Indiana University

Deep learning-enabled volumetric cone photoreceptor segmentation in adaptive optics optical coherence tomography images of normal and diseased eyes

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Deep learning-enabled volumetric cone photoreceptor segmentation in adaptive optics optical coherence tomography images of normal and diseased eyes Objective quantification of photoreceptor cell morphology, such as cell diameter and outer segment length, is crucial for early, accurate, and sensitive diagnosis and prognosis of retinal neurodegenerative diseases. Adaptive optics optical coherence tomography (AO-OCT) provides three-dimensional (3-D) visualization of photoreceptor cells in the living human eye. The current gold standard for extracting cell morphology from AO-OCT images involves the tedious process of 2-D manual marking. To automate this process and extend to 3-D analysis of the volumetric data, we propose a comprehensive deep learning framework to segment individual cone cells in AO-OCT scans. Our automated method achieved human-level performance in assessing cone photoreceptors of healthy and diseased participants captured with three different AO-OCT systems representing two different types of point scanning OCT: spectral domain and swept source.

Association of Brain Volume and Retinal Thickness in the Early Stages of Alzheimer’s Disease

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Background:The eye has been considered a ‘window to the brain,’ and several neurological diseases including neurodegenerative conditions like Alzheimer’s disease (AD) also show changes in the retina. Objective:To investigate retinal nerve fiber layer (RNFL) thickness and its association with brain volume via magnetic resonance imaging (MRI) in older adults with subjective or objective cognitive decline. Methods:75 participants underwent ophthalmological and neurological evaluation including optical coherence tomography and MRI (28 cognitively normal subjects, 26 with subjective cognitive decline, 17 patients diagnosed with mild cognitive impairment, and 4 with AD). Differences in demographics, thickness of RNFL, and brain volume were assessed using ANCOVA, while partial Pearson correlations, covaried for age and sex, were used to compare thickness of the peripapillary RNFL with brain volumes, with p < 0.05 considered statistically significant. Results:Mean RNFL ...

Two concepts for ultra-high-resolution polarization-sensitive optical coherence tomography with a single camera

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Two designs with a multiplexed superluminescent diode for ultra-high-resolution spectral-domain polarization-sensitive optical coherence tomography (UHR-PS-OCT) are introduced. In the first design, a Wollaston prism separates orthogonal polarization states next to each other on one linescan camera; the other design uses a beam displacer to separate orthogonal states onto two lines of a linescan camera with multiple rows of detectors. The coherence lengths measured with the two systems were 3.6 µm and 2.9 µm ( ( Read Full Article )

New imaging technique could speed up development of eye disease treatments

Researchers have developed a simple and fast way to perform optoretinography, an imaging technique that measures light-induced functional activity in the eye's retina, the network of neurons in the back of our eyes responsible for detecting light and initiating vision. More than 50% of people in the U.S. over age 60 are affected by retinal diseases such as macular degeneration and diabetic retinopathy. ( Read Full Article )

Indiana University Receives NIH Grant for Imaging Structure and Function of Photoreceptors.

Indiana University Received a 2022 NIH Grant for $577,031 for Imaging Structure and Function of Photoreceptors. The principal investigator is Donald Miller. Below is a summary of the proposed work. Human vision starts when photoreceptors collect and respond to light. Normal photoreceptor function is essential for normal vision, yet techniques to assess these processes in vivo are limited. New optical modalities that are rapid, specific, and non‐invasive promise to greatly expand our capability to monitor more accurately and completely photoreceptors. This study takes advantage of unique adaptive‐optics OCT instrumentation developed in my laboratory in conjunction with custom algorithms for sub‐cellular image registration and phase‐sensitive detection to measure anatomical and physiological properties of individual photoreceptors. We will use this technique to investigate three specific aims that quantify the spectral sensitivity profiles of photoreceptors, the expression of photorec...

