Abstract: Statins are used widely to treat hypercholesterolemia and atherosclerotic cardiovascular disease. They have inflammatory and immunomodulatory effects potentially useful for managing systemic autoimmune diseases such as rheumatoid arthritis, lupus erythematosus and multiple sclerosis. Statins also have anti-oxidative and large-vessel endothelial supportive properties that occur independent of their lipid-lowering effects. Additionally, statins can suppress macrophage and microglial activation responsible for initiating inflammatory cytokine release. More than forty percent of adults aged 65 years or older use statins in the United States and Australia, a prevalence that increases with age. The effects of statin usage on ophthalmic practice are probably underrecognized. Cardiovascular disease and age-related macular degeneration (AMD) share common risk factors, consistent with the “vascular model” of AMD pathogenesis that implicates impaired choroidal circulation in Bruch’s membrane lipoprotein accumulation. AMD has a complex multifactorial pathogenesis involving oxidative stress, choroidal vascular dysfunction, dysregulated complement-cascade-mediated inflammation and pro-inflammatory and pro-angiogenic growth factors. Many of these components are hypothetically amenable to the primary (cholesterol lowering) and secondary (anti-inflammatory, anti-oxidative, anti-vasculopathy) effects of statin use. Experimental studies have been promising, epidemiological trails have produced conflicting results and three prospective clinical trials have been inconclusive at demonstrating the value of statin therapy for delaying or preventing AMD. Cumulative evidence to date has failed to prove conclusively that statins are beneficial for preventing or treating AMD.

Abstract: In developed countries, age-related macular degeneration (AMD) is the main cause of visual impairment in the elderly. Though the etiology of AMD is still unclear, it has been well understood that vascular endothelial growth factor (VEGF) is involved in the development of aberrant vasculature that represents the neovascular AMD (nAMD). Hence, VEGF inhibition is a more effective way to control nAMD. Pegaptanib, ranibizumab, and aflibercept are three drugs approved by the US Food and Drug Administration (FDA) to treat nAMD. Bevacizumab (an anti-VEGF medication comparable to ranibizumab) is already widely used off label. Existing anti-VEGF medicines are made up of antibodies or pieces of antibodies. Synthetic designed ankyrin repeat proteins (DARPins) imitate antibodies introduced recently by evolutions in bioengineering technology. These agents are designed to have high specificity and affinity to a specific target, smaller molecular size, and better tissue penetration, making them more stable and longer-acting at less concentration. Abicipar pegol (Allergan, Dublin, Ireland) is a DARPin that interlocks all VEGF-A isoforms. It has a greater affinity for VEGF and a longer intraocular half-life than ranibizumab, making it a feasible anti-VEGF agent. This review describes the properties and efficacy of abicipar, the new anti-VEGF agent, in clinical practice, which aims to improve outcomes, safety, and treatment burden of nAMD.

Abstract: The purpose of this article is to review current literature and data regarding treatment options for age-related macular degeneration (AMD) related to mitochondrial therapy. This article considers the presence of flavoprotein fluorescence as a potential biomarker to test the effectiveness of the treatments. We focus primarily on two major mitochondrial targets, nuclear factor erythroid 2-related factor (NFE2L2) and PGC-1α, that function in controlling the production and effects of reactive oxidative species (ROS) directly in the mitochondria. PU-91 is an FDA approved drug that directly targets and upregulates PGC-1α in AMD cybrid cell lines. Although neither NFE2L2 nor PGC1-α have yet been tested in clinical trials, their effects have been studied in rodent models and offer promising results. MTP-131, or elamipretide^?, and metformin are two drugs in phase II clinical trials that focus on the treatment of advanced, non-exudative AMD. MTP-131 functions by associating with cardiolipin (CL) whereas metformin targets adenosine-monophosphate protein kinase (AMPK) in the mitochondria. The current results of their clinical trials are elucidated in this article. The molecular targets and drugs reviewed in this article show promising results in the treatment of AMD. These targets can be further pursued to improve and refine treatment practices of this diagnosis.

