Glaucomatous Optic Nerve Research Articles

Use of a Novel Virtual Reality-Based Pupillography Device for Glaucoma Management: Cross-Sectional Cohort Pilot Study.

Current standard methods in monitoring glaucoma progression, like optical coherence tomography (OCT) and standard automated perimetry (SAP), have limitations in certain cases. Automated relative afferent pupillary defect (RAPD) and pupillary light reflex (PLR) testing may offer more objective alternatives. This pilot study aimed to evaluate whether RAPD could sufficiently distinguish between the two eyes in asymmetrical glaucoma, and thus could lay the foundation for using the PLR of a single eye to monitor progression longitudinally. Twenty-one patients underwent quantitative PLR measurements using a virtual reality headset. RAPD was calculated by subtracting the amplitude of PLRs between eyes. Both RAPD and relative SAP (measured using the mean defect or MD) results were correlated to the thickness of the peripapillary retinal nerve fiber layer (RNFL), as measured by OCT. Data from 18 patients was analyzed after exclusions. RAPD significantly correlated with differences between the two eyes as measured by RNFL thickness (Pearson r = 0.79, p = 0.05). MD differences correlated slightly better with RNFL differences (Pearson r = 0.87, p < 0.05). RAPD and MD combined yielded an improved prediction of RNFL differences by 5% compared to using MD only. RAPD measurements reliably detected asymmetries in optic nerve damage in glaucoma patients. SAP measurements correlated better with OCT results than RAPD results. However, SAP and RAPD combined led to an improved prediction of RNFL thickness. This could possibly allow us to use PLR only over longer periods of time to monitor glaucomatous optic nerve damage in a single eye in the future.

Controlled Elevation of Intraocular Pressure (CEI) Glaucoma Model in Rats.

Experimental elevation of intraocular pressure (IOP), a major glaucoma risk factor, has been a mainstay of research into mechanisms of glaucomatous optic nerve damage for decades. Methods that produce sustained IOP elevation can mimic the chronic nature of glaucoma and produce optic nerve damage. However, the pressure course for individual animals can be variable, unpredictably high at times, and difficult to monitor with current tonometry methods. All of this can complicate correlations of pressure history with axonal injury. An alternative is to control the extent and duration of IOP elevation over a period of several hour-long enough to produce axonal injury and gene expression changes within the optic nerve head that may indicate cellular mechanisms of glaucomatous optic nerve damage. The prolonged general anesthesia that this requires does have the potential to reduce systemic blood pressure, which may contribute to axonal injury in the face of elevated IOP. This chapter will describe our Controlled Elevation of IOP (CEI) model in laboratory rats. We will include methods for applying this to several animals at a time, as well as how to maintain blood pressure, oxygenation, and body temperature to ensure that the resulting injury and tissue events reflect the effects of elevated IOP on optic nerve tissues and not simply reduced ocular perfusion and ischemia.

Complement Factor B Inhibition or Deletion Is Not Sufficient to Prevent Neurodegeneration in a Murine Model of Glaucoma.

Purpose: Activation of the classical complement pathway is thought to contribute to the development and progression of glaucoma. The role of alternative complement or amplification pathways in glaucoma is not well understood. We evaluated complement factor B (FB) expression in postmortem human ocular tissues with or without glaucoma and the effect of FB inhibition and deletion in a mouse ocular hypertensive model of glaucoma induced by photopolymerized hyaluronic acid glycidyl methacrylate (HAGM). Methods: Human CFB mRNA in human eyes was assessed by RNAscope and TaqMan. HAGM model was performed on C57BL6/J mice. The effect of FB in HAGM model was evaluated with an oral FB inhibitor and Cfb-/- mice. Complement mRNA and proteins in mouse eyes were assessed by TaqMan and western blot, respectively. Results: CFB mRNA in human glaucomatous macular neural retina and optic nerve head was upregulated. Cfb mRNA is also upregulated in the HAGM model. Oral FB inhibitor, ED-79-GX17, dosed daily at 200 mg/kg for 3 days after intraocular pressure (IOP) induction in wild-type mice showed complement inhibition in ocular tissues and significantly inhibited systemic complement levels. Daily dosing of ED-79-GX17 for 30 days or Cfb deletion was also unable to prevent retinal ganglion cell or axon loss 30 days after IOP induction in mice. Conclusion: The alternative complement component FB may not substantially contribute to RGC loss in the HAGM mouse glaucoma model despite upregulation of Cfb expression and activation of the alternative pathway. The relevance of these findings to human glaucoma remains to be determined.

