Mengyu Wang

Associations between Optic Nerve Head–Related Anatomical Parameters and Refractive Error over the Full Range of Glaucoma Severity

Purpose To evaluate the associations between optic disc (OD)-related anatomical parameters (interartery angle [IAA] between superior and inferior temporal retinal arteries, OD tilt [TL], rotation [ROT], and torsion [TO], OD surface curvature [CUR], and central retinal vessel trunk entry point location [CRVTL] on OD) and the spherical equivalent of refractive error (SE), and to assess the impact of glaucoma severity on these relationships. Methods Cirrus optical coherence tomography (OCT) fundus images and 24-2 visual fields of 438 patients were included. Ellipses were fitted to OD borders. IAA was calculated between marked retinal artery locations on a circle around OD. Blood vessel entry point on OD was marked to locate CRVTL. TL was measured as the angle between the lines fitted to OD clinical boundary and the Bruchs membrane edges on the horizontal B-scans. Ellipse rotation relative to the vertical axis defined ROT. Angle between the long axis of OD and the interartery line defined TO. CUR was determined by the inner limiting membrane on the horizontal B-scans. Linear regression models evaluated by Bayes Factors (BF) were used to determine the covariance structure between the parameters and SE as well as possible impacts of mean deviation (MD). Results Our results showed that CRVTL had the strongest relationship with SE, followed by ROT, TL, and IAA (BFs: 3.59 × 107, 2645, 1126, and 248, respectively). MD did not significantly modulate the relationship between ONH parameters and SE. Conclusion Our results suggest that SE should be considered when interpreting the OD and its circumpapillary region for diagnostic purposes. Translational Relevance The reported relationships between OD-related parameters and ametropia may help to decrease false-positive clinical diagnoses of optic neuropathies.

The Interrelationship between Refractive Error, Blood Vessel Anatomy, and Glaucomatous Visual Field Loss

Purpose We quantified the interrelationship between retinal blood vessel (BV) anatomical variation, spherical equivalent (SE) of refractive error, and functional diagnostic parameters in glaucoma to identify optimal parameters for the improvement of optical coherence tomography (OCT) retinal nerve fiber layer thickness (RNFLT) norms. Methods A trained observer marked the intersections of the main superior/inferior temporal arteries and veins with concentric circles around the optic nerve head (ONH) center on fundus images. The interrelationship of BV, SE, and visual field global parameters was analyzed by multivariate regression and model comparison. Results A total of 445 eyes of 445 patients in a large glaucoma practice were selected. Of all investigated BV parameters, interartery angles (IAA) between superior and inferior arteries at a radius of 1.73 mm around the ONH center demonstrated the strongest relationship to SE (Bayesian information criterion difference to null model, 11.9). SE and BV parameters are unrelated to functional parameters, including mean deviation (MD), pattern standard deviation, and glaucoma hemifield test results. Conclusions BV locations outside the ONH are sufficiently stable over glaucoma severity to represent individual eye anatomy, and the IAA at 1.73 mm eccentricity is the optimal parameter to be considered for novel OCT RNFLT norms. Translational Relevance Among a large set of BV location parameters, considering IAA may improve RNFLT norms optimally and thereby increase the accuracy of clinical glaucoma diagnosis.

Quantifying positional variation of retinal blood vessels in glaucoma

We studied the relationship between major retinal blood vessel (BV) positions and glaucoma parameters based on pairs of Cirrus optical coherence tomography scans and Humphrey visual fields of 445 eyes from 445 glaucoma patients in our cross-sectional study. A trained observer marked the major superior and inferior temporal BV (artery and vein) positions on four concentric circles around the optic disc. Analysis of variance was performed to analyze the group differences of BV positions related to the factors of radius, BV type, myopia status and glaucoma stage. Subsequent t-tests were implemented to further study the effect of glaucoma stage on BV positions. The radial variations of BV positions were correlated to mean deviation and circumpapillary retinal nerve fiber layer thickness (cpRNFLT). We found significant main effects of BV type, radius and myopia status for superior and inferior BV positions and of glaucoma stage for superior BV positions (all p≤0.006) with significant superior artery nasalization in advanced compared to mild glaucoma on the two smallest circles (subsequent t-tests, p<0.05). In addition, MD (r = -0.10, p = 0.04) and cpRNFLT (r = -0.12, p = 0.02) were significantly correlated to the angle difference of superior arteries between the innermost and outermost circles. In conclusion, we demonstrated that peripapillary superior artery positions are significantly nasalized for advanced glaucoma.

