Introduction 

Ophthalmology is a rapidly growing field of medicine. Fueled by increased funding, ophthalmology research and ocular drug development efforts produce novel innovations and cutting-edge treatments for sight-threatening diseases. In tandem, contract research organizations (CROs) are making significant investments to expand their expertise in ophthalmology, ready to partner with biotechnology and pharmaceutical companies in their clinical development journeys. In this eye-opener, we explore some of the ground-breaking strides in the world of ophthalmology research. 

 

Ophthalmology Research Trends 

A recent analysis of ophthalmology research trends from 2000 to 2022 found that the knowledge foundations of global ophthalmologic randomized controlled trials (RCTs) were mainly retinopathy, glaucoma, dry eye disease (DED), and cataracts. Top research highlights were anti-vascular endothelial growth factor (VEGF) therapy for age-related macular degeneration (AMD), diabetic macular edema (DME), and DED, the use of new diagnostic tools, and myopia. 

 

Artificial Intelligence (AI) 

Artificial intelligence (AI) is revolutionizing ophthalmology through automated disease detection and diagnosis, personalized treatment plans, and streamlined workflows and increased efficiency. International publications on AI-related ophthalmology research have been growing. Studying publication trends, Jiang et al.,  identified several topics that they anticipate will continue to be top research areas in 2024 and over the next few years: the association between eye and systemic biomarkers, telemedicine, real-world studies, and the application of new AI algorithms, e.g., visual converters.   

Most ophthalmology AI studies have focused on diabetic retinopathy, AMD, glaucoma, and cataracts. According to Choi & Yoo, AI has been used in refractive correction surgery, ocular disease treatment, and oculomics. A number of AI-based systems received U.S. Food and Drug Administration (FDA) approval for diabetic retinopathy detection. Research on the application of generative pre-trained transformer-4 (GPT-4) in ophthalmology is still limited. 

Myopia is a global public health concern with an increasing burden on health systems. Ongoing research in myopia aims to determine the role of AI and digital technologies in the early identification of complications, timely intervention, and treatment through automated detection for screening and risk stratification, individualized prediction, and prognostication of disease progression. In this evolving field, novel AI tech includes multimodal AI, explainable AI, and federated learning, while digital tech advancements include digital therapeutics, self-monitoring devices, and wearables.  

 

Gene Therapy 

In recent years, there have been several breakthroughs in ophthalmology research, including exciting developments in gene therapy. In 2017, the FDA approved a retinal gene therapy for hereditary retinal dystrophies caused by RPE65 gene mutations. Priglinger et al. suggest that the success of this gene augmentation therapy encouraged research based on the concept of gene supplementation to extend to non-genetic diseases like AMD.  

Glaucoma is one of the leading causes of acquired irreversible blindness, but timely treatment to lower intraocular pressure (IOP) is effective in slowing the rate of vision loss. Studying glaucoma research activities now and beyond, Jayaram et al. suggest that future research will focus on IOP-independent neuroprotective treatments, personalized treatment utilizing genetic risk profiling, and advanced cellular and gene therapies. 

Retinal vein occlusion is the second leading cause of retinal vascular disorders. New imaging techniques have improved the understanding of the pathophysiology of retinal vein occlusion. In addition to laser treatment, which was once the only treatment option, VEGF and steroid injections are preferred in most cases while more interventions are under development, including new intravitreal drugs and gene therapy.  

Retinitis pigmentosa (RP) is a leading cause of visual disability and blindness in people below 60 years of age, affecting more than 1.5 million people globally. There is currently no curative treatment, and only a small group of patients with confirmed gene mutations are eligible to receive the only gene therapy available. Wu et al. reviewed therapeutic approaches under development, including gene and cell therapy and novel potential drug targets for RP. 

 

Cell-based therapies  

Ophthalmology research in cell therapy has made significant progress, with the first-in-human transplantation of autologous induced pluripotent stem (iPS) cell-derived retinal pigment epithelium (RPE) cells for patients with AMD underway. Cell therapy for RP has also been developed. Different sources, e.g., embryonic stem cells or iPS cells, can be used for transplantation. 

More on RP, its unknown pathology mechanism, and the difficulty of treatment underlines the need to perform more spatially informed molecular biology studies. Zhou et al. used spatial transcriptomic analysis to study changes in retinal layers of rd1 mice at various ages. It concluded that applying spatial transcriptomics can help elucidate RP’s important pathogenesis. 