Glaucoma, More than Meets the Eye: Patterns of Demyelination Revealed in Human Postmortem Glaucomatous Optic Nerve.

Glaucoma is a neurodegenerative disease affecting millions worldwide, characterised by retinal ganglion cell (RGC) degeneration which leads to blindness in more advanced cases. Although the pathogenesis and underlying mechanisms of glaucoma are not fully understood, there are theories that hint at demyelination playing a role in the disease process. Demyelination, or the degeneration of the myelin sheath surrounding axons, has been found in previous studies using animal models of glaucoma and clinical assessments of glaucoma patients. However, this has not been fully realised or quantified in glaucoma patients. Utilising postmortem optic nerve samples from glaucoma and healthy subjects, various immunohistochemical and morphological assessments were performed to determine the extent, if any, of demyelination in glaucomatous optic nerves. Our findings revealed that alongside nerve shrinkage and degeneration of nerve tissue fascicles, there were significantly less myelin proteins, specifically myelin basic protein (MBP), in glaucoma optic nerves. Additionally, the loss of MBP was correlated with decreased oligodendrocyte (OLG) precursors and increasing glial activity. This further supports previous evidence that demyelination may be a secondary degenerative process associated with glaucoma disease progression. Not only do these results provide evidence for potential disease mechanisms, but this is also the first study to quantify optic nerve demyelination in glaucoma postmortem tissue.

Myopia and Other Refractive Error and Their Relationships to Glaucoma Screening.

A large disk, a large parapapillary delta zone and a long axial length may be used as screening criteria to detect glaucomatous optic neuropathy in highly myopic eyes. To describe aspects for screening of glaucomatous optic neuropathy in dependence of refractive error, under special consideration of high myopia. Studies on the anatomy of the myopic optic nerve head and results of investigations on the relationship between glaucomatous optic neuropathy and axial myopia were included. In the range from hyperopia to moderate myopia, refractive error is not a strong glaucoma risk factor and may not be included in glaucoma screening strategies. Care should be taken, that in moderate myopia, a shift of Bruch´s membrane opening usually into the temporal direction leads to parapapillary gamma zone and a corresponding shortening of the horizontal disk diameter. In these moderately myopic eyes, a secondarily small optic disk with a correspondingly small optic cup should not lead to an overlooking of intrapapillary glaucomatous changes. Prevalence of glaucomatous or glaucoma-like optic nerve atrophy (GOA) steeply increases with longer axial length in highly myopic eyes (cutoff approximately -8 diopters/axial length 26.5mm), with prevalences higher than 50% in extremely high myopia. Besides longer axial length, morphological parameters associated with GOA in highly myopic eyes are a secondarily enlarged disk and large parapapillary delta zone. Both parameters, together with long axial length, may be used as screening criteria in high myopia for GOA. The latter is characterized by an abnormal neuroretinal rim shape, that is, vessel kinking close to the intrapapillary disk border. Factors associated with nonglaucomatous optic neuropathy are larger gamma zone and longer axial length, potentially due to an axial elongation-related retinal nerve fiber stretching.

