Retinal Degeneration Associated With Biallelic RDH12 Variants: Longitudinal Evaluation of Retinal Structure and Visual Function in Pediatric Patients.

Purpose: The purpose of this study was to determine the natural history of the photoreceptor disease in a large group of pediatric patients with RHD12-associated Leber congenital amaurosis (RDH12-LCA), to estimate the changes expected over the duration of a clinical trial, and to define the relationship between the photoreceptor loss and visual dysfunction.

Methods: Forty-six patients representing 36 families were included. The great majority of patients were under the age of 18 years.

Retinal Sensitivity in Comparison to Cone Density in Choroideremia.

Purpose: Choroideremia (CHM) is an X-linked inherited retinal degeneration causing loss of photoreceptors, retinal pigment epithelium, and choriocapillaris. Structural abnormalities of the cone photoreceptor mosaic have been reported even within the retained island of functioning retina. Here, we describe the relationship between cone density and visual sensitivity within the retained central retina in CHM.

Safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D: a phase 1/2, multicentre, open-label, unilateral dose escalation study.

Background: Leber congenital amaurosis 1 (LCA1), caused by mutations in GUCY2D, is a rare inherited retinal disease that typically causes blindness in early childhood. The aim of this study was to evaluate the safety and preliminary efficacy of ascending doses of ATSN-101, a subretinal AAV5 gene therapy for LCA1.

Methods: 15 patients with genetically confirmed biallelic mutations in GUCY2D were included in this phase 1/2 study.

Report From the Second Global Scientific Conference on Clinical Trial Design and Outcome Measures for RDH12-Associated Inherited Retinal Degeneration.

A multi-stakeholder, patient centric approach will be critical to the design of future successful clinical trials with outcome measures relevant to the RDH12-IRD population.

-TRPM1 autoantibody-positive unilateral melanoma associated retinopathy (MAR) triggered by immunotherapy recapitulates functional and structural details of -associated congenital stationary night blindness.

Purpose: To describe the retinal phenotype of an unusual case of anti-TRPM1 autoantibody-positive unilateral melanoma-associated retinopathy (MAR) triggered by nivolumab therapy and compare with the phenotype of -associated Congenital Stationary Night Blindness (-CSNB).

Observations: Unilateral MAR was diagnosed 3 months after starting nivolumab therapy for consolidation of a successfully treated melanoma. Retinal autoantibodies against TRPM1 were identified.

Intraretinal hemorrhages and detailed retinal phenotype of three patients with Alagille syndrome.

Purpose: To explore patterns of disease expression in Alagille syndrome (ALGS).

Methods: Patients underwent ophthalmic examination, optical coherence tomography (OCT) imaging, fundus intravenous fluorescein angiography (IVFA), perimetry and full-field electroretinograms (ffERGs). An adult ALGS patient had multimodal imaging and specialized perimetry.

Detailed phenotype and long-term follow-up of associated cone-rod dystrophy.

Purpose: To gain an insight into the pathophysiology of associated inherited retinal degeneration through detailed phenotyping and long-term longitudinal follow-up.

Methods: The patient underwent complete ophthalmic examinations. Visual function was assessed with microperimetry, full-field electroretinography (ffERG), imaging with optical coherence tomography (OCT), short-wave (SW), and near-infrared (NIR) fundus autofluorescence (FAF).

FOVEAL PHENOTYPES IN CHOROIDEREMIA ON ADAPTIVE OPTICS SCANNING LIGHT OPHTHALMOSCOPY.

Purpose: Choroideremia is an X-linked inherited retinal degeneration involving the choriocapillaris, retinal pigment epithelium, and photoreceptors. Adaptive optics scanning light ophthalmoscopy allows visualization of retinal structure at the level of individual cells and is well poised to provide insight into the pathophysiologic mechanisms underpinning the retinal degeneration in choroideremia.

Methods: Foveal adaptive optics scanning light ophthalmoscopy images of 102 eyes of 54 individuals with choroideremia were analyzed.

Stimulus type and duration affect magnitude and evolution of flicker-induced hyperemia measured by laser speckle flowgraphy at the optic disc and peripapillary vessels.

Neurovascular coupling is a vital mechanism employed by the cerebrovascular system, including the eye, to regulate blood flow in periods of neuronal activation. This study aims to investigate if laser speckle flowgraphy (LSFG) can detect coupling response elicited by flickering light stimuli and how variations in stimulus type and duration can affect the magnitude and evolution of blood flow in the optic nerve head (ONH) and peripapillary vessels. Healthy adults were exposed to two types of 10-Hz flicker stimuli: a photopic negative response-like stimulus (PhNR-S) or a visual evoked potential-like stimulus (VEP-S)-each presented in separate 10- and 60-s epochs.

Retinal response to light exposure in BEST1-mutant dogs evaluated with ultra-high resolution OCT.

