Retinal Structure Research Articles

Therapeutic Potential of Quercetin in Diabetic Neuropathy and Retinopathy: Exploring Molecular Mechanisms.

Diabetes mellitus poses a significant health challenge globally, often leading to debilitating complications, such as neuropathy and retinopathy. Quercetin, a flavonoid prevalent in fruits and vegetables, has demonstrated potential therapeutic effects in these conditions due to its antioxidant, anti-inflammatory, and neuroprotective properties. This review summarizes and provides a comprehensive understanding of the molecular mechanisms underlying the efficacy of quercetin in ameliorating diabetic neuropathy and retinopathy. A thorough search was carried out across scientific databases, such as SciFinder, PubMed, and Google Scholar, to gather pertinent literature regarding the effect of quercetin on diabetic neuropathy and retinopathy till February 2024. Preclinical studies indicate that quercetin mitigates neuropathic pain, sensory deficits, and nerve damage associated with diabetic neuropathy by improving neuronal function, reducing DNA damage, regulating pro-inflammatory cytokines, enhancing antioxidant enzyme levels and endothelial function, as well as restoring nerve injuries. In diabetic retinopathy, quercetin shows the potential to preserve retinal structure and function, inhibiting neovascularization, preventing retinal cell death, reducing pro-inflammatory cytokines, and increasing neurotrophic factor levels. Moreover, through modulating key signaling pathways, such as AMP-activated Protein Kinase (AMPK) activation, Glucose Transporter 4 (GLUT 4) upregulation, and insulin secretion regulation, quercetin demonstrates efficacy in reducing oxidative stress and inflammation, thereby protecting nerve and retinal tissues. Despite promising preclinical findings, challenges, such as limited bioavailability, necessitate further research to optimize quercetin's clinical application in order to establish its optimal dosage, formulation, and long-term efficacy in clinical settings.

Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR)- the new lacunae: a case report

BackgroundMicrocephaly with or without chorioretinopathy, lymphedema, or mental retardation is a rare autosomal dominant disease caused by mutations in KIF11 which disrupt EG5 protein function, impacting the development and maintenance of retinal and lymphatic structures due to its expression in the retinal photoreceptor cilia. The primary ocular finding in MCLMR is chorioretinopathy. Additional features can include microphthalmia, angle-closure glaucoma, persistent hyperplastic primary vitreous, cataract, pseudo-coloboma, persistent hyaloid artery, and myopic or hypermetropic astigmatism. The appearance of the chorioretinal lesions as white to pinkish, round, non-elevated atrophic areas devoid of blood vessels resembles the lacunae in Aicardy syndrome. Due to the lack of systematic description of the lesions and significant phenotypical variability, there is an impending need for a detailed report of each case.Case presentationA child with microcephaly detected in the third trimester of gestation began her following in the ophthalmology department due to a non-visually significant cataract. Shortly after, she developed nystagmus and large-angle alternating esotropia with cross-fixation. Her fundus initially showed a pallid optic disc and pigmentary changes, developing thereafter retinal lacunae and a retinal fold. Her differential diagnosis accompanied the dynamic changes in her fundus, which included congenital infections, Leber´s Congenital Amaurosis and Aicardy syndrome. At 19 months old, genetic testing identified a heterozygous mutation (c.1159 C > T, p.Arg387*) in the KIF11 gene. The patient underwent bilateral medial rectus muscle recession surgery at 2 years old for persistent esotropia, with significant improvement. Refraction revealed a hyperopic astigmatism in both eyes (+ 0.25 -2.50 × 180 OD and + 0.75 -2.00 × 170 OS). She continues to require right eye patching for 2 hours daily.ConclusionsThis case report expands the phenotypic spectrum of MCLMR by demonstrating a unique combination of retinal features which sheds new light on differential diagnosis from Aicardy syndrome. Our findings emphasize the significant phenotypic variability associated with MCLMR, particularly regarding ocular involvement. This underscores the importance of detailed clinical evaluation and comprehensive reporting of cases to improve our understanding of the disease spectrum and genotype-phenotype correlations.

Impact of cumulative dose of hydroxychloroquine on retinal structures.

