Cause Of Vision Loss Research Articles

Long-term follow-up results and visual outcomes of childhood glaucoma in the black sea region of turkey.

To investigate long-term visual outcomes and factors associated with low vision in patients with childhood glaucoma. A retrospective review was conducted on the medical records of pediatric glaucoma patients at the Ondokuz Mayıs University Ophthalmology Clinic from 2005 to 2023. The patients were categorized into three groups: primary congenital glaucoma (PCG), secondary childhood glaucoma, and glaucoma following cataract surgery (GFCS). Groups were analyzed regarding visual acuity (VA), ocular conditions and comorbidities, and the cause of visual impairment. The study also investigated the potential risk factors associated with visual impairment. A total of 105 eyes of 60 patients with a mean age of 9.7 ± 5.5years were included in the study. The mean VA in logMAR was 0.59 ± 0.52. At the final follow-up, 34.1% had good VA (≥ 20/50), 29.5% had moderate VA (20/50-20/200), and 36.4% had poor VA (< 20/200). The final mean intraocular pressure (IOP) was 16.2 ± 6.2mmHg. Amblyopia was the leading cause of vision loss (38.2%), followed by glaucomatous damage (36.4%). Patients with GFCS had a higher rate of visual impairment (42.4%) and refractive error. The results of the regression analysis showed that low vision was associated with undergoing more than two surgeries, high IOP at baseline, high initial and final cup-to-disc (C/D) ratio, and high initial central corneal thickness (CCT) (CI 95%, p = 0.018, p= 0.017, p = 0.013, p = 0.003, p = 0.001, respectively). Good VA can be achieved in 34.1% of childhood glaucoma cases. However, the VA prognosis may be worse in patients with GFCS. Achieving good visual outcomes in childhood glaucoma requires timely and effective treatment, consideration of risk factors, and management of amblyopia and ocular comorbidities.

Demystifying the role of magnetic resonance in identifying intraocular foreign bodies: a case of ocular siderosis

BackgroundOcular siderosis (OS) is a significant cause of visual loss due to retained ferrous intraocular foreign bodies (IOFB). Despite its rarity, OS can lead to severe visual impairment if not promptly diagnosed and treated. This case is notable due to the occult nature of the IOFB, which was undetected by standard imaging modalities, emphasizing the critical role of magnetic resonance imaging (MRI) in such scenarios.Case presentationA 51-year-old Caucasian male presented with progressive vision loss in his right eye over 20 days. Best corrected visual acuity (BCVA) was 20/1000 in the right eye and 20/20 in the left eye. Intraocular pressure (IOP) was 9 mmHg in both eyes. Slit-lamp examination revealed a small linear corneal wound and an iris defect in the right eye, along with a cataract featuring brownish deposits on the anterior capsule. The left eye was normal. Fundus examination of the right eye was hindered by media opacities. Ultrasonography showed a flat retina and choroid with no detectable IOFB. Despite a strong clinical suspicion of OS, computed tomography (CT) did not detect any IOFB. MRI subsequently identified an artifact in the inferior sectors of the right eye, indicative of a metallic IOFB. Surgical intervention involved a 23-gauge vitrectomy, phacoemulsification, IOFB removal and silicon oil (SO) tamponade resulting in a fully restored VA of 20/20 and normal IOP one month post-operation. SO was removed 2 months later. The retina remained adherent with no PVR development, and optical coherence tomography (OCT) scans showed a normal macula.ConclusionsThis case underscores the importance of considering OS in patients with unexplained vision loss and history of ocular trauma, even when initial imaging fails to detect an IOFB. MRI proved crucial in identifying the IOFB, highlighting its value in the diagnostic process. Early detection and surgical removal of IOFBs are essential to prevent irreversible visual damage. This case demonstrates that MRI should be employed when CT and ultrasonography are inconclusive, ensuring accurate diagnosis and timely intervention to preserve vision.

