Irreversible Blindness Research Articles

Ventriculoperitoneal shunt patients and glaucoma: a cohort analysis of the NPH registry

BackgroundIdiopathic Normal Pressure Hydrocephalus (iNPH) is a chronic condition affecting the elderly. It is characterized by a triad of symptoms and radiological findings. Glaucoma is the leading cause of irreversible blindness worldwide. Earlier studies have proposed that the rate of glaucoma is higher in iNPH patients, and of a possible link between ventriculoperitoneal shunt (VP) treatment and the development of glaucoma.ObjectivesThis study aimed to determine the prevalence of glaucoma among iNPH patients and assess the impact of VPs on glaucoma prevalence.MethodsA cohort study was conducted at Kuopio University Hospital (KUH), including 262 patients with a ventriculoperitoneal shunt. Clinical data were obtained from the Kuopio NPH Registry and medical records. Patients were grouped by iNPH status: iNPH (+) – probable/possible iNPH (n = 192), and iNPH (-) – other causes of hydrocephalus (congenital, secondary, obstructive) (n = 70). We conducted statistical analysis using the Independent Samples T-test, Fisher’s exact test, and Pearson Chi-Square. We compared demographics, glaucoma prevalence, brain biopsies positive for Amyloid-β (Aβ) and hyperphosphorylated tau (HPτ) as well as comorbidities for hypertension and diabetes medication. Age stratification assessed glaucoma prevalence in the full cohort.ResultsBoth iNPH (+) and iNPH (-) groups had comparable demographic and comorbidity profiles. The prevalence of glaucoma in the iNPH (+) group was 11.5% (n = 22) and 11.4% (n = 8) in the iNPH (-) group without a statistically significant difference (p = 1.000). Brain biopsies positive for Amyloid-β (Aβ) and hyperphosphorylated tau (HPτ) were similar.ConclusionsNeither shunted iNPH patients nor those with a comorbid condition other than iNPH showed a markedly higher prevalence of glaucoma. Instead, both groups exhibited age-related increases in glaucoma prevalence, similar to the trends observed in population-based studies. Our data does not suggest a correlation between VP shunts and an elevated rate of glaucoma.

Causal relationship between central corneal thickness and open-angle glaucoma: Evidence from Mendelian randomization

Glaucoma is the leading cause of irreversible blindness worldwide. Previous observational studies have suggested a relationship between central corneal thickness (CCT) and glaucoma; however, the results are inconsistent. This study aimed to investigate whether CCT is associated with a risk for developing open-angle glaucoma (OAG). We employed two-sample Mendelian randomization to assess the relationship between CCT and OAG, namely, primary open-angle glaucoma (POAG) and suspected glaucoma. Genetic instruments composed of variants associated with CCT at genome-wide significance (P < 5 × 10−8) were obtained from published genome-wide association studies from Iglesias et al. for discovery and Bonnemaijer et al. for replication. Summary-level statistics for these instruments for the OAG were obtained from the FinnGen Project (Release 10). Inverse-variance-weighted regression of genetic susceptibility predicted that increased CCT was positively associated with an increased risk for POAG (odds ratio [OR], 1.005; 95% confidence interval [CI], 1.002–1.008; P = 0.001) and suspected glaucoma (OR, 1.006; 95% CI, 1.003–1.009; P < 0.001). In the replication sample of CCT, increased CCT was also positively associated with an increased risk for POAG (OR, 1.004; 95% CI, 1.000–1.008; P = 0.029) and suspected glaucoma (OR, 1.005; 95% CI, 1.001–1.008; P = 0.013).We found genetic evidence supporting a potential causal association between increased CCT and the risk of POAG and suspected glaucoma in the European population. This findings indicates the clinical significance of CCT in the diagnosis and treatment of glaucoma. Further studies are needed to elucidate the underlying mechanisms of this causal relationship.

