Clinical Evidence of a Photoreceptor Origin in Diabetic Retinal Disease.

Clinical Relevance: Although diabetes is associated with a classic microvascular disease of the retina, it is also increasingly being recognized as a cause of retinal neuropathy. Preclinical evidence suggests that retinal neuropathy in diabetes manifests in part as photoreceptor dysfunction, preceding the development of vascular features in experimental models. It remains unknown whether such findings are relevant to patients with diabetes. Methods: Here, we review 4 lines of clinical evidence suggesting that diabetes-associated photoreceptor pathology is linked to the development of retinal microvascular disease. Results: First, a major population-based investigation of susceptibility loci for diabetic retinopathy (DR) implicated a photoreceptor protein product as a protective factor. Next, electroretinography and other studies of visual function collectively show that rod and/or cone-derived abnormalities occur decades before the development of vascular features of DR. Third, protection from DR seemingly develops in patients with coincident retinitis pigmentosa, as suggested by several case series. Finally, based on anatomic features, we propose that the beneficial effect of macular laser in DR occurs via ablation of diseased photoreceptors. Conclusions: The evidence we present is limited due to the small patient populations used in the studies we cite and due to the lack of methodologies that allow causative relationships to be inferred. Collectively, however, these clinical observations suggest that photoreceptors are involved in early diabetic retinal disease and may in fact give rise to the classic features of DR. Financial Disclosures: Proprietary or commercial disclosures may be found in the Footnotes and Disclosures at the end of this article.

Severity Scale of Diabetic Macular Ischemia Based on the Distribution of Capillary Nonperfusion in OCT Angiography.

Purpose: To evaluate the severity scales of diabetic macular ischemia (DMI) by analyzing the quantity and distribution of capillary nonperfusion using OCT angiography (OCTA) images. Design: A single-center, prospective case series. Participants: Three hundred one eyes from 301 patients with diabetic retinopathy. Methods: We acquired 3 × 3-mm swept-source OCTA images and created en face images within a central 2.5-mm circle. The circle was divided into 15 × 15-pixel squares and nonperfusion squares (NPSs) were defined as those without retinal vessels. Eyes with high-dimensional spatial data were arranged on a 2-dimensional space using the uniform manifold approximation and projection (UMAP) algorithm and classified by clustering into 5 groups: Initial, Mild, Superficial, Moderate, and Severe. Main Outcome Measures: Development of a severity scale for DMI. Results: Eyes arranged on a 2-dimensional UMAP space were divided into 5 clusters, based on the similarity of nonperfusion area distribution. Nonperfusion square counts in the deep layer increased in eyes of the Initial, Mild, Moderate, and Severe groups in a stepwise manner. In contrast, there were no significant changes in superficial NPS counts between eyes of the Initial and Mild groups. In the intermediate stage, eyes of the Superficial group exhibited higher NPS counts in the central sector of the superficial layer compared with those of the Moderate group. The foveal avascular zone extended into the temporal subfield of the deep layer in eyes of the Moderate group. Eyes of the Severe group had significantly poorer visual acuity that was more frequently accompanied with proliferative diabetic retinopathy. Conclusions: The application of dimensionality reduction and clustering has facilitated the development of a novel severity scale for DMI based on the distribution of capillary nonperfusion in OCTA images. Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

Comparison of Machine Learning Models to a Novel Score in the Identification of Patients at Low Risk for Diabetic Retinopathy.

