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Progressive optic neuropathies such as glaucoma are major causes of blindness globally. Multiple sources of subjectivity and analytical challenges are often encountered by the clinicians in the process of early diagnosis and clinical management of these diseases. In glaucoma, the structural damage is often characterized by neuroretinal rim (NRR) thinning of the optic nerve head, and other clinical parameters. Optical coherence tomography (OCT) is a popular and quantitative eye imaging platform for precise and reproducible measurement of such parameters in the clinic.Baseline structural heterogeneity in the eyes can play a key role in the progression of optic neuropathies, and thus present challenges to clinical decision-making. To address this, large and diverse normative OCT databases with mathematically precise description of phenotypes can help with early detection and characterization of the different phenotypes that are encountered in the clinic. In this study, we generated a new large dataset of OCT generated high-resolution circular data on NRR phenotypes, along with other clinical covariates, of nearly 4,000 healthy eyes as part of a well-established clinical cohort (LVPEI-GLEAMS) of Asian Indian participants.In this study, we (1) generated high-resolution circular OCT measurements of NRR thickness in a given eye, (2) introduced CIFU, a new computational pipeline for CIrcular FUnctional data modeling and analysis that is demonstrated using the OCT dataset, and (3) addressed the disparity of representation of the Asian Indian population in normative OCT databases. We demonstrated CIFU by unsupervised circular functional clustering of the OCT NRR data, meta-clustering to characterize the clustering output using clinical covariates, and presenting a circular visualization of the results. Upon stratification by age, we identified a healthy NRR phenotype cluster in the age group 40-49 years with predictive potential for glaucoma.

Purpose: To compare onset times of glaucoma progression among different glaucoma tests: disc photography (DP), visual field (VF) testing, 2-dimensional (2D) retinal nerve fiber layer (RNFL) thickness, and 3-dimensional (3D) spectral-domain (SD) OCT neuroretinal rim measurements. Design: Prospective, longitudinal cohort study. Participants: One hundred twenty-four eyes of 124 patients with open-angle glaucoma. Methods: Over a 5-year period, 124 patients with open-angle glaucoma underwent yearly DP, VF testing, SD OCT RNFL thickness scans, and optic nerve volume scans (Spectralis; Heidelberg Engineering), all performed on the same day. From high-density optic nerve volume scans, custom-built software calculated the minimum distance band (MDB) thickness, a 3D neuroretinal rim parameter. Patients were classified as glaucoma progressors or nonglaucoma progressors using event-based analysis. Progression by DP and VF testing occurred when 3 masked glaucoma specialists unanimously concurred. Progression by RNFL and MDB thickness occurred if change of more than test–retest variability was observed. Kaplan-Meier curves were constructed to analyze time-to-progression data. Kappa Coefficients were used to measure agreement of progressing eyes among methods. Main Outcome Measures: Time to glaucoma progression among all 4 methods. Results: Global MDB thickness detected glaucoma progression in the highest percentage of eyes (52.4%) compared with DP (16.1%; P < 0.001) and global RNFL thickness (15.3%; P < 0.001). Global MDB thickness detected glaucoma progression earlier than either DP (23 months vs. 44 months; P < 0.001) or global RNFL thickness (23 months vs. 33 months; P < 0.001). Among MDB progressing eyes, 46.2% were confirmed simultaneously or later by other conventional methods. Agreement of glaucoma-progressing eyes for all 4 methods in paired fashion were slight to fair (κ = 0.095–0.300). Conclusions: High-density 3D SD OCT neuroretinal rim measurements detected glaucoma progression approximately 1 to 2 years earlier compared with current clinically available structural tests (i.e., DP and 2D RNFL thickness measurements).

The disc damage likelihood scale (DDLS) is a tool for classifying glaucomatous structural changes to the optic disc based on the radial width of the neuroretinal rim at its thinnest location, or if no rim is present, the extent of absence of the rim. Unlike cup disc ratio (CDR), the DDLS also considers disc size. Twenty years after its first description, the aim of this review was to critically appraise evidence for the DDLS and evaluate its role in current practice. A literature search by two independent authors identified 33 relevant articles for inclusion. Five studies evaluated reproducibility, 5 diagnostic performance, and 2 studies examined ability to detect progression. Eleven studies evaluated correlation between DDLS and other markers of glaucoma. Despite the widespread availability of imaging devices such as optical coherence tomography (OCT), clinical examination of the optic disc remains an essential component of glaucoma diagnosis and monitoring. The DDLS provides a reliable method for semi-quantitative clinical grading of the optic disc in glaucoma, with higher reproducibility than methods such as CDR.

