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3D Microstructure of the Healthy Non-Human Primate Lamina Cribrosa by Optical Coherence Tomography Imaging

Sainulabdeen, Anoop; Glidai, Yoav; Wu, Mengfei; Liu, Mengling; Alexopoulos, Palaiologos; Ishikawa, Hiroshi; Schuman, Joel S; Wollstein, Gadi
Purpose/UNASSIGNED:The lamina cribrosa (LC) has an important role in the pathophysiology of ocular diseases. The purpose of this study is to characterize in vivo, noninvasively, and in 3D the structure of the LC in healthy non-human primates (NHPs). Methods/UNASSIGNED:Spectral-domain optical coherence tomography (OCT; Leica, Chicago, IL) scans of the optic nerve head (ONH) were obtained from healthy adult rhesus macaques monkeys. Using a previously reported semi-automated segmentation algorithm, microstructure measurements were assessed in central and peripheral regions of an equal area, in quadrants and depth-wise. Linear mixed-effects models were used to compare parameters among regions, adjusting for visibility, age, analyzable depth, graded scan quality, disc area, and the correlation between eyes. Spearmen's rank correlation coefficients were calculated for assessing the association between the lamina's parameters. Results/UNASSIGNED:Sixteen eyes of 10 animals (7 males and 3 females; 9 OD, 7 OS) were analyzed with a mean age of 10.5 ± 2.1 years. The mean analyzable depth was 175 ± 37 µm, with average LC visibility of 25.4 ± 13.0% and average disc area of 2.67 ± 0.45mm2. Within this volume, an average of 74.9 ± 39.0 pores per eye were analyzed. The central region showed statistically significantly thicker beams than the periphery. The quadrant-based analysis showed significant differences between the superior and inferior quadrants. The anterior LC had smaller beams and pores than both middle and posterior lamina. Conclusions/UNASSIGNED:Our study provides in vivo microstructure details of NHP's LC to be used as the foundation for future studies. We demonstrated mostly small but statistically significant regional variations in LC microstructure that should be considered when comparing LC measurements.
PMCID:9034718
PMID: 35435922
ISSN: 2164-2591
CID: 5206252

Virtual Reality Oculokinetic Perimetry Test Reproducibility and Relationship to Conventional Perimetry and OCT

Greenfield, Jason A; Deiner, Michael; Nguyen, Anwell; Wollstein, Gadi; Damato, Bertil; Backus, Benjamin T; Wu, Mengfei; Schuman, Joel S; Ou, Yvonne
Purpose/UNASSIGNED:Vivid Vision Perimetry (VVP; Vivid Vision, Inc) is a novel method for performing in-office and home-based visual field assessment using a virtual reality platform and oculokinetic perimetry. Here we examine the reproducibility of VVP Swift and compare results with conventional standard automated perimetry (SAP) and spectral-domain (SD) OCT. Design/UNASSIGNED:Cross-sectional study. Participants/UNASSIGNED:Fourteen eyes of 7 patients with open-angle glaucoma (OAG) (average age, 64.6 years; 29% women) and 10 eyes of 5 patients with suspected glaucoma (average age, 61.8 years; 40% women) were enrolled. Methods/UNASSIGNED:Patients with OAG and suspected glaucoma were enrolled prospectively and underwent 2 VVP Swift examinations. Results were compared with 1 conventional SAP examination (Humphrey Visual Field [HVF]; Zeiss) and 1 SD OCT examination. Main Outcome Measures/UNASSIGNED:Mean sensitivity (in decibels) obtained for each eye in 2 VVP Swift test sessions and a conventional SAP examination, thickness of the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) for the SD OCT examination, and mean test durations of the VVP Swift and SAP examinations. Results/UNASSIGNED:< 0.001), respectively. Conclusions/UNASSIGNED:Our results demonstrated that the VVP Swift test can generate reproducible results and is comparable with conventional SAP. This suggests that the device can be used by clinicians to assess visual function in glaucoma.
PMCID:9562375
PMID: 36276927
ISSN: 2666-9145
CID: 5359242

