Effects of Myopia and Glaucoma on the Neural Canal and Lamina Cribrosa Using Optical Coherence Tomography.

PRCIS: Glaucoma was associated with axial bowing and rotation of Bruchs membrane opening (BMO) and anterior laminar insertion (ALI), skewed neural canal, and deeper anterior lamina cribrosa surface (ALCS). Longer axial length was associated with wider, longer, and more skewed neural canal and flatter ALCS. PURPOSE: Investigate the effects of myopia and glaucoma in the prelaminar neural canal and anterior lamina cribrosa using 1060-nm swept-source optical coherence tomography. PATIENTS: 19 control (38 eyes) and 38 glaucomatous subjects (63 eyes). MATERIALS AND METHODS: Participants were imaged with swept-source optical coherence tomography, and the images were analyzed for the BMO and ALI dimensions, prelaminar neural canal dimensions, and ALCS depth. RESULTS: Glaucomatous eyes had more bowed and nasally rotated BMO and ALI, more horizontally skewed prelaminar neural canal, and deeper ALCS than the control eyes. Increased axial length was associated with a wider, longer, and more horizontally skewed neural canal and a decrease in the ALCS depth and curvature. CONCLUSION: Our findings suggest that glaucomatous posterior bowing or cupping of lamina cribrosa can be significantly confounded by the myopic expansion of the neural canal. This may be related to higher glaucoma risk associated with myopia from decreased compliance and increased susceptibility to IOP-related damage of LC being pulled taut.

Longitudinal Analysis of Bruch Membrane Opening Morphometry in Myopic Glaucoma.

PRéCIS:: The Bruch membrane opening (BMO) was posteriorly bowed and the degree of nonplanarity increased in stable and progressive glaucoma subjects. BMO became more posterior relative to the Bruch membrane (BM) in control and both stable and progressive glaucoma subjects. PURPOSE: To investigate longitudinal changes in morphologic characteristics of the BMO in control and glaucomatous subjects. MATERIALS AND METHODS: A total of 53 myopic eyes (17 control, 6 suspect, 20 stable glaucoma, and 10 progressing glaucoma) were followed for an average of 4.2±1.4 years and imaged at the baseline and 2 follow-up appointments using a 1060 nm swept-source optical coherence tomography system. BM and BMO were segmented, and 4 morphometric BMO parameters (area, ellipse ratio, nonplanarity, and depth) were measured. RESULTS: There were no significant changes in BMO area or ellipse ratio for all groups. BMO nonplanarity was shown to increase in the glaucoma groups. BMO depth relative to BM increased in all groups except the suspects (control: 8.1 µm/y, P=0.0001; stable glaucoma: 3.5 µm/y, P=0.0001; progressing glaucoma: 14.0 µm/y, P=0.0026). In linear mixed-model analysis, axial length was positively associated with BMO area in all groups except for progressing glaucoma, and with BMO nonplanarity in stable glaucoma. It was not a significant factor to the slopes of the BMO parameters in the ANCOVA analysis of slopes. CONCLUSIONS: Longitudinally, BMO increased in nonplanarity in the glaucoma eyes, and its axial position relative to BM became more posterior in both control and glaucoma eyes.

Age and Glaucoma-Related Characteristics in Retinal Nerve Fiber Layer and Choroid: Localized Morphometrics and Visualization Using Functional Shapes Registration.

Optical coherence tomography provides high-resolution 3D imaging of the posterior segment of the eye. However, quantitative morphological analysis, particularly relevant in retinal degenerative diseases such as glaucoma, has been confined to simple sectorization and averaging with limited spatial sensitivity for detection of clinical markers. In this paper, we present point-wise analysis and visualization of the retinal nerve fiber layer and choroid from cross-sectional data using functional shapes (fshape) registration. The fshape framework matches two retinas, or generates a mean of multiple retinas, by jointly optimizing the surface geometry and functional signals mapped on the surface. We generated group-wise mean retinal nerve fiber layer and choroidal surfaces with the respective layer thickness mapping and showed the difference by age (normal, younger vs. older) and by disease (age-matched older, normal vs. glaucomatous) in the two layers, along with a more conventional sector-based analysis for comparison. The fshape results visualized the detailed spatial patterns of the differences between the age-matched normal and glaucomatous retinal nerve fiber layers, with the glaucomatous layers most significantly thinner in the inferior region close to Bruch's membrane opening. Between the young and older normal cases, choroid was shown to be significantly thinner in the older subjects across all regions, but particularly in the nasal and inferior regions. The results demonstrate a comprehensive and detailed analysis with visualization of morphometric patterns by multiple factors.

