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Thick Prelaminar Tissue Decreases Lamina Cribrosa Visibility

Lucy, Katie A; Wang, Bo; Schuman, Joel S; Bilonick, Richard A; Ling, Yun; Kagemann, Larry; Sigal, Ian A; Grulkowski, Ireneusz; Liu, Jonathan J; Fujimoto, James G; Ishikawa, Hiroshi; Wollstein, Gadi
Purpose: Evaluation of the effect of prelaminar tissue thickness on visualization of the lamina cribrosa (LC) using optical coherence tomography (OCT). Methods: The optic nerve head (ONH) region was scanned using OCT. The quality of visible LC microstructure was assessed subjectively using a grading system and objectively by analyzing the signal intensity of each scan's superpixel components. Manual delineations were made separately and in 3-dimensions quantifying prelaminar tissue thickness, analyzable regions of LC microstructure, and regions with a visible anterior LC (ALC) boundary. A linear mixed effect model quantified the association between tissue thickness and LC visualization. Results: A total of 17 healthy, 27 glaucoma suspect, and 47 glaucomatous eyes were included. Scans with thicker average prelaminar tissue measurements received worse grading scores (P = 0.007), and superpixels with low signal intensity were associated significantly with regions beneath thick prelaminar tissue (P < 0.05). The average prelaminar tissue thickness in regions of scans where the LC was analyzable (214 mum) was significantly thinner than in regions where the LC was not analyzable (569 mum; P < 0.001). Healthy eyes had significantly thicker average prelaminar tissue measurements than glaucoma or glaucoma suspect eyes (both P < 0.001), and glaucoma suspect eyes had significantly thicker average prelaminar tissue measurements than glaucoma eyes (P = 0.008). Significantly more of the ALC boundary was visible in glaucoma eyes (63% of ONH) than in healthy eyes (41%; P = 0.005). Conclusions: Thick prelaminar tissue was associated with impaired visualization of the LC. Healthy subjects generally had thicker prelaminar tissue, which potentially could create a selection bias against healthy eyes when comparing LC structures.
PMCID:5361612
PMID: 28324116
ISSN: 0146-0404
CID: 2494492

Adaptive optics optical coherence tomography in glaucoma

Dong, Zachary M; Wollstein, Gadi; Wang, Bo; Schuman, Joel S
Since the introduction of commercial optical coherence tomography (OCT) systems, the ophthalmic imaging modality has rapidly expanded and it has since changed the paradigm of visualization of the retina and revolutionized the management and diagnosis of neuro-retinal diseases, including glaucoma. OCT remains a dynamic and evolving imaging modality, growing from time-domain OCT to the improved spectral-domain OCT, adapting novel image analysis and processing methods, and onto the newer swept-source OCT and the implementation of adaptive optics (AO) into OCT. The incorporation of AO into ophthalmic imaging modalities has enhanced OCT by improving image resolution and quality, particularly in the posterior segment of the eye. Although OCT previously captured in-vivo cross-sectional images with unparalleled high resolution in the axial direction, monochromatic aberrations of the eye limit transverse or lateral resolution to about 15-20 mum and reduce overall image quality. In pairing AO technology with OCT, it is now possible to obtain diffraction-limited resolution images of the optic nerve head and retina in three-dimensions, increasing resolution down to a theoretical 3 mum3. It is now possible to visualize discrete structures within the posterior eye, such as photoreceptors, retinal nerve fiber layer bundles, the lamina cribrosa, and other structures relevant to glaucoma. Despite its limitations and barriers to widespread commercialization, the expanding role of AO in OCT is propelling this technology into clinical trials and onto becoming an invaluable modality in the clinician's arsenal.
PMCID:5350038
PMID: 27916682
ISSN: 1873-1635
CID: 2354152

Reply [Letter]

Schuman, Joel S; Ishikawa, Hiroshi; Wollstein, Gadi
PMID: 28219506
ISSN: 1549-4713
CID: 2458112

