The increasing global prevalence of myopia presents a significant public health concern, and growing evidence has demonstrated that myopia is a major risk factor for the development of open-angle glaucoma. Therefore, timely detection and management of glaucoma in myopic patients are crucial; however, identifying the structural alterations of glaucoma in the optic nerve head (ONH) and retinal tissues of myopic eyes using standard diagnostic tools such as fundus photography, optical coherence tomography (OCT), and OCT angiography (OCTA) presents challenges. Additionally, myopia-related perimetric defects can be confounded with glaucoma-related defects. We comprehensively examine the challenges encountered in evaluating glaucoma in myopic eyes through various diagnostic tools, including fundus photography, OCT of the ONH, retinal nerve fiber layer, and macular ganglion cell layer, OCTA, and perimetry. We also explore potential opportunities to address these challenges, providing insights for clinicians to effectively manage myopic glaucoma patients in clinical practice.

Ocular hypertension (OHT) is the most significant risk factor for glaucoma. We aimed to develop a model for predicting OHT progression to early glaucoma and to identify key predictors.

Patients with OHT with at least two follow-up visits within 3 years were categorized into non-progressive and progressive groups based on optic nerve morphology and/or functional changes during follow-up. Data were split into training and testing sets (8:2 ratio). Least absolute shrinkage and selection operator regression and logistic regression were used to select predictors. Machine learning models were constructed using the selected predictors as input and evaluated using area under the receiver operating characteristic (AUC) and precision-recall (AP) curve values. The optimal model was further evaluated using 10-fold cross-validation and a validation set. The Shapley additive explanations method was applied to interpret the predictors.

Overall, 395 eyes from 395 patients were included (non-progressive: n = 295; progressive: n = 100). The random forest model outperformed all others, achieving AUC values of 0.881 (95 % confidence interval [CI]: 0.835-0.926) in the training set and 0.937 (95 % CI: 0.884-0.991) in the testing set. In the independent validation set (n = 82), the AUC and AP values were 0.865 (95 % CI: 0.782-0.947) and 0.707, respectively. Key predictors were baseline intraocular pressure, rim area, ganglion cell-inner plexiform layer (GCIPL) inferior-temporal thickness difference, and GCIPL superior-temporal thickness difference. Family history and male sex also contributed.

The developed model could effectively predict the risk for OHT progression to early glaucoma and may aid devising individualized treatment plans and follow-up protocols.

To compare retinal nerve fiber layer (RNFL) thickness rates of change and their variability between 2 commercial OCT devices.

Prospective cohort study.

Ninety-four glaucoma eyes (94 patients) with central damage or moderate to advanced glaucoma with ≥ 2 years of follow-up and ≥ 4 pairs of OCT scans.

A bivariate longitudinal Bayesian model was designed to compare inferences on RNFL rates of change from the 2 devices, both globally and in 12 clock hour sectors. Optic nerve OCT scans were acquired with Spectralis and Cirrus OCT devices in the same session. We inspected longitudinal RNFL profile plots from both OCT devices for all subjects across all sectors and globally.

The rates of change, longitudinal variances, and proportions of significant negative and positive slopes (slope < 0 or > 0 μm/year and 1-sided P < 0.025, respectively) were compared between the devices.

The mean (standard deviation) baseline 24-2 visual field mean deviation and median (range) follow-up time were -8.2 (5.5) dB and 4.5 (2.2-6.7) years, respectively. The mean (95% credible interval [CrI]) estimated global baseline RNFL thickness for Spectralis and Cirrus OCTs were 61.5 (58.6-64.1) and 65.3 (63.2-67.4) μm, respectively. The global RNFL rates of change for Spectralis and Cirrus OCTs were -0.70 μm/year (95% CrI = -0.88 to -0.51 μm/year) and -0.45 μm/year (95% confidence interval = -0.63 to -0.27 μm/year) and were significantly faster for Spectralis compared to Cirrus OCT (difference = -0.24 μm/year, 95% CrI -0.45 to -0.04 μm/year, P < 0.001) as were sectoral rates in 5 out of 12 sectors. Higher proportions of significant negative RNFL rates of change were found with Spectralis OCT globally and in clock hour sectors 2 to 6 and 8 to 10 (corresponding to nasal, inferonasal, inferotemporal, and temporal regions). The proportions of significant positive rates of change were small (0%-3%) across sectors and similar between the devices.

Spectralis OCT rates of RNFL change were faster compared to those from Cirrus OCT. Spectralis OCT detected a higher proportion of significant negative rates globally and in some sectors. OCT devices are not comparable regarding detection of change in eyes with central damage or moderate to advanced glaucoma.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A cross-sectional pilot study to compare macular oxygen saturation (sO2) and associated clinical measurements between normal and glaucoma subjects and to evaluate whether macular sO2 can be a diagnostic metric for early-stage glaucoma.

Forty-eight eyes of 35 subjects from three groups were included: normal subjects (16 eyes, 10 subjects), suspect/pre-perimetric glaucoma (GS/PPG) subjects (17 eyes, 12 subjects), and perimetric glaucoma (PG) subjects (15 eyes, 13 subjects). We performed retinal oximetry of visible light optical coherence tomography (VIS-OCT) in macular vessels, with 512 × 256 sampling points over a 5 × 5 mm2 area. Zeiss Cirrus OCT scans and a 24-2 visual field test (VFT) were conducted. Statistical analysis was conducted.

Significant differences were observed among the three groups for all VIS-OCT, Zeiss OCT, and VFT variables. As glaucoma severity increased, macular AsO2 (arterial sO2) and A-V sO2 (arteriovenous sO2 difference) decreased, whereas macular VsO2 (venous sO2) increased. Macular AsO2 and A-V sO2 were found to be statistically correlated with ganglion cell layer + inner plexiform layer (GCL+IPL) and circumpapillary retinal nerve fiber layer in all eyes, as well as in PG eyes. Within the PG group, a dominant correlation between AsO2 and ganglion cell layer + inner plexiform layer was observed in the more damaged lower hemifield.

Glaucoma subjects showed altered macular sO2, indicating reduced oxygen consumption. The sO2 measured by VIS-OCT could be a potential metric for early glaucoma diagnosis.

This study shows macular sO2 measurements via VIS-OCT could bridge advanced imaging technology and clinical glaucoma detection.

Optical coherence tomography angiography was used to compare the changes of capillary density and thickness of the peripapillary retinal nerve fiber layer in patients with diabetes mellitus (DM) without diabetic retinopathy (DR) and patients with mild nonproliferative diabetic retinopathy (NPDR).

In this prospective cross-sectional study, 62, 85, and 75 eyes of normal control group (NC), DM group, and NPDR group were included, respectively. All subjects received an optic-disc-centered 6 × 6-mm fundus scan. The annular region outside the optic disc boundary was divided into eight sectors: nasal superior, nasal inferior, inferior nasal (IN), inferior temporal (IT), temporal superior, temporal inferior, superior nasal, and superior temporal (ST). The average retinal nerve fiber layer thickness, average capillary density, and changes in thickness and capillary density of each sector in the annular region were calculated.

Compared with the NC group, the average capillary density of pRNFL in patients with DM and NPDR groups decreased significantly (p < 0.001), and there were significant differences in capillary density in all sectors except the IN sector in the DM group. There was no significant difference in the average thickness of pRNFL between the groups. Only the thickness of ST and IT in DM group and NPDR group, respectively, were significantly lower than that in the control group. In addition, the ROC curve of pRNFL average capillary density has high sensitivity and specificity in distinguishing DR from healthy eyes (AUC = 0.852).

The pRNFL average capillary density in diabetic patients without DR and patients with mild NPDR, respectively, were significantly lower than that in healthy controls, especially in the NPDR group.

