Treatment Of Eye Diseases Research Articles

Seeing in the Future - a Perspective on Combining Light with Chemical Biology Approaches to Treat Retinal Pathologies.

New concepts to treat eye diseases have emerged that elegantly combine unnatural light exposure with chemical biology approaches to achieve superior cellular specificity and, as a result, improvement of visual function. Historically, light exposure without further molecular eye treatment has offered limited success including photocoagulation to halt pathological blood vessel growth or low light exposure to stimulate retinal cell viability. To add cellular specificity to such treatments, researchers have introduced various biological or chemical light-sensing molecules and combined those with light exposure. (Pre-)clinical trials describe the use of optogenetics and channelrhodpsins, i. e. light-sensitive ion channels, in patient vision restoration. In the chemical arena, pharmacological agents, rendered light-sensitive by reversible modification with photosensitive protecting compounds ("caging"), have been applied to eyes of living mice to photo-release specific cellular activities. Among these were successful proof-of-principle experiments that were conducted to establish photo-sensitive gene therapies in the eye. For light-mediated treatment in combination with chemical biology, we wish to describe here the current frontiers of research in vision restoration with an eye on differences between biological and chemical light-sensing molecules, patient requirements, and future outlooks.

Gene therapy targets the retina to treat eye disease

Gene therapy targets the retina to treat eye disease

Advances in adhesive hydrogels applied for ophthalmology: An overview focused on the treatment.

Adhesive hydrogels, composed of hydrophilic polymers arranged in a three-dimensional network, have emerged as a pivotal innovation in ophthalmology due to their ability to securely adhere to ocular tissues while providing sustained therapeutic effects. The eye, with its delicate structure and specific needs, presents unique challenges for drug delivery and tissue regeneration. This review explores the transformative potential of adhesive hydrogels in addressing these challenges across a range of ocular conditions, including corneal injuries, cataracts, glaucoma, vitreoretinal disorders, and ocular trauma. By detailing the mechanisms of polymerization and adhesion, this paper highlights how these materials can be customized for specific ophthalmic applications, offering insights into their current use and future possibilities. The emphasis is placed on the clinical significance and future directions of adhesive hydrogels in advancing ophthalmic therapy, potentially revolutionizing the treatment of complex eye diseases.

Reply Re: “Teprotumumab for the Treatment of Recalcitrant Thyroid Eye Disease”

Reply Re: “Teprotumumab for the Treatment of Recalcitrant Thyroid Eye Disease”

The role of PPAR in fungal keratitis

The treatment of fungal keratitis(FK) remains challenging due to delayed fungal detection and the limited effectiveness of antifungal drugs. Fungal infection can activate both innate and adaptive immune responses in the cornea. Fungi stimulate the production of oxidative stress-related biomarkers and mediate the infiltration of neutrophils, macrophages, and T cells. These cells can induce infiltration of cytokines, chemokines, and matrix metalloproteinases (MMPs), leading to corneal tissue damage and even corneal perforation. The signaling pathway regulates the expression of inflammatory cytokines in fungal keratitis. Immune inflammatory damage is the main mechanism of FK, and oxidative stress damage is also involved in this infection process. Peroxisome proliferator-activated receptor (PPAR) is a member of the nuclear hormone receptor superfamily, with different subtypes of PPAR a, PPAR β/δ, and PPARγ. PPARs play important roles in the antioxidant response, anti-inflammatory, lipid metabolism, neuroprotection, and immune regulation processes. PPAR γ can promote macrophage polarization and reduce oxidative stress damage by regulating ROS production. PPAR has made some progress in the treatment of eye diseases: PPARa agonists can inhibit diabetes keratopathy and corneal neuropathy. PPARa agonists inhibit early immature angiogenesis in corneal alkali burns and have potential therapeutic effects on inflammatory corneal angiogenesis. PPARs can control the progression of dry eye disease and improve the condition of meibomian gland dysfunction. Based on this, we explored the potential roles of PPARs in the treatment of FK.

Efficacy, Safety, and Recurrence in Older Thyroid Eye Disease Patients Undergoing Teprotumumab Treatment.

