Safety of silicone oils as intraocular medical device: An in vitro cytotoxicity study.

This study aimed to assess the cytotoxic effect of low molecular weight components (LMWC) and conventional silicone oils (SOs) 1000 cSt with different degree of purification (raw, intermediate, and purified) using in vitro cytotoxicity tests. Direct contact cytotoxicity tests were performed in BALB 3T3 and human retinal pigment epithelial cells (ARPE-19) using quantitative and qualitative evaluation according to the ISO 10993-5 (2009) standards. Conventional SOs 1000 cSt in form of raw, intermediate (intermediate product obtained during distillation process), and purified SO (final product after distillation) and a concentrate of LMWC (including siloxane chains with molecular weight up to 1557 g/mol) were directly applied to 100% of cell layer area for 24 h. Cell viability was quantified using 3-(4,5-dimethylthiazole-2-yl)-2,5-28 diphenyltetrazolium bromide (MTT) and neutral red uptake assays in ARPE-19 and BALB3T3, respectively. All tested samples, including the concentrate of LMWC, resulted to be not cytotoxic according to ISO 10993-5 in both qualitative and quantitative evaluations. However, the cellular viability was significantly higher in the intermediate and purified SO compared with the raw SO in ARPE-19 cells. No reduction in cell viability was detected by LMWC. The absence of cytotoxicity was observed for all tested samples in both BALB3T3 and ARPE-19 after 24 h of application. A direct cytotoxic effect is not likely to be involved in the potential complications related to SO and LMWC. Long-term potential adverse effects of SO could be related to the raw material and to different concentrations of LMWC.

Emerging muscarinic receptor antagonists for the treatment of asthma.

INTRODUCTION: The increased acetylcholine signaling in asthma pathophysiology offers the rationale for the use of LAMAs in the treatment of asthmatic patients. Tiotropium is still the only LAMA approved for use in asthma but there is a real interest in developing novel LAMAs for the treatment of asthma, or at least to extend this indication to other LAMAs already on the market. AREAS COVERED: We examined and discussed trials and research that have studied or are evaluating the role of LAMAs already on the market in asthma and possible novel muscarinic acetylcholine receptor antagonists. EXPERT OPINION: Glycopyrronium and umeclidinium will soon be included in the GINA strategy with the same current indications of tiotropium. It is likely that the choice of the LAMA will be influenced not so much by its pharmacological profile as by the type of triple therapy chosen. It is extremely difficult to identify a new LAMA that is more effective than tiotropium, but is it plausible that new technologies that will allow delivering the drug in a more targeted way and with a lower risk of adverse effects may represent the real progress in the use of LAMAs in asthma in the coming years.

Corneal UV Protective Effects of a Topical Antioxidant Formulation: A Pilot Study on In Vivo Rabbits.

This study aimed to evaluate the protective effect of a topical antioxidant and ultraviolet (UV) shielding action formulation containing riboflavin and D-α-tocopherol polyethylene glycol succinate (TPGS) vitamin E against corneal UV-induced damage in vivo rabbit eyes. In vivo experiments were performed using male albino rabbits, which were divided into four groups. The control group (CG) did not receive any UV irradiation; the first group (IG) was irradiated with a UV-B-UV-A lamp for 30 min; the second (G30) and third (G60) groups received UV irradiation for 30 and 60 min, respectively, and were topically treated with one drop of the antioxidant and shielding formulation every 15 min, starting one hour before irradiation, until the end of UV exposure. The cornea of the IG group showed irregular thickening, detachment of residual fragments of the Descemet membrane, stromal fluid swelling with consequent collagen fiber disorganization and disruption, and inflammation. The cornea of the G30 group showed edema, a mild thickening of the Descemet membrane without fibrillar collagen disruption and focal discoloration, or inflammation. In the G60 group, the cornea showed a more severe thickening, a more abundant fluid accumulation underneath the Descemet membrane with focal detachment, and no signs of severe tissue alterations, as were recorded in the IG group. Our results demonstrate that topical application of eye drops containing riboflavin and TPGS vitamin E counteracts UV corneal injury in exposed rabbits.