Purpose To assess the structure-function relationship in glaucoma using Humphrey visual field (HVF) perimetry and a three-dimensional neuroretinal rim parameter derived from spectral domain optical coherence tomography (SD-OCT) volume scans. Methods Structure-function correlation was analyzed globally and regionally (four quadrants and four sectors). Structural data included peripapillary retinal nerve fiber layer (RNFL) thickness and minimum distance band (MDB) neuroretinal rim thickness, defined as the shortest distance between the inner cup surface and the outer retinal pigment epithelium/Bruch's membrane complex. Logarithmic regression analyses were performed and Pearson correlation coefficients determined to assess relationship strength. Results The study consisted of 102 open-angle glaucoma patients and 58 healthy subjects. The Pearson correlation coefficient for global MDB thickness (R = 0.585) was higher than for global RNFL thickness (R = 0.492), but the difference was not statistically significant (P = 0.18). The correlation coefficients for regional MDB thicknesses and corresponding HVF sensitivities were higher than those for regional RNFL thicknesses and HVF in six out of eight regions (P = 0.08 to 0.47). In the remaining two out of eight regions, the correlation coefficients were higher for RNFL thickness than for MDB thickness (P = 0.15 to 0.20). Conclusions Three-dimensional MDB neuroretinal rim thickness relates to visual function as strongly as the most commonly used SD-OCT parameter for glaucoma, two-dimensional peripapillary RNFL thickness. Translational relevance This paper illustrates the potential for 3D OCT algorithms to improve in vivo imaging in glaucoma.

BACKGROUND We evaluated the usefulness of neuroretinal rim (NRR) thicknesses, measured in clock-hour sectors with Cirrus HD optical coherence tomography, for diagnosing preperimetric glaucoma (PPG). METHODS This prospective study included 39 eyes of 39 patients with PPG and 39 eyes of 39 controls that were matched to patients for age and refractive error. We measured the circumpapillary retinal nerve fiber layer (cpRNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness, and optic nerve head (ONH) parameters with optical coherence tomography. The clock-hour NRR thicknesses were derived from a 360° circumferential rim thickness curve. We analyzed the area under the receiver operating characteristics curve (AUROC), cutoff values, and sensitivities at specificities of 90% and 95%. RESULTS The largest area under the receiver operating characteristics curves were observed for the NRR thickness at 6 o'clock (0.823), the inferior RNFL thickness (0.821), the average RNFL thickness (0.819), and the NRR thickness at 7 o'clock (0.818). The performance of the NRR thickness at 6 o'clock was comparable to the best performances of the cpRNFL, GCIPL, and ONH parameters (all p > 0.05). CONCLUSION The ability of the clock-hour NRR thickness assessment to diagnose PPG was comparable to the diagnostic abilities of cpRNFL, GCIPL, and ONH parameters. The best indicator of PPG was the NRR thickness parameter that was at 6 o'clock. This finding could play a role in detecting early structural changes in PPG.

Purpose: The optic nerve head (ONH) is a part of the brain that can be evaluated through the transparent medium of the eye. The purpose of this study was to explore the possible correlations among the properties of the optic nerve head, maternal factors during pregnancy and neonatal parameters in a randomized sample of a birth cohort. Methods: The Northern Finland 1966 Birth Cohort has been prospectively monitored since their antenatal period. Data on pregnancy and neonatal period were collected during gestation and right after birth in 1966. A randomized sample of 3070 subjects underwent an ophthalmic assessment at the age of 46–48 years. The examination protocol included scanning laser ophthalmoscopy with the Heidelberg Retina Tomograph. The ophthalmological parameters assessed were the disc area and the neuroretinal rim volume of the ONH. Results: We found that chronic pulmonary disease of the mother (p = 0.007), the number of gestational weeks (p = 0.030) and the mother’s highest measured systolic blood pressure (p = 0.035) during pregnancy had a statistically significant effect on the disc area. Smaller disc size was associated with pulmonary disease and early gestation. There was a significant difference in rim volume between genders (p