Anterior Segment Optical Coherence Tomography for Targeted Transconjunctival Suture Placement in Overfiltering Trabeculectomy Blebs.

PURPOSE: To demonstrate the utility of swept-source anterior segment optical coherence tomography (SS-AS-OCT) in guiding placement of transconjunctival sutures in hypotonous patients after a trabeculectomy. PATIENTS AND METHODS: This is a longitudinal case series of 10 eyes from 10 patients who required transconjunctival sutures after a trabeculectomy. SS-AS-OCT was used to aid in the placement of the sutures to improve the function of the overfiltering bleb. RESULTS: SS-AS-OCT reliably identified localized areas of overfiltering, allowing for targeted suture placement in 8 eyes. The 2 eyes in which localized areas of overfiltering were not found required further surgical intervention. CONCLUSIONS: SS-AS-OCT enhances transconjunctival suturing for overfiltering blebs when focal fluid accumulation is visualized.

Quantifying Variability in Longitudinal Peripapillary RNFL and Choroidal Layer Thickness Using Surface Based Registration of OCT Images.

PURPOSE: To assess within-subject variability of retinal nerve fiber layer (RNFL) and choroidal layer thickness in longitudinal repeat optical coherence tomography (OCT) images with point-to-point measurement comparison made using nonrigid surface registration. METHODS: Nine repeat peripapillary OCT images were acquired over 3 weeks from 12 eyes of 6 young, healthy subjects using a 1060-nm prototype swept-source device. The RNFL, choroid and the Bruch's membrane opening (BMO) were segmented, and point-wise layer thicknesses and BMO dimensions were measured. For each eye, the layer surfaces of eight follow-up images were registered to those of the baseline image, first by rigid alignment using blood vessel projections and axial height and tilt correction, followed by nonrigid registration of currents-based diffeomorphisms algorithms. This mapped all follow-up measurements point-wise to the common baseline coordinate system, allowing for point-wise statistical analysis. Measurement variability was evaluated point-wise for layer thicknesses and BMO dimensions by time-standard deviation (tSD). RESULTS: The intraclass correlation coefficients (ICCs) of BMO area and eccentricity were 0.993 and 0.972, respectively. Time-mean and tSD were computed point-wise for RNFL and choroidal thickness and color-mapped on the baseline surfaces. tSD was less than two coherence lengths of the system 2ℓ = 12 µm at most vertices. High RNFL thickness variability corresponded to the locations of retinal vessels, and choroidal thickness varied more than RNFL thickness. CONCLUSIONS: Our registration-based end-to-end pipeline produced point-wise correspondence among time-series retinal and choroidal surfaces with high measurement repeatability (low variability). Blood vessels were found to be the main sources contributing to the normal variability of the RNFL thickness measure. The computational pipeline with a measurement of normal variability can be used in future longitudinal studies to identify changes that are above the threshold of normal point-wise variability and track localized changes in retinal layers in high spatial resolution. TRANSLATIONAL RELEVANCE: Using the registration-based approach presented in this study, longitudinal changes in retinal and choroidal layers can be detected with higher sensitivity and spatial precision.

Retinal optical coherence tomography at 1 µm with dynamic focus control and axial motion tracking.

High-resolution optical coherence tomography (OCT) retinal imaging is important to noninvasively visualize the various retinal structures to aid in better understanding of the pathogenesis of vision-robbing diseases. However, conventional OCT systems have a trade-off between lateral resolution and depth-of-focus. In this report, we present the development of a focus-stacking OCT system with automatic focus optimization for high-resolution, extended-focal-range clinical retinal imaging by incorporating a variable-focus liquid lens into the sample arm optics. Retinal layer tracking and selection was performed using a graphics processing unit accelerated processing platform for focus optimization, providing real-time layer-specific en face visualization. After optimization, multiple volumes focused at different depths were acquired, registered, and stitched together to yield a single, high-resolution focus-stacked dataset. Using this system, we show high-resolution images of the retina and optic nerve head, from which we extracted clinically relevant parameters such as the nerve fiber layer thickness and lamina cribrosa microarchitecture.

