Real-world experience with fluocinolone acetonide intravitreal implant in patients with diabetic macular edema.

OBJECTIVES: to evaluate long-term effectiveness and safety of fluocinolone acetonide (FAc) implant used as second-line treatment in patients with persistent diabetic macular edema (DME). METHODS: retrospective data chart review of 241 pseudophakic eyes of 178 patients treated with FAc from July 2017 to December 2021 in 10 medical retinal units in Italy. The primary endpoint was the change of best-corrected visual acuity (BCVA) and central macular thickness (CMT) at 2 years. A Student's paired t-test was used. Additional therapies for DME and intraocular pressure (IOP)-related events were also evaluated. RESULTS: efficacy of FAc was assessed in a subset of 111 eyes with at least 24 months of follow-up. Mean BCVA increased at 2 years by 5.1 ETDRS letters (95%CI = 2.6-7.5; p < 0.001) while mean CMT decreased by 189 µm (95% CI 151-227; p < 0.001). Thirty-eight of these eyes (34.2%) needed additional intravitreal treatments, mainly anti-VEGF. Safety was evaluated on the entire cohort of 241 eyes treated with FAc. Overall, 66 eyes (27.4%) required emergent IOP-lowering medications (typically within the first-year post FAc) while 14 eyes (5.8%) underwent trabeculectomy, mostly during the second year of follow-up. CONCLUSION: FAc implant provides a substantial long-term functional and anatomical benefit when used as second-line treatment in eyes with DME. IOP rise can be adequately managed with topical agents although some eyes may require IOP-lowering surgery.

PERSEUS-IT 24-month analysis: a prospective observational study to assess the effectiveness of intravitreal aflibercept in routine clinical practice in Italy in patients with neovascular age-related macular degeneration.

PURPOSE: PERSEUS-IT (NCT02289924) was a prospective, observational, 2-year study evaluating the effectiveness and treatment patterns of intravitreal aflibercept (IVT-AFL) in patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice in Italy. METHODS: Treatment-naïve patients with nAMD receiving IVT-AFL per routine clinical practice were enrolled. The primary endpoint was mean change in visual acuity (VA; decimals) from baseline to month (M) 12 and M24. Outcomes were evaluated for the overall study population and independently for the 2 treatment cohorts: regular (3 initial monthly doses, ≥ 7 injections by M12, and ≥ 4 injections between M12 and M24) and irregular (any other pattern). RESULTS: Of 813 patients enrolled, 709 were included in the full analysis set (FAS); VA assessments were available for 342 patients at M12 (FAS1Y, 140 regular and 202 irregular) and 233 patients at M24 (FAS2Y, 37 regular and 196 irregular). In the overall FAS, the mean ± SD change in VA from baseline to M12 and M24 was + 0.09 ± 0.24 and + 0.02 ± 0.25 decimals, and there was a statistically significant difference between the regular and irregular cohorts in both FAS1Y (p = 0.0034) and FAS2Y (p = 0.0222). Ocular treatment-emergent adverse events were reported in 4.1% (n = 33/810 [safety set]) of patients. CONCLUSION: In PERSEUS-IT, clinically relevant functional and anatomic improvements were observed within the first 12 months of IVT-AFL treatment in routine clinical practice in Italy in patients with treatment-naïve nAMD. These gains were generally maintained across the 2-year study. The safety profile of IVT-AFL was consistent with prior studies. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02289924. DATE OF REGISTRATION: November 13, 2014.

Realizing Simultaneous Detrimental Reactions Suppression and Multiple Benefits Generation from Nickel Doping toward Improved Protonic Ceramic Fuel Cell Performance.

Anode-supported protonic ceramic fuel cells (PCFCs) are highly promising and efficient energy conversion systems. However, several challenges need to be overcome before these systems are used more widely, including the poor sintering of recently developed proton-conducting oxides and the decreased proton conductivity due to detrimental reactions between the nickel from anode and the electrolyte occurring during high-temperature co-sintering. Herein, a Ni doping strategy to increase the electrolyte sintering, suppress the detrimental phase reactions, and generate stable Ni nanoparticles for enhanced performance is proposed. A nickel-doped perovskite oxide is developed with the nominal composition of Ba(Zr0.1 Ce0.7 Y0.1 Yb0.1 )0.95 Ni0.05 O3- δ . Acting as a sintering aid, such a small amount of nickel effectively improves the sintering of the electrolyte. Concomitantly, reactions between nickel and the Ni-doped ceramic phase are suppressed, turning detrimental phase reactions into benefits. The nickel doping further promotes the formation of Ni nanoparticles, which enhance the electrocatalytic activity of the anode toward the hydrogen oxidation reaction and improve the charge transfer across the anode-electrolyte interface. As a result, highly efficient PCFCs are developed. The innovative anode developed in this work also shows favorable activity toward ammonia decomposition, making it highly promising for use in direct ammonia fuel cells.

