Oxyopia Vision Science Seminars

Oxyopia Seminars (2015-2016)

Oxyopia, the Greek word meaning "acute vision," is the title of the weekly vision science seminars presented at the Indiana University School of Optometry in conjunction with graduate course V765. The seminars serve a twofold purpose in that they:
  1. stimulate intellectual activity among the faculty, and
  2. provide a learning environment for graduate students.

Oxyopia presenters are IU School of Optometry faculty members and graduate students as well as visiting lecturers from other departments, universities, research facilities, private practices, industry, etc.


8/28/2015 No Oxyopia

Malika Valapala

Induction of Lysosomal Function for the Treatment of Age-related Macular Degeneration Age-related macular degeneration (AMD) is a progressive degenerative disease of the eye and is the most common cause of visual loss among the elderly. Atrophic degeneration of retinal pigment epithelial (RPE) cells is a major contributor to the pathogenesis of age-related macular degeneration (AMD). In order to develop better therapeutics, it is imperative to understand the signaling mechanisms that lead to RPE degeneration. Recent evidence suggests that in AMD, reduced lysosomal function leads to the accumulation of lipofuscin and intracellular lipids resulting in progressive degeneration of the RPE. Lysosomes are crucial for proper functioning of the RPE, since these cells are subjected to the daily burden of phagocytosis of photoreceptor outer segments (POS) and autophagic degradation of cellular metabolic waste. It has also been shown that mouse models of inherited lysosomal storage diseases show striking signs of AMD, including accumulation of lipofuscin, loss of RPE cells, and degeneration of POS. The signaling mechanisms that regulate lysosomal function and thereby influence clearance mechanisms in the RPE are not well understood. The research focus of my laboratory is to identify molecular mechanisms regulating lysosomal activity and to use this knowledge to develop effective therapeutic strategies to restore or enhance lysosomal function in the RPE. The transcription factor EB (TFEB) has been identified as a master regulator of lysosomal function. TFEB is a member of the basic helix-loop-helix leucine-zipper family of transcription factors that controls lysosome biogenesis and autophagy by co-ordinated upregulation of a family of genes belonging to the Coordinated Lysosomal Expression and Regulation (CLEAR) network. Our studies show that TFEB-regulated transcriptional program induces flux through lysosomal degradative pathways in the RPE. Our future studies are directed to explore mechanisms by which the activity of TFEB can be modulated in order to induce lysosomal function, alleviate abnormal substrate accumulation and inhibit degenerative loss of RPE. We believe that these studies will enhance our understanding of RPE lysosomal biology and provide us with better avenues for therapeutic intervention.
9/11/2015 Wendy Harrison Seeing Unexplained Vision Loss  Diabetes is the leading cause of blindness in working aged Americans.  The vascular changes to the retina, diabetic retinopathy, are responsible for the majority of this vision loss.  Neural changes are also occurring in the retina at the same time or earlier than the vascular changes. These changes can be measured easily with a multifocal electroretinogram. It is possible that these neural changes hold the key to a better understanding of the diabetic retina. This talk will focus on retinal changes in diabetes and ocular neuropathy. It will review what is already known about ocular neuropathy and new directions this research is taking.
9/18/2015 Chia-Yang Liu Gene Regulatory Networks Governing Goblet Cell Differention In Ocular Surface Epithelium
The content of this lecture will cover our recent finding concerning the cellular signaling pathway(s) network in controlling normal ocular surface morphogenesis and the pathogenesis of Keratoconjunctivitis sicca (KCS or dry eye). Specifically, we focus on two important cellular signaling pathways: 1) Notch signaling activates Klf4/5 transcription factor which in turn regulates goblet cell differentiation and mucin synthesis; 2) TGFb signaling in regulating goblet cell differentiation by negative regulation of transcription factor Spdef in conjunctival epithelium. Moreover, we also found that inhibition of Notch dampened Klf4/5 expression and diminished Spdef and Muc5/ac synthesis in the conjunctival epithelium, suggesting that there is interaction between Notch and TGFb signaling pathways to control goblet cell differentiation in conjunctival epithelium. Our data may implicate that fine-tune Notch activation to control Klf4/5 expression and/or TGFβ to control Spdef can be a potential strategy to treat KCS with mucins deficient dry eye.
9/25/2015 Yujin Zhang Wnt/beta-catenin signaling modulates corneal epithelium stratification via inhibition of Bmp4 during mouse development The development of organs with an epithelial parenchyma relies on reciprocal mesenchymal-epithelial communication. Mouse corneal epithelium stratification is the consequence of a coordinated developmental process based on mesenchymal-epithelial interactions. The molecular mechanism underlying these interactions remains unclear. The Wnt/b-catenin signaling pathway involves fundamental aspects of development through the regulation of various growth factors. Here, we show that conditional ablation of either b-catenin (Ctnnb1cKO) in corneal stromal cells results in precocious stratification of the corneal epithelium. On the contrary, ectopic expression of a murine Ctnnb1 gain-of-function mutant (Ctnnb1cGOF) retards corneal epithelium stratification. We also discovered that Bmp4 is up-regulated in the absence of b-catenin in keratocytes, which further triggers ERK1/2 and Smad1/5 phosphorylation and enhances transcription factor p63 expression in mouse corneal basal epithelial cells and in a human corneal epithelial cell line (HTCE). Interestingly, mouse neonates given a subconjunctival BMP4 injection displayed a phenotype resembling Ctnnb1cKO. These data support the concept that cross-talk between the Wnt/b-catenin/Bmp4 axis (in the stromal mesenchyme) and Bmp4/p63 signaling (in the epithelium) plays a pivotal role in epithelial stratification during corneal morphogenesis.
10/2/2015 Nicholas Port