Comparison of the clinical disc margin seen in stereo disc photographs with neural canal opening seen in optical coherence tomography images.

PURPOSE: To compare neural canal opening (NCO) with the clinical optic disc margin (DM) seen and to investigate the planarity of the NCO in normal human optic nerve heads (ONH). METHODS: Sixteen eyes were imaged. Twelve healthy eyes were selected for planarity and 9 for NCO and DM correspondence. All subjects were subjected to a visual field examination, stereo disc photograph (SDP), scanning laser ophthalmoscopy, clinical examination with a fellowship trained glaucoma specialist, and optical coherence tomography imaging. Three reviewers delineated the NCO and inner limiting membrane on optical coherence tomography images. The clinical DM was delineated by a glaucoma specialist while viewing SDPs. Plane error was calculated for NCO and for Bruch membrane (BM) at distances 80 and 120 µm from NCO. RESULTS: The NCO segmentation interrater variability was low with an average coefficient of variation of 2.7%. A regional variation of the SDP and NCO correspondence was observed, wherein the temporal region had the largest coefficient of variation. The plane error of the NCO and BM were similar and was approximately 12 µm, which is small relative to an average DM diameter of 1.7 mm. CONCLUSIONS: The BM opening has a good correspondence with the clinical DM seen in SDPs. NCO delineation seemed to be reliable. The BM and NCO are relatively planar in normal humans and can be further evaluated for longitudinal studies to observe stability.

Optic nerve head and peripapillary morphometrics in myopic glaucoma.

PURPOSE: To investigate morphological characteristics of optic nerve head and peripapillary region with myopia and glaucoma. METHODS: Ten normal and 17 glaucomatous myopic participants were imaged with a custom 1060-nm swept-source optical coherence tomography system. The three-dimensional images were processed and segmented for inner limiting membrane (ILM), posterior border of retinal nerve fiber layer (RNFL), Bruch's membrane (BM), and posterior border of choroid. Seven shape parameters were measured: nerve fiber layer (NFL) thickness; Bruch's membrane opening (BMO) area, eccentricity, and planarity; BMO and BM depths; and choroidal thickness. The results were analyzed by group and regional sector, and multiple regression was performed on each shape parameter with age, axial length, and glaucoma severity, measured by mean deviation (MD). RESULTS: Bruch's membrane opening area (P < 0.001), eccentricity (P = 0.025), and planarity (P = 0.019) were correlated with axial length but not with MD, such that larger, more elliptical, and less planar BMO was associated with longer axial length. Several BMOs displayed a saddle-like shape configuration whose orientation appeared to be aligned with that of the BMO ellipse. All BM showed posterior deformation toward BMO such that BM closer to BMO was more posterior than that farther from BMO. Bruch's membrane depth was correlated with axial length (P = 0.014) and MD (P = 0.040) in intersubject regression, and BMO depth (P = 0.003) and BM depth (P = 0.006) were correlated with MD in intereye regression. Bruch's membrane depth was also associated with age. Choroidal thickness was negatively correlated with age (P = 0.001) and with axial length to a smaller degree (P = 0.034), but not with glaucoma severity. CONCLUSIONS: Axial length was a significant factor in BMO and BM shape in normal and glaucomatous myopic subjects. Posterior deformation of BM was observed in all eyes and significantly associated with functional glaucomatous damage and age.

Does an association exist between pseudoexfoliation syndrome and chronic kidney disease?