What is known • Hydroxychloroquine (HCQ) is widely used for autoimmune disorders but is associated with the risk of retinal toxicity. • Early detection of retinal structural changes due to HCQ toxicity remains challenging, and cumulative HCQ dose as a risk factor has conflicting clinical relevance. What Is New • Higher cumulative HCQ doses are significantly associated with thinner outer retinal layers (foveal, parafoveal, and perifoveal regions). • No significant associations were found between HCQ cumulative dose and inner retinal thickness or age.

Association of outer retinal and choroidal alterations with neuroimaging and clinical features in posterior cortical atrophy

BackgroundPosterior cortical atrophy (PCA) is a rare condition characterized by early-onset and progressive visual impairment. Individuals with PCA have relatively early-onset and progressive dementia, posing certain needs for early detection. Hence, this study aimed to investigate the association of alterations in outer retinal and choroidal structure and microvasculature with PCA neuroimaging and clinical features and the possible effects of apolipoprotein E(APOE) ε4 allele on outer retinal and choroidal alterations in participants with PCA, to detect potential ocular biomarkers for PCA screening.MethodsThis cross-sectional study included PCA and age- and sex-matched healthy control participants from June 2022 to December 2023. All participants with PCA completed a comprehensive neurological evaluation. All participants were recorded baseline information and underwent an ophthalmic evaluation. Quantitative analyses were performed using swept-source optical coherence tomography (SS-OCT) and angiography (SS-OCTA). Adaptive optics scanning laser ophthalmoscopy (AO-SLO) was performed in some patients. In participants with PCA, the influence of APOE ε4 on outer retinal and choroidal alterations and the correlation of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA were investigated.ResultsA total of 28 participants (53 eyes) with PCA and 56 healthy control participants (112 eyes) were included in the current study. Compared with healthy control participants, participants with PCA had significantly reduced outer retinal thickness (ORT) (p < 0.001), choriocapillaris vessel density (VD) (p = 0.007), choroidal vascular index (CVI) (p = 0.005) and choroidal vascular volume (CVV) (p = 0.003). In participants with PCA, APOE ε4 carriers showed thinner ORT (p = 0.009), and increased choriocapillaris VD (p = 0.004) and CVI (p = 0.004). The PCA neuroimaging features were positively associated with the ORT, CVI and CVV. Furthermore, differential correlations were observed of PCA clinical features with the CRT, CVV and CVI.ConclusionsOur findings highlighted the association of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA. Noninvasive SS-OCT and SS-OCTA can provide potential biomarkers for the diagnosis and management of PCA, improving awareness of PCA syndrome among ophthalmologists, neurologists, and primary care providers.

ANATOMIC OUTCOMES OF LENS-SPARING VITRECTOMY FOR STAGE 3 OR 4 FAMILIAL EXUDATIVE VITREORETINOPATHY.

To report the anatomic outcomes and retinal structure changes from lens-sparing vitrectomy (LSV) for eyes with Stage 3 or 4 familial exudative vitreoretinopathy (FEVR). Overall, 133 consecutive eyes of 119 patients with Stage 3 (51 eyes) or 4 (82 eyes) FEVR who underwent LSV between January 2012 and May 2023 were retrospectively reviewed. One hundred twenty-nine eyes (97.0%) achieved traction relief through one LSV operation. The extent of retinal detachment improved in 98 eyes (73.7%), remained stable in 32 eyes (24.1%), and progressed in three eyes (2.3%). At long-term follow-up, 39 (29.3%) and 60 (45.1%) eyes had completely or partially reattached retina, respectively. The median change of venular angle was 3.6° (95% CI, 3.5-10.5; P < 0.001) and -9.9° (95% CI, -15.8 to -4.6; P < 0.001) for temporal and nasal vessels, respectively. The mean disk-fovea distance was 0.3 papillary diameter shorter (95% CI, -0.4 to -0.2; P < 0.001), and the mean temporal venular arcade distance was 0.02 papillary diameter larger (95% CI, -0.16 to 0.21; P = 0.361). These results suggest that LSV can relieve vitreoretinal traction and reattach the retina in late-stage FEVR eyes. Improvements in temporal and nasal venular angle and disk-fovea distance reflect positive retinal structure changes for patients.

Subthreshold Micropulse Laser Versus Oral Spironolactone in Chronic Central Serous Chorioretinopathy: A Quasi-Randomized Controlled Trial.