Saccadic and pursuit ocular motor deficits among individuals afflicted with Schizophrenia and their first degree relatives

The prevalence of smooth pursuit deficit among persons with schizophrenia and their first-degree relatives is one of the most replicated and robust findings within the psychophysiological literature (O'Driscoll and Callahan, 2008).  Relatively few studies, however, have examined both the smooth pursuit and saccadic systems within a sample of patients and their first-degree relatives.  The first objective of this paper was therefore to apply a broad range of classic and sensitive techniques, using a wide range of velocities and amplitudes, for evaluating smooth pursuit and saccades within a large sample of carefully documented schizophrenia patients (n = 41), their asymptomatic first-degree relatives (n = 19) and matched controls (n = 40).  Tasks examined included a visual guided horizontal main-sequence (8 amplitudes), saccadic adaptation, sinusoidal tracking (4 frequency), the Rashbass Step Ramp (3 velocities and 2 directions), and a visually guided classic center out task (to check for lateropulsion of saccades).  Our second objective was to evaluate patient and relative ocular motor deficits in relation to the cognitive dysmetria hypothesis of schizophrenia (Andreasen et al., 1996), for which impairment of the cortico-thalamic cerebellar cortical circuit (CTCCC) is theorized.  Whereas saccade kinematics in the main sequence, center out, and saccadic adaptation did not differ by group, across several tasks, we found both hypometria and longer response times for patients and relatives.  In addition we conformed the well-known pursuit deficits and found a increased pursuit lag.  Our results therefore support the idea of cerebellar involvement in schizophrenia.
10/9/2015 NO OXYOPIA (Fall Break)
10/16/2015 Gareth Hastings Scaling Wavefront Aberrations when Changing Pupil Size B Wavefront aberrometers provide arguably the most comprehensive description of the refractive errors of an eye and have become commonplace in both clinical and research settings. However, wavefront errors are typically only meaningfully described for one pupil size at a time. This presents a challenge when comparing aberrations at different pupil sizes across individuals (or even in the same individual at different time-points or under different conditions), as well as when applying a wavefront guided refractive correction (for instance via laser-ablation or in a contact lens) over a different sized area to that over which the aberration was measured. This talk will utilize recently published evidence to elaborate on the usefulness and benefits of scaling, while also discussing the limitations of some common methods of scaling.
10/23/2015 Renfeng Xu

strategies for expanding the
depth of focus
of presbyopes

Presbyopia is the condition in which with age, the lens loses its ability to accommodate, limiting the range of target distances that be well focused  Although
attempts have been made to re-­‐establish active accommodation, current surgical and intraocular lens (IOL) approaches have proves ineffective Therefore,
there are two general non-­‐accommodating strategies to treat presbyopia without glasses:
(1) include bifocal/multifocal optics in contact lenses (CL) or IOLs;or
(2) reduce pupil size and thus expand Depth of Focus. 

Both of the above methods have shown positive results clinically.