Increasing life expectancy and an aging population have preserved quality of life decisions into older adulthood, defined by some clinical standards as greater than 75 years of age. While teprotumumab may represent a breakthrough in the treatment of thyroid eye disease, the teprotumumab phase III trial included only 2 patients aged over 75. Four female patients between the ages of 78 and 86-of whom 3 completed 8 infusions and 1 completed 7 infusions before discontinuation-were included in our study with a mean initial Clinical Activity Score score of 5.5, subjective diplopia, and proptosis. All patients experienced reduction in Clinical Activity Score with teprotumumab treatment. Two patients were subjective diplopia responders. Of the 6 eyes with collected measurements, all demonstrated a ≥2 mm reduction in post-treatment Hertel measurements. Most common adverse events were hyperglycemia, dysgeusia, fatigue, and alopecia. One patient with diabetes experienced an A1C rise requiring insulin. One patient had recurrence with increasing proptosis and recurrence of diplopia.

Botulinum Toxin Treatment in Thyroid Eye Disease: A Systematic Review and Meta-analysis.

Thyroid eye disease-related retraction and strabismus treatment is complicated by the activity level of the disease. Botulinum toxin injection can provide relief of symptoms in lieu of, or while waiting for surgery, radiation, or alternative medications. This study reviews techniques, outcomes, and effectiveness of botulinum toxin usage in thyroid eye disease. A systematic review was conducted using PubMed, Embase, Web of Science, and Cochrane to identify research investigating botulinum toxin treatment of thyroid eye disease through May 2024. A meta-analysis was performed on change in marginal reflex distance in retraction patients, resolution of diplopia in strabismus patients, necessity of further strabismus surgery, and side effects. Of 157 studies screened by 2 reviewers, 30 underwent analysis. In 19 upper eyelid retraction studies (299 patients), 1.5 to 15 U Botox (onabotulinum toxin A) or 10 to 40 U Dysport (abobotulinum toxin A) was administered to the superior tarsal border, with an 84% success rate and an average decrease in marginal reflex distance of 2.42 mm lasting 1 to 6 months. In 10 strabismus studies (205 patients), 5 to 20 U Botox or 25 U Dysport was administered in extraocular muscles; 24% achieved resolution of diplopia lasting 2 to 6 months, while 58% required further surgical management. In upper eyelid retraction studies, side effects included ptosis (13%) and diplopia (2%). In strabismus studies, side effects included ptosis (2%). This systematic review and meta-analysis confirmed that botulinum toxin is an effective treatment for thyroid eye disease-related lid retraction and strabismus. Randomized controlled studies are warranted to optimize botulinum toxin administration.

In vitro screening of potential echinochrome delivery systems for the treatment of eye diseases

An important task of topical application of medicines in the treatment of eyes is to achieve a compromise between their effectiveness and safety. The development of new multifunctional local ophthalmic drug delivery systems and in vitro screening of potential medicinal eye products are key areas in solving this problem. In this study, primary in vitro screening of the effect of echinochrome (Ech), the carrageenan complex of echinochrome (CRG/Ech) and its liposomal form (CRG/Ech-Lip) was performed on cultured epithelial cells of the outer shell of the eyeball: conjunctival epithelial cells (Chang Conjunctiva, Clone 1-5c-4) and corneal epithelium human (HCE). The cell viability was assessed by their morphology and metabolic activity using light microscopy and MTT test methods. The direct dependence of the intensity of the cytotoxic effect of Ech on its concentration in the nutrient medium, the form of use, the cellular test system and the incubation time of cells was revealed. Ech in the form of an alcoholic solution in its final concentration of 0.1 mg/ml of the nutrient medium exhibits pronounced cytoxicity against both cellular test systems. The same final concentration of Ech in the nutrient medium, but already as part of the carrageenan complex of echinochrome (CRG/Ech), turned out to be critical only for the viability of corneal epithelial cells, the survival rate of conjunctival cells under these conditions was about 50 %. A high biocompatibility of the liposomal form of the carrageenan complex of echinochrome (CRG/Ech-Lip) with cells of both test systems and a stimulating cytoprotective effect against the cells of the conjunctiva epithelium was revealed.

