Advancements in Nanosystems for Ocular Drug Delivery: A Focus on Pediatric Retinoblastoma.

The eye's complex anatomical structures present formidable barriers to effective drug delivery across a range of ocular diseases, from anterior to posterior segment pathologies. Emerging as a promising solution to these challenges, nanotechnology-based platforms-including but not limited to liposomes, dendrimers, and micelles-have shown the potential to revolutionize ophthalmic therapeutics. These nanocarriers enhance drug bioavailability, increase residence time in targeted ocular tissues, and offer precise, localized delivery, minimizing systemic side effects. Focusing on pediatric ophthalmology, particularly on retinoblastoma, this review delves into the recent advancements in functionalized nanosystems for drug delivery. Covering the literature from 2017 to 2023, it comprehensively examines these nanocarriers' potential impact on transforming the treatment landscape for retinoblastoma. The review highlights the critical role of these platforms in overcoming the unique pediatric eye barriers, thus enhancing treatment efficacy. It underscores the necessity for ongoing research to realize the full clinical potential of these innovative drug delivery systems in pediatric ophthalmology.

Towards Precision Ophthalmology: The Role of 3D Printing and Bioprinting in Oculoplastic Surgery, Retinal, Corneal, and Glaucoma Treatment.

In the forefront of ophthalmic innovation, biomimetic 3D printing and bioprinting technologies are redefining patient-specific therapeutic strategies. This critical review systematically evaluates their application spectrum, spanning oculoplastic reconstruction, retinal tissue engineering, corneal transplantation, and targeted glaucoma treatments. It highlights the intricacies of these technologies, including the fundamental principles, advanced materials, and bioinks that facilitate the replication of ocular tissue architecture. The synthesis of primary studies from 2014 to 2023 provides a rigorous analysis of their evolution and current clinical implications. This review is unique in its holistic approach, juxtaposing the scientific underpinnings with clinical realities, thereby delineating the advantages over conventional modalities, and identifying translational barriers. It elucidates persistent knowledge deficits and outlines future research directions. It ultimately accentuates the imperative for multidisciplinary collaboration to enhance the clinical integration of these biotechnologies, culminating in a paradigm shift towards individualized ophthalmic care.

Nonspecific Orbital Inflammation (NSOI): Unraveling the Molecular Pathogenesis, Diagnostic Modalities, and Therapeutic Interventions.

Nonspecific orbital inflammation (NSOI), colloquially known as orbital pseudotumor, sometimes presents a diagnostic and therapeutic challenge in ophthalmology. This review aims to dissect NSOI through a molecular lens, offering a comprehensive overview of its pathogenesis, clinical presentation, diagnostic methods, and management strategies. The article delves into the underpinnings of NSOI, examining immunological and environmental factors alongside intricate molecular mechanisms involving signaling pathways, cytokines, and mediators. Special emphasis is placed on emerging molecular discoveries and approaches, highlighting the significance of understanding molecular mechanisms in NSOI for the development of novel diagnostic and therapeutic tools. Various diagnostic modalities are scrutinized for their utility and limitations. Therapeutic interventions encompass medical treatments with corticosteroids and immunomodulatory agents, all discussed in light of current molecular understanding. More importantly, this review offers a novel molecular perspective on NSOI, dissecting its pathogenesis and management with an emphasis on the latest molecular discoveries. It introduces an integrated approach combining advanced molecular diagnostics with current clinical assessments and explores emerging targeted therapies. By synthesizing these facets, the review aims to inform clinicians and researchers alike, paving the way for molecularly informed, precision-based strategies for managing NSOI.

The Use of Functional Biomaterials in Aesthetic and Functional Restoration in Orbital Surgery.

The integration of functional biomaterials in oculoplastic and orbital surgery is a pivotal area where material science and clinical practice converge. This review, encompassing primary research from 2015 to 2023, delves into the use of biomaterials in two key areas: the reconstruction of orbital floor fractures and the development of implants and prostheses for anophthalmic sockets post-eye removal. The discussion begins with an analysis of orbital floor injuries, including their pathophysiology and treatment modalities. It is noted that titanium mesh remains the gold standard for orbital floor repair due to its effectiveness. The review then examines the array of materials used for orbital implants and prostheses, highlighting the dependence on surgeon preference and experience, as there are currently no definitive guidelines. While recent innovations in biomaterials show promise, the review underscores the need for more clinical data before these new materials can be widely adopted in clinical settings. The review advocates for an interdisciplinary approach in orbital surgery, emphasizing patient-centered care and the potential of biomaterials to significantly enhance patient outcomes.