Measurement of leaf lamina moisture with a low-cost electrical humidity sensor: case study on a wheat water-mutant.

BACKGROUND: The presence and persistence of water on the leaf can affect crop performance and thus might be a relevant trait to select for or against in breeding programmes. Low-cost, rapid and relatively simple methods are of significant importance for screening of large populations of plants for moisture analysis of detached leaves. Leaf moisture can be detected using an electric circuit, where the resistance changes are proportional to the moisture of the measured surface. In this study, we present a protocol to analyse genotypic differences through the electrical properties of living or stored tissues, performed using a commercial device. Expanded and non-expanded leaves were compared to determine the effects of leaf maturity on these data. Two wheat genotypes that differ in tissue affinity for bound water were used to define the influence of water status. RESULTS: The device indirectly estimates leaf moisture content using two electrodes applied to the leaf lamina of fresh and stored samples. Single moisture readings using this moisture meter had mean execution time of ~ 1.0 min. Exponential associations provided good fits for relationships between the moisture meter reading (MMR) and the electrical resistance applied to the electrodes. MMR normalised for the water/ dry matter ratio (MMRnorm) was lower for mature leaves of the water-mutant than those of wild-type, for the fully hydrated fresh leaves. MMR of fully mature leaves when partially dehydrated and measured after 10 min at 27 °C and 40% relative humidity was greater for the water-mutant than the wild-type. CONCLUSIONS: This case study provides a low-cost tool to compare electrical-resistance estimates of leaf moisture content, together with a promising and rapid phenotyping protocol for genotypic screening of wheat under standard environmental conditions. Measurement of changes in MMR with time, of fresh and partially dehydrated leaves, or of MMR normalised to tissue water content allowed for differentiation between the genotypes. Furthermore, the differences observed between genotypes that here relate particular to tissue affinity for bound water suggest that not only the free-water fraction, but also other water fractions, can affect these electrically estimated leaf moisture measures.

Multi-Crop Green LAI Estimation with a New Simple Sentinel-2 LAI Index (SeLI).

The spatial quantification of green leaf area index (LAIgreen), the total green photosynthetically active leaf area per ground area, is a crucial biophysical variable for agroecosystem monitoring. The Sentinel-2 mission is with (1) a temporal resolution lower than a week, (2) a spatial resolution of up to 10 m, and (3) narrow bands in the red and red-edge region, a highly promising mission for agricultural monitoring. The aim of this work is to define an easy implementable LAIgreen index for the Sentinel-2 mission. Two large and independent multi-crop datasets of in situ collected LAIgreen measurements were used. Commonly used LAIgreen indices applied on the Sentinel-2 10 m × 10 m pixel resulted in a validation R² lower than 0.6. By calculating all Sentinel-2 band combinations to identify high correlation and physical basis with LAIgreen, the new Sentinel-2 LAIgreen Index (SeLI) was defined. SeLI is a normalized index that uses the 705 nm and 865 nm centered bands, exploiting the red-edge region for low-saturating absorption sensitivity to photosynthetic vegetation. A R² of 0.708 (root mean squared error (RMSE) = 0.67) and a R² of 0.732 (RMSE = 0.69) were obtained with a linear fitting for the calibration and validation datasets, respectively, outperforming established indices. Sentinel-2 LAIgreen maps are presented.

Analysis of differences in intraocular pressure evaluation performed with contact and non-contact devices.