Purpose: To investigate the factors associated with an increase in the neuroretinal rim (NRR) thickness measured based on Bruch’s membrane opening-minimum rim width (BMO-MRW) after trabeculectomy in patients with primary open-angle glaucoma (POAG). Methods: We analyzed the BMO-MRW using spectral-domain optical coherence tomography (SD-OCT) of patients with POAG who underwent a trabeculectomy for uncontrolled intraocular pressure (IOP) despite maximal IOP reduction treatment. The BMO-MRW was measured before and after trabeculectomy in patients with POAG. Demographic and systemic factors, ocular factors, pre- and post-operative IOP, and visual field parameters were collected, together with SD-OCT measurements. A regression analysis was performed to investigate the factors that affected the change in the BMO-MRW after the trabeculectomy. Results: Forty-four eyes of 44 patients were included in the analysis. The IOP significantly decreased from a preoperative 27.0 mmHg to a postoperative 10.5 mmHg. The mean interval between the trabeculectomy and the date of post-operative SD-OCT measurement was 3.3 months. The global and sectoral BMO-MRW significantly increased after trabeculectomy, whereas the peripapillary retinal nerve fiber layer thickness did not show a difference between before and after the trabeculectomy. Younger age and a greater reduction in the IOP after the trabeculectomy were significantly associated with the increase in the BMO-MRW after trabeculectomy. Conclusions: The NRR thickness measured based on the BMO-MRW increased with decreasing IOP after trabeculectomy, and the increase in the BMO-MRW was associated with the young age of the patients and greater reduction in the IOP after trabeculectomy. Biomechanically, these suggest that the NRR comprises cells and substances that sensitively respond to changes in the IOP and age.

AimsTo evaluate the accuracy of the ISNT rule (I=inferior, S=superior, N=nasal, T=temporal) and its variants with neuroretinal rim width and retinal nerve fibre layer (RNFL) thickness measurements differentiating normal from glaucomatous eyes.MethodsThe diagnosis accuracy of the ISNT rule and its variants was evaluated in a population-based study. Neuroretinal rim widths were measured on monoscopic optic disc photographs with an image-processing program. RNFL thickness measurements were obtained with spectral-domain optical coherence tomography (SD-OCT).ResultsIn this study including 940 normal subjects and 93 patients with glaucoma, the sensitivity of the ISNT rule with optic disc photographs was 94.1% (95% CI 90.2 to 98.1), whereas its specificity was 49.2% (46.9 to 51.6). When using the IST rule, the sensitivity decreased to 69.9% (62.1 to 77.6) with a higher specificity, 87.0% (85.3 to 88.6). All the diagnosis indicators were somewhat lower for the different rules using RNFL thickness: the sensitivity of the ISNT rule was 79.4% (72.6 to 86.2) and its specificity was 34.1% (31.9 to 36.4). With the IST rule, the sensitivity decreased to 50.0% (41.6 to 58.4) while the specificity increased to 64.9% (62.7 to 67.2).ConclusionsThe ISNT and IST rules applied to neuroretinal rim width measurement by optic disc photographs are useful and simple tools for differentiating normal from glaucomatous eyes. The translation of these rules to RNFL thickness by SD-OCT is of limited value.

