Investigative Ophthalmology & Visual Science

PURPOSE: The purpose of this study was to understand how monocular luminance reduction affects binocular balance and examine whether it differentially influences fusion and mixed perception in amblyopia. METHODS: Twenty-three normally sighted observers and 12 adults with amblyopia participated in this study. A novel binocular rivalry task was used to measure the phase duration of four perceptual responses (right- and left-tilts, fusion, and mixed perception) before and after a neutral density (ND) filter was applied at various levels to the dominant eye (DE) of controls and the fellow eye (FE) of patients with amblyopia...

PURPOSE: Achromatopsia (ACHM) is an autosomal recessive retinal disease associated with reduced or absent cone function. There is debate regarding the extent to which cone structure shows progressive degeneration in patients with ACHM. Here, we used optical coherence tomography (OCT) images to evaluate outer nuclear layer (ONL) thickness and ellipsoid zone (EZ) integrity over time in individuals with ACHM. METHODS: Sixty-three individuals with genetically confirmed ACHM with follow-up ranging from about 6 months to 10 years were imaged using either Bioptigen or Cirrus OCT...

PURPOSE: Fuchs endothelial corneal dystrophy (FECD) is a progressive blinding disorder, characterized by increased corneal endothelial excrescences (guttae), corneal endothelial cell loss, and edema. These symptoms are hypothesized to be caused by changes in the extracellular matrix (ECM) and mitochondrial dysfunction in the corneal endothelium. Despite this clinical and biological relevance, a comprehensive animal model that recapitulates all the major disease characteristics is currently unavailable...

PURPOSE: Retinal ganglion cell (RGC) loss provides the basis for diagnosis and stage determination of many optic neuropathies, and quantification of RGC survival is a critical outcome measure in models of optic neuropathy. This study examines the accuracy of manual RGC counting using two selective markers, Brn3a and RBPMS. METHODS: Retinal flat mounts from 1- to 18-month-old C57BL/6 mice, and from mice after microbead (MB)-induced intraocular pressure (IOP) elevation, are immunostained with Brn3a and/or RBPMS antibodies...

PURPOSE: Axenfeld-Rieger syndrome (ARS) is characterized by ocular anomalies including posterior embryotoxon, iridocorneal adhesions, corectopia/iris hypoplasia, and developmental glaucoma. Although anterior segment defects and glaucoma contribute to decreased visual acuity, the role of potential posterior segment abnormalities has not been explored. We used high-resolution retinal imaging to test the hypothesis that individuals with ARS have posterior segment pathology. METHODS: Three individuals with FOXC1-ARS and 10 with PITX2-ARS completed slit-lamp and fundus photography, optical coherence tomography (OCT), OCT angiography, and adaptive optics scanning light ophthalmoscopy (AOSLO)...

PURPOSE: This study aims to examine the short-term peripheral choroidal thickness (PChT) response to signed defocus blur, both with and without native peripheral aberrations. This examination will provide insights into the role of peripheral aberration in detecting signs of defocus. METHODS: The peripheral retina (temporal 15°) of the right eye was exposed to a localized video stimulus in 11 young adults. An adaptive optics system induced 2D myopic or hyperopic defocus onto the stimulus, with or without correcting native peripheral ocular aberrations (adaptive optics [AO] or NoAO defocus conditions)...

PURPOSE: In a previous study, we documented that the Intravitreal injections (IVIs) of bevacizumab in rats caused a retinal inflammatory response. We now study whether the IVI of other humanized anti-VEGF: ranibizumab and aflibercept also cause an inflammatory reaction in the rat retina and if it depends on the dose administered. Finally, we study whether this reaction affects retinal ganglion cell (RGC) survival. METHODS: Albino Sprague-Dawley rats received a single IVI of 5 µL of PBS or ranibizumab or aflibercept at the concentration used in clinical practice (10 µg/µL or 40 µg/µL) or at a lower concentration (0...

PURPOSE: Our primary aim was to compare adult full-field ERG (ffERG) responses in albinism, idiopathic infantile nystagmus (IIN), and controls. A secondary aim was to investigate the effect of within-subject changes in nystagmus eye movements on ffERG responses. METHODS: Dilated Ganzfeld flash ffERG responses were recorded using DTL electrodes under conditions of dark (standard and dim flash) and light adaptation in 68 participants with albinism, 43 with IIN, and 24 controls...

PURPOSE: To explore the genetic background of choroidal and ciliary body melanoma among children and young adults, with special focus on BAP1 germline variants in this age group. METHODS: Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor. Next-generation sequencing using Ion Torrent platform was used to determine pathogenic variants of BAP1, EIF1AX, SF3B1, GNAQ and GNA11 and chromosome 3 status in the tumor or in DNA extracted from blood or saliva...

PURPOSE: The purpose of this study was to assess motion-defined form perception, including the association with clinical and sensory factors that may drive performance, in each eye of children with deprivation amblyopia due to unilateral cataract. METHODS: Coherence thresholds for orientation discrimination of motion-defined form were measured using a staircase procedure in 30 children with deprivation amblyopia and 59 age-matched controls. Visual acuity, stereoacuity, fusion, and interocular suppression were also measured...