Abstract: Intraocular foreign body residue following ophthalmic surgery is rare but may cause severe postoperative occult inflammation. In some cases, small foreign bodies located in the anterior chamber angle may be missed by follow-up ultrasound biomicroscopy (UBM). We report the case of an elderly female whose right eye was injured by a nail and received corneal repair surgery in our hospital. Eleven days post-surgery, we found a mobile, short, translucent, rod-shaped foreign body in the upper corner of the right eye and another in the iris root at 7 o’clock. Two months post-surgery, the patient consulted a doctor due to right eye redness, pain, and vision loss, which was ultimately shown to be associated with foreign body residue resulting in a delayed postoperative inflammatory response. The patient was cured by surgeries and active anti-inflammatory and anti-infection treatments, but the final diagnosis of the patient was infectious endophthalmitis misdiagnosed as uveitis, which worths our consideration. We also review relevant literature on the differentiation of postoperative infectious endophthalmitis from noninfectious uveitis. It’s a reminder that patients with delayed endophthalmitis after open ocular trauma should not exclude the possibility of intraocular foreign bodies. As well clinicians can distinguish infectious endophthalmitis from uveitis by needle aspiration biopsy or vitrectomy for microbial culture in order to determine the need for antibiotic treatment.

Abstract: The most prominent causes of loss of vision in individuals over 50 years include age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR). While it is important to screen for these diseases effectively, current eye care is not properly doing so for much of the population, resulting in unfortunate visual disability and high costs for patients. Innovative functional testing can be unified with other screening methods for a more robust and safer screening and prediction of disease. The goal in the creation of functional testing modalities is to develop highly sensitive screening tests that are easy to use, accessible to all users, and inexpensive. The tests herein are deployed on an iPad with easily understood and intuitive instructions for rapid, streamlined, and automatic administration. These testing modalities could become highly sensitive screenings for early detection of potentially blinding diseases. The applications from our collaborators at AMA Optics include a cone photostress recovery test for detection of AMD and diabetic macular edema (DME), brightness balance perception for optic nerve dysfunction and especially glaucoma, color vision testing which is a broad screening tool, and visual acuity test. Machine learning with the combined structural and functional data will optimize identification of disease and prediction of outcomes. Here, we review and assess various tests of visual function that are easily administered on a tablet for screening in primary care. These user-friendly and simple screening tests allow patients to be identified in the early stages of disease for referral to specialists, proper assessment and treatment.

Abstract: Pediatric glaucoma is a potentially sight-threatening disease and is considered the second leading cause of treatable childhood blindness. Pediatric glaucoma is a clinical entity including a wide range of conditions: primary congenital glaucoma, glaucoma secondary to ocular (e.g., aniridia, Peter’s anomaly), or systemic disease (e.g., Sturge Weber) and glaucoma secondary to acquired condition (pseudophakic, traumatic, uveitic glaucoma). The treatment algorithm of childhood glaucoma is a step-by-step approach, often starting with surgery, as in primary congenital glaucoma cases. Medical therapy is also crucial in the management of pediatric glaucoma. Here we reported the results of the randomized, controlled, clinical trials carried out in children treated with topical anti-glaucoma drugs. It is worth knowing that prostaglandin analogues showed an excellent systemic safety profile, while serious systemic events have been reported in children taking topical beta-blockers. Angle surgery is the first surgical option in patients diagnosed with primary congenital glaucoma, with ab interno and ab externo approaches showing similar outcomes. Trabeculectomy in children can be troublesome, as mitomycin C (MMC) can lead to bleb complications and a higher endophthalmitis rate than in adults. Glaucoma drainage devices (GDD) are no longer a last resort and can be considered a suitable option for the management of uncontrolled pediatric glaucoma after angle surgery failure.

Abstract: Our increase in knowledge of the pathophysiology of non-infectious uveitis (NIU) and other immune-mediated diseases has been mirrored over the last two decades by the expansion of therapeutic options in the realm of immunosuppressive medications. Principal among these advances is the emergence of biologics, which offer the promise of targeted therapy and the hope of reduced toxicity when compared to corticosteroids and “standard” immunosuppression. Among the biologics, monoclonal antibodies blocking tumor necrosis factor alpha (TNF-α) have been shown to be a very effective therapeutic target for uveitis and many associated systemic inflammatory diseases. Multiple TNF blockers have shown benefit for uveitis, and in 2016, adalimumab became the first biologic and non-corticosteroid immunosuppressive to obtain Food and Drug Administration (FDA) approval in the treatment of NIU. Although effective, TNF blockers are not universally so, and safety concerns such as infection and demyelinating disease must be carefully considered and ruled out prior to their use, especially in patients with intermediate uveitis with which multiple sclerosis is a known association. Ongoing study has identified novel targets for regulation in the treatment of immune-mediated and inflammatory diseases. Interferons, interleukin and Janus kinase inhibitors in addition to antibodies targeting T cell and B cell activation highlight the expanding field of treatment modalities in NIU. Ongoing study will be required to better determine the safety and efficacy of biologics in the armamentarium of immunosuppressive treatments for NIU.