Ting Luo

Essam Saad Almutleb

Behavior of the retinal vasculature for normal and diabetes

Simulation of a Central Scotoma Using Contact Lenses with an Opaque Center

The branching of the retinal vasculature is constrained by physical principles expressed in Murray’s law, part of which states that the diameter relation between a parent vessel and the daughter branches follows a cube law i.e. the cube of the parent is equal to the sum of the cubes of the branches. Studies have suggested that Murray’s law is followed relatively well for the large vessels of the eye and deviates for smaller vessels within the range of vessels measurable by standard fundus photography. In the current study, we use the Indiana Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO) to extend this range to smaller arterioles and venules in both normal and diabetic patients.  Murray’s law also predicts the vessel bifurcation angle based on the model of the vasculature minimum pumping power and lumen volume. We calculate the bifurcation angle predicted by Murray in both normal and diabetes, comparing our measured results with other prediction models.

This pilot study evaluated the feasibility of using contact lenses (CL) with an opaque center (black pupil) to induce central scotomas that move with the eye. We examined the geometrical optics prediction that scotoma size will vary with size of the CL’s opaque center and with the ocular pupil size, and we tested the hypothesis that high environmental light levels will ensure that the ocular pupil will remain small enough even with black pupil CLs to generate these scotomas.

11/6/2015 Eli Peli

Diplopia and confusion partners in discomfort mostly together but sometime separate

With misalignment of the eyes double vision results. The two components: diplopia and confusion appear to be coexisting.   Usually only diplopia is reported. This may be a result of the statistics of natural images.   Binocular confusion is the main tool used for prismatic expansion of visual fields.   With visual field loss alone, and with use of prism segments for field expansion the two phenomena may exist in isolation, diplopia without confusion, and confusion without diplopia. The roles both play in vision rehabilitation will be explained for common and rare conditions.

11/13/2015 Ray Applegate Corneal refractive surgery: Treating the wrong location with the wrong correction

Purpose:  To examine the claim that displacing the corneal ablation from the pupil center to a location closer to the Purkinje I reflex leads to better visual outcomes.

Methods:  Modeling

Results:  Current systems apparently do not keep tract of eye rotations and may be basing corrections for the biomechanical response and angle of incidence correction at an improper location.

Conclusions:  Corneal refractive surgery has over improved outcomes to the point it is arguably good enough.  If the industry wishes to further improve accuracy and precision measurement, correction design and treatment have to be performed using a common reference system.
11/20/2015 Yang Sun

Primary cilia and inositol signaling in the eye

Primary cilium is a conserved cellular organelle that plays mechanosensory roles throughout the body.  Using rare disease models of Lowe syndrome and Joubert syndrome, we are investigating the role of cilia and inositol signaling in eye development and disease.

11/27/2015 NO OXYOPIA (Thanksgiving)

Zhuolin Liu

Jun Zhang

Estimation of Osmolarity within Areas of Tear Breakup

Estimation of Osmolarity within Areas of Tear Breakup


Retinal pigment epithelium (RPE) cells are vital to health of the outer retina, but are often compromised in ageing and major ocular diseases that lead to blindness. Early manifestation of RPE disruption occurs at the cellular level, but while biomarkers at this scale hold considerable promise, RPE cells have proven extremely challenging to image in the living human eye. We present a novel method based on OCT equipped with adaptive optics (AO) that overcomes the associated technical obstacles. The method takes advantage of 3D resolution of AO-OCT, but more critically sub-cellular segmentation and registration algorithms that we have developed and now permit averaging of RPE images without loss of RPE mosaic information. With this method we have observed the RPE mosaic in every subject and retinal location imaged to date (six eyes at 3° and 7° temporal to the fovea) and have quantified RPE packing geometry in terms of cell density, cone-to-RPE ratio, and number of nearest neighbors using Voronoi and power spectra analyses. RPE cell density (cells/mm2) showed no significant difference between 3° (5777±133) and 7° (5797±233). In contrast, cone-to-RPE ratio was significantly higher at 3° (3.19±0.32:1) than 7° (1.89±0.13:1). Voronoi analysis also showed most RPE cells have six nearest neighbors, which was significantly larger than the next two most prevalent associations: five and seven. Averaged across the six subjects, prevalence of cells with six neighbors was 49.1±3.5% at 3°, and 51.0±3.5% at 7°. These results are consistent with histology and in vivo studies using other imaging modalities.