Background: The objective assessment of visual function is crucial in glaucoma management, highlighting the importance of electroretinography (ERG). This study investigates the diagnostic performance of photopic negative response (PhNR) amplitude and the normalized PhNR/b-wave ratio in diagnosing glaucoma, focusing on the impact of myopia. Methods: Ninety-one glaucoma patients and 19 glaucoma suspects were included, defining myopia as axial length (AL) > 24 mm or > 25 mm. Full-field photopic ERG used a red stimulus on a blue background. Results: Myopic glaucoma patients showed a higher PhNR/b-wave ratio than non-myopic patients (p = 0.023). AL negatively correlated with b-wave amplitude (r = -0.239, p = 0.012). PhNR amplitude demonstrated an area under the receiver operating characteristic curve (AUC) of 0.661 (p = 0.028) overall and was less effective in the myopic subgroup (AUC = 0.574, p = 0.082). The diagnostic performance of the PhNR/b-wave ratio did not achieve statistical significance in either the total group (AUC = 0.616, p = 0.114) or the myopic subgroup (AUC = 0.574, p = 0.332). Conclusions: Standardization using the PhNR/b-wave ratio did not enhance diagnostic accuracy over PhNR amplitude, particularly in myopic patients, underscoring the need for careful interpretation in myopia and further research to optimize electrophysiological diagnostics.

To evaluate the 6-year physiological rates-of-change in ganglion cell inner plexiform layer (GCIPL) and retinal nerve fibre layer (RNFL) thickness measured with optical coherence tomography.

We included 2202 out of 2661 subjects from the population-based Singapore Chinese Eye Study who returned for follow-up 6 years after baseline examination (follow-up rate 87.7%). OCT scans with signal strength (SS) <6, imaging errors, and ocular pathologies were excluded. A linear mixed model was used to measure the rates-of-change in GCIPL and RNFL thickness. Time and difference between baseline and follow-up scan SS were modelled as fixed effect. Baseline age, baseline measurement, gender, hypertensive medication, diabetes status, cardiovascular disease, smoking status, body mass index, spherical equivalent (SE), intraocular pressure and optic disc area were each analysed in an interaction term with time.

The adjusted mean rate-of-change in average GCIPL was -0.312 μm/year in males and -0.235 μm/year in females. Older age and thicker GCIPL thickness at baseline were associated with higher rates-of-change while females and more hyperopic SE were associated with lower rates-of-change. The adjusted mean rate-of-change in average RNFL was -0.374 μm, with higher rates-of-change in the vertical quadrants and no differences between genders. Older age and thicker RNFL thickness at baseline were associated with higher rates-of-change in average RNFL and RNFL thickness in the vertical quadrants, and vice versa for each unit increase in scan SS and SE.

Our population cohort provides data on physiological thinning of GCIPL and RNFL with age. Differentiating physiological changes in GCIPL and RNFL is important for more accurate clinical assessment.

Glaucoma is the leading cause of irreversible blindness worldwide. The diagnosis process for glaucoma involves the measurement of the thickness of retinal layers in order to track its degeneration. The elongated shape of highly myopic eyes can hinder this diagnosis process, since it affects the OCT scanning process, producing deformations that can mimic or mask the degeneration caused by glaucoma. In this work, we present the first comprehensive cross-disease analysis that is focused on the anatomical structures most impacted in glaucoma and high myopia patients, facilitating precise differential diagnosis from those solely afflicted by myopia. To achieve this, a fully automatic approach for the retinal layer segmentation was specifically tailored for the accurate measurement of retinal thickness in both highly myopic and emmetropic eyes. To the best of our knowledge, this is the first approach proposed for the analysis of retinal layers in circumpapillary optical coherence tomography images that takes into account the elongation of the eyes in myopia, thus addressing critical diagnostic needs. The results from this study indicate that the temporal superior (mean difference 11.1μm, p<0.05), nasal inferior (13.1μm, p<0.01) and temporal inferior (13.3μm, p<0.01) sectors of the retinal nerve fibre layer show the most significant reduction in retinal thickness in patients of glaucoma and myopia with regards to patients of myopia.

Background/Objectives: The automated analyses of optical coherence tomography (OCT) scans of the retina occasionally suggest the presence of tissue deficits when no visual field defects can be detected. This study was made to find the sources of such alerts. Methods: Data from a population-based cohort of 360 participants aged 30-80 years was analysed for the anatomical sources of alerts after the extensive exclusion of participants where any suspicion of abnormality could be raised. An analysis was made of 12 × 9 mm volume scans centred between the disc and the fovea. The exclusions comprised 107 eyes with definite or borderline abnormal visual fields or other potentially confounding characteristics. A statistical analysis of the thickness patterns was made using the manufacturer's proprietary algorithm. The analysis comprised alerts corresponding to local layer thickness values in the lower 5th percentile of an independent reference population. Results: Of the 613 eligible healthy eyes, thickness deficit alerts were seen in 391. They were related to the angle between the temporal nerve fibre ridges being wider, narrower, or rotated compared to the reference template in 174 eyes and to the variations in the size of the macula in 207 eyes. The source was unidentifiable in 28 eyes. The common sources were a thin papillomacular nerve fibre layer accompanied by arcuate nerve fibre ridges spaced far apart and a thinly, but wider than the normal macular ganglion cell layer. Conclusions: Anatomical variation in the retinal nerve fibre and ganglion cell layers was the source of more than 90% of the thickness deficit alerts in the eyes with normal visual fields.

Our previous study predicted genuine glaucomatous visual field (VF) impairment in the central 10° VF, excluding the effect of cataract, using visual acuity (VA) and global indexes of VF more accurately than pattern deviation (PD). This study aimed to improve the accuracy by using pointwise total deviation (TD) values with the machine-learning method of random forest model (RFM) and to investigate whether incorporating optical coherence tomography-measured ganglion cell-inner plexiform layer (GCIPL) thickness is useful.

This retrospective study included 89 eyes with open-angle glaucoma that underwent successful cataract surgery (with or without iStent implantation or ab interno trabeculotomy). Postoperative TD in each of the 68 VF points was predicted using preoperative (1) PD, (2) VA and VF with a linear regression model (LM), and (3) VA and VF with RFM, and averaged as predicted mean TD (mTDpost). Further prediction was made by incorporating the preoperative GCIPL into the best model.

The mean absolute error (MAE) between the actual and predicted mTDpost with RFM (1.25 ± 1.03 dB) was significantly smaller than that with PD (3.20 ± 4.06 dB, p < 0.01) and LM (1.42 ± 1.06 dB, p < 0.05). The MAEs with the model incorporating GCIPL into RFM (1.24 ± 1.04 dB) and RFM were not significantly different.

Accurate prediction of genuine glaucomatous VF impairment was achieved using pointwise TD with RFM. No merit was observed by incorporating the GCIPL into this model.

This pointwise RFM could clinically reduce cataract effect on VF.

To compare the diagnostic accuracy of thickness measurements of individual and combined macular retinal layers to discriminate 188 glaucomatous and 148 glaucoma suspect eyes from 362 healthy control (HC) eyes on a pixel-by-pixel basis.

For this retrospective study, we manually corrected the segmentations of posterior pole optical coherence tomography (OCT) scans to determine the thickness of the nerve fiber layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL), the ganglion cell complex (GCC), and the total neural retina (TR). For each eye, the total number of pixels with thickness values less than the fifth percentile of the HC distribution was used to create a receiver operating characteristic (ROC) curve for each layer and for layer combinations.

Using total abnormal pixel count criteria to discriminate glaucoma from HC eyes, the individual layers with the highest area under the ROC curve (AUC) were the NFL and GCL; IPL performance was significantly lower (P < 0.05). GCC had a significant higher AUC (94.3%) than individual the AUC of the NFL (92.3%) (P = 0.0231) but not higher than AUC of the GCL (93.4%) (P = 0.3487). The highest AUC (95.4%) and sensitivity (85.1%) at 95% specificity was found for the Boolean combination of NFL or GCL. The highest AUC is not significantly higher (P = 0.0882) than the AUC of the GCC but the highest sensitivity is significantly higher than the sensitivity of the GCC. This pattern was similar for discriminating between suspect and HC eyes (P = 0.0356).

