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: Optical coherence tomography angiography (OCTA) is a fast, non-invasive imaging modality that provides detailed information on retinal and choroidal vascular flow and macular structure. OCTA offers an accurate three-dimensional view of the individual retinal vascular plexuses and the choriocapillaris which facilitates the detection of the microvascular abnormalities in a variety of macular diseases. The perfusion indices (vessel density and flow index) are valuable parameters evaluated by OCTA that allow a quantitative interpretation of changes in the retinal vasculature that can reflect the severity of disease. Crystalline retinopathy encompasses a group of conditions whose distinctive feature is the presence of retinal crystals often located in the posterior pole. Select crystalline retinopathies also demonstrate retinal vascular abnormalities as well. Considering that the OCTA is a novel imaging modality and crystalline retinopathies are relatively rare conditions, there are currently few reports of OCTA findings associated with crystalline retinopathy. The advent of OCTA allows visualization of vascular and structural changes in crystalline retinopathies that are unique and cannot be appreciated on other imaging modalities, including fluorescein angiography (FA). This article reviews novel OCTA findings which provide new insights in the pathogenesis of crystalline retinopathies, including Bietti crystalline retinopathy, talc retinopathy, macular telangiectasia type 2, tamoxifen retinopathy, and Sj?gren-Larsson Syndrome maculopathy.

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: Effective and safe electrical stimulation of the retinal ganglion cells is at the heart of retinal prosthesis design. However, the effectiveness and safety demand of the electrical stimulation is often at odds against each other. Besides, the nerve fiber layer above retinal ganglion cells limits the spatial resolution of stimulation. Also, current retinal prosthesis still cannot selectively activate the ON or OFF visual pathways, thus cannot relay the correct luminance information to the brain. With decades of development, the stimulation protocol for retinal implants began to tackle these problems. We believe that a novel design of electrical stimulation scheme, combined with gene therapy technique, can improve the selectivity and spatial resolution of retinal implants and further lower the damage caused by electric stimulation.

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 (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) 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: In developed countries, age-related macular degeneration (AMD) is the main cause of visual impairment in the elderly. Though the etiology of AMD is still unclear, it has been well understood that vascular endothelial growth factor (VEGF) is involved in the development of aberrant vasculature that represents the neovascular AMD (nAMD). Hence, VEGF inhibition is a more effective way to control nAMD. Pegaptanib, ranibizumab, and aflibercept are three drugs approved by the US Food and Drug Administration (FDA) to treat nAMD. Bevacizumab (an anti-VEGF medication comparable to ranibizumab) is already widely used off label. Existing anti-VEGF medicines are made up of antibodies or pieces of antibodies. Synthetic designed ankyrin repeat proteins (DARPins) imitate antibodies introduced recently by evolutions in bioengineering technology. These agents are designed to have high specificity and affinity to a specific target, smaller molecular size, and better tissue penetration, making them more stable and longer-acting at less concentration. Abicipar pegol (Allergan, Dublin, Ireland) is a DARPin that interlocks all VEGF-A isoforms. It has a greater affinity for VEGF and a longer intraocular half-life than ranibizumab, making it a feasible anti-VEGF agent. This review describes the properties and efficacy of abicipar, the new anti-VEGF agent, in clinical practice, which aims to improve outcomes, safety, and treatment burden of nAMD.