Normative Profile of Retinal Nerve Fiber Layer Thickness and Lamina Cribrosa-Related Parameters in a Healthy Non-Glaucoma Cynomolgus Monkey Colony.

Purpose: The purpose of this study was to investigate the normal range of ophthalmic parameters and the correlations between systematic and ocular parameters and retinal nerve fiber layer (RNFL) thickness among a healthy non-glaucoma cynomolgus monkey colony. Methods: All included monkeys were given detailed ophthalmic examinations, including anterior and posterior segments. Furthermore, univariate and multivariate linear regression models were conducted to estimate the relationship between systemic and ophthalmic parameters and global RNFL thickness. Results: A total of 349 non-glaucoma monkeys (18.69 ± 2.88 years old) were collected. The global RNFL thickness was 94.61 ± 10.13 µm, and sex-specific differences existed in all sectors. The decreasing trend of RNFL is as follows: inferotemporal, superotemporal, inferonasal, superonasal, temporal, and nasal. For lamina cribrosa (LC)-related parameters, cup depth (P < 0.01), LC thickness (P = 0.014), and Bruch's membrane opening (BMO) - minimum rim width 2 (P = 0.002) were greater in the male group. However, LC depth (P = 0.02), anterior laminar insertion depth-1 (P = 0.009), and mean anterior laminar insertion depth (P = 0.029) of female monkeys were greater than those of male monkeys. In multivariate linear regression, only older age was significantly related to reduced global RNFL thickness (P < 0.001). Conclusions: Our findings suggest the differences in RNFL thickness distribution and sex between non-glaucoma cynomolgus monkeys and humans. Therefore, the impact of this difference on outcomes should be fully considered in laboratory animal studies. Our findings are also significant in terms of developing a normative optical coherence tomography (OCT) database in nonhuman primates (NHPs). Translational Relevance: We found that the differences in RNFL thickness distribution and sex between non-glaucoma cynomolgus monkey colonies and humans should be thoroughly taken into account in laboratory animal studies.

Evaluation of lamina cribrosa parameters, nerve fiber thickness, and macular thickness in primary open-angle glaucoma and pseudoexfoliation glaucoma using optical coherence tomography.

PURPOSE: To evaluate the lamina cribrosa, retinal nerve fiber layer (RNFL), and macula in patients with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG) and healthy individuals using enhanced depth imaging (EDI) of spectral-domain optical coherence tomography (SD-OCT). METHODS: A total of 158 eyes were included in the study, comprising 58 eyes of 29 patients with POAG, 50 eyes of 25 patients with PEXG, and 50 eyes of 25 healthy individuals. The lamina cribrosa thickness (LCT) (at three locations), lamina cribrosa depth (LCD), RNFL thickness, and the macular thickness were measured using the EDI mode of the SD-OCT. The results were compared among the three groups. RESULTS: In both POAG and PEXG groups, the LCT was significantly thinner in the center, mid-superior, and mid-inferior areas in both eyes than in the control group (p < 0.001). However, no statistically significant difference was observed between the POAG and PEXG groups in terms of LCT at all three measurement locations in both eyes (p > 0.05). The LCD was significantly lower in the control group compared to the POAG and PEXG groups (p < 0.05), but there was no significant difference between the POAG and PEXG groups (p > 0.05). The RNFL thickness was significantly lower in both the POAG and PEXG groups compared to the control group in both eyes (p < 0.05). CONCLUSION: The LCT and LCD of patients with POAG and PEXG were thinner than those of healthy individuals, but there was no significant difference between the patients with POAG and PEXG.

Long-Term Rate of Optic Disc Rim Loss in Glaucoma Patients Measured From Optic Disc Photographs With a Deep Neural Network.