Ó�The books and the nightÓ�, neurological perspective on Jorge Luis BorgesÓ? blindness

The works of Argentinian scholar Jorge Luis Borges (1899-1986) have captivated physicians. An assiduous reader, he was given, with magnificent irony, "books and the night". Borges suffered from chronic and irreversible blindness, which influenced much of his work and has been the subject of different literary and diagnostic analyses from the ophthalmological point of view. However, the characteristics of his visual impairment have escaped the neurological approach, which is why we reviewed his work looking for data suggesting a concomitant brain injury. On his autobiography, he recounts how, during an episode of septicemia, he suffered hallucinations and loss of speech; in addition, in some poems and essays he describes data that suggest "phantom chromatopsia", a lesion of cortical origin. After that accident, Borges survived with a radical change in literary style. Although a precise diagnosis is impossible, his literary work allows recognizing some elements in favor of concomitant brain involvement.

Lycium ruthenicum water extract preserves retinal ganglion cells in chronic ocular hypertension mouse models.

Lycium ruthenicum Murray (LR), known as "black goji berry" or "black wolfberry", is widely utilized in chinese herbal medicine. LR fruit showed its antioxidant and/or anti-inflammation activity in treating cardiac injury, experimental colitis, nonalcoholic fatty liver disease, fatigue, and aging. Glaucoma is the leading cause of irreversible blindness. Besides elevated intraocular pressure (IOP), oxidative stress and neuroinflammation were recognized to contribute to the pathogenesis of glaucoma. This study investigated the treatment effects of LR water extract (LRE) on retinal ganglion cells (RGCs) threatened by sustained IOP elevation in a laser-induced chronic ocular hypertension (COH) mouse model and the DBA/2J mouse strain. The antioxidation and anti-inflammation effects of LRE were further tested in the H2O2-challenged immortalized microglial (IMG) cell line in vitro. LRE oral feeding (2g/kg) preserved the function of RGCs and promoted their survival in both models mimicking glaucoma. LRE decreased 8-hydroxyguanosine (oxidative stress marker) expression in the retina. LRE reduced the number of Iba-1+ microglia in the retina of COH mice, but not in the DBA/2J mice. At the mRNA level, LRE reversed the COH induced HO-1 and SOD-2 overexpressions in the retina of COH mice. Further in vitro study demonstrated that LRE pretreatment to IMG cells could significantly reduce H2O2 induced oxidative stress through upregulation of GPX-4, Prdx-5, HO-1, and SOD-2. Our work demonstrated that daily oral intake of LRE can be used as a preventative/treatment agent to protect RGCs under high IOP stress probably through reducing oxidative stress and inhibiting microglial activation in the retina.

Small extracellular vesicles derived from microRNA-22-3p-overexpressing mesenchymal stem cells protect retinal ganglion cells by regulating MAPK pathway

Glaucoma is the leading cause of irreversible blindness and is characterized by progressive retinal ganglion cell (RGC) loss and retinal nerve fiber layer thinning. Currently, no existing treatment is effective for the preservation of RGCs. MicroRNA-22-3p (miR22) and small extracellular vesicles derived from mesenchymal stem cells (MSC-sEVs) have neuroprotective effects. In this study, we apply miR22-overexpressing MSC-sEVs in an N-methyl-D-aspartic acid (NMDA)-induced RGC injury model to assess their short-term therapeutic effects and explore the underlying mechanisms. We find that mice in the miR22-sEVs-treated group have thicker retinas, fewer apoptotic cells, more reserved RGCs, better retinal function, and lower expression levels of Bax and caspase-3. MiR22-sEVs treatment promotes viability, inhibits apoptosis and inhibits Bax and caspase-3 expression in RGC-5 cells. MiR22 targets mitogen-activated protein kinase kinase kinase 12 to inhibit apoptosis by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Collectively, our results suggest that miR22-sEVs ameliorate NMDA-induced RGC injury through the inhibition of MAPK signaling pathway-mediated apoptosis, providing a potential therapy for glaucoma and other diseases that involve RGC damage.