PURPOSE: To determine whether pseudoexfoliation (PEX) syndrome is associated with an increased risk of chronic kidney disease (CKD). PATIENTS AND METHODS: In this cross-sectional study, 271 consecutive patients were recruited into 3 study groups---PEX syndrome (n=86), primary open-angle glaucoma (POAG) (n=91), and nonglaucoma controls (n=94)---and underwent serum creatinine testing to determine their glomerular filtration rates (eGFR). Repeat eGFR and testing for urine albumin:creatinine ratio were performed a minimum of 3 months later if the initial eGFR was less than 60 mL/min/1.73 m. CKD was diagnosed if both eGFR levels were less than 45 mL/min/1.73 m or both eGFR levels were less than 60 mL/min/1.73 m and the urine albumin:creatinine ratio was greater than 2.0. The main outcome measure was the rate of CKD for each group. RESULTS: The CKD rate for the control group (11.7%, 11 of 94) was statistically higher than the PEX (3.5%, 3 of 86, P=0.050) and the POAG (3.3%, 3 of 91, P=0.049) groups. However, there was a significantly higher rate of diabetes mellitus, a known risk factor for CKD, in the control group than the PEX and POAG groups. After adjusting for the differences in the rate of diabetes mellitus and mean age (another risk factor for CKD) between groups, a multivariate logistic regression analysis showed that none of the study groups was a predictor of an increased rate of CKD. A post-hoc analysis performed with all patients with diabetes mellitus removed also showed no statistical difference between groups for CKD rates and mean eGFR levels. CONCLUSIONS: Compared with age-matched patients with POAG and nonglaucoma controls, PEX syndrome was not found to be associated with an increased prevalence of CKD.

Real-time high-speed volumetric imaging using compressive sampling optical coherence tomography.

Volumetric imaging of the Optic Nerve Head (ONH) morphometry with Optical Coherence Tomography (OCT) requires dense sampling and relatively long acquisition times. Compressive Sampling (CS) is an emerging technique to reduce volume acquisition time with minimal image degradation by sparsely sampling the object and reconstructing the missing data in software. In this report, we demonstrated real-time CS-OCT for volumetric imaging of the ONH using a 1060nm Swept-Source OCT prototype. We also showed that registration and averaging of CS-recovered volumes enhanced visualization of deep structures of the sclera and lamina cribrosa. This work validates CS-OCT as a means for reducing volume acquisition time and for preserving high-resolution in volume-averaged images. Compressive sampling can be integrated into new and existing OCT systems without changes to the optics, requiring only software changes and post-processing of acquired data.

Rapid volumetric OCT image acquisition using compressive sampling.

Acquiring three dimensional image volumes with techniques such as Optical Coherence Tomography (OCT) relies on reconstructing the tissue layers based on reflection of light from tissue interfaces. One B-mode scan in an image is acquired by scanning and concatenating several A-mode scans, and several contiguous slices are acquired to assemble a full 3D image volume. In this work, we demonstrate how Compressive Sampling (CS) can be used to accurately reconstruct 3D OCT images with minimal quality degradation from a subset of the original image. The full 3D image is reconstructed from sparsely sampled data by exploiting the sparsity of the image in a carefully chosen transform domain. We use several sub-sampling schemes, recover the full 3D image using CS, and show that there is negligible effect on clinically relevant morphometric measurements of the optic nerve head in the recovered image. The potential outcome of this work is a significant reduction in OCT image acquisition time, with possible extensions to speeding up acquisition in other imaging modalities such as ultrasound and MRI.

Evaluating optic nerve damage: pearls and pitfalls.

Primary open-angle glaucoma is a progressive optic neuropathy involving loss of retinal ganglion cells and their axons at the level of the optic nerve head. This change manifests as thinning and excavation of the neural tissues and nerve fiber layer. Therefore, it has long been known that the structural appearance of the optic nerve head is paramount to both glaucoma diagnosis and to the detection of progression [1-4]. Quantitative imaging methods such as Heidelberg Retinal Tomography (HRT) and Ocular Coherence Tomography (OCT) show great promise for the diagnosis and management of glaucoma and as these technologies continue to improve, they will become more important in the care of glaucoma. However, these tests cannot replace good clinical examination and indeed they depend upon clinical correlation for correct interpretation. Thus, careful and systematic clinical examination of the optic nerve remains a cornerstone of glaucoma management. In this paper, we outline a few pearls for the examination of the optic nerve and some of the pitfalls to be avoided in optic disc examination.

Applications of the polymerase chain reaction in clinical ophthalmology.

