Acta Ophthalmologica最新文献

Aims/Purpose: To investigate the anti-inflammatory effects of citicoline and coenzyme Q10 (COQUN Combo) in an experimental model of ocular hypertension (OHT).

Methods: Swiss albino mice were used: vehicle control (Vehicle n = 6), COQUN Combo control (COQUN Combo n = 5), laser vehicle (LG+Veh, n = 6), and laser COQUN Combo (LG+COQUN Combo, n = 6). COQUN Combo was administered daily with gelatin 15 days prior to laser induction and 3 days post-induction in COQUN Combo and LG+COQUN Combo groups. The Vehicle and LG+Veh groups received neutral gelatin. OHT was induced in the left eye by laser photocoagulation of the limbal and episcleral veins, analyzing hypertensive eyes and their contralateral eyes. Retinal whole-mounts were processed with: 1) Anti Iba-1 to quantify: Number of Iba-1+ cells (Iba1-cn) in outer segments (OS), outer plexiform layer (OPL) and inner plexiform layer (IPL); Retinal area occupied by Iba-1+ cells (Iba1-RA) in the nerve fiber layer-ganglion cell layer (NFL-GCL); Cell body area (Iba1-cba) of Iba-1+ cells in OPL, IPL and NFL-GCL; and arbor area (Iba1-aa) of Iba-1+ cells in OPL and IPL. 2) Anti-P2RY12 to differentiate activated microglia.

Results: No significant differences were observed between the control groups. Both OHT eyes and their contralaterals of LG+Veh, as well as LG+COQUN Combo OHT eyes and their contralaterals, showed significant differences compared to controls in Iba1-cn, Iba1- RA, Iba1-cba, and Iba1-aa in all layers analyzed. However, these changes were significantly smaller in LG+COQUN Combo OHT and their contralateral eyes compared to LG+Veh OHT and their contralateral eyes. In the Vehicle, Iba-1+ cells were P2RY12+. P2RY12 expression was downregulated in both OHT eyes of LG+Veh and LG+ COQUN Combo; however, this downregulation was less pronounced in the OHT eyes of LG+COQUN Combo. In the contralateral eyes, P2RY12 expression remained similar to that of the controls

Conclusions: COQUN Combo can attenuate the inflammatory process in glaucoma.

Adaptive Optics (AO) refers to a technique to compensate for distortions caused by optical aberrations in the media between the camera and the object being imaged. It was originally developed for use in astronomical telescopes to compensate for optical distortions induced by the inhomogeneous earth atmosphere. It has since evolved to become a powerful clinical tool in ophthalmology. In the eye, a “wavefront sensor” (aberrometer) measures the distortion of incoming light induced by inhomogeneities within the cornea and crystalline lens, which is then “undistorted” via reflection by a deformable mirror. AO thus enables imaging of the human retina with unprecedented resolution in vivo, such as revealing individual photoreceptors or the walls of blood vessels. One should note that AO by itself does not provide an image; rather an AO subsystem is incorporated into an existing imaging device. AO subsystems have thus far been successfully integrated into three ophthalmic imaging devices: fundus cameras, scanning laser ophthalmoscopes, and the OCT device. This lecture will introduce the basic principles of AO, illustrate its value with state-of-the-art clinical examples, and discuss potential future applications in ophthalmology.

Aims/Purpose: A new foldable brown-diaphragm intraocular lens (IOL) was preclinically evaluated in vitro and in vivo by comparing its biocompatibility and biosafety with those of a commercially available IOL.

Methods: The new brown-diaphragm IOL is made of hydrophobic acrylic material, with incorporating a transparent optical zone and surrounding brown diaphragm. Cellular experiments evaluating lens epithelial cell morphology, adhesion, and migration were conducted to exclude cytotoxic effects. Twelve New Zealand rabbits had the new brown-diaphragm IOL implanted in one eye and another 12 had a commercially available foldable IOL implanted, followed by slit-lamp evaluations, corneal endothelial cells density measurement and aqueous humor analysis to identify any dye leakage from the brown-diaphragm IOL. Haematoxylin and eosin staining of ocular tissue and scanning electron microscopy (SEM) of the IOL surface were performed after 12-week observation.

Results: In vivo experiments showed there were no statistically significant differences between the two groups in terms of postoperative inflammation and capsular biocompatibility. There were no significant changes in corneal endothelial cell density between before and after surgery in either group. LC-MS/MS analysis showed that the target dye was not detected in aqueous humor samples. Histopathology of ocular sections and SEM imaging of IOL surfaces showed similar changes in both groups.

Conclusions: The newly-invented brown-diaphragm IOL showed good biocompatibility and biosafety. Combined with its foldability and peripheral shading, it could be a new choice for patients with iris defects.