Central retinal thickness fluctuations in patients treated with anti-VEGF for neovascular age related macular degeneration.

PURPOSE: This is a retrospective, single-center, non randomized interventional real life study, investigating the correlation between variability of central retinal thickness (CRT) and functional outcomes during 2 years of anti-VEGF therapy in patients treated for neovascular age related macular degeneration (nAMD). BACKGROUND: CRT fluctuations can depend on various factors such as the correct timing of injections, the therapeutic algorithm, and the number of injections (NI) performed; it is important to understand if CRT fluctuations are responsible for worse visual outcomes and consequently to identify the correct ways to avoid or reduce them. METHODS: Forty-one patients were treated for nAMD with aflibercept: 0.5 mg intravitreal aflibercept was administered every 4 weeks during the first 3 months, then bimonthly over the first year, and after the first year adopting a PRN regimen. Standard deviation of CRT (CRT/SD), BCVA, and NI were recorded. Correlation studies were performed by Pearson's test, Ancova, and Principal Component Analysis. RESULTS: A negative correlation was found between CRT/SD and final BCVA. In patients who lost more than 15 letters, CRT/SD mean was significantly higher in comparison with patients who lost less than 15 letters. Patients with final BCVA >65 letters showed lower CRT/SD values compared to patients with final BCVA ⩽65 letters. Multivariate analysis confirmed that in patients with higher baseline BCVA, improvement of BCVA was correlated to NI, and lower values of CRT fluctuations were observed. CONCLUSIONS: CRT fluctuations, even after an appropriate NI given per year, significantly influence BCVA; a proactive treatment algorithm appears crucial when treating patients with nAMD.

An ultra-low-molecular-weight heparin, fondaparinux, to treat retinal vein occlusion.

Retinal vein occlusions may decrease visual acuity. There is no known therapy to treat ocular thrombosis. The authors used fondaparinux, an ultra-low-molecular-weight heparin, to treat 13 consecutive cases of recent-onset retinal vein occlusions. Two patients with renal insufficiency were not included. Eight central retinal vein occlusions and 5 branch retinal vein occlusions in 13 patients were treated with subcutaneous fondaparinux 2.5 mg once a day. The patients were seen every 2 weeks. Macular edema was treated with intravitreal injections of anti-vascular endothelial growth factor or steroids. Two patients elected to discontinue treatment. Of the remaining 11, 9 occlusions resolved in 1.5 to 13.5 months with rapid resolution of retinal edema and hemorrhage as soon as the occlusions resolved. One patient had a retinal vein that was still occluded after 8 months of therapy and 1 had retinal vein occlusion that partially resolved after 15 months of treatment. Of the 9 eyes with occlusions that resolved, visual acuity improved in 7. In 2, visual acuity decreased due to macular ischemia. Occlusion recurred in 1 2.5 months after the suspension of initial treatment. This patient is again being treated with fondaparinux 2.5 mg. No hemorrhaging occurred. Fondaparinux 2.5 mg can be given subcutaneously once a day to patients with recent-onset retinal vein occlusions without renal insufficiency. An occlusion may take a number of months to resolve. Once the vein occlusion has resolved, retinal edema and hemorrhage rapidly resolve and vision improves. Macular edema should be treated while waiting for the vein occlusion to resolve.

Choroidal neovascular membrane following hormonal stimulation for in vitro fertilization.

PURPOSE: To report the onset of choroidal neovascularization (CNV) following hormonal stimulation for in vitro fertilization (IVF) in a healthy young woman. METHODS: A 31-year-old woman presented with visual impairment following hormonal stimulation for IVF. Clinical history was collected and best-corrected visual acuity (BCVA), complete eye examination, optical coherence tomography (OCT), fluorescein angiography (FA), and indocyanine green angiography were -performed. RESULTS: Clinical history was negative with the exception of the use of medications for IVF in the previous weeks. Ocular examination revealed the presence of a CNV in the right eye, confirmed by OCT and FA, with a BCVA of 0.7 decimal units. Possible ocular and systemic diseases associated with CNV development were investigated and excluded. Treatment with 3 monthly intravitreal injections of anti-vascular endothelial growth factor (VEGF) was effective in reducing CNV size and restoring visual acuity. CONCLUSIONS: This is the first report describing the development of CNV following hormonal stimulation for IVF. The development of CNV may be associated with changes of sex hormones, cytokines, and angiogenic factor levels, including VEGF, induced by hormonal stimulation.

Pain during second eye cataract surgery under topical anesthesia: an intraindividual study.