Comprehensive Comparisons of Different Treatments for Active Graves' Orbitopathy: A Systematic Review and Bayesian Model-Based Network Meta-Analysis.

This study aims to assess the efficacy and safety of various treatments for active thyroid eye disease. We conducted a comprehensive search for randomized controlled trials (RCTs), and ongoing RCTs registered on Controlled Trials, targeting treatments for thyroid eye disease up until November 20, 2024. Employing a Bayesian framework, this network meta-analysis calculated risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs) to size the effects for the predetermined outcomes. The study is registered with PROSPERO (CRD42024548030). The primary outcomes evaluated were overall response rate, clinical activity score(CAS), proptosis, diplopia and adverse events. For the overall response rate, teprotumumab (RR 5.5, 95%CI 2.3 to 16), mycophenolate combined intravenous glucocorticosteroids (IVGCs) demonstrated effectiveness over no treatment, ranked from most to least effective. Notably, teprotumumab showed the highest efficacy in reducing CAS (MD -1.57, 95%CI -3.81 to 0.68) and proptosis (MD -2.29, 95%CI -2.73 to -1.86). For diplopia improvement, teprotumumab and IVGCs were effective compared to no treatment. Teprotumumab emerges as potentially the most effective treatment for reducing inflammation and increasing overall response rates when compared to no treatment, oral mycophenolate combined with intravenous glucocorticosteroids appears to be the best one in improving proptosis. While some treatments raise safety concerns due to reported adverse events, oral methotrexate combined with intravenous glucocorticosteroids appear to offer a favorable balance between efficacy and safety among the evaluated treatments.

Review of Development of Ganciclovir as Potential Ophthalmic Drug Delivery Systems

Ganciclovir (GCV) plays a vital role in the treatment and management of ocular viral infections such as Herpes simplex virus (HSV) and cytomegalovirus (CMV) retinitis. However, GCV has low corneal penetration, is poorly permeable across the membrane, and has poor drug bioavailability, which poses a challenge in treating eye diseases. Besides that, conventional topical eye formulations, such as eye drops, gels, and ointments, have limitations such as poor tear turnover, poor residence time of the drug, frequent dosing intervals, wastage of dosage, and excessive systemic absorption leading to poor ocular bioavailability. Many strategies have been investigated to improve corneal permeation and ocular bioavailability of GCV. The journal review was written using the library study method from 2001-2023, which contained information about the Ganciclovir Formulation for Ophthalmic Drug Delivery System. The journal review discussed some approaches to achieving therapeutic goals for GCV. The results of this review showed that some of these approaches, including liposome, microemulsion, nanoparticle microsphere, polymeric nanoparticles, and gold nanoparticles, can improve the limitation of conventional formulation of GCV by increasing penetration, permeability, as well as bioavailability GCV in the ocular.

Risk of audiologic side effects with teprotumumab treatment for thyroid eye disease: propensity matched analysis.

Patients with thyroid eye disease (TED) taking teprotumumab have reported audiologic symptoms as a side effect; however, limited real world data and large sample sizes have been utilized to evaluate this relationship. A retrospective cohort study was created in TriNetX to identify patients with TED utilizing ICD-10, CPT, and Healthcare Common Procedure coding systems. TED patients with and without teprotumumab treatment were analysed with greedy one-to-one propensity matching. Appearance of one or more new ICD-10 codes corresponding to audiologic outcomes of interest (tinnitus, sensorineural hearing loss, hypoacusis, hyperacusis, autophony, Eustachian tube dysfunction) served as the outcome of interest. Patients with a history of hearing impairment were also evaluated for worsening hearing loss after initiation of teprotumumab. Within the entire TriNetX cohort, 88 out of 441 patients with a diagnosis code for TED treated with teprotumumab had new appearance of an audiologic outcome within TriNetX. After matching, the relative risk for TED patients who were exposed to teprotumumab for new audiologic symptoms was increased with a risk ratio (RR) of 2.85 [95% CI 1.94, 4.20] compared to TED patients not exposed to teprotumumab. Of 51 patients with a history of hearing impairment and TED, 14 had record of new audiologic testing after teprotumumab administration (RR = 1.90 [0.96, 3.78]) compared to unexposed patients. This study affirms previous research stating that TED patients receiving teprotumumab are at an increased risk of new audiologic side effects when compared to TED patients not using teprotumumab.

