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 Animals with spontaneous tumors have largely been replaced by engrafted and genetically engineered models.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: Sodium iodate (SI) is a chemical widely applied to induce retina degeneration in animal models. SI treatment caused formation of rosettes/folds in the outer nuclear layer (ONL) of the rat retina, but it was previously unclear whether SI also forms rosettes in mice. In addition, SI induced retina degeneration was never addressed in non-separate sclerochoroid/retina pigment epithelium/retina whole mount. Here we displayed features of retina degeneration including rosette formation in mice and developed a morphological analytic assessment using sclerochoroid/retina pigment epithelium/retina whole mounts.
Methods: SI was intraperitoneally injected in Sprague-Dawley (SD) rats and C57BL/6J mice using a single dose (50 mg/kg) or with a dose range (10 to 50 mg/kg) in BALB/C mice. Rat retinas were investigated up to 2-week post-injection by histology and whole mounts, and mouse retinas were investigated up to 3-week post-injection by histology, fluorescent staining of sections and/or sclerochoroid/retina pigment epithelium/retina whole mounts for the morphological evaluations of the SI-induced retina damage.
Results: SI-induced retina damage caused photoreceptor (PR) degeneration and rosettes/folds formation, as well as retina pigment epithelium degeneration and inward migration. It displayed mixed nuclei from choroid to PRs, due to layer disorganization, as shown by single horizontal images in the sclerochoroid/retina pigment epithelium/retina whole mounts. Measurement of the PR rosette area induced by SI provided a quantitative, morphological evaluation of retina degeneration.
Conclusions: The method of non-separate sclerochoroid/retina pigment epithelium/retina whole staining and mount allows us to observe the integral horizontal view of damage from sclera to PR layers, which cannot be addressed by using sectioned and separate whole mount methods. This method is applicable for morphological evaluation of retina damage, especially in the subretinal layer.
Abstract: Submacular haemorrhage (SMH) is a sight threatening complication that can occur in exudative age related macular degeneration (AMD), but has been described to occur more frequently in eyes with polypoidal choroidal vasculopathy (PCV). Left untreated, SMH carries a grave visual prognosis. Thus, expedient diagnosis and effective management of this complication is of paramount importance. The treatment strategies for SMH include (I) displacement of blood from the fovea, usually by injection of an expansile gas; (II) pharmacologic clot lysis such as with recombinant tissue plasminogen activator (rtPA); and (III) treatment of the underlying choroidal neovascularization (CNV) or PCV, such as with anti-vascular endothelial growth factor (anti-VEGF) agents. These three strategies have been employed in isolation or in combination, some concurrently and others in stages. rtPA has demonstrable effect on the liquefaction of submacular clots but there are remaining uncertainties with regards to the dose, safety and the timing of initial and repeat treatments. Potential side effects of rtPA include retinal pigment epithelial toxicity, increased risk of breakthrough vitreous haemorrhage and systemic toxicity. In cases presenting early, pneumatic displacement alone with anti-VEGF may be sufficient. Anti-VEGF monotherapy is a viable treatment option particularly in patients with thinner SMH and those who are unable to posture post pneumatic displacement.
Background and Objective: Subthreshold laser therapy has emerged as a therapeutic alternative to traditional laser photocoagulation for certain ophthalmic diseases including central serous chorioretinopathy (CSCR), diabetic macular edema (DME), macular edema secondary to branch retinal vein occlusion (BRVO), and age-related macular degeneration (AMD). The objective of this paper is to review and discuss the clinical applications of subthreshold laser and the mechanisms of different subthreshold laser techniques including subthreshold micropulse laser (SMPL), selective retina therapy (SRT), subthreshold nanosecond laser (SNL), endpoint management (EpM), and transpupillary thermotherapy (TTT).
Methods: A narrative review of English literature and publicly available information published before November 2021 from literature databases and computerized texts. We discuss the currently available subthreshold laser systems and the advancements made to perform different subthreshold laser techniques for various ophthalmic diseases. We highlight various clinical studies and therapeutic techniques that have been conducted to further understand the effectiveness of subthreshold laser in the clinical setting. We conclude the article by covering emerging subthreshold laser systems that are currently being developed for future clinical use. The PubMed database was utilized for peer-reviewed articles and pertinent information on subthreshold systems was cited from publicly available online websites covering specific systems.
Key Content and Findings: Various subthreshold laser systems have been developed to treat certain retinal diseases. Several systems are currently in development for future clinical applications.
Conclusions: While conventional laser photocoagulation has been effective in treating various retinal diseases, subthreshold laser systems aim to provide a therapeutic effect without visible signs of damage to the underlying tissue. This technology may be particularly effective in treating macular disorders. Further clinical studies are needed to evaluate their role in the management of retinal diseases.
Background and Objective: Vitreoretinal surgery requires fine micro-surgical training and handling of delicate tissue. To aid in the training of residents and fellows, unique educational modalities exist to help facilitate the development of these microsurgical skills. From virtual simulators to artificial eye models, simulation of the posterior segment has gained an increased focus in vitreoretinal surgical training programs. Development of surgical curricula for vitreoretinal training and attainment of surgical milestones has been a key component in integrating these educational training modalities. We will explore various simulators, eye models, and potential rubrics and discuss unique ways each may help and complement one another to train future vitreoretinal surgeons.
Methods: We conducted a systematic PubMed search of various review studies (from publications in English ranging from January 1978 to December 2020) discussing surgical simulators, eye models, and surgical rubrics for vitreoretinal surgery and their potential impacts upon training.
Key Contents and Findings: Our review assesses the benefits and applicability of various simulators, eye models, and surgical rubrics upon training.
Conclusions: Utilization of vitreoretinal surgical training tools may aid in complementing the hands-on surgical training experience for vitreoretinal surgical fellows. By using simulators and rubrics, we may better be able to standardize training for reaching vitreoretinal surgical milestones and providing adequate feedback to improve surgical competency and ultimately patient outcomes.