Using pixel-based methods, the diagnostic accuracy of NFL and GCL exceeded that of IPL and TR. GCC had equivalent performance as NFL and GCL. The specific spatial locations within the posterior pole that exhibit best performance vary depending on which layer is being assessed. Recognizing this dependency highlights the importance of considering multiple layers independently, as they offer complementary information for effective and comprehensive diagnosis.

Glaucoma is a leading cause of irreversible blindness worldwide, with its pathophysiology remaining inadequately understood. Among the various proposed theories, the vascular theory, suggesting a crucial role of retinal vasculature deterioration in glaucoma onset and progression, has gained significant attention. Traditional imaging techniques, such as fundus fluorescein angiography, are limited by their invasive nature, time consumption, and qualitative output, which restrict their efficacy in detailed retinal vessel examination. Optical coherence tomography angiography (OCTA) emerges as a revolutionary imaging modality, offering non-invasive, detailed visualization of the retinal and optic nerve head microvasculature, thereby marking a significant advancement in glaucoma diagnostics and management. Since its introduction, OCTA has been extensively utilized for retinal vasculature imaging, underscoring its potential to enhance our understanding of glaucoma's pathophysiology, improving diagnosis, and monitoring disease progression. This review aims to summarize the current knowledge regarding the role of OCTA in glaucoma, particularly its potential applications in diagnosing, monitoring, and understanding the pathophysiology of the disease. Parameters pertinent to glaucoma will be elucidated to illustrate the utility of OCTA as a tool to guide glaucoma management.

Schizophrenia (SZ) and bipolar disorder (BD) are characterized by major symptomatic, cognitive, and neuroanatomical changes. Recent studies have used optical coherence tomography (OCT) to investigate retinal changes in SZ and BD, but their unique and shared changes require further evaluation. Articles were identified using PubMed and Google Scholar. 39 studies met the inclusion criteria. Diagnostic groups were proband (SZ/BD combined), SZ, BD, and healthy control (HC) eyes. Meta-analyses utilized fixed and random effects models when appropriate, and publication bias was corrected using trim-and-fill analysis ("meta" package in R). Results are reported as standardized mean differences with 95% CIs. Data from 3145 patient eyes (1956 SZ, 1189 BD) and 3135 HC eyes were included. Studies identified thinning of the peripapillary retinal nerve fiber layer (pRNFL, overall and in 2 subregions), m-Retina (overall and all subregions), mGCL-IPL, mIPL, and mRPE in SZ patients. BD showed thinning of the pRNFL (overall and in each subregion), pGCC, and macular Retina (in 5 subregions), but no changes in thickness or volume for the total retina. Neither SZ nor BD patients demonstrated significant changes in the fovea, mRNFL, mGCL, mGCC, mINL, mOPL, mONL, or choroid thicknesses. Moderating effects of age, illness duration, and smoking on retinal structures were identified. This meta-analysis builds upon previous literature in this field by incorporating recent OCT studies and examining both peripapillary and macular retinal regions with respect to psychotic disorders. Overall, this meta-analysis demonstrated both peripapillary and macular structural retinal abnormalities in people with SZ or BD compared with HCs.

The study aimed to correlate macular ganglion cell layer + inner plexiform layer (GCL + IPL) thickness and circumpapillary retinal nerve fiber layer (cRNFL) thickness and to determine the validity of GCL + IPL in the evaluation of glaucoma across different stages using the area under the curve (AUC) analysis in comparison to cRNFL.

The charts of 260 adult glaucoma suspect and glaucoma patients having macular ganglion cell analysis, optical coherence tomography (OCT) of the cRNFL and automated visual field (AVF) were reviewed. GCL + IPL thickness (average, minimum and sectoral) and sectoral cRNFL thickness were obtained. Glaucomatous eyes were further classified into stages based on the Hodapp-Anderson-Parrish Visual Field Criteria of Glaucoma Severity. AUC analysis was used to compare GCL + IPL parameters with cRNFL in glaucoma suspects and glaucoma patients.

A total of 122 eyes were included in the study and were grouped into glaucoma suspects (n = 43), early or mild glaucoma (n = 40), and moderate-to-severe glaucoma (n = 39). Both GCL + IPL and cRNFL thickness parameters showed a significant decline with greater glaucoma severity. In the determination of visual field defects across all glaucoma stages, the highest AUC was obtained by minimum GCL + IPL (AUC = 0.859) with cut-off value at ≤70 µm. Average GCL + IPL had the highest AUC (0.835) in detecting progression from glaucoma suspect to mild glaucoma, while the inferior sector of the cRNFL had the highest AUC (0.937) in discerning mild from moderate-to-severe glaucoma.

The results of this study highlight the significance of macular ganglion cell analysis in the screening, detection and staging of glaucoma. Compared to cRNFL, macular ganglion analysis may be more beneficial in glaucoma screening and detecting progression from glaucoma suspect to mild glaucoma.

Using optical coherence tomography (OCT), eyes with advanced glaucoma were found to have a wide range of patterns of damage that were consistent with the natural history of progression based on a model of macular progression.

To understand the patterns of preserved retinal ganglion cells in eyes with advanced glaucoma using OCT and a model of progression of the central macula.

OCT GCL thickness was measured in 94 eyes with advanced glaucoma, defined as glaucomatous eyes with a 24-2 MD (mean deviation) worse than -12 dB. A commercial report supplied the GCL thickness in 6 sectors of the thick, donut-shaped GCL region around the fovea. For each eye, the 6 sectors were coded as green (within normal limits, WNL), yellow (≤5th, ≥1st percentile), or red (<1st percentile).

In all 94 eyes, one or more of the 6 sectors of the donut were abnormal (red or yellow), while all 6 sectors were red in 52 (55%) of the eyes. On the other hand, 33 eyes had one or more sectors WNL (green). While the pattern of donut damage varied widely across these 33 eyes, 61 of the 66 hemiretinas were consistent with a temporal-to-nasal progression of damage within each hemiretina as predicted by our model.

All eyes with advanced glaucoma had damage to the critically important central, donut-shaped GCL region. This region showed a wide range of patterns of damage, but these patterns were consistent with the natural history of progression based on a model of macular progression. These results have implications for the clinical identification of macular progression, as well as for inclusion criteria for clinical trials seeking to preserve central macular function.

An understanding of factors that affect the foveal avascular zone (FAZ) in healthy eyes may aid in the early identification of patients at risk of retinal pathology, thereby allowing better management and preventive measures to be implemented.

The size and shape of the FAZ can change due to retinal diseases associated with oxidative stress, including diabetic retinopathy, glaucoma, and macular degeneration. This study aimed to assess the relationship, if any, between factors that may affect the superficial FAZ (i.e., vessel density, vessel perfusion, overweight/obesity) and possible links with macular pigment optical density in young, healthy participants.

One hundred thirty-nine participants aged 18 to 35 years were recruited to this cross-sectional study. The superficial FAZ area, foveal vascularity, and central macular thickness (CMT) were assessed using the Cirrus 5000. Health parameters, body mass index, trunk fat %, and macular pigment were analyzed to determine possible associations with the superficial FAZ.

Mean FAZ area was 0.23 ± 0.08 mm2. Females had a significantly larger mean FAZ area than males (p=0.002). The FAZ area was positively correlated with body mass index (Pearson's r = 0.189, p=0.026). Significant correlates of the FAZ area in the multivariate model included vessel perfusion (central), CMT, and trunk fat %, collectively explaining 65.1% of the overall variability.

Study findings suggest that reduced vessel perfusion, thinner CMT, and higher trunk fat % are plausible predictors of a larger FAZ area in healthy Caucasian adults. Low macular pigment optical density was, however, not associated with increased FAZ size in young healthy eyes. Noninvasive optical coherence tomography angiography testing, in association with these predictors, may aid in the early detection and monitoring of retinal diseases associated with oxidative stress.

To objectively classify eyes as either healthy or glaucoma based exclusively on data provided by peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform (GCIPL) measurements derived from spectral-domain optical coherence tomography (SD-OCT) using machine learning algorithms.