In vivo MRI evaluation of anterograde manganese transport along the visual pathway following whole eye transplantation

Komatsu, Chiaki; van der Merwe, Yolandi; He, Lin; Kasi, Anisha; Sims, Jeffrey R; Miller, Maxine R; Rosner, Ian A; Khatter, Neil J; Su, An-Jey A; Schuman, Joel S; Washington, Kia M; Chan, Kevin C
BACKGROUND:administration into both native and transplanted eyes. RESULTS: No significant intraocular pressure difference was found between native and transplanted eyes, whereas comparable manganese enhancement was observed between native and transplanted intraorbital optic nerves, suggesting the presence of anterograde manganese transport after WET. No enhancement was detected across the coaptation site in the higher visual areas of the recipient brain. Comparison with Existing Methods: Existing imaging methods to assess WET focus on either the eye or local optic nerve segments without direct visualization and longitudinal quantification of physiological transport along the transplanted visual pathway, hence the development of in vivo MEMRI. CONCLUSION/CONCLUSIONS: Our established imaging platform indicated that essential physiological transport exists in the transplanted optic nerve after WET. As neuroregenerative approaches are being developed to connect the transplanted eye to the recipient's brain, in vivo MEMRI is well-suited to guide strategies for successful WET integration for vision restoration. Keywords (Max 6): Anterograde transport, magnetic resonance imaging, manganese, neuroregeneration, optic nerve, whole-eye transplantation.
PMID: 35202613
ISSN: 1872-678x
CID: 5167792

Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms

McDowell, Colleen M; Kizhatil, Krishnakumar; Elliott, Michael H; Overby, Darryl R; van Batenburg-Sherwood, Joseph; Millar, J Cameron; Kuehn, Markus H; Zode, Gulab; Acott, Ted S; Anderson, Michael G; Bhattacharya, Sanjoy K; Bertrand, Jacques A; Borras, Terete; Bovenkamp, Diane E; Cheng, Lin; Danias, John; De Ieso, Michael Lucio; Du, Yiqin; Faralli, Jennifer A; Fuchshofer, Rudolf; Ganapathy, Preethi S; Gong, Haiyan; Herberg, Samuel; Hernandez, Humberto; Humphries, Peter; John, Simon W M; Kaufman, Paul L; Keller, Kate E; Kelley, Mary J; Kelly, Ruth A; Krizaj, David; Kumar, Ajay; Leonard, Brian C; Lieberman, Raquel L; Liton, Paloma; Liu, Yutao; Liu, Katy C; Lopez, Navita N; Mao, Weiming; Mavlyutov, Timur; McDonnell, Fiona; McLellan, Gillian J; Mzyk, Philip; Nartey, Andrews; Pasquale, Louis R; Patel, Gaurang C; Pattabiraman, Padmanabhan P; Peters, Donna M; Raghunathan, Vijaykrishna; Rao, Ponugoti Vasantha; Rayana, Naga; Raychaudhuri, Urmimala; Reina-Torres, Ester; Ren, Ruiyi; Rhee, Douglas; Chowdhury, Uttio Roy; Samples, John R; Samples, E Griffen; Sharif, Najam; Schuman, Joel S; Sheffield, Val C; Stevenson, Cooper H; Soundararajan, Avinash; Subramanian, Preeti; Sugali, Chenna Kesavulu; Sun, Yang; Toris, Carol B; Torrejon, Karen Y; Vahabikashi, Amir; Vranka, Janice A; Wang, Ting; Willoughby, Colin E; Xin, Chen; Yun, Hongmin; Zhang, Hao F; Fautsch, Michael P; Tamm, Ernst R; Clark, Abbot F; Ethier, C Ross; Stamer, W Daniel
Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings.
PMCID:8842499
PMID: 35129590
ISSN: 1552-5783
CID: 5156372

In Vivo Sublayer Analysis of Human Retinal Inner Plexiform Layer Obtained by Visible-Light Optical Coherence Tomography