Optic nerve head and retinal nerve fiber layer changes by spectral domain optical coherence tomography in glaucoma suspects at tertiary care hospital

Introduction: Glaucoma is a progressive optic neuropathy characterized by functional loss or optic nerve dysfunction which is one of the leading causes of irreversible but preventable blindness. The aim of the study was to determine which of the retinal nerve fiber layer and optic nerve head parameters are reliable markers of optic nerve damage in glaucoma suspects. Methods: Observational cross-sectional study of 250 patient’s including147 glaucoma suspect eyes, 103 normal eyes. All subjects underwent complete eye examination and imaging with the spectral domain optical coherence tomography (SD-OCT) cirrus-TM OCT (Carl Zeiss Meditec, Dublin, CA). Retinal nerve fiber layer (RNFL) and optic nerve head (ONH) OCT protocols were used to evaluate all study participants. The main outcome measures were the difference in OCT parameters among groups. Results: Study shows statistically significant difference in the average RNFL thickness, superior, nasal, inferior, temporal quadrants, rim area, cup volume, average cup to disc ratio (CDR), vertical CDR with P value &lt;0.001 between the two groups. Average CDR, vertical CDR and cup volume had significantly greater AROC values (ROC: 0.99, 0.98, 0.95) than RNFL parameters for discriminating glaucoma suspects from normal eyes. Conclusion: Assessment of RNFL, macular and ONH damage with SD-OCT has been proven useful for diagnosing the disease at different levels of severity, as well as for quantifying risk in glaucoma suspects. In our study ONH measurements, as provided by the SD OCT, have more diagnostic value than RNFL parameters in the diagnosis of glaucoma suspects from normal. Keywords: glaucoma suspects; optic nerve head; retinal nerve fiber layer; optical coherence tomography

Protective Effect of Nicotinamide Riboside on Glucocorticoid-Induced Glaucoma: Mitigating Mitochondrial Damage and Extracellular Matrix Deposition.

Glucocorticoid-induced glaucoma (GIG) is a prevalent complication associated with glucocorticoids (GCs), resulting in irreversible blindness. GIG is characterized by the abnormal deposition of extracellular matrix (ECM) in the trabecular meshwork (TM), elevation of intraocular pressure (IOP), and loss of retinal ganglion cells (RGCs). The objective of this study is to investigate the effects of nicotinamide riboside (NR) on TM in GIG. Primary human TM cells (pHTMs) and C57BL/6J mice responsive to GCs were utilized to establish in vitro and in vivo GIG models, respectively. The study assessed the expression of ECM-related proteins in TM and the functions of pHTMs to reflect the effects of NR. Mitochondrial morphology and function were also examined in the GIG cell model. GIG progression was monitored through IOP, RGCs, and mitochondrial morphology. Intracellular nicotinamide adenine dinucleotide (NAD+) levels of pHTMs were enzymatically assayed. NR significantly prevented the expression of ECM-related proteins and alleviated dysfunction in pHTMs after dexamethasone treatment. Importantly, NR protected damaged ATP synthesis, preventing overexpression of mitochondrial reactive oxygen species (ROS), and also protect against decreased mitochondrial membrane potential induced by GCs in vitro. In the GIG mouse model, NR partially prevented the elevation of IOP and the loss of RGCs. Furthermore, NR effectively suppressed the excessive expression of ECM-associated proteins and mitigated mitochondrial damage in vivo. Based on the results, NR effectively enhances intracellular levels of NAD+, thereby mitigating abnormal ECM deposition and TM dysfunction in GIG by attenuating mitochondrial damage induced by GCs. Thus, NR has promising potential as a therapeutic candidate for GIG treatment.

Harvard Glaucoma Fairness: A Retinal Nerve Disease Dataset for Fairness Learning and Fair Identity Normalization.

