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Toxoplasma gondii, an obligate intracellular parasite, is a globally prevalent pathogen capable of infecting a wide range of warm-blooded animals, including humans. Ocular toxoplasmosis (OT), a severe manifestation of T. gondii infection, can lead to potentially blinding complications. This comprehensive review delves into the current understanding of T. gondii biology, exploring its complex life cycle, diverse transmission routes, and strain diversity. This article provides an in-depth analysis of the clinical manifestations of OT, which can result from both congenital and acquired infections, presenting a spectrum of signs and symptoms. The review examines various diagnostic strategies employed for OT, including clinical examination, multimodal imaging techniques such as fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA), as well as laboratory tests including serology and molecular methods. Despite extensive research, the specific mechanisms underlying ocular involvement in T. gondii infection remain elusive, and current diagnostic options have limitations. Moreover, the treatment of active and recurrent OT remains a challenge. While existing therapies, such as antimicrobial agents and immunosuppressants, can control active infections, they do not offer a definitive cure or completely prevent recurrence. The clinical endpoints for the management of active and recurrent OT are also not yet well-established, and the available treatment methods carry the potential for adverse effects. This article highlights the need for future research to elucidate the pathogenesis of OT, investigate genetic factors influencing susceptibility to infection, and develop more sensitive and specific diagnostic tools. Enhancing global surveillance, implementing robust prevention strategies, and fostering multidisciplinary collaborations will be crucial in reducing the burden of OT and improving patient outcomes. This comprehensive review aims to provide a valuable resource for clinicians, researchers, and policymakers, contributing to a better understanding of T. gondii infection and its impact on ocular health.

Cytomegalovirus (CMV) retinitis is the most common eye disease associated with CMV infection in immunocompromised individuals. The CMVR may initially be asymptomatic; however, relatively mild vitreous inflammation at the onset may be an important differential point from other diseases in HIV patients. Fundus photography, CD4 T-cell count, and telemedicine could be used to screen and monitor the high-risk population, particularly in resource-limited regions. Retinitis generally starts in the peripheral retina and advances toward the posterior pole, which could develop to the characteristic “pizza pie” appearance marked by central retinal necrosis and intraretinal hemorrhage. CMVR causes vision loss if left untreated, and early antiviral therapy significantly reduces the risk of vision loss. Alongside traditional antiviral treatments, immunotherapies including CMV-specific adoptive T-cell therapy and CMV immunoglobulin (CMVIG) are emerging as promising treatment options due to their favorable tolerability and reduced mortality. This review comprehensively examines CMV retinitis, encompassing the clinical features, differential diagnosis, laboratory tests, and updated treatment strategies to inform clinical management.

Biological therapies have revolutionized medical treatment by targeting the key mediators or receptors involved in inflammatory responses, thereby effectively suppressing inflammation and achieving beneficial outcomes. They are more advanced than conventional therapies using corticosteroids and immunosuppressants, offering effective solutions for autoimmune diseases, cancer, transplant rejection, and various infectious diseases, including coronavirus disease 2019. Although they exert low immunosuppressive effects, biological therapies can reactivate specific biological targets associated with infections. This review summarizes the currently available biological therapies and discusses their immunosuppressive mechanisms and clinical applications, highlighting the variations in the types and frequencies of infection recurrence induced by different biological agents. Additionally, this review describes the risk factors associated with various biological agents, thus aiding clinicians in selecting the most appropriate biological therapy.

