A Case for The Use of Artificial Intelligence in Glaucoma Assessment
We hypothesize that artificial intelligence applied to relevant clinical testing in glaucoma has the potential to enhance the ability to detect glaucoma. This premise was discussed at the recent Collaborative Community for Ophthalmic Imaging meeting, "The Future of Artificial Intelligence-Enabled Ophthalmic Image Interpretation: Accelerating Innovation and Implementation Pathways," held virtually September 3-4, 2020. The Collaborative Community in Ophthalmic Imaging (CCOI) is an independent self-governing consortium of stakeholders with broad international representation from academic institutions, government agencies, and the private sector whose mission is to act as a forum for the purpose of helping speed innovation in healthcare technology. It was one of the first two such organizations officially designated by the FDA in September 2019 in response to their announcement of the collaborative community program as a strategic priority for 2018-2020. Further information on the CCOI can be found online at their website (https://www.cc-oi.org/about). Artificial intelligence for glaucoma diagnosis would have high utility globally, as access to care is limited in many parts of the world and half of all people with glaucoma are unaware of their illness. The application of artificial intelligence technology to glaucoma diagnosis has the potential to broadly increase access to care worldwide, in essence flattening the Earth by providing expert level evaluation to individuals even in the most remote regions of the planet.
A novel glaucoma approach: Stem cell regeneration of the trabecular meshwork
Glaucoma is the leading cause of global irreversible blindness, necessitating research for new, more efficacious treatment options than currently exist. Trabecular meshwork (TM) cells play an important role in the maintenance and function of the aqueous outflow pathway, and studies have found that there is decreased cellularity of the TM in glaucoma. Regeneration of the TM with stem cells has been proposed as a novel therapeutic option by several reports over the last few decades. Stem cells have the capacity for self-renewal and the potential to differentiate into adult functional cells. Several types of stem cells have been investigated in ocular regenerative medicine: tissue specific stem cells, embryonic stem cells, induced pluripotent stem cells, and adult mesenchymal stem cells. These cells have been used in various glaucoma animal models and ex vivo models and have shown success in IOP homeostasis and TM cellularity restoration. They have also demonstrated stability without serious side effects for a significant period of time. Based on current knowledge of TM pathology in glaucoma and existing literature regarding stem cell regeneration of this tissue, we propose a human clinical study as the next step in understanding this potentially revolutionary treatment paradigm. The ability to protect and replace TM cells in glaucomatous eyes could change the field forever.
3D Microstructure of the Healthy Non-Human Primate Lamina Cribrosa by Optical Coherence Tomography Imaging
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 Â± 2.1 years. The mean analyzable depth was 175 Â± 37Â Âµm, with average LC visibility of 25.4 Â± 13.0% and average disc area of 2.67 Â± 0.45mm2. Within this volume, an average of 74.9 Â± 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.
Artificial Intelligence for Glaucoma: Creating and Implementing AI for Disease Detection and Progression
On September 3rd, 2020, the Collaborative Community on Ophthalmic Imaging (CCOI) conducted its first two-day virtual workshop on the role of artificial intelligence (AI) and related machine learning (ML) techniques for the diagnosis and treatment of various ophthalmic conditions. In a session entitled, "Artificial Intelligence For Glaucoma", a panel of glaucoma specialists, researchers, industry experts, and patients convened to share current research on the application of AI to commonly used diagnostic modalities including fundus photography, optical coherence tomography imaging, standard automated perimetry, and gonioscopy. The conference participants focused on the use of AI as a tool for disease prediction, highlighted its ability to address inequalities, and presented the limitations and challenges to its real-world clinical application. The panelists' discussion addressed AI and health equities from the clinical, societal and regulatory perspectives.
In vivo MRI evaluation of anterograde manganese transport along the visual pathway following whole eye transplantation
BACKGROUND:administration into both native and transplanted eyes. RESULTS:Â 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:Â 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 ofÂ in vivoÂ MEMRI. CONCLUSION/CONCLUSIONS:Â 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,Â in vivoÂ MEMRI is well-suited to guide strategies for successful WET integration for vision restoration. Keywords (Max 6):Â Anterograde transport, magnetic resonance imaging, manganese, neuroregeneration, optic nerve, whole-eye transplantation.
Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms
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.
In Vivo Sublayer Analysis of Human Retinal Inner Plexiform Layer Obtained by Visible-Light Optical Coherence Tomography
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 Â± 13.4 and 45.4 Â± 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 Â± 1.5 Âµm in glaucomatous and 40.1 Â± 1.7 Âµm 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.
Interplay between intraocular and intracranial pressure effects on the optic nerve head in vivo
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 0.17mm2â€¯at baseline IOP, and contracted BMO area by 0.02â€¯mm2â€¯at high IOP. ICP elevation decreased ALC depth by 10Î¼mâ€¯at baseline IOP, but increased depth by 7â€¯Î¼mâ€¯at high IOP. ALC visibility decreased as ICP increased, both at baseline (-10%) and high IOP (-17%). IOP elevation expanded BMO area by 0.04â€¯mm2â€¯at baseline ICP, and contracted BMO area by 0.09â€¯mm2â€¯at high ICP. On average, IOP elevation caused the ALC to displace 3.3â€¯Î¼m anteriorly at baseline ICP, and 22â€¯Î¼m 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.
Optical Coherence Tomography and Glaucoma
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.
Diffusion Tensor Imaging of Visual Pathway Abnormalities in Five Glaucoma Animal Models
Purpose:To characterize the visual pathway integrity of five glaucoma animal models using diffusion tensor imaging (DTI). Methods:Two experimentally induced and three genetically determined models of glaucoma were evaluated. For inducible models, chronic IOP elevation was achieved via intracameral injection of microbeads or laser photocoagulation of the trabecular meshwork in adult rodent eyes. For genetic models, the DBA/2J mouse model of pigmentary glaucoma, the LTBP2 mutant feline model of congenital glaucoma, and the transgenic TBK1 mouse model of normotensive glaucoma were compared with their respective genetically matched healthy controls. DTI parameters, including fractional anisotropy, axial diffusivity, and radial diffusivity, were evaluated along the optic nerve and optic tract. Results:Significantly elevated IOP relative to controls was observed in each animal model except for the transgenic TBK1 mice. Significantly lower fractional anisotropy and higher radial diffusivity were observed along the visual pathways of the microbead- and laser-induced rodent models, the DBA/2J mice, and the LTBP2-mutant cats compared with their respective healthy controls. The DBA/2J mice also exhibited lower axial diffusivity, which was not observed in the other models examined. No apparent DTI change was observed in the transgenic TBK1 mice compared with controls. Conclusions:Chronic IOP elevation was accompanied by decreased fractional anisotropy and increased radial diffusivity along the optic nerve or optic tract, suggestive of disrupted microstructural integrity in both inducible and genetic glaucoma animal models. The effects on axial diffusivity differed between models, indicating that this DTI metric may represent different aspects of pathological changes over time and with severity.