Purpose: To develop an easily applicable predictor of patients at low risk for diabetic retinopathy (DR). Design: An experimental study on the development and validation of machine learning models (MLMs) and a novel retinopathy risk score (RRS) to detect patients at low risk for DR. Subjects: All individuals aged ≥18 years of age who participated in the telemedicine retinal screening initiative through Temple University Health Systems from October 1, 2016 through December 31, 2020. The subjects must have documented evidence of their diabetes mellitus (DM) diagnosis as well as a documented glycosylated hemoglobin (HbA1c) recorded in their chart within 6 months of the retinal screening photograph. Methods: The charts of 1930 subjects (1590 evaluable) undergoing telemedicine screening for DR were reviewed, and 30 demographic and clinical parameters were collected. Diabetic retinopathy is a dichotomous variable where low risk is defined as no or mild retinopathy using the International Clinical Diabetic Retinopathy severity score. Five MLMs were trained to predict patients at low risk for DR using 1050 subjects and further underwent 10-fold cross validation to maximize its performance indicated by the area under the receiver operator characteristic curve (AUC). Additionally, a novel RRS is defined as the product of HbA1c closest to screening and years with DM. Retinopathy risk score was also applied to generate a predictive model. Main Outcome Measures: The performance of the trained MLMs and the RRS model was compared using DeLong's test. The models were further validated using a separate unseen test set of 540 subjects. The performance of the validation models were compared using DeLong's test and chi-square tests. Results: Using the test set, the AUC for the RRS was not statistically different from 4 out of 5 MLM. The error rate for predicting low-risk patients using the RRS was significantly lower than the naive rate (0.097 vs. 0.19; P < 0.0001), and it was comparable to the error rates of the MLMs. Conclusions: This novel RRS is a potentially useful and easily deployable predictor of patients at low risk for DR. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Analog Spiking U-Net integrating CBAM&ViT for medical image segmentation.

SNNs are gaining popularity in AI research as a low-power alternative in deep learning due to their sparse properties and biological interpretability. Using SNNs for dense prediction tasks is becoming an important research area. In this paper, we firstly proposed a novel modification on the conventional Spiking U-Net architecture by adjusting the firing positions of neurons. The modified network model, named Analog Spiking U-Net (AS U-Net), is capable of incorporating the Convolutional Block Attention Module (CBAM) into the domain of SNNs. This is the first successful implementation of CBAM in SNNs, which has the potential to improve SNN model's segmentation performance while decreasing information loss. Then, the proposed AS U-Net (with CBAM&ViT) is trained by direct encoding on a comprehensive dataset obtained by merging several diabetic retinal vessel segmentation datasets. Based on the experimental results, the provided SNN model achieves the highest segmentation accuracy in retinal vessel segmentation for diabetes mellitus, surpassing other SNN-based models and most ANN-based related models. In addition, under the same structure, our model demonstrates comparable performance to the ANN model. And then, the novel model achieves state-of-the-art(SOTA) results in comparative experiments when both accuracy and energy consumption are considered (Fig. 1). At the same time, the ablative analysis of CBAM further confirms its feasibility and effectiveness in SNNs, which means that a novel approach could be provided for subsequent deployment and hardware chip application. In the end, we conduct extensive generalization experiments on the same type of segmentation task (ISBI and ISIC), the more complex multi-segmentation task (Synapse), and a series of image generation tasks (MNIST, Day2night, Maps, Facades) in order to visually demonstrate the generality of the proposed method.

Role of EYP-1901 in neovascular age-related macular degeneration and diabetic eye diseases: review of Phase I/II trials.

EYP-1901 (Duravyu) has demonstrated promising outcomes in Phases I and II clinical trials for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME)/diabetic retinopathy. This innovative treatment capitalizes on the potent anti-angiogenic properties of vorolanib, an inhibitor that targets all isoforms of VEGF, effectively mitigating the pathological neovascularization and vascular permeability that underpin these retinal conditions. EYP-1901 is integrated with the Durasert drug delivery system to administer a sustained release of vorolanib directly to the posterior segment of the eye. This delivery system ensures a consistent therapeutic effect over an extended period and significantly reduces the frequency of clinical interventions required, offering a more convenient treatment regimen while maintaining patient safety.

Neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR) are eye problems that can make you lose your sight. These eye problems happen when blood vessels in the eye do not work right. Right now, people need lots of shots in their eyes to treat it. EYP-1901 (Duravyu) is a new medicine that helps people with fewer shots in their eyes. It has two parts: one that helps the medicine last longer, and another that helps stop the problem in the eye. Early tests show it works well and helps people keep their sight with fewer treatments.