Purpose:  Previous studies showed that tear breakup (TBU) was associated discomfort (Varikooty et al, 2009; Begley, 2013) and that increased hyperosmolarity within areas of TBU may be a factor in causing the discomfort (Liu, 2010).  The purpose of this study was to estimate tear film osmolarity by fluorescence intensity within areas of TBU using the pain response as a reference. Methods: The tear film fluorescence of 10 subjects was monitored during blink suppression while subjects turned a “pain knob” (0-10 scale) to indicate discomfort level. The percent changes in pixel intensity (PI) within the leading areas of TBU were analyzed by custom MATLAB programs. Due to the uncertainty of the initial fluorescein concentration, tear film osmolarity within TBU was estimated by percent tear thinning using both PI and square root of PI (Nichols, 2012) versus the pain response as a reference (Liu, 2010). Results: TBU ranged from 0.41% to 76.4% of the corneal area, with an average of 13.0%±17.0%. The range and average slope of the pain knob, the TBU% area and the %PI was 0.9-2.9/sec (average of 1.5±0.6sec), 0.01 to 7.86%/sec (average of 2.81±2.41), 2.87-18.35% (average of 7.41±4.87), respectively. Tear film osmolarity estimates within TBU ranged from 400-500mOsm/Kg at pain level 4, 450-600mOsm/Kg at level 6, 500-900mOsm/kg at level 8 and 600-1000mOsm/Kg at level 10, depending on whether PI or square root of the PI was used to determine thinning. The range of estimated osmolarity within TBU at the end of trials was 392-2500 mOsm/Kg using PI and 343-866 mOsm/Kg using the square root of the PI. Conclusion:  This method uses fluorescence intensity and the pain response to estimate increases in the level of hyperosmolarity within areas of TBU. More accurate estimates could include other factors, such as local fluid flow, osmosis and diffusion (Braun 2014).

12/11/2015 Basal Altoaimi

Adaptive optics and
the eye (super
resolution OCT)

The combination of adaptive optics (AO) and optical coherence tomography (OCT) was first reported 8 years ago and has undergone tremendous technological advances since then. The technical benefits of adding AO to OCT (increased lateral resolution, smaller speckle, and enhanced sensitivity) increase the imaging capability of OCT in ways that make it well suited for three-dimensional (3D) cellular imaging in the retina. Today, AO–OCT systems provide ultrahigh 3D resolution (333 lm3) and ultrahigh speed (up to an order of magnitude faster than commercial OCT). AO–OCT systems have been used to capture volume images of retinal structures,  previously only visible with histology, and are being used for studying clinical conditions.  Here, we present representative examples of cellular structures that can be visualized with
AO–OCT. We overview three studies from our laboratory that used ultrahigh-resolution AO–OCT to measure the cross-sectional profiles of individual bundles in the retinal
nerve fiber layer; the diameters of foveal capillaries that define the terminal rim of the foveal avascular zone; and the spacing and length of individual cone photoreceptor outer segments as close as 0.51 from the fovea center.  Eye (2011) 25, 321–330; doi:10.1038/eye.2011.1
12/25/2015-1/8/2016 No Oxyopia (Semester Break)

Huachun Amos Wang

Pupil Miosis benefits for highly aberrated eye

Purpose: High levels of aberrations are the primary optical problem in post-refractive surgery and keratoconic patients. The aim of this study is to examine the impact of small pupils on image quality in these high aberrated eyes at varying light levels from high photopic to low mesopic. Methods: We use a polychromatic eye model including the typical levels of higher order aberrations (HOAs) for keratoconic and post-Lasik eyes, we quantified the improvement in image quality as pupil sizes reduced from large night-time levels (e.g., 7mm) down to 1mm. Results: Small pupils yield the best image quality for these highly aberrated eyes, and this benefit remains even at 0.1 cd/m2 low mesopic light level. Although larger pupils demonstrate multifocal peaks due to highly aberrated peripheral optics, the peak image qualities are lower than that of the small pupils.  Conclusion: For highly aberrated eyes, the image quality gain from reducing HOAs of pupil miosis exceeds the losses due to extra photon noise problems that accompany small pupils.


Ayuob Lassoued

Joel Papay

Transition Zone between Healthy and Diseased Retina in Patients with Retinitis Pigmentosa