Whole-eye transplantation: a look into the past and vision for the future

Bourne, D; Li, Y; Komatsu, C; Miller, M R; Davidson, E H; He, L; Rosner, I A; Tang, H; Chen, W; Solari, M G; Schuman, J S; Washington, K M
Blindness afflicts ~39 million people worldwide. Retinal ganglion cells are unable to regenerate, making this condition irreversible in many cases. Whole-eye transplantation (WET) provides the opportunity to replace diseased retinal ganglion cells, as well as the entire optical system and surrounding facial tissue, if necessary. Recent success in face transplantation demonstrates that this may be a promising treatment for what has been to this time an incurable condition. An animal model for WET must be established to further enhance our knowledge of nerve regeneration, immunosuppression, and technical aspects of surgery. A systematic review of the literature was performed to evaluate studies describing animal models for WET. Only articles in which the eye was completely enucleated and reimplanted were included. Study methods and results were compared. In the majority of published literature, WET can result in recovery of vision in cold-blooded vertebrates. There are a few instances in which mammalian WET models demonstrate survival of the transplanted tissue following neurovascular anastomosis and the ability to maintain brief electroretinogram activity in the new host. In this study we review in cold-blooded vertebrates and mammalian animal models for WET and discuss prospects for future research for translation to human eye transplantation.Eye advance online publication, 16 December 2016; doi:10.1038/eye.2016.272.
PMCID:5306462
PMID: 27983731
ISSN: 1476-5454
CID: 2363702

Age at natural menopause genetic risk score in relation to age at natural menopause and primary open-angle glaucoma in a US-based sample

Pasquale, Louis R; Aschard, Hugues; Kang, Jae H; Bailey, Jessica N Cooke; Lindstrom, Sara; Chasman, Daniel I; Christen, William G; Allingham, R Rand; Ashley-Koch, Allison; Lee, Richard K; Moroi, Sayoko E; Brilliant, Murray H; Wollstein, Gadi; Schuman, Joel S; Fingert, John; Budenz, Donald L; Realini, Tony; Gaasterland, Terry; Gaasterland, Douglas; Scott, William K; Singh, Kuldev; Sit, Arthur J; Igo, Robert P Jr; Song, Yeunjoo E; Hark, Lisa; Ritch, Robert; Rhee, Douglas J; Gulati, Vikas; Havens, Shane; Vollrath, Douglas; Zack, Donald J; Medeiros, Felipe; Weinreb, Robert N; Pericak-Vance, Margaret A; Liu, Yutao; Kraft, Peter; Richards, Julia E; Rosner, Bernard A; Hauser, Michael A; Haines, Jonathan L; Wiggs, Janey L
OBJECTIVE: Several attributes of female reproductive history, including age at natural menopause (ANM), have been related to primary open-angle glaucoma (POAG). We assembled 18 previously reported common genetic variants that predict ANM to determine their association with ANM or POAG. METHODS: Using data from the Nurses' Health Study (7,143 women), we validated the ANM weighted genetic risk score in relation to self-reported ANM. Subsequently, to assess the relation with POAG, we used data from 2,160 female POAG cases and 29,110 controls in the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (NEIGHBORHOOD), which consists of 8 datasets with imputed genotypes to 5.6+ million markers. Associations with POAG were assessed in each dataset, and site-specific results were meta-analyzed using the inverse weighted variance method. RESULTS: The genetic risk score was associated with self-reported ANM (P = 2.2 x 10) and predicted 4.8% of the variance in ANM. The ANM genetic risk score was not associated with POAG (Odds Ratio (OR) = 1.002; 95% Confidence Interval (CI): 0.998, 1.007; P = 0.28). No single genetic variant in the panel achieved nominal association with POAG (P >/=0.20). Compared to the middle 80 percent, there was also no association with the lowest 10 percentile or highest 90 percentile of genetic risk score with POAG (OR = 0.75; 95% CI: 0.47, 1.21; P = 0.23 and OR = 1.10; 95% CI: 0.72, 1.69; P = 0.65, respectively). CONCLUSIONS: A genetic risk score predicting 4.8% of ANM variation was not related to POAG; thus, genetic determinants of ANM are unlikely to explain the previously reported association between the two phenotypes.This is an open-access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share thework provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0.
PMCID:5266624
PMID: 27760082
ISSN: 1530-0374
CID: 2297662