Molecular biology has become a valuable component in many areas of medicine, including ophthalmology. Polymerase chain reaction (PCR) is the most widely used tool. It has proven to be a powerful technique in diagnosis and quantification of microorganisms and antibiotic resistance screening. For a growing number of ophthalmic conditions PCR testing can be conducted. It is therefore important that clinicians be knowledgeable about the indications, strengths, and limitations of the technique. The purpose of this review is to explore the current role of PCR in the diagnosis and management of eye disease.

Vascular anatomy of the optic nerve head.

Although intraocular pressure remains the main modifiable risk factor for open-angle glaucoma, other factors such as vascular perfusion likely play a significant role. It is not clear how mechanical deformation, axonal damage, glial responses, and ischemia interact to lead to the tissue remodeling seen clinically as glaucomatous cupping. To understand the potential role of vascular risk factors in glaucoma, it is important to understand the vascular anatomy of the optic nerve head (ONH). The focus of this review is to provide a description of the vascular anatomy of the ONH and to describe recent work in the central nervous system that suggests that astrocytes play a key role in vascular regulation. Finally, the evidence for vascular regulation in the ONH and retina is reviewed.

Sensitivity and specificity of the optos optomap for detecting peripheral retinal lesions.

PURPOSE: To compare the sensitivity and specificity of the Optomap Panoramic200 wide-field confocal scanning laser imaging system for detecting peripheral retinal lesions. METHODS: Optomap images were obtained in patients with known retinal pathology. Two masked retinal specialists evaluated Optomap images to identify lesions requiring referral to a retinal specialist. Their performance was compared to gold standard examination with scleral indentation performed by a retinal specialist. Sensitivity was calculated overall and again for lesions that were found on clinical examination to require treatment. These sensitivities were calculated separately for lesions posterior and anterior to the equator. Specificity was calculated from fellow eyes that were found to have no pathology on clinical examination. RESULTS: For retinal lesions posterior to the equator, sensitivity was 74% (95% confidence interval [95% CI] 61%-87%) overall for all lesions and 76% (95% CI 59%-93%) for lesions requiring treatment. For anterior lesions, sensitivity was 45% (95% CI 28%-62%) overall and 36% (95% CI 14%-58%) for treatable lesions. Specificity was 85% (95% CI 63%-100%). CONCLUSIONS: The Optomap showed high specificity and moderate sensitivity for lesions posterior to the equator and low sensitivity for lesions anterior to the equator.

Comparison of silicone and polypropylene Ahmed glaucoma valves: two-year follow-up.

BACKGROUND: To compare the safety and efficacy of silicone and polypropylene Ahmed glaucoma drainage devices. METHODS: We studied a retrospective consecutive case series of 91 eyes of 81 patients who were implanted with Ahmed valves by a single surgeon (R.M.S.). The first 43 eyes received polypropylene (model S2) valves; the remaining 48 eyes received silicone (model FP7) valves. Data collection included demographics, type of glaucoma, and sequential measurement of clinical characteristics. The mean outcome measures were visual acuity, intraocular pressure (IOP), number of antiglaucoma medications, and postoperative complications. Data were collected on day 1; weeks 1, 2-3, and 6; months 3-4, 6, and 12; and last visit. RESULTS: Mean follow-up was 27.1 months for the polypropylene valve and 20.1 months for the silicone valve. Mean decrease in IOP at 1 year was significantly greater in the silicone group than in the polypropylene group (t test, p < 0.005); however, this difference disappeared at 2 years. There were no differences between the groups in visual acuity, number of antiglaucoma medications, bleb needlings with 5-fluorouracil, or minor complications. A greater number of serious complications, including valve failures, occurred in the polypropylene group than in the silicone group, and this difference could not be accounted for by the longer follow-up in the polypropylene group. At 2 years follow-up, 82% of patients with silicone valves and 72% of patients with polypropylene valves continued to achieve greater than 30% IOP reduction. INTERPRETATION: Both the silicone and polypropylene Ahmed valves significantly reduced IOP over 2 years. The silicone valve was associated with fewer serious complications.

Gradient steepness influences the pathfinding decisions of neuronal growth cones in vivo.