Cost-effectiveness of incorporating self-imaging optical coherence tomography into fundus photography-based diabetic retinopathy screening

Diabetic macular edema (DME) has emerged as the foremost cause of vision loss in the population with diabetes. Early detection of DME is paramount, yet the prevailing screening, relying on two-dimensional and labor-intensive fundus photography (FP), results in frequent unwarranted referrals and overlooked diagnoses. Self-imaging optical coherence tomography (SI-OCT), offering fully automated, three-dimensional macular imaging, holds the potential to enhance DR screening. We conducted an observational study within a cohort of 1822 participants with diabetes, who received comprehensive assessments, including visual acuity testing, FP, and SI-OCT examinations. We compared the performance of three screening strategies: the conventional FP-based strategy, a combination strategy of FP and SI-OCT, and a simulated combination strategy of FP and manual SD-OCT. Additionally, we undertook a cost-effectiveness analysis utilizing Markov models to evaluate the costs and benefits of the three strategies for referable DR. We found that the FP + SI-OCT strategy demonstrated superior sensitivity (87.69% vs 61.53%) and specificity (98.29% vs 92.47%) in detecting DME when compared to the FP-based strategy. Importantly, the FP + SI-OCT strategy outperformed the FP-based strategy, with an incremental cost-effectiveness ratio (ICER) of $8016 per quality-adjusted life year (QALY), while the FP + SD-OCT strategy was less cost-effective, with an ICER of $45,754/QALY. Our results were robust to extensive sensitivity analyses, with the FP + SI-OCT strategy standing as the dominant choice in 69.36% of simulations conducted at the current willingness-to-pay threshold. In summary, incorporating SI-OCT into FP-based screening offers substantial enhancements in sensitivity, specificity for detecting DME, and most notably, cost-effectiveness for DR screening.

Suppression of inner blood-retinal barrier breakdown and pathogenic Müller glia activation in ischemia retinopathy by myeloid cell depletion

Ischemic retinopathies including diabetic retinopathy are major causes of vision loss. Inner blood-retinal barrier (BRB) breakdown with retinal vascular hyperpermeability results in macular edema. Although dysfunction of the neurovascular unit including neurons, glia, and vascular cells is now understood to underlie this process, there is a need for fuller elucidation of the underlying events in BRB dysfunction in ischemic disease, including a systematic analysis of myeloid cells and exploration of cellular cross-talk. We used an approach for microglia depletion with the CSF-1R inhibitor PLX5622 (PLX) in the retinal ischemia-reperfusion (IR) model. Under non-IR conditions, PLX treatment successfully depleted microglia in the retina. PLX suppressed the microglial activation response following IR as well as infiltration of monocyte-derived macrophages. This occurred in association with reduction of retinal expression of chemokines including CCL2 and the inflammatory adhesion molecule ICAM-1. In addition, there was a marked suppression of retinal neuroinflammation with reduction in expression of IL-1b, IL-6, Ptgs2, TNF-a, and Angpt2, a protein that regulates BRB permeability. PLX treatment significantly suppressed inner BRB breakdown following IR, without an appreciable effect on neuronal dysfunction. A translatomic analysis of Müller glial-specific gene expression in vivo using the Ribotag approach demonstrated a strong suppression of Müller cell expression of multiple pro-inflammatory genes following PLX treatment. Co-culture studies of Müller cells and microglia demonstrated that activated microglia directly upregulates Müller cell-expression of these inflammatory genes, indicating Müller cells as a downstream effector of myeloid cells in retinal IR. Co-culture studies of these two cell types with endothelial cells demonstrated the ability of both activated microglia and Müller cells to compromise EC barrier function. Interestingly, quiescent Müller cells enhanced EC barrier function in this co-culture system. Together this demonstrates a pivotal role for myeloid cells in inner BRB breakdown in the setting of ischemia-associated disease and indicates that myeloid cells play a major role in iBRB dysregulation, through direct and indirect effects, while Müller glia participate in amplifying the neuroinflammatory effect of myeloid cells.

Intravitreal Dexamethasone Implant Switch after Anti-VEGF Treatment in Patients Affected by Retinal Vein Occlusion: A Review of the Literature.