Purpose: This study uses deep neural network-generated rim-to-disc area ratio (RADAR) measurements and the disc damage likelihood scale (DDLS) to measure the rate of optic disc rim loss in a large cohort of glaucoma patients. Methods: A deep neural network was used to calculate RADAR and DDLS for each optic disc photograph (ODP). Patient demographics, diagnosis, intraocular pressure (IOP), and mean deviation (MD) from perimetry were analyzed as risk factors for faster progression of RADAR. Receiver operating characteristic (ROC) curves were used to compare RADAR and DDLS in their utility to distinguish glaucoma from glaucoma suspect (GS) and for detecting glaucoma progression. Results: A total of 13,679 ODPs with evidence of glaucomatous optic nerve damage from 4106 eyes of 2407 patients with glaucoma or GS were included. Of these eyes, 3264 (79.5%) had a diagnosis of glaucoma, and 842 (20.5%) eyes were GS. Mean ± SD baseline RADAR of GS and glaucoma were 0.67 ± 0.13 and 0.57 ± 0.18, respectively (P < 0.001). Older age, greater IOP fluctuation, baseline MD, right eye, and diagnosis of secondary open-angle glaucoma were associated with slope of RADAR. The mean baseline DDLS of GS and glaucoma were 3.78 and 4.39, respectively. Both RADAR and DDLS showed a less steep slope in advanced glaucoma. In glaucoma, the change of RADAR and DDLS correlated with the corresponding change in MD. RADAR and DDLS had a similar ability to discriminate glaucoma from GS and detect disease progression. Area under the ROC curve of RADAR and DDLS was 0.658 and 0.648. Conclusions: Automated calculation of RADAR and DDLS with a neural network can be used to evaluate the extent and long-term rate of optic disc rim loss and is further evidence of long-term nerve fiber loss in treated patients with glaucoma. Translational Relevance: Our study provides a large clinic-based experience for RADAR and DDLS measurements in GS and glaucoma with a neural network.

Hybrid convolutional neural network optimized with an artificial algae algorithm for glaucoma screening using fundus images.

OBJECTIVE: We developed an optimized decision support system for retinal fundus image-based glaucoma screening. METHODS: We combined computer vision algorithms with a convolutional network for fundus images and applied a faster region-based convolutional neural network (FRCNN) and artificial algae algorithm with support vector machine (AAASVM) classifiers. Optic boundary detection, optic cup, and optic disc segmentations were conducted using TernausNet. Glaucoma screening was performed using the optimized FRCNN. The Softmax layer was replaced with an SVM classifier layer and optimized with an AAA to attain enhanced accuracy. RESULTS: Using three retinal fundus image datasets (G1020, digital retinal images vessel extraction, and high-resolution fundus), we obtained accuracy of 95.11%, 92.87%, and 93.7%, respectively. Framework accuracy was amplified with an adaptive gradient algorithm optimizer FRCNN (AFRCNN), which achieved average accuracy 94.06%, sensitivity 93.353%, and specificity 94.706%. AAASVM obtained average accuracy of 96.52%, which was 3% ahead of the FRCNN classifier. These classifiers had areas under the curve of 0.9, 0.85, and 0.87, respectively. CONCLUSION: Based on statistical Friedman evaluation, AAASVM was the best glaucoma screening model. Segmented and classified images can be directed to the health care system to assess patients' progress. This computer-aided decision support system will be useful for optometrists.

True or pseudo optic disc edema: clinically-based approach to the differential diagnosis.

PURPOSE: To present a clinically based approach to the differentiation of optic disc edema (DE) cases, commonly seen in neuro-ophthalmology. METHODS: Consecutive patients who were considered to have unilateral or bilateral DE during examinations in the outpatient clinic and were referred to the neuro-ophthalmology department were included in this prospective study. The examination findings and differential diagnosis based on clinical signs and symptoms, and neuro-ophthalmological approach were evaluated in cases of DE. RESULTS: Of the 119 cases with DE, 69 (58%) were women and 50 (42%) were men, where 89 (75%) had true optic DE (ODE) and 30 (25%) had pseudo optic DE  (PODE). Non-arteritic anterior ischemic optic neuropathy (n = 40), increased intracranial pressure (n = 32), and anterior optic neuritis (n = 17) were determined as the causes of true ODE, whereas small and crowded optic disc (n = 12), tilted optic disc (n = 8), myelinated nerve fibers (n = 5) and optic disc drusen (n = 5) as the causes of PODE. Patients with optic neuritis were the youngest (28.41 years) group of ODE cases while those with non-arteritic anterior ischemic optic neuropathy were the oldest (59.98 years). The first symptoms were sudden and painless loss of vision and/or visual field in cases with non-arteritic anterior ischemic optic neuropathy, pain increasing with eye movements and loss of vision and/or visual field in cases with optic neuritis, headache, and from time to time blurred vision in cases with increased intracranial pressure. Patients having vision loss due to amblyopia constituted (30%) of PODE cases while 70% were determined incidentally and they had the best visual acuity. The accuracy of the preliminary diagnosis based on neuro-ophthalmologic examination findings was 79% in all cases. CONCLUSION: Detailed history taking and neuro-ophthalmological examination are essential in the differential diagnosis of ODE and PODE.

