Precision medicine involves stratifying patients based on extensive datasets, which encompass clinical information, genetic data, and environmental factors, to provide optimal treatment and preventive strategies for each group. In the context of uveitis management, it is essential to select the most suitable treatment for each patient with uveitis based on various factors, such as the stage of uveitis, activity and severity of ocular inflammation, and impact of uveitis on ocular tissues. Although this approach embodies precision medicine, the datasets obtained using existing diagnostic and treatment methods may not be sufficiently comprehensive in both quantity and quality. To address this issue, we aimed to acquire unconventional diagnostic information, develop novel therapeutic approaches, and construct a large-scale database.
I. Development of in vivo imaging systems aiming at "visualization" of ocular inflammation
Ophthalmoscopy has traditionally been the gold standard for assessing intraocular inflammation in patients with uveitis. However, some patients may exhibit chronic progressive retinal damage even when there is only slight intraocular inflammation visible via ophthalmoscopy. This often presents challenges for ophthalmologists in making optimal and timely treatment decisions. To address this issue, we employed optical coherence tomography (OCT), which revealed that the characteristics of vitreous cells are valuable for categorizing uveitis cases. Additionally, we successfully assessed two-dimensional inner retinal damage associated with uveitis using en face slab OCT imaging. Moreover, our study revealed that in vivo imaging of the mouse retina through two-photon microscopy enables the evaluation of the dynamic response of microglia to ocular inflammation. Although the dynamic visualization of inflammatory cells in the living human retina may currently be challenging and impractical, it may become feasible to clinically detect and visualize abnormalities in retinal cells before irreversible structural damage occurs. This can be achieved by applying the insights gained from our research in mouse retinas to the dynamics of a suitable biological probe. Achieving the "visualization" of ocular inflammation through in vivo imaging holds the potential to greatly enhance the precise management of ocular inflammation by enabling a thorough evaluation of both ocular inflammation and retinal tissue damage.
II. Novel filtering surgery for overcoming uveitic glaucoma (UG)
With the recent introduction of biologics and minimally invasive vitreous surgery, it has been proposed that the primary cause of blindness in patients with uveitis is transitioning from macular disorders to secondary glaucoma. UG typically presents with elevated intraocular pressure and a more rapid progression of visual field loss compared with primary open-angle glaucoma (POAG). Consequently, a different management strategy is required for eyes with UG to ensure the long-term preservation of visual function. Our research revealed that some patients with UG responded well to Rho-associated coiled-coil forming kinase (ROCK) inhibitor eye drops. Additionally, the treatment outcomes of ab interno trabeculotomy using the Tanito hook for UG were found to be comparable to those for POAG. The evolution of filtering surgery is crucial for effectively managing UG. The Tenon retractor, which was developed by the author, is a device designed to achieve the benefits of mitomycin C while minimizing its negative impact on the normal conjunctiva by creating a space between the Tenon capsule and the sclera during surgery. Combining this device with a unique scleral flap treatment and an original conjunctival suturing method has led to the development of novel trabeculectomy, which eliminates the need for managing filtering blebs. Furthermore, we incorporated modifications to long-tube shunt glaucoma surgery, which have contributed to minimally invasive filtration surgery for UG. We expect that advancements in the abovementioned treatment methods for UG will ultimately result in the long-term preservation of visual function in patients with uveitis.
III. Approach of precision medicine for autoimmune retinopathy (AIR)
AIR is a rare autoimmune disease that results in subacute and irreversible damage to the retinal photoreceptors, leading to significant visual impairment caused by an autoimmune reaction targeting retinal cells. Several substantial challenges complicate the clinical management of AIR, including the low specificity of antiretinal autoantibodies for diagnosing the condition and the absence of a standardized treatment algorithm. Furthermore, the lack of objective biomarkers, which are capable of indicating the treatment's effectiveness before irreversible damage to visual function occurs, is the main cause rendering the treatment challenging. To address these challenges, in collaboration with the Japanese Ocular Inflammation Society and the Japan Ocular Imaging Registry, we initiated a multicenter study. This study aims to construct a large-scale clinical database of patients with AIR, identify key antiretinal antibodies based on a comprehensive protein array, and explore clinical biomarkers through an integrated analysis of patients' blood metabolite and clinical data. We believe that the utilization of high-quality datasets generated from this study will advance precision medicine for AIR.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 128: 234-255, 2024.