Nowadays, retinal vein occlusion (RVO) is the second most prevalent cause of vision loss associated with retinal vascular disease. Intravitreal injections are currently known as a major advancement in ophthalmology, particularly in the treatment of RVO and other retinal disorders. Particularly, the first line of therapy is usually anti-vascular endothelial growth factor (VEGF) drugs. Notably, for RVO eyes that have not responded to anti-VEGF therapy, an intravitreal dexamethasone (DEX) implant 0.7 mg (Ozurdex®, AbbVie Inc., North Chicago, IL, USA) is considered a suitable therapeutical substitute. Actually, investigations carried out in the real world and clinical trials have shown the safety and the efficacy of intravitreal DEX implants for treating this retinal disease. For this reason, choosing patients carefully may thus be essential to reduce the number of injections that clinics and hospitals have to do to manage RVO and its complications. The primary aim of this review is to summarize the pathophysiology of this retinal vascular disease, as well as the clinical and ocular imaging features that may support a switch from prior anti-VEGF treatment to intravitreal DEX implant, to provide the RVO patients with the best possible treatment to ensure maximum visual recovery.

Predictors of Diabetic Retinopathy in Type 2 Diabetes: A Cross-Sectional Study.

Type 2 diabetes mellitus (T2DM) represents one of the most impacting health issues of the modern era, as it is associated with an extensive range of comorbidities. Diabetic retinopathy (DR) is one the utmost severe diabetes complications as it is one of the major causes of vision loss among these patients. Our present research aims to evaluate the most frequent risk factors related to the occurrence of DR in T2DM patients. This study consisted of a research group of 302 participants, priorly diagnosed with T2DM, that were evaluated for the most important risk factors related to the occurrence of DR. Patients had a median age of 64 years, 48% of them being women, with a 12-year median duration of DM and presenting a deficient glycaemic control echoed by a median HbA1C value of 7.5%. From the total number of participants, the total prevalence of DR in different stages of severity was 34.8% with a 95% CI. Statistically significant values were found regarding DM duration (p = 0.007), HbA1c > 7.2% (p = 0.001) and patients aged over 67 years (p = 0.0035), all these parameters being directly linked to DR. Older patients with T2DM that have a longer disease duration and simultaneous comorbidities present a higher risk of DR development, consequently a stringent management of these pathologies is needed.

Predict and Protect: Evaluating the Double-Layer Sign in Age-Related Macular Degeneration.

Advanced age-related macular degeneration (AMD) is a major cause of vision loss. Therefore, there is interest in precursor lesions that may predict or prevent the onset of advanced AMD. One such lesion is a shallow separation of the retinal pigment epithelium (RPE) and Bruch's membrane (BM), which is described by various terms, including double-layer sign (DLS). In this article, we aim to examine and clarify the different terms referring to shallow separation of the RPE and BM. We also review current evidence on the outcomes associated with DLS: firstly, whether DLS is predictive of exudative neovascular AMD; and secondly, whether DLS has potential protective properties against geographic atrophy. The range of terms used to describe a shallow separation of the RPE and BM reflects that DLS can present with different characteristics. While vascularised DLS appears to protect against atrophy but can progress to exudation, non-vascularised DLS is associated with an increased risk of atrophy. Optical coherence tomography (OCT) angiography (OCTA) is the principal method for identifying and differentiating various forms of DLS. If OCTA is unavailable or not practically possible, simplified classification of DLS as thick or thin, using OCT, enables the likelihood of vascularisation to be approximated. Research is ongoing to automate DLS detection by applying deep-learning algorithms to OCT scans. The term DLS remains applicable for describing shallow separation of the RPE and BM. Detection and classification of this feature provides valuable information regarding the risk of progression to advanced AMD. However, the appearance of DLS and its value in predicting AMD progression can vary between patients. With further research, individualised risks can be confirmed to inform appropriate treatment.

Sulindac prevents increased mitochondrial VDAC1 expression and cell surface mistargeting induced by pathological conditions in retinal cells

