Treatment Of Eye Diseases Research Articles

Long-Term Diabetic Retinopathy Treatment Using Silicon Nanoneedles.

Sustained-release ocular drug delivery systems with minimal invasiveness are critical for managing eye diseases that cause blindness. An innovative platform is presented for painless and long-term sustained ocular drug delivery utilizing controllably biodegradable silicon nanoneedles (Si NNs) conjugated with bevacizumab (Bev) integrated into a tear-soluble subconjunctival patch. The biocompatible patch facilitates easy application in the subconjunctival area of the eye and rapid dissolution in less than one minute upon contact with the tear film in the sclera, eliminating the need for removal procedures. The Si NNs, fabricated with precise control over their degradation kinetics, enable sustained and controlled release of Bev into the ocular tissues. This platform offers enhanced patient comfort, reduced risk of complications, and prolonged therapeutic efficacy. In vivo studies using a rabbit model of retinal neovascularization (RNV), a clinically relevant proliferative diabetic retinopathy (PDR), demonstrate the platform's ability to reduce RNV by 85% over a year, with no observable side effects. These results highlight the potential of this drug delivery method to penetrate the sclera and releaseBev gradually, providing a promising alternative for long-term, controllable ocular therapy. This technology represents a significant advancement in painless, convenient, and effective treatment for eye diseases requiring sustained drug delivery.

Multi-class Classification of Retinal Eye Diseases from Ophthalmoscopy Images Using Transfer Learning-Based Vision Transformers.

This study explores a transfer learning approach with vision transformers (ViTs) and convolutional neural networks (CNNs) for classifying retinal diseases, specifically diabetic retinopathy, glaucoma, and cataracts, from ophthalmoscopy images. Using a balanced subset of 4217 images and ophthalmology-specific pretrained ViT backbones, this method demonstrates significant improvements in classification accuracy, offering potential for broader applications in medical imaging. Glaucoma, diabetic retinopathy, and cataracts are common eye diseases that can cause vision loss if not treated. These diseases must be identified in the early stages to prevent eye damage progression. This paper focuses on the accurate identification and analysis of disparate eye diseases, including glaucoma, diabetic retinopathy, and cataracts, using ophthalmoscopy images. Deep learning (DL) has been widely used in image recognition for the early detection and treatment of eye diseases. In this study, ResNet50, DenseNet121, Inception-ResNetV2, and six variations of ViT are employed, and their performance in diagnosing diseases such as glaucoma, cataracts, and diabetic retinopathy is evaluated. In particular, the article uses the vision transformer model as an automated method to diagnose retinal eye diseases, highlighting the accuracy of pre-trained deep transfer learning (DTL) structures. The updated ViT#5 model with the augmented-regularized pre-trained model (AugReg ViT-L/16_224) and learning rate of 0.00002 outperforms the state-of-the-art techniques, obtaining a data-based accuracy score of 98.1% on a publicly accessible retinal ophthalmoscopy image dataset, which includes 4217 images. In most categories, the model outperforms other convolutional-based and ViT models in terms of accuracy, precision, recall, and F1 score. This research contributes significantly to medical image analysis, demonstrating the potential of AI in enhancing the precision of eye disease diagnoses and advocating for the integration of artificial intelligence in medical diagnostics.

