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Diagnostics
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High-Resolution Retinal Imaging: Hot Topics and Recent Developments
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High-Resolution Retinal Imaging: Hot Topics and Recent Developments

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Medical Imaging and Theranostics".

Deadline for manuscript submissions: 31 May 2025 | Viewed by 8473

Special Issue Editor

Dr. Mircea Mujat

E-Mail Website
Guest Editor
Biomedical Optics Technologies, Physical Sciences Inc., Andover, MA, USA
Interests: adaptive optics; optical coherence tomography; retina; optical imaging; retinal imaging

Special Issue Information

Dear Colleagues,

The building blocks of retinal microstructures need to be accurately identified, counted, segmented, and mapped in the living eye for diagnostic purposes. Various diseases such as diabetes affect the health of the retina by distorting the structural and functional characteristics of retinal components, leading to vision problems. Adaptive optics (AO) has been used in retinal imaging to enhance the resolution and reveal cellular-level details in both scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT). Novel techniques including non-confocal (offset/split/quad) SLO and averaging multiple volumes in high-speed OCT enable the visualization of retinal microstructures and facilitate the quantification of differences between healthy and diseased eyes at the cellular level. Functional testing of retinal circuitry, such as optoretinography (ORG) or neurovascular coupling as a response to controlled light stimulation, can provide an unbiased evaluation of one’s vision and enable the early detection of retinal diseases. The early identification of structural and functional abnormalities may open new treatment avenues for vision preservation.

Our purpose with this Special Issue is to showcase recent developments in high-resolution retinal imaging in terms of imaging techniques, new contrast mechanisms, and analysis methods, or to define and test new biomarkers that help understand the disruption of vision. Original research articles, high-interest reviews, and clinical investigations/case series/case reports of exceptional merit are welcomed.

Dr. Mircea Mujat
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (5 papers)

