Safety, efficacy, and intraoperative characteristics of DisCoVisc and Healon ophthalmic viscosurgical devices for cataract surgery

Satish S Modi1, James A Davison2, Tom Walters3 1Seeta Eye Centers, Poughkeepsie, NY, USA; 2Wolfe Clinic, Marshalltown, IA, USA; 3Texas Eye Care, Austin, TX, USA Purpose: To evaluate the safety and efficacy of DisCoVisc ophthalmic viscosurgical device (OVD, Alcon Laboratories, Inc) with respect to a comparator, Healon OVD (Advanced Medical Optics, Inc). Patients and methods: In this prospective study, patients with cataracts were randomized to an OVD, and then received phacoemulsification and injection of an intraocular lens. After each surgery, unmasked investigators completed subjective questionnaires about OVD characteristics during each stage of the procedure. Masked technicians evaluated objective safety parameters of intraocular pressure (IOP) and endothelial cell density, with 90 days of follow-up. Results: The DisCoVisc OVD group (128 eyes) and the Healon OVD group (121 eyes) had statistically similar outcomes for IOP and for endothelial cell loss. Subjectively assessed viscosity was statistically different (P < 0.0001), with Healon OVD most often rated “cohesive” and DisCoVisc OVD most often rated “both dispersive and cohesive”. Workspace maintenance differed between groups (P < 0.0001), with workspace most frequently rated “full chamber maintained” when using DisCoVisc OVD and most frequently rated “workspace maintained” when using Healon OVD. “Flat” or “shallow” workspace ratings occurred only in the Healon OVD group. Conclusion: DisCoVisc OVD had both cohesive and dispersive properties, and was safe and effective for every stage of cataract surgery. Keywords: cataract, endothelial cell density, viscoelastic, phacoemulsificatio

Open Access Extracts from Acacia catechu suppress HIV-1 replication by inhibiting the activities of the viral

Background: Acacia catechu (Mimosa family) stem bark extracts have been used traditionally as a dietary supplement as well as a folk medicine given its reported anti-inflammatory, immunomodulatory, hepatoprotective, antioxidant, anti-microbial and anti-tumor activities. The present study was undertaken to evaluate the anti-HIV-1 activity of the extracts from stem bark of A. catechu. Methods: The aqueous and 50 % ethanolic extracts of A. catechu stem bark were prepared and 50 % ethanolic extract was further fractioned by successively partitioning with petroleum ether, chloroform and n-butanol. All the extracts and fractions were evaluated for cytotoxicity and anti-HIV-1 activity using different in vitro assays. The active n-butanol fraction was evaluated for its inhibition against HIV-1 reverse transcriptase, integrase, protease, pro-viral genome integration and viral Tat protein mediated transactivation. The effect of n-butanol fraction on the induction of pro-inflammatory cytokines secretion in Vk2/E6E7 cells and transepithelial resistance in Caco-2 and HEC-1A cells was investigated. Results: The aqueous and 50 % ethanolic extracts of A. catechu showed IC50 values of 1.8 ± 0.18 μg/ml and 3.6 ± 0.31 μg/ml, respectively in cell-free virus based assay using TZM-bl cells and HIV-1NL4.3 (X-4 tropic). In the above assay, n-butanol fraction exhibited anti-HIV-1 activity with an IC50 of 1.7 ± 0.12 μg/ml. The n-butanol fractio

Nepafenac 0.3% after Cataract Surgery in Patients with Diabetic Retinopathy: Results of 2 Randomized Phase 3 Studies

Purpose To demonstrate the efficacy and safety of once-daily nepafenac 0.3% ophthalmic suspension versus vehicle, based on clinical outcomes, after cataract surgery in patients with diabetes. Design Two prospective, randomized, multicenter, double-masked, vehicle-controlled phase 3 studies. Participants Total, 615 patients in study 1 and 605 patients in study 2. Methods Patients were randomized (1:1) to topical nepafenac 0.3% or vehicle once-daily starting the day before surgery and continuing for 90 days thereafter. Main Outcome Measures Key efficacy variables were: patients (%) in whom macular edema (ME) developed (≥30% increase from preoperative baseline central subfield macular thickness) within 90 days after cataract surgery and the patients (%) with a best-corrected visual acuity (BCVA) improvement of ≥15 letters from preoperative baseline through day 14 maintained through day 90. Secondary end points included: patients (%) with a BCVA improvement of ≥15 letters from preoperative baseline through days 90 and 60 and safety over 3 months. Results A significantly lower percentage of patients demonstrated ME within 90 days after surgery with nepafenac 0.3% versus vehicle (study 1: 2.3% vs. 17.3%; P P = 0.001; pooled: 4.1% vs. 15.9%; P P P = 0.671) in study 2, and 55.4% versus 46.7% ( P = 0.003) in the pooled analysis. A greater percentage of patients treated with nepafenac 0.3% versus vehicle in study 1 and similar percentage in study 2 had a BCVA improvement of ≥15 letters from preoperative baseline through day 90 (77.2% vs. 67.7% [ P = 0.009] and 65.4% vs. 65.9% [ P = 0.888]) and through day 60 (76.2% vs. 64.7% [ P = 0.002] and 68.9% vs. 62.1% [ P = 0.092]). No unanticipated adverse events were observed. Conclusions These studies demonstrated the clinical benefits of nepafenac 0.3% over vehicle in reducing the risk of postoperative ME, with the integrated analysis showing improved BCVA after cataract surgery in patients with diabetic retinopathy, with no unanticipated safety events

