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Intravitreal (IVT) drug delivery now surpasses cataract surgery as the most commonly performed ophthalmic procedure worldwide. In 2020, nearly 23 million IVT injections were given globally,1 with m...

Uveitis refers to a diverse group of several dozen disorders characterized and connected by the shared presence of intraocular inflammation.1,2 While the etiology of infectious uveitis is often cle...

Tocilizumab (TCZ; Actemra®; Roche/Genentech in the US; Chugai Pharmaceutical Co. in Japan) is a recombinant, humanized monoclonal antibody directed against the interleukin-6 (IL-6) receptor and cur...

To report the clinical findings, anatomical features, and treatment outcomes in subjects with ocular tuberculosis (OTB) at 24 months in the Collaborative Ocular Tuberculosis Study (COTS)-1. Of the ...

Epstein-Barr Virus (EBV), also known as Human HerpesVirus-4 (HHV-4), is a γ-type herpesvirus with a global infection prevalence of over 95%.1,2 Infection, which occurs nasopharyngeally via either a...

Immune checkpoints are endogenous, inhibitory, receptor-mediated regulators of the immune system known to be central to controlling the duration and extent of normal immune responses, thereby maint...

Ultra-wide-field (UWF) imaging has been used clinically in retina practices for nearly two decades to achieve rapid, single-frame photographic access to the mid- and far-retinal periphery.1–5 These...

To review the systemic and ocular manifestations of specific emergent viral infectious diseases relevant to the ophthalmologist with particular emphasis on anterior uveitis Methods: Review of literature.Arboviral diseases are among the most important emergent and resurgent human infections, occurring mostly in tropical and subtropical zones, but appearing in virtually all regions of the world as a result of climate change, travel, and globalization. Arboviral infections are transmitted to humans by the bite of hematophagous arthropods, mainly mosquitoes. Systemic disease may range from asymptomatic to life-threatening. A wide variety of ocular manifestations, including uveitis, has been reported in association with these emerging viral diseases. Numerous viruses other than arboviruses also have been recently recognized as a potential cause of uveitis.Proper clinical diagnosis of any emerging infectious disease is based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. The diagnosis is usually confirmed by detection of virus-specific DNA or antivirus antibodies in serum.

Varicella Zoster Virus (VZV)-associated uveitis1–3 may occur in utero; during primary systemic infection – most common in children with chickenpox; or following viral reactivation along the first, ...

PURPOSE: To analyze the role of polymerase chain reaction (PCR) of ocular fluids in management of tubercular (TB) anterior, intermediate, posterior, and panuveitis. METHODS: In Collaborative Ocular Tuberculosis Study (COTS)-1 (25 centers, n = 962), patients with TB-related uveitis were included. 59 patients undergoing PCR of intraocular fluids (18 females; 53 Asian Indians) were included. RESULTS: 59 (6.13%) of COTS-1 underwent PCR analysis. PCR was positive for Mycobacterium TB in 33 patients (23 males; all Asian Indians). 26 patients were PCR negative (18 males). Eight patients with negative PCR had systemic TB. Anti-TB therapy was given in 18 negative and 31 PCR cases. At 1-year follow-up, five patients with positive PCR (15.15%) and three with negative PCR (11.54%) had persistence/worsening of inflammation. CONCLUSIONS: Data from COTS-1 suggest that PCR is not commonly done for diagnosing intraocular TB and positive/negative results may not influence management or treatment outcomes in the real world scenario.

December 2021 will mark the second anniversary of initial reports from Wuhan, China, of human infection by Severe Acute Respiratory Distress Syndrome Coronavirus-2 (SARS-CoV-2), a novel positive-se...

This coming year will mark the 40th anniversary of the first reports by the Centers for Disease Control (CDC) of the otherwise rare skin cancer Kaposi sarcoma (KS) and an equally uncommon form of p...

Human leukocyte antigen (HLA)-B27-associated anterior uveitis (AU) is the most commonly diagnosed form of AU and represents the largest entity of non-infectious uveitis around the world. The most typical ocular manifestation associated with HLA-B27 consists of unilateral AU of acute onset. The HLA-B27-associated acute AU represents a distinct clinical entity occurring typically in young adults between the ages of 20 and 40 years. HLA-B27-associated acute AU is typically unilateral and lasts usually several weeks and diminishes within 3 months in the majority of patients. The anterior chamber shows typically severe cellular reaction and flare, as well as a fibrinous exudate. Frequently, posterior synechiae are formed and occasionally hypopyon is present. The pattern of the disease is recurrent with a full remission between the attacks. Intraocular pressure during active periods is typically low due to inflammation of ciliary body and decreased aqueous production. Less typical presentations are also recognized and include the development of chronic inflammation, posterior segment involvement, episcleritis, and scleritis. An isolated retinal vasculitis in HLA-B27-positive patients may develop, mostly in those with inflammatory bowel disease. Chronic AU, which may be either unilateral or bilateral affects up to 20% of patients. Ocular complications of HLA-B27-associated AU are diverse and include commonly posterior synechiae, cataract, glaucoma and/or hypotony. The visual outcome and complications of HLA-B27-associated AAU are frequently being compared with HLA B27-negative patients with AU and show that the prognosis of HLA-B27-associated uveitis is rather favorable, as

Ocular hypertension (OHT) and glaucoma are common and often serious complications of uveitis.1–9 Cross-sectional clinic-based studies have suggested a prevalence of OHT among uveitis referral patie...