Polymers and Biomaterials for Posterior Lamella of the Eyelid and the Lacrimal System.

The application of biopolymers in the reconstruction of the posterior lamella of the eyelid and the lacrimal system marks a significant fusion of biomaterial science with clinical advancements. This review assimilates research spanning 2015 to 2023 to provide a detailed examination of the role of biopolymers in reconstructing the posterior lamella of the eyelid and the lacrimal system. It covers the anatomy and pathophysiology of eyelid structures, the challenges of reconstruction, and the nuances of surgical intervention. This article progresses to evaluate the current gold standards, alternative options, and the desirable properties of biopolymers used in these intricate procedures. It underscores the advancements in the field, from decellularized grafts and acellular matrices to innovative natural and synthetic polymers, and explores their applications in lacrimal gland tissue engineering, including the promise of 3D bioprinting technologies. This review highlights the importance of multidisciplinary collaboration between material scientists and clinicians in enhancing surgical outcomes and patient quality of life, emphasizing that such cooperation is pivotal for translating benchtop research into bedside applications. This collaborative effort is vital for restoring aesthetics and functionality for patients afflicted with disfiguring eyelid diseases, ultimately aiming to bridge the gap between innovative materials and their clinical translation.

Diagnosing and Managing Uveitis Associated with Immune Checkpoint Inhibitors: A Review.

This review aims to provide an understanding of the diagnostic and therapeutic challenges of uveitis associated with immune checkpoint inhibitors (ICI). In the wake of these molecules being increasingly employed as a treatment against different cancers, cases of uveitis post-ICI therapy have also been increasingly reported in the literature, warranting an extensive exploration of the clinical presentations, risk factors, and pathophysiological mechanisms of ICI-induced uveitis. This review further provides an understanding of the association between ICIs and uveitis, and assesses the efficacy of current diagnostic tools, underscoring the need for advanced techniques to enable early detection and accurate assessment. Further, it investigates the therapeutic strategies for ICI-related uveitis, weighing the benefits and limitations of existing treatment regimens, and discussing current challenges and emerging therapies in the context of their potential efficacy and side effects. Through an overview of the short-term and long-term outcomes, this article suggests recommendations and emphasizes the importance of multidisciplinary collaboration between ophthalmologists and oncologists. Finally, the review highlights promising avenues for future research and development in the field, potentially informing transformative approaches in the ocular assessment of patients under immunotherapy and the management of uveitis following ICI therapy.

Advances in Sjögren's Syndrome Dry Eye Diagnostics: Biomarkers and Biomolecules beyond Clinical Symptoms.

Sjögren's syndrome dry eye (SSDE) is a subset of Sjögren's syndrome marked by dry eye symptoms that is distinct from non-Sjögren's syndrome dry eye (NSSDE). As SSDE can lead to severe complications, its early detection is imperative. However, the differentiation between SSDE and NSSDE remains challenging due to overlapping clinical manifestations. This review endeavors to give a concise overview of the classification, pathophysiology, clinical features and presentation, ocular and systemic complications, clinical diagnosis, and management of SSDE. Despite advancements, limitations in current diagnostic methods underscore the need for novel diagnostic modalities. Thus, the current review examines various diagnostic biomarkers utilized for SSDE identification, encompassing serum, salivary, and tear analyses. Recent advancements in proteomic research and exosomal biomarkers offer promising diagnostic potential. Through a comprehensive literature review spanning from 2016 to 2023, we highlight molecular insights and advanced diagnostic modalities that have the potential to enhance our understanding and diagnosis of SSDE.

Exploring the Potential of Nanoporous Materials for Advancing Ophthalmic Treatments.

The landscape of ophthalmology is undergoing significant transformations, driven by technological advancements and innovations in materials science. One of the advancements in this evolution is the application of nanoporous materials, endowed with unique physicochemical properties ideal for a variety of ophthalmological applications. Characterized by their high surface area, tunable porosity, and functional versatility, these materials have the potential to improve drug delivery systems and ocular devices. This review, anchored by a comprehensive literature focusing on studies published within the last five years, examines the applications of nanoporous materials in ocular drug delivery systems (DDS), contact lenses, and intraocular lenses. By consolidating the most current research, this review aims to serve as a resource for clinicians, researchers, and material scientists engaged in the rapidly evolving field of ophthalmology.

