The 1-Step Versus 2-Step Subretinal Injection Trial (1,2-SIT)-A Randomized Controlled Trial to Compare Drug Reflux Following Subretinal Injection.

Purpose: To estimate in humans, in vivo, drug retention in the subretinal space following either 1- or 2-step subretinal injection (SRI).

Design: A single-masked, randomized, controlled trial.

Methods: Patients presenting with submacular hemorrhage secondary to age-related macular degeneration were randomly allocated to receive subretinal tissue plasminogen activator (50 µg in 0.

THE FIGHT INHERITED RETINAL BLINDNESS! PROJECT: A New Treatment Outcome and Natural History Registry for Inherited Retinal Disease.

Purpose: To design and build a new disease registry to track the natural history and outcomes of approved gene therapy in patients with inherited retinal diseases.

Methods: A core committee of six members was convened to oversee the construction of the Fight Inherited Retinal Blindness! module. A further 11 experts formed a steering committee, which discussed disease classification and variables to form minimum datasets using a consensus approach.

Mechanisms of cone sensitivity loss in retinitis pigmentosa.

Purpose: To explore the mechanisms of cone sensitivity loss in retinitis pigmentosa by combining two-colour perimetry with threshold versus intensity (tvi) testing.

Methods: Seven subjects with autosomal recessive retinitis pigmentosa and 10 normal subjects were recruited and underwent perimetric testing of one eye using 480- and 640-nm Goldman size V targets presented under scotopic conditions (no background illumination) and against a white background ranging in luminance from -1.5 to 2 log cd m in 0.

Consensus and controversies in the science of endophthalmitis management: Basic research and clinical perspectives.

Infectious endophthalmitis is a severe intraocular infection caused by bacteria, or less commonly by fungi. It can occur after penetrating eye procedures, trauma, or the spread of infection from contiguous structures or via emboli from distant organs. Because of the time-critical nature of the treatment, endophthalmitis is treated with the clinical diagnosis and modified by the microbiological report of the intraocular contents.

Optogenetic restoration of high sensitivity vision with bReaChES, a red-shifted channelrhodopsin.

The common final pathway to blindness in many forms of retinal degeneration is the death of the light-sensitive primary retinal neurons. However, the normally light-insensitive second- and third-order neurons persist optogenetic gene therapy aims to restore sight by rendering such neurons light-sensitive. Here, we investigate whether bReaChES, a newly described high sensitivity Type I opsin with peak sensitivity to long-wavelength visible light, can restore vision in a murine model of severe early-onset retinal degeneration.

Glaucoma diagnosis using multi-feature analysis and a deep learning technique.

In this study, we aimed to facilitate the current diagnostic assessment of glaucoma by analyzing multiple features and introducing a new cross-sectional optic nerve head (ONH) feature from optical coherence tomography (OCT) images. The data (n = 100 for both glaucoma and control) were collected based on structural, functional, demographic and risk factors. The features were statistically analyzed, and the most significant four features were used to train machine learning (ML) algorithms.

IMPAIRMENTS OF L-CONE/M-CONE AND S-CONE-MEDIATED COLOR DISCRIMINATION IN MACULAR TELANGIECTASIA TYPE II.

Purpose: To characterize red-green and tritan color discrimination in eyes with macular telangiectasia Type II (MacTel).

Methods: Color discrimination was assessed by metameric matching methods using an Oculus MR Anomaloscope. Red-green color discrimination was assessed using the Rayleigh equation, and tritan color discrimination was assessed using the Moreland equation.

IMPAIRMENTS IN CONE PIGMENT REGENERATION AND ABSOLUTE THRESHOLD IN MACULAR TELANGIECTASIA TYPE 2.

Purpose: To test the hypothesis that Müller cell dysfunction in macular telangiectasia type 2 (MacTel) results in delayed cone adaptation kinetics and to assess absolute cone and rod thresholds in this condition.

Methods: Adaptation after an approximate 63.5% full-field cone photopigment bleach was assessed for Goldmann size V (1.

Vision at the limits: Absolute threshold, visual function, and outcomes in clinical trials.

The study of individual differences in perception at absolute threshold has a rich history, with much of the seminal work being driven by the need to identify those with superior abilities in times of war. Although the popularity of such testing waned in the latter half of the 20th century, interest in measures of visual function at the absolute limit of vision is increasing, partly in response to emerging treatments for retinal diseases, such as gene therapy and cellular therapies, that demand "new" functional measures to assess treatment outcomes. Conventional clinical, or clinical research, testing approaches generally assess rod sensitivity at or near absolute threshold; however, cone sensitivity is typically assayed in the presence of adapting backgrounds.

Scotopic microperimetry: evolution, applications and future directions.

For many inherited and acquired retinal diseases, reduced night vision is a primary symptom. Despite this, the clinical testing options for spatially resolved scotopic vision have until recently been limited. Scotopic microperimetry is a relatively new visual function test that combines two-colour perimetry with fundus-controlled perimetry performed in scotopic luminance conditions.

Two-step versus 1-step subretinal injection to compare subretinal drug delivery: a randomised study protocol.

Introduction: There is increasing interest in subretinal injections as a surgical procedure, largely as a result of emerging treatments for ocular diseases which necessitate this manoeuvre. However, surgical variables in the efficacy of such treatments have to date been largely overlooked and the proportion of drug which reaches the intended compartment of the subretinal space remains unknown. Our aims are twofold: first, to determine the proportion of subretinally injected medication retained following surgical delivery and second, to compare two different techniques of injection ('1-step' vs '2-step').

Endophthalmitis: Changes in Presentation, Management and the Role of Early Vitrectomy.

