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: Dramatic advances in retinal imaging technology over the last two decades have significantly improved our understanding of the natural history and pathophysiology of non-neovascular age-related macular degeneration (AMD). Currently, aside from micronutrient supplements, there are no proven treatments for non-neovascular or dry AMD. Recently, a number of pharmacological agents have been evaluated or are under evaluation for treatment of patients with end-stage dry AMD manifesting as geographic atrophy (GA). It may preferable, however, to intervene earlier in the disease before the development of irreversible loss of visual function. Earlier intervention would require a more precise understanding of biomarkers which may increase the risk of progression from early and intermediate stages to the late stage of the disease. The development of optical coherence tomography angiography (OCTA) has allowed the layers of the retinal microcirculation and choriocapillaris (CC) to be visualized and quantified. Flow deficits in the CC have been observed to increase with age, particularly centrally, and these flow deficits appear to worsen with development and progression of AMD. As such, OCTA-based CC assessment appears to be a valuable new biomarker in our assessment and risk-stratification of AMD. Alterations in the CC may also provide new insights into the pathophysiology of the disease. Enhancement of choriocapillaris function may also prove to be a target of future therapeutic strategies or as a biomarker to monitor the effectiveness of therapy. As such, CC imaging may be anticipated to be an integral tool in the management of dry AMD.
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.