Comparison of ganglion cell layer thickness and pattern electroretinography among glaucoma suspects and healthy controls.

PURPOSE: To evaluate the difference in ganglion cell layer (GCL) thickness on optical coherence tomography (OCT) and waveform on pattern electroretinography (PERG) among glaucoma suspects and healthy controls. METHODS: An analytical, cross-sectional study was done on 100 eyes of 50 subjects, equally divided in the glaucoma suspect and control group. Subjects with an asymmetrically increased vertical cup-to-disc ratio and without any perimetric change were taken as suspects, and subjects with normal findings were taken as controls. GCL thickness was evaluated on spectral domain OCT at 3 mm, 3.45 mm, and 6 mm centering the foveola, and P50, N95 wave forms were recorded according to the standard PERG protocol. RESULTS: In this study, we observed that the average GCL thickness is significantly less in glaucoma suspects at 3.45 mm (p = 0.045) and at 6 mm (p < 0.001) circle zone. On PERG, P50 amplitude was significantly low in glaucoma suspects in comparison to controls (p = 0.007). There was significantly increased implicit time for both P50 and N95 in glaucoma suspects (p < 0.001). For N95 amplitude, a non-significant (p = 0.127) difference was observed among the two groups. At 3.45 mm, average GCL thickness showed a weak negative correlation with N95 implicit time (r = - 0.286, p = 0.044), a weak positive correlation with P50 amplitude (r = 0.349, p = 0.013), and at 6 mm, a weak positive correlation with P50 amplitude (r = 0.311, p = 0.028) in glaucoma suspects. CONCLUSIONS: Analysing GCL thickness can help in the structural assessment of preperimetric glaucoma. PERG can be used as a valuable tool for the detection of ganglion cell dysfunction, even before cell loss.

Automatic retinal image analysis methods using colour fundus images for screening glaucomatous optic neuropathy.

OBJECTIVES: Train an automatic retinal image analysis (ARIA) method to screen glaucomatous optic neuropathy (GON) on non-mydriatic retinal images labelled with the additional results of optical coherence tomography (OCT) and assess different models for the GON classification. METHODS: All the images were obtained from the hospital for training and 10-fold cross-validation. Two methods were used to improve the classification performance: (1) using images labelled with the additional results of OCT as the reference standard and (2) generating models using retinal features from the entire images, the region of interest (ROI) of the optic disc, and the ROI of the macula, and the combination of all the features. RESULTS: Overall, we collected 1338 images with paired OCT scans. In 10-fold validation, ARIA achieved sensitivities of 92.2 %, 92.7% and 85.7%, specificities of 88.8%, 86.7% and 80.2% and accuracies of 90.6%, 89.9% and 83.1% using the retinal features from the entire images, the ROI of the optic disc and the ROI of the macula, respectively. We found the model combining all the features has the best classification performance and obtained a sensitivity of 92.5%, a specificity of 92.1% and an accuracy of 92.4%, which is significantly different from other models (p<0.001). CONCLUSION: We used two methods to improve the classification performance and found the best model to detect glaucoma on colour fundus retinal images. It can become a cost-effective and relatively more accurate glaucoma screening tool than conventional methods.

Optical coherence tomography angiography analysis of the fellow eye in unilateral pseudoexfoliation syndrome.

