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: 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: Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. AMD most commonly affects older individuals and is characterized by irreversible degeneration of the retinal pigment epithelium and neurosensory retina. Currently, there are limited treatment options for dry AMD outside of lifestyle modification and nutrient supplementation. Risuteganib [Luminate (ALG-1001), Allegro Ophthalmics, CA, USA] is an intravitreally administered inhibitor of integrin heterodimers αVβ3, αVβ5, α5β1, and αMβ2. It is currently undergoing clinical trials for the treatment of dry AMD and diabetic macular edema (DME). Preclinical studies have shown that risuteganib has an effect on the pathways for angiogenesis, inflammation, and vascular permeability. Ongoing clinical trials have had promising results showing improvements in patient best corrected visual acuity (BCVA) and reduced central macular thickness measured by optical coherence tomography (OCT). There is a pressing need for treatments for dry AMD and while risuteganib appears to have a potential benefit for patients, more data are needed before one can truly evaluate its efficacy. This narrative review provides a concise summary of the most up to date data regarding the proposed mechanism of action of risuteganib in the treatment of nonexudative AMD and DME as well as the results from recent phase 1 and phase 2 clinical trials.
Background: To evaluate a fully automated vascular density (VD), skeletal density (SD) and fractal dimension (FD) method for the longitudinal analysis of retinal vein occlusion (RVO) eyes using projection-resolved optical coherence tomography angiography (OCTA) images and to evaluate the association between these quantitative variables and the visual prognosis in RVO eyes.
Methods: Retrospective longitudinal observational case series. Patients presenting with RVO to Creteil University Eye Clinic between October 2014 and December 2018 and healthy controls were retrospectively evaluated. Group 1 consisted of central RVO (CRVO) eyes, group 2 consisted of eyes with branch RVO (BRVO) and group 3 of healthy control eyes. OCTA acquisitions (AngioVue RTVue XR Avanti, Optovue, Inc., Freemont, CA) were performed at baseline and last follow up visit. VD, SD, and FD analysis were computed on OCTA superficial and deep vascular complex (SVC, DVC) images at baseline and final follow up using an automated algorithm. Logistic regression was performed to find if and which variable (VD, SD, FD) was predictive for the visual outcome.
Results: Forty-one eyes, of which 21 consecutive eyes of 20 RVO patients (13 CRVO in group 1, 8 BRVO in group 2), and 20 eyes of 20 healthy controls were included. At the level of SVC, VD and FD were significantly lower in RVO eyes compared to controls (P<0.0001 and P=0.0008 respectively). Best-corrected visual acuity (BCVA) at last follow-up visit was associated with baseline VD (P=0.013), FD (P=0.016), and SD (P=0.01) at the level of the SVC, as well as with baseline FD at the DVC level (P=0.046).
Conclusions: Baseline VD, SD, and FD are associated with the visual outcome in RVO eyes. These parameters seem valuable biomarkers and may help improve the evaluation and management of RVO patients.
Perception is the ability to see, hear, or become aware of external stimuli through the senses. Visual stimuli are electromagnetic waves that interact with the eye and elicit a sensation. Sensations, indeed, imply the detection, resolution, and recognition of objects and images, and their accuracy depends on the integrity of the visual system. In clinical practice, evaluating the integrity of the visual system relies greatly on the assessment of visual acuity, that is to say on the capacity to identify a signal. Visual acuity, indeed, is of utmost importance for diagnosing and monitoring ophthalmological diseases. Visual acuity is a function that detects the presence of a stimulation (a signal) and resolves its detail(s). This is the case of a symbol like “E”: the stimulus is detected, then it is resolved as three horizontal bars and a vertical bar. In fact, within the clinical setting visual acuity is usually measured with alphanumeric symbols and is a three-step process that involves not only detection and resolution, but, due to the semantic content of letters and numbers, their recognition. Along with subjective (psychophysical) procedures, objective methods that do not require the active participation of the observer have been proposed to estimate visual acuity in non-collaborating subjects, malingerers, or toddlers. This paper aims to explain the psychophysical rationale underlying the measurement of visual acuity and revise the most common procedures used for its assessment.