Advancements in Wearable and Implantable Intraocular Pressure Biosensors for Ophthalmology: A Comprehensive Review.

Glaucoma, marked by its intricate association with intraocular pressure (IOP), stands as a predominant cause of non-reversible vision loss. In this review, the physiological relevance of IOP is detailed, alongside its potential pathological consequences. The review further delves into innovative engineering solutions for IOP monitoring, highlighting the latest advancements in wearable and implantable sensors and their potential in enhancing glaucoma management. These technological innovations are interwoven with clinical practice, underscoring their real-world applications, patient-centered strategies, and the prospects for future development in IOP control. By synthesizing theoretical concepts, technological innovations, and practical clinical insights, this review contributes a cohesive and comprehensive perspective on the IOP biosensor's role in glaucoma, serving as a reference for ophthalmological researchers, clinicians, and professionals.

Suprachoroidal Injection: A Novel Approach for Targeted Drug Delivery.

Treating posterior segment and retinal diseases poses challenges due to the complex structures in the eye that act as robust barriers, limiting medication delivery and bioavailability. This necessitates frequent dosing, typically via eye drops or intravitreal injections, to manage diseases, often leading to side effects with long-term use. Suprachoroidal injection is a novel approach for targeted drug delivery to the posterior segment. The suprachoroidal space is the region between the sclera and the choroid and provides a potential route for minimally invasive medication delivery. Through a more targeted delivery to the posterior segment, this method offers advantages over other routes of administration, such as higher drug concentrations, increased bioavailability, and prolonged duration of action. Additionally, this approach minimizes the risk of corticosteroid-related adverse events such as cataracts and intraocular pressure elevation via compartmentalization. This review focuses on preclinical and clinical studies published between 2019 and 2023, highlighting the potential of suprachoroidal injection in treating a variety of posterior segment diseases. However, to fully harness its potential, more research is needed to address current challenges and limitations, such as the need for technological advancements, refinement of injection techniques, and consideration of cost and accessibility factors. Future studies exploring its use in conjunction with biotech products, gene therapies, and cell-based therapies can lead to personalized treatments that can revolutionize the field of ophthalmology.

A New Era in Ocular Therapeutics: Advanced Drug Delivery Systems for Uveitis and Neuro-Ophthalmologic Conditions.

The eye's intricate anatomical barriers pose significant challenges to the penetration, residence time, and bioavailability of topically applied medications, particularly in managing uveitis and neuro-ophthalmologic conditions. Addressing this issue, polymeric nano-based drug delivery systems (DDS) have surfaced as a promising solution. These systems enhance drug bioavailability in hard-to-reach target tissues, extend residence time within ocular tissues, and utilize biodegradable and nanosized polymers to reduce undesirable side effects. Thus, they have stimulated substantial interest in crafting innovative treatments for uveitis and neuro-ophthalmologic diseases. This review provides a comprehensive exploration of polymeric nano-based DDS used for managing these conditions. We discuss the present therapeutic hurdles posed by these diseases and explore the potential role of various biopolymers in broadening our treatment repertoire. Our study incorporates a detailed literature review of preclinical and clinical studies from 2017 to 2023. Owing to advancements in polymer science, ocular DDS has made rapid strides, showing tremendous potential to revolutionize the treatment of patients with uveitis and neuro-ophthalmologic disorders.

Retinal Prostheses: Engineering and Clinical Perspectives for Vision Restoration.

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.

Overcoming Treatment Challenges in Posterior Segment Diseases with Biodegradable Nano-Based Drug Delivery Systems.

Posterior segment eye diseases present a challenge in treatment due to the complex structures in the eye that serve as robust static and dynamic barriers, limiting the penetration, residence time, and bioavailability of topical and intraocular medications. This hinders effective treatment and requires frequent dosing, such as the regular use of eye drops or visits to the ophthalmologist for intravitreal injections, to manage the disease. Moreover, the drugs must be biodegradable to minimize toxicity and adverse reactions, as well as small enough to not affect the visual axis. The development of biodegradable nano-based drug delivery systems (DDSs) can be the solution to these challenges. First, they can stay in ocular tissues for longer periods of time, reducing the frequency of drug administration. Second, they can pass through ocular barriers, offering higher bioavailability to targeted tissues that are otherwise inaccessible. Third, they can be made up of polymers that are biodegradable and nanosized. Hence, therapeutic innovations in biodegradable nanosized DDS have been widely explored for ophthalmic drug delivery applications. In this review, we will present a concise overview of DDSs utilized in the treatment of ocular diseases. We will then examine the current therapeutic challenges faced in the management of posterior segment diseases and explore how various types of biodegradable nanocarriers can enhance our therapeutic arsenal. A literature review of the pre-clinical and clinical studies published between 2017 and 2023 was conducted. Through the advances in biodegradable materials, combined with a better understanding of ocular pharmacology, the nano-based DDSs have rapidly evolved, showing great promise to overcome challenges currently encountered by clinicians.

