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: 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: 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.

Abstract: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, and juvenile idiopathic associated uveitis (JIA-U) is the most frequently noted extra-articular manifestation. JIA-U can present asymptomatically and lead to ocular complications, so regular screening and monitoring are needed to prevent potentially sight-threatening sequelae. Topical glucocorticoids such as prednisolone acetate are usually the first line of treatment for anterior uveitis associated with JIA-U, but long-term use may be associated with cataract, ocular hypertension and glaucoma. Disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate allow tapering of the corticosteroids to prevent long-term complications. Biologic therapies have been increasingly used as targeted therapies for JIA-U, particularly monoclonal antibodies targeting the proinflammatory cytokine TNF-α such as adalimumab and infliximab. One recent, multicenter, prospective, randomized clinical trial provided evidence of the efficacy of adalimumab with methotrexate for JIA-U compared to methotrexate alone. Another clinical trial studying the interleukin-6 inhibitor tocilizumab for JIA-U showed promise in tapering topical corticosteroids. Additionally, JAK inhibitors are emerging biologic therapies for JIA-U in patients refractory to TNF-α inhibitors, with a clinical trial assessing the efficacy of baricitinib for JIA-U underway. While clinical trials on these novel biologics are limited, further investigation of these agents may provide additional therapeutic options for JIA-U.

Abstract: Glaucoma is a group of eye diseases that seriously threaten human visual health. Increased intraocular pressure is the main clinical manifestation and diagnostic basis of glaucoma and is directly related to increased resistance to aqueous circulation channels. The trabecular meshwork (TM) is a multi-layer spongy tissue that filters aqueous humor. Its structure changes and the filtering capacity decreases, leading to an increase in intraocular pressure. Surgical methods for TM are constantly updated. Compared with traditional glaucoma surgical techniques, such as external trabeculectomy, the development of a new surgical technique—minimally invasive glaucoma surgery (MIGS)—enables the operation to reduce intraocular pressure efficiently while further reducing damage to the eye. MIGS achieves the purpose of surgery mainly by optimizing the TM outflow pathway, uveoscleral outflow pathway, and subconjunctival outflow pathway. A new surgical instrument, the Kahook Dual Blade, appears to optimize the TM outflow pathway in the surgical technique. The Kahook Dual Blade is a new type of angle incision instrument. Because of its unique double-edged design, in the process of goniotomy, it can effectively reduce the damage to the anterior chamber angle structure and accurately remove the appropriate amount of TM so that the aqueous humor can flow out smoothly. Kahook Dual Blade goniotomy has the advantages of avoiding complications and foreign body sensation caused by intraocular implants. The operation time is relatively short, the surgical technique is easy to master, and the TM resection scope can be determined based on the patient’s condition. It can be used to treat some clinically meaningful glaucoma. This article is organized as follows. We present the following article following the Narrative Review reporting checklist.

Abstract: In a comprehensive literature review, PubMed, Embasem and Web of Science were searched for studies examining targeted therapy of ocular malignant melanomas to present and discuss targeted therapy treatment options of ocular tumors, mainly conjunctival and uveal melanoma (UM). Conjunctival malignant melanomas showed similarities in clinical and genetic aspects with cutaneous melanomas. Many therapies with checkpoint inhibitors already established for cutaneous melanomas may be a treatment option for conjunctival malignant melanomas with shared traits. Existing targeted therapies are for example checkpoint inhibitors like pembrolizumab or nivolumab. As a corollary, due to marked differences in clinics and genetics between UMs and conjunctival melanomas (CMs) or cutaneous melanomas, it has remained elusive whether the available possibilities of molecular targeted therapy will be an option for the therapy of metastasizing UMs. Possible novel ways of treating UM are being explored. Fotemustine or the inoculation of dendritic cells with tumorous RNA or sunitinib in combination with cisplatin and or tamoxifen may be used in future to treat UM. While CM are treatable using targeted therapies, UM have not been researched enough to find working targeted therapy options. Further research has to be done in order to find acceptable treatment options.