Three clustering methods (k-means, hierarchical cluster analysis -HCA- and model-based clustering-MBC-) were used separately to classify a training sample of 109 eyes as either healthy or glaucomatous using solely 13 SD-OCT parameters: pRNFL average and sector thicknesses and GCIPL average and minimum values together with the six macular wedge-shaped regions. Then, the best-performing algorithm was applied to an independent test sample of 102 eyes to derive close estimates of its actual performance (external validation).

In the training sample, accuracy was 91.7% for MBC, 81.7% for k-means and 78.9% for HCA (p value = 0.02). The best MBC model was that in which subgroups were allowed to have variable volume and shape and equal orientation. The MBC algorithm in the independent test sample correctly classified 98 out of 102 cases for an overall accuracy of 96.1% (95% CI, 92.3-99.8%), with a sensitivity of 94.3 and 100% specificity. The accuracy for pRNFL was 92.2% (95% CI, 86.9-97.4%) and for GCIPL 98.0% (95% CI, 95.3-100%).

Clustering algorithms in general (and MBC in particular) seem promising methods to help discriminate between healthy and glaucomatous eyes using exclusively SD-OCT-derived parameters. Understanding the relative merits of one method over others may also provide insights into the nature of the disease.

Primary open angle glaucoma and pseudoexfoliation glaucoma showed different progression patterns of the retinal nerve fiber layer and ganglion cell-inner plexiform layer thinning in OCT-guided progression analysis.

To compare the patterns of progression of retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thinning by guided progression analysis (GPA) of optical coherence tomography (OCT) in primary open angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG).

The progression of RNFL and GCIPL thinning was assessed by the GPA of Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA). By overlaying the acquired images of the RNFL and GCIPL thickness-change maps, the topographic patterns of progressive RNFL and GCIPL thinning were evaluated. The rates of progression of RNFL and GCIPL thinning were analyzed and compared between patients with POAG and those with PXG.

Of the 248 eyes of 248 patients with POAG (175 eyes of 175 patients) or PXG (73 eyes of 73 patients) enrolled, 156 POAG eyes and 48 PXG eyes were included. Progressive RNFL thinning was significantly more common in PXG than in POAG ( P =0.005). According to the RNFL progression-frequency maps, progression appeared mainly in the superotemporal and inferotemporal areas in POAG, whereas it had invaded more into the temporal area in PXG. According to the GCIPL maps, progression was most common in the inferotemporal area in both POAG and PXG. The average progression rate of GCIPL thinning was faster in PXG than in POAG ( P =0.013), and when analyzed in 2 halves (superior/inferior), the progression rate of the inferior half was faster in PXG than in POAG ( P =0.011).

OCT GPA showed progression patterns of RNFL and GCIPL thinning in POAG and PXG. Understanding the specific patterns of progressive RNFL and GCIPL thinning according to glaucoma type may prove helpful to glaucoma-patient treatment and monitoring.

Evaluation of ganglion cell-inner plexiform layer thickness in the diagnosis of pre-perimetric glaucoma (PPG) and comparison to retinal nerve fiber layers.

This study was a prospective hospital-based study. A total of 30 PPG and control patients were studied for retinal nerve fiber layer thickness (RNFL) and ganglion cell-inner plexiform layer complex (GC-IPL) by spectral-domain optical coherence tomography. PPG was defined as eyes with a normal visual field and one or more localized RNFL defects that were associated with a typical glaucomatous disc appearance. Diagnostic abilities of GC-IPL, optic nerve head (ONH), and RNFL parameters were computed using area under receiver-operating curve (AUROC), sensitivity, and specificity.

GC-IPL parameters showed significant changes in PPG cases as compared to normal subjects in each region ( P value < 0.001). RNFL parameters also differed significantly from normal subjects in all quadrants ( P value 0.003 to < 0.001). Within GC-IPL parameters, the superotemporal region had the maximum area under the curve (AUC), followed by inferior, superior, and inferotemporal regions. Within RNFL parameters, the inferior quadrant had the maximum AUC, followed by superior and nasal quadrants. the GC-IPL parameters in PPG showed that the AUC of the GC-IPL parameters was much higher than those of the ONH and RNFL values.

Although both the parameters RNFL and GC-IPL showed significant changes in PPG patients compared to healthy subjects, a higher AUC of GC-IPL points toward the higher sensitivity of GC-IPL than RNFL for detecting glaucoma in early stages.

To evaluate and correlate the structural changes between peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell layer (GCL) + inner plexiform layer (IPL) in different stages of glaucoma using PanoMap ® optical coherence tomography (OCT).

Retrospective observational study.

Glaucoma diagnostic test data were collected from early to moderate open-angle glaucoma patients. The average and minimum GCL + IPL thickness, sectoral GCL + IPL thickness, and the average and sectoral RNFL thickness were correlated with the different glaucoma stages.

This study included 157 eyes from 157 glaucoma patients. Patients were grouped into pre-perimetric, early, and moderate glaucoma. The mean average RNFL thickness, RNFL thickness per sector, average GCL + IPL thickness, and minimum GCL + IPL thickness were different between the three groups ( P < 0.001), except for the nasal sector ( P = 0.643). The mean GCL + IPL thickness in all six sectors showed differences between the groups ( P < 0.001), except the superonasal sector ( P < 0.002). The inferior GCL + IPL sector is the thinnest, followed by the inferotemporal sector. There was a strong correlation between the mean average RNFL and the average GCL + IPL thickness in the pre-perimetric group ( r = 0.4963, P < 0.001) and the moderate group ( r = 0.6534, P < 0.001). The early glaucoma group did not show significant correlation ( r = 0.2963, P = 0.0536).

Peripapillary RNFL and macular GCL + IPL thinning was evident in different stages of glaucoma, with more thinning observed with increasing glaucoma severity. The peripapillary RNFL and macular GCL + IPL average thickness values were highly correlated in the pre-perimetric and moderate stages of glaucoma.

Background: A relationship between glaucoma and epiretinal membrane (ERM) has been suggested previously. We investigated the association between intraocular pressure (IOP) fluctuation and idiopathic ERM in patients with glaucoma or glaucoma suspect. Methods: Among patients with glaucoma or glaucoma suspect, data from 43 patients with ERM and 41 patients without ERM were reviewed and analyzed in this retrospective study. The long-term fluctuation of IOP was defined based on the standard deviation of IOP across all visits. Results: Patients with ERM were older and had a higher SD of IOP and a higher proportion of having a history of cataract surgery and greater macular thickness (p = 0.018, 0.049, 0.013, and <0.001, respectively). In multiple logistic regression analysis, the high-IOP-fluctuation group was associated with the presence of ERM (p = 0.047). Among patients with ERM, eyes with stage-3 or -4 ERM had worse visual field defects based on mean deviation than those with stage-1 or -2 ERM (p = 0.025). Conclusions: Long-term IOP fluctuation was associated with idiopathic ERM in patients with glaucoma or glaucoma suspect. Idiopathic ERM could serve as a biomarker for long-term IOP fluctuation in glaucoma patients, particularly in clinics where measuring long-term IOP fluctuation during the first visit is not feasible due to its time-consuming nature.

Background: The goal was to evaluate the diagnostic capability of different parameters obtained with the posterior pole (PP) software in Spectralis SD-OCT with the 8 × 8 grid tilted at 7° and horizontalized in glaucomatous eyes. Methods: A total of 299 eyes were included, comprising 136 healthy eyes and 163 with primary open-angle glaucoma (POAG). The following segmentations were evaluated: complete retina, retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), GCL and inner plexiform layer (GCLIPL), ganglion cell complex (GCC), outer plexiform layer and outer nuclear layer (OPLONL), inner retinal layer (IRL), and outer retinal layer (ORL). Different patterns of macular damage were represented using heatmaps for each studied layer, where the areas under the curve (AUROC) values and a retinal thickness cutoff point were defined to discriminate POAG patients. Results: There was not any difference in the diagnostic capability for detecting glaucoma between the grid tilted at 7° and horizontalized. The macular segmentations that offer the highest diagnostic ability in glaucoma discrimination were, in the following order, RNFL (AUROC = 0.796), GCC (AUROC = 0.785), GCL (AUROC = 0.784), GCLIPL (AUROC = 0.770), IRL (AUROC = 0.755), and the complete retina (AUROC = 0.752). In contrast, ORL and OPLONL do not appear to be helpful for discriminating POAG. Conclusions: Some results of PP software may be useful for discriminating POAG.