Axial analysis of cones and adjacent retinal structures using AOSLO


Purpose: Retinitis Pigmentosa (RP) is a major cause of blindness among the young adult population. Although many aspects of the disease are known, it remains a mystery as to why perfectly healthy cones die in a pathology generally caused by a genetic mutation specific to rods. To better address this question we considered the use of in vivo cellular imaging to map the dynamics of cell dystrophy across the RP transition zone, the region separating healthy from diseased retina.  Method: We used the Indiana AO-OCT system to acquire volumes of the retina of 1 adRP subject and 1 control subject. Volumes were acquired along the horizontal meridian, covering the severely diseased zone at the periphery, the healthy central zone, and the transition zone in between. Volumes were registered and segmented at the inner segment/outer segment (IS/OS) junction, the cone outer segment tip (COST), the rod outer segment tip (ROST) and the retinal pigment epithelium (RPE).  Results: At the cellular level, the orderly and laminar profile of the normal retina is visibly degraded in RP retina, regardless of zone location imaged including the healthy central zone. Across the transition zone, COST reflection disappeared before IS/OS. ROST reflection was absent at all retinal eccentricities. In contrast, ROST reflectance increased with eccentricity in the control subject. Cone density and OS length both decreased in the RP subject compared to the normal. Interestingly, at 7.5⁰, commercial OCT did not detect cones, yet AO-OCT did. A sparse array of cones was found whose length and spacing were measured.

PURPOSE. To describe the structural changes in the transition zone from relatively healthy retinal regions to severely affected regions in patients with retinitis pigmentosa (RP) using frequency domain optical coherence tomography (fdOCT).  METHODS. FdOCT line scans of the horizontal meridian were obtained from one eye of 13 patients with RP and 30 control subjects. The patients had normal or near normal foveal sensitivities and visual field diameters  superior to 10°. Using a computer-aided manual segmentation procedure, the locations at which the outer segment (OS) and outer nuclear layer plus outer plexiform layer (ONL+) thicknesses fell below the 95% confidence interval of the controls were measured, as were the locations at which the OS layer disappeared and the locations at which the ONL+ was reduced to an asymptotically small thickness.  RESULTS. The progression from healthy to severely affected regions followed a common pattern in most patients. Region A,  the central region including the foveal center, had normal OS and ONL+ thickness. Region B had abnormal OS but normal ONL+ thickness. Region C had abnormal but measurable OS and ONL+  thicknesses. In Region D, the OS layer disappeared,  as did the IS/OS line, and the ONL+ thickness decreased further. In Region E, the ONL+ reached an asymptotic thickness.  CONCLUSIONS. The structural changes in the transition zone followed an orderly progression from a thinning of the OS layer, to a thinning of the ONL+, to a loss of the OS layer, to an ONL+ reduced to an asymptotically small level. 

We imaged the retina of 10 subjects using the Indiana Adaptive Optics Scanning Laser Ophthalmoscope at approximately 7.5 deg temporal from the fovea.  We took 10 measurements at 10 different axial locations, separated by 0.3 D each.  We measured 10 bright and 10 dim cones for each subject at the 10 depths, with brightness groupings based subjectively on the most superficial location. The axial intensity profile differed for bright vs dimmer cones, with brighter cones having their maxima in the more superficial focal planes. The axial intensity profile varied between cone structures.  Additionally, different image types were computed for each subject, based on the aggregate information of the focal planes, for visualization and interpretation of reflectivity data.


Hind Othman

Muhammed Saad M Alluwimi

Wall To Lumen Ratio (WLR) In Clinically Involved And Uninvolved Areas Within Individual Diabetic Eyes


Targeting damaged RNFL bundles on en face images with closely-spaced Visual Field points

Purpose: To ask whether arterial wall thickening is consequent to local diabetic retinal conditions. Because diabetes and hypertension often occur in a single patient, we ask whether there is an additional change to arteriolar walls attributable to diabetes by comparing retinal vascular changes between more and less affected areas within the same retina.  Methods: Diabetic subjects (12) were selected based on having local areas of diabetic retinal change. All patients were dilated and received a clinical examination and an SD-OCT (Spectralis, Heidelberg, Germany). All patients were imaged using the Indiana AOSLO A series of small, 528-microns x 600-microns, regions were imaged. Imaged regions were then divided into 2 groups for each subject. Group1 regions included involved areas that showed more than 1 sign of clinically detectable diabetic retinopathy (Microaneurysms, hard and soft exudates, hemorrhage and/or neovascularization) or non-clinically detectable but AOSLO visible signs of diabetic retinopathy (focal capillary closure, Microaneurysms or other Microvascular abnormalities). Group2 regions appeared normal by the above criteria. wall-to-lumen ratio (WLR) was calculated. A total of 58 arterioles were identified in group1 and 31 in group2. The vessels were then divided into small (< 50 microns) and large (> 50 microns) subgroups.   Results: Arterioles in Group1 had more abnormalities in their vascular walls, including local wall thickening. Group 1 WLR’s were 0.91 and 1.1(larger and smaller respectively) and Group2 WLR’s were 0.32 and 0.68. These differed significantly (ANOVA p<0.05).   Conclusions: The thickening of vascular walls measured in diabetes seems to include a local component with the walls being relatively thicker in involved regions. This suggests that the vascular consequences of diabetes are not uniform throughout the retina. The question remains as to whether these findings of local vascular wall changes are the cause of these surrounding compromised areas or the consequence of it.