Autoimmune Retinopathy Following COVID-19: A Case Report.

PURPOSE: To present a presumed case of non-paraneoplastic autoimmune retinopathy (nPAIR) following COVID-19 in a healthy woman. METHODS: A single case was evaluated and followed for 32 months. RESULTS: A healthy 32-year-old woman presented with photopsia and paracentral scotoma (OU) after a recent COVID-19 infection. Past medical history and family history were unremarkable. Her visual acuity was normal (OU). Retinal atrophy, mild disc pallor, and foveal reflex attenuation were observed (OU). Optical coherence tomography (OCT) scans showed outer nuclear layer thinning and ellipsoid zone disruption (OU). The visual field test showed blind spot enlargement and arcuate scotomas (OU). Uveitis workup and underlying malignancy investigations were negative. A diagnosis of nPAIR was presumed. At the time, she refused therapy, and 20 months later, her visual acuity was stable, but there were progressive retinal atrophic changes and visual field constriction. After initiation of glucocorticoids and immunosuppressive therapy, flashing lights completely disappeared, her visual field was stabilized without progression, and OCT scans showed partial recovery of ellipsoid zone. CONCLUSION: SARS-CoV-2 infection may be a trigger for nPAIR in susceptible individuals, but further research is needed to determine this association.

'Whatever the GP says, is what I'll do'-A qualitative study of patient perspectives in accessing primary eye care for type 2 diabetes.

INTRODUCTION: To investigate the perspectives of people accessing a general medical practitioner (GP)-optometry model of collaborative care that was established to increase access to diabetes eye care. METHODS: Qualitative study of patient barriers and facilitators to accessing primary diabetes eye care located in a metropolitan area in Australia. One-on-one interviews were recorded, transcribed and thematically analysed using a determinant framework on patient-centred access to health care. RESULTS: Twenty-four people with type 2 diabetes, including 15 males and 9 females, who accessed the service between September 2021 and June 2022 agreed to participate. Mean (SD) age of the participants was 52 (12) years and 50% had been diagnosed with diabetes for <2 years. Facilitators to accessing diabetes eye care included a referral from a GP or GP nurse, fee-free consultations, availability of after-hours appointments and short waiting times. Barriers to access included perceived out-of-pocket costs, competing responsibilities and lack of awareness of diabetic retinopathy screening recommendations. CONCLUSION: Considering diabetic retinopathy may present asymptomatically, primary health practitioners (optometrists and GPs) are well positioned to raise patient awareness of the importance of routine eye examinations. In Australia, access to routine screening could be facilitated by fee-free eye checks and personalised text message reminders implemented at a health system level.

Short pulse grid and subthreshold micropulse laser (the sandwich grid) plus intravitreal ranibizumab for the treatment of diabetic macular edema.

OBJECTIVE: To investigate the effects of two laser treatment procedures combined, short pulse grid laser (SP) and subthreshold micropulse laser (MP) (the sandwich grid [SWG] technique), plus intravitreal ranibizumab (IVR) on central subfield thickness (CSFT), best-corrected visual acuity (BCVA) and macular sensitivity in patients with diabetic macular edema (DME). METHODS: Forty-five eyes (of 33 patients) with center-involving DME were treated with the SWG laser technique plus IVR and followed for 12 months. Laser treatment was performed at baseline: SP laser spots were placed in a grid pattern in the macular area (500 µm from the fovea) according to the extension of DME; subsequently, MP laser was delivered up to the edge of the fovea. MP laser re-treatment sessions could be performed every 3 months if DME was present and CSFT was ≥ 300 µm on SD-OCT. IVR injection was performed at baseline and repeated monthly if CSFT > 300µm. Preoperatively and monthly, ophthalmological examination was performed including measurements of BCVA, CSFT, and macular sensitivity. RESULTS: One-year follow-up data is available for 37 eyes of 27 patients. Mean ± SE CSFT (µm) was 509.36 ± 25.14 and 325.76 ± 15.34 at baseline and 12 months, respectively. A significant reduction in mean CSFT was observed at all study visits compared to baseline (p < 0.001). Mean ± SE BCVA (logMAR) was 0.62 ± 0.04 and 0.45 ± 0.04 at baseline and 12 months, respectively. A significant improvement in mean BCVA was observed at all study visits compared to baseline (p < 0.001). Mean ± SE macular sensitivity (dB) was 17.85 ± 0.80 and improved to 19.05 ± 0.59 after one year of follow-up (p = 0.006). The mean number of IVR injections was 8.29 ± 0.63. The mean number of MP laser procedures including the initial SWG laser session was 3.67 ± 0.22. No ocular or systemic adverse effects were observed. CONCLUSION: The SWG laser technique plus IVR was associated with significant improvement in macular edema, BCVA, and macular sensitivity in patients with center-involving DME. CLINICAL TRIAL NUMBER (CAAE): 22969019.4.0000.5440.

