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.
Background: Soft drusen and basal linear deposit (BLinD) are two forms of the same extracellular lipid rich material that together make up an Oil Spill on Bruch’s membrane (BrM). Drusen are focal and can be recognized clinically. In contrast BLinD is thin and diffusely distributed, and invisible clinically, even on highest resolution OCT, but has been detected on en face hyperspectral autofluorescence (AF) imaging ex vivo. We sought to optimize histologic hyperspectral AF imaging and image analysis for recognition of drusen and sub-RPE deposits (including BLinD and basal laminar deposit), for potential clinical application.
Methods: Twenty locations specifically with drusen and 12 additional locations specifically from fovea, perifovea and mid-periphery from RPE/BrM flatmounts from 4 AMD donors underwent hyperspectral AF imaging with 4 excitation wavelengths (λex 436, 450, 480 and 505 nm), and the resulting image cubes were simultaneously decomposed with our published non-negative matrix factorization (NMF). Rank 4 recovery of 4 emission spectra was chosen for each excitation wavelength.
Results: A composite emission spectrum, sensitive and specific for drusen and presumed sub-RPE deposits (the SDr spectrum) was recovered with peak at 510–520 nm in all tissues with drusen, with greatest amplitudes at excitations λex 436, 450 and 480 nm. The RPE spectra of combined sources Lipofuscin (LF)/Melanolipofuscin (MLF) were of comparable amplitude and consistently recapitulated the spectra S1, S2 and S3 previously reported from all tissues: tissues with drusen, foveal and extra-foveal locations.
Conclusions: A clinical hyperspectral AF camera, with properly chosen excitation wavelengths in the blue range and a hyperspectral AF detector, should be capable of detecting and quantifying drusen and sub-RPE deposits, the earliest known lesions of AMD, before any other currently available imaging modality.
Backgrounds: To assess changes in anterior segment biometry during accommodation using a swept source anterior segment optical coherence tomography (SS-OCT). Methods: One hundred-forty participants were consecutively recruited in the current study. Each participant underwent SS-OCT scanning at 0 and -3 diopter (D) accommodative stress after refractive compensation, and ocular parameters including anterior chamber depth (ACD), anterior and posterior lens curvature, lens thickness (LT) and lens diameter were recorded. Anterior segment length (ASL) was defined as ACD plus LT. Lens central point (LCP) was defined as ACD plus half of the LT. The accommodative response was calculated as changes in total optical power during accommodation. Results: Compared to non-accommodative status, ACD (2.952±0.402 vs. 2.904±0.382 mm, P<0.001), anterior (10.771±1.801 vs. 10.086±1.571 mm, P<0.001) and posterior lens curvature (5.894±0.435 vs. 5.767±0.420 mm, P<0.001), lens diameter (9.829±0.338 vs. 9.695±0.358 mm, P<0.001) and LCP (4.925±0.274 vs. 4.900±0.259 mm, P=0.010) tended to decreased and LT thickened (9.829±0.338 vs. 9.695±0.358 mm, P<0.001), while ASL (6.903±0.279 vs. 6.898±0.268 mm, P=0.568) did not change significantly during accommodation. Younger age (β=0.029, 95% CI: 0.020 to 0.038, P<0.001) and larger anterior lens curvature (β=-0.071, 95% CI: -0.138 to -0.003, P=0.040) were associated with accommodation induced greater steeping amplitude of anterior lens curvature. The optical eye power at 0 and -3 D accommodative stress was 62.486±2.284 and 63.274±2.290 D, respectively (P<0.001). Age was an independent factor of accommodative response (β=-0.027, 95% CI: -0.038 to -0.016, P<0.001). Conclusions: During -3 D accommodative stress, the anterior and posterior lens curvature steepened, followed by thickened LT, fronted LCP and shallowed ACD. The accommodative response of -3 D stimulus is age-dependent.
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.
