Retinal Morphology Research Articles

Visualization of Optic Nerve Structural Patterns in Papilledema Using Deep Learning Variational Autoencoders.

To visualize and quantify structural patterns of optic nerve edema encountered in papilledema during treatment. A novel bi-channel deep-learning variational autoencoder (biVAE) model was trained using 1498 optical coherence tomography (OCT) scans of 125 subjects over time from the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) and 791 OCT scans of 96 control subjects from the University of Iowa. An independent test dataset of 70 eyes from 70 papilledema subjects was used to evaluate the ability of the biVAE model to quantify and reconstruct the papilledema spatial patterns from input OCT scans using only two variables. The montage color maps of the retinal nerve fiber layer (RNFL) and total retinal thickness (TRT) produced by the biVAE model provided an organized visualization of the variety of morphological patterns of optic disc edema (including differing patterns at similar thickness levels). Treatment effects of acetazolamide versus placebo in the IIHTT were also demonstrated in the latent space. In image reconstruction, the mean signed peripapillary retinal nerve fiber layer thickness (pRNFLT) difference ± SD was -0.12 ± 17.34 µm, the absolute pRNFLT difference was 13.68 ± 10.65 µm, and the RNFL structural similarity index reached 0.91 ± 0.05. A wide array of structural patterns of papilledema, integrating the magnitude of disc edema with underlying disc and retinal morphology, can be quantified by just two latent variables. A biVAE model encodes structural patterns, as well as the correlation between channels, and may be applied to visualize individuals or populations with papilledema throughout treatment.

Is Primary Open-Angle Glaucoma a Vascular Disease? Assessment of the Relationship between Retinal Arteriolar Morphology and Glaucoma Severity Using Adaptive Optics.

Retinal vascular abnormalities may be associated with glaucomatous damage. Adaptive optics (AO) is a new technology that enables the analysis of retinal vasculature at the cellular level in vivo. The purpose of this study was to evaluate retinal arteriolar parameters using the rtx1 adaptive optics fundus camera (AO-FC) in patients with primary open-angle glaucoma (POAG) at different stages and to investigate the relationship between these parameters and changes in spectral-domain optical coherence tomography (SD-OCT) and perimetry. Parameters of the retinal supratemporal and infratemporal arterioles (wall thickness (WT), lumen diameter (LD), total diameter (TD), wall-to-lumen ratio (WLR), and cross-sectional area of the vascular wall (WCSA)) were analysed with the rtx1 in 111 POAG eyes, which were divided into three groups according to the severity of the disease, and 70 healthy eyes. The associations between RTX1 values and the cup-to-disk ratio, SD-OCT parameters, and visual field parameters were assessed. Compared with the control group, the POAG groups showed significantly smaller TD and LD values (p < 0.05) and significantly higher WLR and WT values (p < 0.05) for the supratemporal and infratemporal arterioles. TD was significantly positively correlated with the retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) (p < 0.05). LD was significantly positively correlated with the RNFL, GCC, and rim area (p < 0.05). The WLR was significantly negatively correlated with the RNFL, GCC, rim area, and MD (p < 0.05), while it was significantly positively correlated with the cup-to-disc ratio and PSD (p < 0.05). The results suggest that vascular dysfunction is present in POAG, even at a very early stage of glaucoma, and increases with the severity of the disease.

SNAP-25, but not SNAP-23, is essential for photoreceptor development, survival, and function in mice

SNARE-mediated vesicular transport is thought to play roles in photoreceptor glutamate exocytosis and photopigment delivery. However, the functions of Synaptosomal-associated protein (SNAP) isoforms in photoreceptors are unknown. Here, we revisit the expression of SNAP-23 and SNAP-25 and generate photoreceptor-specific knockout mice to investigate their roles. Although we find that SNAP-23 shows weak mRNA expression in photoreceptors, SNAP-23 removal does not affect retinal morphology or vision. SNAP-25 mRNA is developmentally regulated and undergoes mRNA trafficking to photoreceptor inner segments at postnatal day 9 (P9). SNAP-25 knockout photoreceptors develop normally until P9 but degenerate by P14 resulting in severe retinal thinning. Photoreceptor loss in SNAP-25 knockout mice is associated with abolished electroretinograms and vision loss. We find mistrafficked photopigments, enlarged synaptic vesicles, and abnormal synaptic ribbons which potentially underlie photoreceptor degeneration. Our results conclude that SNAP-25, but not SNAP-23, mediates photopigment delivery and synaptic functioning required for photoreceptor development, survival, and function.

Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness—a protocol for a randomised controlled trial (ASTUTE trial)

IntroductionAdalimumab is an effective treatment for autoimmune non-infectious uveitis (ANIU), but it is currently only funded for a minority of patients with ANIU in the UK as it is restricted...

Presentation of cases who underwent vitrectomy for the management of idiopathic epiretinal membranes (iERM)

Epiretinal membrane (ERM) is a term used to describe cellular avascular membranes that form on the inner retinal surface, causing distortion and a decrease in the best corrected visual acuity (BCVA). The prevalence of ERM ranges from 7% to 29% in the general population. Pre‐macular fibroplasia, macular pucker, cellophane maculopathy and pre‐macular fibrosis have also been used to describe this condition. The majority of ERM's have no associated ocular abnormality and are termed idiopathic while the secondary ERM's are associated with preexisting or coexisting conditions such as diabetic retinopathy, cataract surgery, retinal detachment and retinal detachment surgery.Patients with ERM are usually monitored by measuring BCVA and retinal morphology. Last decades a valuable tool in diagnosis, grading, follow up and post‐surgical evaluation of ERM is Optical Coherence Tomography (OCT). OCT can demonstrate the presence of ERM, degree of traction, the presence of cystoid macular edema and various biomarkers such us the disorganization of the inner retinal layers (DRIL).ERM may remain stationary with minimal effect on visual performance. However, some cases may progress with worsening of symptoms, increasing retinal thickness and traction. In those symptomatic cases, surgical peeling of ERM through pars plana vitrectomy (PPV) is the treatment of choice. Some surgeons prefer to peel the Internal limiting membrane (ILM) during primary vitrectomy. Previous studies showed that 40–83% of patients gain on average of 2 or more lines of BCVA after ERM surgery.We present three cases of successful surgical ERM repair. The first patient had a longstanding ERM with DRIL, his symptoms were metamorphopsia and low vision. One month following vitrectomy gained 5 lines. BCVA improved from CF pre‐op to 5/10 Snellen chart 1 month post‐op, with good macular anatomical restoration. The second patient, 1 month postoperatively, had also good anatomical result but presented an eccentric macular hole even though we did not perform an ILM peel. The third patient, 18 months after a successful vitrectomy for ERM peel in his only eye and BCVA 8/10 cc on Snellen chart the first 6 months, he experienced a decline in his vision and an OCT revealed a full thickness macular hole. Hence, a second operation was performed with ILM peel and good anatomical and functional restoration.

Functional and morphological characterization of ocular phenotype in C3H/HeOuJ (Pde6b‐rd1) mice

Aims: C3H/HeOuJ mice (The Jackson Laboratory strain #000635) are homozygous for the retinal degeneration 1 mutation Pde6brd1 (rd1) causing severe visual deficits. The purpose of this study was to characterize the ocular phenotype of male and female mice with the rd1 mutation.Methods: The ophthalmic phenotype of mixed sex rd1 and aged‐matched C57BL/6J wild type (WT) mice (6 females and 4 males for rd1 group, 6 females and 5 males for WT group) was assessed at 3 months of age. Retinal photoreceptor function was quantified using scotopic flash electroretinography (fERG) with six different light intensities: 0.003, 0.01, 0.1, 1, 3 and 10 cd.s/m2 (Celeris, Diagnosys LLC). Retinal morphology was evaluated with spectral domain optical coherence tomography (SD‐OCT) (Envisu R2200, Bioptigen Inc./Leica Microsystems). Retinal thickness was measured from SD‐OCT images using a proprietary convolutional neural network. Optomotor reflex (OMR) was measured as photopic visual acuity and contrast sensitivity at 0.019 and 0.06 cyc/° (OptoDrum Plus, Striatech GmbH). Data were analysed by unpaired t‐test or Mann–Whitney test.Results: At 3 months of age, the rd1 mutation resulted in significant impairment of visual function in both male and female mice compared to age‐matched WT. fERG a and b‐wave amplitudes were decreased by 90% in both sexes (p &lt; 0.001). The rd1 mice had only minimal visual acuity and contrast sensitivity assessed by OMR. Functional decline correlated with structural changes, notably the significant thinning of the retina (p &lt; 0.001).Conclusions: The Pde6brd1 mutation resulted in severe functional and structural changes at 3 months of age. The mice presented significantly decreased but detectable fERG amplitudes, however, they had no functional vision as assessed by OMR. Combining fERG and OMR offers longitudinal in‐life quantification of retinal circuitry and functional vision with great utility for evaluation of novel therapeutic approaches for regeneration of the visual system.