RETINAL BURNS IN PHOTIC RETINOPATHY: THREE CASE REPORTS.

Photic retinopathy (PR) is due to retinal phototoxicity, especially affecting the macula, resulting from exposure to sun, welding devices and lasers. It leads to oxidative damage to the retinal pigment epithelium (RPE) and the surrounding photoreceptors. Early recognition of this visual threatening condition, follow-up lesion evolution, and prevention of prolonged ocular exposure to lights is warranted. We herein report the three principal types of retinal burns due to solar retinopathy, laser pointer-induced maculopathy and arc welding maculopathy.

La rétinopathie photique (RP) est secondaire à une phototoxicité rétinienne, affectant particulièrement la macula, résultant de l'exposition au soleil, aux appareils de soudure et aux lasers. Elle entraîne un dommage oxydatif de l'épithélium pigmentaire de la rétine (EPR) et des photorécepteurs. Il s'avère primordial de reconnaître précocement cette affection menaçant la vision, de suivre l'évolution des lésions et de prévenir une exposition oculaire prolongée aux lumières. Nous rapportons ici les trois principaux types de brûlures rétiniennes, dues à la rétinopathie solaire, à la maculopathie induite par un pointeur laser et à la maculopathie de soudure à l'arc.

Exploring the Association of VEGF-A and ANGPTL2 with the Prognosis of Non-proliferative and Proliferative Diabetic Retinopathy.

Introduction Diabetic retinopathy (DR) is a microvascular ailment that can arise from the long-term effects of diabetes mellitus. It can potentially cause retinal damage that could endanger vision and cause blindness. The worsening of DR is mainly linked to poor glycemic control, uncontrolled hypertension, and dyslipidemia. There is a need for alternative and clinically significant novel molecules involved in the pathogenesis of DR because the diagnostic and prognostic markers have reached a limit. Materials and method This study included sex and age-matched diabetic patients with proliferative stage (N = 70), non-proliferative stage (N = 80), and control (N = 80, without the sign of DR). These patients were recruited from outpatients in the Department of Ophthalmology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India. A random blood sample was collected from each study participant, and the serum was separated after centrifugation and stored at -80 °C for batch analysis. The biomarkers vascular endothelial growth factor (VEGF-A) and angiopoietin-like protein-2 (ANGPTL2) were measured using a sandwich enzyme-linked immunosorbent assay (ELISA) technique, and the laboratory parameters such as fasting blood sugar (FBS), lipid profile, blood urea nitrogen (BUN), creatine, and glycated hemoglobin (HbA1C) were also assessed. Results We observed statistically significant differences in the duration of diabetes, FBS, total cholesterol (TC), triglyceride level (TGL), BUN, and creatine (p<0.05), and the mean age of study participants was 52.95±8.20 years in the control group, 53.85±10.20 years in the proliferative diabetic retinopathy (PDR) group, and 55.02±7.65 in the non-proliferative diabetic retinopathy (NPDR) group. Furthermore, ANGPTL2 levels were statistically significant according to the severity of the disease (p<0.001*), and they were also linked (p<0.05) with established markers such as VEGF-A. Conclusion Thus, our research implies that the up-regulated markers might be linked to the disease's advancement and could serve as a prognostic indicator or therapeutic target for DR.