Mapping in-vivo optic nerve head strains caused by intraocular and intracranial pressures

Tran, H; Grimm, J; Wang, B; Smith, M A; Gogola, A; Nelson, S; Tyler-Kabara, E; Schuman, J; Wollstein, G; Sigal, I A
Although it is well documented that abnormal levels of either intraocular (IOP) or intracranial pressure (ICP) can lead to potentially blinding conditions, such as glaucoma and papilledema, little is known about how the pressures actually affect the eye. Even less is known about potential interplay between their effects, namely how the level of one pressure might alter the effects of the other. Our goal was to measure in-vivo the pressure-induced stretch and compression of the lamina cribrosa due to acute changes of IOP and ICP. The lamina cribrosa is a structure within the optic nerve head, in the back of the eye. It is important because it is in the lamina cribrosa that the pressure-induced deformations are believed to initiate damage to neural tissues leading to blindness. An eye of a rhesus macaque monkey was imaged in-vivo with optical coherence tomography while IOP and ICP were controlled through cannulas in the anterior chamber and lateral ventricle, respectively. The image volumes were analyzed with a newly developed digital image correlation technique. The effects of both pressures were highly localized, nonlinear and non-monotonic, with strong interactions. Pressure variations from the baseline normal levels caused substantial stretch and compression of the neural tissues in the posterior pole, sometimes exceeding 20%. Chronic exposure to such high levels of biomechanical insult would likely lead to neural tissue damage and loss of vision. Our results demonstrate the power of digital image correlation technique based on non-invasive imaging technologies to help understand how pressures induce biomechanical insults and lead to vision problems.
PMCID:5880553
PMID: 29618852
ISSN: 0277-786x
CID: 3025772

Signal Normalization Reduces Image Appearance Disparity Among Multiple Optical Coherence Tomography Devices

Chen, Chieh-Li; Ishikawa, Hiroshi; Wollstein, Gadi; Bilonick, Richard A; Kagemann, Larry; Schuman, Joel S
PURPOSE: To assess the effect of the previously reported optical coherence tomography (OCT) signal normalization method on reducing the discrepancies in image appearance among spectral-domain OCT (SD-OCT) devices. METHODS: Healthy eyes and eyes with various retinal pathologies were scanned at the macular region using similar volumetric scan patterns with at least two out of three SD-OCT devices at the same visit (Cirrus HD-OCT, Zeiss, Dublin, CA; RTVue, Optovue, Fremont, CA; and Spectralis, Heidelberg Engineering, Heidelberg, Germany). All the images were processed with the signal normalization. A set of images formed a questionnaire with 24 pairs of cross-sectional images from each eye with any combination of the three SD-OCT devices either both pre- or postsignal normalization. Observers were asked to evaluate the similarity of the two displayed images based on the image appearance. The effects on reducing the differences in image appearance before and after processing were analyzed. RESULTS: Twenty-nine researchers familiar with OCT images participated in the survey. Image similarity was significantly improved after signal normalization for all three combinations (P
PMCID:5338476
PMID: 28275528
ISSN: 2164-2591
CID: 2476322

NEOVASCULAR GLAUCOMA

Chapter by: Goel, Manik; Schuman, Joel S.
in: ANTI-VEGF: USE IN OPHTHALMOLOGY by
pp. 167-176
ISBN: 978-1-63091-321-2
CID: 4366422

In-vivo effects of intraocular and intracranial pressures on the lamina cribrosa microstructure