A number of studies have reported discordance between the patterns of perimetric defects and structural damage in glaucoma. Several studies proposed that this discordance would be minimized by increasing the number of visual field (VF) points at the damaged areas. However, these studies were limited by 1) prolonged perimetric testing and 2) only imaging the superficial depths of the retinal nerve fiber layer (RNFL). We conducted a pilot study to assess the potential of presenting closely-spaced VF points at retinal locations of glaucomatous damage, consuming a relative short time for the perimetric test. Damage was observed using images of RNFL bundles at both superficial and deep depths.

2/5/2016 Tao Liu

Interaction of axial and oblique astigmatism in theoretical and physical eye models

Astigmatism is a defect of optical systems that causes light from a single luminous point source to focus in a pair of line images at different axial locations.  In a rotationally symmetric system, oblique astigmatism occurs for object points displaced from the axis of symmetry as described quantitatively by Coddington’s equations for obliquely-incident rays.  In systems lacking rotational symmetry (e.g. toroidal refracting surfaces), axial astigmatism occurs even for point sources on the system’s optical axis due to variation of surface curvature for different meridians. In this study we investigate the interaction of these two types of astigmatism to produce a net astigmatism that varies across the visual field. We anticipate the results may have broad applicability for a variety of topics in clinical and visual science, including (1) the origin of foveal astigmatism, (2) visual performance for tasks involving stimuli in the peripheral field of healthy and diseased eyes, (3) the role of peripheral refractive errors in emmetropization, and (4) meridional amblyopia and neural development of the visual system.


Wenlin Zhang

Bright Senyo Ashimatey

Slc4a11 knock-out model of Endothelial Corneal Dystrophy reveals a phenotype consistent with ammonia toxicity

Between-subject variability in healthy eyes as a primary source of structural-functional discordance in patients with Glaucoma

Mutations in NH3:H+ transporter SLC4A11 result in Congenital Hereditary Endothelial Dystrophy (CHED) and Fuchs’ Endothelial Corneal Dystrophy (FECD). In Slc4a11 knock-out mouse model, we observed signs of ammonia intoxication in corneal endothelium, implicating ammonia toxicity may play a role in pathogenesis of the disease.

Structural and functional testing of ganglion cell integrity provide the clinician with separate but complementary findings that guide the diagnosis and management of glaucoma. A setback to the intended complementary effects of structural and functional testing is the discordance between the structural and functional measures (referred to as structural-functional discordance). Hood et al. (IOVS, 2009) proposed between-subject variability in healthy eyes to be the primary source of structural-functional discordance in patients with glaucoma. Swanson et al. (OVS, 2014) found that the limits of agreement of the discordance in controls came close to the limits of agreement of the discordance in patients on a Bland and Altman plot, consistent with the finding of Hood et al.

 We integrate the Hood et al. (IOVS, 2009) function (relating perimetric sensitivity to retinal nerve fiber layer thickness measures) with the Bland and Altman analysis approach used by Swanson et al. (OVS, 2014) to test on an independent data set the finding that between-subject variability in healthy eyes is the primary source of structural-functional discordance in patients with glaucoma. We extend the hypothesis to include a structural-structural comparison and apply the findings from the structural–structural comparison to inform the discussion of the sources of structural-functional discordance.  

2/19/2016 Bruce Cumming TBD

Edmund Arthur

Yifei Wu

Optical Coherence Tomography transverse imaging of diabetic retinas

Modeling the pupil image of eccentric photorefraction using Zemax

The compromise of the inner and outer retinal blood barriers, which occur in diabetic retinopathy (DR) and diabetic macular edema (DME), leads to the formation of intraretinal cysts along with the build-up of subretinal fluid. Retinal thickness using OCT is the standard clinical measurement, but DR and DME also leads to the disorganization of retinal layers, even without clinically significant DME (e.g. Sun, 2014, 2015; Elsner and King, 2015).  Intraretinal changes that occur in DR and DME have been associated with visual acuity changes; hence, the axial location and size delineation of such changes is imperative. Although, Fluorescein Angiography and Indocyanine Green Angiography are considered gold standards for imaging retinal and choroidal vessels respectively, both are invasive methods and are not depth resolved as well. My talk will be about applying a software technique to provide a transverse view of the retina, which is a 3D noninvasive technique based on a dataset of OCT images from the Spectralis (Heidelberg Engineering, Germany).  We generate transverse images of diabetic retinas with the aim of investigating these images for structural changes to the retinal and subretinal tissues and describing perifoveal vessels, as well."