Standardizing the diagnosis and treatment of ocular hypertension based on evidence-based medicine

Ocular hypertension (OHT) refers to a condition in which the intraocular pressure increases without causing glaucomatous optic nerve changes or visual field damage. The incidence rate of OHT in people over 40 years old is as high as 4% to 10%. According to the OHT Treatment Study (OHTS), the incidence of primary open angle glaucoma (POAG) among OHT patients is increasing year by year, so it is necessary to conduct long-term follow-up. This article elaborates on five major risk factors for the progression of OHT to POAG: age, intraocular pressure, vertical cup-disc ratio, pattern standard deviation of visual field, and central corneal thickness. It also summarizes other potential risk factors, such as long-term fluctuations in intraocular pressure, asymmetry of intraocular pressure and visual field between the two eyes, structural phenotypes of the optic disk, and optic disk hemorrhage. Predicting the risk of OHT progression to POAG based on risk factors, patients with different risk levels require different timing for treatment initiation and follow-up intervals. Those with higher risks should start preventive treatment earlier and have shorter follow-up intervals. Both drug therapy and selective laser trabeculoplasty can serve as initial treatment options for OHT. Combining evidence-based medicine research and individualized evaluation of treatment can enhance the clinical diagnosis and treatment level of OHT.

Prevalence and Associated Factors of Cataract, Cataract Surgery and Postoperative Outcome in an Old Population in Russia: The Ural Very Old Study

PurposeTo assess prevalence of cataract and cataract surgery in a very old population in Russia. DesignPopulation-based study. ParticipantsThe Ural Very Old Study included 1526 (81.1%) participants out of 1882 eligible individuals aged 85+ years. MethodsBased on anterior and posterior segment imaging, we assessed the prevalence of cataract, cataract surgery and other ocular disorders affecting best corrected visual acuity (BCVA). Main outcome measuresPrevalence of cataract and cataract surgery. ResultsThe study included 1163 (76.3%) individuals with lens information. Cataract surgery had been performed in 469 right eyes (41.0%;95%CI:38.1,43.9) (92.1% with posterior chamber IOL; 4.7% with multifocal IOL) and 479 left eyes (41.6%;95%CI:38.7,44.4) (92.7% with posterior chamber IOL; 4.2% with multifocal IOL). Among the 1163 study participants, 610 (52.5%) individuals had undergone cataract surgery in at least one eye. Higher prevalence of previous cataract surgery correlated (multivariable analysis) with lower IOP (OR:0.92;95%CI:0.88,0.95;P<0.001), glaucomatous optic nerve damage stage (OR:1.20;95%CI:1.05,1.36;P=0.006), and better visual acuity (OR:0.67;95%CI:0.51,0.89;P=0.005). Postoperative BCVA (mean:0.83±1.43logMAR) was reduced to moderate-to-severe vision impairment (MSVI) in 202 eyes (44.6%;95%CI:40.0,49.2) and to blindness in 53 eyes (11.7%;95%CI:8.7,14.7). Causes of postoperative MSVI were age-related macular degeneration (AMD) (34.2%), glaucoma (13.9%), and secondary cataract (5.4%). Causes for blindness were AMD (24.5%), glaucoma (18.9%), corneal opacifications (15.8%) and myopic macular degeneration (11.3%). YAG-laser capsulotomy had been performed in 6 (1.3%) out 469 right eyes after cataract surgery and in 12 (2.5%) out of 479 left eyes after cataract surgery. Prevalence of nuclear cataract and cortical cataract was 604/671 (90.0% in phakic eyes 51.9% in the whole study population) and 97.9% eyes (48.4% in total study population). Cataract caused bilateral MSVI and blindness in 28.2% (95%CI:25.6,30) and 2.9% (95%CI:1.9,3.9), respectively, of all study participants. ConclusionsDespite a relatively high prevalence of cataract surgery, this multiethnic cohort aged 85+ years from Russia showed a high prevalence of cataract-related MSVI and blindness, due to the old age of the participants. After cataract surgery, main causes for MSVI (prevalence:44.6%) and blindness (prevalence:11.7%) were AMD, glaucoma, corneal opacifications, and myopic macular degeneration. Almost all individuals aged 85+ years need cataract surgery, despite limited chance of postoperative good vision.