BACKGROUND: To evaluate differences of intraocular pressure (IOP) measurements performed with Goldmann applanation tonometer (GAT), dynamic contour tonometer (DCT), rebound tonometry (RT), Ocular Response Analyzer (ORA) and Corvis ST (CST) in eyes screened for refractive surgery. METHODS: One eye, only the right one, of 146 patients was included in this study. Each participant was submitted to a corneal analysis with Scheimpflug camera and IOP evaluation with GAT, DCT, RT, ORA and CST. Differences in IOP values obtained thanks to each instruments were compared and then correlations between these discrepancies and morphological features such as mean keratometry (MK) and central corneal thickness (CCT) provided by Pentacam were studied. Software used to run statistical evaluations was SPSS, version 18.0. RESULTS: Study participants had a mean age of 33.1 ± 9.2 years old. IOP values observed in this study were 15.97 ± 2.47 mmHg (GAT), 17.55 ± 2.42 mmHg (DCT), 17.49 ± 2.08 mmHg (RT), 18.51 ± 2.59 mmHg (ORA) and 18.33 ± 2.31 mmHg (CST). The mean CCT was 560.23 ± 31.00 µm, and the mean MK was 43.33 ± 1.35 D. GAT provided significant lower values in comparison to all other devices. DCT and RT gave significantly lower intermediate IOP values than those measured with ORA and CST. All the IOP measures and the differences between devices were significantly correlated with CCT. CONCLUSIONS: According to our data, although our findings should be confirmed in further studies, GAT tonometer cannot be used interchangeably with DCT, RT, ORA and CST.

Functional, histological and biomechanical characterization of wheat water-mutant leaves.

A wheat (Triticum turgidum subsp. durum) mutant, generated with sodium azide from wild-type (WT) cv. 'Trinakria', differs in its water affinity of dry leaves, and was designated as a water-mutant. Compared with the WT, water-mutant leaves have lower rates of water uptake, while stomatal and cuticular transpiration do not differ. The nuclear magnetic resonance proton signals used for image reconstruction of leaf cross sections showed differences between these genotypes for the T1 proton spin-density and the T2 proton spin-spin relaxation time. Structural and histochemical analyses at midrib level showed that the water-mutant has thinner leaves, with more and smaller cells per unit area of mesophyll and sclerenchyma, and has altered staining patterns of lignin and pectin-like substances. Stress-strain curves to examine the rheological properties of the leaves showed a biphasic trend, which reveals that the tensile strength at break load and the elastic modulus of the second phase of the water-mutant are significantly higher than for the WT. These data support the proposal of interrelationships among local biophysical properties of the leaf, the microscopic water structure, the rheological properties and the water flux rate across the leaf. This water-mutant can be used for analysis of the genetic basis of these differences, and for identification of gene(s) that govern these traits.

TREATMENT OF EXUDATIVE AGE-RELATED MACULAR DEGENERATION WITH RANIBIZUMAB COMBINED WITH KETOROLAC EYEDROPS OR PHOTODYNAMIC THERAPY.

PURPOSE: To evaluate whether ketorolac eyedrops plus intravitreal ranibizumab (IVR) or verteporfin photodynamic therapy plus IVR provides additional benefit over IVR monotherapy for treatment of choroidal neovascularization in age-related macular degeneration. METHODS: This was a prospective, randomized, pilot study in 75 patients with naive choroidal neovascularization. Patients were randomized 1:1:1 into 3 groups: ranibizumab monotherapy (RM), ranibizumab plus ketorolac, or ranibizumab plus loading-phase reduced-fluence verteporfin photodynamic therapy (RV) groups. RESULTS: At 12 months, all groups showed significant improvement in both best-corrected visual acuity and central retinal thickness. The mean best-corrected visual acuity change from baseline to 12 months was -0.14 ± 0.52 logMAR (20/73 ± 20/29), -0.25 ± 0.60 logMAR (20/46 ± 20/27), and -0.10 ± 0.30 (20/97 ± 20/40) logMAR in RM, ranibizumab plus ketorolac, and RV groups, respectively. The mean central retinal thickness change from baseline to 12 months was -125 ± 15 µm, -141 ± 21 µm, and -130 ± 15 µm in RM, ranibizumab plus ketorolac, and RV groups, respectively. Both ranibizumab plus ketorolac and RV groups required fewer IVR treatments than RM. CONCLUSION: Compared with RM and ranibizumab plus verteporfin photodynamic therapy, the combination of 0.45% ketorolac eyedrops 3 times a day and ranibizumab in patients with choroidal neovascularization provided superior best-corrected visual acuity and central retinal thickness outcomes. Both combination regimens required fewer IVR injections than RM during the 12-month follow-up period.

Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration.

Macular degenerations represent leading causes of central blindness or low vision in developed countries. Most of these severe visual disabilities are due to age-related macular degeneration (AMD) and pathologic myopia (PM), both of which are frequently complicated by subfoveal choroidal neovascularization (CNV). Photodynamic therapy with verteporfin (PDT-V) is still employed for CNV treatment in selected cases or in combined regimen. In Caucasian patients, the common polymorphism G185T of factor XIII-A gene (FXIII-A-G185T; rs5985) has been described as predictor of poor angiographic CNV responsiveness to PDT-V. Nevertheless, the prognostic implications of this pharmacogenetic determinant on long-term visual outcome after a PDT-V regimen have not been evaluated. We retrospectively selected Caucasian patients presenting with treatment-naive CNV and receiving standardized PDT-V protocol for two years. The study population included patients affected by subfoveal CNV secondary to AMD or PM. We assessed the correlations between the polymorphic allele T of FXIII-A-G185T and: (1) total number of photodynamic treatments; and (2) change in visual acuity from baseline to the end of the follow-up period. Considering a total study population of 412 patients with neovascular AMD or PM, the carriers of 185 T-allele of FXIII-A (GT or TT genotype) received a higher number of photodynamic treatments than patients without it (GG wild-type genotype) (p < 0.01; mean number of PDT-V: 5.51 vs. 3.76, respectively). Moreover, patients with 185 T-allele of FXIII-A had a more marked worsening of visual acuity at 24 months than those with the GG-185 wild genotype (p < 0.01; mean difference in logMAR visual acuity: 0.22 vs. 0.08, respectively). The present findings show that the G185T polymorphism of the FXIII-A gene is associated with significant differences in the long-term therapeutic outcomes of patients treated with standardized PDT-V protocol. The comprehensive appraisal of both anti-thrombophilic effects due to FXIII-A G185T variant and photo-thrombotic action of PDT-V toward CNV provides several clues about the rationale of this intriguing pharmacogenetic correlation. Further investigations are warranted to outline the appropriate paradigm for guiding PDT-V utilization in the course of the combined therapeutic protocol for neovascular macular degeneration.

Changes in macular pigment optical density after full-thickness macular hole closure using inverted flap technique.

Full-thickness macular hole (FTMH) is a debilitating retinal disorder, particularly in its advanced forms, necessitating surgical intervention for vision restoration. This case report details the successful closure of a large FTMH using the inverted flap technique, highlighting the essential role of multimodal imaging, and particularly macular pigment optical density (MPOD) assessment, in preoperative and postoperative evaluation. A 55-year-old patient presented with severe vision loss in one eye due to a large FTMH. Surgery was performed by an expert vitreoretinal surgeon, resulting in significant postoperative improvements in visual acuity and retinal architecture. Multimodal imaging, including MPOD assessment, played a pivotal role in preoperative evaluation and postoperative monitoring. The notable increase in MPOD following successful surgery suggests its potential role as a valuable adjunctive biomarker associated with a good visual prognosis following this type of macular hole surgical interventions.

Choroidal Thickness and brolucizumab intravitreal injection: Cause or effect of intraocular inflammation?

PURPOSE: to analyze the structural changes of choroidal thickness in patients with brolucizumab-related exudative vitritis after intravitreal injection, using EDI-OCT. METHODS: One hundred eyes of one hundred patients, affected by exudative age related-macular degeneration treated with brolucizumab intravitreal injection between January 2022 and august 2023 at Eye clinic of University of Federico II Naples, were enrolled. All eyes underwent macular examination using Enhanced Deep Imaging-OCT (Spectralis, Heidelberg Engineering inc.) preoperatively and at each postoperative check (1, 3, 6, 12 months). Anterior segment evaluation at slit lamp before and after injection was performed. RESULTS: Of the 100 treated eyes, 4 showed inflammatory signs related to exudative vitreitis, with inflammation signs at slit lamp examination and confirmed by OCT and B scan ecography. EDI-OCT revealed, in all of these 4 patients, a significant increase of choroidal thickness compared to baseline. CONCLUSION: choroidal thickness could be correlated in the inflammatory response generated in patients undergoing treatment with brolucizumab.

