Faculty Bibliography

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.

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.

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.

Background: Retinal imaging by optical coherence tomography (OCT) has gained increasing attention in multiple sclerosis and other neuroinflammatory and neurodegenerative disorders. Ambiguous and incomplete reporting of methodology and OCT-derived data have limited the ability to compare data and to apply and generalize findings in the past. To improve this situation, the Advised Protocol for Optical coherence tomography Study Terminology and Elements (APOSTEL) recommendations have been developed to outline core information to be provided when reporting quantitative OCT studies with help of a 9-point checklist (Cruz-Herranz and Balk et al., Neurology 2016). The APOSTEL recommendations currently have the evidence level of an expert opinion (Class IV). Objective: To advance the APOSTEL recommendations for OCT reporting in a formalized procedure towards evidence-based guidelines. Methods: Studies reporting quantitative OCT results published within the last 24 months have been identified by a Pubmed search. The corresponding authors of these 1472 articles will be contacted and asked to participate in an online survey to evaluate and give feedback on the initial APOSTEL recommendations. The feedback obtained will be anonymized and distributed to a panel of international experts for evaluation and revision of the recommendations. After the initial round the corresponding authors who gave feedback will be informed about the intermediate results and asked to participate in the survey for a second time. This procedure will be repeated if necessary following the consensus-building procedure of a DELPHI process. To this end, for each round the feedback obtained as well as any revisions made to the APOSTEL recommendations will be summarized and questionnaires will be used for evaluation in order to reach consensus and to develop evidencebased guidelines for prospective OCT studies. Results: The degree of consensus of the survey's participants will be reported for the initial and the revised versions of the recommendations as well as the revisions made to the initial version. Conclusion: Formal guidelines for the reporting of quantitative OCT studies will be presented as well as the process of how they were developed

PURPOSE/OBJECTIVE:To measure the waste generation and lifecycle environmental emissions from cataract surgery via phacoemulsification in a recognized resource-efficient setting. SETTING/METHODS:Two tertiary care centers of the Aravind Eye Care System in southern India. DESIGN/METHODS:Observational case series. METHODS:Manual waste audits, purchasing data, and interviews with Aravind staff were used in a hybrid environmental lifecycle assessment framework to quantify the environmental emissions associated with cataract surgery. Kilograms of solid waste generated and midpoint emissions in a variety of impact categories (eg, kilograms of carbon dioxide equivalents). RESULTS:Aravind generates 250 grams of waste per phacoemulsification and nearly 6 kilograms of carbon dioxide-equivalents in greenhouse gases. This is approximately 5% of the United Kingdom's phaco carbon footprint with comparable outcomes. A majority of Aravind's lifecycle environmental emissions occur in the sterilization process of reusable instruments because their surgical system uses largely reusable instruments and materials. Electricity use in the operating room and the Central Sterile Services Department (CSSD) accounts for 10% to 25% of most environmental emissions. CONCLUSIONS:Surgical systems in most developed countries and, in particular their use of materials, are unsustainable. Results show that ophthalmologists and other medical specialists can reduce material use and emissions in medical procedures using the system described here.

Ocular imaging has been heavily incorporated into glaucoma management and provides important information that aids in the detection of disease progression. Longitudinal studies have shown that the circumpapillary retinal nerve fiber layer is an important parameter for glaucoma progression detection, whereas other studies have demonstrated that macular parameters, such as the ganglion cell inner plexiform layer and optic nerve head parameters, also are useful for progression detection. The introduction of novel technologies with faster scan speeds, wider scanning fields, higher resolution, and improved tissue penetration has enabled the precise quantification of additional key ocular structures, such as the individual retinal layers, optic nerve head, choroid, and lamina cribrosa. Furthermore, extracting functional information from scans such as blood flow rate and oxygen consumption provides new perspectives on the disease and its progression. These novel methods promise improved detection of glaucoma progression and better insight into the mechanisms of progression that will lead to better targeted treatment options to prevent visual damage and blindness.