To compare the efficacy and safety of subthreshold micropulse laser (SML) and spironolactone therapy for treating chronic central serous chorioretinopathy (CSC). This was a quasi-randomized controlled trial. Eligible patients were quasi-randomized at a 1:1 ratio to receive SML or oral spironolactone and were assessed at 3months after treatment. A total of 84 patients (90 eyes) were randomly assigned to receive SML (n = 45) or spironolactone (n = 39) initially. At last follow-up, 59.5% of patients in the SML group had complete resolution of subretinal fluid (SRF) compared to 43.6% in spironolactone group (P = 0.362). The mean visual acuity did not significantly improve between the two groups (0.38 ± 0.44 vs. 0.43 ± 0.43 logMAR). The central retinal thickness was decreased from 335.06 ± 120.25µm to 222.15 ± 94.90µm in the SML group and from 308.02 ± 90.69µm to 257.27 ± 102.28µm in the spironolactone group. After treatment, subfoveal choroidal thickness, total choroidal area, and stromal and luminal choroidal area were significantly lower in the spironolactone group as compared to the SML group. During the entire visit, the recurrence rate of SRF was 9.1% in the SML group compared to 35.3% in the spironolactone group. Slight adverse events occurred more frequently in the spironolactone group (0% vs. 16%). Both SML and oral spironolactone were effective and safe treatments to ameliorate retinal anatomical structures for chronic CSC. A lower recurrence rate and fewer adverse effects were observed in the SML group, and better choroidal structure recovery was seen in the spironolactone group. The investigation of SML and oral spironolactone may inform evidence-based clinical decisions for chronic CSC patients.

Retina as a potential biomarker for the early stage of Alzheimer's disease spectrum.

To characterize the retinal microvasculature and structure in subjective cognitive decline (SCD) and identify the potential biomarker for the early stage of the Alzheimer's disease (AD) spectrum. In this study, 35 patients with SCD, 36 with cognitive impairment, and 29 with normal cognition (NC) were enrolled. Optical coherence tomography angiography was employed to assess retinal vascular density, fovea avascular zone area, and retinal thickness. The parameters reflecting retinal perfusion and structure were compared among the three groups. In addition, the association between retinal parameters, cerebral blood flow (CBF), and peripheral blood biomarkers in the SCD stage was analyzed. The superficial vascular complex (SVC) vascular density in the macula and retinal nerve fiber layer thickness in the peripapillary were significantly reduced in individuals with SCD compared to NC. Furthermore, there was a positive correlation between macular ganglion cell complex thickness and CBF in SCD. The retinal microvasculature and structure exhibit alterations in individuals with SCD. Macular ganglion cell complex thickness demonstrates correlations with cerebral perfusion. The retina holds potential as a novel biomarker for early detection of AD.

Preservation of retinal structure and function in two mouse models of inherited retinal degeneration by ONL1204, an inhibitor of the Fas receptor

Due to the large number of genes and mutations that result in inherited retinal degenerations (IRD), there has been a paucity of therapeutic options for these patients. There is a large unmet need for therapeutic approaches targeting shared pathophysiologic pathways in a mutation-independent manner. The Fas receptor is a major activator and regulator of retinal cell death and inflammation in a variety of ocular diseases. We previously reported the activation of Fas-mediated photoreceptor (PR) cell death in two different IRD mouse models, rd10 and P23H, and demonstrated the protective effect of genetic Fas inhibition. The purpose of this study was to examine the effects of pharmacologic inhibition of Fas in these two models by intravitreal injection with a small peptide inhibitor of the Fas receptor, ONL1204. A single intravitreal injection of ONL1204 was given to one eye of rd10 mice at P14. Two intravitreal injections of ONL1204 were given to the P23H mice, once at P14 and again at 2-months of age. The fellow eyes were injected with vehicle alone. Fas activation, rate of PR cell death, retinal function, and the activation of immune cells in the retina were evaluated. In both rd10 and P23H mice, ONL1204 treatment resulted in decreased number of TUNEL (+) PRs, decreased caspase 8 activity, enhanced photoreceptor cell counts, and improved visual function compared with vehicle treated fellow eyes. Treatment with ONL1204 also reduced immune cell activation in the retinas of both rd10 and P23H mice. The protective effect of pharmacologic inhibition of Fas by ONL1204 in two distinct mouse models of retinal degeneration suggests that targeting this common pathophysiologic mechanism of cell death and inflammation represents a potential therapeutic approach to preserve the retina in patients with IRD, regardless of the genetic underpinning.