PURPOSE: To compare the macular and optic disc vascular parameters in the unaffected fellow eyes of subjects with unilateral pseudoexfoliation syndrome (PXS) and controls using optical coherence tomography angiography (OCTA). METHODS: The medical records of 61 eyes of 61 patients were analyzed in a retrospective study. Of these, 30 eyes were unaffected fellow eyes and 31 eyes were control eyes. The vessel density (VD), perfusion density (PD) and foveal avascular zone (FAZ)-related parameters of the superficial capillary plexus (SCP) in the circumpapillary and macular area and the VD and PD of the deep capillary plexus (DCP) in the macular area were measured using OCTA after dilatation and were compared between two groups after adjustment for age, sex and axial length. RESULTS: There were no statistically significant differences in sex ratio or mean age, central corneal thickness measurements, refractive errors, intraocular pressures and axial length between both groups (all P > 0.05). In the circumpapillary area, inferior VD and PD in the inner zone, as well as average, temporal, inferior, and nasal VD and PD in the outer zone were significantly reduced in the unaffected fellow eyes with unilateral PXS, while the circumpapillary retinal nerve fiber layer (RNFL) thicknesses were similar between groups. In the macular SCP, VDs were significantly lower in all sectors in the inner area and in the outer zones (p < 0.05 for all), PDs were significantly lower in all sectors (p < 0.05 for all) except the nasal sector of the outer zone (p = 0.003 for average, p = 0.029 for superior sector, p = 0.004 for temporal sector, p < 0.001 for inferior sector), and the FAZ circularity (p = 0.037) were significantly lower in the unaffected fellow eyes with unilateral PXS, whereas macular ganglion cell inner plexiform layer (GCIPL) thickness was similar between the two groups. CONCLUSIONS: Although circumpapillary RNFL and GCIPL thicknesses were similar between the two groups, VDs and PDs in the circumpapillary and macular SCP and FAZ circularity were significantly lower in the fellow eye of subjects with unilateral PXS.

Comparative of OCT and OCTA parameters in patients with early chronic angle-closure glaucoma and early pituitary adenoma.

Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) have the potential application in evaluating pathological structural change of the optic nerve. We aimed to evaluate the value of the OCT and OCTA parameters of the optic disk and macular in differentiating early chronic primary angle-closure glaucoma (CPACG) and early pituitary adenoma (PA) in case of mild visual field defects (the mean defect (MD) > 6 dB). The results showed that regarding OCTA parameters, CPACG patients had lower retinal blood flow density of most layers of the optic disk and macular than PA patients. Regarding OCT parameters, CPACG patients had thinner circumpapillary retinal nerve fiber layer (CP-RNFL) in all quadrants and average CP-RNFL, ganglion cell layer (GCL) and macular ganglion cell complex (GCC) in each quadrant of macular inner and outer rings, and inner plexus layer (IPL) of macular inner ring, superior-outer ring and temporal-outer ring than PA patients. The Z test indicated that OCTA parameters and OCT parameters had similar value in the diagnosis of disease. In conclusion, in the case of similar visual field damage, early CPACG patients have smaller blood flow density and thinner optic disk and macular than early PA. OCTA has similar performance to OCT in diagnosing CPACG and PA.

Impact of acquisition area on deep-learning-based glaucoma detection in different plexuses in OCTA.

Glaucoma is a group of neurodegenerative diseases that can lead to irreversible blindness. Yet, the progression can be slowed down if diagnosed and treated early enough. Optical coherence tomography angiography (OCTA) can non-invasively provide valuable information about the retinal microcirculation that has shown to be correlated with the onset of the disease. The vessel density (VD) is the most commonly used biomarker to quantify this vascular information. However, different studies showed that there is a great impact of the acquisition area on the performance of the VD to distinguish between glaucoma patients and a healthy control group. It also seems that the separate capillary plexuses are differently affected by the disease and therefore also influence the results. So in this study we investigate the impact of the acquisition area (3 × 3 mm macular scan, 6.44 × 6.4 mm macular scan, 6 × 6 mm optic nerve head (ONH) scan) and the different plexuses on the machine-learning-based distinction between glaucoma patients and healthy controls. The results yielded that the 6 × 6 mm ONH show the best performance over all plexuses. Moreover the deep learning-based approach outperforms the VD as a biomarker on every acquisition area and plexus. In addition to that, it also performs better than traditional biomarkers obtained from the OCT scans that are used in the clinical routine for diagnosis and progression tracking of glaucoma. Consequently, OCTA scans of the ONH might be a useful addition to OCT when studying glaucoma.

