Abstract: Age-related macular degeneration (ARMD), one of the most common causes of blindness, should be considered more due to its exponential increase in the coming 20 years as a result of increasing the age of the population. Whereas more recent studies offered newer scaling systems for ARMD, traditionally it is classified as the early and late stages. The main injury in this disease occurred in retinal pigment epithelium (RPE) and the retina. RPE cells have a crucial role in hemostasis and supporting photoreceptors. In the early stages, damages to RPE are minimal and mainly no treatment is needed because most patients are asymptomatic. However, in the late stages, RPE impairment may lead to the invasion of choroidal vessels into the retina. Although anti-angiogenic agents can inhibit this abnormal growth of blood vessels, they cannot stop it completely, and finally, total loss of retinal cells may occur (geographical atrophy). Since this prevalent disease has not had any cure yet, the concept of substituting the RPE cells should be considered. Repairing the injury to central nervous system cells is almost impossible because the regenerative capacity of these cells is limited. Recently, the use of regenerative substitutes has been suggested to replace damaged tissues. Amniotic membrane (AM) has been raised as a suitable substitute for damaged RPE cells due to all of its unique properties: pluripotency, anti-angiogenic effect, and anti-inflammatory effect. Based on the few studies that have been published so far, it seems that the use of this membrane in the treatment of ARMD can be helpful, but more studies are needed.
Abstract: Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. AMD most commonly affects older individuals and is characterized by irreversible degeneration of the retinal pigment epithelium and neurosensory retina. Currently, there are limited treatment options for dry AMD outside of lifestyle modification and nutrient supplementation. Risuteganib [Luminate (ALG-1001), Allegro Ophthalmics, CA, USA] is an intravitreally administered inhibitor of integrin heterodimers αVβ3, αVβ5, α5β1, and αMβ2. It is currently undergoing clinical trials for the treatment of dry AMD and diabetic macular edema (DME). Preclinical studies have shown that risuteganib has an effect on the pathways for angiogenesis, inflammation, and vascular permeability. Ongoing clinical trials have had promising results showing improvements in patient best corrected visual acuity (BCVA) and reduced central macular thickness measured by optical coherence tomography (OCT). There is a pressing need for treatments for dry AMD and while risuteganib appears to have a potential benefit for patients, more data are needed before one can truly evaluate its efficacy. This narrative review provides a concise summary of the most up to date data regarding the proposed mechanism of action of risuteganib in the treatment of nonexudative AMD and DME as well as the results from recent phase 1 and phase 2 clinical trials.
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: 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: Animal models are crucial for the study of tumorigenesis and therapies in oncology research. Though rare, uveal melanoma (UM) is the most common intraocular tumor and remains one of the most lethal cancers. Given the limitations of studying human UM cells in vitro, animal models have emerged as excellent platforms to investigate disease onset, progression, and metastasis. Since Greene’s initial studies on hamster UM, researchers have dramatically improved the array of animal models. Animals with spontaneous tumors have largely been replaced by engrafted and genetically engineered models. Inoculation techniques continue to be refined and expanded. Newer methods for directed mutagenesis have formed transgenic models to reliably study primary tumorigenesis. Human UM cell lines have been used to generate rapidly growing xenografts. Most recently, patient-derived xenografts have emerged as models that closely mimic the behavior of human UM. Separate animal models to study metastatic UM have also been established. Despite the advancements, the prognosis has only recently improved for UM patients, especially in patients with metastases. There is a need to identify and evaluate new preclinical models. To accomplish this goal, it is important to understand the origin, methods, advantages, and disadvantages of current animal models. In this review, the authors present current and historic animal models for the experimental study of UM. The strengths and shortcomings of each model are discussed and potential future directions are explored.
Background: Retinopathy of prematurity (ROP) is considered as the most common reason for blindness in children, particularly in preterm infants. The disease is characterized by the dysregulation of angiogenic mechanisms due to preterm birth, leading ultimately to vascular abnormalities and pathological neovascularization (NV). Retinal detachment and vision loss could represent a concrete risk connected to the most severe forms of ROP, also characterized by inflammation and retinal cell death.
Methods: During the last decades, many animal models of oxygen-induced retinopathy (OIR) have been recognized as useful tools to study the mechanisms of disease, since they reproduce the hallmarks typical of human ROP. Indeed, modulation of retinal vascular development by exposure to different oxygen protocols is possible in these animals, reproducing the main pathological phenotypes of the disease. The easy quantification of abnormal NV and the possibility to perform electrophysiologic, histological and molecular analyses on these models, make OIR animals a fundamental instrument in studying the pathophysiology of ROP and the effects of novel treatments against the disease.
Discussion: Here, the most commonly used OIR protocols in rodents, such as mice and rats, are described as well as the main pathological outcomes typical of these models. Despite their limitations and variables which should be considered whilst using these models, OIR models display several characteristics which have also been confirmed in human patients, validating the usefulness of such animals in the pre-clinical research of ROP.
Background and Objective: Subthreshold laser technologies and their applications in ophthalmology have greatly expanded in the past few decades. Initially used for retinal diseases such as central serous chorioretinopathy and diabetic macular edema, subthreshold lasers have recently shown efficacy in the treatment of various types of glaucoma. Our primary objectives are to review the clinical applications of subthreshold laser in the context of glaucoma treatment and discuss the mechanisms of different subthreshold laser techniques, including subthreshold selective laser trabeculoplasty (SSLT), micropulse laser trabeculoplasty (MLT), pattern-scanning laser trabeculoplasty (PSLT), titanium laser trabeculoplasty (TLT), and micropulse transscleral cyclophotocoagulation (MP-TSCPC).
Methods: This was a narrative review compiled from literature of PubMed and Google Scholar. The review was performed from March 2021 to October 2021 and included publications in English. We also included information from web pages to cover details of relevant laser systems. We discuss the history of subthreshold laser, recent advancements in subthreshold techniques, and commercially available systems that provide subthreshold capabilities for glaucoma. We highlight basic science and clinical studies that deepen the understanding of treatment mechanisms and treatment effectiveness in the clinical setting respectively. We review commonly used parameters for each technique and provide comparisons to conventional treatments.
Key Content and Findings: We found five distinct types of subthreshold laser used in the management of glaucoma. Numerous subthreshold laser systems are commercially available and can provide this treatment. Therefore, understanding the differences between subthreshold techniques and laser systems will be critical in utilizing subthreshold laser in the clinical setting.
Conclusions: Traditional laser trabeculoplasty (LT) and cyclophotocoagulation (CPC) have shown effectiveness in the treatment of various types of glaucoma but are associated with visible damage to the underlying tissue and adverse effects. Subthreshold laser systems aim to provide the therapeutic effect found in traditional lasers, while minimizing unwanted treatment related effects. Further clinical studies are needed to evaluate the role of subthreshold lasers in the management of glaucoma.
