Abstract: Inherited retinal diseases (IRD) are a leading cause of blindness in the working age population. The advances in ocular genetics, retinal imaging and molecular biology, have conspired to create the ideal environment for establishing treatments for IRD, with the first approved gene therapy and the commencement of multiple therapy trials. The scope of this review is to familiarize clinicians and scientists with the current landscape of retinal imaging in IRD. Herein we present in a comprehensive and concise manner the imaging findings of: (I) macular dystrophies (MD) [Stargardt disease (ABCA4), X-linked retinoschisis (RS1), Best disease (BEST1), pattern dystrophy (PRPH2), Sorsby fundus dystrophy (TIMP3), and autosomal dominant drusen (EFEMP1)], (II) cone and cone-rod dystrophies (GUCA1A, PRPH2, ABCA4 and RPGR), (III) cone dysfunction syndromes [achromatopsia (CNGA3, CNGB3, PDE6C, PDE6H, GNAT2, ATF6], blue-cone monochromatism (OPN1LW/OPN1MW array), oligocone trichromacy, bradyopsia (RGS9/R9AP) and Bornholm eye disease (OPN1LW/OPN1MW), (IV) Leber congenital amaurosis (GUCY2D, CEP290, CRB1, RDH12, RPE65, TULP1, AIPL1 and NMNAT1), (V) rod-cone dystrophies [retinitis pigmentosa, enhanced S-Cone syndrome (NR2E3), Bietti crystalline corneoretinal dystrophy (CYP4V2)], (VI) rod dysfunction syndromes (congenital stationary night blindness, fundus albipunctatus (RDH5), Oguchi disease (SAG, GRK1), and (VII) chorioretinal dystrophies [choroideremia (CHM), gyrate atrophy (OAT)].

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: Vogt-Koyanagi-Harada syndrome (VKH) is a bilateral granulomatous panuveitis associated with serous retinal detachments and vitritis, and can be associated with extraocular manifestations of meningismus, poliosis, vitiligo, hearing loss, and headaches. It is mediated by CD4+ T cells that target melanocytes in the eye, ear, meninges, and skin. It classically presents in 4 different phases: prodromal, uveitic, convalescent, and recurrent. There have been considerable advances in our understanding of the disease in recent years, and options for treatment have also expanded beyond systemic corticosteroids though these remain the mainstay of therapy in patients with VKH. This brief review will focus on updates in the diagnosis and treatment of VKH, specifically advances in imaging techniques including the use of optical coherence tomography angiography (OCTA) and enhanced depth imaging (EDI) optical coherence tomography (OCT). OCT parameters that are diagnostically predictive of acute VKH compared to other exudative maculopathies include the presence of subretinal membranous structures, a high retinal detachment, subretinal hyperreflective dots, and RPE folds. Evaluations of choroidal thickness using EDI-OCT demonstrate predominant involvement of the outer choroid in the acute inflammatory phase of VKH, consistent with histopathological analysis. OCTA may emerge as an alternative to fluorescein angiography (FA) and indocyanine angiography (ICGA) but is limited at this time due to its small field of view. While the mainstay of treatment of acute VKH continues to be systemic corticosteroids, biological response modifiers (BRMs) such as adalimumab and infliximab have been shown to be effective in the management of adult and pediatric VKH with one benefit being a faster onset of action compared to conventional immunosuppression. Literature Search: A literature search was done in PubMed using the words “Vogt Koyanagi Harada” “imaging” “diagnosis” “treatment” “therapy “posterior uveitis”.

Abstract: Optical coherence tomography (OCT) is a technology that is widely used to assess structural abnormalities in the retina for a variety of pediatric conditions. The introduction of this instrument has allowed for widespread access to minimally invasive standardized, reproducible quantified structural assessments of the optic nerve and retina. This has had important implications in pediatric optic neuropathies, populations in whom monitoring of disease activity is essential to making treatment decisions. OCT has had particular relevance for inflammatory optic neuropathies, as onset of an inflammatory optic neuropathy may herald the onset of a chronic inflammatory disorder of the central nervous system (CNS) such as multiple sclerosis, neuromyelitis optica spectrum disorder (aquaporin 4 antibody positive), and myelin oligodendrocyte glycoprotein (MOG) associated disorders. This paper will focus on the application of OCT technology to this group of disorders in pediatrics. After reviewing pediatric-specific anatomic and practical issues pertinent to OCT, we will review knowledge related to the use of OCT in inflammatory pediatric optic neuropathies, with a focus on structural outcomes and their correlation with functional outcome metrics.

Abstract: Pediatric uveitis is an inflammatory ocular disease that can lead to sight-threatening complications. Pediatric patients have distinct challenges in the diagnosis and management of uveitis, secondary to difficulties in performing ophthalmic examinations in young children, delayed diagnosis due to lack of adherence with recommended screening schedules, medication side-effects, and increased burden of disease into adulthood. Measurement of outcomes in pediatric uveitis has traditionally relied upon the ophthalmic examination and general quality of life (QOL) measures. However, the ophthalmic examination does not take into account the impact of uveitis on a child’s QOL and general QOL measures do not adequately assess the specific effects of vision. Several vision-related quality of life (VR-QOL) instruments have been used to measure outcomes in both adults and children including: the National Eye Institute Visual Function Questionnaire (NEI VFQ-25), Vision-related Quality of Life of Children and Young People (VQoL_CYP), the Children’s Visual Function Questionnaire (CVFQ), and the Effect of Youngsters’ Eyesight on Quality of Life (EYE-Q). However, the NEI VFQ-25 is not a valid or applicable measure in children, and the VQoL_CYP and CVFQ are not uveitis specific and may not characterize disease specific burdens. The EYE-Q is the only uveitis-specific pediatric questionnaire that measures visual functioning and VR-QOL in 5–18 years old children and adolescents with uveitis. It has been shown to be a valid and reliable assessment tool in several cohorts of children with uveitis. A comprehensive assessment of the impact of uveitis on a child that includes a vision-specific measure, such as the EYE-Q, allows for better understanding of the true burden of uveitis in children. For this review, we describe traditional outcome measures in uveitis studies, general QOL measures and vision-specific measures in adults and in children.

Abstract: Hereditary, metabolic and toxic optic neuropathies cause bilateral, central vision loss and therefore can result in severe impairment in visual function. Accurate, early diagnosis is critical, as nutritional and toxic optic neuropathies may be reversible if identified early, and diagnosis of hereditary optic neuropathies can prevent unnecessary invasive workup, provide prognostic information, and allow for effective genetic counseling. Optical coherence tomography (OCT) is a valuable tool that aids in the diagnosis and prognostication of optic neuropathies as it allows for quantification of changes in the retinal ganglion cells (RGCs) and retinal nerve fiber layer (RNFL) over time. We review the characteristic clinical presentations of hereditary, metabolic and toxic optic neuropathies, with an emphasis on OCT findings.

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: 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.