Peripheral Superficial Retina Vascular Density and Area of Radial Peripapillary Capillaries Changes in Myopic Individuals: A Wide-Field OCT Angiography Study.

Purpose: Using swept-source optical coherence tomography (SS-OCT) to explore the effect of high myopia on superficial retina vascular density (SVD) of the peripheral region and the area of radial peripapillary capillaries (RPCs). Methods: In this cross-sectional study, a total of 91 volunteers (34 male subjects and 57 female subjects) were recruited and 34 individuals in the high myopic group (group A) and 57 individuals in the low myopic group (group B). Using the wide-field OCT-angiography (OCTA; 24 × 20 mm, 120 degrees angular field) compared the peripheral SVD and the area of RPC between the two groups and investigated its correlation with ocular axial length and diopter. Results: Peripheral SVD of group B around the supratemporal (SVD1), supranasal (SVD2), infratemporal (SVD3), and infranasal (SVD4) directions were significantly higher than those of group A (all P < 0.05). The RPC area of group B around the supranasal (RPC2) and infranasal (RPC4) were significantly larger than that of group A (all P < 0.01). Ocular axial length and diopter were significantly correlated with SVD2 and SVD4 (all P < 0.05), and they also have a significant correlation with the supratemporal (RPC1), RPC2, and RPC4 (all P < 0.05). Conclusions: Peripheral SVD was decreased and the RPC area was mainly reduced on the nasal side in the high myopic group. Peripheral SVD and area of RPC are significantly correlated with ocular axial length and diopter. Translational Relevance: The wide-field OCTA can be used for new detection of myopia's impact on the retinal peripheral SVD and area of peripapillary RPC, offering new insights into the progression of myopia.

Evaluation of choroidal thickness and optic disc parameters in patients with chronic phase gout.

PURPOSE: This study aims to assess the disparities in choroidal thickness and optic disc parameters between individuals diagnosed with chronic gout and an age- and gender-matched control cohort. METHODS: This cross-sectional study involved 30 gout patients receiving treatment at the Rheumatology clinic, alongside 30 healthy control individuals matched for age and gender. A comprehensive ophthalmological assessment, encompassing visual acuity measurement, intraocular pressure evaluation, slit-lamp biomicroscopy, and dilated fundus examination, was conducted for all participants. Peripapillary retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), and subfoveal choroidal thickness (SFCT) were quantified utilizing Spectral Domain Optical Coherence Tomography. RESULTS: The mean age within the study group was 54.53 ± 9.43 years, while the control group's mean age was 53.20 ± 10.36 years. In both the gout and control cohorts, there were 28 men and 2 women. No significant differences were observed in age and gender between the groups. Gout patients manifested thinner RNFL and GCC across all quadrants; however, statistically significant thinning was only evident in the nasal and inferior quadrants for RNFL. Despite a thinner SFCT observed in gout patients compared to controls, this discrepancy did not attain statistical significance. CONCLUSION: Chronic phase gout patients may display alterations in optic disc and macular parameters, alongside potential variations in choroidal thickness. Nevertheless, more controlled studies encompassing a larger participant pool are imperative to substantiate our findings.

Using Multi-Layer Perceptron Driven Diagnosis to Compare Biomarkers for Primary Open Angle Glaucoma.