PURPOSE: No large-mammal surgical models exist for geographic atrophy (GA), choroidal neovascularization (CNV), and pachychoroidal vascular remodeling. Our goal was to develop a porcine RPE debridement model of advanced macular degeneration to study photoreceptor cell loss and choroidal remodeling. METHODS: Seven 2-month-old female domestic pigs were used for this study. After 25G vitrectomy, the area centralis was detached via subretinal bleb. A nitinol wire (Finesse Flex Loop) was used to debride RPE cells across a 3- to 5-mm diameter region...

PURPOSE: Intravitreal injection of drugs is commonly used for treatment of chorioretinal ocular pathologies, such as age-related macular degeneration. Injection causes a transient increase in the intraocular volume and, consequently, of the intraocular pressure (IOP). The aim of this work is to investigate how intravitreal flow patterns generated during the post-injection eye deflation influence the transport and distribution of the injected drug. METHODS: We present mathematical and computational models of fluid motion and mass transport in the vitreous chamber during the transient phase after injection, including the previously unexplored effects of globe deflation as ocular volume decreases...

PURPOSE: Antibodies against collagen XIII have previously been identified in patients with active thyroid-associated ophthalmopathy (TAO). Although collagen XIII expression has been described in extraocular muscles and orbital fat, its detailed localization in extraocular and thyroid tissues and the connection to autoimmunity for collagen XIII remain unclear. Our objective was to map the potential targets for these antibodies in the tissues of the orbit and thyroid. METHODS: We evaluated the expression of collagen XIII in human patient and mouse orbital and thyroid tissues with immunostainings and RT-qPCR using Col13a1-/- mice as negative controls...

PURPOSE: This study investigates the temporal relationship between blood flow changes and alterations in retinal nerve fiber layer thickness (RNFLT) and mean deviation (MD) in individuals with glaucoma. METHODS: Blood flow, measured by mean blur rate in optic nerve head vessels (MBRv) and tissues (MBRt) using laser speckle flowgraphy (LSFG)-NAVI, was analyzed using structural equation models (SEMs). SEMs assessed whether the previous rate of one parameter predicted the current rate of the other parameter, adjusted for its own rate in the previous time interval...

PURPOSE: The purpose of this study is to report five novel FZD4 mutations identified in familial exudative vitreoretinopathy (FEVR) and to analyze and summarize the pathogenic mechanisms of 34 of 96 reported missense mutations in FZD4. METHODS: Five probands diagnosed with FEVR and their family members were enrolled in the study. Ocular examinations and targeted gene panel sequencing were conducted on all participants. Plasmids, each carrying 29 previously reported FZD4 missense mutations and five novel mutations, were constructed based on the selection of mutations from each domain of FZD4...

PURPOSE: To investigate the relationship between unilateral metamorphopsia, characterized by visual distortions in one eye, and impaired stereopsis. METHODS: Utilizing both near and distance measurements through advanced testing systems, including 4K smartphones and an active shutter three-dimensional system, we simulated varying degrees of unilateral metamorphopsia in 30 healthy young adults aged between 21 and 29 years. Two types of contour-based stereotest symbols, lines and squares, were developed...

PURPOSE: To describe and evaluate a novel method to determine the validity of measurements made using cycle-by-cycle (CxC) recording techniques in patients with advanced retinal degenerations (RD) having low-amplitude flicker electroretinogram (ERG) responses. METHODS: The method extends the original CxC recording algorithm introduced by Sieving et al., retaining the original recording setup and the preliminary analysis of raw data. Novel features include extended use of spectrum analysis, reduction of errors due to known sources, and a comprehensive statistical assessment using three different tests...

PURPOSE: To examine lens phenotypic characteristics in βA3ΔG91 mice and determine if βA3ΔG91 affects autophagy in the lens. METHODS: We generated a βA3ΔG91 mouse model using CRISPR/Cas9 methodology. Comparative phenotypic and biochemical characterizations of lenses from postnatal day 0 (P0), P15, and 1-month-old βA3ΔG91 and wild-type (WT) mice were performed. The methodologies used included non-invasive slit-lamp examination, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot, and immunohistochemical (IHC) analyses to determine the levels of autophagy-related genes and proteins...

PURPOSE: We aimed to determine the impact of artificial sweeteners (AS), especially saccharin, on the progression and treatment efficacy of patients with neovascular age-related macular degeneration (nAMD) under anti-vascular endothelial growth factor (anti-VEGF-A) treatment. METHODS: In a cross-sectional study involving 46 patients with nAMD undergoing intravitreal anti-VEGF therapy, 6 AS metabolites were detected in peripheral blood using liquid chromatography - tandem mass spectrometry (LC-MS/MS)...

PURPOSE: Symptomatic vitreous opacifications, so-called floaters, are difficult to objectively assess majorly limiting the possibility of in vitro studies. Forward light scattering was found previously to be increased in eyes with symptomatic floaters. Using an objective setup to measure forward light scattering, we studied the effects of enzymatically digesting the components of the vitreous body on straylight to develop an in vitro model of vitreous opacifications. METHODS: Fifty-seven porcine vitreous bodies were digested using hyaluronidase, collagenase, trypsin, and bromelain, as well as using a combination of hyaluronidase + collagenase and hyaluronidase + bromelain...