Aims/Purpose: Corneal perforation is a medical emergency that can lead to blindness. Treatment options encompass cyanoacrylate or fibrin glue, both linked to side effects, including cytotoxicity. Gelatin methacryloyl-based biomaterials offer an alternative to these adhesives [1, 2]. Achieving optical clarity and smooth surface integrity is crucial for the restoration of vision in treated corneal wounds.

Methods: Currently, the delivery of corneal biomaterials utilizes standard syringe systems, which lack the accuracy to reconstruct the cornea's shape. Therefore, the use of a laser bioprinting technology, developed in the Boutopoulos lab [3], for achieving precise in-situ corneal wound repair was examined. We used a photocrosslinkable ink comprising Gelatin Methacryloyl (GelMa), hydroxyethyl acrylate (HEA), and Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) as a photoinitiator.

Results: Printability was optimized by generating nanoliter-volume individual droplets using 230 μJ laser energy, a flow rate 20 microliter per minute, and a temperature of 37°C. Rheology, optical characterization, and bursting pressure measurements assessed its potential to seal corneal perforations. Results indicated a hydrogel storage modulus of 1.31 ± 0.31 KPa for printed LiQD cornea and a bursting pressure of 38 ± 6 mmHg when used to seal full thickness cornea perforation in cadaveric pig eyes. Optical clarity akin to the native cornea was observed (%light transmission: 93.12 ± 1.02 printed vs 92.61 ± 1.50). The OCT results showed that the LIST technique could potentially fill the corneal wounds and reconstruct the natural curvature of the wounded cornea.

Conclusions: In conclusion, a precise printing system for delivering adhesive corneal regenerative biomaterials to wounds was developed and characterized.

References

1. Sharifi, S., et al., 2021. 6(11): p. 3947-3961.

2. Barroso, I.A., et al., 2022. 9(2).

3. Ebrahimi Orimi, H., et al., Sci Rep, 2020. 10(1): p. 9730.

Aims/Purpose: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. To date, there are no effective therapies to counteract the AMD towards the most severe stages characterized by a progressive loss of photoreceptors triggered by retinal pigmented epithelium dysfunction. Given their easily source and their high proliferative potential, Dental Pulp Stem Cells (DPSCs) showed promise for regenerative medicine. The main advantage of DPSCs is related to their immunosuppressive and immunoregulatory abilities, including the capability to promote regeneration of damaged tissues. It is well known the therapeutic potential of DPSCs secretome (conditioned media, CM), including trophic factors and cytokines, as a treatment of neurogenerative diseases. We evaluated the capability of DPSCs-CM cultured in hypoxia and normoxic conditions to counteract retinal degeneration in an animal model of AMD.

Methods: DPSCs-CM were intravitreally injected the day before the exposure of albino rats to high intensity light (LD). We evaluated the retinal function, and we performed morphological and molecular analysis a week after the LD, in accordance with the well-established protocol of our light damage model.

Results: DPSCs-CM obtained from hypoxia or normoxia, were able to preserve the retinal function, to reduce microglial activation and their migration toward outer nuclear layer (ONL). Furthermore, we demonstrated that the treatment with normoxic DPSCs-CM limited the hot spot extension and preserved the ONL thickness better than the hypoxic DPSCs-CM. The different concentrations of growth factors and cytokines detected in both CM played a key role in the understanding of the greatest protective effect of the normoxic-CM compared to hypoxic-CM.

Conclusions: Taken together, our study demonstrated that normoxic DPSCs-CM represents an eligible candidate to counteract retinal degeneration and, therefore, a promising therapeutic agent for AMD.

Aims/Purpose: The aim of this study was to evaluate the longitudinal effect on axial eye length in myopic children and adolescents treated with orthokeratology (OK) lenses compared to spectacles (GL), through a systematic review and meta-analysis

Methods: We conducted a systematic search of PubMed and Google Scholar databases for randomized controlled trials and cohort studies investigated the effects of longitudinal axial length difference, using the keyword “Axial Length” AND “orthokeratology” AND “spectacles”. From the initial 91 studies, we excluded 13 review studies, 10 meta-analysis studies, 7 systematic reviews and 37 studies that did not meet the inclusion criteria. Of the 24 selected studies, detailed information was available at 24, 18, 12, 6, 3 and 1 month, with 10, 8, 19, 17, 2 and 3 studies respectively, allowing for the comparison between 2172 eyes treated with orthokeratology and 2095 eyes with glasses.

