Search Results (41)

Background/Objectives: Neovascular age-related macular degeneration (nAMD) poses a serious threat to the eyesight of older adults, representing a leading cause of irreversible vision loss. Anti-vascular endothelial growth factor (anti-VEGF) treatments are effective but require repeated intraocular injections and show poor responses in some patients. CGK012 is a novel derivative of decursin that inhibits the Wnt/β-catenin pathway. This study aimed to elucidate the mode of action of CGK012 and examine its therapeutic effects. Methods: We performed in vitro cellular studies in a retinal pigment epithelial (RPE) cell line (ARPE-19) and human umbilical vein endothelial cells (HUVECs). We examined the in vivo efficacy of CGK012-loaded implants in laser-induced choroidal neovascularization (CNV) rabbit models. We also determined the implants’ in vitro dissolution, intraocular release, and disposition characteristics. Results: CGK012 decreased angiogenic/proinflammatory factor expression and suppressed the epithelial–mesenchymal transition (EMT) in RPE cells by promoting intracellular β-catenin degradation. Additionally, it repressed the expression of cyclin D1 and c-myc, downstream target genes of β-catenin, and inhibited HUVEC capillary tube formation. CGK012-loaded poly (lactic-co-glycolic acid) (PLGA) intravitreal implants significantly reduced vascular leakage in a laser-induced CNV rabbit model. Notably, CGK012 released from the implant was highly permeable to retina/choroid tissue and downregulated β-catenin, angiogenic/inflammatory factors, and vimentin in the rabbit model. The CGK012 concentration reached a plateau at 28–42 days in the vitreous humor and decayed with a half-life of 14 days without systemic exposure. Conclusions: Our findings demonstrate that CGK012 implants prevent choroidal neovascularization through the Wnt/β-catenin pathway suppression and produce high concentrations of CGK012 in the posterior eye segment with prolonged release. Thus, these implants provide more therapeutic choices for nAMD treatment. Full article

Until now, the ultimate solution for blind people has not been achieved, because challenges still exist. Retinal implants have emerged as a promising solution for restoring vision in individuals suffering from retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration. Central to the efficacy of these implants is the design and functionality of the electrode arrays responsible for stimulating retinal neurons. This review evaluates the evolution of retinal implants, with particular emphasis on electrode specifications, physiological considerations for electrical stimulation, and recent advancements in electrode design. A comprehensive analysis of state-of-the-art published studies provides a detailed cross-comparison of electrode characteristics, offering insights into current state-of-the-art technologies and future directions. Full article

Age-related macular degeneration (AMD), a progressive neurodegenerative disorder affecting the central retina, is pathologically defined by the irreversible degeneration of photoreceptors and retinal pigment epithelium (RPE), coupled with extracellular drusen deposition and choroidal neovascularization (CNV), and AMD constitutes the predominant etiological factor for irreversible vision impairment in adults aged ≥60 years. Cell-based or cell-biomaterial scaffold-based approaches have been popular in recent years as a major research direction for AMD; monotherapy with cell-based approaches typically involves subretinal injection of progenitor-derived or stem cell-derived RPE cells to restore retinal homeostasis. Meanwhile, cell-biomaterial scaffolds delivered to the lesion site by vector transplantation have been widely developed, and the implanted cell-biomaterial scaffolds can promote the reintegration of cells at the lesion site and solve the problems of translocation and discrete cellular structure produced by cell injection. While these therapeutic strategies demonstrate preliminary efficacy, rigorous preclinical validation and clinical trials remain imperative to validate their long-term safety, functional durability, and therapeutic consistency. This review synthesizes current advancements and translational challenges in cell-based and cell-biomaterial scaffold approaches for AMD, aiming to inform future development of targeted interventions for AMD pathogenesis and management. Full article