Lycium barbarum glycopeptide promotes neuroprotection in ET-1 mediated retinal ganglion cell degeneration

BackgroundVascular dysregulation is one of the major risk factors of glaucoma, and endothelin-1 (ET-1) may have a role in the pathogenesis of vascular-related glaucoma. Fruit extract from Lycium Barbarum (LB) exhibits anti-ageing and multitarget mechanisms in protecting retinal ganglion cells (RGC) in various animal models. To investigate the therapeutic efficacy of LB glycoproteins (LbGP) in ET-1 induced RGC degeneration, LbGP was applied under pre- and posttreatment conditions to an ET-1 mouse model. Retina structural and functional outcomes were characterised using clinical-based techniques.MethodsAdult C57BL/6 mice were randomly allocated into four experimental groups, namely vehicle control (n = 9), LbGP-Pretreatment (n = 8), LbGP-Posttreatment (day 1) (n = 8) and LbGP-Posttreatment (day 5) (n = 7). Oral administration of LbGP 1 mg/Kg or PBS for vehicle control was given once daily. Pre- and posttreatment (day 1 or 5) were commenced at 1 week before and 1 or 5 days after intravitreal injections, respectively, and were continued until postinjection day 28. Effects of treatment on retinal structure and functions were evaluated using optical coherence tomography (OCT), doppler OCT and electroretinogram measurements at baseline, post-injection days 10 and 28. RGC survival was evaluated by using RBPMS immunostaining on retinal wholemounts.ResultsET-1 injection in vehicle control induced transient reductions in arterial flow and retinal functions, leading to significant RNFL thinning and RGC loss at day 28. Although ET-1 induced a transient loss in blood flow or retinal functions in all LbGP groups, LbGP treatments facilitated better restoration of retinal flow and retinal functions as compared with the vehicle control. Also, all three LbGP treatment groups (i.e. pre- and posttreatments from days 1 or 5) significantly preserved thRNFL thickness and RGC densities. No significant difference in protective effects was observed among the three LbGP treatment groups.ConclusionLbGP demonstrated neuroprotective effects in a mouse model of ET-1 induced RGC degeneration, with treatment applied either as a pretreatment, immediate or delayed posttreatment. LbGP treatment promoted a better restoration of retinal blood flow, and protected the RNFL, RGC density and retinal functions. This study showed the translational potential of LB as complementary treatment for glaucoma management.

Arylphthalide Delays Diabetic Retinopathy via Immunomodulating the Early Inflammatory Response in an Animal Model of Type 1 Diabetes Mellitus.

Diabetic retinopathy (DR) is one of the most prevalent secondary complications associated with diabetes. Specifically, Type 1 Diabetes Mellitus (T1D) has an immune component that may determine the evolution of DR by compromising the immune response of the retina, which is mediated by microglia. In the early stages of DR, the permeabilization of the blood-retinal barrier allows immune cells from the peripheral system to interact with the retinal immune system. The use of new bioactive molecules, such as 3-(2,4-dihydroxyphenyl)phthalide (M9), with powerful anti-inflammatory activity, might represent an advance in the treatment of diseases like DR by targeting the immune systems responsible for its onset and progression. Our research aimed to investigate the molecular mechanisms involved in the interaction of specific cells of the innate immune system during the progression of DR and the reduction in inflammatory processes contributing to the pathology. In vitro studies were conducted exposing Bv.2 microglial and Raw264.7 macrophage cells to proinflammatory stimuli for 24 h, in the presence or absence of M9. Ex vivo and in vivo approaches were performed in BB rats, an animal model for T1D. Retinal explants from BB rats were cultured with M9. Retinas from BB rats treated for 15 days with M9 via intraperitoneal injection were analyzed to determine survival, cellular signaling, and inflammatory markers using qPCR, Western blot, or immunofluorescence approaches. Retinal structure images were acquired via Spectral-Domain-Optical Coherence Tomography (SD-OCT). Our results show that the treatment with M9 significantly reduces inflammatory processes in in vitro, ex vivo, and in vivo models of DR. M9 works by inhibiting the proinflammatory responses during DR progression mainly affecting immune cell responses. It also induces an anti-inflammatory response, primarily mediated by microglial cells, leading to the synthesis of Arginase-1 and Hemeoxygenase-1(HO-1). Ultimately, in vivo administration of M9 preserves the retinal integrity from the degeneration associated with DR progression. Our findings demonstrate a specific interaction between both retinal and systemic immune cells in the progression of DR, with a differential response to treatment, mainly driven by microglia in the anti-inflammatory action. In vivo treatment with M9 induces a switch in immune cell phenotypes and functions that contributes to delaying the DR progression, positioning microglial cells as a new and specific therapeutic target in DR.

