Abstract: Uveitis can cause significant visual morbidity and often affects younger adults of working age. Anterior uveitis, or inflammation limited to the anterior chamber (AC), iris, and/or ciliary body comprises the majority of uveitis cases. Current clinical biomarkers and conventional grading scales for intraocular inflammation are mostly subjective and have only a moderate degree of interobserver reliability, and as such they have significant limitations when used in either clinical practice or research related to uveitis. In recent years, novel imaging techniques and applications have emerged that can supplement exam findings to detect subclinical disease, monitor quantitative biomarkers of disease progression or treatment effect, and provide overall a more nuanced understanding of disease entities. The first part of this review discusses automated algorithms for optical coherence tomography (OCT) image processing and analysis as a means to assess and describe intraocular inflammation with higher resolution than that afforded by conventional AC and vitreous cell ordinal grading scales. The second half of the review focuses on anterior segment OCT and OCT angiography (OCTA) in scleritis and iritis, especially with regards to their ability to directly image and characterize the pathologic structures and vasculature underlying these diseases. Finally, we briefly review experimental animal research with promising but more distant human clinical applications, including in vivo molecular microscopy of inflammatory markers and investigation of gold nanoparticles as a potential contrast agent in OCT imaging. Imaging modalities are discussed in the broader context of trends within the field of uveitis towards greater objectivity and quantifiable outcome measures and biomarkers.
Abstract: Optical coherence tomography (OCT) provides a non-invasive analysis of the retina in vivo. Lesions which compress the anterior visual pathway can cause anterograde and retrograde neuro-degeneration. Retrograde structural changes to the retina can be detected by OCT. Analyzing patterns of change on OCT can guide diagnostic and treatment decisions for lesions compressing the optic nerve and chiasm to minimize loss of visual function. From our review of current literature, it is clear that thinning of both the retinal nerve fiber and ganglion cell layers (GCLs) can indicate compression. These parameters correlate with visual function loss as detected by perimetry. Furthermore, these measurements have shown to be the most reliable biomarkers to date in predicting visual recovery after treatment of these compressive lesions.
Abstract: Optical coherence tomography (OCT) is a widely used non-invasive medical imaging technology that has revolutionized clinical care in ophthalmology. New developments, such as OCT angiography (OCTA) are expected to contribute even further to the widespread use of OCT-based imaging devices in the diagnosis and monitoring of patients with ophthalmic diseases. In recent years, many of the disadvantages such as limited field of view and imaging artefacts have been substantially reduced. Similar to the progress achieved in the assessment of retinal disorders, OCT is expected to change the approach to patients seen in the neuro-ophthalmology clinic. In this article, we review the technical features of OCT and OCT-based imaging techniques, highlighting the specific factors that should be taken into account when interpreting OCT in the field of neuro-ophthalmology.
Abstract: Focal intraretinal alterations have been studied to advance our understanding of the pathology of neurodegenerative diseases. The current literature involving focal alterations in the intraretinal layers was reviewed through PubMed using the search terms “focal alteration”, “region of interest”, “optical coherence tomography”, “glaucoma”, “multiple sclerosis”, “Alzheimer’s disease”, “Parkinson disease”, “neurodegenerative diseases” and other related items. It was found that focal alterations of intraretinal layers were different in various neurodegenerative diseases. The typical focal thinning might help differentiate various ocular and cerebral diseases, track disease progression, and evaluate the outcome of clinical trials. Advanced exploration of focal intraretinal alterations will help to further validate their clinical and research utility.
Abstract: Idiopathic intracranial hypertension (IIH) is a condition in which elevated pressure in the cerebrospinal fluid can lead to optic nerve head (ONH) dysfunction and subsequent visual impairment. Physicians are currently limited in their ability to monitor and manage this condition, as clinical symptoms and exam findings are often delayed in response to changes in intracranial pressure. In order to find other biomarkers of disease, researchers are using imaging modalities such as optical coherence tomography (OCT) to observe microscopic changes in the eye in this condition. OCT can create 2-dimensional and 3-dimensional high definition images of the retina of the ONH and has been used to study various conditions such as glaucoma and multiple sclerosis. Numerous studies have used OCT in IIH as well, and they have shown that certain retinal layers and the ONH change in thickness and shape in both the short and long term with intracranial pressure changes. OCT is a promising modality for clinical and scientific evaluation of IIH as it is a noninvasive and practical tool to obtain in depth images. This review will discuss how OCT can be used to assess a patient with IIH, both before and after treatment, along with its limitations and future applications.
Abstract: Age-related macular degeneration (AMD) remains a leading cause of severe visual impairment in developing countries. Although dry-type AMD and geographic atrophy (GA) are progressive conditions with the associated decrease of visual functions, no well-established treatment regimen was proposed for the disease. Wet-type AMD is effectively treated with intravitreal anti-angiogenic agents, but frequent injections are a major issue for the affected patients. Recent advances in AMD genetics have provided new insights into the pathogenesis and novel therapeutic targets of AMD, but the benefits of using genetic testing and genotype-based risk models for AMD development and progression still lacks evidence. Novel AMD treatments aim to increase the interval among intravitreal injections through new therapeutic agents and modern delivery devices. Simultaneously, gene therapy for dry and wet AMD is widely studied. Although gene therapy possesses a major superiority over other novel treatments regarding a persistent cure of disease, many challenges exist in the way of its broad impact on the ocular health of AMD patients.
Abstract: Macular neovascularization (MNV) is the hallmark of neovascular age-related macular degeneration (nAMD), one of the leading causes of vision loss in the developed world. The current MNV standard of care including frequent intravitreal anti-vascular endothelial growth factor (VEGF) injections, although has revolutionized favorably the treatment, places a substantial burden on patients, caregivers, and physicians. Brolucizumab is a newly developed single-chain antibody fragment that inhibits activation of VEGF receptor 2 with in vitro affinity and potency comparable to commercially-available anti-VEGF agents. Its small molecular weight and its design allow for high solubility and retinal tissue penetration, and improve bynding affinity to the target. Also a high clearance rate leading to minimal systemic exposure was observed. Brolucizumab has shown similar gains in visual acuity compared with other anti-VEGF molecules but a higher and earlier resolution of nAMD related fluid, achieving sustained macular dryness with longer mantainance injection interval ranging from 8 to 12 weeks after monthly loading doses. Rare cases of ocular inflammation also including retinal vasculitis and retinal vascular occlusions referred to an immune-mediated reaction posed safety concerns on selected patients and mantainance treatment interval shorter than 8 weeks.The present review summarizes several key points including the molecular structure and pharmacokinetics, the preclinical and clinical evidence of brolucizumab administration evaluating its efficacy, tolerability, and safety, extended dosing regimens and other indications still under clinical investigation.
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.