Purpose: To compare the rates of clinically significant artifacts for two-dimensional peripapillary retinal nerve fiber layer (RNFL) thickness versus three-dimensional (3D) neuroretinal rim thickness using spectral-domain optical coherence tomography (SD-OCT). Methods: Only one eye per patient was used for analysis of 120 glaucoma patients and 114 normal patients. For RNFL scans and optic nerve scans, 15 artifact types were calculated per B-scan and per eye. Neuroretinal rim tissue was quantified by the minimum distance band (MDB). Global MDB neuroretinal rim thicknesses were calculated before and after manual deletion of B-scans with artifacts and subsequent automated interpo-lation. A clinically significant artifact was defined as one requiring manual correction or repeat scanning. Results: Among glaucomatous eyes, artifact rates per B-scan were significantly more common in RNFL scans (61.7%, 74 of 120) compared to B-scans in neuroretinal rim volume scans (20.9%, 1423 of 6820) (95% confidence interval [CI], 31.6–50.0; P < 0.0001). For clinically significant artifact rates per eye, optic nerve scans had significantly fewer artifacts (15.8% of glaucomatous eyes, 13.2% of normal eyes) compared to RNFL scans (61.7% of glaucomatous eyes, 25.4% of normal eyes) (glaucoma group: 95% CI, 34.1–57.5, P < 0.0001; normal group: 95% CI, 1.3–23.3, P = 0.03). Conclusions: Compared to the most commonly used RNFL thickness scans, optic nerve volume scans less frequently require manual correction or repeat scanning to obtain accurate measurements. Translational Relevance: This paper illustrates the potential for 3D OCT algorithms to improve in vivo imaging in glaucoma.

Précis: Neuroretinal rim minimum distance band (MDB) thickness is significantly lower in older subjects and African Americans compared with whites. It is similar in both sexes. Purpose: To evaluate the relationship between age, race, and sex with the neuroretinal rim using high-density spectral-domain optical coherence tomography optic nerve volume scans of normal eyes. Methods: A total of 256 normal subjects underwent Spectralis spectral-domain optical coherence tomography optic nerve head volume scans. One eye was randomly selected and analyzed for each subject. Using custom-designed software, the neuroretinal rim MDB thickness was calculated from volume scans, and global and quadrant neuroretinal rim thickness values were determined. The MDB is a 3-dimensional neuroretinal rim band comprised of the shortest distance between the internal limiting membrane and the termination of the retinal pigment epithelium/Bruch’s membrane complex. Multiple linear regression analysis was performed to determine the associations of age, race, and sex with neuroretinal rim MDB measurements. Results: The population was 57% female and 69% white with a mean age of 58.4±15.3 years. The mean MDB thickness in the normal population was 278.4±47.5 µm. For this normal population, MDB thickness decreased by 0.84 µm annually (P

Purpose: To evaluate the efficacy of the ISNT rule in normal eyes of Koreans. Methods: We retrospectively reviewed medical records of 890 subjects with fundus photographs and evaluated the presence of the cup and ISNT rule satisfaction. If the ISNT rule was violated, the quadrants in which the neuroretinal rim was thinnest and thickest, respectively, were evaluated. Results: Among 890 eyes, 84.7% showed the cup. The subjects without the cup were significantly younger and more hyperopic. Among 754 eyes with the cup, 53.5% showed ISNT rule satisfaction. In 351 eyes violating the ISNT rule, the most common quadrant showing the thickest neuroretinal rim was the inferior (65.5%), and the thinnest, the temporal (98.3%). Conclusion: The cup was absent in 15% of the assessed eyes. Only about half of eyes with the cup showed ISNT rule satisfaction. Even in eyes violating ISNT rule, the inferior was the most common quadrant with the thickest neuroretinal rim and the temporal, the thinnest.

Purpose To review the published literature on the use of swept-source (SS) OCT for evaluating the lamina cribrosa in glaucoma. Methods A PubMed and Cochrane Library literature search initially conducted on March 3, 2017, and updated on June 26, 2018, yielded a total of 64 articles. Articles that were reviews or that were not published in English were excluded, and 29 were found to fit the inclusion criteria. The panel methodologist then assigned a level of evidence rating to each study. Fifteen studies were rated level III, 14 studies were rated level II, and no studies were rated level I. Results Different aspects of the lamina cribrosa were studied using SS-OCT, including the anterior lamina cribrosa curvature, anterior lamina cribrosa depth, anterior lamina cribrosa insertions, laminar thickness, focal lamina cribrosa defects (FLCDs), and lamina cribrosa microarchitecture. In general, imaging of the anterior lamina can be achieved reliably, although shadowing from blood vessels at the neuroretinal rim remains an issue. Imaging of the posterior lamina can be achieved with varying levels of success. In glaucoma, there is posterior migration of the anterior lamina cribrosa insertions as well as increased thinning and posterior curvature of the lamina cribrosa. Focal lamina cribrosa defects appear more commonly in glaucoma, and this may hint at the pathogenesis of axonal damage. In addition, there may be remodeling of the microarchitecture of the lamina, resulting in more variable laminar pores. There are limited studies comparing SS-OCT with spectral-domain (SD) OCT with regard to imaging of the lamina, but the difference in image quality between enhanced depth imaging (EDI) with SD-OCT and SS-OCT seems minimal. Conclusions Imaging of the lamina cribrosa using SS-OCT has demonstrated that the lamina cribrosa is likely biomechanically active and that significant changes occur in glaucoma. The diagnostic utility of SS-OCT for lamina cribrosa imaging is promising, but standardized nomenclature, automated measurements, and longitudinal studies with larger and more diverse sample sizes are needed.

