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Segmentation of the Optic Nerve Head Based on Deep Learning to Determine its Hemoglobin Content in Normal and Glaucomatous Subjects
摘要： Objective: To determine the limits of the optic nerve head (ONH) in color fundus images using Deep learning (DL) for the estimation of its hemoglobin topographic distribution. Also, to evaluate the usefulness of that distribution in glaucoma diagnosis singly or in association with perimetry. Methods: A DL method was trained using 40000 fundus images and applied to 89 normal eyes and 77 confirmed or suspect glaucomas. DL and manual segmentation were compared. The eyes were also examined once with TOP perimetry (Octopus 300) and Spectralis-OCT and twice with Cirrus-OCT and Laguna ONhE, a program which estimates hemoglobin from color photographs, using improved criteria from previous studies. Results: The Sorensen-Dice similarity index between manual and automatic segmentations was 0.993. Intra-class correlation coefficients were similar when comparing the results of the Laguna ONhE indices using the manual and automatic segmentations (confidence intervals: 0.933-0.978). For specificity close to 95%, the GDF index, a factor that measures the distribution of hemoglobin at the nerve, obtained sensitivities between 70.1 and 74.0% (manual vs. automatic segmentations). The retinal nerve fiber layer thickness (RNFLT) of both OCTs provided sensitivities between 67.1 and 68.8% and the BMO-RMW of Spectralis-OCT 69.7%. Associating several normalized indices, e.g. a new visual field harmony index (Threshold Coefficient of Variation, TCV) and GDF, provided 85.7% sensitivity for 97.8% specificity. GDF correlation with Spectralis-OCT BMO-RMW index was similar to that obtained between this index and the RNFLT of the same instrument. For 95% specificity, the diagnostic concordance (kappa value) between both Spectralis-OCT indices was 0.694 and between its BMO-RMW and Laguna ONhE GDF 0.804-0.828. Conclusion: A fully automatic delimitation of the optic nerve head allows the correct, reproducible and efficient use of the Laguna ONhE method, and its effectiveness is greatly increased if associated with a perimetric harmony index.
关键词： Glaucoma,Visual field,Hemoglobin,Perfusion,Morphology,Perimetry,Optic nerve head
更新于2025-09-19 17:15:36
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Optic Nerve Head Astrocytes Display Axon-Dependent and -Independent Reactivity in Response to Acutely Elevated Intraocular Pressure
摘要： PURPOSE. Optic nerve head (ONH) astrocytes provide support for axons, but exhibit structural and functional changes (termed reactivity) in a number of glaucoma models. The purpose of this study was to determine if ONH astrocyte structural reactivity is axon-dependent. METHODS. Using rats, we combine retrobulbar optic nerve transection (ONT) with acute controlled elevation of intraocular pressure (CEI), to induce total optic nerve axon loss and ONH astrocyte reactivity, respectively. Animals were euthanized immediately or 1 day post CEI, in the presence or absence of ONT. ONH sections were labeled with fluorescent-tagged phalloidin and antibodies against b3 tubulin, phosphorylated cortactin, phosphorylated paxillin, or complement C3. ONH label intensities were quantified after confocal microscopy. Retrobulbar nerves were assessed for axon injury by light microscopy. RESULTS. While ONT alone had no effect on ONH astrocyte structural orientation, astrocytes demonstrated significant reorganization of cellular extensions within hours after CEI, even when combined with ONT. However, ONH astrocytes displayed differential intensities of actin (phosphorylated cortactin) and focal adhesion (phosphorylated paxillin) mediators in response to CEI alone, ONT alone, or the combination of CEI and ONT. Lastly, label intensities of complement C3 within the ONH were unchanged in eyes subjected to CEI alone, ONT alone, or the combination of CEI and ONT, relative to controls. CONCLUSIONS. Early ONH astrocyte structural reactivity to elevated IOP is multifaceted, displaying both axon dependent and independent responses. These findings have important implications for pursuing astrocytes as diagnostic and therapeutic targets in neurodegenerative disorders with fluctuating levels of axon injury.