Purpose: To use neural network machine learning (ML) models to identify the most relevant ocular biomarkers for the diagnosis of primary open-angle glaucoma (POAG). Methods: Neural network models, also known as multi-layer perceptrons (MLPs), were trained on a prospectively collected observational dataset comprised of 93 glaucoma patients confirmed by a glaucoma specialist and 113 control subjects. The base model used only intraocular pressure, blood pressure, heart rate, and visual field (VF) parameters to diagnose glaucoma. The following models were given the base parameters in addition to one of the following biomarkers: structural features (optic nerve parameters, retinal nerve fiber layer [RNFL], ganglion cell complex [GCC] and macular thickness), choroidal thickness, and RNFL and GCC thickness only, by optical coherence tomography (OCT); and vascular features by OCT angiography (OCTA). Results: MLPs of three different structures were evaluated with tenfold cross validation. The testing area under the receiver operating characteristic curve (AUC) of the models were compared with independent samples t-tests. The vascular and structural models both had significantly higher accuracies than the base model, with the hemodynamic AUC (0.819) insignificantly outperforming the structural set AUC (0.816). The GCC + RNFL model and the model containing all structural and vascular features were also significantly more accurate than the base model. Conclusions: Neural network models indicate that OCTA optic nerve head vascular biomarkers are equally useful for ML diagnosis of POAG when compared to OCT structural biomarker features alone.

Peripapillary Retinal Nerve Fiber Layer and Macular Ganglion Cell-Inner Plexiform Layer Parameters and Their Associated Factors in Cynomolgus Macaques.

Purpose: The purpose of this study was to define the normal range of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer (mGCL), and macular inner plexiform layer (mIPL) thickness in cynomolgus macaques, and explore their inter-relationship and correlation with age, refractive errors, and axial length (AL). Methods: In this cross-sectional study, we measured biometric and refractive parameters, and pRNFL/mGCL/mIPL thickness in 357 healthy cynomolgus macaques. Monkeys were divided into groups by age and spherical equivalent (SE). Correlation and regression analyses were used to explore the relationship between pRNFL and mGCL/mIPL thickness, and their correlation with the above parameters. Results: The mean age, SE, and AL were 14.46 ± 6.70 years, -0.96 ± 3.23 diopters (D), and 18.39 ± 1.02 mm, respectively. The mean global pRNFL thickness was 95.06 ± 9.42 µm (range = 54-116 µm), with highest values in the inferior quadrant, followed by the superior, temporal, and nasal quadrants (P < 0.001). Temporal pRNFL thickness correlated positively with age (r = 0.218, P < 0.001) and AL (r = 0.364, P < 0.001), and negatively with SE (r = -0.270, P < 0.001). In other quadrants, pRNFL thickness correlated negatively with age and AL, but positively with SE. In the multivariable linear regression model, adjusted for sex and AL, age (ß = -0.350, P < 0.001), and SE (ß = 0.206, P < 0.001) showed significant associations with global pRNFL thickness. After adjusting for age, sex, SE, and AL, pRNFL thickness positively correlated with mGCL (ß = 0.433, P < 0.001) and mIPL thickness (ß = 0.465, P < 0.001). Conclusions: The pRNFL/mGCL/mIPL thickness distribution and relationship with age, AL, and SE in cynomolgus macaques were highly comparable to those in humans, suggesting that cynomolgus monkeys are valuable animal models in ophthalmic research.

The Role of αvß3 Integrin in Lamina Cribrosa Cell Mechanotransduction in Glaucoma.

Purpose: Glaucoma, one of the leading causes of irreversible blindness, is a common progressive optic neuropathy characterised by visual field defects and structural changes to the optic nerve head (ONH). There is extracellular matrix (ECM) accumulation and fibrosis of the lamina cribrosa (LC) in the ONH, and consequently increased tissue stiffness of the LC connective tissue. Integrins are cell surface proteins that provide the key molecular link connecting cells to the ECM and serve as bidirectional sensors transmitting signals between cells and their environment to promote cell adhesion, proliferation, and remodelling of the ECM. Here, we investigated the expression of αVß3 integrin in glaucoma LC cell, and its effect on stiffness-induced ECM gene transcription and cellular proliferation rate in normal (NLC) and glaucoma (GLC) LC cells, by down-regulating αVß3 integrin expression using cilengitide (a known potent αVß3 and αVß5 inhibitor) and ß3 integrin siRNA knockdown. Methods: GLC cells were compared to age-matched controls NLC to determine differential expression levels of αVß3 integrin, ECM genes (Col1A1, α-SMA, fibronectin, vitronectin), and proliferation rates. The effects of αVß3 integrin blockade (with cilengitide) and silencing (with a pool of four predesigned αVß3 integrin siRNAs) on ECM gene expression and proliferation rates were evaluated using both reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting in the human NLC cells cultured on soft (4 kPa) and stiff (100 kPa) substrate and in GLC cells grown on standard plastic plates. Results: αVß3 integrin gene and protein expression were enhanced (p < 0.05) in GLC cells as compared to NLC. Both cilengitide and siRNA significantly reduced αVß3 expression in GLC. When NLC were grown in the stiff substrate, cilengitide and siRNA also significantly reduced the increased expression in αVß3, ECM components, and proliferation rate. Conclusions: Here, we provide evidence of cilengitide- and siRNA-mediated silencing of αVß3 integrin expression, and inhibition of ECM synthesis in LC cells. Therefore, αVß3 integrin may be a promising target for the development of novel anti-fibrotic therapies for treating the LC cupping of the ONH in glaucoma.