Multimodal Retinal Imaging Classification for Parkinson's Disease Using a Convolutional Neural Network.

Changes in retinal structure and microvasculature are connected to parallel changes in the brain. Two recent studies described machine learning algorithms trained on retinal images and quantitative data that identified Alzheimer's dementia and mild cognitive impairment with high accuracy. Prior studies also demonstrated retinal differences in individuals with PD. Herein, we developed a convolutional neural network (CNN) to classify multimodal retinal imaging from either a Parkinson's disease (PD) or control group. We trained a CNN to receive retinal image inputs of optical coherence tomography (OCT) ganglion cell-inner plexiform layer (GC-IPL) thickness color maps, OCT angiography 6 × 6-mm en face macular images of the superficial capillary plexus, and ultra-widefield (UWF) fundus color and autofluorescence photographs to classify the retinal imaging as PD or control. The model consists of a shared pretrained VGG19 feature extractor and image-specific feature transformations which converge to a single output. Model results were assessed using receiver operating characteristic (ROC) curves and bootstrapped 95% confidence intervals for area under the ROC curve (AUC) values. In total, 371 eyes of 249 control subjects and 75 eyes of 52 PD subjects were used for training, validation, and testing. Our best CNN variant achieved an AUC of 0.918. UWF color photographs were the most effective imaging input, and GC-IPL thickness maps were the least contributory. Using retinal images, our pilot CNN was able to identify individuals with PD and serves as a proof of concept to spur the collection of larger imaging datasets needed for clinical-grade algorithms. Developing machine learning models for automated detection of Parkinson's disease from retinal imaging could lead to earlier and more widespread diagnoses.

Electroacupuncture improves retinal function in myopia Guinea pigs probably via inhibition of the RhoA/ROCK2 signaling pathway

ObjectiveTo investigate the effect of electroacupuncture (EA) on retinal function in guinea pigs with negative lens-induced myopia (LIM) by inhibiting the RhoA/ROCK2 signaling pathway. MethodsGuinea pigs were randomly divided into normal control (NC) group, LIM group, EA group, SHAM acupoint (SHAM) group, and electro-acupuncture + ROCK pathway inhibitor Y27632 (EA + Y27632) group. The refraction, axial length, retinal blood flow density, choroidal vascular index, retinal physiological function, the contents of total antioxidant capacity (T-AOC), catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) of each group were determined. The changes in retinal tissue structure were observed by hematoxylin and eosin (H&E) staining, and the expression of the RhoA/ROCK2 signaling pathway-related molecules in the retina was measured by real-time quantitative polymerase chain reaction (qPCR) and Western blot. ResultsMyopic refraction, AL, and MDA content in the LIM and SHAM groups were significantly increased, retinal blood flow density and CVI, SOD, GSH, CAT, T-AOC content were decreased. After EA intervention, myopic refraction, AL, and MDA content decreased, retinal blood flow density and CVI, SOD, GSH, CAT, T-AOC content were increased. H&E staining showed that the thickness of the guinea pig retina, the thickness of the inner and outer layers of the nucleus, and the number of cells were significantly increased after EA intervention. qPCR and western blot analyses showed that the expression of RhoA、ROCK2、MLC、CollagenⅠ、MMP-2、TIMP-2 and α-SMA were elevated in the LIM and SHAM group than those in the NC group. Compared with the LIM group, the expression of EA group was significantly decreased. ConclusionsElectroacupuncture can improve retinal function by improving retinal blood flow, reducing retinal oxidative damage, inhibiting RhoA/ROCK2 signaling pathway and controlling extracellular matrix remodeling, thus delaying the occurrence and development of myopia.