Background: Neuroprosthetics for vision restoration have advanced significantly, incorporating technologies like retinal implants, cortical implants, and non-invasive stimulation methods. These advancements hold the potential to tackle major challenges in visual prosthetics, such as enhancing functionality, improving biocompatibility, and enabling real-time object recognition. Aim: The aim of this review overview is to provide a comprehensive analysis of the latest advancements in ocular neuroprostheses. Methods: A narrative review was conducted, focusing on the latest developments in visual neuroprosthetics. Comprehensive searches were carried out on Google Scholar, PubMed, and Scopus using specific keywords. A specific narrative checklist was applied, alongside a tailored quality assessment methodology, to evaluate the quality of the studies included. A total of sixteen relevant studies from the past three years were included in the review. Results and discussion: The integration of artificial retinas, cortical implants, high technology-enabled prosthetics, gene therapies, nanotechnology, and bioprinting has shown significant promise in enhancing the quality and functionality of vision restoration systems, offering potential to address complex visual impairments and improve independence and mobility for individuals with blindness. These innovations appear to have the potential to transform healthcare systems in the future by enabling more efficient and personalized therapies and prosthetic devices. However, challenges such as energy efficiency, scalability, and the neural dynamics of vision restoration persist, requiring continued interdisciplinary collaboration to refine these technologies, overcome ethical and regulatory hurdles, and ensure their effectiveness in real-world applications. Conclusions: While visual neuroprosthetics have made remarkable progress, addressing challenges related to energy consumption and regulatory and ethical concerns will be crucial for ensuring that neuroprosthetic devices can effectively meet the needs of individuals with visual impairments. Full article

Retinal prosthetic devices aim to repair some vision in visually impaired patients by electrically stimulating neural cells in the visual system. Although there have been several notable advancements in the creation of electrically stimulated small dot-like perceptions, a deeper comprehension of the physical properties of phosphenes is still necessary. This study analyzes the influence of two independent electrode array topologies to achieve single-localized stimulation while the retina is electrically stimulated: a two-dimensional (2D) hexagon-shaped array reported in clinical studies and a patented three-dimensional (3D) linear electrode carrier. For both, cell stimulation is verified in COMSOL Multiphysics by developing a lifelike 3D computational model that includes the relevant retinal interface elements and dynamics of the voltage-gated ionic channels. The evoked percepts previously described in clinical studies using the 2D array are strongly associated with our simulation-based findings, allowing for the development of analytical models of the evoked percepts. Moreover, our findings identify differences between visual sensations induced by the arrays. The 2D array showed drawbacks during stimulation; similarly, the state-of-the-art 2D visual prostheses provide only dot-like visual sensations in close proximity to the electrode. The 3D design could offer a technique for improving cell selectivity because it requires low-intensity threshold activation which results in volumes of stimulation similar to the volume surrounded by a solitary RGC. Our research establishes a proof-of-concept technique for determining the utility of the 3D electrode array for selectively activating individual RGCs at the highest density via small-sized electrodes while maintaining electrochemical safety. Full article

The management of vision-threatening retinal diseases remains challenging due to the lack of an effective drug delivery system. Encapsulated cell therapy (ECT) offers a promising approach for the continuous delivery of therapeutic agents without the need for immunosuppressants. In this context, an injectable and terminable collagen–alginate composite (CAC) ECT gel, designed with a Tet-on pro-caspase-8 system, was developed as a safe intraocular drug delivery platform for the sustained release of glial-cell-line-derived neurotrophic factor (GDNF) to treat retinal degenerative diseases. This study examined the potential clinical application of the CAC ECT gel, focusing on its safety, performance, and termination through doxycycline (Dox) administration in the eyes of healthy New Zealand White rabbits, as well as its therapeutic efficacy in rabbits with sodium-iodate (SI)-induced retinal degeneration. The findings indicated that the CAC ECT gel can be safely implanted without harming the retina or lens, displaying resistance to degradation, facilitating cell attachment, and secreting bioactive GDNF. Furthermore, the GDNF levels could be modulated by the number of implants. Moreover, Dox administration was effective in terminating gel function without causing retinal damage. Notably, rabbits with retinal degeneration treated with the gels exhibited significant functional recovery in both a-wave and b-wave amplitudes and showed remarkable efficacy in reducing photoreceptor apoptosis. Given its biocompatibility, mechanical stability, controlled drug release, terminability, and therapeutic effectiveness, our CAC ECT gel presents a promising therapeutic strategy for various retinal diseases in a clinical setting, eliminating the need for immunosuppressants. Full article