(1) Background: The fundus examination is one of the best and popular methods in the assessment of vascular status in the human body. Direct viewing of retinal vessels by ophthalmoscopy has been utilized in judging hypertensive change or arteriosclerosis. Recently, fundus imaging with the non-mydriatic scanning laser ophthalmoscope (SLO) has been widely used in ophthalmological clinics since it has multimodal functions for optical coherence tomography or angiography with contrast agent dye. The purpose of this study was to examine the utility in detecting arteriosclerosis of retinal vessels in SLO images; (2) Methods: Both color and blue standard field SLO images of eyes with diabetic retinopathy (DR) were examined retrospectively. Retinal arteriosclerosis in color SLO images was graded according to the Scheie classification. Additionally, characteristics of retinal arterioles in blue SLO images were identified and examined for their relevance to arteriosclerosis grades, stages of DR or general complications; (3) Results: Relative to color fundus images, blue SLO images showed distinct hyper-reflective retinal arterioles against a monotone background. Irregularities of retinal arterioles identified in blue SLO images were frequently observed in the eyes of patients with severe arteriosclerosis (Grade 3: 79.0% and Grade 4: 81.8%). Furthermore, the findings on arterioles were more frequently associated with the eyes of DR patients with renal dysfunction (p < 0.05); (4) Conclusions: While color SLO images are equally as useful in assessing retinal arteriosclerosis as photography or ophthalmoscopy, the corresponding blue SLO images show arteriosclerotic lesions with high contrast in a monotone background. Retinal arteriosclerosis in eyes of advanced grades or advanced DR frequently show irregularities of retinal arterioles in the blue images. The findings of low, uneven, or discontinuous attenuation were easier to find in blue than in color SLO images. Consequently, blue SLO images can show pathological micro-sclerosis in retinal arterioles and are potentially one of the safe and practical methods for the vascular assessment of diabetic patients.

Vaccination is a public health cornerstone that protects against numerous infectious diseases. Despite its benefits, immunization implications on ocular health warrant thorough investigation, particularly in the context of vaccine-induced ocular inflammation. This review aimed to elucidate the complex interplay between vaccination and the eye, focusing on the molecular and immunological pathways implicated in vaccine-associated ocular adverse effects. Through an in-depth analysis of recent advancements and the existing literature, we explored various mechanisms of vaccine-induced ocular inflammation, such as direct infection by live attenuated vaccines, immune complex formation, adjuvant-induced autoimmunity, molecular mimicry, hypersensitivity reactions, PEG-induced allergic reactions, Type 1 IFN activation, free extracellular RNA, and specific components. We further examined the specific ocular conditions associated with vaccination, such as uveitis, optic neuritis, and retinitis, and discussed the potential impact of novel vaccines, including those against SARS-CoV-2. This review sheds light on the intricate relationships between vaccination, the immune system, and ocular tissues, offering insights into informed discussions and future research directions aimed at optimizing vaccine safety and ophthalmological care. Our analysis underscores the importance of vigilance and further research to understand and mitigate the ocular side effects of vaccines, thereby ensuring the continued success of vaccination programs, while preserving ocular health.

Human T-cell leukemia virus type 1 (HTLV-1), a virus that affects 5–10 million people globally, causes several diseases, including adult T-cell leukemia-lymphoma and HTLV-1-associated uveitis (HU). HU is prevalent in Japan and often leads to secondary glaucoma, which is a serious complication. We investigated the efficacy of ripasudil, a Rho-associated coiled coil-forming protein kinase inhibitor, in alleviating changes in human trabecular meshwork cells (hTM cells) infected with HTLV-1. HTLV-1-infected hTM cells were modeled in vitro using MT-2 cells, followed by treatment with varying concentrations of ripasudil. We assessed changes in cell morphology, viability, and inflammatory cytokine levels, as well as NF-κB activation. The results showed that ripasudil treatment changed the cell morphology, reduced the distribution of F-actin and fibronectin, and decreased the levels of certain inflammatory cytokines, such as interleukin (IL)-6, IL-8, and IL-12. However, ripasudil did not significantly affect NF-κB activation or overall cell viability. These findings suggest that ripasudil has the potential to treat secondary glaucoma in patients with HU by modulating cytoskeletal organization and alleviating inflammation in HTLV-1-infected hTM cells. This study lays the foundation for further clinical studies exploring the effectiveness of ripasudil for the treatment of secondary glaucoma associated with HU.

mRNA COVID-19 vaccines have been reported as protecting against COVID-19 and reducing its severity, and we have recognized post-vaccination symptoms recently. This research investigates the clinical trajectories of ocular disorders in a 51-year-old female who received a second dose of the BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine. Exhibiting fever and blurred vision within 24 h post-vaccination, with progressive blurry vision over two months, she underwent in-depth ophthalmologic examinations, revealing intraocular cellular infiltration in anterior chamber, vitreous opacity, and frosted branch angiitis in both eyes. Comprehensive evaluations, including systemic workups as well as ocular and blood specimen analyses, excluded autoimmune and infectious etiologies, consolidating the diagnosis of vaccine-induced ocular inflammation. Despite adherence to prevailing therapeutic protocols, her condition showed no significant improvement over 18 months, pointing to a possible long post-COVID vaccination syndrome. Such persistent sequelae underscore the need for detailed studies to discern the interactions between vaccine-induced immune responses and the development of post-vaccination sequelae. Continual documentation of patients with long post-COVID vaccination syndrome is now essential to better understand the vaccine’s immunological effects, aiding in improving global vaccination strategies.