Fairness (also known as equity interchangeably) in machine learning is important for societal well-being, but limited public datasets hinder its progress. Currently, no dedicated public medical datasets with imaging data for fairness learning are available, though underrepresented groups suffer from more health issues. To address this gap, we introduce Harvard Glaucoma Fairness (Harvard-GF), a retinal nerve disease dataset including 3,300 subjects with both 2D and 3D imaging data and balanced racial groups for glaucoma detection. Glaucoma is the leading cause of irreversible blindness globally with Blacks having doubled glaucoma prevalence than other races. We also propose a fair identity normalization (FIN) approach to equalize the feature importance between different identity groups. Our FIN approach is compared with various state-of-the-art fairness learning methods with superior performance in the racial, gender, and ethnicity fairness tasks with 2D and 3D imaging data, demonstrating the utilities of our dataset Harvard-GF for fairness learning. To facilitate fairness comparisons between different models, we propose an equity-scaled performance measure, which can be flexibly used to compare all kinds of performance metrics in the context of fairness. The dataset and code are publicly accessible via https://ophai.hms.harvard.edu/datasets/harvard-gf3300/.

Apple Vision Pro’s new technology as a head-mounted perimetry device for glaucoma and other potential applications

Abstract Glaucoma is a leading cause of irreversible blindness worldwide and poses a significant public health challenge. Primary open-angle glaucoma (POAG) is the most common form of glaucoma and is marked by progressive optic nerve damage and peripheral visual field loss. Early detection and management of glaucoma are essential to prevent severe vision impairment. Perimetry measures visual field sensitivity and is a crucial tool for diagnosing and the progression of glaucoma. However, traditional perimetry devices are bulky, expensive, and require specialized settings, thereby limiting their accessibility. Studies indicate the evolving role of portable and home-based visual field testing, where the efficacy of virtual reality (VR) devices such as the VisuALL against traditional perimetry tools. Apple Vision Pro’s integration into glaucoma management could address the limitations of conventional perimetry, and thus making monitoring more feasible and less burdensome. In this manuscript, we explore the potential of Apple Vision Pro’s technology as a head-mounted perimetry device for glaucoma. The Apple Vision Pro headset leverages advances in augmented reality and wearable computing to offer a portable, cost-effective solution for visual field testing. Its compact design enables patients to perform tests at home, thus reducing the need for clinical visits and improving adherence to monitoring protocols. This portability is also particularly beneficial in space environments, such as on the International Space Station, where regular monitoring of visual health of astronauts is critical.

Big data in visual field testing for glaucoma.

Recent technological advancements and the advent of ever-growing databases in health care have fueled the emergence of "big data" analytics. Big data has the potential to revolutionize health care, particularly ophthalmology, given the data-intensive nature of the medical specialty. As one of the leading causes of irreversible blindness worldwide, glaucoma is an ocular disease that receives significant interest for developing innovations in eye care. Among the most vital sources of data in glaucoma is visual field (VF) testing, which stands as a cornerstone for diagnosing and managing the disease. The expanding accessibility of large VF databases has led to a surge in studies investigating various applications of big data analytics in glaucoma. In this study, we review the use of big data for evaluating the reliability of VF tests, gaining insights into real-world clinical practices and outcomes, understanding new disease associations and risk factors, characterizing the patterns of VF loss, defining the structure-function relationship of glaucoma, enhancing early diagnosis or earlier detection of progression, informing clinical decisions, and improving clinical trials. Equally important, we discuss current challenges in big data analytics and future directions for improvement.

Advances in Glaucoma Drug Therapy

Abstract Glaucoma remains the leading cause of irreversible blindness, but timely treatment to lower intraocular pressure is effective at slowing the rate of vision loss from glaucoma. Medical management remains the first line of treatment in adult glaucoma, and the evolution of medical therapy for glaucoma has followed an exponential curve. This narrative review briefs the rapid development of new medications and drug delivery systems in recent years. Newer medications may be able to extend the duration of medically controlled glaucoma, delaying or possibly eliminating the need for glaucoma surgery for some patients. Alternative methods of delivery for glaucoma medications may be a key factor in improving outcomes with currently available medications.

Single-cell RNA sequencing in exploring the pathogenesis of diabetic retinopathy.