Phase 3, Randomized, 20-Month Study of the Efficacy and Safety of Bimatoprost Implant in Patients with Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 2)

Objective- To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods- This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 µg bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Results- Both 10 and 15 µg bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2–7.4, 6.5–7.8, and 6.1–6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 µg implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 µg implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 µg implant group compared with the timolol group. Conclusions- The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 µg implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management

Decidualized endometrial stromal cell derived factors promote trophoblast invasion

Objective: To evaluate the effects of decidua-derived factors on trophoblast invasion. Design Experimental study. Settings Research institute. Patient(s) In vitro decidualized human endometrial cells, trophoblast cell lines JEG-3, and ACH-3P. Intervention(s) The effect of decidual conditioned medium (DCM) on the invasion of trophoblast cells lines via JEG-3 and ACH-3P was investigated using a Matrigel invasion assay. The changes in expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and integrins in response to DCM in the trophoblast cells was also evaluated. Main Outcome Measure(s) Response of the trophoblast cells to the conditioned medium from decidual cells in terms of their invasive capability, and expression on invasion related molecules was measured. Result(s) DCM increased the invasion of both the cell lines by approximately 1.8-2.2-fold, compared with control condition medium. The increase in invasion was associated with elevated levels of MMP2, MMP3, and MMP9 mRNA and increased activity of MMP2 and MMP9 in DCM-treated ACH-3P, but not JEG-3 cells. DCM treatment led to a reduction in TIMP1 and TIMP3 and increased TIMP2 mRNA in JEG-3, cells but not ACH-3P cells. Compared with CCM-treated controls, DCM treatment led to a significant increase in the mRNA expression of integrin a5 and a6, but not integrin aV subunit in both cell lines. Conclusion(s) Decidua-derived factors increase the invasiveness of trophoblast cell lines and alter the expression of integrins, MMPs, and TIMPs

Effects of latent iron deficiency on auditory neural maturation during early infancy in infants above 35 weeks’ gestation

Background: Latent iron deficiency (LID) at birth is associated with prolonged latencies in auditory brainstem response (ABR), a surrogate for neural maturation. This study aimed to compare wave and inter-peak latencies of ABR at birth and at 4-6 months of age in infants ≥35 weeks of gestation with normal iron status (NIS) and LID. Methods: Neonates born at ≥35 weeks were screened. Cord ferritin value ≤ 75 ng/mL and >75 ng/mL were classified as LID and NIS, respectively. ABR was performed within 48 h of birth. The absolute latencies of waves I, III, and V, and inter-peak latencies I-III, III-V, and I-V were computed. Infants were reassessed at 4–6 months of age for hemoglobin, serum ferritin levels, and ABR latencies. Results: In total, 160 neonates were enrolled. The mean (SD) birth weight and gestational age of the study population were 2843 (384) g and 38.3 (1.1) weeks, respectively. Approximately 122 infants completed follow-up until 4–6 months of age: 37 in the LID group and 85 in the NIS group. Overall, the wave and interpeak latencies in both groups at birth were comparable. At 4–6 months, the absolute latencies of waves I, III, and V, and inter-peak latencies I-III, III-V, and I-V were decreased and were comparable in both groups. Among small-for-gestational-age neonates, inter-peak latencies in I-III and I-V at birth were significantly longer in the LID group than in the NIS group. Nine (24.3%) infants in the LID group and none in the NIS group were iron-deficient at 4–6 months of age. Conclusion: There was no difference in wave or inter-peak latencies at birth and at 4–6 months of age in neonates aged ≥35 weeks with or without LID. However, infants with LID at birth have a significant risk of iron deficiency at 4–6 months of age.CTRI/2017/08/009379 (www.ctri.nic.in)

Rhodium(II) acetate-catalyzed stereoselective synthesis, SAR and anti-HIV activity of novel oxindoles bearing cyclopropane ring

Novel oxindole derivatives bearing substituted cyclopropane ring have been designed on the basis of docking studies with HIV-1 RT using the software DS 2.5 and synthesized as probable NNRTIs against HIV-1 using rhodium(II) acetate-catalyzed stereoselective cyclopropanation reaction. The cyclopropane isomer, having trans relationship with respect to carbonyl of lactam moiety and functional group on the cyclopropane ring, was the major product in all cases along with a small amount of cis and methylene products. The trans isomers interacted well with HIV-1 RT through H-bonding with amino acids, like Lys101, Lys103, His235, Tyr318, constituting the non-nucleoside inhibitor binding pocket (NNIBP) during docking experiments. However, the compounds showed very little activity when subjected to in vitro anti-HIV-1 screening using β-galactosidase assay (TZM-bl cells) and GFP quantification (CEM-GFP cells). The very low level of in vitro HIV inhibition, in comparison to predicted EC50 values on the basis of computational studies, during CEM-GFP screening using AZT as positive control indicated that probably the HIV RT is not the viral target and the molecules work through some different mechanism