Hongli Yang

Précis: This study shows that GCC thickness is most sensitive for detecting progression at the onset of glaucoma, but less sensitive than cpRNFL thickness. These findings suggest no clear additional value of GCC thickness over cpRNFL overall, although further evaluation in larger cohorts with advanced glaucoma is warranted. Purpose: To compare the sensitivity of ganglion cell complex (GCC) thickness in the macula to circumpapillary retinal nerve fiber layer (cpRNFL) thickness from OCT, and Mean Deviation (MD) and Visual Field Index (VFI) from Standard Automated Perimetry (SAP), for detecting glaucomatous progression across glaucoma stages. Methods: Using longitudinal data from 205 eyes (125 participants), contrast-to-noise ratios (CNRs) were calculated for GCC, cpRNFL, MD and VFI. Glaucoma stage was defined by MD. Contrast was the parameter difference between two stages; noise was the variability from linear regression residuals from five consecutive OCT scans and HFA 24-2 tests per eye. Higher CNR indicates greater sensitive for detecting progression between stages. Results: CNRs ranged from 3.7 to 13.2. In the transition from suspect to mild glaucoma, cpRNFL (13.2) and GCC (8.7) had significantly higher CNRs than MD (4.5) and VFI CNR (4.8); cpRNFL was also significantly higher than GCC. No significant CNR differences were found between structural and functional measures in later stages. Conclusions: GCC thickness is more sensitive than functional measures, but less than cpRNFL thickness, for detecting progression at glaucoma onset. In later stages, structural and functional parameters showed comparable sensitivity within the limits of the available data.

Purpose: 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. Methods: 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. Results: 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). Conclusions: 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.

Purpose: It has been hypothesized that compromised ocular circulation in glaucoma may be concomitant of systemic changes. The purpose of this study is to test whether systemic blood flow pulse waveform patterns differ between individuals with glaucoma (GL), glaucoma suspects (GLS), and normal healthy controls (HC). Methods: The study included 35 bilateral GL, 67 bilateral GLS, 29 individuals with unilateral GL who were considered GLS in the other eye, and 44 healthy controls. Systemic pulsatile blood pressure waveforms were recorded using a finger cuff. A continuous 200 Hz plethysmography recording is made to obtain a pulse waveform. Waveform parameters were extracted using custom software from an average of eight pulse cycles. These were compared between GL, GLS, and HC groups on a per-eye basis, using generalized estimating equation models to account for intereye correlations; and plotted against disease severity by visual field linearized mean deviation (MD_lin) and retinal nerve fiber layer thickness (RNFLT). Results: Averaged blood pressure was significantly lower in the HC group (mean ± standard deviation 91.7 ±11.7 mm Hg) than the GLS (102.4 ± 13.9) or GL (102.8 ± 13.7) groups, with P < 0.0001 (generalized estimating equation regression). Waveform parameters representing vascular resistance were higher in both GLS and GL groups than the HC group; and were correlated with RNFLT and MD_lin (P ≤ 0.05). Conclusions: The shape of the systemic pulsatile waveform differs in individuals with GL/GLS suspects, compared to HC eyes. Blood pressure changes more rapidly in individuals with GL, which suggests higher arterial stiffness.

Glaucoma is the second leading cause of blindness worldwide and is characterized by the death of retinal ganglion cells (RGCs), the cells that send vision information to the brain. Their axons exit the eye at the optic nerve head (ONH), the main site of damage in glaucoma. The importance of biomechanics in glaucoma is indicated by the fact that elevated intraocular pressure (IOP) is a causative risk factor for the disease. However, exactly how biomechanical insult leads to RGC death is not understood. Although rat models are widely used to study glaucoma, their ONH biomechanics have not been characterized in depth. Therefore, we aimed to do so through finite element (FE) modeling. Utilizing our previously described method, we constructed and analyzed ONH models with individual-specific geometry in which the sclera was modeled as a matrix reinforced with collagen fibers. We developed eight sets of scleral material parameters based on results from our previous inverse FE study and used them to simulate the effects of elevated IOP in eight model variants of each of seven rat ONHs. Within the optic nerve, highest strains were seen inferiorly, a pattern that was consistent across model geometries and model variants. In addition, changing the collagen fiber direction to be circumferential within the peripapillary sclera resulted in more pronounced decreases in strain than changing scleral stiffness. The results from this study can be used to interpret data from rat glaucoma studies to learn more about how biomechanics affects RGC pathogenesis in glaucoma.