Harnessing the power of artificial intelligence for glaucoma diagnosis and treatment

Artificial intelligence (AI) has great potential for diagnosing and managing glaucoma, a disease that causes irreversible vision loss. Early detection is paramount to prevent visual field loss. AI algorithms demonstrate promising capabilities in analyzing various glaucoma investigations. In analyzing retinal fundus photographs, AI achieves high accuracy in detecting glaucomatous optic nerve cupping, a hallmark feature. AI can also analyze optical coherence tomography (OCT) images of the retinal nerve fiber layer(RNFL) and ganglion cell complex, identifying structural changes indicative of glaucoma and also Anterior Segment OCT(AS-OCT) for angle closure disease. OCT interpretation may even be extended to diagnose early features of systemic neurodegenerative diseases such as Alzheimer’s Disease and Parkinson’s Disease. Furthermore, AI can assist in interpreting visual field (VF) tests, including predicting future VF loss patterns for the next 5 years. The ability of AI to integrate data from multiple modalities, including fundus photographs, Intra Ocular Pressure(IOP) measurements, RNFL OCT, AS-OCT, and VF tests, paves the way for a more comprehensive glaucoma assessment. This approach has the potential to revolutionize ophthalmology by enabling teleophthalmology and facilitating the development of personalized treatment plans. However, the authors emphasize the crucial role of human judgement and oversight in interpreting AI-generated results. Ultimately, ophthalmologists must make the final decisions regarding diagnosis and treatment strategies.

Evaluation of glaucomatous macular and optic nerve vascular damage by optical coherence tomography angiography

Purpose The aim of this study was to compare the macular and optic nerve head vessel perfusion density in mild primary open-angle glaucoma (POAG) and moderate–severe POAG patients to normal eyes as a control cohort. Patients and methods This is a retrospective comparative case–control study that included 80 eyes of 46 participants. The study included 60 eyes of 36 POAG patients and 20 eyes of 10 healthy participants (control group). The patients underwent 3.0×3.0 mm optical coherence tomography angiography (OCTA) scans centered on the macula and 4.5×4.5 mm scans on the optic disc. Results The OCTA scans of the glaucomatous eyes revealed a reduction in microvasculature in the peripapillary area, which was absent in the control cohort. The whole disc vessel density (VD) was significantly less in the glaucomatous eyes (mean=38.02±8.74) compared to the control cohort (mean=50.41±2.58, P&lt;0.001). The severity of glaucoma was linked to a decrease in macular VD percentage, with a mean superficial VD of 36.09±5.67 in the glaucoma cohorts and 46.64±5.53 in the control cohort (P&lt;0.001), which was more pronounced than in the deep layer (P&lt;0.008). There was no statistically significant difference in the foveal avascular zone size between the control and glaucoma cohorts at any stage (P=0.999). Conclusion The OCTA vascular density accurately distinguished the glaucoma from healthy eyes, with superior performance in the peripapillary region. The foveal avascular zone size did not indicate glaucoma severity. The OCTA noninvasive assessment of the capillary networks showed a potential for managing the glaucoma patients by characterizing the retinal vascular changes.

Contemporary Approach to Narrow Angles.

Glaucoma is the leading cause of irreversible blindness worldwide. Among all glaucoma types, primary angle closure glaucoma (PACG) affects approximately 23 million people worldwide, and is responsible for 50% of glaucoma-related blindness, highlighting the devastating consequences of this disease. The main mechanism of PACG is relative pupillary block. High-risk populations are female gender, Asian ethnicity, high hyperopia, short axial length, and a thick/anteriorly positioned lens. This review discusses the clinical diagnosis, classification, and management of patients with a narrow angle with and without intraocular pressure (IOP) elevation and glaucomatous optic nerve damage, including laser peripheral iridotomy (LPI), endocycloplasty (ECPL), lens extraction, and goniosynechialysis.