关键词： elevated intraocular pressure,glaucoma,optic nerve head,axon,astrocyte reactivity
更新于2025-09-19 17:15:36
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<p>Correlation between laser speckle flowgraphy and optical coherence tomography angiography measurements in normal and glaucomatous eyes</p>
摘要： Purpose: To investigate the relationship between laser speckle ?owgraphy (LSFG) and optical coherence tomography angiography (OCTA) measurements of the peripapillary retina and optic nerve head (ONH) in normal eyes and eyes with primary open-angle glaucoma (POAG). Patients and methods: One eye from each of 46 normal subjects and mild and moderate/advanced POAG patients were included. ONH blood ?ow acquired by LSFG, circumpapillary vessel density (cpVD, a 250 μm-wide elliptical annulus around the optic disc), and intra-papillary vessel density (ipVD, a 1.5×1.5 mm scan ?eld) acquired by OCTA were measured. Their values were compared among normal controls and patients at each stage of glaucoma using one-way ANOVA, and the correlation between measurements obtained by the two methods was examined by univariate regression analysis. Results: ONH tissue blood ?ow, tissue mean blur rate (MBR-T), and cpVD in the outer layer of the retina signi?cantly decreased with the progression of glaucoma stage, although the latter showed no signi?cant difference between normal subjects and mild-stage glaucoma patients. MBR-T was signi?cantly correlated with cpVD, but not with ipVD, in the retinal outer layer. Conclusion: A correlation was found only between MBR-T and cpVD in the retinal outer layer. A difference in MBR-T, but not in cpVD, was detected between normal controls and mild glaucoma patients.
关键词： optic nerve head,blood ?ow,laser speckle ?owgraphy,optical coherent tomography angiography
更新于2025-09-16 10:30:52
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Custom Optical Coherence Tomography Parameters for Distinguishing Papilledema from Pseudopapilledema
摘要： SIGNIFICANCE: Causes of papilledema can be life-threatening; however, distinguishing papilledema from pseudopapilledema is often challenging. The conventional optical coherence tomography (OCT) scan for assessing the optic nerve often fails to detect mild papilledema. Our study suggests that parameters derived from volumetric OCT scans can provide additional useful information for detecting papilledema. PURPOSE: Optical coherence tomography analysis of the optic nerve commonly measures retinal nerve fiber layer thickness (RNFLT) along a 1.73-mm-radius scan path. This conventional scan, however, often fails to detect mild papilledema. The purpose of this study was to evaluate additional OCT-derived measures of the optic nerve head (ONH) and peripapillary retina for differentiating papilledema (all grades and mild) from pseudopapilledema. METHODS: Cirrus OCT ONH volume scans were acquired from 21 papilledema (15 mild papilledema), 27 pseudopapilledema, and 42 control subjects. Raw scan data were exported, and total retinal thickness within Bruch’s membrane opening (BMO) plus RNFLT and total retinal thickness at the following eccentricities were calculated using custom algorithms: BMO to 250, 250 to 500, 500 to 1000, and 1000 to 1500 μm. Minimum rim width was calculated, and BMO height was measured from a 4-mm Bruch’s membrane reference plane centered on the BMO. RESULTS: Retinal nerve fiber layer thickness from BMO to 250 μm, minimum rim width, and BMO height had significantly greater areas under the receiver operating characteristic curve than did conventional RNFLT for differentiating mild papilledema from pseudopapilledema (P < .0001) and greater sensitivities at 95% specificity. Using cutoff values at 95% specificity, custom parameters detected 10 mild papilledema patients, and conventional RNFLT detected only 1. Bruch’s membrane opening heights above the reference plane were observed in papilledema only, although many papilledema cases had a neutral or negative BMO height. CONCLUSIONS: Using OCT volumetric data, additional parameters describing peripapillary tissue thickness, neuroretinal rim thickness, and ONH position can be calculated and provide valuable measures for differentiating mild papilledema from pseudopapilledema.
关键词： optical coherence tomography,papilledema,optic nerve head,pseudopapilledema,retinal nerve fiber layer thickness
更新于2025-09-12 10:27:22
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Electrical synapses interconnecting axons revealed in the optic nerve head – a novel model of gap junctions’ involvement in optic nerve function
摘要： Purpose: To characterize newly discovered electrical synapses, formed by connexin (Cx) 36 and 45, between neighbouring axons within the optic nerve head. Methods: Twenty-?ve Wistar rats were killed by CO2 inhalation. Proximal and distal optic nerve (ON) stumps were collected and processed for immunostainings, electron microscopy (EM) with immunogold labelling, PCR and Western blots (WB). Additional 15 animals were deeply anaesthetized, and ?ash visual evoked potentials (fVEP) after retrobulbar injection of saline (negative control) or 100 lM meclofenamic acid solution (gap junctions’ blocker) were recorded. Human para?n cross-sections of eyeballs for immunostainings were obtained from the Human Eye Biobank for Research. Results: Immunostainings of both rat and human ON revealed the presence of Cx45 and 36 colocalizing with b3-tubulin, but not with glial ?brillary acidic protein (GFAP). In WB, Cx36 content in optic nerve was approximately halved when compared with retina (0.58 (cid:1) 0.005 in proximal stump and 0.44 (cid:1) 0.02 in distal stump), Cx45 showed higher levels (0.68 (cid:1) 0.01 in proximal stump and 0.9 (cid:1) 0.07 in distal stump). In immunogold-EM of optic nerve sections, we found electric synapses (formed mostly by Cx45) directly coupling neighbouring axons. In fVEP, blocking of gap junctions with meclofenamic acid resulted in signi?cant prolongation of the latency of P1 wave up to 160% after 30 min (p < 0.001). Conclusions: Optic nerve (ON) axons are equipped with electrical synapses composed of neuronal connexins, especially Cx45, creating direct morphological and functional connections between each other. This ?nding could have substantial implications for understanding of the pathogenesis of various optic neuropathies and identi?es a new potential target for a therapeutic approach.
