1) immunostaining. Tie2 blocking was induced in-vivo by intraperitoneal injection of Tie2 kinase inhibitor and in-vitro by incubation with anti Tie2 antibodies. APC treatment dramatically inhibited the generation of newly formed CNV leakage sites and reversed leakage in 85% of the pre-existing CNV leaking sites. In RPE cell culture, APC induced translocation of ZO1 to the cell membrane, accompanied by reduction in permeability of the monolayer. Inhibition of Tie2 significantly decreased APC protective activities in both the mouse model and the RPE cell culture. Our results show that APC treatment significantly inhibits the leakage and growth of newly formed, as well as pre-existing CNV, and its protective activities are partially mediated via the Tie2 receptor. The data suggest that APC should be further investigated as a possible effective treatment for CNV.