Surgical Timing for Patients with Thyroid Eye Disease Treated with Teprotumumab: A Collaborative Multicenter Study.

To compare regression rates, characteristics, and surgical outcomes of thyroid eye disease patients who underwent orbit, strabismus, or eyelid surgery at various times during or after teprotumumab treatment. Multicenter, retrospective, observational cohort study. Adult patients (age >18) with a minimum of 4 infusions of teprotumumab treatment for thyroid eye disease who had had eye surgery during or after treatment. Two groups were formed based on surgery timing: group 1 (G1) (<180 days since last infusion) and group 2 (G2) (≥180 days since last infusion). The primary outcome was postoperative regression rates. Secondary outcomes were postoperative regression characteristics, regression treatment, and orbital decompression proptosis reduction. This study evaluated 53 patients (81% female) who underwent 78 surgeries. G1 comprised 24 individuals with 34 surgeries, while G2 comprised 29 patients with 44 surgeries. Regression rates did not significantly differ between G1 and G2 (20.8% vs. 14.7%, p = 0.611). Compared with G1 patients, patients in G2 who regressed showed a significant mean increase in Clinical Activity Score (4.2 vs. 6.1, p = 0.027) and a nonsignificant yet measured increase in proptosis when compared with those in G1 (2.9 vs. 4.25, p = 0.298) at the time of regression. Compared with G1 patients, G2 patients who regressed were equally likely to undergo a repeat course of teprotumumab as group 1 (p = 0.14) but underwent a higher number of additional surgical procedures (p = 0.057). Thyroid stimulating immunoglobin levels uptrended more often in patients who regressed. Our study suggests that while the rate of regression may not differ significantly, the severity, clinical impact, and need for additional surgery might be more pronounced for patients who have surgery more than 6 months after their last teprotumumab dose.

EyeMatics: An Ophthalmology Use Case Within the German Medical Informatics Initiative.

The EyeMatics project, embedded as a clinical use case in Germany's Medical Informatics Initiative, is a large digital health initiative in ophthalmology. The objective is to improve the understanding of the treatment effects of intravitreal injections, the most frequent procedure to treat eye diseases. To achieve this, valuable patient data will be meaningfully integrated and visualized from different IT systems and hospital sites. EyeMatics emphasizes a governance framework that actively involves patient representatives, strictly implements interoperability standards, and employs artificial intelligence methods to extract biomarkers from tabular and clinical data as well as raw retinal scans. In this perspective paper, we delineate the strategies for user-centered implementation and health care-based evaluation in a multisite observational technology study.

Sustained release of RNA nanoparticles from reservoir implant for ocular delivery.

Previous studies of RNA nanoparticles have demonstrated the potential of these nanoparticles in ocular delivery via the subconjunctival route. Sustained ocular delivery is beneficial for chronic eye disease treatment, and utilizing a reservoir implant in the periocular space (e.g., episcleral implant) can prolong ocular delivery of these nanoparticles. The objectives of the present study were to (a) demonstrate the fabrication of the reservoir implants, (b) evaluate the performance of the implants with model permeants and RNA nanoparticles in vitro, and (c) investigate the applicability of hindered transport theory for the release kinetics from the implants. In vitro release testing was performed with the implants to determine the release kinetics and implant membrane permeability. In addition to RNA nanoparticles, model permeants fluorescein-isothiocyanate (FITC) labeled dextrans (10, 40, and 150 kDa) were examined. The results indicated that the rates of permeant release from the implants were a function of the (a) size and structure of the permeant/nanoparticle and (b) type and pore size of the implant membrane. The model analyses provided insights into implant membrane transport and ocular pharmacokinetics of the nanoparticles for transscleral delivery. The results suggested the potential of prolonged delivery of the RNA nanoparticles with the episcleral implant approach.

Hyaluronan-modified nanoceria for dry eye disease treatment.