Mesenchymal Stem Cell-Derived Exosomes in Ophthalmology: A Comprehensive Review.

Over the past decade, the field of mesenchymal stem cell (MSC) therapy has exhibited rapid growth. Due to their regenerative, reparatory, and immunomodulatory capacities, MSCs have been widely investigated as therapeutic agents in the cell-based treatment of chronic ophthalmic pathologies. However, the applicability of MSC-based therapy is limited by suboptimal biocompatibility, penetration, and delivery to the target ocular tissues. An emerging body of research has elucidated the role of exosomes in the biological functions of MSCs, and that MSC-derived extracellular vesicles (EVs) possess anti-inflammatory, anti-apoptotic, tissue repairing, neuroprotective, and immunomodulatory properties similar to MSCs. The recent advances in MSCs-derived exosomes can serve as solutions to the challenges faced by MSCs-therapy. Due to their nano-dimensions, MSC-derived exosomes can rapidly penetrate biological barriers and reach immune-privileged organs, allowing for efficient delivery of therapeutic factors such as trophic and immunomodulatory agents to ocular tissues that are typically challenging to target by conventional therapy and MSCs transplantation. In addition, the use of EVs minimizes the risks associated with mesenchymal stem cell transplantation. In this literature review, we focus on the studies published between 2017 and 2022, highlighting the characteristics of EVs derived from MSCs and their biological functions in treating anterior and posterior segment ocular diseases. Additionally, we discuss the potential use of EVs in clinical settings. Rapid advancements in regenerative medicine and exosome-based drug delivery, in conjunction with an increased understanding of ocular pathology and pharmacology, hold great promise for the treatment of ocular diseases. The potential of exosome-based therapies is exciting and can revolutionize the way we approach these ocular conditions.

Breaking Barriers in Eye Treatment: Polymeric Nano-Based Drug-Delivery System for Anterior Segment Diseases and Glaucoma.

The eye has anatomical structures that function as robust static and dynamic barriers, limiting the penetration, residence time, and bioavailability of medications administered topically. The development of polymeric nano-based drug-delivery systems (DDS) could be the solution to these challenges: it can pass through ocular barriers, offering higher bioavailability of administered drugs to targeted tissues that are otherwise inaccessible; it can stay in ocular tissues for longer periods of time, requiring fewer drug administrations; and it can be made up of polymers that are biodegradable and nano-sized, minimizing the undesirable effects of the administered molecules. Therefore, therapeutic innovations in polymeric nano-based DDS have been widely explored for ophthalmic drug-delivery applications. In this review, we will give a comprehensive overview of polymeric nano-based drug-delivery systems (DDS) used in the treatment of ocular diseases. We will then examine the current therapeutic challenges of various ocular diseases and analyze how different types of biopolymers can potentially enhance our therapeutic options. A literature review of the preclinical and clinical studies published between 2017 and 2022 was conducted. Thanks to the advances in polymer science, the ocular DDS has rapidly evolved, showing great promise to help clinicians better manage patients.

Retinitis Pigmentosa: Novel Therapeutic Targets and Drug Development.