We aimed to characterize and compare the occurrence of peripapillary microvasculature dropout (MvD) between glaucoma suspects and patients with glaucoma. In addition, the factors related to the development of parapapillary MvD in glaucoma suspects and patients with glaucoma were investigated. Of a total 150 eyes, 68 eyes of glaucoma suspects and 82 eyes of glaucoma patients were analyzed in this study. Univariate and multivariate logistic regression analyses were used to identify factors associated with MvD development. The classification of glaucoma patients or glaucoma suspects was not significantly associated with MvD development (beta 1.368, 95% CI, 0.718-2.608, p = 0.341). In the regression analysis of the glaucoma suspect group, greater axial length (beta 1.520, 95% CI, 1.008-2.291, p = 0.046) and baseline cup volume (beta 3.993, 95% CI, 1.292-12.345, p = 0.035) among the baseline factors and the slope of ganglion cell-inner plexiform layer (GCIPL) thickness (beta 0.027, 95% CI, 0.072-0.851, p = 0.027) and central visual field (VF) progression (beta 7.040, 95% CI, 1.781-16.306, p = 0.014) among follow-up factors were significantly associated with MvD development. In the glaucoma group, central VF progression (beta 5.985, 95% CI, 1.474-24.083, p = 0.012) and ONH depression (beta 3.765, 95% CI, 1.301-10.895, p = 0.014) among follow-up elements were observed as significant factors and the baseline factor had little relationship. MvD appears not only as a result of the progression of axonal loss of RGC in glaucoma but may also be developed due to structural changes and mechanical susceptibility of the ONH associated with baseline characteristics. Analyzing the structural susceptibility of the ONH can predict the occurrence of MvD, which can be helpful in predicting the progression of glaucoma.

Oxygen saturation (sO2) plays a critical role in retinal pathophysiology, especially at the macula, which undergoes significant energy consumption. While macular damage has been suggested to be involved in early-stage glaucoma, there has been no report to date on non-invasive macular sO2 in glaucoma. Therefore, we conducted this study to compare macular sO2 associated with other clinical measurements between normal and glaucoma subjects and evaluate whether there are significant differences.

This is a cross-sectional study. We used visible light optical coherence tomography (VIS-OCT) for retinal oximetry in perifoveal vessels. The subjects from groups of normal, suspect/pre-perimetric glaucoma (GS/PPG) and perimetric glaucoma (PG) were scanned using VIS-OCT in the macular region with a sampling density of 512×256 in an area of 5×5 mm2. 48 eyes (16 normal, 17 GS/PPG and 15 PG) were included for the analysis. For each eye, we measured the sO2 of arterioles (AsO2), venules (VsO2), and calculated the difference between arterioles and venules (A-V sO2=AsO2-VsO2), oxygen extraction (OE=(AsO2-VsO2)/AsO2 ×100%). Additionally, we included Zeiss Cirrus OCT scans and 24-2 visual field test (VFT) for clinical benchmark. One-way ANOVA was used to compare the differences among the three groups. Spearman correlation tests were used for correlation sO2 markers to standard metrics including the thickness of ganglion cell layer and inner plexiform layer (GCL+IPL), circumpapillary retinal nerve fiber layer (cpRNFL) and mean deviation (MD) in VFT.

Significant differences were found among three groups for all VIS-OCT, Zeiss OCT, and VFT variables. Macular AsO2, A-V sO2, OE decreased, and VsO2 increased along with severity. Macular AsO2 and A-V sO2 were statistically correlated with GCL+IPL and cpRNFL in all eyes, as well as only PG eyes. Within PG eyes, the correlation between AsO2 and GCL+IPL is dominant in more damaged lower hemifield.

The GS/PPG and PG subjects had significantly higher macular VsO2, lower A-V sO2 and OE indicating less oxygen consumption. The sO2 measured by retinal oximetry of VIS-OCT can be a potential metric for the early diagnosis of glaucoma.

The central macula contains a thick donut shaped region of the ganglion cell layer (GCL) that surrounds the fovea. This region, which is about 12 degrees (3.5 mm) in diameter, is essential for everyday functions such as driving, reading, and face recognition. Here, we describe a model of progression of glaucomatous damage to this GCL donut. This model is based upon assumptions supported by the literature, and it predicts the patterns of glaucomatous damage to the GCL donut, as seen with optical coherence tomography (OCT). After describing the assumptions and predictions of this model, we test the model against data from our laboratory, as well as from the literature. Finally, three uses of the model are illustrated. One, it provides an aid to help clinicians focus on the essential central macula and to alert them to look for other, non-glaucomatous causes, when the GCL damage does not fit the pattern predicted by the model. Second, the patterns of progression predicted by the model suggest alternative end points for clinical trials. Finally, the model provides a heuristic for future research concerning the anatomic basis of glaucomatous damage.

To identify the spatial relationship between disc haemorrhage (DH) on the fovea-disc axis and retinal nerve fibre layer (RNFL) defect in the papillomacular bundle (PMB) using ancillary PanoMap optical coherence tomography (OCT).

We investigated the presence and progression of spatially corresponding PMB defects in glaucomatous eyes with temporally located DH on the fovea-disc axis (FoDi-DH). We identified PMB defects using ancillary PanoMap OCT with guided progression analysis, in addition to red-free photographs.

We studied 36 eyes of 35 glaucoma patients with FoDi-DH, pre-existing PMB defects were observed in 18 eyes (50.0%) at the time and location of the initial FoDi-DH occurrence, 14 (38.9%) of which progressed during the follow-up period. New development of PMB defects occurred in 15 (41.7%) of 18 eyes without pre-existing PMB defects. Overall, FoDi-DH was associated with PMB defects in 33 (91.7%) eyes at locations spatially overlapping the PMB defect. Red-free photography and OCT were complementary in detecting PMB defects and progression. Among 47 cases, 20 were concordant, while 10 and 17 were detected only in photography and OCT, respectively. The central visual field defect increased significantly throughout the follow-up period (p=0.006).

Most FoDi-DH cases were related to the presence and progression of glaucomatous PMB defects at locations spatially overlapping the defect. OCT helped clarify changes in PMB defects detected by red-free photograph and the detection of photo-negative PMB defects as well. Similar to inferotemporal and superotemporal-direction DH, temporal DH on the PMB may be an indicator of ongoing RNFL damage that deserves close attention.

To analyse retinal nerve fibre layer (RNFL) defect measurements obtained from red-free fundus photography and optical coherence tomography (OCT) en face imaging, respectively, and to compare them for the strength of the structure-function association.

Two hundred and fifty-six glaucomatous eyes of 256 patients with localized RNFL defect on red-free fundus photography were enrolled. A subgroup analysis included 81 highly myopic eyes (≤ -6.0 dioptres). Angular width of RNFL defect was compared between red-free fundus photography (i.e., red-free RNFL defect) and OCT en face imaging (i.e., en face RNFL defect). The correlation between angular width of each RNFL defect and functional outcomes, reported as mean deviation (MD) and pattern standard deviation (PSD), were assessed and compared.

The angular width of en face RNFL defect was measured smaller than that of red-free RNFL defect in 91.0% eyes (mean difference, 19.98°). The association of en face RNFL defect with MD and PSD was stronger (R2 = 0.311 and R2 = 0.372, respectively) than that of red-free RNFL defect with MD and PSD (R2 = 0.162 and R2 = 0.137, respectively) (P < 0.05 for all). Especially in highly myopic eyes, the association of en face RNFL defect with MD and PSD was much stronger (R2 = 0.503 and R2 = 0.555, respectively) than that of red-free RNFL defect with MD and PSD (R2 = 0.216 and R2 = 0.166, respectively) (P < 0.05 for all).