Wang, Bo; Tran, Huong; Smith, Matthew A; Kostanyan, Tigran; Schmitt, Samantha E; Bilonick, Richard A; Jan, Ning-Jiun; Kagemann, Larry; Tyler-Kabara, Elizabeth C; Ishikawa, Hiroshi; Schuman, Joel S; Sigal, Ian A; Wollstein, Gadi
There is increasing clinical evidence that the eye is not only affected by intraocular pressure (IOP), but also by intracranial pressure (ICP). Both pressures meet at the optic nerve head of the eye, specifically the lamina cribrosa (LC). The LC is a collagenous meshwork through which all retinal ganglion cell axons pass on their way to the brain. Distortion of the LC causes a biological cascade leading to neuropathy and impaired vision in situations such as glaucoma and idiopathic intracranial hypertension. While the effect of IOP on the LC has been studied extensively, the coupled effects of IOP and ICP on the LC remain poorly understood. We investigated in-vivo the effects of IOP and ICP, controlled via cannulation of the eye and lateral ventricle in the brain, on the LC microstructure of anesthetized rhesus monkeys eyes using the Bioptigen spectral-domain optical coherence tomography (OCT) device (Research Triangle, NC). The animals were imaged with their head upright and the rest of their body lying prone on a surgical table. The LC was imaged at a variety of IOP/ICP combinations, and microstructural parameters, such as the thickness of the LC collagenous beams and diameter of the pores were analyzed. LC microstructure was confirmed by histology. We determined that LC microstructure deformed in response to both IOP and ICP changes, with significant interaction between the two. These findings emphasize the importance of considering both IOP and ICP when assessing optic nerve health.
PMCID:5697865
PMID: 29161320
ISSN: 1932-6203
CID: 2919442

An imaged-based inverse finite element method to determine in-vivo mechanical properties of the human trabecular meshwork

Pant, Anup D; Kagemann, Larry; Schuman, Joel S; Sigal, Ian A; Amini, Rouzbeh
Aim/UNASSIGNED:Previous studies have shown that the trabecular meshwork (TM) is mechanically stiffer in glaucomatous eyes as compared to normal eyes. It is believed that elevated TM stiffness increases resistance to the aqueous humor outflow, producing increased intraocular pressure (IOP). It would be advantageous to measure TM mechanical properties in vivo, as these properties are believed to play an important role in the pathophysiology of glaucoma and could be useful for identifying potential risk factors. The purpose of this study was to develop a method to estimate in-vivo TM mechanical properties using clinically available exams and computer simulations. Design/UNASSIGNED:Inverse finite element simulation. Methods/UNASSIGNED:A finite element model of the TM was constructed from optical coherence tomography (OCT) images of a healthy volunteer before and during IOP elevation. An axisymmetric model of the TM was then constructed. Images of the TM at a baseline IOP level of 11, and elevated level of 23 mmHg were treated as the undeformed and deformed configurations, respectively. An inverse modeling technique was subsequently used to estimate the TM shear modulus (G). An optimization technique was used to find the shear modulus that minimized the difference between Schlemm's canal area in the in-vivo images and simulations. Results/UNASSIGNED:Upon completion of inverse finite element modeling, the simulated area of the Schlemm's canal changed from 8,889 µm2 to 2,088 µm2, similar to the experimentally measured areal change of the canal (from 8,889 µm2 to 2,100 µm2). The calculated value of shear modulus was found to be 1.93 kPa, (implying an approximate Young's modulus of 5.75 kPa), which is consistent with previous ex-vivo measurements. Conclusion/UNASSIGNED:The combined imaging and computational simulation technique provides a unique approach to calculate the mechanical properties of the TM in vivo without any surgical intervention. Quantification of such mechanical properties will help us examine the mechanistic role of TM biomechanics in the regulation of IOP in healthy and glaucomatous eyes.
PMCID:5766041
PMID: 29338062
ISSN: 2468-3930
CID: 2915542