Cytidine 5’-diphosphocholine has been widely studied in systemic neurodegenerative diseases, like Alzheimer’s disease, Parkinson’s disease, and brain ischemia. The rationale for the use of citicoline in ophthalmological neurodegenerative diseases, including glaucoma, anterior ischemic optic neuropathy, and diabetic retinopathy, is founded on its multifactorial mechanism of action and the involvement in several metabolic pathways, including phospholipid homeostasis, mitochondrial dynamics, as well as cholinergic and dopaminergic transmission, all being involved in the complexity of the visual transmission. This narrative review is aimed at reporting both pre-clinical data regarding the involvement of citicoline in such metabolic pathways (including new insights about its role in the intracellular proteostasis through an interaction with the proteasome) and its effects on clinical psychophysical, electrophysiological, and morphological outcomes following its use in ophthalmological neurodegenerative diseases (including the results of the most recent prospective randomized clinical trials).
13 April 2020 in European Journal of Clinical Pharmacology
Purpose To evaluate the penetration of levofloxacin and dexamethasone sodium phosphate into the aqueous humour (AH) after administration in combination and as single molecules. Evaluation of the penetration of those agents in the site of action and their pharmacodynamic potential activity in view of the intended clinical use after cataract surgery. Methods Randomised, assessor-blinded, parallel-group. Patients scheduled for cataract surgery were assigned in a 1:1:1 ratio to: levofloxacin + dexamethasone sodium phosphate (L-DSP), Levofloxacin (L) or Dexamethasone sodium phosphate (DSP) eye drops. Either test or reference drugs were instilled in the cul-de-sac twice, 90 and 60 min before paracentesis. Results A total of 125 patients completed the study. Fraction of dose absorbed in the anterior chamber was 3.8–4.2 · 10−4 for levofloxacin and 0.3–0.4 · 10−4 for dexamethasone, respectively. No notable differences in concentration of levofloxacin were found between L-DSP arm (1.970 nmol/ml) and L arm (2.151 nmol/ml). The concentrations of levofloxacin were well above the MICs for the most frequent Gram-positive and Gram-negative eye pathogens. Dexamethasone concentrations were slightly lower in L-DSP arm (0.030 nmol/ml) than in DSP arm (0.042 nmol/ml), but still in the pharmacodynamically active range in the site of action. The difference was not clinically relevant. DSP was not detected in any HA sample, suggesting its full hydrolysis to free dexamethasone. Conclusion Our results confirm that no interaction is evident on the corneal penetration of levofloxacin and dexamethasone which reach pharmacologically active concentrations when instilled as fixed combination eye drops to patients undergoing cataract surgery. Trial registration ClinicalTrials.gov Identifier: NCT03740659
Background: Ocular surface frequently affects glaucoma patients. In this paper we aimed at evaluating the impact of glaucoma surgery on the ocular surface of patients who received unilateral trabeculectomy. Methods: 26 consecutive patients successfully treated with trabeculectomy on one eye (Trab Eye) and under control with topical treatments on the fellow eye (Med Eye) were included in this observational study. They received IDEEL and OSDI questionnaires, Tear Film Osmolarity (TFO), grading of conjunctival hyperemia, fluorescein tear break-up time (tBUT), grading of corneal staining and Schirmer test. Results: IDEEL and OSDI scores were 48 ± 38 and 11 ± 12, respectively, with moderate correlation (r = 0.50, p = 0.03). Compared with Med eyes, Trab Eyes had higher tBUT (6.5 ± 3.5 vs. 5.1 ± 2.7 s, p = 0.004), lower conjunctival hyperemia (0.8 ± 0.9 and 1.7 ± 1.1 respectively, p < 0.001) and lower corneal staining (0.3 ± 0.5 and 0.6 ± 0.5, respectively, p = 0.03). Correlation between corneal staining and conjunctival hyperemia was 0.55 in Trab Eyes (p = 0.01) and 0.44 in Med Eyes (p > 0.05). Patients with bilateral corneal staining had had threefold worse questionnaire scores (p < 0.05). The duration of treatment and the daily exposure to preservatives did not directly affect OS parameters in this cohort of patients. Conclusions: Patients receiving successful trabeculectomy showed better OS homeostasis (higher TBUT, lower grading of conjunctival hyperemia and corneal staining) than fellow medically treated eyes. Presence of corneal epithelial damage in both eyes is the factor more consistently affecting questionnaire scores.