Abstract: In the early days of deciphering the injured neuronal tissues led to the realization that contrast is necessary to discern the parts of the recovering tissues from the damaged ones. Early attempts relied on available (and often naturally occurring) staining substances. Incidentally, the active ingredients of most of them were small molecules. With the advent of time, the knowledge of chemistry helped identify compounds and conditions for staining. The staining reagents were even found to enhance the visibility of the organelles. Silver impregnation identification of Golgi bodies was discovered in owl optic nerve. Staining reagents since the late 1800s were widely used across all disciplines and for nerve tissue and became a key contributor to advancement in nerve-related research. The use of these reagents provided insight into the organization of the neuronal tissues and helped distinguish nerve degeneration from regeneration. The neuronal staining reagents have played a fundamental role in the clinical research facilitating the identification of biological mechanisms underlying eye and neuropsychiatric diseases. We found a lack of systematic description of all staining reagents, whether they had been used historically or currently used. There is a lack of readily available information for optimal staining of different neuronal tissues for a given purpose. We present here a grouping of the reagents based on their target location: (I) the central nervous system (CNS), (II) the peripheral nervous system (PNS), or (III) both. The biochemical reactions of most of the staining reagents is based on acidic or basic pH and specific reaction partners such as organelle or biomolecules that exists within the given tissue type. We present here a summary of the chemical composition, optimal staining condition, use for given neuronal tissue and, where possible, historic usage. Several biomolecules such as lipids and metabolites lack specific antibodies. Despite being non-specific the reagents enhance contrast and provide corroboration about the microenvironment. In future, these reagents in combination with emerging techniques such as imaging mass spectrometry and kinetic histochemistry will validate or expand our understanding of localization of molecules within tissues or cells that are important for ophthalmology and vision science.
Background and Objective: Intraocular lymphoma (IOL) is a heterogenous category of rare malignancies that are often misdiagnosed and underrecognized. The rarity of IOL impedes clinical research and contributes to difficulty in standardizing its management. In this article we review the existing scientific literature to identify the current diagnostic tools and discuss comprehensive management of various categories of IOL. Our objective is to increase disease recognition of IOL as a whole and explore updated management options for each subtype.
Methods: PubMed and Embase were searched for publications using the terms ‘intraocular lymphoma’, ‘vitreoretinal lymphoma’, ‘uveal lymphoma’, ‘iris lymphoma’, ‘choroidal lymphoma’ and ‘ciliary body lymphoma’ published from 1990 to June 2021. Inclusion criteria were English language articles. Exclusion criteria were non-English language articles, case reports and animal studies.
Key Content and Findings: IOL often presents in middle-aged and older patients with symptoms of floaters and vision changes, but a broad array of clinical signs and symptoms are possible depending upon subtype. IOL can be subdivided by location of involvement into vitreoretinal and uveal lymphoma. These subtypes express key differences in their pathophysiology, clinical presentation, histology, prognosis, and treatment. Primary vitreoretinal lymphomas (PVRL) generally originate from B-lymphocytes and are associated with central nervous system (CNS) lymphoma. Ophthalmic findings include retinal pigment epithelium changes with yellow subretinal deposits known as “leopard spotting.” Primary uveal lymphomas generally originate from low-grade B-lymphocytes invading the choroid and carry an improved prognosis compared to vitreoretinal lymphomas. Funduscopic findings of primary uveal lymphoma include yellow to pink-yellow choroidal swelling with infiltrative subconjunctival “salmon-patch” lesions. Diagnosis for IOL is often delayed due to insidious onset, low prevalence, and tendency to mimic diseases such as uveitis. Diagnosis may be challenging, often relying on biopsy with specialized laboratory testing for confirmation of IOL. Optimal treatment regimens are currently debated among experts. Management of IOL is best coordinated in association with neuro-oncology clinicians due to the tendency for intracranial involvement.
Conclusions: IOL represents a group of multiple malignancies with distinct clinicopathologic features. Future outlook for treatment and prognosis of IOL is likely to improve with less invasive molecular diagnostic techniques and increased awareness. Clinicians should be circumspect in all patients with possible IOL and promptly refer to oncologic specialists for rapid evaluation and treatment.
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.