Diabetic retinopathy (DR) continues to be the primary cause of vision loss in poorly controlled diabetic subjects. The molecular mechanisms underlying retinal pigment epithelium (RPE) cell dysfunction in DR still remain elusive. We investigated the role of mitochondrial volt-age-dependent anion channel 1 (VDAC1) in RPE dysfunction under glucotoxic and inflammatory conditions. Our results demonstrate that both glucotoxicity and cytokine treatment reduces cellular viability accompanied by increased VDAC1 and inducible nitric oxide synthase (iNOS) expression, concomitant with decreased expression of mitochondrial VDAC2 and constitutively ex-pressed endothelial NOS (eNOS). Increased VDAC1 expression during these conditions leads to its mistargeting to the cell surface, leading to ATP loss. Additionally, VDAC1 upregulation by glucotoxicity and inflammatory cytokines induces leakage of mitochondrial DNA (mtDNA) into the cytosol. Sulindac, a nonsteroidal anti-inflammatory agent, mitigates the adverse effects associated with increased VDAC1 level under pathophysiological conditions, by suppressing VDAC1 expression. The effect of sulindac on restoring cell viability could be comparably achieved only with VDAC1 inhibitor (VBIT-4) or VDAC1-specific antibody and not with the iNOS inhibitor aminoguanidine.Our findings suggest that sulindac's beneficial effects on ARPE-19 cell function are mediated by prevention of increased VDAC1 expression under pathological conditions, thus preventing mtDNA leakage and ATP loss, which are the key steps in induction of cellular inflammatory responses involved in the development of DR.

Epidemiology of eye diseases in Bangladesh

Bangladesh is densely populated country in South Asia, faces significant challenges in eye health due to various socioeconomic, environmental, and healthcare access factors. Limited access to quality eye care services, poor hygiene practices, prevalence of infectious diseases, and a high burden of non-communicable diseases contribute to the prevalence of eye disorders in the region. This study aims to comprehensively analyze the prevalence, distribution, and risk factors associated with various eye diseases among the population of Bangladesh. A systematic review and meta-analysis were conducted to gather data on the epidemiology of eye diseases in Bangladesh. Published studies, national surveys, and reports from relevant health organizations were reviewed to compile data on the prevalence, distribution, and risk factors of common eye conditions, including cataracts, refractive errors, conjunctivitis, glaucoma, diabetic retinopathy, and age-related macular degeneration. The prevalence of eye diseases in Bangladesh is relatively high, with conditions such as refractive errors, cataracts, glaucoma, and corneal diseases being major concerns. Refractive errors, including myopia, hyperopia, and astigmatism, affect a substantial portion of the population, particularly among children and young adults. Cataracts, a leading cause of blindness worldwide, also pose a significant burden in Bangladesh, with prevalence increasing with age. While the prevalence of glaucoma in Bangladesh is lower compared to some other countries, the condition remains a cause of concern due to its impact on quality of life and the healthcare system. Diabetic retinopathy, a complication of diabetes mellitus, affects the retina and is a leading cause of vision loss and blindness globally in the elderly. In Bangladesh, the rising prevalence of diabetes, fueled by changing lifestyles and an aging population, has contributed to an increasing burden of diabetic retinopathy. Conjunctivitis is prevalent, particularly in densely populated urban areas and rural communities with limited access to clean water and sanitation facilities.Collaborative efforts involving government agencies, healthcare providers, non-governmental organizations, and the community are essential to effectively address the burden of eye diseases in Bangladesh. By implementing preventive measures and improving access to quality eye care services, it is possible to mitigate the impact of these eye diseases and improve visual health outcomes for the population.

Pericyte loss via glutaredoxin2 downregulation aggravates diabetes-induced microvascular dysfunction

Diabetic retinopathy (DR) is the leading cause of vision loss and blindness among working-age adults. Pericyte loss is an early pathological feature of DR. Under hyperglycemic conditions, reactive oxygen species (ROS) production increases, leading to oxidative stress and subsequent mitochondrial dysfunction and apoptosis. Dysfunctional pericyte can cause retinal vascular leakage, obliteration, and neovascularization. Glutaredoxin 2 (Grx2) is a mitochondrial glutathione-dependent oxidoreductase which protects cells against oxidative insults by safeguarding mitochondrial function. Whether Grx2 plays a protective role in diabetes-induced microvascular dysfunction remains unclear. Our findings revealed that diabetes-related stress reduced Grx2 expression in pericytes, but not in endothelial cells. Grx2 knock-in ameliorated diabetes-induced microvascular dysfunction in vivo DR models. Decreased Grx2 expression led to significant pericyte apoptosis, and pericyte dysfunction, namely reduced pericyte recruitment towards endothelial cells and increased endothelial cell permeability. Conversely, upregulating Grx2 reversed these effects. Furthermore, Grx2 regulated pericyte apoptosis by modulating complex I activity, which is crucial for pericyte mitochondrial function. Overall, our study uncovered a novel mechanism whereby high glucose inhibited Grx2 expression in vivo and in vitro. Grx2 downregulation exacerbated pericyte apoptosis, pericyte dysfunction, and retinal vascular dysfunction by inactivating complex I and mediating mitochondrial dysfunction in pericytes.