Tear metabolomics for the diagnosis of primary open-angle glaucoma

Primary Open-Angle Glaucoma (POAG) is the most prevalent glaucoma type, and the leading cause of irreversible visual impairment and blindness worldwide. Identification of early POAG biomarkers is of enormous value, as there is not an effective treatment for the glaucomatous optic nerve degeneration (OND). In this pilot study, a metabolomic analysis, by using proton (1H) nuclear magnetic resonance (NMR) spectroscopy was conducted in tears, in order to determine the changes of specific metabolites in the initial glaucoma eyes and to discover potential diagnostic biomarkers. A classification model, based on the metabolomic fingerprint in tears was generated as a non-invasive tool to support the preclinical and clinical POAG diagnosis. 1H NMR spectra were acquired from 30 tear samples corresponding to the POAG group (n = 11) and the control group (n = 19). Data were analysed by multivariate statistics (partial least squares-discriminant analysis: PLS-DA) to determine a model capable of differentiating between groups. The whole data set was split into calibration (65%)/validation (35%), to test the performance and the ability for glaucoma discrimination. The calculated PLS-DA model showed an area under the curve (AUC) of 1, as well as a sensitivity of 100% and a specificity of 83.3% to distinguish POAG group versus control group tear data. This model included 11 metabolites, potential biomarkers of the disease. When comparing the study groups, a decrease in the tear concentration of phenylalanine, phenylacetate, leucine, n-acetylated compounds, formic acid, and uridine, was found in the POAG group. Moreover, an increase in the tear concentration of taurine, glycine, urea, glucose, and unsaturated fatty acids was observed in the POAG group. These results highlight the potential of tear metabolomics by 1H NMR spectroscopy as a non-invasive approach to support early POAG diagnosis and in order to prevent visual loss.

Glaucoma as a cause of optic nerve abnormalities on magnetic resonance imaging.

To report a series of patients with glaucoma and optic nerve abnormalities on magnetic resonance imaging (MRI) in at least one-eye, and to determine whether these findings correlate with the severity of glaucoma. Retrospective study of all patients who underwent a brain/orbits MRI without and with contrast at our institution between 07/1/2019-6/30/2022. Patients with optic nerve T2-hyperintensity and/or MRI optic nerve atrophy in at least one-eye and a diagnosis of isolated glaucoma in at least one-eye were included. Demographic information, glaucoma clinical characteristics, glaucoma severity parameters, and MRI indication were collected. Fifty-six patients (112 eyes) (age 65 years-old [range 26-88]; 70% male) had isolated bilateral glaucoma with at least one-eye MRI optic nerve abnormality. The indication for MRI was atypical/asymmetric glaucoma in 91% of patients. Of the 112 eyes, 23 had optic nerve T2-hyperintensity alone; 33 had both optic nerve T2-hyperintensity and MRI optic nerve atrophy; 34 had MRI optic nerve atrophy alone; and 22 did not have abnormal optic nerve MRI-findings. None had optic nerve enhancement. A statistically significant association between optic nerve T2-hyperintensity or MRI optic nerve atrophy and glaucoma severity parameters was found. Glaucoma is a clinical diagnosis and MRI brain is usually not required, except in atypical or asymmetric cases. Optic nerve T2-hyperintensity and MRI optic nerve atrophy are nonspecific MRI-findings that can be found in severe glaucomatous optic nerves and should not systematically prompt investigations for another cause of optic neuropathy.

In vivo assessment of the ocular biomechanical properties in patients with idiopathic normal pressure hydrocephalus

PurposeIdiopathic normal pressure hydrocephalus (iNPH) is associated with an increased prevalence of open-angle glaucoma, attributed to variations of the pressure gradient between intraocular and intracranial compartments at the level of the lamina cribrosa (LC). As ocular biomechanics influence the behavior of the LC, and a lower corneal hysteresis (CH) has been associated to a higher risk of glaucomatous optic nerve damage, in this study we compared ocular biomechanics of iNPH patients with healthy subjects.Methods Twenty-four eyes of 24 non-shunted iNPH patients were prospectively recruited. Ocular biomechanical properties were investigated using the ocular response analyzer (Reichert Instruments) for the calculation of the CH, corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and corneal-compensated intraocular pressure (IOPcc). Results were compared with those of 25 eyes of 25 healthy subjects.Results In iNPH eyes, the median CH value and interquartile range (IQR) were 9.7 mmHg (7.8–10) and 10.6 mmHg (9.3–11.3) in healthy controls (p = 0.015). No significant differences were found in IOPcc [18.1 mmHg (14.72–19.92) vs. 16.4 mmHg (13.05–19.6)], IOPg [15.4 mmHg (12.82–19.7) vs. 15.3 mmHg (12.55–17.35)], and CRF [9.65 mmHg (8.07–11.65) vs. 10.3 mmHg (9.3–11.5)] between iNPH patients and controls.Conclusions In iNPH patients, the CH was significantly lower compared to healthy subjects. This result suggests that ocular biomechanical properties may potentially contribute to the risk of development of glaucomatous optic nerve damage in iNPH patients.