Congenital Optic Disc Anomalies: Insights from Multimodal Imaging.

In this comprehensive review, we delve into the significance of multimodal imaging in diagnosing and managing complications of congenital optic disc anomalies. While the fundus examination is the gold standard tool in the diagnosis of these pathologies, spectral domain (SD) optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) could shed light on the pathogenesis and treatment. Moreover, this review seeks to offer a comprehensive insight into the multimodal approach of these rare congenital pathologies. In conclusion, congenital anomalies of the optic nerve represent a major challenge for ophthalmologists. Further research could be useful to clarify the pathophysiology of these diseases and define a correct and more specific treatment approach.

Exploring the Impact of Glycemic Control on Diabetic Retinopathy: Emerging Models and Prognostic Implications.

This review addresses the complexities of type 1 diabetes (T1D) and its associated complications, with a particular focus on diabetic retinopathy (DR). This review outlines the progression from non-proliferative to proliferative diabetic retinopathy and diabetic macular edema, highlighting the role of dysglycemia in the pathogenesis of these conditions. A significant portion of this review is devoted to technological advances in diabetes management, particularly the use of hybrid closed-loop systems (HCLSs) and to the potential of open-source HCLSs, which could be easily adapted to different patients' needs using big data analytics and machine learning. Personalized HCLS algorithms that integrate factors such as patient lifestyle, dietary habits, and hormonal variations are highlighted as critical to reducing the incidence of diabetes-related complications and improving patient outcomes.

Compatibility of a New Ocular Surface Dye with Disposable and Bi-Weekly Soft Contact Lenses: An Experimental Study.

Ocular surface staining for assessing corneal and conjunctival epithelium integrity is typically conducted using fluorescein, lissamine green, or rose Bengal dyes. Recently, a novel vital dye, REmark®, based on riboflavin, has been proposed for ocular surface examination. In the management of corneal and ocular surface diseases (OSD), the use of contact lenses is integral to therapeutic strategies. This study explores the compatibility of REmark® with four different types of disposable or bi-weekly soft contact lenses. Morphological variations observed under stereomicroscopy and ultraviolet (UV) ray transmittance in the visible spectrum (VIS) were evaluated at 2 and 4 h post-immersion of the contact lenses in both the original fluid and the new dye. The findings indicate no significant differences between the group treated with the original liquid and those immersed in REmark®, except for a yellow hue observed in the latter group, which dissipates after 8 h in physiological solution. This study highlights the potential of utilizing the new vital dye for ophthalmologic examinations even in the presence of applied soft contact lenses, offering a promising avenue for improved diagnostic practices and patient comfort.

Reply to Wostyn, P. Targeting the Cerebrospinal Fluid Compartment in Glaucoma: Still the Dark Side of the Moon? Comment on "Passaro et al. Glaucoma as a Tauopathy-Is It the Missing Piece in the Glaucoma Puzzle? J. Clin. Med. 2023, 12, 6900".

We are grateful to the author of the comment [...].

Corneal collagen cross-linking in patients with keratoconus from the Dresden protocol to customized solutions: theoretical basis.

Keratoconus is an ectatic condition characterized by gradual corneal thinning, corneal protrusion, progressive irregular astigmatism, corneal fibrosis, and visual impairment. The therapeutic options regarding improvement of visual function include glasses or soft contact lenses correction for initial stages, gas-permeable rigid contact lenses, scleral lenses, implantation of intrastromal corneal ring or corneal transplants for most advanced stages. In keratoconus cases showing disease progression corneal collagen crosslinking (CXL) has been proven to be an effective, minimally invasive and safe procedure. CXL consists of a photochemical reaction of corneal collagen by riboflavin stimulation with ultraviolet A radiation, resulting in stromal crosslinks formation. The aim of this review is to carry out an examination of CXL methods based on theoretical basis and mathematical models, from the original Dresden protocol to the most recent developments in the technique, reporting the changes proposed in the last 15y and examining the advantages and disadvantages of the various treatment protocols. Finally, the limits of non-standardized methods and the perspectives offered by a customization of the treatment are highlighted.