Association of serum lipid profile and other systemic risk factors with retinal hard exudates in diabetic retinopathy

PurposeDiabetic macular edema is one of the leading causes of vision loss across the world. Hard exudates at the macula can lead to structural abnormalities in the retina leading to irreversible vision loss. Systemic dyslipidemia and other modifiable risk factors when identified and treated early may help prevent substantial vision loss. The purpose of this study was to study the association between serum lipid levels and other systemic risk factors like hemoglobin, HbA1c, and serum creatinine with hard exudates and macular edema in patients with diabetic retinopathy.MethodsIt is a prospective cross-sectional study conducted in a tertiary health care center in South India. 96 patients having diabetic retinopathy with hard exudates were included. Modified Airlie house classification was used to grade the hard exudates. Blood investigations including serum lipid profile, hemoglobin, HbA1c, and serum creatinine were carried out. Central subfield macular thickness was measured using optical coherence tomography.Results96 patients of type II DM with diabetic retinopathy were divided into three groups of hard exudates. A statistically significant correlation was observed between the severity of hard exudates and total cholesterol (p = 0.00), triglycerides (p = 0.00), LDL (p = 0.00), and VLDL (p = 0.00). HbA1c levels showed a statistically significant correlation with the severity of hard exudates (p = 0.09), no significant correlation was noted between hard exudates and hemoglobin levels (p = 0.27) and with serum creatinine (p = 0.612). A statistically significant association between CSMT and hard exudates (p = 0.00) was noted.ConclusionIn our study, we concluded that the severity of hard exudates is significantly associated with increasing levels of serum total cholesterol, triglycerides, LDL, VLDL, and HbA1c levels in type II DM patients presenting with diabetic retinopathy. The increasing duration of diabetes is significantly associated with increasing severity of hard exudates. Central subfield macular thickness increases with increasing severity of hard exudates in diabetic retinopathy.

Injectable, antioxidative, and loaded with exosomes/Liproxstatin-1 hydrogel as a potential treatment for retinal ischemia–reperfusion by inhibiting ferroptosis and apoptosis

Retinal ischemia–reperfusion is a major cause of vision loss in a variety of ocular diseases, including glaucoma, age-related macular degeneration, diabetic retinopathy, and central retinal artery occlusion. Previous studies have reported the protective effects of injectable hydrogels in optic nerve injury, but reports of multifunctional hydrogels loaded with drugs and bioactive substances that synergistically promote neuroprotection are rare. Here, we designed an injectable, drug-loaded, and reactive oxygen species responsive multifunctional hydrogel. Upon intravitreal injection into a retinal ischemia–reperfusion injury model in mice, the hydrogel released exosomes and liproxstatin-1 over an extended period exceeding a month, leading to a significant recovery of visual function and reduction of retinal ganglion cell loss. The effect was superior to that of the common drug and exosome combination. The results of this study suggest that this multifunctional hydrogel is expected to advance retinal tissue engineering and provide an innovative strategy for acute neuroprotection in retinal ischemia–reperfusion injury.

Glucose-Regulated Protein 78, via Releasing β-Catenin from Adherens Junctions, Facilitates Its Interaction with STAT3 in Mediating Retinal Neovascularization