“Dual‐pressure theory” in pathogenesis of glaucomatous optic neuropathy from the Beijing intracranial and intraocular pressure study

AbstractThe mechanical theory of glaucoma indicates that high intraocular pressure (IOP) leads to glaucomatous optic nerve damage. However, nearly half of primary open‐angle glaucoma patients with normal intraocular pressure also exhibit progression of what appears to be glaucomatous optic nerve damage. Our earlier prospective study identified for the first time that the relatively low intracranial pressure (ICP) is also an important risk factor for progressive glaucomatous injury of normal‐tension glaucoma. When considering the results of studies in nonhuman primates, clinical research, large‐scale natural‐population studies, and basic laboratory investigations, a new understanding of the pathophysiology of glaucoma, the “Dual‐Pressure Theory”, has been proposed. This theory states that “either high IOP or low ICP contributes to increasing the translaminar cribrosa pressure difference; it is the pressure difference rather than the IOP alone that results in the glaucomatous optic neuropathy”. Here, we provide a systematic introduction to Dual‐Pressure Theory relating to glaucoma, the form of a research map, an outline of basic laboratory investigations, the main methodology, and research updates.

Glaucoma, More than Meets the Eye: Patterns of Demyelination Revealed in Human Postmortem Glaucomatous Optic Nerve.

Glaucoma is a neurodegenerative disease affecting millions worldwide, characterised by retinal ganglion cell (RGC) degeneration which leads to blindness in more advanced cases. Although the pathogenesis and underlying mechanisms of glaucoma are not fully understood, there are theories that hint at demyelination playing a role in the disease process. Demyelination, or the degeneration of the myelin sheath surrounding axons, has been found in previous studies using animal models of glaucoma and clinical assessments of glaucoma patients. However, this has not been fully realised or quantified in glaucoma patients. Utilising postmortem optic nerve samples from glaucoma and healthy subjects, various immunohistochemical and morphological assessments were performed to determine the extent, if any, of demyelination in glaucomatous optic nerves. Our findings revealed that alongside nerve shrinkage and degeneration of nerve tissue fascicles, there were significantly less myelin proteins, specifically myelin basic protein (MBP), in glaucoma optic nerves. Additionally, the loss of MBP was correlated with decreased oligodendrocyte (OLG) precursors and increasing glial activity. This further supports previous evidence that demyelination may be a secondary degenerative process associated with glaucoma disease progression. Not only do these results provide evidence for potential disease mechanisms, but this is also the first study to quantify optic nerve demyelination in glaucoma postmortem tissue.

Diagnosis and management of secondary glaucoma: Dural fistula and intracranial hypotension

Glaucoma can occur as a secondary disorder in two situations. Firstly, where there is episcleral venous hypertension. In cases of dural fistula the diagnosis is straightforward: presentation, diagnosis and management will be discussed. In other situations the aetiology of episcleral venous hypertension is controversial, such as the Radius Maumenee syndrome. Secondly there has been recent interest in the importance of the pressure gradient across the lamina cribrosa. The occurrence of papilloedema in cases of low intra‐ocular pressure is well established while glaucomatous optic nerve damage in cases of intra‐cranial hypotension is controversial. The evidence will be reviewed.