The choroidal vasculature is the primary source of both oxygen and blood-borne nutrients to the outer retina, including the retinal pigment epithelium (RPE), photoreceptors, and otherwise avascular...

Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disorder characterized in its complete form by the occurrence of bilateral uveitis accompanied by dermatologic as well as neurologic or auditory ...

Mooren’s ulcer (MU) is an inflammatory peripheral ulcerative keratopathy that occurs most commonly in the developing world. Recent evidence supports the notion that autoimmune mechanisms are involved in the pathogenesis of this disease. Patients with MU typically develop painful, progressive peripheral ulceration of the cornea that, if untreated, can lead to corneal perforation and blindness. Risk factors for the development of MU include HLA-DR17 haplotype expression, prior corneal surgery or trauma, and hookworm infestation. A thorough ocular and systemic history and clinical examination, together with directed laboratory testing, should be carried out to rule out other causes of corneal ulceration, including both infectious keratitis and peripheral ulcerative keratitis secondary to an underlying systemic autoimmune disease. Treatment of MU is often challenging, but typically includes local and/or systemic corticosteroids. Noncorticosteroid immunosuppressive agents, conjunctival resection or advancement...

Necrotizing herpetic retinitis (NHR) is an uncommon, but serious infection of the retina caused by one of the human herpesviruses (HHV).1,2 In immunocompetent patients, most cases of NHR result fro...

Since their introduction more than 15 years ago, tumor necrosis factor-alpha (TNF-α) inhibitors have assumed an important role in the management of moderate to severe systemic autoimmune disease, i...

Pegaptanib sodium is a selective RNA aptamer that inhibits the 165 isoform of vascular endothelial growth factor (VEGF), a key regulator of pathological vascular growth and permeability and a contributor to vision loss in diseases such as age-related macular degeneration (AMD), diabetic retinopathy and retinal vein occlusion. The development of pegaptanib represented an important achievement in that it was both the first approved anti-VEGF agent for the treatment of ocular disease and the first clinically validated aptamer therapeutic. The safety and efficacy of pegaptanib for the treatment of neovascular AMD were established in the VEGF Inhibition Study in Ocular Neovascularization (VISION) trials. Investigations into the use of pegaptanib have now been expanded to include diabetic macular edema, macular edema secondary to central retinal vein occlusion and other ocular vascular diseases. Pegaptanib is also being used investigationally in combination with other agents.

The treatment of noninfectious uveitis traditionally has involved the use of local and systemic corticosteroids in the short term,1,2 together with systemic noncorticosteroid immunosuppressive agen...

NF-kappaB corresponds to an inducible eukaryotic transcription factor complex that is negatively regulated in resting cells by its physical assembly with a family of cytoplasmic ankyrin-rich inhibitors termed IkappaB. Stimulation of cells with various proinflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), induces nuclear NF-kappaB expression. TNF-alpha signaling involves the recruitment of at least three proteins (TRADD, RIP, and TRAF2) to the type 1 TNF-alpha receptor tail, leading to the sequential activation of the downstream NF-kappaB-inducing kinase (NIK) and IkappaB-specific kinases (IKKalpha and IKKbeta). When activated, IKKalpha and IKKbeta directly phosphorylate the two N-terminal regulatory serines within IkappaB alpha, triggering ubiquitination and rapid degradation of this inhibitor in the 26S proteasome. This process liberates the NF-kappaB complex, allowing it to translocate to the nucleus. In studies of NIK, we found that Thr-559 located within the activation loop of its kinase domain regulates NIK action. Alanine substitution of Thr-559 but not other serine or threonine residues within the activation loop abolishes its activity and its ability to phosphorylate and activate IKKalpha. Such a NIK-T559A mutant also dominantly interferes with TNF-alpha induction of NF-kappaB. We also found that ectopically expressed NIK both spontaneously forms oligomers and displays a high level of constitutive activity. Analysis of a series of NIK deletion mutants indicates that multiple subregions of the kinase participate in the formation of these NIK-NIK oligomers. NIK also physically assembles with downstream IKKalpha; however, this interaction is mediated through a discrete C-terminal domain within NIK located between amino acids 735 and 947. When expressed alone, this C-terminal NIK fragment functions as a potent inhibitor of TNF-alpha-mediated induction of NF-kappaB and alone is sufficient to disrupt the physical association of NIK and IKKalpha. Together, these findings provide new insights into the molecular basis for TNF-alpha signaling, suggesting an important role for heterotypic and possibly homotypic interactions of NIK in this response.

The fact that both hemifacial spasm and pain can be caused by vascular compression of the nerve has been known anatomically for some time. It was not until the use of the MRI which allowed us to look in the posterior fossa that we can now identify this anatomical variant without doing invasive studies. The paper reports on three cases from the author's series of ten such cases.

There are estimated to be over 300 million visually impaired people in the world today. Approximately 45 million of these, or one in seven, are blind [101], defined by the WHO as persons with eithe...