Retinopathy due to neovascularization is one of the major causes of vision loss. To understand the mechanisms underlying retinal neovascularization, using the oxygen-induced retinopathy (OIR) model, we performed two-dimensional gel matrix-assisted laser desorption/ionization time-of-flight/time-of-flight analysis of normoxic and 24-hour post-OIR mice pups' retinas. Two-dimensional gel analysis revealed that glucose-regulated protein 78 (GRP78) is one of the several molecules induced by OIR in the retinal endothelial cells (ECs). Vascular endothelial growth factor A (VEGFA) also induced GRP78 expression independent of endoplasmic reticulum stress response in human retinal microvascular endothelial cells, and depletion of its levels reduced VEGFA-induced EC angiogenic responses. Consistent with these observations, EC-specific deletion of GRP78 inhibited OIR-induced retinal neovascularization. In exploring the mechanisms, we found that GRP78 binds with vascular endothelial-cadherin and releases adherens junction- but not Wnt-mediated β-catenin and that β-catenin, in turn, via interacting with STAT3, triggers cyclin D1 expression. Furthermore, depletion of β-catenin or cyclin D1 levels negated VEGFA-induced EC angiogenic responses and OIR-induced retinal neovascularization. EC-specific deletion of GRP78 also suppressed OIR-induced vascular leakage. In elucidating the upstream signaling, we found that activating transcription factor 6 mediates GRP78 induction in the modulation of VEGFA-induced EC angiogenic responses and OIR-induced retinal neovascularization. Together, these observations reveal that GRP78, independent of its response to endoplasmic reticulum stress, is involved in mediating EC angiogenic responses by VEGFA and retinal neovascularization by OIR. In view of these findings, it appears that GRP78 could be a desirable target for drug development against diabetic retinopathy.

Inducible RPE-specific GPX4 knockout causes oxidative stress and retinal degeneration with features of age-related macular degeneration

Age-related macular degeneration (AMD) is one of the leading causes of vision loss in the elderly. This disease involves oxidative stress burden in the retina leading to death of retinal pigment epithelial (RPE) cells and photoreceptors. The retina is susceptible to oxidative stress, in part due to high metabolic activity and high concentration of polyunsaturated fatty acids that undergo lipid peroxidation chain reactions. Antioxidant enzymes exist in the retina to combat this stress, including glutathione peroxidase 4 (GPX4). GPX4 specifically reduces oxidized lipids, protecting against lipid peroxidation-induced oxidative stress, which is noted in dry AMD. We hypothesize that Gpx4 knockout within the RPE will result in an environment of chronic oxidative stress yielding degeneration akin to AMD. C57BL/6J mice with a floxed Gpx4 gene were mated with Rpe65Cre/ER mice. Offspring containing Rpe65Cre ± alleles and either Gpx4 WT or Gpx4 fl/fl alleles were administered tamoxifen to induce Gpx4 knockout in Gpx4 fl/fl mice. At sequential timepoints, retinal phenotypes were assessed via in vivo imaging utilizing confocal scanning laser ophthalmoscopy and optical coherence tomography (OCT), and visual function was probed by electroretinography. Retinas were studied post-mortem by immunohistochemical analyses, electron microscopy, plastic sectioning, and quantitative polymerase chain reaction and Western analyses. The RPE-specific Gpx4 knockout model was validated via Western analysis indicating diminished GPX4 protein only within the RPE and not the neural retina. Following Gpx4 knockout, RPE cells became dysfunctional and died, with significant cell loss occurring 2 weeks post-knockout. Progressive thinning of the photoreceptor layer followed RPE degeneration and was accompanied by loss of visual function. OCT and light microscopy showed hyperreflective foci and enlarged, pigmented cells in and above the RPE layer. Electron microscopy revealed decreased mitochondrial cristae and loss of basal and apical RPE ultrastructure. Finally, there was increased carboxyethylpyrrole staining, indicating oxidation of docosahexaenoic acid, and increased levels of mRNAs encoding oxidative stress-associated genes in the RPE and photoreceptors. Overall, we show that RPE-localized GPX4 is necessary for the health of the RPE and outer retina, and that knockout recapitulates phenotypes of dry AMD.

Management of open globe injury: a narrative review.

Open globe injuries are a significant global cause of visual loss, including unilateral and bilateral blindness. Prognosis is predicted by injury severity, with lower presenting visual acuity and more posterior injuries associated with poor visual outcomes, although even the most severely injured eyes with no perception of light vision may regain some visual function. In addition to severity of the primary injury, the secondary injuries and complications causing poor outcomes include proliferative vitreoretinopathy (PVR) and endophthalmitis. Endophthalmitis is common after open globe injury, affecting up to 16.5% of patients. Systemic antibiotic prophylaxis is commonly used, with a limited evidence base, while intraocular antibiotics are less commonly used but have stronger supporting evidence of efficacy. Endophthalmitis rates are also reduced by prompt primary repair, which may also support recovery of visual acuity. PVR is not prevented or treated by any pharmacologic interventions in current clinical practice, but the incidence of post-traumatic PVR may be reduced by early vitrectomy within the first 4-7 days after injury. Ocular trauma training is often limited in Western ophthalmic surgical training programmes, and patients with ocular trauma often require the input of multiple subspecialists. In this context, it is important that patients have an overview and coordination of the different aspects of their care, with ownership by one lead clinician.