Long-Term Changes in Lamina Cribrosa Curvature Index After Trabeculectomy in Glaucomatous Eyes.

Purpose: This study aimed to evaluate both short-term and long-term changes in the lamina cribrosa curvature index (LCCI) following trabeculectomy and investigate the factors influencing these changes. Methods: In this retrospective, observational study, 40 eyes of 40 patients with glaucoma who underwent trabeculectomy and had a follow-up of at least 2 years were included. Optic nerve head area was scanned by using spectral-domain optical coherence tomography before surgery (Pre_OP), within 6 months postoperatively (Post_OP1), and at the last visit (Post_OP2). LCCI values calculated from B-scan images at six different planes (0°, 30°, 60°, 90°, 120°, and 150°) and their mean values were compared. Univariate and multivariate linear regression analyses were used to identify the clinical factors associated with the amount of LCCI changes. Results: The mean follow-up time was 38.3 ± 16.8 months. At Post_OP1, the mean LCCI decreased from 9.28 ± 2.58 to 7.91 ± 2.57 (P < 0.001), and the mean intraocular pressure decreased from 22.0 ± 7.6 mm Hg to 12.2 ± 3.8 mm Hg (P = 0.001). At Post_OP2, the mean LCCI was maintained at 7.74 ± 2.49 (P = 0.56 when compared to Post_OP1 and P < 0.001 when compared to Pre_OP). The mean intraocular pressure was 12.6 ± 5.4 mm Hg (P = 0.67 when compared to Post_OP1 and P < 0.001 when compared to Pre_OP). Long-term LCCI changes were associated with baseline age (P = 0.04), spherical equivalent (P = 0.02), mean IOP during follow-ups (P = 0.02), and preoperative LCCI (P = 0.04). Conclusions: Glaucomatous eyes undergoing trabeculectomy demonstrated reductions in the LCCI after a mean follow-up of over 3 years. Greater long-term LCCI reduction was associated with younger age, lower mean IOP during follow-up period, greater spherical equivalent refractive error, and preoperative LCCI.

Lamina Cribrosa Microstructure in Nonhuman Primates With Naturally Occurring Peripapillary Retinal Nerve Fiber Layer Thinning.

Purpose: The lamina cribrosa (LC) is hypothesized to be the site of initial axonal damage in glaucoma with the circumpapillary retinal nerve fiber layer thickness (RNFL-T) widely used as a standard metric for quantifying the glaucomatous damage. The purpose of this study was to determine in vivo, 3-dimensional (3D) differences in the microstructure of the LC in eyes of nonhuman primates (NHPs) with naturally occurring glaucoma. Methods: Spectral-domain optical coherence tomography (OCT) scans (Leica, Chicago, IL, USA) of the optic nerve head were acquired from a colony of 50 adult rhesus monkeys suspected of having high prevalence of glaucoma. The RNFL-T was analyzed globally and in quadrants using a semi-automated segmentation software. From a set of 100 eyes, 18 eyes with the thinnest global RNFL-T were selected as the study group and 18 eyes with RNFL-T values around the 50th percentile were used as controls. A previously described automated segmentation algorithm was used for LC microstructure analysis. Parameters included beam thickness, pore diameter and their ratio (beam-to-pore ratio [BPR]), pore area and shape parameters, beam and pore volume, and connective tissue volume fraction (CTVF; beam volume/total volume). The LC microstructure was analyzed globally and in the following volumetric sectors: quadrants, central and peripheral lamina, and three depth slabs (anterior, middle, and posterior). Results: Although no significant difference was detected between groups for age, weight, or disc size, the study group had significantly thinner RNFL than the control group (P < 0.01). The study group had significantly smaller global and sectoral pore diameter and larger BPR compared with the control group. Across eyes, the global RNFL-T was associated positively with pore diameter globally. BPR and CTVF were significantly and negatively associated with the corresponding RNFL-T in the superior quadrant. Conclusions: Global and sectoral microstructural differences were detected when comparing thin and normal RNFL-T eyes. Whether these LC differences are the cause of RNFL damage or the result of remodeling of the LC requires further investigation. Translational Relevance: Our findings indicate structural alterations in the LC of NHP exhibiting natural thinning of the RNFL, a common characteristic of glaucomatous damage.