Impact of anatomical parameters on optical coherence tomography retinal nerve fiber layer thickness abnormality patterns

Purpose: To evaluate the effects of four anatomical parameters (angle between superior and inferior temporal retinal arteries [inter-artery angle, IAA], optic disc [OD] rotation, retinal curvature, and central retinal vessel trunk entry point location [CRVTL]) on retinal nerve fiber layer thickness (RNFLT) abnormality marks by OCT machines. Methods: Cirrus OCT circumpapillary RNFLT measurements and Humphrey visual fields (HVF 24-2) of 421 patients from a large glaucoma clinic were included. Ellipses were fitted to the OD borders. Ellipse rotation relative to the vertical axis defined OD rotation. CRVTL was manually marked on the horizontal axis of the ellipse on the OCT fundus image. IAA was calculated between manually marked retinal artery locations at the 1.73mm radius around OD. Retinal curvature was determined by the inner limiting membrane on the horizontal B-scan closest to the OD center. For each location on the circumpapillary scanning area, logistic regression was used to determine if each of the four parameters had a significant impact on RNFLT abnormality marks independent of disease severity. The results are presented on spatial maps of the entire scanning area. Results: Variations in IAA significantly influenced abnormality marks on 38.8% of the total scanning area, followed by CRVTL (19.2%) and retinal curvature (18.7%). The effect of OD rotation was negligible (<1%). Conclusions: A natural variation in IAA, retinal curvature, and CRVTL can affect OCT abnormality ratings, which may bias clinical diagnosis. Our spatial maps may help OCT manufacturers to introduce location specific norms to ensure that abnormality marks indicate ocular disease instead of variations in eye anatomy.

Ametropia, retinal anatomy, and OCT abnormality patterns in glaucoma. 1. Impacts of refractive error and interartery angle

Abstract. Retinal nerve fiber layer thickness (RNFLT) measured by optical coherence tomography (OCT) is widely used in clinical practice to support glaucoma diagnosis. Clinicians frequently interpret peripapillary RNFLT areas marked as abnormal by OCT machines. However, presently, clinical OCT machines do not take individual retinal anatomy variation into account, and according diagnostic biases have been shown particularly for patients with ametropia. The angle between the two major temporal retinal arteries (interartery angle, IAA) is considered a fundamental retinal ametropia marker. Here, we analyze peripapillary spectral domain OCT RNFLT scans of 691 glaucoma patients and apply multivariate logistic regression to quantitatively compare the diagnostic bias of spherical equivalent (SE) of refractive error and IAA and to identify the precise retinal locations of false-positive/negative abnormality marks. Independent of glaucoma severity (visual field mean deviation), IAA/SE variations biased abnormality marks on OCT RNFLT printouts at 36.7%/22.9% of the peripapillary area, respectively. 17.2% of the biases due to SE are not explained by IAA variation, particularly in inferonasal areas. To conclude, the inclusion of SE and IAA in OCT RNFLT norms would help to increase diagnostic accuracy. Our detailed location maps may help clinicians to reduce diagnostic bias while interpreting retinal OCT scans.

Age, ocular magnification, and circumpapillary retinal nerve fiber layer thickness

Abstract. Optical coherence tomography (OCT) manufacturers graphically present circumpapillary retinal nerve fiber layer thickness (cpRNFLT) together with normative limits to support clinicians in diagnosing ophthalmic diseases. The impact of age on cpRNFLT is typically implemented by linear models. cpRNFLT is strongly location-specific, whereas previously published norms are typically restricted to coarse sectors and based on small populations. Furthermore, OCT devices neglect impacts of lens or eye size on the diameter of the cpRNFLT scan circle so that the diameter substantially varies over different eyes. We investigate the impact of age and scan diameter reported by Spectralis spectral-domain OCT on cpRNFLT in 5646 subjects with healthy eyes. We provide cpRNFLT by age and diameter at 768 angular locations. Age/diameter were significantly related to cpRNFLT on 89%/92% of the circle, respectively (pointwise linear regression), and to shifts in cpRNFLT peak locations. For subjects from age 42.1 onward but not below, increasing age significantly decreased scan diameter (r=−0.28, p<0.001), which suggests that pathological cpRNFLT thinning over time may be underestimated in elderly compared to younger subjects, as scan diameter decrease correlated with cpRNFLT increase. Our detailed numerical results may help to generate various correction models to improve diagnosing and monitoring optic neuropathies.

Predicting Refractive Outcome of Small Incision Lenticule Extraction for Myopia Using Corneal Properties

Purpose To investigate whether preoperative corneal topographic and biomechanical parameters (CTBPs) predict postoperative residual refractive error (RRE). Methods We retrospectively included 151 eyes from 151 patients of small-incision lenticule extraction (SMILE) with target RRE of plano and 3-month measurements of refractive error from Tianjin Eye Hospital. Multivariate linear/logistic regressions were performed to associate age, gender, preoperative refractive error, lenticule thickness, and CTBPs with postoperative RRE/the occurrence of myopic RRE ≤ −0.25 diopter (D). Stepwise regression was used for feature selection. Leave-one-cross-validation was used for model evaluation by the area under the receiver operating characteristic curve (AUC). Results From linear regression, more myopic RRE was associated with higher preoperative myopia, intraocular pressure (IOP), flattest curvature of anterior cornea (AC), and highest concavity deformation (HCD), and was associated with lower anterior elevation, anterior asphericity, steepest curvature of AC, and second applanation velocity. The occurrence of ≤ −0.25 D RRE was associated with higher myopia, IOP, posterior elevation and asphericity, flattest curvature of AC, first applanation velocity and HCD, and was associated with lower first applanation stiffness parameter, central corneal thickness, anterior elevation and asphericity, steepest curvature of AC, and second applanation velocity as well as thinner lenticule thickness. Compared to the baseline model using age, gender, and preoperative refractive error, adding CTBPs significantly (P < 0.001) improved the AUC performance to 0.771 from 0.615. Conclusions Postoperative outcomes of SMILE can be predicted by individual CTBPs. Translational Relevance Our findings could be used to customize a refractive nomogram based on individual corneal properties improving outcomes and patient satisfaction.