Tissue engineering is considered a promising approach to treating advanced degenerative maculopathies such as nonexudative age-related macular degeneration (AMD), the leading cause of blindness worldwide. The retina consists of several hierarchical tissue layers, each of which is supported by a layer underneath. Each of these layers has a different morphology and requires distinct conditions for proper assembly. In fact, a prerequisite step for the assembly of each of these layers is the organization of the layer underneath. Advanced retinal degeneration includes degeneration of the other retina layers, including the choroid, the retinal pigmented epithelium (RPE), and the photoreceptors. Here, we report a step-by-step fabrication process of a three-layer retina-like structure. The process included the 3D printing of a choroid-like structure in an extracellular matrix (ECM) hydrogel, followed by deposition of the RPE monolayer. After the formation of the blood vessel–RPE interface, the photoreceptor cells were deposited to interact with the RPE layer. At the end of the fabrication process, each layer was characterized for its morphology and expression of specific markers, and the integration of the three-layer retina was evaluated. We envision that such a retina-like structure may be able to attenuate the deterioration of a degenerated retina and improve engraftment and regeneration. This retinal implant may potentially be suitable for a spectrum of macular degenerative diseases for which there are currently no cures and may save millions from complete blindness. Full article

(1) Background: We reviewed a stem cell-derived therapeutic strategy for advanced neovascular age-related macular degeneration (nAMD) using a human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) monolayer delivered on a coated, synthetic basement membrane (BM)—the patch—and assessed the presence and distribution of hESC-RPE over 5 years following transplantation, as well as functional outcomes. (2) Methods: Two subjects with acute vision loss due to sub-macular haemorrhage in advanced nAMD received the hESC-RPE patch. Systematic immunosuppression was used peri-operatively followed by local depot immunosuppression. The subjects were monitored for five years with observation of RPE patch pigmentation, extension beyond the patch boundary into surrounding retina, thickness of hESC-RPE and synthetic BM and review for migration and proliferation of hESC-RPE. Visual function was also assessed. (3) Results: The two study participants showed clear RPE characteristics of the patch, preservation of some retinal ultrastructure with signs of remodelling, fibrosis and thinning on optical coherence tomography over the 5-year period. For both participants, there was evidence of pigment extension beyond the patch continuing until 12 months post-operatively, which stabilised and was preserved until 5 years post-operatively. Measurement of hESC-RPE and BM thickness over time for both cases were consistent with predefined histological measurements of these two layers. There was no evidence of distant RPE migration or proliferation in either case beyond the monolayer. Sustained visual acuity improvement was apparent for 2 years in both subjects, with one subject maintaining the improvement for 5 years. Both subjects demonstrated initial improvement in fixation and microperimetry compared to baseline, at year 1, although only one maintained this at 4 years post-intervention. (4) Conclusions: hESC-RPE patches show evidence of continued pigmentation, with extension, to cover bare host basement membrane for up to 5 years post-implantation. There is evidence that this represents functional RPE on the patch and at the patch border where host RPE is absent. The measurements for thickness of hESC-RPE and BM suggest persistence of both layers at 5 years. No safety concerns were raised for the hypothetical risk of RPE migration, proliferation or tumour formation. Visual function also showed sustained improvement for 2 years in one subject and 5 years in the other subject. Full article

Artificial retinas have revolutionized the lives of many blind people by enabling their ability to perceive vision via an implanted chip. Despite significant advancements, there are some limitations that cannot be ignored. Presenting all objects captured in a scene makes their identification difficult. Addressing this limitation is necessary because the artificial retina can utilize a very limited number of pixels to represent vision information. This problem in a multi-object scenario can be mitigated by enhancing images such that only the major objects are considered to be shown in vision. Although simple techniques like edge detection are used, they fall short in representing identifiable objects in complex scenarios, suggesting the idea of integrating primary object edges. To support this idea, the proposed classification model aims at identifying the primary objects based on a suggested set of selective features. The proposed classification model can then be equipped into the artificial retina system for filtering multiple primary objects to enhance vision. The suitability of handling multi-objects enables the system to cope with real-world complex scenarios. The proposed classification model is based on a multi-label deep neural network, specifically designed to leverage from the selective feature set. Initially, the enhanced images proposed in this research are compared with the ones that utilize an edge detection technique for single, dual, and multi-object images. These enhancements are also verified through an intensity profile analysis. Subsequently, the proposed classification model’s performance is evaluated to show the significance of utilizing the suggested features. This includes evaluating the model’s ability to correctly classify the top five, four, three, two, and one object(s), with respective accuracies of up to 84.8%, 85.2%, 86.8%, 91.8%, and 96.4%. Several comparisons such as training/validation loss and accuracies, precision, recall, specificity, and area under a curve indicate reliable results. Based on the overall evaluation of this study, it is concluded that using the suggested set of selective features not only improves the classification model’s performance, but aligns with the specific problem to address the challenge of correctly identifying objects in multi-object scenarios. Therefore, the proposed classification model designed on the basis of selective features is considered to be a very useful tool in supporting the idea of optimizing image enhancement. Full article