Association between rest-activity rhythm and diabetic retinopathy among US middle-age and older diabetic adults.

Background: The disruption of circadian rhythm has been reported to aggravate the progression of diabetic retinopathy (DR). Rest-activity rhythm (RAR) is a widely used method for measuring individual circadian time influencing behavior. In this study, we sought to explore the potential association between RAR and the risk of DR. Methods: Diabetic participants aged over 40 from 2011-2014 National Health and Nutrition Examination Survey (NHANES) were enrolled. Data from the wearable device ActiGraph GT3X was used to generate RAR metrics, including interdaily stability (IS), intradaily variability (IV), most active 10-hour period (M10), least active 5-hour period (L5), and Relative amplitude (RA). Weighted multivariable logistic regression analysis and restricted cubic spline analysis were conducted to examine the association between RAR metrics and DR risk. Sensitivity analysis was also conducted to examine the robustness of the findings. An unsupervised K-means clustering analysis was conducted to identify patterns in IV and M10. Results: A total of 1,096 diabetic participants were enrolled, with a DR prevalence of 20.53%. The mean age of participants was 62.3 years, with 49.57% being male. After adjusting covariates, IV was positively associated with DR (ß: 3.527, 95%CI: 1.371-9.073). Compared with the lowest quintile of IV, the highest quintile of IV had 136% higher odds of DR. In contrast, M10 was negatively associated with DR (ß: 0.902, 95%CI: 0.828-0.982), with participants in the highest M10 quintile showing 48.8% lower odds of DR. Restricted cubic spline analysis confirmed that these associations were linear. Meanwhile, sensitivity analysis confirmed the robustness. K-means clustering identified three distinct clusters, with participants in Cluster C (high-IV, low-M10) had a significantly higher risk of DR comparing with Cluster A (low-IV, high-M10). Conclusion: A more fragmented rhythm and lower peak activity level might be associated with an increased risk of DR. These findings indicate that maintaining a more rhythmic sleep-activity behavior might mitigate the development of DR. Further research is necessary to establish causality and understand the underlying mechanisms, and focus on whether interventions designed to enhance daily rhythm stability and increase diurnal activity level can effectively mitigate the risk of progression of DR.

An unusual pAIR: Anti-PKM2 antibody and occult pancreatic adenocarcinoma.

Purpose: To describe the clinical, laboratory and multimodal imaging findings in paraneoplastic autoimmune retinopathy (p-AIR) associated with anti-pyruvate kinase M2 antibody (anti-PKM2) and occult pancreatic adenocarcinoma. Observations: A 70 year old male with blurred vision, nyctalopia and concurrent difficulty with glucose control had retinal vascular attenuation and diffuse punctate pigment clumping in both eyes. Multimodal imaging demonstrated corresponding stippled hypofluorescence on fluorescein angiography, stippled hyperautofluorescence and a hyperautoflourescent macular ring with fundus autofluorescence, and focal hyperreflectivity at the level of the RPE-Bruch's membrane complex with diffuse loss of outer retinal layers on ocular coherence tomography. In addition, diffuse ganglion cell loss and severe visual field constriction were present. Genetic testing for retinitis pigmentosa was normal. Screening for anti-retinal antibodies was positive for only anti-PKM2. Systemic evaluation revealed previously undiagnosed adenocarcinoma of the pancreas. Conclusions and importance: Anti-PKM2 in the setting of autoimmune retinopathy may be associated with occult pancreatic cancer. The diagnosis of pAIR should be considered and systemic investigation for occult malignancy initiated even in the absence of more commonly associated anti-retinal antibodies.

Sex differences in the development of experimental diabetic retinopathy.