Gradients of chemotropic molecules are generally thought to be fundamental for the guidance of neuronal growth cones in the developing embryo. Here we show that the grasshopper-secreted semaphorin Sema 2a is expressed in a gradient during the period of tibial Ti1 pioneer axon pathfinding into the CNS. At two critical Ti1 growth cone choice points, the Sema 2a gradient differs in steepness, whereas the absolute concentration is the same. Although Ti1 growth cones enter and extend up both steep and shallow gradients of Sema 2a, fewer projection errors occur along the steep gradient, suggesting that the steepness of the gradient encodes the critical guidance information into the pathfinding growth cone. In contrast, an increase in the absolute concentration of Sema 2a appears to constrain the Ti1 growth cone size. Using these in vivo gradients, we provide evidence that the Ti1 growth cone detects the Sema 2a gradient by measuring the fractional change in Sema 2a concentration, thereby demonstrating one mechanism that neuronal growth cones may use to detect and read gradients in vivo.

Validity of the SF-12 quality of life instrument in patients with retinal diseases.

OBJECTIVE: To investigate the construct validity and reliability of the SF-12 with the SF-36 composite scores in patients with retinal diseases. DESIGN: Cross-sectional study. PARTICIPANTS: One thousand eighty-one patients with retinal disease presenting for care at a tertiary referral university-based retina practice. METHODS: Each patient completed the SF-36 before his or her initial ocular examination. The SF-12 is based on a subset of 12 items from the SF-36. MAIN OUTCOME MEASURES: Physical Composite Score (PCS) and Mental Composite Score (MCS) as determined by the SF-36 and SF-12. RESULTS: Eight hundred thirty-nine (78%) of the participants had scorable PCS and MCS scores on the SF-12. No significant differences were found between the SF-36 and SF-12 for the PCS and MCS overall and stratified by the four most frequently occurring disease categories (all P > 0.20). There were statistically significant differences across the disease categories in the mean PCS scores (P < 0.001) on the SF-36 and SF-12 and the MCS score on the SF-36 (P = 0.04). The SF-12 PCS and MCS scores were highly correlated with similar indicators (composite scores and subscales) on the SF-36. CONCLUSIONS: The SF-12 is a valid measure of general health status for ophthalmic research, as long as differences in mental composite scores do not need to be demonstrated between different ocular disease groups. The benefit of reduced administration time makes the SF-12 a recommended general quality-of-life outcomes tool.

Assessment of vision-related function in patients with age-related macular degeneration.

OBJECTIVE: To investigate the validity of the visual function index (VF-14) in assessing visual function in patients with age-related macular degeneration (AMD). DESIGN: Prospective noncomparative observational case series. PARTICIPANTS: One hundred fifty-nine consecutive patients attending a sole practitioner's academic retina-only clinic from May 1998 through August 1998 and from May 1999 through August 1999. MAIN OUTCOME MEASURES: Correlations were calculated between the VF-14 scores and the medical outcomes study 36-item short form (SF-36), weighted comorbidity scale, visual acuity and clinical AMD severity (stage), and vision self-assessment scales. Documentation of the severity of macular degeneration was performed by a sole examiner. RESULTS: There was a moderately strong correlation between visual acuity and trouble with vision (r = 0.51), satisfaction with vision (r = -0.50), and overall quality of vision (r = -0.56). A strong correlation was noted between VF-14 score and patients' self-rating of amount of trouble with vision (r = -0.67), satisfaction with vision (r = 0.62), and overall quality of vision (r = 0.67). In comparison, correlations between SF-36 score and patients' self-rating of amount of trouble with vision, satisfaction with vision, and overall quality of vision ranged from r = 0.37 to r = -0.40. Linear regression analysis for the overall study population indicated that AMD severity was not an independently significant predictor of VF-14 score after adjusting for visual acuity. However, among patients with 20/20 vision in the better eye, AMD severity was an independently significant predictor of VF-14 score after adjusting for visual acuity in the worse eye. CONCLUSIONS: The VF-14 exhibits a considerable degree of validity as a measure of functional impairment in patients with AMD. Age-related macular degeneration severity was an independently significant predictor of VF-14 score in the group of patients with 20/20 vision in the better eye, but this did not hold true for the overall study population. Age-related macular degeneration is associated with substantial impairment in reported visual function.