NetraDeep: An Integrated Deep Learning and Image Processing System for Precise Detection of Hard Exudates

Hard Exudate (HE) is a common manifestation of various eye diseases, such as diabetic retinopathy (DR), and a prominent cause of vision loss and blindness. Researchers aim to visualize and quantify these exudates using deep learning (DL) and image processing (IP) models from retinal images. However, the requirement for a large number of labelled image datasets for DL models to work on diverse and poor-quality images makes this task challenging. To address this challenge, we introduce NetraDeep, a system that integrates data-driven DL and rule-based IP techniques for exudate segmentation. Our system uses IP models to detect and extract some features and assists DL models in detecting more advanced features and vice versa. The IP models are rule-based and use predefined rules to process images, while the DL models are data-driven and learn from the input data. NetraDeep provides visual and quantitative assessments while mitigating noise and other confounding factors such as artifacts and noise. The training of DL models of this system requires only a limited number of labelled fundus images from publicly available datasets. It provides accurate pixel-wise segmentation results on the public and private image datasets collected from local eye hospitals. Through extensive evaluation, our system achieved remarkable performance, with a dice coefficient of \(0.84\) for the public dataset and a rating of \(9.78\) and \(9.43\) out of 10, as corroborated by two medical experts with experience of more than 20 and 5 years, respectively, for the private image dataset.

Off-Label Use of Bevacizumab in Patients Diagnosed with Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.

Age-related macular degeneration (AMD) is the leading cause of vision loss in elderly people. Current pharmacological treatment in vascular AMD includes anti-VEGF agents, such as ranibizumab and aflibercept. Additionally, the off-label use of bevacizumab has been shown to be effective and has a lower cost, making it an interesting pharmacological approach; however, there is no consensus about its use. Therefore, this systematic review and meta-analysis aims to evaluate the efficacy, safety, and efficiency of bevacizumab in AMD patients. This review only focused on randomized controlled clinical trials published in 2010 in the MEDLINE database that compared the effect of bevacizumab with ranibizumab. The risk of bias in each included study was assessed using the CASP Randomised Clinical Trials checklist. Twelve studies were included for qualitative synthesis, and nine of them were considered for meta-analysis. Bevacizumab-treated patients showed a significantly reduced neovascularization in a longer spectrum of time; however, they had a higher incidence of endophthalmitis than those treated with ranibizumab. Regarding efficiency, the mean number of administrations was reduced in the treatment with bevacizumab in comparison to ranibizumab. Clinical evidence demonstrates that bevacizumab has efficacy and safety profiles comparable with ranibizumab; however, it is relatively more efficient.

Improved diabetic retinopathy severity classification using squeeze-and-excitation and sparse light weight multi-level attention u-net with transfer learning from xception.

Diabetic Retinopathy (DR) is a significant cause of vision loss in diabetic patients, making early detection and accurate severity classification essential for effective management and prevention. This study aims to develop an enhanced DR severity classification approach using advanced model architectures and transfer learning to improve diagnostic accuracy and support better patient care. We propose a novel model, Xception Squeeze-and-Excitation Sparse Lightweight Multi-Level Attention U-Net (XceSE_SparseLwMLA-UNet), designed to classify DR severity using fundus images from the Messidor 1 and Messidor 2 datasets. The XceSE_SparseLwMLA-UNet integrates several advanced mechanisms: the Squeeze-and-Excitation (SE) mechanism for adaptive feature recalibration, the Sparse Lightweight Multi-Level Attention (SparseLwMLA) mechanism for effective contextual information integration, and transfer learning from the Xception architecture to enhance feature extraction capabilities. The SE mechanism refines channel-wise feature responses, while SparseLwMLA enhances the model's ability to identify complex DR patterns. Transfer learning utilizes pre-trained weights from Xception to improve generalization across DR severity levels. The proposed XceSE_SparseLwMLA-UNet model demonstrates superior performance in DR severity classification, achieving higher accuracy and improved multi-class F1 scores compared to existing models. The model's color-coded segmentation outputs offer interpretable visual representations, aiding medical professionals in assessing DR severity levels. The XceSE_SparseLwMLA-UNet model shows promise for advancing early DR diagnosis and management by enhancing classification accuracy and providing valuable visual insights. Its integration of advanced architectural features and transfer learning contributes to better patient care and improved visual health outcomes.