Since the introduction of combination antiretroviral therapy (cART) in Japan in 2008, the spectrum of ocular manifestations in patients with human immunodeficiency virus (HIV) has changed. This study, conducted at Tokyo Medical and Dental University Hospital between January 2012 and August 2023, aimed to understand the epidemiology and clinical features of ocular manifestations in patients with HIV during the cART era. Of the 218 patients diagnosed with HIV, 23 (10.55%) exhibited ocular manifestations; all were male, aged 32–73. The most prevalent ocular complication was uveitis (60.67%). Notably, the prevalence of uveitis in this cART era has surged compared to earlier Japanese studies. Our data also suggest a potential direct link between uveitis and HIV, particularly in patients who have not yet undergone cART. However, cytomegalovirus retinitis, another prevalent ocular disease in our study, appeared more strongly associated with patients who commenced cART. Neither ocular condition was significantly correlated with CD4+ T-cell count. Importantly, our observed ocular manifestation prevalence (10.55%) was lower than that in previous studies, emphasizing the potential influence of cART and national healthcare support. These findings provide unique insights into the evolution of ocular manifestations in patients with HIV in Japan amidst cART availability.

The association between vaccines and ocular disorders has attracted significant attention in scientific research. Numerous mainstream vaccines are associated with a range of uveitis types, including anterior, intermediate, and posterior uveitis. Additionally, they are associated with distinct ocular diseases such as multifocal choroiditis, Vogt–Koyanagi–Harada (VKH) disease, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and multiple evanescent white dot syndrome (MEWDS). These ocular conditions are often transient, with a vast majority of patients experiencing improvement after steroid intervention. To date, numerous cases of vaccine-induced uveitis have been reported. This study analyzed the correlation between antiviral vaccines, including the hepatitis B virus (HBV), human papillomavirus (HPV), measles–mumps–rubella (MMR), varicella zoster virus (VZV), and influenza vaccines, and different manifestations of uveitis. This is the first comprehensive study to offer a detailed analysis of uveitis types induced by antiviral vaccines. Through an extensive database search, we found a particularly strong link between influenza vaccines, followed by VZV and HPV vaccines. While anterior uveitis is common, conditions such as APMPPE, MEWDS, and VKH are particularly notable and merit careful consideration in clinical practice. Corticosteroid treatment was effective; however, half of the observed patients did not achieve full recovery, indicating potentially prolonged effects of the vaccine.

At present, the world is at the tipping point of the outbreak of mpox. The World Health Organization has declared the current mpox outbreak a ‘public health emergency of international concern’. Mpox has been shown to be associated with several ocular manifestations. Given the current state of the mpox outbreak, healthcare providers, particularly ophthalmologists, need to be aware of these ophthalmic symptoms and how to manage them. In this review, we highlight current knowledge on the ocular symptoms of mpox virus (MPXV) infections and how to detect them. In addition, we summarize the treatment strategies for these ocular manifestations of MPXV infections and outline the relationship between vaccination and the ocular symptoms of mpox.

Uveitis is one of the most common ocular complications in people living with the Human immunodeficiency virus (HIV) and can be classified into HIV-induced uveitis, co-infection related uveitis, immune recovery uveitis, and drug-induced uveitis. The introduction of antiretroviral therapy has considerably changed the incidence, diagnosis, and treatment of different types of HIV-related uveitis. Furthermore, the specific immune condition of patients infected with HIV makes diagnosing HIV-related uveitis difficult. Recent studies have focused on the growing prevalence of syphilis/tuberculosis co-infection in uveitis. Simultaneously, more studies have demonstrated that HIV can directly contribute to the incidence of uveitis. However, the detailed mechanism has not been studied. Immune recovery uveitis is diagnosed by exclusion, and recent studies have addressed the role of biomarkers in its diagnosis. This review highlights recent updates on HIV-related uveitis. Furthermore, it aims to draw the attention of infectious disease physicians and ophthalmologists to the ocular health of patients infected with HIV.