Correlation of Visual System Biomarkers With Motor Deficits in Experimental Autoimmune Encephalomyelitis-Optic Neuritis.

Experimental autoimmune encephalomyelitis (EAE) scoring, the most commonly used primary outcome metric for an in vivo model of multiple sclerosis (MS), is highly variable and subjective. Here we explored the use of visual biomarkers in EAE as more objective and clinically relevant primary outcomes. Motor impairment in myelin oligodendrocyte glycoprotein-immunized C57BL/6J mice was quantified using a five-point EAE grading scale. Pattern electroretinography (pERG) and retinal ganglion cell/inner plexiform layer (RGC/IPL) complex thickness were measured 60 days after induction. Optic nerve histopathology was analyzed at endpoint. EAE mice displayed motor impairments ranging from mild to severe. Significant correlations were seen between pERG amplitude and last EAE score, mean EAE score, and cumulative EAE score. Optical coherence tomography (OCT) analysis demonstrated a significant correlation between thinning of the RGC/IPL complex and both EAE score and pERG amplitude. Optic nerve histopathology showed significant correlations between demyelination and cumulative EAE score, pERG amplitude, and RGC/IPL complex thickness, as well as between immune cell infiltration and cumulative EAE score, pERG amplitude, and RGC/IPL complex thickness in EAE mice. Unlike EAE scoring, pERG and OCT show direct measurement of retinal structure and function. Therefore we conclude that visual outcomes are well suited as a direct assessment of optic nerve involvement in this EAE model of MS while also being indicative of motor impairment. Standardizing directly translatable measurements as primary outcome parameters in the murine EAE model could lead to more rapid and relevant testing of new therapeutic approaches for mitigating MS.

OCT Biomarkers in Ocular CLN2 Disease in Patients Treated With Intraventricular Enzyme Replacement Therapy.

Bilateral progressive, symmetrical loss of central retinal thickness (CRT) has been described in neuronal ceroid lipofuscinosis type 2 (CLN2) disease. This study details the pattern of morphological changes underlying CRT loss and disease progression in patients receiving intracerebroventricular (ICV) enzyme replacement therapy (ERT) with cerliponase alfa. Spectral-domain optical coherence tomography macular cube scans were collected from 16 patients with classic CLN2 disease receiving ICV ERT. Detailed retinal structure analyses were performed on manually segmented horizontal B-scans through the fovea to determine the thickness of six retinal parameters and the extent of ellipsoid zone (EZ) loss. Anatomical changes primarily occurred in photoreceptor (PR)-related retinal parameters and correlated with ocular disease severity. Retinal degeneration began with initial focal parafoveal EZ discontinuities signaling the onset of rapid PR degeneration in a predictable pattern: parafoveal PR involvement with foveal sparing followed by profound parafoveal and foveal PR loss with additional thinning beyond the central retina. PR degeneration began with outer segment loss and progressed to outer nuclear layer (ONL) involvement. Longitudinal analyses confirmed these observations. The rate of PR loss was fastest at the fovea at ∼58 mm per year and became slower at locations farther away from the fovea. Retinal degeneration in CLN2 disease is primarily associated with PR loss in a predictable pattern, with EZ disruption signaling early PR stress. CRT, ONL thickness, and PR layer thickness are useful anatomical biomarkers for understanding disease progression and treatment efficacy in CLN2. Studies using en face images will further clarify CLN2-related retinal degeneration.

Eye-brain connections revealed by multimodal retinal and brain imaging genetics

The retina, an anatomical extension of the brain, forms physiological connections with the visual cortex of the brain. Although retinal structures offer a unique opportunity to assess brain disorders, their relationship to brain structure and function is not well understood. In this study, we conducted a systematic cross-organ genetic architecture analysis of eye-brain connections using retinal and brain imaging endophenotypes. We identified novel phenotypic and genetic links between retinal imaging biomarkers and brain structure and function measures from multimodal magnetic resonance imaging (MRI), with many associations involving the primary visual cortex and visual pathways. Retinal imaging biomarkers shared genetic influences with brain diseases and complex traits in 65 genomic regions, with 18 showing genetic overlap with brain MRI traits. Mendelian randomization suggests bidirectional genetic causal links between retinal structures and neurological and neuropsychiatric disorders, such as Alzheimer’s disease. Overall, our findings reveal the genetic basis for eye-brain connections, suggesting that retinal images can help uncover genetic risk factors for brain disorders and disease-related changes in intracranial structure and function.