Resilience and neuroprotection: The efficacy of saffron Repron® in counteracting the progression of inherited retinal degeneration

E‐mail: ilaria.piano@unipi.it.Retinal diseases can be induced by several factors, including genetic mutations, environmental stresses, and dysmetabolic processes. The result is a progressive loss of visual function, that can leading to total blindness. Among the diseases still orphaned of an effective therapy for slowing retinal degeneration is Retinitis Pigmentosa (RP). RP is one of the inherited retinal degenerative diseases (IRDs) whose cause is attributed to genetic mutations mainly at the level of rod‐specific genes. To date, about 150 mutations out of 60 different genes have been identified.Several therapeutic strategies are being investigated, although the results are still mostly unsatisfactory and limited to specific diseases, particularly in the case of gene therapy, which is applicable only to specific mutations and therefore not applicable on a large scale. Most of the proposed treatments have been tested in animal models, but few have progressed to human clinical trials. An important approach is to identify targets at the level of those mechanisms that are in common in all forms of RP and that drive disease progression, such as stress‐oxidative and inflammation that all together are known as oxinflammation. Here we provide data showing that in RP natural compounds are effective in slowing down the progression of the disease mainly counteracting oxinflammation. Specifically, saffron “Repron” was proved to be effective in AMD and Stargardt patients as well as in pre‐clinical models both “in vitro” and “in vivo.” We tested this treatment in a IRD model. Preliminary obtained in an animal model of RP (rd10 mice) where saffron treatment was able to slow down even the degeneration of rod due to a genetic mutation. In this study, the treatment began in rd10 pregnant females and continued throughout the weaning phase and then in pups that had become autonomous. Functional, immunohistochemical, molecular biology and biochemical analyses were performed at multiple time points from P20 to P120. The results obtained show a protective effect of saffron on both retinal function and morphology, opening a prospect of preventive treatment for those inherited diseases whose progression is known.

Evaluating the neuroprotective potential of MSC secretome for retinal neurodegenerative diseases

Retinal neurodegenerative diseases (RND), including age‐related macular degeneration, glaucoma, diabetic retinopathy, retinitis pigmentosa, and others, are the most common cause of irreversible low vision and blindness. Although the aetiology and clinical characteristics of retinal RND can differ phenotypically, the neurodegenerative mechanisms of these diseases share common cellular and molecular signalization pathways. No cures are available for most RND, and cell‐based therapy may be a potential treatment through the paracrine properties of mesenchymal stromal cells (MSC). Furthermore, developing cell‐free compositions based on the production of “MSC secretome cocktails” is a promising therapeutic strategy and has significant advantages over using living cells in clinical practice.Ex vivo neuroretina models are adequate tools for evaluating retinal physiology and pathobiology. Neuroretina explant cultures closely resemble in vivo conditions, thus, preserving complex in vivo neuronal connections and retaining the functionality of non‐neuronal cells of the retina. Furthermore, cellular and molecular biology techniques can be applied to retinal explant cultures.In the ex vivo spontaneous neuroretinal degeneration model, the MSC secretome preserves retinal morphology and limits pro‐apoptotic‐ and pro‐necroptotic‐related genes and protein expression. Furthermore, the MSC secretome modulates autophagy‐related genes and proteins and stimulates the activation of antioxidant‐associated genes. Therefore, the neuroprotective ability of the MSC secretome is associated with the inhibition of apoptosis and necroptosis, modulation of autophagy, and activation of the antioxidant machinery during retinal degeneration.MSC secretome shows neuroprotective properties and the potential to modulate retinal responses to neurodegeneration, thus reinforcing the idea that MSC secretome may be a therapeutic strategy for treating RND.