Results: The analysis of the 24 studies (which included 59 comparisons from 1 month to 24 months) showed no statistically significant differences in initial axial length [AL(GL) = 24.39 ± 0.34 mm; AL(OK) = 24.44 ± 0.38 mm] and initial refractive error [M(GL) = -2.59 ± 0.70 D; M(OK) = -2.53 ± 0.44 D] between the two treatment groups (p > 0.565, independent samples t-test) and for the evolution time intervals (p > 0.591, ANOVA). This analysis encompassed 4267 eyes with a mean age of 10.23 ± 1.21 years. Forest plot provided in an overall effect size of myopic defocus AL = -0.16 com IC 95% -0.19 a -0.14, Z = 12.71 p < 0.001. A random effects model was used considering the heterogeneity observed (I² = 97%; p < 0.001, df = 58). There was a greater myopia control effect at 24 months (AL = -0.26, 95% IC -0.29 to -0.22, Z = 13.71 p < 0.001; I² = 0%; p = 0.95) than to treatments of less than 3 months (AL = -0.04, 95% IC -0.06 to -0.01, Z = 2.60 p = < 0.009; I² = 86%; p < 0.001).

Conclusions: While the treatment at 24 months shows an homogeneous behaviour among studies, shorter follow-up times renders a larger heterogeneity and for that reason, longer follow-up periods should be preferred to estimate a more solid effect size. Orthokeratology treatment has been shown to be effective in myopia control progression for short or longer longitudinal treatments in children and young people with spectacles comparison.

Aims/Purpose: The aim of the study is to create a microbead induced ocular hypertension (OHT) model in rabbits, and to evaluate the effects of intravitreal and intraperitoneal injections of Adalimumab (ADA) on the number of retinal ganglion cells (RGC), retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness.

Methods: 15 rabbits of mixed strain (9–12 months old, 3.5-4kg) were randomized into 4 groups. OHT was induced with microbead injection into the anterior chamber of right eyes. On 7th, 14th days of OHT, ADA was injected at one of two concentrations (2.5mg group 1: G1/5mg group 2:G2) into right eyes of two groups, intraperitoneally 5mg/kg into the third group (G3), and balanced salt solution into fourth group (sham). The left eyes were used as controls. At 40^th day, the rabbits were euthanized. Retinal and optic nerve head (ONH) histology was studied with hematoxylin-eosin and toluidine blue staining.

Results: OHT was induced with microbeads in 13 eyes. 2 rabbits were excluded (endophthalmitis, total hyphema). The average pre-OHT IOP from all eyes 9.7±09mmHg (8-11). Statistically significant IOP increase was observed in all subject eyes on day 7 (14±1.4 (12-18)) (p = 0.01) and maintained until ADA injection (day 21). RGCs in the eyes with elevated IOP were 7.2±1.2 and 7.6±1.5, 6.3+1.1 cells in ADA treated groups, G1, G2, G3, respectively. There was no statistically significant difference between treatment groups. The average RNFL was 125.9±10.9 μm in control, 60.2±9.4 μm in G1, 45.7±2.9 μm in G2, 22.8±2.9 μm in G3, 21.7±10 μm in sham. Significant elevation was observed in G1 compared to all treatment groups. (p = 0.01). The average GCC of control was 45.5±1.9 μm, G1 41.2±2.2 μm, G2 39.3±3.3 μm, G3 34.1±1.6 μm, sham was 38.3±1.1 μm. Significant increase was observed in G1 compared to G3. (p = 0.01).

Conclusions: OHT triggers inflammatory response in which TNF-α expression is increased around the ONH. Blocking TNF-α might prevent axonal degeneration and RGC loss by inhibiting this response. These findings may further contribute to the literature for a new treatment strategy for glaucoma using TNF-α antagonists or inflammation suppressors.

The International Consensus Statement on the Clinical and Therapeutic Management of Leber Hereditary Optic Neuropathy was published in 2017 based on data available in 2016. The intent was to provide expert consensus statements for the clinical and therapeutic management of LHON based on the currently available evidence. It provided the guidelines for clinical and therapeutic management of LHON. It established a number of benchmarks such as clinical staging of LHION into Asymptomatic (mutation carriers), Subacute (<6 months from onset), Dynamic (6–12 months) and Chronic (>12 months) stages. We can all agree on the criteria for the diagnosis of LHON, based on a careful history, evaluation of key structural and functional visual parameters, and on a molecular confirmation of a pathogenic mtDNA mutation. On management it is clearly highly important to include genetic counselling and informing the patient about potentially preventable lifestyle risk factors. The use of idebenone is more debated and much has changed. Further studies and case series have been published and issues around when to start, how long to treat for and whether to treat chronic patients have all emerged. In this debate we shall raise a number of these issues and provide a reflection of the available data, their validity and clinical relevance and debate next steps.