关键词： electrical synapses,optic nerve,retinal ganglion cell axons,impulse conduction,conduction resistance
更新于2025-09-11 14:15:04
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Spectral Domain Optical Coherence Tomography Assessment of Macular and Optic Nerve Alterations in Patients with Glaucoma and Correlation with Visual Field Index
摘要： Introduction. To evaluate the sectorial thickness of single retinal layers and optic nerve using spectral domain optic coherence tomography (SD-OCT) and highlight the parameters with the best diagnostic accuracy in distinguishing between normal and glaucoma subjects at di?erent stages of the disease. Material and Methods. For this cross-sectional study, 25 glaucomatous (49 eyes) and 18 age-matched healthy subjects (35 eyes) underwent a complete ophthalmologic examination including visual ?eld testing. Sectorial thickness values of each retinal layer and of the optic nerve were measured using SD-OCT Glaucoma Module Premium Edition (GMPE) software. Each parameter was compared between the groups, and the layers and sectors with the best area under the receiver operating characteristic curve (AUC) were identi?ed. Correlation of visual ?eld index with the most relevant structural parameters was also evaluated. Results and Discussion. All subjects were grouped according to stage as follows: Controls (CTRL); Early Stage Group (EG) (Stage 1 + Stage 2); Advanced Stage Group (AG) (Stage 3 + Stage 4 + Stage 5). mGCL TI, mGCL TO, mIPL TO, mean mGCL, cpRNFLt NS, and cpRNFLt TI showed the best results in terms of AUC according classi?cation proposed by Swets (0.9 < AUC < 1.0). These parameters also showed signi?cantly di?erent values among group when CTRL vs EG, CTRL vs AG, and EG vs AG were compared. SD-OCT examination showed signi?cant sectorial thickness di?erences in most of the macular layers when glaucomatous patients at di?erent stages of the disease were compared each other and to the controls.
关键词： glaucoma,spectral domain optical coherence tomography,macular thickness,optic nerve,visual field index
更新于2025-09-11 14:15:04
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Intravitreal AAV-Delivery of Genetically Encoded Sensors Enabling Simultaneous Two-Photon Imaging and Electrophysiology of Optic Nerve Axons
摘要： Myelination of axons by oligodendrocytes is a key feature of the remarkably fast operating CNS. Oligodendrocytes not only tune axonal conduction speed but are also suggested to maintain long-term axonal integrity by providing metabolic support to the axons they ensheath. However, how myelinating oligodendrocytes impact axonal energy homeostasis remains poorly understood and difficult to investigate. Here, we provide a method of how to study electrically active myelinated axons expressing genetically encoded sensors by combining electrophysiology and two-photon imaging of acutely isolated optic nerves. We show that intravitreal adeno-associated viral (AAV) vector delivery is an efficient tool to achieve functional sensor expression in optic nerve axons, which is demonstrated by measuring axonal ATP dynamics following AAV-mediated sensor expression. This novel approach allows for fast expression of any optical sensor of interest to be studied in optic nerve axons without the need to go through the laborious process of producing new transgenic mouse lines. Viral-mediated biosensor expression in myelinated axons and the subsequent combination of nerve recordings and sensor imaging outlines a powerful method to investigate oligodendroglial support functions and to further interrogate cellular mechanisms governing axonal energy homeostasis under physiological and pathological conditions.