Glaucoma, a progressive and degenerative disease of the optic nerve, is the second leading cause of blindness worldwide. Mechanical deformation of the lamina cribrosa (LC) under high intraocular pressure (IOP) can lead to axonal death of optic nerve fibers. To explore the effect of pressure on the LC, we utilize an experimental setup where longitudinal 3D optical coherence tomography (OCT) images are acquired at different levels of IOP administered via a well-controlled external force. Structural changes are measured via image deformations which map all observed images simultaneously into a common coordinate space. These deformations encode local patterns of structural and volume change across the image sequence, resulting in quantification of the spatiotemporal deformation pattern of the LC due to variation of pressure. We also describe a 3D segmentation algorithm to restrict our deformation analysis separately to the beams or pores of the LC. A single case study demonstrates the potential of the proposed methodology for non-invasive in-vivo analysis of LC dynamics in individual subjects

PURPOSE: To compare longitudinal glaucoma progression detection using optical coherence tomography (OCT) and visual field (VF). DESIGN: Validity assessment METHOD: We analyzed subjects with more than 5 follow-up visits (every 6 months) in the multi-center Advanced Imaging for Glaucoma Study. Fourier-domain optical coherence tomography (OCT) was used to map the thickness of the peripapillary retinal nerve fiber layer (NFL) and ganglion cell complex (GCC). OCT-based progression detection was defined as a significant negative trend for either NFL or GCC. VF progression was reached if either the event or trend analysis reached significance. RESULT: The analysis included 417 glaucoma suspect/pre-perimetric glaucoma (GS/PPG) eyes and 377 perimetric glaucoma (PG) eyes. In the GS/PPG group, progression was detect in 38.9% of eyes by OCT, significantly more (P<0.001) than the detection rate of 18.7% by VF. In severity-stratified analysis of PG eyes, OCT had significantly higher detection rate in early PG (49.7% vs. 32.0%, p=0.02), but not significantly different in moderate and advanced PG. The rate of NFL thinning declined dramatically in advanced PG, but GCC thinning rate remained relatively steady and allowed good progression detection even in advanced disease. The rate of false positive progression detection in permutated series was over 10% for VF trend analysis in both GS/PPG and PG group, while under 7% for both GCC and NFL. CONCLUSION: OCT is a more sensitive than VF for the detection of progression in early glaucoma. While the value of NFL declines in advanced glaucoma, GCC appears to be a useful progression detector from early to advanced stages.

Advances in imaging have made it increasingly common to study soft tissues without first embedding them in plastic or paraffin and without using labels or stains. The process, however, usually still involves fixation and cryosectioning, which could deform the tissues. Our goal was to quantify the morphological changes of ocular tissues caused by formalin fixation and cryosectioning. From each of 6 porcine eyes, 4 regions were obtained: cornea, equatorial and posterior sclera, and posterior pole containing the optic nerve head. Samples were imaged using visible light microscopy fresh, 1-minute and 24-hours post-fixation, and post-cryosectioning. Effects were assessed by 14 parameters representing sample size and shape. Overall, formalin fixation and sectioning caused only minimal changes to the ocular tissues, with average percentage parameter differences of 0.1%, 1%, and 1.2% between fresh and post-fixing by 1 minute, 24 hours, and post-cryosectioning, respectively. Parameter changes were not directional, and were only weakly dependent on the duration of fixation and the region of the eye. These results demonstrate that formalin fixation and cryosectioning are good choices for studying ocular tissue morphology and structure, as they do not cause the large tissue shrinkage or distortions typically associated with other, more complicated, techniques.

Glaucoma is a leading cause of blindness that leads to characteristic changes in the optic nerve head (ONH) region, such as nasalization of vessels. It is unknown whether the spatial location of this vessel shift inside the ONH occurs within the lamina cribrosa (LC) or the prelaminar tissue. The purpose of this study was to compare the location of the central retinal vessel trunk (CRVT) in the LC and prelaminar tissue in living healthy and glaucomatous eyes. We acquired 3-dimensional ONH scans from 119 eyes (40 healthy, 29 glaucoma suspect, and 50 glaucoma) using optical coherence tomography (OCT). The CRVT location was manually delineated in separate projection images of the LC and prelamina. We found that the CRVT in glaucoma suspect and glaucomatous eyes was located significantly more nasally compared to healthy eyes at the level of the prelamina. There was no detectable difference found in the location of the CRVT at the level of the LC between diagnostic groups. While the nasal location of the CRVT in the prelamina has been associated with glaucomatous axonal death, our results suggest that the CRVT in the LC is anchored in the tissue with minimal variation in glaucomatous eyes.