The optic nerve in glaucoma

Purpose: To describe particularities of the optic nerve head of axially highly myopic eyes.Methods: Measurements were obtained from enucleated globes and from population‐based studies.Results: Morphologic optic disc particularities in high axial myopia included enlarged disc size (secondary macrodisc), widening and temporal translocation of the papillary Bruch's membrane (BM) opening, parapapillary gamma and delta zone, elongation and thinning of lamina cribrosa and peripapillary scleral flange, steeper translamina cribrosa pressure gradient, decreased peripapillary choroid thickness, longer distance between peripapillary arterial circle and optic disc, optic cup flattening, presumably a stretching of the lamina cribrosa pores, and peripapillary intrachoroidal cavitations. These changes may be explained by growth of new BM in the retroequatorial region in the process of emmetropization or myopization as “overshooting” of the emmetropization process.Conclusions: The intrapapillary and parapapillary changes in the highly myopic optic nerve head may be reason for the increased susceptibility for glaucomatous optic nerve damage in high axial myopia. The widening of the papillary BM opening and the potential shift of the optic nerve head's 3 layer into temporal direction, both potentially leading to the development of parapapillary gamma zone may be of interest for elucidating the process of emmetropization/myopization.

Reduced glutathione level in the aqueous humor of patients with primary open-angle glaucoma and normal-tension glaucoma

Glaucoma is a leading cause of blindness worldwide in older people. Profiling the aqueous humor, including the metabolites it contains, is useful to understand physiological and pathological conditions in the eye. In the current study, we used mass spectrometry (MS) to characterize the aqueous humor metabolomic profile and biological features of patients with glaucoma. Aqueous humor samples were collected during trabeculectomy surgery or cataract surgery and analyzed with global metabolomics. We included 40 patients with glaucoma (32 with POAG, 8 with NTG) and 37 control subjects in a discovery study. VIP analysis revealed five metabolites that were elevated and three metabolites that were reduced in the glaucoma patients. The identified metabolomic profile had an area under the receiver operating characteristic curve of 0.953. Among eight selected metabolites, the glutathione level was significantly decreased in association with visual field defects. Moreover, in a validation study to confirm the reproducibility of our findings, the glutathione level was reduced in NTG and POAG patients compared with a cataract control group. Our findings demonstrate that aqueous humor profiling can help to diagnose glaucoma and that various aqueous humor metabolites are correlated with clinical parameters in glaucoma patients. In addition, glutathione is clearly reduced in the aqueous humor of glaucoma patients with both IOP-dependent and IOP-independent disease subtypes. These findings indicate that antioxidant agents in the aqueous humor reflect glaucomatous optic nerve damage and that excessive oxidative stress may be involved in the pathogenesis of glaucoma.

Predicting glaucoma progression using deep learning framework guided by generative algorithm

Glaucoma is a slowly progressing optic neuropathy that may eventually lead to blindness. To help patients receive customized treatment, predicting how quickly the disease will progress is important. Structural assessment using optical coherence tomography (OCT) can be used to visualize glaucomatous optic nerve and retinal damage, while functional visual field (VF) tests can be used to measure the extent of vision loss. However, VF testing is patient-dependent and highly inconsistent, making it difficult to track glaucoma progression. In this work, we developed a multimodal deep learning model comprising a convolutional neural network (CNN) and a long short-term memory (LSTM) network, for glaucoma progression prediction. We used OCT images, VF values, demographic and clinical data of 86 glaucoma patients with five visits over 12 months. The proposed method was used to predict VF changes 12 months after the first visit by combining past multimodal inputs with synthesized future images generated using generative adversarial network (GAN). The patients were classified into two classes based on their VF mean deviation (MD) decline: slow progressors (< 3 dB) and fast progressors (> 3 dB). We showed that our generative model-based novel approach can achieve the best AUC of 0.83 for predicting the progression 6 months earlier. Further, the use of synthetic future images enabled the model to accurately predict the vision loss even earlier (9 months earlier) with an AUC of 0.81, compared to using only structural (AUC = 0.68) or only functional measures (AUC = 0.72). This study provides valuable insights into the potential of using synthetic follow-up OCT images for early detection of glaucoma progression.

Impact of a short online course on the accuracy of non-ophthalmic diabetic retinopathy graders in recognising glaucomatous optic nerves in Vietnam

PurposeTo test an online training course for non-ophthalmic diabetic retinopathy (DR) graders for recognition of glaucomatous optic nerves in Vietnam.MethodsThis was an uncontrolled, experimental, before-and-after study in which 43 non-ophthalmic...