Evaluation of ophthalmic vascular and neuroretinal alterations in fibromyalgia syndrome: a cross-sectional comparative study

IntroductionFibromyalgia syndrome (FMS) is a prevalent rheumatic disorder, and its pathogenesis includes genetic, neuroendocrine, and autonomic abnormalities, which may impact ocular structures. The aim was to conduct a comparative analysis of the ophthalmic vasculature and the retinal nerve fiber layer (RNFL) thickness between FMS and control groups using optical coherence tomography (OCT) and OCT angiography (OCTA).MethodsThis cross-sectional comparative study included 43 FMS patients and 40 healthy controls recruited from a tertiary education and research hospital between January 2024 and May 2024. All patients satisfied the 2016 American College of Rheumatology criteria for FMS and consented. OCT and OCTA were used to assess the RNFL thickness and the retinal microvasculature structure. The Fibromyalgia Impact Questionnaire (FIQ) was performed to evaluate disease severity.ResultsThe study found significantly higher total retinal parafoveal thickness and foveal density in FMS patients (p = 0.017 and p = 0.044, respectively). Nevertheless, there were no significant differences among the groups concerning total retinal foveal thickness, foveal avascular zone characteristics, superficial and deep capillary plexus densities, choriocapillaris flow area, and outer retinal flow area values (p > 0.05). The RNFL thickness in all quadrants did not reveal significant differences between the groups (p > 0.05). Furthermore, there was no significant correlation between FIQ scores and OCTA parameters or RNFL thickness values (p > 0.05).ConclusionThe study revealed slight differences in retinal parafoveal thickness and foveal density in FMS patients, but no substantial vascular or neurodegenerative alterations were observed compared to healthy controls. These data indicate that FMS may not substantially affect ocular structures, contrary to earlier hypotheses.

Unet retinal vessel image segmentation algorithm based on coordinate attention mechanism and Min-ASPP module optimisation

In this paper, the Unet image segmentation algorithm is optimised and improved by introducing the coordinate attention mechanism and integrating the Min-ASPP module, and compared with the traditional Unet model, targeting the segmentation of retinal blood vessel images, which is a key problem in the field of medical image processing. The experimental results show that the optimised Unet algorithm combining the coordinate attention mechanism and Min-ASPP module has a smoother performance in the loss curve, faster convergence speed, and lower final converged loss value, which has an obvious advantage compared with the traditional Unet algorithm. Meanwhile, the optimised Unet algorithm shows higher accuracy and stability in the prediction results, providing ophthalmologists with more reliable information about the retinal vascular structure. Therefore, the research results of this paper show that the Unet image segmentation algorithm optimised by combining the coordinate attention mechanism and Min-ASPP module has better application prospects and effects in the retinal blood vessel image segmentation task, which provides a useful exploration and practice for improving the level of medical image processing technology.

The protective role of Cordyceps cicadae and its active ingredient myriocin against sodium iodate-induced age-related macular degeneration via an anti-necroptotic TNF-RIPK1/3 pathway