Trailblazer Tepezza for thyroid

Dear Editor, Teprotumumab is a human monoclonal antibody that blocks the insulin-like growth factor-1 receptor (IGF- 1R). Approved by the Food and Drug Administration (FDA) on January 21st, 2020, under the brand name Tepezza, to be used as the treatment for Graves eye disease in adults based on its landmark success in the randomised double-blind clinical trials named OPTIC study. [1] A meta-analysis published in the International Journal of Clinical Practice in 2023 stated that at week 24 of treatment, Teprotumumab had been shown to significantly improve proptosis in 71.86% participants, diplopia in 73.65% of participants and decrease tissue inflammation, as measured by the clinical activity score to zero or one, thus improving the overall quality of life. [2] Even though the drug has adverse effects namely alopecia, fatigue and headache, the risk of these occurring was the same as the placebo group. Other potential side effects included nausea, dry skin and muscle spasms which were deemed mild.[3] One manageable side effect reported was hypoglycaemia, especially in individuals already diagnosed with diabetes, which could be corrected by adjusting their anti-diabetic medication. Importantly, this drug should be avoided in pregnancy due to its prospective teratogenic effects [2]. The promising statistics outweigh the risks associated with the drug and make teprotumumab a game-changer for thyroid eye disease patients. Pakistan has a 2% prevalence of hyperthyroidism, with a major (90%) contribution from Graves’ disease. [4] Although this 2% seems insignificant, yet it amounts up to 4.2 million people. Unfortunately, this drug has not reached Pakistan yet and we still resort to using conventional treatments namely lubricants and steroids despite their worrying side effects and contraindications in patients having other comorbid conditions which majority of the people of Pakistan suffer from such as diabetes, hypertension, osteoporosis and hepatic dysfunction. [5] The government should subsidize the use of this novel drug in TED patients by incentivizing its availability and training physicians to monitor the patients taking the infusions. The patients will need to be educated about the adverse profile and danger signs when to report their symptoms to the doctor. Teprotumumab is not just a treatment, it is a cure for most patients. Should we not switch from using the current harmful conventional drugs to the more contemporary ones with better outcomes?

Construction of a thermosensitive gel based on hydroxypropyl-β-cyclodextrin/meloxicam inclusion complexes for improving meloxicam solubility and prolonging drug retention time in the cornea.

The eyes are easily stimulated by external factors, which can cause inflammation. Anti-inflammatory drugs are usually used to inhibit the production of inflammatory factors. Many nonsteroidal anti-inflammatory drugs have been used for the eye, but due to the poor solubility of meloxicam, there are currently no marketed meloxicam preparations for the treatment of eye diseases. This article uses hydroxypropyl-β-CD (HP-β-CD) to encapsulate meloxicam and combined with thermosensitive gel to prepare an HP-β-CD/meloxicam inclusion complex eye thermosensitive gel, which can improved the water solubility of meloxicam and extend the retention time of the drug in the cornea, and achieve the goal of slow release through continuous dissolution. It not only has the advantages of convenient administration and accurate dosage of eye drops, but also overcomes the disadvantage of easy loss of eye drops, showing the advantages of long retention time and fewer administration times, and provides a basis for the development of other dosage forms of meloxicam.

Comparison of different decellularization methods for human anterior lens capsules

BackgroundHuman anterior lens capsules (ALCs) have great potential in the treatment of multiple eye diseases, including corneal ulcers, glaucoma, age-related macular degeneration and macular holes. ALCs are also regarded as promising scaffolds for various ocular cells. Here, we investigated different decellularization methods for removing lens epithelial cells (LECs) that adhered to ALCs.MethodsHuman ALCs were treated with various solutions, including 2% lidocaine, 10% sodium chloride, 50% glucose and sterile water. Trypan blue and alizarin red (TB-AR) staining, H&E staining and hydroxyproline assays were used to assess the degree of decellularization. The impacts of acellular ALCs on cell viability and cell-tissue interaction were investigated in vitro.ResultsThese findings revealed that 2% lidocaine, 10% sodium chloride, 50% glucose, and sterile water had the capacity to decellularize ALCs at 37 °C. The structure of ALCs in all decellularization groups was similar to that of intact ALCs. The effects of 10% sodium chloride and sterile water on decellularization were significantly better than those of 2% lidocaine and 50% glucose. The H&E staining revealed that the different decellularization methods maintained the integrity of the lens capsular structure. Compared with sterile water, 10% sodium chloride preserved a better level of hydroxyproline. The ALCs in the 10% sodium chloride-treated group and the sterile water-treated group were shown to be suitable for cell adhesion in vitro.ConclusionThis study identified two optimal decellularization methods for acellular ALCs: using 10% sodium chloride and using sterile water. The obtained acellular ALCs could be promising scaffolds for ocular cells. In addition, acellular ALCs do not need resterilization and may be directly used for autologous lens capsule transplantation in clinical applications.