Eccentric photorefraction is a technique used to estimate refractive state remotely in young children for vision screening and research purposes. The estimation is based on empirical calibrations and many factors could affect the calibration function such as lens vertex distances, pupil size and higher order monochromatic aberrations (Roorda, Campbell & Bobier, 1997; Wesemann, Norcia & Allen, 1991). The aim of this study is to simulate a two-dimensional pupil image of eccentric photorefraction using Zemax, in order to understand how much calibration variation might be introduced by the different factors mentioned above. Inward and outward path models were built separately to simulate light from the eccentric source entering and exiting the eye to be captured by the camera. In practice, the results will be helpful in interpreting the data we are collecting from clinical high hyperopes wearing spectacle corrections

3/4/2016 Tim Kern



Eric Seemiller

Meznah Almutairi

Eye Position Stability in 5- to 10-Week-Olds

Binocular Static Accommodation of Early Presbyopes

Infants have poor spatial vision relative to adults and older children. A number of immaturities have been proposed to contribute to their reduced performance, including an underdeveloped retina and increased internal noise. However, little is currently understood about the role of eye movements in the development of spatial vision. Are instabilities in the monocular and binocular alignments of the developing infant also likely to limit performance? In this experiment, we showed adults and 5- to 10-week-old human infants a dynamic random noise stimulus that updated at 3 Hz. Horizontal and vertical eye positions were recorded from both eyes at 250 Hz. Adult like saccades were detected and removed and inter-saccade intervals were normalized. These intervals provided an estimate of the stability of fixation in the absence of a sustained feature in the visual scene. Interestingly, neither monocular stability (left and right eye positions in 2D space) nor vergence stability (horizontal and vertical) was significantly different between infants and adults. This suggests that for this task, infants had adult-like eye position stability to the sensitivity of the eye-tracker, and that it may not be a significant contributing factor to poor spatial vision. Implications for typical development will be discussed.

Monovision is widely used for correcting presbyopia, and often prescribed to emerging presbyopes with residual accommodation. To evaluate the impact of monovision on retinal image quality, we measured the accommodation of emerging presbyopes viewing through monovision corrections. Binocular distance and binocular near corrections were used as controls. A clinical COAS Shack-Hartmann aberrometers was used to evaluate refractive state, pupil diameter and image quality for each target distance.  With bilateral distance corrections, both accommodative amplitude and gain declined with increase in age from age 30 to 50.  With +2D bilateral near corrections, subjects refrained from accommodating until the target was closer than 50 cm.  As targets came closer than the 50 cm far point, some early presbyopes accommodated accurately until their maximum accommodation amplitude was reached, while others responded over a large target vergence range but with a small proportion of the accommodation necessary to focus the stimulus. With monovision, early presbyopes typically accommodated to focus the distance corrected eye, but other early presbyopes switched from focusing with the distance corrected eye to the near corrected eye as target distance is reduced. This switching behavior maximized the dioptric range of high quality retinal images.

3/18/2016 NO OXYOPIA (Spring Break)
3/25/2016 Shannon Risacher Visual Measures as Biomarkers of Alzheimer's Disease

Deficits in contrast sensitivity (CS) have been reported in Alzheimer’s disease (AD). However, the extent of these deficits in prodromal AD stages, including mild cognitive impairment (MCI) or even earlier, has not been investigated. In this study, CS was assessed using frequency doubling technology in older adults with AD (n ¼ 10), amnestic MCI (n ¼ 28), cognitive complaints without performance deficits (CC; n ¼ 20), and healthy controls (HC; n ¼ 29). The association between CS and cognition was also evaluated. Finally, the accuracy of CS measures for classifying MCI versus HC was evaluated. CS deficits were found in AD and MCI, while CC showed intermediate performance between MCI and HC. Upper right visual field CS showed the most significant difference among groups. CS was also associated with cognitive performance. Finally, CS measures accurately classified MCI versus HC. The CS deficits in AD and MCI, and intermediate performance in CC, indicate that these measures are sensitive to early AD-associated changes.  Therefore,  frequency  doubling  technology-based  measures  of  CS  may  have  promise  as a novel AD biomarker.