Ghassabi, Zeinab; Kuranov, Roman V; Schuman, Joel S; Zambrano, Ronald; Wu, Mengfei; Liu, Mengling; Tayebi, Behnam; Wang, Yuanbo; Rubinoff, Ian; Liu, Xiaorong; Wollstein, Gadi; Zhang, Hao F; Ishikawa, Hiroshi
Purpose/UNASSIGNED:Growing evidence suggests that dendrite retraction or degeneration in a subpopulation of the retinal ganglion cells (RGCs) may precede detectable soma abnormalities and RGC death in glaucoma. Visualization of the lamellar structure of the inner plexiform layer (IPL) could advance clinical management and fundamental understanding of glaucoma. We investigated whether visible-light optical coherence tomography (vis-OCT) could detect the difference in the IPL sublayer thicknesses between small cohorts of healthy and glaucomatous subjects. Method/UNASSIGNED:We imaged nine healthy and five glaucomatous subjects with vis-OCT. Four of the healthy subjects were scanned three times each in two separate visits, and five healthy and five glaucoma subjects were scanned three times during a single visit. IPL sublayers were manually segmented using averaged A-line profiles. Results/UNASSIGNED:The mean ages of glaucoma and healthy subjects are 59.6 ± 13.4 and 45.4 ± 14.4 years (P = 0.02.) The visual field mean deviations (MDs) are -26.4 to -7.7 dB in glaucoma patients and -1.6 to 1.1 dB in healthy subjects (P = 0.002). Median coefficients of variation (CVs) of intrasession repeatability for the entire IPL and three sublayers are 3.1%, 5.6%, 6.9%, and 5.6% in healthy subjects and 1.8%, 6.0%, 7.7%, and 6.2% in glaucoma patients, respectively. The mean IPL thicknesses are 36.2 ± 1.5 µm in glaucomatous and 40.1 ± 1.7 µm in healthy eyes (P = 0.003). Conclusions/UNASSIGNED:IPL sublayer analysis revealed that the middle sublayer could be responsible for the majority of IPL thinning in glaucoma. Vis-OCT quantified IPL sublayers with good repeatability in both glaucoma and healthy subjects.
PMID: 35024761
ISSN: 1552-5783
CID: 5118912

Comprehensive Glaucoma Imaging

Chapter by: Glidai, Yoav; Kahook, Malik Y.; Noecker, Robert J.; Wollstein, Gadi; Schuman, Joel S.
in: Albert and Jakobiec's Principles and Practice of Ophthalmology: Fourth Edition by
[S.l.] : Springer International Publishing, 2022
pp. 2099-2119
ISBN: 9783030426330
CID: 5500852

Cycloablation

Chapter by: Liebenthal, Rebecca; Kahook, Malik Y.; Noecker, Robert J.; Schuman, Joel S.
in: Albert and Jakobiec's Principles and Practice of Ophthalmology: Fourth Edition by
[S.l.] : Springer International Publishing, 2022
pp. 2463-2479
ISBN: 9783030426330
CID: 5500652

The Development and Clinical Application of Innovative Optical Ophthalmic Imaging Techniques

Alexopoulos, Palaiologos; Madu, Chisom; Wollstein, Gadi; Schuman, Joel S
The field of ophthalmic imaging has grown substantially over the last years. Massive improvements in image processing and computer hardware have allowed the emergence of multiple imaging techniques of the eye that can transform patient care. The purpose of this review is to describe the most recent advances in eye imaging and explain how new technologies and imaging methods can be utilized in a clinical setting. The introduction of optical coherence tomography (OCT) was a revolution in eye imaging and has since become the standard of care for a plethora of conditions. Its most recent iterations, OCT angiography, and visible light OCT, as well as imaging modalities, such as fluorescent lifetime imaging ophthalmoscopy, would allow a more thorough evaluation of patients and provide additional information on disease processes. Toward that goal, the application of adaptive optics (AO) and full-field scanning to a variety of eye imaging techniques has further allowed the histologic study of single cells in the retina and anterior segment. Toward the goal of remote eye care and more accessible eye imaging, methods such as handheld OCT devices and imaging through smartphones, have emerged. Finally, incorporating artificial intelligence (AI) in eye images has the potential to become a new milestone for eye imaging while also contributing in social aspects of eye care.
PMCID:9279625
PMID: 35847772
ISSN: 2296-858x
CID: 5278832