Dry eye disease (DED), a prevalent ocular disorder, affects nearly half the global population, bringing enormous health and economic burden. Currently, the predominant treatments for DED involve the administration of artificial tears, which is often hindered by continuous administration and constant reactive oxygen species (ROS) stimulus. Therefore, hyaluronan (HA)-modified cerium oxide (CeO2) nanoparticles, HA-CeO2, were developed to achieve simultaneous ROS scavenging and enhanced tear film stability. HA-CeO2 was demonstrated to effectively scavenge ROS while concurrently downregulating the expression of inflammatory factors, such as MMP9 and IL-1β. Moreover, the anti-oxidative and anti-inflammatory effects of HA-CeO2 were further confirmed through a DED mouse model. In addition, the biocompatibility and safety of HA-CeO2 make it a promising treatment option for DED associated with inflammation and oxidative stress, offering novel insights into utilizing nanozymes in treating inflammation-oxidative stress-related diseases.

Vitamin D Supplementation and Remission from Chronic Anterior Uveitis

ABSTRACT Purpose Chronic anterior uveitis (CAU) often requires suppressive therapy, which has potential side effects including cataract, ocular hypertension, and increased risk of infection. No remittive therapy is currently available; however, several studies have demonstrated an association between low 25-hydroxy Vitamin D (25OHD) levels and either uveitis incidence or uveitis disease activity. This study investigates the potential of Vitamin D supplementation as a remittive treatment for CAU. Methods We conducted a retrospective analysis using data from the Systemic Immunosuppressive Therapy for Eye Disease (SITE) cohort study, which included patients with ocular inflammatory disease seen at U.S. tertiary centers between 1979 and 2010. Vitamin D supplementation data was analyzed for patients with CAU. Eyes were considered in remission if they remained quiet for at least 90 days off all anti-inflammatory treatment for eye disease. Results Among 2688 patients who never used Vitamin D, the cumulative adjusted CAU remission incidence was 13.5% at the 16-month follow-up. In contrast, among 75 patients who used Vitamin D for a duration of ≤1 year, the cumulative adjusted CAU remission incidence was 28% at 16 months. The use of Vitamin D was associated with a crude hazard ratio for remission of 2.14 [95% confidence interval (CI) 1.23–3.71, p = 0.0071], and an adjusted hazard ratio for remission of 2.43 [95% CI: 1.36–4.33, p = 0.0027]. Conclusion In the SITE Cohort, Vitamin D supplementation is associated with a significantly increased incidence of remission. Vitamin D supplementation should be explored in a prospective trial as the next step of evaluation.

Preparation and Characterization of Ozonated Liposomes Loaded with Curcumin: A Potential Approach for Diabetic Retinopathy Treatment

Background: Limitations in drug penetration are overcome by nanotechnology, particularly liposomes, which enhance targeted administration of ocular medications. Liposomes can augment the therapeutic effects of curcumin, a natural compound with positive impacts on the retina. Treatments for eye diseases can also benefit from the antibacterial properties of ozonated oil liposomes. Objectives: This study aims to develop and evaluate ozonated liposomes loaded with curcumin for ocular drug delivery applications, specifically targeting diabetic retinopathy (DR). Methods: Liposomal nanoparticles were prepared using thin-film hydration, incorporating phospholipids, lecithin, cholesterol, ozonated oil, and curcumin. We assessed physicochemical properties including particle size, zeta potential, encapsulation efficiency (EE), and morphology. Drug release profiles and stability studies were also conducted. Results: The optimized liposomes showed a particle size of 84.77 nm, a zeta potential of -16.8 mV, and an EE of 94.73%. The formulation exhibited sustained curcumin release over 24 hours, reaching 82.09% cumulative release. Stability studies indicated minimal changes in key parameters over three months at room temperature. Conclusions: The developed ozonated liposomal formulation demonstrates promising characteristics for curcumin delivery, potentially enhancing its therapeutic efficacy in ocular applications, particularly for DR.

Developments in Emerging Topical Drug Delivery Systems for Ocular Disorders.