Neurons build vast gap junction-coupled networks (GJ-nets) that are permeable to ions or small molecules, enabling lateral signaling. Herein, we investigate (1) the effect of blinding diseases on GJ-nets in mouse retinas and (2) the impact of electrical stimulation on GJ permeability. GJ permeability was traced in the acute retinal explants of blind retinal degeneration 1 (rd1) mice using the GJ tracer neurobiotin. The tracer was introduced via the edge cut method into the GJ-net, and its spread was visualized in histological preparations (fluorescent tagged) using microscopy. Sustained stimulation was applied to modulate GJ permeability using a single large electrode. Our findings are: (1) The blind rd1 retinas displayed extensive intercellular coupling via open GJs. Three GJ-nets were identified: horizontal, amacrine, and ganglion cell networks. (2) Sustained stimulation significantly diminished the tracer spread through the GJs in all the cell layers, as occurs with pharmaceutical inhibition with carbenoxolone. We concluded that the GJ-nets of rd1 retinas remain coupled and functional after blinding disease and that their permeability is regulatable by sustained stimulation. These findings are essential for understanding molecular signaling in diseases over coupled networks and therapeutic approaches using electrical implants, such as eliciting visual sensations or suppressing cortical seizures. Full article

Three-dimensional (3D) printing is a process in which materials are added together in a layer-by-layer manner to construct customized products. Many different techniques of 3D printing exist, which vary in materials used, cost, advantages, and drawbacks. Medicine is increasingly benefiting from this transformative technology, and the field of ophthalmology is no exception. The possible 3D printing applications in eyecare are vast and have been explored in the literature, such as 3D-printed ocular prosthetics, orbital implants, educational and anatomical models, as well as surgical planning and training. Novel drug-delivery platforms have also emerged because of 3D printing, offering improved treatment modalities for several ocular pathologies. Innovative research in 3D bioprinting of viable tissues, including the cornea, retina, and conjunctiva, is presenting an avenue for regenerative ophthalmic therapies in the future. Although further development in printing capabilities and suitable materials is required, 3D printing represents a powerful tool for enhancing eye health. Full article

Diabetic macular edema (DME)’s therapeutic approach can frequently be challenging. The purpose of the review is to propose evidence-based recommendations on the employment of intravitreal dexamethasone implants (DEX) when approaching patients suffering from DME. Seven national consensuses redacted by different groups of retina specialists from Europe and Asia were examined and confronted. Each consensus was redacted utilizing a Delphi approach, in person meetings, or by reviewing the literature. DEX can be studied as a first-line strategy in individuals suffering from DME with inflammatory OCT biomarkers, in vitrectomized eyes, in patients with recent cardiovascular events, in pregnant women, in patients scheduled to undergo cataract surgery or with poor compliance. The other parameters considered were the indications to the DME treatment, when to switch to DEX, the definition of non-responder to anti-VEGFs agents and to the DEX implant, whether to combine DEX with laser photocoagulation, the association between glaucoma and DEX, and the management of DEX and the cataract. Although several years have passed since the introduction of DEX implants in the DME treatment, there is still not a unified agreement among retina specialists. This paper compares the approach in the DME treatment between countries from different continents and provides a broader and worldwide perspective of the topic. Full article