Measurement of the Tilt Angle of the Optic Disc Using Spectral-Domain Optical Coherence Tomography and Related Factors in Myopia.

Purpose: This study presents a novel, three-dimensional method for measuring the tilt angle of the tilted optic disc (TOD) using spectral-domain optical coherence tomography (SD-OCT) and investigates the correlation between ocular-related parameters and TOD. Methods: We included the right eyes of 243 healthy young individuals, categorized by axial length. We measured the ovality index (OI) and dihedral angle (DA) using SD-OCT infrared ray fundus photographs and high-resolution cross-sectional images of the optic disc, respectively. The relationships between OI, DA, and ocular-related parameters were analyzed. Results: Eyes in the longer axial length group exhibited a lower OI and a higher DA, along with thinner nasal and inferonasal circumpapillary retinal nerve fiber layer (cpRNFL) and thicker temporal and superotemporal cpRNFL. There was a significant relationship between DA and cpRNFL thickness. The new method utilizing DA to measure the tilt angle of TOD demonstrated high repeatability. Conclusions: We propose a novel, three-dimensional, and quantitative method for evaluating the tilt degree of TOD. A higher degree of myopia indicated a greater tilt angle of the TOD, and a greater TOD suggested additional changes in cpRNFL thickness. These findings should be considered when interpreting increased susceptibility and early assessment of glaucoma in myopia. Translational Relevance: DA could serve as a superior indicator for describing TOD morphology during eyeball elongation and evaluating its impact on related parameters of the optic disc and peripapillary structures in the myopic population.

Retinal nerve fiber layer thickness and radial peripapillary capillaries density in myopic adults with optical coherence tomography angiography.

PURPOSE: To evaluate retinal nerve fiber layer thickness (RNFLT) and radial peripapillary capillaries (RPC) density in adults with different degrees of myopia using optical coherence tomography angiography (OCTA) and explore their relationship with ocular factors, such as axial length (AL) and disc area. METHODS: A total of 188 subjects were included in this cross-sectional study. The eyes were divided into four groups according to AL. OCTA was used for the assessment of RNFLT, RPC density, and other optic disc measurements, such as disc area. One-way analysis of variance was performed to compare differences between four groups, and P value < 0.01 was considered significant. RESULTS: The RNFLT was significantly thinner in high myopia (HM) group at inferior nasal (IN) quadrant (P = 0.004) than low myopia (LM) group, but thicker at temporal inferior (TI) quadrant (P = 0.006). The RPC density of nasal superior (NS) quadrant, nasal inferior (NI) quadrant, and inferior nasal (IN) quadrant significantly decreased as AL increasing. By simple linear regression analysis, the inside disc RPC (iRPC) density tended to be correlated significantly with AL (0.3997%/mm, P < 0.0001). Peripapillary RPC (pRPC) density was in significant correlation with AL (-0.2791%/mm, P = 0.0045), and peripapillary RNFLT (pRNFLT) was in significant correlation with disc area (0.2774%/mm2, P = 0.0001). CONCLUSION: RNFLT and RPC density were closely associated with AL and disc area. They might be new indexes in assessing and detecting myopia development via OCTA.