 

Nanotechnology  

Due to anatomical and physiological barriers unique to the eye, ocular drug delivery has posed challenges for ophthalmologists and researchers. The application of nanoporous materials, characterized by their high surface area, tunable porosity, and functional versatility, holds considerable potential for improving ocular devices and the passive and active targeting within ocular drug delivery systems (DDS). Further, engineered nanomedicines are promising to enhance drug penetration, while DNA carriers have emerged as a cutting-edge class of active-targeting structures14. Currently, nanotechnology-based ophthalmic drugs are on the market and in clinical trials. 

Characteristics of nano-based DDS include nano micelles, nanoparticles, nanosuspensions, microemulsions, nanofibers, dendrimers, liposomes, nano wafers, contact lenses, hydrogels, microneedles, and innovative gene therapy employing nano-based ocular delivery techniques. Liu et al. emphasize the need for further research to address potential safety and toxicity concerns.  

Ocular surface neovascularization is a major cause of vision loss—factors such as infection, trauma, and ocular surface surgery trigger neovascularization. Yang et al.  review the research and recent advances in antiangiogenic drugs, nanotechnology, gene therapy, surgical equipment and techniques, animal models, and drug delivery strategies, which provide a range of novel treatment options for ocular surface neovascularization.  

 

Wearable Tech 

Glaucoma is associated with IOP and is a predominant cause of non-reversible vision loss. Current research areas include innovative engineering solutions for IOP monitoring and developing wearable and implantable sensors for glaucoma management. The implications of these innovations in clinical practice include real-world applications, patient-centered strategies, and future development in IOP control.  

Over 300 million people worldwide are affected by low vision. Although rehabilitative training and vision assistive equipment (VAE) may help, some patients cannot attend in-person visits to benefit from them. Bittner et al. explored telerehabilitation and found similar efficacy between telerehabilitation with a therapist and an active control intervention of self-guided training.  

AMD has a wide-ranging detrimental impact on daily living. A study by Miller et al.20  on assistive technology found that wearable electronic vision enhancement systems (wEVES) provide hands-free magnification and image enhancement. This results in significant improvements in acuity, contrast sensitivity, and aspects of lab-simulated daily activity. The researchers call for further patient-centered research to assess the benefits of wEVES in user-led activities vs. alternative coping strategies. 

Smart eyewear and head-worn wearable devices can potentially transform teleophthalmology care. A review by RaviChandran et al., found that rapid technological advancements and the integration of AI are expanding the application of smart eyewear in healthcare, including remote assessments, real-time monitoring, telehealth consultations, and personalized interventions. By leveraging AI, the rich, continuous, objective, and individual-specific data such wearables collect can help identify at-risk patients, recognize behavioral patterns, and administer timely and cost-effective personalized treatment.  

 

3D printing 

Blindness caused by corneal damage affects millions worldwide, and corneal transplantation is one of the treatments available for severe corneal diseases. Research on bioprinting artificial cornea has induced interest in the materials and cells that can be selected as bio-inks for optimal clarity, biocompatibility, and tectonic strength. With continued research into advancing biomaterials science and printing technology, Jia et al., suggest that bioprinted cornea will one day possess the clinical functionality and practicality to replace donated corneal tissues. Current research on 3D bioprinting in corneal reconstruction and regeneration includes bioprinting strategies, 3D corneal modeling, material options, and cellularization strategies. 

For glaucoma diagnosis, Jang et al., studied 3D superstructures fabricated through evaporation-induced microprinting to analyze the metabolome. A Deep Neural Network (DNN) classification model accurately classified glaucoma patients. The researchers noted the advantage of 3D superstructures is their versatility in accommodating different target materials. They suggest that they can be utilized for various metabolic analyses and disease diagnoses. 

 

Ophthalmology Contract Research Organization (CRO) of Choice 

TFS HealthScience Ophthalmology has been the CRO of choice for over 65 biotechnology and pharmaceutical clinical research projects in 24 countries. It has an established presence in over 600 sites globally for clients ranging from industry leaders to early-stage companies and private practitioners, covering a variety of ocular pathologies from anterior to posterior segments. In recent news, TFS HealthScience announced the acquisition of Appletree CI Group to enhance the company’s existing expertise in the complex fields of ophthalmology, dermatology, medical devices, and pediatric studies.  

 

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