En face RNFL defect showed a higher correlation with severity of visual field loss than did red-free RNFL defect. The same dynamic was observed for highly myopic eyes.

This study aimed to compare the thickness of different macular retinal layers in glaucomatous eyes and healthy controls, and evaluate the diagnostic performance of spectral domain optical coherence tomography (SD-OCT) parameters.

In this cross-sectional comparative study, 48 glaucomatous eyes and 44 healthy controls were included. The thickness of the total retina and all retinal layers were obtained using the Early Treatment Diagnostic Retinopathy Study (ETDRS) grid. The minimal and average values of outer and inner ETDRS-rings were calculated. The diagnostic performance for detection of glaucoma was evaluated using the area under the receiver operating characteristic curve (AUC).

The thickness of the total retina, ganglion cell layer (GCL), and inner-plexiform layer (IPL) was significantly thinner in glaucomatous eyes in all sectors except the center (all p<0.05). The thickness of retinal nerve fiber layer (RNFL) was significantly thinner in the glaucoma group except in the center, nasal inner, and temporal outer sectors (all p<0.05). Layer thinning advanced with glaucoma severity. The minimal outer GCL thickness showed the highest AUC value for discrimination between glaucomatous eyes and healthy controls(0.955). The minimal outer IPL showed the highest AUC value for discriminating early-stage glaucomatous eyes from healthy controls (0.938).

Glaucomatous eyes were found to have significant thinning in the macular region. GCL and IPL showed high ability to discriminate glaucomatous and early-stage glaucomatous eyes from controls. Applying the minimal value to the ETDRS grid has the potential to provide good diagnostic abilities in glaucoma screening.

Early diagnosis and detection of disease progression are critical to successful therapeutic intervention in glaucoma, the leading cause of irreversible blindness worldwide. Optical coherence tomography (OCT) is a non-invasive imaging technique that allows objective quantification in vivo of key glaucomatous structural changes in the retina and the optic nerve head (ONH). Advances in OCT technology have increased the scan speed and enhanced image quality, contributing to early glaucoma diagnosis and monitoring, as well as the visualization of critically important structures deep within the ONH, such as the lamina cribrosa. OCT angiography (OCTA) is a dye-free technique for noninvasively assessing ocular microvasculature, including capillaries within each plexus serving the macula, peripapillary retina and ONH regions, as well as the deeper vessels of the choroid. This layer-specific assessment of the microvasculature has provided evidence that retinal and choroidal vascular impairments can occur during early stages of glaucoma, suggesting that OCTA-derived measurements could be used as biomarkers for enhancing detection of glaucoma and its progression, as well as to reveal novel insights about pathophysiology. Moreover, these innovations have demonstrated that damage to the macula, a critical region for the vision-related quality of life, can be observed in the early stages of glaucomatous eyes, leading to a paradigm shift in glaucoma monitoring. Other advances in software and hardware, such as artificial intelligence-based algorithms, adaptive optics, and visible-light OCT, may further benefit clinical management of glaucoma in the future. This article reviews the utility of OCT and OCTA for glaucoma diagnosis and disease progression detection, emphasizes the importance of detecting macula damage in glaucoma, and highlights the future perspective of OCT and OCTA. We conclude that the OCT and OCTA are essential glaucoma detection and monitoring tools, leading to clinical and economic benefits for patients and society.

To evaluate the early changes in ganglion cell-inner plexiform layer thickness and macular microvasculature in Posner-Schlossman syndrome (PSS) with a binocular control study involving optical coherence tomography angiography (OCTA). Twenty-six patients with unilateral PSS were included in this cross-sectional study. All subjects underwent a thorough ocular examination. Macular ganglion cell-inner plexiform layer (mGCIPL) and superficial macular microvasculature measurements, including vessel density (VD), perfusion density (PD) and the foveal avascular zone (FAZ), were recorded. In PSS-affected eyes, the mGCIPL thickness was significantly lower in all quadrants than in the contralateral eyes (all p < 0.05). Significant macular microvascular damage was found in the PSS-affected eyes, including whole-image VD (wiVD), wiPD, perifoveal VD (periVD) and periPD (all p < 0.05); but there was no obvious difference in parafoveal VD (paraVD), paraPD and FAZ parameters (all p > 0.05). In addition, a decreased wiVD and wiPD were significantly correlated with a smaller mGCIPL thickness and a decreased MD (all p < 0.05). These parameters may contribute to the early detection of glaucomatous damage and timely supervision of disease progression in PSS.

In a cross-sectional study from a Brazilian multiracial population, minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness measurements from OCT showed comparable diagnostic performance in discriminating early to moderate glaucoma from healthy eyes.

The purpose of this study is to compare the ability of MRW and peripapillary retinal nerve fiber layer thickness (RNFLT) measurements in discriminating early to moderate glaucoma from healthy eyes in a Brazilian population.

A total of 155 healthy controls and 118 patients with mild to moderate glaucoma (mean deviation >-12 dB) underwent MRW and RNFLT measurements with optical coherence tomography. Only 1 eye per patient was included in the analysis. A receiver operating characteristic (ROC) regression model was used to evaluate the diagnostic accuracy of MRW and RNFLT, whereas adjusting for age and Bruch membrane opening area. Sensitivities at fixed specificities of 95% were calculated for each parameter.

Global RNFLT and MRW showed comparable area under the ROC curves [0.93 (0.91-0.96) and 0.93 (0.89-0.96), respectively; P =0.973]. Both parameters had similar sensitivities (75% vs. 74%, respectively; P =0.852) at a fixed specificity of 95%. The best sector for diagnosing glaucoma for both parameters was the temporal inferior sector, which showed an area under the ROC curve of 0.93 (0.87-0.96) for RNFLT and 0.91 (0.86-0.95) for MRW ( P =0.320). The temporal inferior sector showed similar sensitivities for RNFLT and MRW measurements (83% vs. 77%, respectively) at a fixed specificity of 95% (P =0.230).

MRW and RNFLT measurements showed comparable diagnostic performance in discriminating early to moderate glaucoma from healthy eyes in a Brazilian multiracial population.

Identifying the clinical relevance of superficial versus deep layer macular vessel density (mVD) in glaucoma is important for monitoring glaucoma patients. Our current retrospective longitudinal study investigated the association of superficial and deep layer mVD parameters with glaucomatous visual field (VF) progression in mild to moderate open-angle glaucoma (OAG) eyes with central visual field (CVF) damage. Serial optical coherence tomography (OCT) angiography-derived mVD measurements were obtained in 182 mild to moderate OAG eyes (mean deviation ≥ -10 decibels). Forty-eight eyes (26.4%) showed VF progression during a mean follow-up of 3.5 years. The parafoveal and perifoveal mVDs of both superficial and deep layers showed significantly faster reduction rates in the VF progressors than in the non-progressors according to linear mixed effects models (P < 0.05). Cox and linear regression analyses showed that greater reduction rates of both the superficial layer parafoveal and perifoveal mVDs, but not their deep layer counterparts, were significant predictors of VF progression and faster VF loss (P < 0.05). In conclusion, faster rates of change in superficial but not deep layer mVD parameters are significantly associated with subsequent VF progression and faster VF deterioration in mild to moderate OAG eyes with CVF damage.

To investigate early changes in the intraocular pressure (IOP) and macular microvascular structure in eyes with branch retinal vein occlusion (BRVO) treated with intravitreal Ranibizumab injection.

This study enrolled 30 patients (one eye per patient) who received intravitreal injections (IVI) of ranibizumab for macular edema secondary to BRVO. IOP were measured before, 30 min (min) and 1 month following IVI. Changes in macular microvascular structure were examined via assessment of foveal avascular zone (FAZ) parameters, vascular density (VD) of superficial vascular complex (SVC), and deep vascular complex (DVC) in whole macula, central fovea and parafovea area which were measured automatically by optical coherence tomography angiography (OCTA) on the same time as IOP examinations. Paired t test and Wilcoxon test were used to compare pre- and post-injection values. The correlation between IOP and OCTA findings was assessed.