Retinitis pigmentosa (RP) is a heterogeneous group of hereditary diseases characterized by progressive degeneration of retinal photoreceptors leading to progressive visual decline. It is the most common type of inherited retinal dystrophy and has a high burden on both patients and society. This condition causes gradual loss of vision, with its typical manifestations including nyctalopia, concentric visual field loss, and ultimately bilateral central vision loss. It is one of the leading causes of visual disability and blindness in people under 60 years old and affects over 1.5 million people worldwide. There is currently no curative treatment for people with RP, and only a small group of patients with confirmed RPE65 mutations are eligible to receive the only gene therapy on the market: voretigene neparvovec. The current therapeutic armamentarium is limited to retinoids, vitamin A supplements, protection from sunlight, visual aids, and medical and surgical interventions to treat ophthalmic comorbidities, which only aim to slow down the progression of the disease. Considering such a limited therapeutic landscape, there is an urgent need for developing new and individualized therapeutic modalities targeting retinal degeneration. Although the heterogeneity of gene mutations involved in RP makes its target treatment development difficult, recent fundamental studies showed promising progress in elucidation of the photoreceptor degeneration mechanism. The discovery of novel molecule therapeutics that can selectively target specific receptors or specific pathways will serve as a solid foundation for advanced drug development. This article is a review of recent progress in novel treatment of RP focusing on preclinical stage fundamental research on molecular targets, which will serve as a starting point for advanced drug development. We will review the alterations in the molecular pathways involved in the development of RP, mainly those regarding endoplasmic reticulum (ER) stress and apoptotic pathways, maintenance of the redox balance, and genomic stability. We will then discuss the therapeutic approaches under development, such as gene and cell therapy, as well as the recent literature identifying novel potential drug targets for RP.

An Overview of the Dry Eye Disease in Sjögren's Syndrome Using Our Current Molecular Understanding.

Sjögren's syndrome is a chronic and insidious auto-immune disease characterized by lymphocyte infiltration of exocrine glands. The patients typically present with ocular surface diseases related to dry eye and other systemic manifestations. However, due to the high prevalence of dry eye disease and the lack of objective and clinically reliable diagnostic tools, discriminating Sjögren's syndrome dry eye (SSDE) from non-Sjögren's syndrome dry eye (NSSDE) remains a challenge for clinicians. Diagnosing SS is important to improve the quality of life of patients through timely referral for systemic workups, as SS is associated with serious systemic complications such as lymphoma and other autoimmune diseases. The purpose of this article is to describe the current molecular understanding of Sjögren's syndrome and its implications for novel diagnostic modalities on the horizon. A literature review of the pre-clinical and clinical studies published between 2016 and 2022 was conducted. The SSDE pathophysiology and immunology pathways have become better understood in recent years. Novel diagnostic modalities, such as tear and saliva proteomics as well as exosomal biomarkers, provide hope on the horizon.

Hydrogels in Ophthalmology: Novel Strategies for Overcoming Therapeutic Challenges.

The human eye's intricate anatomical and physiological design necessitates tailored approaches for managing ocular diseases. Recent advancements in ophthalmology underscore the potential of hydrogels as a versatile therapeutic tool, owing to their biocompatibility, adaptability, and customizability. This review offers an exploration of hydrogel applications in ophthalmology over the past five years. Emphasis is placed on their role in optimized drug delivery for the posterior segment and advancements in intraocular lens technology. Hydrogels demonstrate the capacity for targeted, controlled, and sustained drug release in the posterior segment of the eye, potentially minimizing invasive interventions and enhancing patient outcomes. Furthermore, in intraocular lens domains, hydrogels showcase potential in post-operative drug delivery, disease sensing, and improved biocompatibility. However, while their promise is immense, most hydrogel-based studies remain preclinical, necessitating rigorous clinical evaluations. Patient-specific factors, potential complications, and the current nascent stage of research should inform their clinical application. In essence, the incorporation of hydrogels into ocular therapeutics represents a seminal convergence of material science and medicine, heralding advancements in patient-centric care within ophthalmology.

Management of Sjogren's Dry Eye Disease-Advances in Ocular Drug Delivery Offering a New Hope.

Sjögren's syndrome is a chronic and insidious autoimmune disease characterized by lymphocyte infiltration of exocrine glands. Patients typically present with dry eye, dry mouth, and other systemic manifestations. Currently, the available molecules and drug-delivery systems for the treatment of Sjögren's syndrome dry eye (SSDE) have limited efficacy since they are not specific to SSDE but to dry eye disease (DED) in general. The current treatment modalities are based on a trial-and-error approach using primarily topical agents. However, this approach gives time for the vicious cycle of DED to develop which eventually causes permanent damage to the lacrimal functional unit. Thus, there is a need for more individualized, specific, and effective treatment modalities for SSDE. The purpose of this article is to describe the current conventional SSDE treatment modalities and to expose new advances in ocular drug delivery for treating SSDE. A literature review of the pre-clinical and clinical studies published between 2016 and 2022 was conducted. Our current understanding of SSDE pathophysiology combined with advances in ocular drug delivery and novel therapeutics will allow the translation of innovative molecular therapeutics from the bench to the bedside.