Retinal debris triggers cytotoxic damage in cocultivated primary porcine RPE cells.

One of the most common causes of vision loss in the elderly population worldwide is age-related macular degeneration (AMD). Subsequently, the number of people affected by AMD is estimated to reach approximately 288 million by the year 2040. The aim of this study was to develop an ex vivo model that simulates various aspects of the complex AMD pathogenesis. For this purpose, primary porcine retinal pigment epithelial cells (ppRPE) were isolated and cultured. One group was exposed to medium containing sodium iodate (NaIO3) to induce degeneration. The others were exposed to different supplemented media, such as bovine serum albumin (BSA), homogenized porcine retinas (HPR), or rod outer segments (ROOS) for eight days to promote retinal deposits. Then, these ppRPE cells were cocultured with porcine neuroretina explants for another eight days. To assess the viability of ppRPE cells, live/dead assay was performed at the end of the study. The positive RPE65 and ZO1 area was evaluated by immunocytochemistry and the expression of RLBP1, RPE65, and TJP1 was analyzed by RT-qPCR. Additionally, drusen (APOE), inflammation (ITGAM, IL6, IL8, NLRP3, TNF), oxidative stress (NFE2L2, SOD1, SOD2), and hypoxia (HIF1A) markers were investigated. The concentration of the inflammatory cytokines IL-6 and IL-8 was determined in medium supernatants from day 16 and 24 via ELISA. Live/dead assay suggests that especially exposure to NaIO3 and HPR induced damage to ppRPE cells, leading in a significant ppRPE cell loss. All supplemented media resulted in decreased RPE-characteristic markers (RPE65; ZO-1) and gene expression like RLBP1 and RPE65 in the cultured ppRPE cells. Besides, some inflammatory, oxidative as well as hypoxic stress markers were altered in ppRPE cells cultivated with NaIO3. The application of HPR induced an enhanced APOE expression. Pre-exposure of the ppRPE cells led to a diminished number of cones in all supplemented media groups compared to controls. Overall, this novel coculture model represents an interesting initial approach to incorporating deposits into coculture to mimic AMD pathogenesis. Nevertheless, the effects of the media used need to be investigated in further studies.

Comparative Proteomic Analysis of Type 2 Diabetic versus Non-Diabetic Vitreous Fluids.

Diabetic retinopathy (DR) is a leading cause of vision loss, with complex mechanisms. The study aimed to comprehensively explore vitreous humor of diabetic and non-diabetic individuals, paving the way for identifying the potential molecular mechanisms underlying DR. Vitreous samples from type 2 diabetic and non-diabetic subjects, collected post-mortem, were analyzed using liquid chromatography-mass spectrometry. Pathway enrichment and gene ontology analyses were conducted to identify dysregulated pathways and characterize protein functions. Pathway analysis revealed dysregulation in multiple metabolic and signaling pathways associated with diabetes, including glycerolipid metabolism, histidine metabolism, and Wnt signaling. Gene ontology analysis identified proteins involved in inflammation, immune response dysregulation, and calcium signaling. Notably, proteins such as Inositol 1,4,5-trisphosphate receptor type 2 (ITPR2), Calcium homeostasis endoplasmic reticulum protein (CHERP), and Coronin-1A (CORO1A) were markedly upregulated in diabetic vitreous, implicating aberrant calcium signaling, inflammatory responses, and cytoskeletal reorganization in DR. Our study provides valuable insights into the intricate mechanisms underlying DR and highlights the significance of inflammation, immune dysregulation, and metabolic disturbances in disease progression. Identification of specific proteins as potential biomarkers underscores the multifactorial nature of DR. Future research in this area is vital for advancing therapeutic interventions and translating findings into clinical practice.