According to the current information, using nano gels in the eyes have therapeutic benefits. Industry growth in the pharmaceutical and healthcare sectors has been filled by nanotechnology. Traditional ocular preparations have a short retention duration and restricted drug bioavailability because of the eye's architectural and physiological barriers, a big issue for physicians, patients, and chemists. In contrast, nano gels can encapsulate drugs within threedimensional cross-linked polymeric networks. Because of their distinctive structural designs and preparation methods, they can deliver loaded medications in a controlled and sustained manner, enhancing patient compliance and therapeutic efficacy. Due to their excellent drugloading capacity and biocompatibility, nano-gels outperform other nano-carriers. This study focuses on using nano gels to treat eye diseases and provides a brief overview of their creation and response to stimuli. Our understanding of topical drug administration will be advanced using nano gel developments to treat common ocular diseases such as glaucoma, cataracts, dry eye syndrome, bacterial keratitis, and linked medication-loaded contact lenses and natural active ingredients.

Smart Vision Transparency: Efficient Ocular Disease Prediction Model Using Explainable Artificial Intelligence

The early prediction of ocular disease is certainly an obligatory concern in the domain of ophthalmic medicine. Although modern scientific discoveries have shown the potential to treat eye diseases by using artificial intelligence (AI) and machine learning, explainable AI remains a crucial challenge confronting this area of research. Although some traditional methods put in significant effort, they cannot accurately predict the proper ocular diseases. However, incorporating AI into diagnosing eye diseases in healthcare complicates the situation as the decision-making process of AI demonstrates complexity, which is a significant concern, especially in major sectors like ocular disease prediction. The lack of transparency in the AI models may hinder the confidence and trust of the doctors and the patients, as well as their perception of the AI and its abilities. Accordingly, explainable AI is significant in ensuring trust in the technology, enhancing clinical decision-making ability, and deploying ocular disease detection. This research proposed an efficient transfer learning model for eye disease prediction to transform smart vision potential in the healthcare sector and meet conventional approaches’ challenges while integrating explainable artificial intelligence (XAI). The integration of XAI in the proposed model ensures the transparency of the decision-making process through the comprehensive provision of rationale. This proposed model provides promising results with 95.74% accuracy and explains the transformative potential of XAI in advancing ocular healthcare. This significant milestone underscores the effectiveness of the proposed model in accurately determining various types of ocular disease. It is clearly shown that the proposed model is performing better than the previously published methods.

Perceptions and Misconceptions About Eye Disease Treatment: A Cross-Sectional Study From Jazan, Saudi Arabia.

Eye diseases such as cataracts and glaucoma significantly contribute to vision impairment and blindness worldwide. While cataracts are the leading cause of preventable blindness, glaucoma, often referred to as the "silent thief of sight", can lead to irreversible vision loss if untreated. Despite their prevalence, awareness and understanding of these conditions remain low, particularly in regions like Saudi Arabia, where demographic changes and rising diabetes rates exacerbate the burden of eye diseases. This study aims to assess the knowledge and perceptions of cataracts and glaucoma among residents of Jazan to identify gaps and inform public health interventions. A cross-sectional online survey was conducted among participants aged 18 years and older in Jazan. The structured questionnaire assessed demographic information, awareness of cataracts and glaucoma, understanding of symptoms, and perceptions of treatment options. Data collection took place over four weeks, with statistical analysis performed using descriptive statistics to summarize findings. A total of 426 participants completed the survey. Of these, 43.9% (n = 186) were aware of cataracts, while only 28.1% (n = 119) recognized glaucoma. Awareness of cataract symptoms varied, with 43.4% (n = 184) identifying blurred vision; however, 71.5% (n = 303) reported being unaware of glaucoma. A significant majority (68.2%, n = 289) recognized surgical treatment for cataracts, but only 27.8% (n = 118) were aware of treatment options for glaucoma. High levels of uncertainty about both conditions suggest a critical lack of understanding in the community. This study emphasizes the need for improved awareness and understanding of cataracts and glaucoma in Jazan, Saudi Arabia. By implementing targeted public health strategies, healthcare providers can enhance knowledge, encourage regular eye examinations, and ultimately reduce the burden of visual impairment in the community.