BACKGROUND: Aim of the study was to investigate: 1) if second eye cataract surgery under topical anesthesia is more painful than surgery on the first eye, 2) if pain experienced during the procedure on the first eye may predict the pain of the second procedure, and 3) if patients' cooperation is different between the first and the second eye procedure. METHODS: Seventy-three consecutive patients undergoing bilateral non-simultaneous cataract surgery were prospectively included in the study. Surgical technique was sutureless clear corneal phacoemulsification under topical anesthesia. Immediately after surgery every patient graded the pain experienced using a visual analogue scale (VAS) from 0 (no pain) to 10 (unbearable pain). At the end of each procedure the surgeon graded patients' cooperation using a 4-point scale. RESULTS: Mean VAS score was 2.35 (SD 2.63) for the first eye and 2.89 (SD 2.93) for the second eye. Such a difference was not statistically significant (p = 0.1777, Wilcoxon test). The correlation between the VAS score of the first and that of the second procedure was statistically significant (r = 0.5514, p < 0.0001, Spearman rank correlation). Patients' cooperation was 2.64 (SD 0.63) during the first procedure and 2.52 (SD 0.79) during the second procedure; this difference was not statistically significant (p = 0.1769, Wilcoxon matched-pairs signed-ranks test). CONCLUSIONS: After uneventful cataract surgery under topical anesthesia, pain experienced and cooperation did not differ between first and second eye procedures. A correlation was found between pain scores of the first and the second eye procedures.

Efficacy of topical plus intracameral anesthesia for cataract surgery in high myopia: randomized controlled trial.

PURPOSE: To assess the efficacy of intracameral lidocaine supplementation of topical anesthesia during cataract surgery in eyes with high myopia. SETTING: Department of Ophthalmology, Ospedale San Pietro-Fatebenefratelli, Rome, Italy. METHODS: This prospective double-blind study comprised 120 highly myopic eyes with an axial length (AL) greater than 26.0 mm scheduled for routine cataract surgery. Cases were divided into 2 groups of 60 eyes each. One group received a placebo of balanced salt solution (BSS) (control group) and the other group, a supplement of 0.1 mL preservative-free lidocaine hydrochloride 1% injected in the capsular bag during hydrodissection (lidocaine group). Intraoperative pain was assessed by recording spontaneous patient reports of sensation of pain or ocular discomfort during 3 surgical stages: phaco tip insertion, irrigation/aspiration (I/A) system insertion for cortical aspiration, I/A system insertion for ophthalmic viscosurgical device removal after intraocular lens implantation. Postoperative pain was assessed on a visual analog scale (range 0 to 10). Data were compared by chi-square and Mann-Whitney U tests. RESULTS: The overall mean AL was 28.58 mm (28.57 mm control group; 28.50 mm lidocaine group). Fewer patients in the lidocaine group reported intraoperative pain, ocular discomfort, or tissue manipulation (odds ratio=0.36; 95% confidence interval, 0.16-0.80; P= .019). The mean postoperative pain score was 1.88+/-2.17 (SD) in the control group and 1.36+/-2.02 in the lidocaine group; the difference was not statistically significant (P= .21). CONCLUSION: Intracameral lidocaine supplementation for cataract surgery may improve intraoperative comfort under topical anesthesia in highly myopic eyes.

Lidocaine 2% gel versus lidocaine 4% unpreserved drops for topical anesthesia in cataract surgery: a randomized controlled trial.

OBJECTIVE: To compare intracameral levels and clinical efficacy of lidocaine 2% gel with lidocaine 4% unpreserved drops. DESIGN: Double-blind, randomized, one-surgeon, controlled trial. PARTICIPANTS: One hundred seven consecutive cataract cases eligible for topical anesthesia. INTERVENTION: Patients were randomly assigned to receive 20 mg of lidocaine either as lidocaine 2% gel (1 ml) or as lidocaine 4% unpreserved eyedrops (0.5 ml) before clear corneal phacoemulsification. MAIN OUTCOME MEASURES: Aqueous samples were taken to measure lidocaine intraocular levels. Intraoperative pain was quantified a few minutes after surgery using a 0 to 10 visual analog scale. SECONDARY OUTCOME MEASURES: Patients were asked to grade the degree to which they were bothered by tissue manipulation. The surgeon graded patients' cooperation. The anesthesiologist recorded any increase in pulse or blood pressure and the need for supplemental topical anesthesia or intravenous sedation. Duration of surgery and intraoperative complications were also recorded. RESULTS: In the gel group intracameral lidocaine levels were significantly higher (P < 0.001) and patient-reported intraoperative pain scores were significantly lower (P = 0.026). Patients in the gel group were bothered by tissue manipulation to a lesser extent (P = 0.028), and their cooperation was better (P = 0.002). Increases in blood pressure were more frequent in the eyedrops group. Supplemental anesthesia was required in two cases (3.70%) in the gel group versus eight cases in the eyedrops group (15.09%). No correlation between intracameral lidocaine levels and intraoperative pain scores was found (r = -0.026, P = 0.789). CONCLUSIONS: If administered by means of gel, the same amount of lidocaine gives significantly higher intracameral levels of lidocaine, better analgesia, better patient cooperation, and less need for intraoperative supplemental anesthesia. Lower pain scores do not correlate with intracameral lidocaine levels.