IOP Measurements at 30 min post-IVI (17.91 ± 3.36 mmHg) increased significantly from baseline (15.07 ± 2.58 mmHg, p < 0.001), then became similar with baseline after 1 month (15.00 ± 3.16 mmHg, p = 0.925). 30 min past the injection, the parameters of VD of the SCP significantly decreased in comparison to baseline, then became similar with baseline after one month, while there were no significant changes in other OCTA parameters, including parameters of VD of the DCP and the FAZ. At 1 month after IVI, in comparison to baseline, no significant changes were observed in all of the OCTA parameters (P > 0.05). There were no significant correlations between IOP and OCTA findings no matter 30 min or 1 month post-IVI (P > 0.05).

Transient IOP elevation and decreased superficial macular capillary perfusion density were detected 30 min post-IVI, however, no potential continual macular microvascular damage was suspected.

In eyes with suspected glaucoma, it is clinically relevant to find diagnostic tests for the risk of development of perimetric glaucoma.

To investigate the association between rates of ganglion cell/inner plexiform layer (GCIPL) and circumpapillary retinal nerve fiber layer (cpRNFL) thinning and the development of perimetric glaucoma in eyes with suspected glaucoma.

This observational cohort study used data collected in December 2021 from a tertiary center study and a multicenter study. Participants with suspected glaucoma were followed up for 3.1 years. The study was designed in December 2021 and finalized in August 2022.

Development of perimetric glaucoma was defined as having 3 consecutive results showing abnormal visual fields. Using linear mixed-effect models, rates of GCIPL were compared between eyes with suspected glaucoma that did and did not develop perimetric glaucoma. A joint longitudinal multivariable survival model was used to investigate the performance of rates of GCIPL and cpRNFL thinning in predicting the risk of developing perimetric glaucoma.

Rates of GCIPL thinning and hazard ratio (HR) of developing perimetric glaucoma.

Among a total of 462 participants, the mean (SD) age was 63.3 (11.1) years, and 275 patients (60%) were female. Of 658 eyes, 153 eyes (23%) developed perimetric glaucoma. The mean rates of GCIPL thinning were faster in eyes that developed perimetric glaucoma (-1.28 vs -0.66 μm/y for minimum GCIPL thinning; difference, -0.62; 95% CI, -1.07 to -0.16; P = .02). Based on the joint longitudinal survival model, every 1-μm/y faster rate of minimum GCIPL and rate of global cpRNFL thinning were associated with a 2.4 and 1.9 higher risk of developing perimetric glaucoma, respectively (HR, 2.4; 95% CI, 1.8 to 3.2, and HR, 1.99; 95% CI, 1.76 to 2.22, respectively; P < .001). Among the predictive factors, African American race (HR, 1.56; 95% CI, 1.05 to 2.34; P = .02), male sex (HR, 1.47; 95% CI, 1.02 to 2.15; P = .03), 1-dB higher baseline visual field pattern standard deviation (HR, 1.73; 95% CI, 1.56 to 1.91; P < .001), and 1-mm Hg higher mean intraocular pressure during follow-up (HR, 1.11; 95% CI, 1.05 to 1.17; P < .001) were associated with higher risk of developing perimetric glaucoma.

This study found that faster rates of GCIPL and cpRNFL thinning were associated with higher risks of developing perimetric glaucoma. Rates of cpRNFL thinning and specifically GCIPL thinning may be useful measures for monitoring eyes with suspected glaucoma.

(1) To assess the performance of geometric deep learning in diagnosing glaucoma from a single optical coherence tomography (OCT) scan of the optic nerve head and (2) to compare its performance to that obtained with a three-dimensional (3D) convolutional neural network (CNN), and with a gold-standard parameter, namely, the retinal nerve fiber layer (RNFL) thickness.

Scans of the optic nerve head were acquired with OCT for 477 glaucoma and 2296 nonglaucoma subjects. All volumes were automatically segmented using deep learning to identify seven major neural and connective tissues. Each optic nerve head was then represented as a 3D point cloud with approximately 1000 points. Geometric deep learning (PointNet) was then used to provide a glaucoma diagnosis from a single 3D point cloud. The performance of our approach (reported using the area under the curve [AUC]) was compared with that obtained with a 3D CNN, and with the RNFL thickness.

PointNet was able to provide a robust glaucoma diagnosis solely from a 3D point cloud (AUC = 0.95 ± 0.01).The performance of PointNet was superior to that obtained with a 3D CNN (AUC = 0.87 ± 0.02 [raw OCT images] and 0.91 ± 0.02 [segmented OCT images]) and with that obtained from RNFL thickness alone (AUC = 0.80 ± 0.03).

We provide a proof of principle for the application of geometric deep learning in glaucoma. Our technique requires significantly less information as input to perform better than a 3D CNN, and with an AUC superior to that obtained from RNFL thickness.

Geometric deep learning may help us to improve and simplify diagnosis and prognosis applications in glaucoma.

To compare the performance of 2 relatively recent geometric deep learning techniques in diagnosing glaucoma from a single optical coherence tomographic (OCT) scan of the optic nerve head (ONH); and to identify the 3-dimensional (3D) structural features of the ONH that are critical for the diagnosis of glaucoma.

Comparison and evaluation of deep learning diagnostic algorithms.

In this study, we included a total of 2247 nonglaucoma and 2259 glaucoma scans from 1725 participants. All participants had their ONHs imaged in 3D with Spectralis OCT. All OCT scans were automatically segmented using deep learning to identify major neural and connective tissues. Each ONH was then represented as a 3D point cloud. We used PointNet and dynamic graph convolutional neural network (DGCNN) to diagnose glaucoma from such 3D ONH point clouds and to identify the critical 3D structural features of the ONH for glaucoma diagnosis.

Both the DGCNN (area under the curve [AUC]: 0.97±0.01) and PointNet (AUC: 0.95±0.02) were able to accurately detect glaucoma from 3D ONH point clouds. The critical points (ie, critical structural features of the ONH) formed an hourglass pattern, with most of them located within the neuroretinal rim in the inferior and superior quadrant of the ONH.

The diagnostic accuracy of both geometric deep learning approaches was excellent. Moreover, we were able to identify the critical 3D structural features of the ONH for glaucoma diagnosis that tremendously improved the transparency and interpretability of our method. Consequently, our approach may have strong potential to be used in clinical applications for the diagnosis and prognosis of a wide range of ophthalmic disorders.

To test the hypothesis that macular ganglion cell layer (GCL) measurements detect early glaucoma with higher accuracy than ganglion cell/inner plexiform layer (GCIPL) thickness measurements.

Cross-sectional study.

The first cohort included 58 glaucomatous eyes with visual field mean deviation (MD) ≥ -6 dB and 125 normal eyes. The second cohort included 72 glaucomatous and 73 normal/glaucoma suspect (GS) eyes with scans able to create GCL/GCIPL deviation maps.

In the first cohort, 8 × 8 GCL and GCIPL grids were exported and 5 superior and inferior sectors were defined. Global and sectoral GCL and GCIPL measures were used to predict glaucoma. In the second cohort, proportions of scan areas with abnormal (< 5% and < 1% cutoffs) and supernormal (> 95% and > 99% cutoffs) thicknesses on deviation maps were calculated. The extents of GCL and GCIPL abnormal areas were used to predict glaucoma.

Extents of abnormal GCL/GCIPL regions and areas under receiver operating characteristic curves (AUROC) for prediction of glaucoma were compared between GCL or GCIPL measures.

