Retina Update: Entering an Era of Personalized Medicine in Ophthalmology

The impact of retinal diseases continues to impart burdens on patients and health care systems around the world. The way we assess disease activity and how impairments and treatment burdens affect patients also continue to evolve. Improvements in the understanding of the disease processes, new technologies and treatments, patient-reported outcome measures, and multimodal imaging have enabled personalized medicine in several therapeutic areas including ophthalmology. Age-related macular degeneration (AMD), diabetic retinopathy, and retinal vein occlusion are major causes of vision impairment affecting the elderly population within developed countries.1,2 Significant therapeutic and surgical advancements have occurred in the past decades; however, given the global aging trend, there is an increasing need to optimize the management of these retinopathies to combat potential vision loss and burdens associated with these diseases. The blend of recent technological advancements and further insights into disease pathophysiology brings us into a new era of disease management, one that has become patient-centric and individualized. Although many new and exciting innovations are on the horizon, several uncertainties and challenges also emerge, which need to be recognized for the effective delivery of eye care. The purpose of this special issue is to provide a comprehensive update on several upcoming areas of interest in retinal disease, with a focus on AMD and retinal vein occlusion, along with other areas of significant interest. Three major themes are reflected across the papers included in this issue: a deeper understanding of diseases, technological advancements, and patient-focused outcomes. The role of inflammation in retinal disease is well documented, and our understanding of the pathophysiology continues to grow with new diagnostic modalities. Improved identification of inflammation and other biomarkers have been achieved through laboratory assessments and noninvasive multimodal imaging techniques. Inflammation has long been known to be involved in the pathogenesis of AMD but was predominately related to the “wet” or neovascular form. Focus has now shifted to target its role in “dry” AMD, as currently there are no approved treatments to control this form of advanced AMD. Several potential therapies are currently being developed to slow disease progression. Alongside the identification of new therapeutic targets, the dynamic between both arms of advanced AMD is something that is currently not completely understood and not fully investigated in clinical trials. Key interests are the development of macular atrophy and the inflammatory side-effect profile occurring during the treatment of neovascular AMD with anti-vascular endothelial growth factor, given that they are a major cause of poor long-term treatment outcomes with limited visual function.3 Given the broad influence of inflammation in AMD, both dry and wet AMD may one day be managed as a single entity. Technology has now been integrated into medical and surgical therapies. This can be seen from the availability of multimodal imaging techniques in recent years. In retinal vein occlusion, for example, classification systems and management approaches have not been well established. However, a universally acknowledged concern is the identification of retinal ischemia, as it is related to significant vision loss and neovascular complications. Fortunately, there are now tools at our disposal to aid in this diagnosis. Ultra-widefield fundus angiography and optical coherence tomography angiography are 2 powerful techniques which allow the retinal vasculature to be observed with greater detail and in the latter case, noninvasively. Meanwhile, macular perimetry has been an underappreciated tool which allows reproducible assessment of macular function. Combined with existing procedures, the correlation between functional and anatomic changes can be explored. This has great potential and is gaining application in a range of retinal diseases particularly geographic atrophy in AMD and guiding surgical decisions for various macular pathologies. Artificial Intelligence promises to develop the diagnosis and care of patients. In the real world, this technology will empower our patients in interacting with eye care professionals within the ecosystem. There will be opportunities for patients to be involved in their own care with improved understanding and control of their disease with potentially better outcomes. Improved patient outcomes are the heart of all advancements. By considering genetic and systemic factors, shifts have been made toward a holistic approach to patient care, which provides another layer of personalization during treatment. Relationships between a number of systemic medications and their impact on retinal function have been established and need to be further explored, especially with the ever-increasing numbers of new medications reaching the market. Gene therapy is another frontier in the treatment of AMD and other disorders, particularly retinal degenerations. It is now possible to perform a detailed investigation of genetic influences on an individual level. In epidemiological studies, this has been applied to accumulate large amounts of genetic data and should subsequently help identify the genetic effects underlying disease states. In a clinical setting, this provides the potential for screening programs to identify at-risk individuals and for treatment responses to be predicted in existing patients, but this is where a major challenge still lies. The funding and appropriate equitable allocation of resources to implement widespread and routine genetic analysis is something that will need to be considered. A further development with the aid of genetic analysis is the increased understanding of atypical disease variants such as polypoidal choroidal vasculopathy, which now appears to be a distinct entity to AMD that contains a racial/genetic predilection.4 This produces a need for global clinical trials to provide further insight into the racial differences in disease processes and their response to therapy. Currently, patient-related outcomes, along with treatment burdens, remain a very significant factor that guides treatment decisions, funding opportunities from stakeholders and underlies the rationale behind the development of several novel therapeutics and drug delivery systems. The situation surrounding the clinical use of brolucizumab highlights that while reductions in treatment burdens have been a driving factor behind its effectiveness, safety remains the ultimate decisive factor for use within the real-world setting. In summary, the management of vitreoretinal diseases, both from the standpoint of treatment, along with prevention, is truly exciting. Advances in our understanding is exponentially expanding along with the vast array of treatment options. Due to space limitations, we have not touched the point of the advances and application of artificial intelligence, but we are incredibly happy to share the advances of retinal diseases in this special issue with the readership of the APJO.5–9