Ethnopharmacological relevanceCordyceps cicadae (C.cicadae), named “Chan Hua”, an anamorph of Isaria cicadae Miquel, is an entomogenous complex formed by fungi parasitizing on the larvae of cicadas and belongs to the Claviciptaceae family and the genus Codyceps, which traditionally holds a significant place in Chinese ethnopharmacology, specifically for eye clarity and as a remedy for age-related ocular conditions. The underlying mechanisms contributing to its eyesight enhancement and potential effectiveness against Age-related macular degeneration (AMD) remain unexplored. Aim of the studyThis study aims to elucidate the protective role of C.cicadae and its active ingredient, Myriocin (Myr), against AMD. Materials and methodsA chemical inducer was employed to make retinal pigment epithelium (RPE) damage in vitro and in vivo. The key ingredients of C.cicadae and their related mechanisms for anti-AMD were studied through bioinformatic analysis and molecular biological approaches. ResultsMyr was identified through high-performance liquid chromatography (HPLC) as an active ingredient in C.cicadae, and demonstrated a protective effect on RPE cells, reducing the structural damage and cell death induced by sodium iodate (SI). Further, Myr reduced eyelid secretions in AMD mice and restored their retinal structure and function. The differentially expressed genes (DEGs) in Myr treatment are primarily associated with TNF and Necroptosis signaling pathways. Molecular docking indicated a strong affinity between TNF and Myr. Myr inhibited the TNF signaling pathway thereby reducing the expression of inflammatory factors in ARPE-19 cells. Additionally, Myr had consistent action with the necroptosis inhibitor Necrostatin-1 (Nec-1), inhibited the RIPK1/RIPK3/MLKL pathway thereby protecting ARPE-19 cells. ConclusionThe findings present Myr, as a potent protector against SI-induced AMD, predominantly through modulation of the TNF-RIPK1/RIPK3/MLKL signaling pathway, offering the insights of therapeutic C.cicadae as viable candidates for AMD treatment.

Association between three-dimensional morphological features and functional indicators of neovascular age-related macular degeneration

PurposeTo investigate the correlation between morphological lesions and functional indicators in eyes with neovascular age-related macular degeneration (nAMD). MethodsThis was a prospective observational study of treatment-naïve nAMD eyes. Various morphological lesions and impaired retinal structures were manually measured at baseline and month-3 in three-dimensional optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images, including the volumes (mm3) of macular neovascularization (MNV), avascular subretinal hyperreflective material (avascular SHRM), subretinal fluid (SRF), intraretinal fluid (IRF), serous pigment epithelial detachment (sPED) and the impaired area (mm2) of ellipsoid zone (EZ), external limiting membrane (ELM) and outer nuclear layer (ONL). ResultsSixty-three eyes were included. The volume of avascular SHRM showed persistent positive associations with the area of EZ damage, both at baseline, month-3, and change values (all P < 0.001). Poor BCVA (month-3) was associated with larger volumes of baseline IRF (β = 0.377, P < 0.001), avascular SHRM (β = 0.306, P = 0.032), and ELM impairment area (β = 0.301, P = 0.036) in multivariate model. EZ and ELM impairment were primarily associated with baseline avascular SHRM (β = 0.374, p = 0.003; β = 0.388, P < 0.001, respectively), while ONL impairment primarily associated with MNV (β = 0.475, P < 0.001). ConclusionThe utilization of three-dimensional measurements elucidates the intrinsic connections among various lesions and functional outcomes. In particular, avascular SHRM plays an important role in prognosis of nAMD.

Randomized 20-year infancy-onset dietary intervention, life-long cardiovascular risk factors and retinal microvasculature.

Retinal microvasculature characteristics predict cardiovascular morbidity and mortality. This study investigated associations of lifelong cardiovascular risk factors and effects of dietary intervention on retinal microvasculature in young adulthood. The cohort is derived from the longitudinal Special Turku Coronary Risk Factor Intervention Project study. The Special Turku Coronary Risk Factor Intervention Project is a 20-year infancy-onset randomized controlled dietary intervention study with frequent study visits and follow-up extending to age 26 years. The dietary intervention aimed at a heart-healthy diet. Fundus photographs were taken at the 26-year follow-up, and microvascular measures [arteriolar and venular diameters, tortuosity (simple and curvature) and fractal dimensions] were derived (n = 486). Cumulative exposure as the area under the curve for cardiovascular risk factors and dietary components was determined for the longest available time period (e.g. from age 7 months to 26 years). The dietary intervention had a favourable effect on retinal microvasculature resulting in less tortuous arterioles and venules and increased arteriolar fractal dimension in the intervention group when compared with the control group. The intervention effects were found even when controlled for the cumulative cardiovascular risk factors. Reduced lifelong cumulative intake of saturated fats, main target of the intervention, was also associated with less tortuous venules. Several lifelong cumulative risk factors were independently associated with the retinal microvascular measures, e.g. cumulative systolic blood pressure with narrower arterioles. Infancy-onset 20-year dietary intervention had favourable effects on the retinal microvasculature in young adulthood. Several lifelong cumulative cardiovascular risk factors were independently associated with retinal microvascular structure.