BackgroundTo investigate the thinning rate of three-dimensional neuroretinal rim thickness (3D-NRT) in glaucoma eyes with optic disc haemorrhage (DH) and its relationship to retinal nerve fibre layer thickness (RNFLT) progression.MethodsNinety-five (95) eyes of 95 glaucoma patients with initial DH in the inferotemporal (n=69) and superotemporal (n=26) regions and 48 eyes of 48 glaucoma patients without DH were retrospectively reviewed. The rates of change for 3D-NRT and RNFLT were compared by linear mixed-effect model. For the direct comparison between 3D-NRT and RNFLT, dynamic-range-based normalised coefficient was used. The effect of DH frequency on the rates of thinning of 3D-NRT and RNFLT was evaluated.ResultsDuring a mean 7-year follow-up, the rates of thinning of 3D-NRT (–5.69±4.88 µm/year) and RNFLT (–2.03±2.03 µm/year) at 7 o’clock were faster than those at other locations (all pConclusionDH eyes are associated with the progression of both 3D-NRT and RNFLT, especially in the inferotemporal region. DH eyes show a relatively faster thinning rate of average RNFLT than 3D-NRT. The frequency of DH can affect the progression of 3D-NRT as well as RNFLT.

The mean prevalence of high myopia increases over time in Egypt Prevalence of high myopia in Egypt which was 0.2%, in 1960 increased to 7.4% in 1976 and 10.8% in 2015. Optical coherence tomography (OCT) is a noninvasive, painless and quick precise technology that can be used for interpreting tissue structure and function. Time-domain OCT was fast enough to scan a circle centered on the optic nerve head (circumpapillary) to assess the retinal nerve fiber layer (RNFL) thickness. Glaucoma Module Premium Edition (GMPE) is a new, objective method of ONH analysis using BMO. The termination of Bruch's membrane at the ONH marks the opening through which RGC axons exit the eye to form the choroidal and scleral portions of the neural canal, this anatomic opening, termed Bruch's membrane opening (BMO). The minimum distance from the BMO to the internal limiting membrane represents the most geometrically accurate measurement of neuroretinal rim width. This neuroretinal rim measurement has been termed Bruch's Membrane Opening-Minimum Rim Width (BMO-MRW).

Myopia is an important risk factor for glaucoma. The prevalence of myopia is increasing dramatically, and thus too, myopic glaucoma will be more often encountered. Recent advances in Spectral-Domain Optical Coherence Tomography (SD-OCT) technology enable fast, objective, and quantitative structural imaging of the optic nerve head (ONH), retinal nerve fiber layer (RNFL), and macula for facilitated and enhanced glaucoma diagnostics. However, myopic eyes have unique structural features, which might cause artifacts in OCT imaging or induce false positivity or negativity in interpreting OCT results. For correct diagnosis of glaucoma, it is essential to understand myopic eyes’ structural features that might affect imaging and interpretation of OCT. The key OCT parameters in glaucoma diagnosis include peripapillary RNFL thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness, and neuroretinal rim thickness measurements. Here, I review the anatomical features of these structures in myopia, how they affect imaging and the diagnostic performance of OCT, how these structures and tests might be misinterpreted, and how to overcome pitfalls and to make correct diagnoses of myopic eyes with or without glaucoma.

Diagnosis of glaucoma requires more than the optic nerve head (ONH) evaluation findings alone, but ONH assessment is crucial to detection of glaucoma, assessment of severity, and monitoring for disease progression. Objective assessment of the ONH must be done independent of other clinical features. This chapter explores the process of examining the disc for glaucoma, where errors may occur, and strategies to avoid them.