Mutations in BEST1 cause an autosomal recessive disease in dogs where the earliest changes localize to the photoreceptor-RPE interface and show a retina-wide micro-detachment that is modulated by light exposure. The purpose of this study was to define the spatial and temporal details of the outer retina and its response to light with ultra-high resolution OCT across a range of ages and with different BEST1 mutations. Three retinal regions were selected in each eye: near the fovea-like area, near the optic nerve, both in the tapetal area, and inferior to the optic nerve in the non-tapetal area.

OUTER RETINOPATHY AND MICROANGIOPATHY IN ACUTE MYELOGENOUS LEUKEMIA.

Purpose: To describe a patient with acute myelogenous leukemia who presented with a recurrent, bilateral, outer retinopathy, before and after consolidative peripheral blood stem cell transplantation complicated by chronic graft-versus-host disease.

Methods: This is a retrospective review of records from a 23-year-old woman with acute myelogenous leukemia who underwent comprehensive ophthalmic evaluations for over a year including chromatic perimetry and multifocal electroretinograms, imaging with spectral domain optical coherence tomography, near-infrared and short-wavelength fundus reflectance and autofluorescence, fluorescein and optical coherence tomography angiography.

Results: The patient presented with recurrent, unilateral paracentral scotomas.

CHOROIDAL NEOVASCULAR MEMBRANES ASSOCIATED WITH PAPILLITIS IN A PATIENT ON CHECKPOINT INHIBITOR.

Purpose: The purpose of this study was to describe a case of bilateral peripapillary choroidal neovascular membranes in the setting of a patient with papillitis associated with pembrolizumab for Stage IIIA adenocarcinoma of the lung.

Methods: This was a retrospective case report with fundus photography, fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography.

Results: A 59-year-old woman with Stage IIIA adenocarcinoma of the lung on pembrolizumab therapy presented with symptoms of blurry vision.

A Phase II Open-Label Trial of Binimetinib and Hydroxychloroquine in Patients With Advanced KRAS-Mutant Non-Small Cell Lung Cancer.

Background: In RAS-mutant tumors, combined MEK and autophagy inhibition using chloroquine demonstrated synthetic lethality in preclinical studies. This phase II trial evaluated the safety and activity of the MEK inhibitor binimetinib combined with hydroxychloroquine (HCQ) in patients with advanced KRAS-mutant non-small cell lung cancer (NSCLC).

Methods: Eligibility criteria included KRAS-mutant NSCLC, progression after first-line therapy, ECOG PS 0-1, and adequate end-organ function.

Motion-selective areas V5/MT and MST appear resistant to deterioration in choroideremia.

Choroideremia (CHM) is an X-linked recessive form of hereditary retinal degeneration, which preserves only small islands of central retinal tissue. Previously, we demonstrated the relationship between central vision and structure and population receptive fields (pRF) using functional magnetic resonance imaging (fMRI) in untreated CHM subjects. Here, we replicate and extend this work, providing a more in-depth analysis of the visual responses in a cohort of CHM subjects who participated in a retinal gene therapy clinical trial.

Retinal photoreceptor layer thickness has disease specificity and distinguishes predicted FTLD-Tau from biomarker-determined Alzheimer's disease.

While Alzheimer's disease (AD) is associated with inner retina thinning (retinal nerve fiber layer and ganglion cell layer), we have observed photoreceptor outer nuclear layer (ONL) thinning in patients with frontotemporal lobar degeneration tauopathy (FTLD-Tau) compared to normal controls. We hypothesized that ONL thinning may distinguish FTLD-Tau from patients with biomarker evidence of AD neuropathologic change (ADNC) and will correlate with FTLD-Tau disease severity. Predicted FTLD-Tau (pFTLD-Tau; n = 21; 33 eyes) and predicted ADNC (pADNC; n = 24; 46 eyes) patients were consecutively enrolled, underwent optical coherence tomography macula imaging, and disease was categorized (pFTLD-Tau vs.

Optimization and Validation of a Virtual Reality Orientation and Mobility Test for Inherited Retinal Degenerations.

Purpose: To optimize a virtual reality (VR) orientation and mobility (O&M) test of functional vision in patients with inherited retinal degenerations (IRDs).

Methods: We developed an O&M test using commercially available VR hardware and custom-generated software. Normally sighted subjects (n = 20, ages = 14-67 years) and patients with IRDs (n = 29, ages = 15-63 years) participated.

DANON DISEASE: A MODEL OF PHOTORECEPTOR DEGENERATION SECONDARY TO PRIMARY RETINAL PIGMENT EPITHELIUM DISEASE.

Purpose: To describe in detail the retinal phenotype of LAMP2-associated Danon disease.

Methods: Three LAMP2-positive patients from two unrelated families were studied with spectral-domain optical coherence tomography and with short-wavelength and near-infrared fundus autofluorescence (FAF) imaging. Visual function was measured with full-field electroretinography and chromatic perimetry.