4/1/2016 Gordon Legge TBD

Furu Zhang

Kaitlyn Sapoznik

Cone outer segment disc shedding imaged in the living human eye

Multimodal imaging of retinal sequelae of choroidal nevus

Photoreceptors undergo a daily renewal and shedding of outer segment (OS) discs. These fundamental processes maintain the health of outer retina, thus are of significant clinical interest. While OS renewal and shedding have been extensively studied in animal models in postmortem eyes, little is known about them in the living human eye, where this knowledge can make its largest impact for improved diagnostics and therapeutics. Only recently has renewal been observed in the living human eye optically, but the complementary shedding has proven more elusive to detect.

In this study, we took advantage of the 3D resolution of adaptive optics optical coherence tomography (AO-OCT) and custom tracking software to capture OS shedding events in the living human eye. Two normal subjects were imaged at 3 degree temporal retina for 90 minutes at 3 minutes interval. This 90-minute imaging session was repeated three times (morning, afternoon, and evening) to test the influence of time-of-day on percentage of cones that shed. AO-OCT images captured the 3D reflectance profile of individual cones, and their profiles were tracked over time to detect shedding events based on the temporal and spatial behavior of the reflections at the inner segment / outer segment junction (IS/OS) and cone outer segment tip (COST).

While the IS/OS reflection remained relatively stable over the imaging sessions, the COST reflection of some cones underwent dramatic change. Specifically, the COST disappeared entirely, returning minutes later but displaced axially that resulted in a slightly shortened OS. This dynamic we interpret as a shedding event. For cones successfully tracked in both subjects (n=1000), those that shed had an average loss duration in the COST reflection of 9.9±16.8 minutes, and an average length loss of the OS of 2.2±1.0 μm. Shedding was elevated in the morning compared to the afternoon and evening.

Purpose: To investigate in vivo cellular change over time in subjects with subretinal fluid (SRF) associated with choroidal nevi.  Adaptive optics (AO) imaging enables in vivo retinal imaging at the cellular level. By combining optical coherence tomography (OCT) and AO imaging, it is possible to measure detailed cellular changes associated with choroidal nevus and its sequelae.   Methods: With the Indiana AOSLO, confocal and multiply-scattered light imaging was performed on two subjects with foveal SRF associated with choroidal nevi. SD-OCT scans were acquired at each visit and used to guide AOSLO imaging. The first subject, a 31 yo WF, was imaged 16 times over 12 months and the second subject, a 52 yo WF, was imaged 6 times over 15 months. Each subject underwent focal laser coagulation for SRF between the first and second imaging sessions. Each session focused on ROIs including laser burns, photoreceptor (PR) changes, and areas of cellular changes. AOSLO images were averaged with custom Matlab software, montaged, and imported into Photoshop CS6. Retinal areas of interest were identified, measured, and compared over time and to SD-OCT images.   Results: In both subjects, hyper-reflective cellular structures ranging in diameter from 11-29 µm were located in regions of PR disruption. These appeared cellular and contained multiple hyper-reflective particles within them. Retinal appearance varied markedly over time and in one subject the RPE mosaic was directly imaged in areas with SRF. In the same subject, the location of a focal laser burn was identified via AOSLO imaging and after treatment appeared to be rapidly infiltrated with cells  and then over time these cells decreased.   Conclusion: The in vivo imaging allows measurement of the dynamic changes as the retina responds to disease and treatment. These changes are presumed to be secondary to microglial and RPE changes, PR loss and disruption, and macrophage infiltration. The AOSLO provides a complementary view of many features that are utilized in the clinical differentiation of choroidal nevus and melanoma.


Olivia Reed

Ashly Ryckman



4/22/2016 Rob deRuyter


4/29/2016 Susana Marcos


Presbyopia, the loss of crystalline lens accommodation wih age affects 100% of the population older than 45 years of age, yet there is not a solution that restores the dynamic accommodation ability of the young eye. In this talk, I will present advances in the understanding of the crystalline lens optics and morphology, through the use of aberrometry and 3D quantitative Optical Coherence Tomography, and their change with accommodation and aging. I will discuss current solutions of presbyopia including multifocal IOLs and accommodative IOLs. Adaptive Optics and Simultaneous Vision Simulators are valuable tools to understand and optimize multifocal designs. New prospects for accommodating IOLs will be discussed

5/6/2016 NO OXYOPIA - Graduation TBD