As with any other disease, the severity of glaucoma varies and the disease progression happens at a variable pace. Understanding the importance of the severity of a finding in terms its significance for the particular person under consideration should be clear, but is often not considered. This chapter stresses the importance of assessing this issue of severity, and, additionally, shares a method of how that can be done. This method not only applies to every type of glaucoma, but also for any disease process.

Optic nerve head appearance can vary significantly in glaucomatous as well as non-glaucomatous eyes. This creates difficulties in correct classification of the discs from glaucoma point of view, more so where the underlying structure is unexpected or not clearly identified. This chapter addresses some basic aspects that pose difficulty in interpretation and some aberrant discs that pose a diagnostic dilemma.

To investigate the clinical characteristics and long-term outcomes of primary congenital glaucoma (PCG) patients.In this retrospective, longitudinal, cohort study, PCG patients with reliable visual field (VF) tests and optical coherence tomography (OCT) were included. Disease progression was detected using guided progression analysis with OCT and the change analysis of mean deviation (MD) slope with VF tests. Factors associated with the disease progression and visual prognosis were analyzed.Twenty-nine eyes from 11 bilateral and 7 unilateral PCG patients were enrolled. LogMAR visual acuity declined (0.15 vs. 0.40, P 0.001). The change rate of the average retinal nerve fiber layer thickness was - 0.83 ± 1.45 µm/year, and 28% of eyes showed glaucoma progression on OCT. The median of the MD slope was 0.16 (- 1.19 to 1.07) dB/year, and 14% of eyes showed glaucoma progression on the VF test. Higher average intraocular pressure (IOP) (P = 0.046) and IOP fluctuation (P = 0.031) predicted disease progression. None of the fellow eyes of unilateral PCG patients developed glaucoma during the follow-up. At last, 59% of eyes had visual acuity 20/70, and 31% had MD - 6 dB. Patients with worse baseline visual acuity (P = 0.027), worse baseline MD (P 0.001), and smaller neuroretinal rim area (P 0.001) showed worse final MD values.Aggressive IOP control is necessary to prevent structural and functional decline in PCG patients. Their fellow eyes are not at risk of glaucoma. Baseline neuroretinal rim area can predict the functional outcome.

Purpose Ocular rigidity (OR) is an important biomechanical property, thought to be relevant in the pathophysiology of open-angle glaucoma (OAG). This study aims to evaluate the relationship between OR and neuroretinal damage caused by glaucoma. Methods One hundred eight subjects (22 with healthy eyes, 23 with suspect discs, and 63 with OAG) were included in this study. OR was measured using a noninvasive optical coherence tomography (OCT)-based method developed by our group. We also measured central corneal thickness (CCT), corneal hysteresis (CH), and corneal resistance factor (CRF). Pearson and partial correlations were performed to evaluate the relationship between OR and glaucomatous damage represented by ganglion cell complex (GCC), retinal nerve fiber layer (RNFL) thicknesses, and neuroretinal rim area. Results Significant positive correlations were found between OR and minimum GCC thickness (r = 0.325, P = 0.001), average GCC thickness (r = 0.320, P = 0.002), rim area (r = 0.344, P < 0.001), and RNFL thickness in the superior (r = 0.225, P = 0.023), and inferior (r = 0.281, P = 0.004) quadrants. These correlations were generally greater than those found for CCT, CH, and CRF. Furthermore, no correlation was found between OR and corneal biomechanical parameters. After adjusting for age, sex, and ethnicity, significant correlations were found between OR and minimum and average GCC thickness (r = 0.357, P = 0.001 and r = 0.344, P = 0.001, respectively), rim area (r = 0.327, P = 0.001), average RNFL thickness (r = 0.331, P = 0.001), and RNFL thickness in the superior (r = 0.296, P = 0.003) and inferior (r = 0.317, P = 0.001) quadrants. Conclusions In this study, we found a positive correlation between structural OCT-based parameters and OR, indicating more neuroretinal damage in eyes with lower OR. These findings could provide insight into the pathophysiology of OAG.