Purpose To assess changes in the position of lamina cribrosa pores (LCPs) induced by acute intraocular pressure (IOP) elevation. Methods A prospective observational study. Acute angle-closure suspects who underwent the 2-hour dark room prone provocative test (DRPPT) were included. At baseline and within 5 min after the DRPPT end, tonometry, fundus photography and optical coherence tomography were performed. Optic disc photos taken before and after the DRPPT were aligned and moving distance of each visible LCP was measured (LCPMD). Results 38 eyes from 27 participants (age: 52.5±10.8 years) were included. The IOP rose from 16.7±3.2 mm Hg at baseline to 23.9±4.3 mm Hg at the DRPPT end. The mean lateral LCPMD was 28.1±14.6 µm (range: 5.0–77.2 µm), which increased with higher IOP rise (p=0.01) and deeper optic cup (p=0.02) in multivariate analysis. The intralamina range and SD of the LCPMD increased with younger age (p=0.01 and p=0.02, respectively) and with wider optic cup (p=0.01 and p=0.02, respectively). The LCP movements were headed to the superior direction in 12 (33%) eyes, inferior direction in 10 (28%) eyes, temporal direction in 9 (25%) eyes, and nasal direction in 5 (14%) eyes. Conclusions IOP rise is associated with LCP movements in the frontal plane, which are more pronounced with higher IOP rise and deeper optic cup. The intralamina variability in the IOP rise-associated LCPMD increased with younger age and wider optic cup. IOP variation-associated lateral LCP movements may be of interest to elucidate glaucomatous optic nerve damage.

Purpose: To quantify peripapillary choroidal thickness (PCT) and the factors that influence it in healthy participants who represent the racial and ethnic composition of the U.S. population. Methods: A total of 362 healthy participants underwent optical coherence tomography (OCT) enhanced depth imaging of the optic nerve head with a 24 radial B-scan pattern aligned to the fovea to Bruch's membrane opening axis. Bruch's membrane, anterior scleral canal opening (ASCO), and the anterior scleral surface were manually segmented. PCT was measured at 100, 300, 500, 700, 900, and 1100 μm from the ASCO globally and within 12 clock-hour sectors. The effects of age, axial length, intraocular pressure, ethnicity, sex, sector, and ASCO area on PCT were assessed by ANOVA and univariable and multivariable regressions. Results: Globally, PCT was thicker further from the ASCO border and thinner with older age, longer axial length, larger ASCO area, European descent, and female sex. Among these effectors, age and axial length explained the greatest proportion of variance. The rate of age-related decline increased further from the ASCO border. Sectorally, the inferior-temporal sectors were thinnest (10.7%–20.0% thinner than the thickest sector) and demonstrated a higher rate of age-related loss (from 15.6% to 20.7% faster) at each ASCO distance. Conclusions: In healthy eyes, PCT was thinnest in the inferior temporal sectors and thinner PCT was associated with older age, European descent, longer axial length, larger ASCO area, and female sex. Among these associations, age had the strongest influence, and its effect was greatest within the inferior temporal sectors.

Glaucoma is the leading cause of irreversible blindness and involves the death of retinal ganglion cells (RGCs). Although biomechanics likely contributes to axonal injury within the optic nerve head (ONH), leading to RGC death, the pathways by which this occurs are not well understood. While rat models of glaucoma are well-suited for mechanistic studies, the anatomy of the rat ONH is different from the human, and the resulting differences in biomechanics have not been characterized. The aim of this study is to describe a methodology for building individual-specific finite element (FE) models of rat ONHs. This method was used to build three rat ONH FE models and compute the biomechanical environment within these ONHs. Initial results show that rat ONH strains are larger and more asymmetric than those seen in human ONH modeling studies. This method provides a framework for building additional models of normotensive and glaucomatous rat ONHs. Comparing model strain patterns with patterns of cellular response seen in studies using rat glaucoma models will help us to learn more about the link between biomechanics and glaucomatous cell death, which in turn may drive the development of novel therapies for glaucoma.