The average ± standard deviation MDs were -3.7 ± 1.6 dB and -2.7 ± 1.8 dB in glaucomatous eyes in the first and second cohorts, respectively. Global GCIPL thickness measures (central 18° × 18° macular region) performed better than GCL for early detection of glaucoma (AUROC, 0.928 vs. 0.884, respectively; P = 0.004). Superior and inferior sector 3 thickness measures provided the best discrimination with both GCL and GCIPL (inferior GCL AUROC, 0.860 vs. GCIPL AUROC, 0.916 [P = 0.001]; superior GCL AUROC, 0.916 vs. GCIPL AUROC, 0.900 [P = 0.24]). The extents of abnormal GCL regions at a 1% cutoff in the central elliptical area were 17.5 ± 22.2% and 6.4 ± 10.8% in glaucomatous and normal/GS eyes, respectively, versus 17.0 ± 22.2% and 5.7 ± 10.5%, respectively, for GCIPL (P = 0.06 for GCL and 0.002 for GCIPL). The extents of GCL and GCIPL supernormal regions were mostly similar in glaucomatous and normal eyes. The best performance for prediction of glaucoma in the second cohort was detected at a P value of < 1% within the entire scan for both GCL and GCIPL (AUC, 0.681 vs. 0.668, respectively; P = 0.29).

Macular GCL and GCIPL thicknesses are equivalent for identifying early glaucoma with current OCT technology. This is likely explained by limitations of inner macular layer segmentation and concurrent changes within the inner plexiform layer in early glaucoma.

To assess the variance of macular sublayers' volume in glaucoma patients compared with normal individuals.

This case-control observational study included 63 cases of primary open-angle glaucoma and 57 healthy controls. Macular volumetric scans were captured at the 6 mm ETDRS circle for each retinal sublayer using Spectralis OCT2. The studied macular sublayers included the retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, and outer retinal layers (external limiting membrane to the retinal pigment epithelium). Standard deviation (SD) and coefficient of variation (CoV) of macular sublayers' volume were calculated. An unpaired Student t test (or its nonparametric equivalent) was used to compare each variable between groups. The receiver operating characteristic curve (ROC) was used to investigate the discriminative ability of each parameter.

There was no significant difference for age or sex between the groups. The SD (of all sublayers' volume) was greater in the glaucomatous eyes compared with controls (0.620 ± 0.073vs.0.524 ± 0.056  mm³, respectively; P < 0.001). The same pattern was observed for CoV (7.890 ± 0.979vs.6.128 ± 0.583; P < 0.001). The area under curves (AUCs) for SD and CoV were 0.855and0.930, respectively (P = 0.05). The best cutoff value for the CoV was 6.712. The CoV and ganglion cell layer (GCL) volume revealed similar sensitivity (80.75) at 95% specificity for diagnosing glaucoma. The CoV detected 5 patients with glaucoma who had normal GCC volume.

This study showed that the macular sublayers' volume variance parameters could be viable OCT biomarkers for detecting glaucomatous changes.

Despite the diagnostic accuracy of advanced neurodiagnostic procedures, the detection of Alzheimer's disease (AD) remains poor in primary care. There is an urgent need for screening tools to aid in the detection of early AD.

This study examines the predictive ability of structural retinal biomarkers in detecting cognitive impairment in a primary care setting.

Participants were recruited from Alzheimer's Disease in Primary Care (ADPC) study. As part of the ADPC Retinal Biomarker Study (ADPC RBS), visual acuity, an ocular history questionnaire, eye pressure, optical coherence tomography (OCT) imaging, and fundus imaging was performed.

Data were examined on n = 91 participants. The top biomarkers for predicting cognitive impairment included the inferior quadrant of the outer retinal layers, all four quadrants of the peripapillary retinal nerve fiber layer, and the inferior quadrant of the macular retinal nerve fiber layer.

The current data provides strong support for continued investigation into structural retinal biomarkers, particularly the retinal nerve fiber layer, as screening tools for AD.

Glaucoma is one of the irreversible ocular diseases that can cause vision loss in some serious cases. Although Triggerfish has been commercialized for monitoring intraocular pressure in glaucoma, there is no smart contact lens to monitor intraocular pressure and take appropriate drug treatment in response to the intraocular pressure levels. Here, we report a precisely integrated theranostic smart contact lens with a sensitive gold hollow nanowire based intraocular pressure sensor, a flexible drug delivery system, wireless power and communication systems and an application specific integrated circuit chip for both monitoring and control of intraocular pressure in glaucoma. The gold hollow nanowire based intraocular pressure sensor shows high ocular strain sensitivity, chemical stability and biocompatibility. Furthermore, the flexible drug delivery system can be used for on-demand delivery of timolol for intraocular pressure control. Taken together, the intraocular pressure levels can be successfully monitored and controlled by the theranostic smart contact lens in glaucoma induced rabbits. This theranostic smart contact lens would be harnessed as a futuristic personal healthcare platform for glaucoma and other ocular diseases.

Optic coherence tomography imaging in preperimetric open angle glaucoma (OAG) differed between young-age-onset and old-age-onset eyes. Inferior and superior quadrants were thinner in young and old-age-onset eyes, respectively. Understanding the specific patterns of early glaucomatous damage based on age-at-onset may improve glaucoma diagnosis and monitoring.

To investigate the patterns of retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thinning in preperimetric OAG by optical coherence tomography based on age at onset ("young-age onset (<40 y)" vs. "old-age onset (≥40 y)".

The RNFL and GCIPL deviation images were acquired by Cirrus HD-optical coherence tomography, and overlaid, thus converted to a "deviation frequency map", respectively. The topographic thinning patterns and parameters of RNFL and GCIPL thickness measurements were compared.

A total of 194 eyes of 194 patients with preperimetric OAG and 97 eyes of 97 age-matched normal subjects were analyzed. Young-age-onset eyes of preperimetric OAG mainly had RNFL defects inferotemporally (264-296 degrees) with GCIPL defects in the inferior region (213-357 degrees). Old-age-onset preperimetric OAG eyes had RNFL defects inferotemporally (266-294°) and superotemporally (33-67 degrees), with GCIPL defects in the inferior and superior regions (206-360 degrees, 0-22 degrees). The inferior quadrant of RNFL and GCIPL thicknesses were significantly thinner in young-age-onset eyes compared with old-age-onset eyes ( P =0.012, 0.016), while the superior quadrant of those were significantly thinner in the old-age-onset eyes ( P =0.003, 0.005).

Young-age-onset and old-age-onset eyes of preperimetric OAG present different specific patterns of RNFL and GCIPL thinning.

Both macular superficial vessel density and ganglion cell complex (GCC) thickness measurement are significantly associated with regional and global 10-degree central visual field (VF) sensitivity in advanced glaucoma.

The purpose of this study was to evaluate the regional and global structure-function relationships between macular vessel density (MVD) assessed by optical coherence tomography angiography (OCTA) and 10-2 VF sensitivity in advanced open angle glaucoma eyes.

Macular OCTA and 10-2 VF sensitivity of 44 patients [mean deviation (MD) <-10 dB] were evaluated. Regional and global VF mean sensitivity (MS) was calculated from total deviation plots. Superficial and deep MVD were obtained from 3 × 3 and 6×6 mm 2 OCTA scans using 2 sectoral definitions. Spectral-domain optical coherence tomography macular GCC thickness was obtained simultaneously from the same scan as the MVD measurements. Linear regression models were used to assess the associations ( R2 ).

Lower MS was significantly associated with a reduction in superficial MVD and GCC in each region of both scan sizes for both maps. Associations were weaker in the individual sectors of the whole image grid than the Early Treatment Diabetic Retinopathy Study map. Deep-layer MVD was not associated with central MS. Although 6×6 mm 2 and perifoveal vessel density had better associations with central 10-degree MS compared with GCC thickness (eg, R2 from 25.7 to 48.1 µm and 7.8% to 32.5%, respectively), GCC associations were stronger than MVD associations in the central 5-degree MS.

Given a stronger MVD-central 10-degree VF association compared with GCC, as well as stronger GCC-central 5-degree VF association compared with MVD, MVD and GCC are complementary measurements in eyes with advanced glaucoma. A longitudinal analysis is needed to determine the relative utility of the GCC and MVD measurements.