关键词： genetically encoded sensors,myelinated axons,intravitreal AAV injection,ATP-sensor ATeam1.03YEMK,optic nerve recording,two-photon imaging
更新于2025-09-10 09:29:36
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Evaluation of optic nerve head blood flow in response to increase of intraocular pressure
摘要： The time course of the changes in the optic nerve head (ONH) blood flow in response to changes in the ocular perfusion pressure (OPP) induced by an artificial elevation of the intraocular pressure (IOP) has not been determined. We measured the blood flow, represented by the mean blur rate (MBR), on the ONH determined by laser speckle flowgraphy. The MBR was determined before, during, and after the IOP was elevated by 20 or 30 mmHg by pressure applied on the eye by an ophthalmodynamometer in a total of 27 healthy eyes. For an IOP elevation of 20 mmHg, the percentage reduction in the MBR-vessel was ?24.7%, and in the MBR-tissue was ?16.0% (P < 0.001). For an IOP elevation of 30 mmHg, the percentage reduction of the MBR-vessel was ?35.3% and the MBR-tissue was ?24.7% (P < 0.001). During the 30 mmHg IOP elevation for 10 minutes, both the MBR-vessel and MBR-tissue began returning to the baseline level from 1 minute after the beginning of the IOP elevation (P < 0.01, P < 0.05, respectively) and continued returning during the 10 minutes IOP elevation (P < 0.001, P < 0.01, respectively). We conclude that the ONH can autoregulate its blood flow in response to experimental changes in OPP induced by IOP elevations.
关键词： optic nerve head,autoregulation,laser speckle flowgraphy,blood flow,intraocular pressure
更新于2025-09-10 09:29:36
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Optic Nerve Head Measurements With Optical Coherence Tomography: A Phantom-Based Study Reveals Differences Among Clinical Devices
摘要： PURPOSE. Optical coherence tomography (OCT) can monitor for glaucoma by measuring dimensions of the optic nerve head (ONH) cup and disc. Multiple clinical studies have shown that different OCT devices yield different estimates of retinal dimensions. We developed phantoms mimicking ONH morphology as a new way to compare ONH measurements from different clinical OCT devices. METHODS. Three phantoms were fabricated to model the ONH: One normal and two with glaucomatous anatomies. Phantoms were scanned with Stratus, RTVue, and Cirrus clinical devices, and with a laboratory OCT system as a reference. We analyzed device-reported ONH measurements of cup-to-disc ratio (CDR) and cup volume and compared them with of?ine measurements done manually and with a custom software algorithm, respectively. RESULTS. The mean absolute difference between clinical devices with device-reported measurements versus of?ine measurements was 0.082 vs. 0.013 for CDR and 0.044 mm3 vs. 0.019 mm3 for cup volume. Statistically signi?cant differences between devices were present for 16 of 18 comparisons of device-reported measurements from the phantoms. Of?ine Cirrus measurements tended to be signi?cantly different from those from Stratus and RTVue. CONCLUSIONS. The interdevice differences in CDR and cup volume are primarily caused by the devices’ proprietary ONH analysis algorithms. The three devices yield more similar ONH measurements when a consistent of?ine analysis technique is applied. Scan pattern on the ONH also may be a factor in the measurement differences. This phantom-based study has provided unique insights into characteristics of OCT measurements of the ONH.
关键词： phantom,optical coherence tomography,optic nerve head
更新于2025-09-10 09:29:36
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Parameters of ocular fundus on spectral-domain optical coherence tomography for glaucoma diagnosis
摘要： In this review, we summarize the progression of several parameters assessed by spectral-domain optical coherence tomography (SD-OCT) in recent years for the detection of glaucoma. Monitoring the progression of defects in the retinal nerve fiber layer (RNFL) thickness is essential. Imaging and analysis of retinal ganglion cells (RGCs) and inner plexiform layer (IPL), respectively, have been of great importance. Optic nerve head (ONH) topography obtained from 3D SD-OCT images is another crucial step. Other important assessments involve locating the Bruch’s membrane opening (BMO), estimating the optic disc size and rim area, and measuring the lamina cribrosa displacement. Still other parameters found in the past three years for glaucoma diagnosis comprise central retinal artery resistive index, optic disc perfusion in optical coherence tomography angiography (OCTA) study, peripapillary choroidal thickness, and choroidal area in SD-OCT. Recently, several more ocular fundus parameters have been found, and compared with the earlier parameters to judge the accuracy of diagnosis. While a few of these parameters have been widely used in clinical practice, a fair number are still in the experimental stage.
关键词： optic nerve head,retinal nerve fiber layer,lamina cribrosa,optical coherence tomography,macular thickness,ganglion cells,glaucoma progression
更新于2025-09-09 09:28:46