Comparison of retinal parameters between rhesus and cynomolgus macaques.

Nonhuman primates are important research models for basic vision research, preclinical pathogenesis, and treatment studies due to strong similarities in retinal structure and function with humans. We compared retinal parameters between 10 healthy normal rhesus macaques (Macaca mulatta) and 10 cynomolgus macaques (Macaca fascicularis) by optical coherence tomography and electroretinography. The Heidelberg Spectralis® HRA+OCT and Roland multifocal electrophysiometer were used to analyze retinal morphology, multifocal electroretinograms (mfERGs), and full-field electroretinograms (ff-ERGs). Mean retinal thickness was lowest in the central fovea of macaques and did not differ significantly between species, but the retinal thicknesses of the nerve fiber ganglion cell layer and the inner plexiform layer were significantly different. The amplitude density of the N1 wave was lower in rhesus macaques than in cynomolgus macaques in ring and quadrant areas. Dark-adapted 3.0 oscillatory potentials (reflection of amacrine cell activity) and light-adapted 30-hz flicker ERG (a sensitive cone-pathway-driven response) waveforms of the ff-ERG were similar in both species, while the times to peaks in dark-adapted 0.01 ERG (the rod-driven response of bipolar cells) and dark-adapted 3.0 ERG (combined rod and cone system responses) as well as the implicit times of the a- and b-waves in light-adapted 3.0 ERG (the single-flash cone response) were substantially different. This study provides normative retinal parameters for nonhuman primate research on basic and clinical ophthalmology, as well as a reference for researchers in the appropriate selection of rhesus or cynomolgus macaques as models for ophthalmology studies.

Metabolomics combined with intestinal microbiota reveals the mechanism of compound Qilian tablets against diabetic retinopathy.

Diabetic retinopathy (DR) is one of the common chronic complications of diabetes mellitus, which has developed into the leading cause of irreversible visual impairment in adults worldwide. Compound Qilian tablets (CQLT) is a traditional Chinese medicine (TCM) developed for treating DR, but its mechanism is still unclear. This study explored the mechanism of action of CQLT in treating DR through metabolomics and intestinal microbiota. Histopathologic examination of the pancreas and retina of Zucker diabetic fatty (ZDF) rats and immunohistochemistry were used to determine the expression levels of retinal nerve damage indicators ionized calcium binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP). Rat fecal samples were tested by LC-MS metabolomics to search for potential biomarkers and metabolic pathways for CQLT treatment of DR. Characteristic nucleic acid sequences of rat intestinal microbiota from each group were revealed using 16S rDNA technology to explore key microbes and related pathways for CQLT treatment of DR. At the same time, we investigated the effect of CQLT on the gluconeogenic pathway. After CQLT intervention, islet cell status was improved, Iba-1 and GFAP expression were significantly decreased, and abnormal retinal microvascular proliferation and exudation were ameliorated. Metabolomics results showed that CQLT reversed 20 differential metabolites that were abnormally altered in DR rats. Intestinal microbiota analysis showed that treatment with CQLT improved the abundance and diversity of intestinal flora. Functional annotation of metabolites and intestinal flora revealed that glycolysis/gluconeogenesis, alanine, aspartate and glutamate metabolism, starch and sucrose metabolism were the main pathways for CQLT in treating DR. According to the results of correlation analysis, there were significant correlations between Iba-1, GFAP, and intestinal microbiota and metabolites affected by CQLT. In addition, we found that CQLT effectively inhibited the gluconeogenesis process in diabetic mice. In conclusion, CQLT could potentially reshape intestinal microbiota composition and regulate metabolite profiles to protect retinal morphology and function, thereby ameliorating the progression of DR.