Diabetic retinopathy (DR) is a leading cause of irreversible blindness in the working-age populations. Despite decades of research on the pathogenesis of DR for clinical care, a comprehensive understanding of the condition is still lacking due to the intricate cellular diversity and molecular heterogeneity involved. Single-cell RNA sequencing (scRNA-seq) has made the high-throughput molecular profiling of cells across modalities possible which has provided valuable insights into complex biological systems. In this review, we summarise the application of scRNA-seq in investigating the pathogenesis of DR, focusing on four aspects. These include the identification of differentially expressed genes, characterisation of key cell subpopulations and reconstruction of developmental 'trajectories' to unveil their state transition, exploration of complex cell‒cell communication in DR and integration of scRNA-seq with genome-wide association studies to identify cell types that are most closely related to DR risk genetic loci. Finally, we discuss the future challenges and expectations associated with studying DR using scRNA-seq. We anticipate that scRNA-seq will facilitate the discovery of mechanisms and new treatment targets in the clinical care landscape for patients with DR. KEY POINTS: Progress in scRNA-seq for diabetic retinopathy (DR) research includes studies on DR patients, non-human primates, and the prevalent mouse models. scRNA-seq facilitates the identification of differentially expressed genes, pivotal cell subpopulations, and complex cell-cell interactions in DR at single-cell level. Future scRNA-seq applications in DR should target specific patient subsets and integrate with single-cell and spatial multi-omics approaches.

The Visual Outcome of Gunshot Injury after Last Civil War in Tobruk-Libya: A Retrospective Study

Ocular trauma is one of the most common causes of acquired blindness. This study aims to determine the epidemiology of ocular trauma in all the age groups in Tobruk Medical Centre- Libya. A retrospective study was conducted in our hospital for one year and all the aged group presenting with ocular trauma in the Ophthalmology and Emergency Departments were enrolled in the study. Age, sex distribution, presentation duration, mode of injury, type of injury, and final visual outcome were analyzed. There were 201 patients, 76% of the patients were male. Injuries usually occurred at home (54%) followed by accidents at workplaces (18%), car accidents (10.5%), fighting (15%), and at school (2.5%). There were 100/201 patients (49%) of cases that required hospital admission and (40.8%) needed surgical interventions. The most common traumas were blunt trauma in 124/201 patients (61.7%). Penetrating trauma with an intraocular foreign body (IOFB) accounted for (11.5%) of cases. The visual outcome was recorded in 200 patients. 22/201 patients (11%) ended with severe impairment of vision (vision hand movement (HM) or less). Blindness with no perception of light (no PL) was the result in 3.5% of trauma cases, while 11/16 patients (86%) with gunshot injuries through fighting have complete irreversible blindness (no PL). We concluded, that most open-globe injuries can cause severe vision impairment. In this study, gunshot injury is the leading cause of permanent loss of vision.

Circulating Small Extracellular Vesicles Involved in Systemic Regulation Respond to RGC Degeneration in Glaucoma.

Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) degeneration and vision loss. Since irreversible neurodegeneration occurs before diagnosable, early diagnosis and effective neuroprotection are critical for glaucoma management. Small extracellular vesicles (sEVs) are demonstrated to be potential novel biomarkers and therapeutics for a variety of diseases. In this study, it is found that intravitreal injection of circulating plasma-derived sEVs (PDEV) from glaucoma patients ameliorated retinal degeneration in chronic ocular hypertension (COH) mice. Moreover, it is found that PDEV-miR-29s are significantly upregulated in glaucoma patients and are associated with visual field defects in progressed glaucoma. Subsequently, in vivo and in vitro experiments are conducted to investigate the possible function of miR-29s in RGC pathophysiology. It is showed that the overexpression of miR-29b-3p effectively prevents RGC degeneration in COH mice and promotes the neuronal differentiation of human induced pluripotent stem cells (hiPSCs). Interestingly, engineered sEVs with sufficient miR-29b-3p delivery exhibit more effective RGC protection and neuronal differentiation efficiency. Thus, elevated PDEV-miR-29s may imply systemic regulation to prevent RGC degeneration in glaucoma patients. This study provides new insights into PDEV-based glaucoma diagnosis and therapeutic strategies for neurodegenerative diseases.

Innovative Nanotechnology in Drug Delivery Systems for Advanced Treatment of Posterior Segment Ocular Diseases.