Endophthalmitis is a sight-threatening condition, and its timely and appropriate management is essential in preventing permanent vision loss. Recent changes in clinical practice in endophthalmitis and advances in modern vitreoretinal surgery may limit the applicability of established randomised clinical trial evidence to current management. This review discusses the epidemiology, pathophysiology, changing patient presentation, diagnosis and advances in the management of endophthalmitis, presenting the existing literature on this topic and results from Sydney Eye Hospital.

Structural and Functional Characteristics of Color Vision Changes in Choroideremia.

Color vision is considered a marker of cone function and its assessment in patients with retinal pathology is complementary to the assessments of spatial vision [best-corrected visual acuity (BCVA)] and contrast detection (perimetry). Rod-cone and chorioretinal dystrophies-such as choroideremia-typically cause alterations to color vision, making its assessment a potential outcome measure in clinical trials. However, clinical evaluation of color vision may be compromised by pathological changes to spatial vision and the visual field.

Retinal Stem/Progenitor Cells Derived From Adult Müller Glia for the Treatment of Retinal Degeneration.

Over the past two decades, progress in our understanding of glial function has been revolutionary. Within the retina, a subset of glial cells termed the "Müller glia (MG)," have been demonstrated to play key roles in retinal homeostasis, structure and metabolism. Additionally, MG have also been shown to possess the regenerative capacity that varies across species.

The Role of Inflammation and Infection in Age-Related Neurodegenerative Diseases: Lessons From Bacterial Meningitis Applied to Alzheimer Disease and Age-Related Macular Degeneration.

Age-related neurodegenerative diseases, such as Alzheimer disease (AD) and age-related macular degeneration (AMD), are multifactorial and have diverse genetic and environmental risk factors. Despite the complex nature of the diseases, there is long-standing, and growing, evidence linking microbial infection to the development of AD dementia, which we summarize in this article. Also, we highlight emerging research findings that support a role for parainfection in the pathophysiology of AMD, a disease of the neurosensory retina that has been shown to share risk factors and pathological features with AD.

Intravitreal anti-vascular endothelial growth factor versus panretinal LASER photocoagulation for proliferative diabetic retinopathy: a systematic review and meta-analysis.

Objective: To systematically review and perform a meta-analysis on the available evidence for anti-vascular endothelial growth factor (anti-VEGF) monotherapy versus panretinal photocoagulation (PRP) for proliferative diabetic retinopathy (PDR).

Design: Systematic review and meta-analysis PARTICIPANTS: Randomized clinical trials included participants ≥18 years old with clinical or angiographic evidence of PDR. Interventions included were anti-VEGF monotherapy and PRP.

SURGICAL RETINAL EXPLANTS AS A SOURCE OF RETINAL PROGENITOR CELLS.

Purpose: To describe the novel observation of spontaneously migrating retinal cells from living donor surgical retinal explants that express progenitor cell markers in the absence of exogenous growth factors.

Methods: Surgical retinal explants were harvested from 5 consecutive patients undergoing 23 G pars plana vitrectomy for the management of rhegmatogenous detachment. During surgery, equatorial flap tears were trimmed with the vitreous cutter and aspirated.

Threshold versus intensity functions in two-colour automated perimetry.

Purpose: Two-colour computerised perimetry is a technique developed for assessing cone- and rod-function at fixed background luminances in retinal disease. However, the state of adaptation during testing is unknown but crucial in the interpretation of results. We therefore aimed to determine the adaptational state of rod- and cone-mechanisms in two-colour perimetry.

Ab-externo drainage with continuous anterior chamber infusion for non-resolving exudative retinal detachment: a case report.

Background: Drainage of exudative retinal detachment may be necessary for either therapeutic or diagnostic purposes (or both). Here, we describe an external drainage technique for non-resolving vision-threatening exudative retinal detachment which combines the advantages of internal drainage (widefield viewing and intraocular pressure control using continuous anterior chamber infusion) with those of external drainage (drainage of sub-retinal fluid without vitrectomy).

Case Presentation: To illustrate this technique, we present a 13-year-old girl with macula-off exudative retinal detachment secondary to Vogt-Koyanagi-Harada syndrome, which was unresponsive to aggressive medical management.

Sodium Fluorescein as an Optical Label to Evaluate Subretinal Injection.

Purpose: There is renewed interest in subretinal drug delivery as the result of novel and emerging treatments for retinal diseases, including retinal gene therapy. However, our knowledge of the distribution of subretinally delivered drugs is incomplete; herein, we describe a qualitative and quantitative means of surveying the early intraocular distribution of subretinally delivered drugs using dilute sodium fluorescein (NaFl).

Methods: Sodium fluorescein 10% was serially diluted and mixed with a solution containing tissue plasminogen activator (tPA) at a final concentration of 0.

Post-surgical versus post-intravitreal injection endophthalmitis: changing patterns in causative flora.

Importance: Endophthalmitis is a serious complication of intraocular procedures: knowledge of its causative organisms and outcomes may guide prevention and treatment.

Background: To determine the outcomes and spectrum of causative organisms in acute post-procedural endophthalmitis.

Design: A retrospective observational case series performed at a tertiary referral hospital during the period 1 July 2012 to 31 July 2017.

Colour discrimination ellipses in choroideremia.

Purpose: The purpose of this study was to characterise alterations in colour discrimination in a cohort of patients with choroideremia prior to gene therapy, using a test previously validated for use in patients with retinal dystrophies.

Methods: We tested 20 eyes of 10 patients with a diagnosis of choroideremia and an age-matched cohort of 10 eyes of 10 normal controls using the "Cambridge Colour Test" (CCT), in which subjects are required to distinguish the gap in a C presented in one of 4 orientations in a Stilling-type array. Colour discrimination was probed along eight axes in the CIE L*u*v* colour space, and the resulting data were plotted in the CIE 1976 chromaticity diagram and fitted with least-squares ellipses.