Adaptive Illuminance Effects on Retinal Morphology and Refraction: A Comprehensive Study of Night Myopia.

We aimed to study the optical and retinal modifications that occur after adapting to different lighting conditions including photopic, mesopic, scotopic, blue light and red light conditions. Thirty young healthy subjects with a mean age of 23.57 ± 3.45 years were involved in the study (both eyes included). They underwent aberrometry and optical coherence tomography at both the central and peripheral retina with the 3 × 3 mm2 macular cube protocol before starting adaptation to the illuminations (baseline) and after remaining for 5 min under the five different lighting conditions inside a controlled lighting cabinet. Significant myopization (p = 0.002) was observed under scotopic and mesopic lighting conditions, while hypermetropization occurred under the influence of blue LED light. In the central retina, a significant thickening of the inner temporal (p = 0.025) and outer inferior (p = 0.021) areas was observed in the scotopic area, and the thickening increased even more under blue and red light. The mean central thickness decreased significantly under photopic lighting conditions (p = 0.038). There was an increase in the mean volume of the central retinal area with red light and a reduction in the volume under photopic lighting (p = 0.039). In the peripheral retina, no significant thickness changes were observed after adapting to any of the lighting conditions (p > 0.05). Regarding morphological changes, a significant increase in retinal eccentricity (p = 0.045) and the shape factor (p = 0.036) was found. In addition, a significant correlation was found only between the eccentricity and volume of the central retina in scotopic conditions (r = -0.265; p = 0.041), meaning that a higher volume was associated with lower retinal eccentricity. When exposed to different lighting conditions, the retina changes in shape, and ocular refraction is modified to adapt to each condition, revealing the phenomenon of night myopia when transitioning from photopic to scotopic regimes.

Retrospective analysis of the progression of early dry age-related macular degeneration in patients receiving versus not receiving a multi-component nutraceutical for four years

Purpose: To retrospectively analyze the optical coherence tomography (OCT) changes in retinal morphology and progression in these changes in patients with early dry age-related macular degeneration (AMD) receiving versus not receiving a multi-component nutraceutical daily for four years. Material and Methods: We retrospectively analyzed disease progression in 52 patients (98 eyes) with early dry AMD who had been regularly followed up for four years. Group 1 was comprised of 24 patients (98 eyes) who had been receiving vitamin and mineral tablets containing the AREDS2 formulation plus resveratrol and vitamin D daily for four years. Group 2 was comprised of 28 patients (53 eyes) who had not been receiving any nutritional supplement. Retinal morphology was assessed by OCT and OCT angiography. Results: In group 1, best-corrected visual acuity (BCVA) did not change after completion of the 4-year observation period compared to baseline (0.6 ± 02, p = 0.72). In group 2, BCVA was 0.6 ± 0.2 at baseline and decreased to 0.2 ± 0.2 in four years (p ≤ 0.001). In patients with a low to moderate risk of progression in groups 1 and 2, the four-year progression rate was 15.4% and 45.4%, respectively, which corresponds to an annual progression rate of 3.8% and 11.3%, respectively. In patients with a high risk of progression in groups 1 and 2, the four-year progression rate was 26.3% and 80%, respectively, which corresponds to an annual progression rate of 6.5% and 20%, respectively. Patients who had early dry AMD eyes with a low to moderate risk of progression (and a high risk of progression) at baseline and were not taking the nutritional supplement, had 4.58 greater odds (95% CI, 1.291 – 16.267; р = 0.018) [and 11.2 greater odds (95% CI, 2.505 – 50.081; р = 0.0016)] of having AMD progression than those receiving the nutritional supplement daily for four years. Conclusion: A regular intake of tablets containing the AREDS2 formulation plus resveratrol and vitamin D slows the progression of early dry AMD, especially in eyes with a high risk of disease progression, and contributes to the preservation of visual function.

Advancing Diabetic Retinopathy Diagnosis: Leveraging Optical Coherence Tomography Imaging with Convolutional Neural Networks.