Interplay between intraocular and intracranial pressure effects on the optic nerve head in vivo

Zhu, Ziyi; Waxman, Susannah; Wang, Bo; Wallace, Jacob; Schmitt, Samantha E; Tyler-Kabara, Elizabeth; Ishikawa, Hiroshi; Schuman, Joel S; Smith, Matthew A; Wollstein, Gadi; Sigal, Ian A
Intracranial pressure (ICP) has been proposed to play an important role in the sensitivity to intraocular pressure (IOP) and susceptibility to glaucoma. However, the in vivo effects of simultaneous, controlled, acute variations in ICP and IOP have not been directly measured. We quantified the deformations of the anterior lamina cribrosa (ALC) and scleral canal at Bruch's membrane opening (BMO) under acute elevation of IOP and/or ICP. Four eyes of three adult monkeys were imaged in vivo with OCT under four pressure conditions: IOP and ICP either at baseline or elevated. The BMO and ALC were reconstructed from manual delineations. From these, we determined canal area at the BMO (BMO area), BMO aspect ratio and planarity, and ALC median depth relative to the BMO plane. To better account for the pressure effects on the imaging, we also measured ALC visibility as a percent of the BMO area. Further, ALC depths were analyzed only in regions where the ALC was visible in all pressure conditions. Bootstrap sampling was used to obtain mean estimates and confidence intervals, which were then used to test for significant effects of IOP and ICP, independently and in interaction. Response to pressure manipulation was highly individualized between eyes, with significant changes detected in a majority of the parameters. Significant interactions between ICP and IOP occurred in all measures, except ALC visibility. On average, ICP elevation expanded BMO area by 0.17mm2 at baseline IOP, and contracted BMO area by 0.02 mm2 at high IOP. ICP elevation decreased ALC depth by 10μm at baseline IOP, but increased depth by 7 μm at high IOP. ALC visibility decreased as ICP increased, both at baseline (-10%) and high IOP (-17%). IOP elevation expanded BMO area by 0.04 mm2 at baseline ICP, and contracted BMO area by 0.09 mm2 at high ICP. On average, IOP elevation caused the ALC to displace 3.3 μm anteriorly at baseline ICP, and 22 μm posteriorly at high ICP. ALC visibility improved as IOP increased, both at baseline (5%) and high ICP (8%). In summary, changing IOP or ICP significantly deformed both the scleral canal and the lamina of the monkey ONH, regardless of the other pressure level. There were significant interactions between the effects of IOP and those of ICP on LC depth, BMO area, aspect ratio and planarity. On most eyes, elevating both pressures by the same amount did not cancel out the effects. Altogether our results show that ICP affects sensitivity to IOP, and thus that it can potentially also affect susceptibility to glaucoma.
PMID: 34736887
ISSN: 1096-0007
CID: 5038392

Optical Coherence Tomography and Glaucoma

Geevarghese, Alexi; Wollstein, Gadi; Ishikawa, Hiroshi; Schuman, Joel S
Early detection and monitoring are critical to the diagnosis and management of glaucoma, a progressive optic neuropathy that causes irreversible blindness. Optical coherence tomography (OCT) has become a commonly utilized imaging modality that aids in the detection and monitoring of structural glaucomatous damage. Since its inception in 1991, OCT has progressed through multiple iterations, from time-domain OCT, to spectral-domain OCT, to swept-source OCT, all of which have progressively improved the resolution and speed of scans. Even newer technological advancements and OCT applications, such as adaptive optics, visible-light OCT, and OCT-angiography, have enriched the use of OCT in the evaluation of glaucoma. This article reviews current commercial and state-of-the-art OCT technologies and analytic techniques in the context of their utility for glaucoma diagnosis and management, as well as promising future directions.
PMID: 34242054
ISSN: 2374-4650
CID: 5011472