Impact of Natural Blind Spot Location on Perimetry

We study the spatial distribution of natural blind spot location (NBSL) and its impact on perimetry. Pattern deviation (PD) values of 11,449 reliable visual fields (VFs) that are defined as clinically unaffected based on summary indices were extracted from 11,449 glaucoma patients. We modeled NBSL distribution using a two-dimensional non-linear regression approach and correlated NBSL with spherical equivalent (SE). Additionally, we compared PD values of groups with longer and shorter distances than median, and larger and smaller angles than median between NBSL and fixation. Mean and standard deviation of horizontal and vertical NBSL were 14.33° ± 1.37° and −2.06° ± 1.27°, respectively. SE decreased with increasing NBSL (correlation: r = −0.14, p < 0.001). For NBSL distances longer than median distance (14.32°), average PD values decreased in the upper central (average difference for significant points (ADSP): −0.18 dB) and increased in the lower nasal VF region (ADSP: 0.14 dB). For angles in the direction of upper hemifield relative to the median angle (−8.13°), PD values decreased in lower nasal (ADSP: −0.11 dB) and increased in upper temporal VF areas (ADSP: 0.19 dB). In conclusion, we demonstrate that NBSL has a systematic effect on the spatial distribution of VF sensitivity.

Combining retinal nerve fiber layer thickness with individual retinal blood vessel locations allows modeling of central vision loss in glaucoma

Purpose: To assess whether modeling of central vision loss (CVL) due to glaucoma by optical coherence tomography (OCT) retinal nerve fiber (RNF) layer thickness (RNFLT) can be improved by including the location of the major inferior temporal retinal artery (ITA), a known correlate of individual RNF geometry. Methods: Pat- tern deviations of the two locations of the Humphrey 24-2 visual field (VF) known to be specifically vulnerable to glaucomatous CVL and OCT RNFLT on the corresponding circumpapillary sector around the optic nerve head within the radius of 1.73mm were retrospectively selected from 428 eyes of 428 patients of a large clinical glaucoma service. ITA was marked on the 1.73mm circle by a trained observer. Linear regression models were fitted with CVL as dependent variable and VF mean deviation (MD) plus either of (1) RNFLT, (2) ITA, and (3) their combination, respectively, as regressors. To assess CVL over all levels of glaucoma severity, the three models were compared to a null model containing only MD. A Baysian model comparison was performed with the Bayes Factor (BF) as measure of strength of evidence (BF<3: no evidence, 3-20: positive evidence, >20: strong evidence over null model). Results: Neither RNFLT (BF=0.9) nor ITA (BF=1.4) alone provided positive evidence over the null model, but their combination resulted in a model with strong evidence (BF=21.4). Conclusion: While the established circumpapillary RNFLT sector, based on population statistics, could not satisfactorily model CVL, the inclusion of a retinal parameter related to individual eye anatomy yielded a strong structure-function model.

The relationship between 3D morphology of optic disc and spatial patterns of visual field loss in glaucoma

Purpose: Optic disc tilt defined over 3D optic disc morphology has been shown to be associated with the location of initial glaucomatous damages. In this work, we study the impact of optic cup depth (OCD) on spatial patterns of visual field loss in glaucoma. Methods: Pairs of reliable Cirrus OCT scans around optic disc and Humphrey visual fields of glaucoma patients without visually significant cataract and age-related macular degeneration were selected. The most recent visit of a randomly selected eye of each patient was chosen. The OCD was automatically calculated on the superior-inferior cross sectional image passing through the optic disc center. The correlations between the mean pattern deviation (PD) of each sector in glaucoma hemifield test (GHT) and Garway-Heath scheme and OCD were evaluated for all severities glaucoma and mild glaucoma (mean deviation ≥ -5 dB), respectively. Results: 424 eyes of 424 patients passed the data reliability criteria with 346 mild glaucoma patients. For all severities glaucoma, there was no significant correlation between the mean sector PD and OCD. For mild glaucoma, OCD was uniquely correlated to the mean PD of the inferior pericentral sector (r=-0.18, p=0.01) in GHT, which was independent of mean deviation and retinal nerve fiber layer thickness (p<0.001 for both). Conclusion: OCD was uniquely correlated to the vision loss of the inferior pericentral sector in GHT and Garway- Health scheme for mild glaucoma. Future advancement of OCT imaging techniques may provide better clinical diagnosis for early glaucoma by focusing on 3D morphological variation of the optic disc.