Diabetic retinopathy (DR) is a vision-threatening complication of diabetes, necessitating early and accurate diagnosis. The combination of optical coherence tomography (OCT) imaging with convolutional neural networks (CNNs) has emerged as a promising approach for enhancing DR diagnosis. OCT provides detailed retinal morphology information, while CNNs analyze OCT images for automated detection and classification of DR. This paper reviews the current research on OCT imaging and CNNs for DR diagnosis, discussing their technical aspects and suitability. It explores CNN applications in detecting lesions, segmenting microaneurysms, and assessing disease severity, showing high sensitivity and accuracy. CNN models outperform traditional methods and rival expert ophthalmologists' results. However, challenges such as dataset availability and model interpretability remain. Future directions include multimodal imaging integration and real-time, point-of-care CNN systems for DR screening. The integration of OCT imaging with CNNs has transformative potential in DR diagnosis, facilitating early intervention, personalized treatments, and improved patient outcomes. Abbreviations: DR = Diabetic Retinopathy, OCT = Optical Coherence Tomography, CNN = Convolutional Neural Network, CMV = Cytomegalovirus, PDR = Proliferative Diabetic Retinopathy, AMD = Age-Related Macular Degeneration, VEGF = vascular endothelial growth factor, RAP = Retinal Angiomatous Proliferation, OCTA = OCT Angiography, AI = Artificial Intelligence.

Long-term tralopyril exposure results in endocrinological and transgenerational toxicity: A two-generation study of marine medaka (Oryzias melastigma)

This study aims to investigate the impact of tralopyril, a newly developed marine antifouling agent, on the reproductive endocrine system and developmental toxicity of offspring in marine medaka. The results revealed that exposure to tralopyril (0, 1, 20 μg/L) for 42 days resulted in decreased reproductive capacity in marine medaka. Moreover, it disrupted the levels of sex hormones E2 and T, as well as the transcription levels of genes related to the HPG axis, such as cyp19b and star. Sex-dependent differences were observed, with females experiencing more pronounced effects. Furthermore, intergenerational toxicity was observed in F1 offspring, including increased heart rate, changes in retinal morphology and cartilage structure, decreased swimming activity, and downregulation of transcription levels of relevant genes (HPT axis, GH/IGF axis, cox, bmp4, bmp2, runx2, etc.). Notably, the disruption of the F1 endocrine system by tralopyril persisted into adulthood, indicating a transgenerational effect. Molecular docking analysis suggested that tralopyril's RA receptor activity might be one of the key factors contributing to the developmental toxicity observed in offspring. Overall, our study highlights the potential threat posed by tralopyril to the sustainability of fish populations, as it can disrupt the endocrine system and negatively impact aquatic organisms for multiple generations.

Does Background Matter? A Comparative Characterization of Mouse Models of Autosomal Retinitis Pigmentosa rd1 and Pde6b-KO.

Many retinal degenerative diseases result in vision impairment or permanent blindness due to photoreceptor loss or dysfunction. It has been observed that Pde6brd1 mice (rd1), which carry a spontaneous nonsense mutation in the pde6b gene, have a strong phenotypic similarity to patients suffering from autosomal recessive retinitis pigmentosa. In this study, we present a novel mouse model of retinitis pigmentosa generated through pde6b gene knockout using CRISPR/Cas9 technology. We compare this Pde6b-KO mouse model to the rd1 mouse model to gain insights into the progression of retinal degeneration. The functional assessment of the mouse retina and the tracking of degeneration dynamics were performed using electrophysiological methods, while retinal morphology was analyzed through histology techniques. Interestingly, the Pde6b-KO mouse model demonstrated a higher amplitude of photoresponse than the rd1 model of the same age. At postnatal day 12, the thickness of the photoreceptor layer in both mouse models did not significantly differ from that of control animals; however, by day 15, a substantial reduction was observed. Notably, the decline in the number of photoreceptors in the rd1 model occurred at a significantly faster rate. These findings suggest that the C3H background may play a significant role in the early stages of retinal degeneration.

Essential Role of XBP1 in Maintaining Photoreceptor Synaptic Integrity in Early Diabetic Retinopathy.