Targeting shared pathways in tauopathies and age-related macular degeneration: implications for novel therapies.

The intricate parallels in structure and function between the human retina and the central nervous system designate the retina as a prospective avenue for understanding brain-related processes. This review extensively explores the shared physiopathological mechanisms connecting age-related macular degeneration (AMD) and proteinopathies, with a specific focus on tauopathies. The pivotal involvement of oxidative stress and cellular senescence emerges as key drivers of pathogenesis in both conditions. Uncovering these shared elements not only has the potential to enhance our understanding of intricate neurodegenerative diseases but also sets the stage for pioneering therapeutic approaches in AMD.

Intravitreal pegaptanib sodium (Macugen) for treatment of myopic choroidal neovascularization: a morphologic and functional study.

BACKGROUND: To report the morphologic and functional outcomes resulting from the use of intravitreal pegaptanib (IVP) sodium (Macugen) in patients with myopic choroidal neovascularization. METHODS: An open-label, nonrandomized, prospective clinical trial was performed. Morphologic outcome, such as foveal thickness, was assessed by optical coherence tomography, whereas functional outcomes were assessed by best-corrected visual acuity and microperimetry. Treatment protocol consisted of 3 consecutive IVP (0.3 mg/0.05 mL; baseline, 6th week, and 12th week). Follow-up checks were scheduled at the following intervals: baseline, 18, 24, 36, and 48 weeks. RESULTS: Twenty eyes from 20 patients were studied. All patients completed follow-up at 48 weeks. After IVP, a significant decrease in foveal thickness occurred (-20%), and at the end of follow-up, choroidal neovascularization closure was obtained in all eyes. An improvement of functional parameters was recorded in all patients (best-corrected visual acuity from 25.5 ± 8.09 letters to 45.5 ± 8.16 letters, P < 0.0001; microperimetry from 8.40 ± 2.14 dB to 10.8 ± 2.05 dB, P < 0.01). The mean number of IVP was 3, and none of patients met the re-treatment criterion during the entire follow-up period. Neither ocular nor systemic side effects were observed. CONCLUSION: The findings demonstrate that the selective inhibition of VEGF-165 isoform by IVP is an effective treatment for myopic choroidal neovascularization.

Long-term effects of early/late-onset visual deprivation on macular and retinal nerve fibers layer structure: A pilot study.

BACKGROUND/AIMS: Tomographic analysis of macular and peripapillary retinal nerve fibers layer (RNFL) thickness in patients with history of congenital (CC) and developmental cataract (DC). METHODS: Analysis of macular and RNFL thickness using a spectral-domain optical coherence tomography was performed. Retinal layers thickness was measured using the internal segmentation software. Measurements of affected (unilateral and bilateral), contralateral eyes and control eyes were compared. RESULTS: Patients with history of CC or DC (n = 13 and 11 respectively) and 35 healthy control subjects were enrolled. Thicker inner and outer nuclear layers (INL, ONL) and thicker ONL were found when CC and DC group when compared to controls respectively. Bilateral CC showed the most relevant differences. Slight thickening of CC inner retinal layers were found when compared to DC. Increased superonasal RNFL thickness was found in CC group when compared to DC and controls. Thickening of RNFL of contralateral unaffected eyes of unilateral CC were found when compared to controls. CONCLUSION: Significant macular and RNFL thickness changes between CC, DC patients and controls that partially involve also contralateral unaffected eyes of unilateral congenital cataract were found. CC and DC groups show significant differences only in inner retinal layers thickness. Our data suggest that early visual deprivation may influence retinal arrangements occurring during development involving predominantly the outer nuclear layer and para/perifoveal inner retinal layers, and confirm that early treatment of CC allow to achieve better long-term visual outcome. Moreover functional and structural data support the hypothesis that unilateral amblyopia is not exclusively an unilateral issue.