This study aimed to characterize the role of female sex in the pathogenesis of diabetic retinopathy. In the retinae of female Ins2Akita-diabetic mice (F-IA), ovariectomized female Ins2Akita-diabetic mice (F-IA/OVX), male Ins2Akita-diabetic mice (M-IA), and female STZ-diabetic mice (F-STZ), the formation of reactive metabolites and post-translational modifications, damage to the neurovascular unit, and expression of cellular stress response genes were analyzed. Compared to the male diabetic retina, the concentrations of the glycation adduct fructosyl-lysine, the Maillard product 3-deoxyglucosone, and the reactive metabolite methylglyoxal were significantly reduced in females. In females, there was also less evidence of diabetic damage to the neurovascular unit, as shown by decreased pericyte loss and reduced microglial activation. In the male diabetic retina, the expression of several members of the crystallin gene family (Cryab, Cryaa, Crybb2, Crybb1, and Cryba4) was increased. Clinical data from type 1 diabetic females showed that premenopausal women had a significantly lower prevalence of diabetic retinopathy compared to postmenopausal women stratified for disease duration and glycemic control. These data emphasize the importance of estradiol in protecting the diabetic retina and highlight the pathogenic relevance of sex in diabetic retinopathy.

An ultra-sensitive suboptimal protospacer adjacent motif enhanced rolling circle amplification assay based on CRISPR/Cas12a for detection of miR-183.

Introduction: MicroRNAs (miRNAs) have been recognized as promising diagnostic biomarkers for Diabetic Retinopathy (DR) due to their notable upregulation in individuals with the condition. However, the development of highly sensitive miRNAs assays for the rapid diagnosis of DR in clinical settings remains a challenging task. Methods: In this study, we introduce an enhanced CRISPR/Cas12a assay, leveraging suboptimal PAM (sPAM)-mediated Cas12a trans-cleavage in conjunction with rolling circle amplification (RCA). sPAM was found to perform better than canonical PAM (cPAM) in the detection of Cas12a-mediated ssDNA detection at low concentrations and was used instead of canonical PAM (cPAM) to mediate the detection. The parameters of reactions have also been optimized. Results and discussion: In comparison with cPAM, sPAM has higher sensitivity in the detection of ssDNA at concentrations lower than 10 pM by Cas12a. By replacing cPAM with sPAM in the padlock template of RCA, ultra-high sensitivity for miR-183 detection is achieved, with a detection limit of 0.40 aM. within 25 min and a linear range spanning from 1 aM. to 1 pM. Our assay also exhibits exceptional specificity in detecting miR-183 from other miRNAs. Furthermore, the applicability of our assay for the sensitive detection of miR-183 in clinical serum samples is also validated. This study introduces a groundbreaking assay with excellent performance through a simple modification, which not only addresses existing diagnostic challenges, but also opens exciting new avenues for clinical diagnosis in the realm of DR.

Evaluation of Foveal Vasculature by Optical Coherence Tomography Angiography after Pan-Retinal Photocoagulation versus Intravitreal Anti-VEGF Injections.

Purpose: This study aimed to compare macular vascular changes one and three months after treatment with either panretinal photocoagulation (PRP) or intravitreal bevacizumab (IVB). Methods: A total of 62 eyes with very severe non-proliferative diabetic retinopathy or early proliferative diabetic retinopathy without center-involved diabetic macular edema, were included in this retrospective study. Thirty-nine eyes were allocated to the PRP group, while 23 eyes were treated with IVB. Optical coherence tomography angiography (OCTA) was performed to measure foveal avascular zone (FAZ) characteristics as well as the densities of superficial and deep capillary plexuses (SCP and DCP). Results: In the IVB group, the FAZ area and perimeter expanded at month one but returned to baseline level after three months. In the PRP group, however, the FAZ area and perimeter were rather steady. Changes in the FAZ area were significantly different between the treatment groups at month one (P = 0.02), but not at month three (P = 0.31). There was no significant difference in the change in FAZ circularity index between the two groups at each time point (P = 0.55 and P = 0.31). Similarly, changes in SCP density were not statistically significant between the two groups at both time points (all Ps > 0.05). A comparison of the two treatment arms based on the mean change in DCP density revealed a significant difference at month one, but not at month three (P = 0.01 and P = 0.49, respectively). Conclusion: Although bevacizumab and PRP have different short-term macular vascular responses, both therapies have the ability to normalize or stabilize vascular measures over time.