Précis: Using iCare Home2 (iCare, Finland) rebound tonometry, self-measurement of intraocular pressure has demonstrated good reliability and ease of use. Purpose: To investigate the reliability and repeatability of self-measured intraocular pressure (IOP) with rebound tonometry using iCare Home2. Patients and Methods: One hundred four patients out of 110 consecutive patients were recruited for this observational cross-sectional study. One randomly selected eye from each patient underwent 6 consecutive IOP measurements with Goldmann applanation tonometry (GAT), iCare IC200, and iCare Home2. Every eye was tested twice with each device, in random order, by an ophthalmologist for GAT and IC200, and by the patient itself for Home2. In addition, central corneal thickness (CCT) has been collected. The reliability of Home2 has been tested by calculating limits of agreement (LoA) between self-measured and physician-measured IOP, using the Bland-Altman analysis. The repeatability of each device has been tested by calculating the limits of repeatability (LoR) with the same method. Pearson correlation coefficient was used to determine the correlation between differences in IOP measurements and CCT. Results: The mean difference between GAT and iCare Home2 was −0.28±1.57 mmHg (P=0.070), 95%-LoA: (−3.36 to 2.79 mmHg). The mean difference between IC200 and iCare Home2 was 0.92±1.48 mmHg (P<0.0001), 95%-LoA (−1.98 to 3.82 mmHg). The mean difference between the first and second measurements with GAT, iCare IC200, and iCare Home2 measurements was 0.21±0.98 mmHg (P=0.03), −0.02±1.11 mmHg (P=0.88) and −0.23±1.04 mmHg (P=0.05). Conclusions: Self-measured IOP with rebound tonometry showed good reliability and repeatability when compared with physician-measured IOP with both standard GAT and rebound tonometry.
Electrical stimulation (ES) of the eye represents a therapeutic approach in various clinical applications ranging from retinal dystrophies, age-related macular degeneration, retinal artery occlusion and nonarteritic ischemic optic neuropathy. In clinical practice, ES of the eye is mainly performed with a transcorneal or transpalpebral approach. These procedures are non-invasive and well-tolerated by the patients, reporting only minimal and transient adverse events, while serious adverse effects were not observed. Despite the growing literature on animal models, only clinical parameters have been investigated in humans and few data are available about biochemical changes induced by ES of the eye. The purpose of this study is to investigate the possible mechanism that regulates the beneficial effects of ES on retinal cells function and survival in humans. 28 patients undergoing pars plana vitrectomy (PPV) for idiopathic epiretinal membrane (iERM) were randomly divided in two groups: 13 patients were treated with transpalpebral ES before surgery and 15 underwent surgery with no prior treatment. Vitreous samples were collected for biochemical analysis during PPV. ES treatment leads to a reduction in the vitreous expression of both proinflammatory cytokines, namely IL-6 and IL-8, and proinflammatory lipid mediators, such as lysophosphatidylcholine. Indeed, we observed a 70% decrease of lysophosphatidylcholine 18:0, which has been proven to exert the greatest proinflammatory activities among the lysophosphatidylcholine class. The content of triglycerides is also affected and significantly decreased following ES application. The vitreous composition of patients undergoing PPV for iERM displays significant changes following ES treatment. Proinflammatory cytokines and bioactive lipid mediators expression decreases, suggesting an overall anti-inflammatory potential of ES. The investigation of the mechanism by which this treatment alters the retinal neurons leading to good outcomes is essential for supporting ES therapeutic application in various types of retinal diseases.
Purpose: To describe a case of extensive macular atrophy with pseudodrusen-like appearance complicated by Bruch membrane rupture and choroidal neovascularization, treated with intravitreal injection of an antivascular endothelial growth factor drug. Methods: A 54-year-old woman, affected by extensive macular atrophy with pseudodrusen-like appearance, has developed Bruch membrane rupture and choroidal neovascularization. This report discusses the development of the disease and the improvement after a single intravitreal injection of Avastin. Results: After treatment, the visual acuity increased from 20/400 to 20/200; clinical and anatomical improvement remained stable with a 2-month follow-up. Conclusion: Extensive macular atrophy with pseudodrusen-like appearance could be complicated by Bruch membrane rupture and subsequent choroidal neovascularization. Antivascular endothelial growth factor intravitreal injection could have beneficial effects on this entity, but concern could raise in respect of possible increase of chorioretinal atrophy.