Diabetic retinopathy (DR) is a leading cause of blindness in working-age adults characterized by retinal dysfunction and neurovascular degeneration. We previously reported that deletion of X-box binding protein 1 (XBP1) leads to accelerated retinal neurodegeneration in diabetes; however, the mechanisms remain elusive. The goal of this study is to determine the role of XBP1 in the regulation of photoreceptor synaptic integrity in early DR. Diabetes was induced by streptozotocin in retina-specific XBP1 conditional knockout (cKO) or wild-type (WT) mice to generate diabetic cKO (cKO/DM) or WT/DM mice for comparison with nondiabetic cKO (cKO/NDM) and WT/NDM mice. Retinal morphology, structure, and function were assessed by immunohistochemistry, optical coherence tomography, and electroretinogram (ERG) after 3months of diabetes. The synapses between photoreceptors and bipolar cells were examined by confocal microscopy, and synaptic integrity was quantified using the QUANTOS algorithm. We found a thinning of the outer nuclear layer and a decline in the b-wave amplitude in dark- and light-adapted ERG in cKO/DM mice compared to all other groups. In line with these changes, cKO mice showed increased loss of synaptic integrity compared to WT mice, regardless of diabetes status. In searching for candidate molecules responsible for the loss of photoreceptor synaptic integrity in diabetic and XBP1-deficient retinas, we found decreased mRNA and protein levels of DLG4/PSD-95 in cKO/DM retina compared to WT/DM. These findings suggest that XBP1 is a crucial regulator in maintaining synaptic integrity and retinal function, possibly through regulation of synaptic scaffold proteins.

Optometry in adults with microdeletion 22q11.2: The eye as a window to the brain

PurposeThe 22q11.2 deletion syndrome (22q11.2DS) has an estimated prevalence of 1:2148 live births and is associated with an increased risk of schizophrenia, cognitive decline and early-onset Parkinson’s disease. Because retinal and cerebral tissue share embryological, physiological and anatomical characteristics, retinal blood vessel morphology and retinal nerve fiber layer (RNFL) thickness have been proposed as non-invasive biomarkers for psychiatric and neurodegenerative disorders. In this exploratory study, we examined these potential biomarkers in adults with 22q11.2DS relative to controls, and in relation to age. MethodsCentral retinal artery and vein equivalent, fractal dimension, and vascular tortuosity, obtained through fundoscopy, and peripapillary RNFL and macular thickness, obtained through optical coherence tomography, were compared between adults with 22q11.2DS and sex- and age-matched controls. ResultsMean retinal vascular fractal dimension and tortuosity values were significantly higher in the group of adults with 22q11.2DS than in controls (p < 0.001; p < 0.001). RNFL was thicker in the nasal segment (p = 0.002) in 22q11.2DS, and a trend for thinner RNFL in the nasal and temporal inferior segments (p = 0.05 and p = 0.06, respectively) was found. There were significant negative correlations with age for fractal dimension (p < 0.001) and RNFL thickness in the global (p = 0.007), temporal inferior (p = 0.005) and temporal superior (p = 0.04) segments in adults with 22q11.2DS, but not in controls. ConclusionsOur results indicate higher retinal vascular fractal dimension and tortuosity, and a decrease in fractal dimension and RNFL thickness in relation to age in adults with 22q11.2DS. Our findings support future studies that focus on retinal fractal dimension and RNFL thickness as potential biomarkers for age-related manifestations in 22q11.2 including psychotic and (early) neurodegenerative disorders.

Central macular morphology and optic nerve fibre layer thickness in young adults born premature and screened for retinopathy of prematurity.