Cancer-associated retinopathy secondary to gallbladder carcinoma.

Objective: To present a rare case of cancer-associated retinopathy secondary to gallbladder carcinoma. Methods: Retrospective case report. Drugs used in case report: methylprednisolone (Medrol), CAS number: 83-43-2, producer: Pfizer; carboplatin, CAS number: 41575-94-4, producer: Accor; etoposide, CAS number: 33419-42-0, producer: Teva; methotrexate (Ledertrexate), CAS number: 59-05-2, producer: Pfizer. Results: A 57-year-old Moroccan man was referred with bilateral progressive vision loss in the last 4 months. At presentation, best corrected visual acuity (BCVA) was counting fingers for the right eye and 20/500 for the left eye. Examination demonstrated signs of vitritis, an electronegative full-field electroretinography (FF-ERG), ocular coherence tomography (OCT) abnormalities and multiple hyperautofluorescent round lesions on fundus autofluorescence imaging (FAF). The diagnosis of cancer-associated retinopathy (CAR) was considered, thus a positron emission tomography-computed tomography (PET-CT) was performed and revealed the presence of a metastasized gallbladder carcinoma. Additional fluorescence in situ hybridization (FISH) showed seropositivity for anti-retinal autoantibodies. High-dose corticosteroids together with anti-tumoral medication (carboplatin-etoposide) gradually improved the BCVA to 20/66 for the right eye and 20/20 for the left eye. Conclusions: Consider the diagnosis of CAR in patients with progressive concentric visual field loss, uveitis and fundus abnormalities, especially if bilateral. If CAR is suspected, perform a full work-up: FF-ERG, OCT, and whole-body PET-CT. In the treatment of CAR, immunosuppressives are mostly used, combined with antitumoral therapy. However, in the long-term, progressive visual loss is expected in most cases.

Functions of TRPs in retinal tissue in physiological and pathological conditions.

The Transient Receptor Potential (TRP) constitutes a family of channels subdivided into seven subfamilies: Ankyrin (TRPA), Canonical (TRPC), Melastatin (TRPM), Mucolipin (TRPML), no-mechano-potential C (TRPN), Polycystic (TRPP), and Vanilloid (TRPV). Although they are structurally similar to one another, the peculiarities of each subfamily are key to the response to stimuli and the signaling pathway that each one triggers. TRPs are non-selective cation channels, most of which are permeable to Ca2+, which is a well-established second messenger that modulates several intracellular signaling pathways and is involved in physiological and pathological conditions in various cell types. TRPs depolarize excitable cells by increasing the influx of Ca2+, Na+, and other cations. Most TRP families are activated by temperature variations, membrane stretching, or chemical agents and, therefore, are defined as polymodal channels. All TPRs are expressed, at some level, in the central nervous system (CNS) and ocular-related structures, such as the retina and optic nerve (ON), except the TRPP in the ON. TRPC, TRPM, TRPV, and TRPML are found in the retinal pigmented cells, whereas only TRPA1 and TRPM are detected in the uvea. Accordingly, several studies have focused on the search to unravel the role of TRPs in physiological and pathological conditions related to the eyes. Thus, this review aims to shed light on endogenous and exogenous modulators, triggered cell signaling pathways, and localization and roles of each subfamily of TRP channels in physiological and pathological conditions in the retina, optic nerve, and retinal pigmented epithelium of vertebrates.

Glucagon-Like Peptide-1 Receptor Agonists are Not Associated with an Increased Risk of Progressing to Vision-Threatening Diabetic Retinopathy.

PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used to treat type 2 diabetes mellitus (DM) by augmenting insulin release and sensitivity. We assessed the overall risk for development of vision-threatening diabetic retinopathy (VTDR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME), among GLP-1RA users. METHODS: A retrospective cohort of patients with NPDR newly started on a GLP-1RA from a national insurance claims database was compared to a cohort of patients treated with other oral anti-diabetic agents and matched for age, sex, race, index year, and number of active diabetic medications. Exclusions occurred for < 2 years in the database before diagnosis; prior diagnoses of PDR, DME, vitreous hemorrhage, and/or other retinal vascular diseases; and prior intraocular treatment for VTDR. RESULTS: A total of 6093 users of GLP-1RA were matched to 14,122 controls. In the GLP-1RA cohort, 632 (10.1%), 76 (1.2%), and 544 (8.9%) patients progressed to VTDR, PDR, or DME, respectively. This is compared to 1332 (9.5%) VTDR, 165 (1.2%) PDR, or 1148 (8.1%) DME in the control group. Accounting for underlying DM severity with IPTW, no difference in hazard was seen in the GLP-1RA cohort compared to controls for progression to VTDR (HR = 1.02, 95%CI: 0.92-1.14 p = 0.69), DME (HR = 1.06, 95%CI: 0.95-1.1.9, p = 0.31), or PDR (HR = 0.81, 95%CI: 0.58-1.12, p = 0.20). CONCLUSION: We found no difference in the risk for vision-threatening diabetic retinopathy, nor for its component diseases, DME or PDR, with GLP-1RA use compared to other oral anti-hyperglycemic agents in patients with NPDR.

Complications of Silicone Oil as Vitreous Tamponade in Pars Plana Vitrectomy: A Mini Review.

PURPOSE: Silicone oil (SO) has been used as a vitreous tamponade for decades. Surgical complications such as glaucoma, cataract, or emulsification are well known. Despite that, increasing case reports of unexplained visual loss after SO removal is concerning because there is no treatment available. This article describes practical complications related to SO use and advantages/disadvantages for consideration regarding the choice of a vitreous substitute in practice. METHODS: A literature review was conducted for publications related to silicone oil, heavy silicone oil, and vitreous substitutes. RESULTS: This article summarizes the SO chemical and physical properties including both SO and heavy SO and postoperative complications such as corneal decompensation, glaucoma, hypotony, cataract, optic neuropathy. Surgical complications such as over/underfilling, SO migration/emulsification, sticky SO and proliferative vitreoretinopathy (PVR) simulating epiretinal membranes formation, recurrent retinal detachments, SO unexplained visual loss, and permanent SO, are described. A brief overview on potential vitreous substitutes is presented. CONCLUSION: The decision to use SO as vitreous substitute in daily practice is based on the severity of retinal diseases and surgeon experience. SO potential complications must not be underestimated. The pursuit of novel safer vitreous substitutes is imperative.

Scoring and validation of a simple model for predicting diabetic retinopathy in patients with type 2 diabetes based on a meta-analysis approach of 21 cohorts.

AIM: To develop and validate a model for predicting diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: All risk factors with statistical significance in the DR prediction model were scored by their weights. Model performance was evaluated by the area under the receiver operating characteristic (ROC) curve, Kaplan-Meier curve, calibration curve and decision curve analysis. The prediction model was externally validated using a validation cohort from a Chinese hospital. RESULTS: In this meta-analysis, 21 cohorts involving 184,737 patients with type 2 diabetes were examined. Sex, smoking, diabetes mellitus (DM) duration, albuminuria, glycated haemoglobin (HbA1c), systolic blood pressure (SBP) and TG were identified to be statistically significant. Thus, they were all included in the model and scored according to their weights (maximum score: 35.0). The model was validated using an external cohort with median follow-up time of 32 months. At a critical value of 16.0, the AUC value, sensitivity and specificity of the validation cohort are 0.772 ((95% confidence interval (95%CI): 0.740-0.803), p < .01), 0.715 and 0.775, respectively. The calibration curve lied close to the ideal diagonal line. Furthermore, the decision curve analysis demonstrated that the model had notably higher net benefits. The external validation results proved the reliability of the risk prediction model. CONCLUSIONS: The simple DR prediction model developed has good overall calibration and discrimination performance. It can be used as a simple tool to detect patients at high risk of DR.