Funduscopic diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), significantly impact global visual health, leading to impaired vision and irreversible blindness. Delivering drugs to the posterior segment of the eye remains a challenge due to the presence of multiple physiological and anatomical barriers. Conventional drug delivery methods often prove ineffective and may cause side effects. Nanomaterials, characterized by their small size, large surface area, tunable properties, and biocompatibility, enhance the permeability, stability, and targeting of drugs. Ocular nanomaterials encompass a wide range, including lipid nanomaterials, polymer nanomaterials, metal nanomaterials, carbon nanomaterials, quantum dot nanomaterials, and so on. These innovative materials, often combined with hydrogels and exosomes, are engineered to address multiple mechanisms, including macrophage polarization, reactive oxygen species (ROS) scavenging, and anti-vascular endothelial growth factor (VEGF). Compared to conventional modalities, nanomedicines achieve regulated and sustained delivery, reduced administration frequency, prolonged drug action, and minimized side effects. This study delves into the obstacles encountered in drug delivery to the posterior segment and highlights the progress facilitated by nanomedicine. Prospectively, these findings pave the way for next-generation ocular drug delivery systems and deeper clinical research, aiming to refine treatments, alleviate the burden on patients, and ultimately improve visual health globally.

Whole-eye transplantation: Current challenges and future perspectives.

Whole-eye transplantation emerges as a frontier in ophthalmology, promising a transformative approach to irreversible blindness. Despite advancements, formidable challenges persist. Preservation of donor eye viability post-enucleation necessitates meticulous surgical techniques to optimize retinal integrity and ganglion cell survival. Overcoming the inhibitory milieu of the central nervous system for successful optic nerve regeneration remains elusive, prompting the exploration of neurotrophic support and immunomodulatory interventions. Immunological tolerance, paramount for graft acceptance, confronts the distinctive immunogenicity of ocular tissues, driving research into targeted immunosuppression strategies. Ethical and legal considerations underscore the necessity for stringent standards and ethical frameworks. Interdisciplinary collaboration and ongoing research endeavors are imperative to navigate these complexities. Biomaterials, stem cell therapies, and precision immunomodulation represent promising avenues in this pursuit. Ultimately, the aim of this review is to critically assess the current landscape of whole-eye transplantation, elucidating the challenges and advancements while delineating future directions for research and clinical practice. Through concerted efforts, whole-eye transplantation stands to revolutionize ophthalmic care, offering hope for restored vision and enhanced quality of life for those afflicted with blindness.

Agreement of tonometer for measuring intraocular pressure in Wistar rats: a systematic review

Glaucoma is the most common cause of irreversible blindness in the world. It is associated with elevated intraocular pressure (IOP). Fluctuations in tonometer readings have implications for glaucoma research, where accurate IOP measurements are vital for evaluating disease progression and treatment efficacy. Researchers should carefully select the appropriate tonometer and consider biases associated with different tonometers. Validation against standard measurements can improve IOP measurement accuracy in rat models. In conclusion, this systematic review will emphasize on the importance of selecting the appropriate tonometer for IOP measurement in rat models, considering potential biases and their implications for glaucoma research. Accurate and consistent IOP measurement in rat models is crucial for understanding glaucoma pathophysiology and developing effective treatments. This systematic review aims to assess agreement among tonometers used for measuring IOP in Wistar rat models primarily focusing on TonoLab, TonoVet, and Tono-pen. The review was conducted using PRISMA guidelines. Two articles were included for qualitative synthesis. The studies compared manometric IOP with TonoLab, rebound tonometer, and Tono-pen XL readings. It was observed that TonoLab consistently underestimated IOP, while Tono-pen XL tended to overestimate IOP compared to manometric measurements. The study’s findings will help researchers in making decisions about tonometer selection, leading to more reliable outcomes in glaucoma research using rat models. Further research, specifically RCT’s (randomized controlled trial) is needed to confirm the results and enhance IOP measurement precision in rat models.

TLR4 deficiency does not alter glaucomatous progression in a mouse model of chronic glaucoma.