To investigate central retinal morphology and optic retinal nerve fibre layer (RNFL) in prematurely born young adults and compare to term born controls. The participants were 59 prematurely born individuals, with a birthweight ≤1.500 g, and 44 term born controls, all 25-29 years of age. Visual acuity (VA) and contrast sensitivity (CS) were assessed. The retinal macular thickness, ganglion cell-inner plexiform layer (GC-IPL) thickness and RNFL thickness were assessed with Cirrus optical coherence tomography (OCT). Central macular thickness was increased (mean 26.7 μm) in prematurely born individuals compared to controls. The macular GC-IPL was thinner (mean 3.84 μm), also when excluding those with previous retinopathy of prematurity (ROP) and those with neurological complications. Gestational age at birth and previous treatment of ROP were risk factors for a thicker macula, however, not for reduced GC-IPL. The average peripapillary RNFL was thinner (mean 4.61 μm) in the prematurely born individuals, also when excluding those with previous ROP and/or neurological complications. Within the prematurely born group, treated ROP was correlated with increased average RNFL. Further, both better VA and CS were associated with thinner optic nerve RNFL and thicker average GC-IPL. Macular and optic nerve morphology were influenced by premature birth as assessed with OCT in adult individuals. Gestational age at birth and treatment for ROP seemed to affect central macular thickness, and treated ROP affected the peripapillary RNFL. Thus, retinal sequelae remained in adulthood.

Bisphenol A alters retinal morphology, visually guided behavior, and thyroid hormone levels in zebrafish larvae

Bisphenols are industrial chemicals that are produced in large quantities and have been detected in all parts of the environment as well as in a multitude of different organisms including humans and fish. Several bisphenols, such as bisphenol A (BPA) and bisphenol F, have been shown to disrupt endocrine systems thereby affecting development and reproduction. While numerous studies investigated the effect of bisphenols on estrogen signaling, their impact on the thyroid hormone system (THS), which is vital for neurodevelopment including sensory development, has been explored to a lesser extent. The present work selected BPA as a representative for structurally similar bisphenols and assessed its impact on the THS as well as sensory development and function in zebrafish. To this end, zebrafish were exposed to BPA until up to 8 days post fertilization (dpf) and thyroid hormone levels, eye morphology, and sensory-mediated behaviors were analyzed. Zebrafish larvae exposed to BPA showed altered retinal layering, decreased motility across varying light conditions, and a loss of responsiveness to red light. Furthermore, whole-body levels of the thyroid hormones thyroxine (T4) and 3,5-diiodothyronine (3,5-T2) were significantly decreased in 5 dpf zebrafish. Taken together, BPA disrupted THS homeostasis and compromised visual development and function, which is pivotal for the survival of fish larvae. This work underlines the necessity for ongoing research on BPA and its numerous substitutes, particularly concerning their effects on the THS and neurodevelopment, to ensure a high level of protection for the environment and human health.

Arteriovenous Length Ratio: A Novel Method for Evaluating Retinal Vasculature Morphology and Its Diagnostic Potential in Eye-Related Diseases.

Retinal imaging is a non-invasive technique used to scan the back of the eye, enabling the extraction of potential biomarkers like the artery and vein ratio (AVR). This ratio is known for its association with various diseases, such as hypertensive retinopathy (HR) or diabetic retinopathy, and is crucial in assessing retinal health. HR refers to the morphological changes in retinal vessels caused by persistent high blood pressure. Timely identification of these alterations is crucial for preventing blindness and reducing the risk of stroke-related fatalities. The main objective of this paper is to propose a new method for assessing one of the morphological changes in the fundus through morphometric analysis of retinal images. The proposed method in this paper introduces a novel approach called the arteriovenous length ratio (AVLR), which has not been utilized in previous studies. Unlike commonly used measures such as the arteriovenous width ratio or tortuosity, AVLR focuses on assessing the relative length of arteries and veins in the retinal vasculature. The initial step involves segmenting the retinal blood vessels and distinguishing between arteries and veins; AVLR is calculated based on artery and vein caliber measurements for both eyes. Nine equations are used, and the length of both arteries and veins is measured in the region of interest (ROI) covering the optic disc for each eye. Using the AV-Classification dataset, the efficiency of the iterative AVLR assessment is evalutaed. The results show that the proposed approach performs better than the existing methods. By introducing AVLR as a diagnostic feature, this paper contributes to advancing retinal imaging analysis. It provides a valuable tool for the timely diagnosis of HR and other eye-related conditions and represents a novel diagnostic-feature-based method that can be integrated to serve as a clinical decision support system.