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.

Mesenchymal Stem Cell-Sourced Exosomes as Potentially Novel Remedies for Severe Dry Eye Disease.

Severe dry eye disease (DED) is an inflammatory condition characterized by a lack of sufficient moisture or lubrication on the surface of the eye, significantly impacting the quality of life and visual function. Since detrimental immune response is crucially responsible for the development and aggravation of DED, therapeutic agents which modulate phenotype and function of eye-infiltrated inflammatory immune cells could be used for the treatment of severe DED. Due to their potent immunomodulatory properties, mesenchymal stem cells (MSCs) represent potentially new remedies for the treatment of inflammatory eye diseases. The majority of MSC-sourced bioactive factors are contained within MSC-derived exosomes (MSC-Exos), nano-sized extracellular vesicles which, due to their nanosize dimension and lipid envelope, easily by pass all biological barriers in the body and deliver their cargo directly into the target immune cells. MSC-Exos contain a variety of bioactive proteins (growth factors, immunoregulatory molecules, cytokines, and chemokines) lipids, and microRNAs (miRNAs) which affect viability, proliferation, phenotype, and function of eye-infiltrated immune cells. Accordingly, MSC-Exos may modulate the progression of inflammatory eye diseases, including DED. Therefore, in this review article, we summarized the current knowledge regarding molecular and cellular mechanisms which were responsible for trophic, anti-inflammatory, immunoregulatory, and regenerative properties of MSC-Exos in the treatment of severe DED. For this purpose, an extensive literature review was carried out in February 2024 across several databases (Medline, Embase, and Google Scholar), from 2000 to the present. Eligible studies delineated molecular and cellular mechanisms responsible for the MSC-Exos-based modulation of immune cell-driven eye inflammation in DED, and their findings were analyzed in this review. Results obtained in these studies demonstrated beneficial effects of MSC-Exos in the treatment of severe DED, paving the way for their future clinical use in ophthalmology. Trial Registration: ClinicalTrials.gov identifier: NCT04213248, NCT06475027, NCT06543667, NCT05738629.

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

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

Tear substitutes and native tear protein interaction. A pilot study to evaluate possible chemical structural interferences

Aims/Purpose: The loss of ocular surface homeostasis leads to the Dry Eye Disease (DED) onset. Although tear substitutes are the front‐line treatment for DED, recent advances suggest new therapeutic approaches to modulate the different mechanisms leading to the ocular surface impairment [1]. For this reason, there is a need to better understand the specific interactions between the new formulations and the native components of the tears. This pilot study is focused on assessing the chemical stability of two major human tear proteins, lysozyme C (LYS‐C) and lactoferrin (Lf), after the contact with formulations containing trehalose (Thealoz Duo, A) and trehalose plus N‐acetyl‐aspartyl‐glutamic acid (Thealoz Total, B).Methods: Human LYS‐C and Lf (Sigma) were resuspended in saline, incubated at 37°C with A and B previously diluted to simulate the final concentration in a real‐life condition, up to 2 hours. The chemical structures of LYS‐C and Lf were analyzed by circular dichroism (CD) (J‐815, Jasco) as alone, and after the incubation with A and B, with blank subtraction performed on saline.Results: Data from CD showed that the contribution of both formulations had no impact on the structural conformation change of both LYS‐C and Lf. The spectra of the protein structures remained unchanged showing a chemically matched profile of the secondary structure elements in native proteins (Wavelength 208‐222 nm). Further studies will be focused on assessing if protein stability could be affected after longer incubation times.Conclusions: Thealoz Duo and Thealoz Total did not produce any conformational change in native LYS‐C and Lf. Data suggest that analysis of possible chemical interactions with the native tear proteins could be of benefit during the process of new tear substitute formulation.References Barabino, S et al.“Dry eye disease treatment: the role of tear substitutes, their future, and an updated classification.” Eur Rev Med Pharmacol Sci.2020; 24(17): 8642‐8652.

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.