Little is known regarding anterior uveitis (AU), the most common ocular disease associated with cytomegalovirus (CMV) infection in immunocompetent populations. CMV AU is highly prevalent in Asia, with a higher incidence in men. Clinically, it manifests mainly as anterior chamber inflammation and elevated intraocular pressure (IOP). Acute CMV AU may resemble Posner–Schlossman syndrome with its recurrent hypertensive iritis, while chronic CMV AU may resemble Fuchs uveitis because of its elevated IOP. Without prompt treatment, it may progress to glaucoma; therefore, early diagnosis is critical to prognosis. Knowledge regarding clinical features and aqueous humor analyses can facilitate accurate diagnoses; so, we compared and summarized these aspects. Early antiviral treatment reduces the risk of a glaucoma surgery requirement, and therapeutic effects vary based on drug delivery. Both oral valganciclovir and topical ganciclovir can produce positive clinical outcomes, and higher concentration and frequency are beneficial in chronic CMV retinitis. An extended antiviral course could prevent relapses, but should be limited to 6 months to prevent drug resistance and side effects. In this review, we have systematically summarized the pathogenesis, clinical features, diagnostic and therapeutic aspects, and immunological mechanisms of CMV AU with the goal of providing a theoretical foundation for early clinical diagnosis and treatment.

Advancement of imaging technology in retinal diseases provides us more precise understanding and new insights into the diseases’ pathologies. Diabetic retinopathy (DR) is one of the leading causes of sight-threatening retinal diseases worldwide. Colour fundus photography and fluorescein angiography have long been golden standard methods in detecting retinal vascular pathology in this disease. One of the major advancements is macular observation given by optical coherence tomography (OCT). OCT dramatically improves the diagnostic quality in macular edema in DR. The technology of OCT is also applied to angiography (OCT angiograph: OCTA), which enables retinal vascular imaging without venous dye injection. Similar to OCTA, in terms of their low invasiveness, single blue color SLO image could be an alternative method in detecting non-perfused areas. Conventional optical photography has been gradually replaced to scanning laser ophthalmoscopy (SLO), which also make it possible to produce spectacular ultra-widefield (UWF) images. Since retinal vascular changes of DR are found in the whole retina up to periphery, it would be one of the best targets in UWF imaging. Additionally, evolvement of artificial intelligence (AI) has been applied to automated diagnosis of DR, and AI-based DR management is one of the major topics in this field. This review is trying to look back on the progress of imaging of DR comprehensively from the past to the present.

Myopia is a global health issue, and the prevalence of high myopia has increased significantly in the past five to six decades. The high incidence of myopia and its vision-threatening course emphasize the need for automated methods to screen for high myopia and its serious form, named pathologic myopia (PM). Artificial intelligence (AI)-based applications have been extensively applied in medicine, and these applications have focused on analyzing ophthalmic images to diagnose the disease and to determine prognosis from these images. However, unlike diseases that mainly show pathologic changes in the fundus, high myopia and PM generate even more data because both the ophthalmic information and morphological changes in the retina and choroid need to be analyzed. In this review, we present how AI techniques have been used to diagnose and manage high myopia, PM, and other ocular diseases and discuss the current capacity of AI in assisting in preventing high myopia.

HTLV-1 uveitis (HU) is the third clinical entity to be designated as an HTLV-1-associated disease. Although HU is considered to be the second-most frequent HTLV-1-associated disease in Japan, information on HU is limited compared to that on adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy (HAM). Recent studies have addressed several long-standing uncertainties about HU. HTLV-1-related diseases are known to be caused mainly through vertical transmission (mother-to-child transmission), but emerging HTLV-1 infection by horizontal transmission (such as sexual transmission) has become a major problem in metropolitan areas, such as Tokyo, Japan. Investigation in Tokyo showed that horizontal transmission of HTLV-1 was responsible for HU with severe and persistent ocular inflammation. The development of ATL and HAM is known to be related to a high provirus load and hence involves a long latency period. On the other hand, factors contributing to the development of HU are poorly understood. Recent investigations revealed that severe HU occurs against a background of Graves’ disease despite a low provirus load and short latency period. This review highlights the recent knowledge on HU and provides an update on the topic of HU in consideration of a recent nationwide survey.