Glaucoma is a leading cause of irreversible blindness worldwide. Toll-like receptor 4 (TLR4) is a pattern-recognition transmembrane receptor that induces neuroinflammatory processes in response to injury. Tlr4 is highly expressed in ocular tissues and is known to modulate inflammatory processes in both anterior and posterior segment tissues. TLR4 activation can lead to mitochondrial dysfunction and metabolic deficits in inflammatory disorders. Due to its effects on inflammation and metabolism, TLR4 is a candidate to participate in glaucoma pathogenesis. It has been suggested as a therapeutic target based on studies using acute models, such as experimentally raising IOP to ischemia-inducing levels. Nevertheless, its role in chronic glaucoma needs further evaluation. In the current study, we investigated the role of TLR4 in an inherited mouse model of chronic glaucoma, DBA/2J. To do this, we analyzed the effect of Tlr4 knockout (Tlr4 -/-) on glaucoma-associated phenotypes in DBA/2J mice. Our studies found no significant differences in intraocular pressure, iris disease, or glaucomatous progression in Tlr4 -/- compared to Tlr4 +/+ DBA/2J mice. These data do not identify a role for TLR4 in this chronic glaucoma, but further research is warranted to understand its role in other glaucoma models and different genetic contexts.

Integrating Deep Learning with Electronic Health Records for Early Glaucoma Detection: A Multi-Dimensional Machine Learning Approach.

Recent advancements in deep learning have significantly impacted ophthalmology, especially in glaucoma, a leading cause of irreversible blindness worldwide. In this study, we developed a reliable predictive model for glaucoma detection using deep learning models based on clinical data, social and behavior risk factor, and demographic data from 1652 participants, split evenly between 826 control subjects and 826 glaucoma patients. We extracted structural data from control and glaucoma patients' electronic health records (EHR). Three distinct machine learning classifiers, the Random Forest and Gradient Boosting algorithms, as well as the Sequential model from the Keras library of TensorFlow, were employed to conduct predictive analyses across our dataset. Key performance metrics such as accuracy, F1 score, precision, recall, and the area under the receiver operating characteristics curve (AUC) were computed to both train and optimize these models. The Random Forest model achieved an accuracy of 67.5%, with a ROC AUC of 0.67, outperforming the Gradient Boosting and Sequential models, which registered accuracies of 66.3% and 64.5%, respectively. Our results highlighted key predictive factors such as intraocular pressure, family history, and body mass index, substantiating their roles in glaucoma risk assessment. This study demonstrates the potential of utilizing readily available clinical, lifestyle, and demographic data from EHRs for glaucoma detection through deep learning models. While our model, using EHR data alone, has a lower accuracy compared to those incorporating imaging data, it still offers a promising avenue for early glaucoma risk assessment in primary care settings. The observed disparities in model performance and feature significance show the importance of tailoring detection strategies to individual patient characteristics, potentially leading to more effective and personalized glaucoma screening and intervention.

Exploring the Ocular Surface Microbiome and Tear Proteome in Glaucoma.

Although glaucoma is a leading cause of irreversible blindness worldwide, its pathogenesis is incompletely understood, and intraocular pressure (IOP) is the only modifiable risk factor to target the disease. Several associations between the gut microbiome and glaucoma, including the IOP, have been suggested. There is growing evidence that interactions between microbes on the ocular surface, termed the ocular surface microbiome (OSM), and tear proteins, collectively called the tear proteome, may also play a role in ocular diseases such as glaucoma. This study aimed to find characteristic features of the OSM and tear proteins in patients with glaucoma. The whole-metagenome shotgun sequencing of 32 conjunctival swabs identified Actinobacteria, Firmicutes, and Proteobacteria as the dominant phyla in the cohort. The species Corynebacterium mastitidis was only found in healthy controls, and their conjunctival microbiomes may be enriched in genes of the phospholipase pathway compared to glaucoma patients. Despite these minor differences in the OSM, patients showed an enrichment of many tear proteins associated with the immune system compared to controls. In contrast to the OSM, this emphasizes the role of the proteome, with a potential involvement of immunological processes in glaucoma. These findings may contribute to the design of new therapeutic approaches targeting glaucoma and other associated diseases.