This prospective study aimed to evaluate the impact of Visian Implantable Collamer Lens (ICL) V4c implantation on retinal and choroidal morphology in patients with high myopia. A total of 97 eyes from 52 high myopic patients who underwent ICL V4c implantation were followed up for 12 months. Preoperative and postoperative evaluations included comprehensive ophthalmic assessments and enhanced depth imaging optical coherence tomography (EDI-OCT) to analyze changes in central retinal thickness (CRT), retinal volume (CRV), choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), and choroidal vascular index (CVI). Repeated measures mixed-effects models were used for comparing pre- and postoperative measurement variables and exploring relationships among age, axial length (AL), spherical equivalent refraction (SER), and postoperative retinal and choroidal changes, with statistical significance set at p < 0.05. Follow-up assessments were conducted at various time points, with participation rates ranging from 21% to 98%. Baseline characteristics showed a median age of 26.7 years, −10.14 diopters of SER, and an AL of 27.44 mm. Throughout the 12-month follow-up, CRT and 3.0 mm CRV consistently increased compared to the baseline, with statistically significant rises observed at postoperative day 1, week 1, and month 12. Most ChT measurements, including subfoveal ChT, declined over the 12 months, except at postoperative 6 months. Horizontal and vertical TCA and LA values significantly increased throughout the follow-up, except for month 6. After surgery, both horizontal and vertical CVI parameters exhibited an increase compared to the baseline, with some changes reaching statistical significance. Correlation analysis performed by repeated measures mixed-effects models showed that no relationship was found between age, AL, and SER and changes in postoperative retinal parameters and CVI parameters. However, postoperative changes in ChT and choroidal area parameters showed a negative correlation with AL and a positive correlation with SER. Our research demonstrated that ICL V4c implantation resulted in noteworthy alterations in retinal and choroidal morphology over a 1-year follow-up period. Moreover, in patients with high myopia, individuals with longer AL and higher degrees of myopia exhibited more pronounced postoperative changes in the choroid and retina. Further studies with extended follow-up durations are necessary to comprehensively understand the long-term effects of ICL implantation on retinal and choroidal morphology and function. Full article

A retinal prosthesis, also known as a bionic eye, is a device that can be implanted to partially restore vision in patients with retinal diseases that have resulted in the loss of photoreceptors (e.g., age-related macular degeneration and retinitis pigmentosa). Recently, there have been major breakthroughs in retinal prosthesis technology, with the creation of numerous types of implants, including epiretinal, subretinal, and suprachoroidal sensors. These devices can stimulate the remaining cells in the retina with electric signals to create a visual sensation. A literature review of the pre-clinical and clinical studies published between 2017 and 2023 is conducted. This narrative review delves into the retinal anatomy, physiology, pathology, and principles underlying electronic retinal prostheses. Engineering aspects are explored, including electrode–retina alignment, electrode size and material, charge density, resolution limits, spatial selectivity, and bidirectional closed-loop systems. This article also discusses clinical aspects, focusing on safety, adverse events, visual function, outcomes, and the importance of rehabilitation programs. Moreover, there is ongoing debate over whether implantable retinal devices still offer a promising approach for the treatment of retinal diseases, considering the recent emergence of cell-based and gene-based therapies as well as optogenetics. This review compares retinal prostheses with these alternative therapies, providing a balanced perspective on their advantages and limitations. The recent advancements in retinal prosthesis technology are also outlined, emphasizing progress in engineering and the outlook of retinal prostheses. While acknowledging the challenges and complexities of the technology, this article highlights the significant potential of retinal prostheses for vision restoration in individuals with retinal diseases and calls for continued research and development to refine and enhance their performance, ultimately improving patient outcomes and quality of life. Full article

Age-related macular degeneration (AMD) causes severe vision impairments, including blindness. An option to improve vision in AMD patients is through intraocular lenses and optics. Among others, implantable miniaturized telescopes, which direct light to healthy lateral regions of the retina, can be highly effective in improving vision in AMD patients. Yet, the quality of the restored vision might be sensitive to the optical transmission and aberrations of the telescope. To shed light on these points, we studied the in vitro optical performance of an implantable miniaturized telescope, namely, the SING IMT™ (Samsara Vision Ltd., Far Hills, NJ, USA) designed to improve vision in patients affected by late-stage AMD. Specifically, we measured the optical transmission in the spectral range 350–750 nm of the implantable telescope with a fiber-optic spectrometer. Wavefront aberrations were studied by measuring the wavefront of a laser beam after passing through the telescope and expanding the measured wavefront into a Zernike polynomial basis. Wavefront concavity indicated that the SING IMT™ behaves as a diverging lens with a focal length of −111 mm. The device exhibited even optical transmission in the whole visible spectrum and effective curvature suitable for retinal images magnification with negligible geometrical aberrations. Optical spectrometry and in vitro wavefront analysis provide evidence supporting the feasibility of miniaturized telescopes as high-quality optical elements and a favorable option for AMD visual impairment treatments. Full article