An improved method for murine laser-induced choroidal neovascularization lesion quantification from optical coherence tomography images

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Laser-induced choroidal neovascularization (L-CNV) in murine models is a standard method for assessing therapies, genetics, and mechanisms relevant to the blinding eye disease neovascular or “wet” age-related macular degeneration. The ex vivo evaluation of these lesions involves confocal microscopy analysis. In vivo evaluation via optical coherence tomography (OCT) has previously been established and allows longitudinal assessment of lesion development. However, to produce robust data, evaluation of many lesions may be required, which can be a slow, arduous process. A prior, manual method for quantifying these lesions as ellipsoids from orthogonal OCT images was effective but time consuming. We therefore investigated if OCT lesion quantification could be simplified, streamlined, and made less time-consuming. ( Read Full Article )

The effect of axial length to basement-membrane opening to fovea distance on optical coherence tomography

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Background: Optical Coherence Tomography (OCT) lateral scaling is influenced by axial length (AL). There is a need to incorporate a method to correct this measurement bias for accurate lateral OCT measurement. Purpose: To identify the correlation of optic-nerve-to-fovea distance measurement to AL by OCT) as an internal factor for lateral scaling. Methods: Using Heidelberg Spectralis OCT, distance from the basement membrane opening at the optic disc margin to the centre of the fovea (BMO-fovea distance) was measured in 135 eyes (77 subjects, ages 25-85). These measurements were correlated with AL measurements from Zeiss IOLMaster 700 using linear regression before and after correction for ocular magnification. Statistical analysis including Shapiro-Wilk test for normality, Pearson correlation, and multivariate analysis of the association between disc-fovea distance and AL was performed using Wizard statistical software for mac. Results: After lateral scaling, the mean distance betwee...

Reflectance-Based Structural Quantification of the Healthy and Glaucomatous Retinal Nerve …

Glaucoma is a group of progressive optic neuropathies that can lead to irreversible vision loss if left untreated. Spectral-domain optical coherence tomography (SD-OCT) is an important imaging tool used in the diagnosis and management of glaucoma. It provides thickness measurements of the retinal nerve fiber layer (RNFL), a useful index for monitoring progressive thinning that occurs from damage. However, there exists high between-subject variability in RNFL thickness in people free of eye disease. Another approach is RNFL reflectance, proposed in 1921 when reduction in reflectance was observed in damaged RNFL. Despite numerous reports from the past century supporting this, clinically applied quantification of RNFL reflectance using OCT is possible but lacking. First, I assessed healthy and glaucomatous eyes for the presence of presumed activated astrocytes and Müller cells (ARAM), a superficial retinal gliosis that could complicate reflectance-based measurements of the RNFL an...

Valve-Like Outflow System Behavior With Motion Slowing in Glaucoma Eyes: Findings Using a Minimally Invasive Glaucoma Surgery-MIGS-Like Platform and Optical Coherence Tomography Imaging

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Purpose: This study aimed to investigate anatomic relationships and biomechanics of pressure-dependent trabecular meshwork and distal valve-like structure deformation in normal and glaucoma eyes using high-resolution optical coherence tomography (HR-OCT). Methods: We controlled Schlemm's canal (SC) pressure during imaging with HR-OCT in segments of three normal (NL) and five glaucomatous (GL) ex vivo eyes. The dissected limbal wedges were studied from 15 locations (5 NL and 10 GL). A minimally invasive glaucoma surgery (MIGS)-like cannula was inserted into the SC lumen, whereas the other end was attached to a switch between two reservoirs, one at 0, the other at 30 mm Hg. A steady-state pressure of 30 mm Hg was maintained to dilate SC and collector channels (CC) during 3D volume imaging. The resulting 3D lumen surface relationships were correlated with internal structural features using an image mask that excluded tissues surrounding SC and CC. While imaging with HR-OCT, real-time m...

PhD Student Opening in Advanced Imaging at Indiana University

A PhD student position is available in Don Miller’s laboratory on advanced ophthalmic imaging at Indiana University ( The laboratory is looking for a highly motivated student in engineering, optical physics, or a related discipline with an interest to develop cutting-edge optical instrumentation to study noninvasively the retina at the cellular level. The laboratory’s primary focus is on the development and use of adaptive optics and optical coherence tomography, technologies the laboratory has been advancing for the past two decades. Some of our recent work can be found in PNAS:,, The student position is part of the IU Vision Science Graduate Program. The Program provides a vibrant and collegial environment and has existing strengths in visual optics, retinal Imaging, optical engineering, neur...

Development of high-speed, integrated high-resolution optical coherence microscopy and dual-channel fluorescence microscopy for the simultaneous co-registration of reflectance and fluorescence signals


Optical coherence microscopy is an imaging technique capable of generating three-dimensional images of structures in tissue, but with limited functional imaging ability. Fluorescence microscopy offers functional information of cellular activities. The integration of both imaging modalities can enable the evaluation of the impact of structural information on cells activities. To develop an integrated system combining high-resolution optical coherence microscopy (HR-OCM) and dual-channel scanning confocal fluorescence microscopy (DC-SCFM) to enable the co-registration of structural and functional information. Different strategies to enable the simultaneous recording of information, as well as to overcome the focal plane mismatch between both imaging modalities were developed. The system's performances were evaluated in imaging fluorescence microspheres embedded in multi-layer tape and silicone phantom. HR-OCM achieved an axial resolution of 2.4-µm in tissue over an imaging depth...

Cross-Polarization Optical Coherence Tomographic Assessment of In situ Simulated Erosive Tooth Wear

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This clinical study tested cross-polarization optical coherence tomography (CP-OCT) monitoring of erosive tooth wear (ETW). Twenty participants completed a 14-day/arm, 3-arm crossover study simulating different ETW severities. Participants received two enamel specimens (per arm) and were randomized to: severe (s-ETW, lemon juice/pH:2.5/4.25%w/v citric acid), moderate (m-ETW, grapefruit juice/pH:3.5/1.03%w/v citric acid), and non-ETW (water). Enamel thickness was measured with CP-OCT (day(D) 0, 7, 14) and micro-computed tomography (μ-CT; D14). Enamel surface loss was determined with CP-OCT and optical profilometry (OP; D7, D14). CP-OCT showed higher enamel surface loss for D14 than D7 for m-ETW (p=0.009) and s-ETW (p=0.040) and differentiated severity at D14 (s-ETW>non-ETW, p=0.027). OP was able to differentiate surface loss between days (D7<D14, p<0.001) for m-ETW and s-ETW, and ETW severity effect after 7 and 14 days (non-ETW<m-ETW<s-ETW, p<0.001). At D14, CP-O...

AI spots neurons better than human experts

A new combination of optical coherence tomography (OCT), adaptive optics and deep neural networks should enable better diagnosis and monitoring for neuron-damaging eye and brain diseases like glaucoma. Biomedical engineers at Duke University led a multi-institution consortium to develop the process, which easily and precisely tracks changes in the number and shape of retinal ganglion cells in the eye. This work appears in a paper published on May 3 in the journal Optica . The retina of the eye is an extension of the central nervous system. Ganglion cells are one of the primary neurons in the eye that process and send visual information to the brain. In many neurodegenerative diseases like glaucoma, ganglion cells degenerate and disappear, leading to irreversible blindness. Traditionally, researchers use OCT, an imaging technology similar to ultrasound that uses light instead of sound, to peer beneath layers of eye tissue to diagnose and track the progression of glaucoma and other ey...

Weakly supervised individual ganglion cell segmentation from adaptive optics OCT images for glaucomatous damage assessment

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Cell-level quantitative features of retinal ganglion cells (GCs) are potentially important biomarkers for improved diagnosis and treatment monitoring of neurodegenerative diseases such as glaucoma, Parkinson’s disease, and Alzheimer’s disease. Yet, due to limited resolution, individual GCs cannot be visualized by commonly used ophthalmic imaging systems, including optical coherence tomography (OCT), and assessment is limited to gross layer thickness analysis. Adaptive optics OCT (AO-OCT) enables in vivo imaging of individual retinal GCs. We present an automated segmentation of GC layer (GCL) somas from AO-OCT volumes based on weakly supervised deep learning (named WeakGCSeg), which effectively utilizes weak annotations in the training process. Experimental results show that WeakGCSeg is on par with or superior to human experts and is superior to other state-of-the-art networks. The automated quantitative features of individual GCLs show an increase in structure–fun...

Phase II multi-center trial of optical coherence tomography as an adjunct to white light cystoscopy for intravesical real time imaging and staging of bladder cancer

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Background: Optical coherence tomography (OCT) is a novel imaging modality that provides microstructural information of different tissue layers using near-infrared light. This prospective, multicenter phase II trial aimed to assess the accuracy of OCT-assisted cystoscopy for bladder tumor staging. Methods: Patients with primary or recurrent bladder tumors (Ta,T1) identified by outpatient cystoscopy were included. The primary objective was to assess the accuracy and positive predictive value of for determining tumor stage ≥T1 correlated by histopathology. 72 suspicious lesions from 63 patients were eligible to analyze in the study. All suspected lesions were evaluated with conventional cystoscopy, interpreted in real-time using OCT, and then resected. All results were compared to pathology. A total of 363 OCT images of tumor and normal mucosa in 25 patients were obtained to evaluate diagnostic efficacy of the computer-aided texture analysis algorithm. Results: Sensitivity and spec...


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