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Research

12 pages, 4694 KiB  
Article
Compact Linear Flow Phantom Model for Retinal Blood-Flow Evaluation
by Achyut J. Raghavendra, Abdelrahman M. Elhusseiny, Anant Agrawal, Zhuolin Liu, Daniel X. Hammer and Osamah J. Saeedi
Diagnostics 2024, 14(15), 1615; https://doi.org/10.3390/diagnostics14151615 - 26 Jul 2024
Viewed by 818
Abstract
Impaired retinal blood flow is associated with ocular diseases such as glaucoma, macular degeneration, and diabetic retinopathy. Among several ocular imaging techniques developed to measure retinal blood flow both invasively and non-invasively, adaptive optics (AO)-enabled scanning laser ophthalmoscopy (AO-SLO) resolves individual red blood [...] Read more.
Impaired retinal blood flow is associated with ocular diseases such as glaucoma, macular degeneration, and diabetic retinopathy. Among several ocular imaging techniques developed to measure retinal blood flow both invasively and non-invasively, adaptive optics (AO)-enabled scanning laser ophthalmoscopy (AO-SLO) resolves individual red blood cells and provides a high resolution with which to measure flow across retinal microvasculature. However, cross-validation of flow measures remains a challenge owing to instrument and patient-specific variability in each imaging technique. Hence, there is a critical need for a well-controlled clinical flow phantom for standardization and to establish blood-flow measures as clinical biomarkers for early diagnosis. Here, we present the design and validation of a simple, compact, portable, linear flow phantom based on a direct current motor and a conveyor-belt system that provides linear velocity tuning within the retinal microvasculature range (0.5–7 mm/s). The model was evaluated using a sensitive AO-SLO line-scan technique, which showed a <6% standard deviation from the true velocity. Further, a clinical SLO instrument showed a linear correlation with the phantom’s true velocity (r2 > 0.997). This model has great potential to calibrate, evaluate, and improve the accuracy of existing clinical imaging systems for retinal blood flow and aid in the diagnosis of ocular diseases with abnormal blood flow. Full article
(This article belongs to the Special Issue High-Resolution Retinal Imaging: Hot Topics and Recent Developments)
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17 pages, 13894 KiB  
Article
The Surviving, Not Thriving, Photoreceptors in Patients with ABCA4 Stargardt Disease
by Hanna De Bruyn, Megan Johnson, Madelyn Moretti, Saleh Ahmed, Mircea Mujat, James D. Akula, Tomislav Glavan, Ivana Mihalek, Sigrid Aslaksen, Laurie L. Molday, Robert S. Molday, Bruce A. Berkowitz and Anne B. Fulton
Diagnostics 2024, 14(14), 1545; https://doi.org/10.3390/diagnostics14141545 - 17 Jul 2024
Viewed by 1021
Abstract
Stargardt disease (STGD1), associated with biallelic variants in the ABCA4 gene, is the most common heritable macular dystrophy and is currently untreatable. To identify potential treatment targets, we characterized surviving STGD1 photoreceptors. We used clinical data to identify macular regions with surviving STGD1 [...] Read more.
Stargardt disease (STGD1), associated with biallelic variants in the ABCA4 gene, is the most common heritable macular dystrophy and is currently untreatable. To identify potential treatment targets, we characterized surviving STGD1 photoreceptors. We used clinical data to identify macular regions with surviving STGD1 photoreceptors. We compared the hyperreflective bands in the optical coherence tomographic (OCT) images that correspond to structures in the STGD1 photoreceptor inner segments to those in controls. We used adaptive optics scanning light ophthalmoscopy (AO-SLO) to study the distribution of cones and AO-OCT to evaluate the interface of photoreceptors and retinal pigment epithelium (RPE). We found that the profile of the hyperreflective bands differed dramatically between patients with STGD1 and controls. AO-SLOs showed patches in which cone densities were similar to those in healthy retinas and others in which the cone population was sparse. In regions replete with cones, there was no debris at the photoreceptor-RPE interface. In regions with sparse cones, there was abundant debris. Our results raise the possibility that pharmaceutical means may protect surviving photoreceptors and so mitigate vision loss in patients with STGD1. Full article
(This article belongs to the Special Issue High-Resolution Retinal Imaging: Hot Topics and Recent Developments)
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15 pages, 2576 KiB  
Article
Quantification of Human Photoreceptor–Retinal Pigment Epithelium Macular Topography with Adaptive Optics–Optical Coherence Tomography
by Zhuolin Liu, Samira Aghayee, Somayyeh Soltanian-Zadeh, Katherine Kovalick, Anant Agrawal, Osamah Saeedi, Catherine Cukras, Emily Y. Chew, Sina Farsiu and Daniel X. Hammer
Diagnostics 2024, 14(14), 1518; https://doi.org/10.3390/diagnostics14141518 - 15 Jul 2024
Viewed by 1284
Abstract
Photoreceptors (PRs) and retinal pigment epithelial (RPE) cells form a functional unit called the PR-RPE complex. The PR-RPE complex plays a critical role in maintaining retinal homeostasis and function, and the quantification of its structure and topographical arrangement across the macula are important [...] Read more.
Photoreceptors (PRs) and retinal pigment epithelial (RPE) cells form a functional unit called the PR-RPE complex. The PR-RPE complex plays a critical role in maintaining retinal homeostasis and function, and the quantification of its structure and topographical arrangement across the macula are important for understanding the etiology, mechanisms, and progression of many retinal diseases. However, the three-dimensional cellular morphology of the PR-RPE complex in living human eyes has not been completely described due to limitations in imaging techniques. We used the cellular resolution and depth-sectioning capabilities of a custom, high-speed Fourier domain mode-locked laser-based adaptive optics–optical coherence tomography (FDML-AO-OCT) platform to characterize human PR-RPE complex topography across the temporal macula from eleven healthy volunteers. With the aid of a deep learning algorithm, key metrics were extracted from the PR-RPE complex of averaged AO-OCT volumes including PR and RPE cell density, PR outer segment length (OSL), and PR/RPE ratio. We found a tight grouping among our cohort for PR density, with a mean (±SD) value of 53,329 (±8106) cells/mm2 at 1° decreasing to 8669 (±737) cells/mm2 at 12°. We observed a power function relationship between eccentricity and both PR density and PR/RPE ratio. We found similar variability in our RPE density measures, with a mean value of 7335 (±681) cells/mm2 at 1° decreasing to 5547 (±356) cells/mm2 at 12°, exhibiting a linear relationship with a negative slope of −123 cells/mm2 per degree. OSL monotonically decreased from 33.3 (±2.4) µm at 1° to 18.0 (±1.8) µm at 12°, following a second-order polynomial relationship. PR/RPE ratio decreased from 7.3 (±0.9) µm at 1° to 1.5 (±0.1) µm at 12°. The normative data from this investigation will help lay a foundation for future studies of retinal pathology. Full article
(This article belongs to the Special Issue High-Resolution Retinal Imaging: Hot Topics and Recent Developments)
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16 pages, 31210 KiB  
Article
Comparison between Two Adaptive Optics Methods for Imaging of Individual Retinal Pigmented Epithelial Cells
by Elena Gofas-Salas, Daniel M. W. Lee, Christophe Rondeau, Kate Grieve, Ethan A. Rossi, Michel Paques and Kiyoko Gocho
Diagnostics 2024, 14(7), 768; https://doi.org/10.3390/diagnostics14070768 - 4 Apr 2024
Cited by 1 | Viewed by 2589
Abstract
The Retinal Pigment Epithelium (RPE) plays a prominent role in diseases such as age-related macular degeneration, but imaging individual RPE cells is challenging due to their high absorption and low autofluorescence emission. The RPE lies beneath the highly reflective photoreceptor layer (PR) and [...] Read more.
The Retinal Pigment Epithelium (RPE) plays a prominent role in diseases such as age-related macular degeneration, but imaging individual RPE cells is challenging due to their high absorption and low autofluorescence emission. The RPE lies beneath the highly reflective photoreceptor layer (PR) and contains absorptive pigments, preventing direct backscattered light detection when the PR layer is intact. Here, we used near-infrared autofluorescence adaptive optics scanning laser ophthalmoscopy (NIRAF AOSLO) and transscleral flood imaging (TFI) in the same healthy eyes to cross-validate these approaches. Both methods revealed a consistent RPE mosaic pattern and appeared to reflect a distribution of fluorophores consistent with findings from histological studies. Interestingly, even in apparently healthy RPE, we observed dynamic changes over months, suggesting ongoing cellular activity or alterations in fluorophore distribution. These findings emphasize the value of NIRAF AOSLO and TFI in understanding RPE morphology and dynamics. Full article
(This article belongs to the Special Issue High-Resolution Retinal Imaging: Hot Topics and Recent Developments)
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11 pages, 5774 KiB  
Article
Motion Contrast, Phase Gradient, and Simultaneous OCT Images Assist in the Interpretation of Dark-Field Images in Eyes with Retinal Pathology
by Mircea Mujat, Konstantina Sampani, Ankit H. Patel, Ronald Zambrano, Jennifer K. Sun, Gadi Wollstein, R. Daniel Ferguson, Joel S. Schuman and Nicusor Iftimia
Diagnostics 2024, 14(2), 184; https://doi.org/10.3390/diagnostics14020184 - 15 Jan 2024
Cited by 1 | Viewed by 1593
Abstract
The cellular-level visualization of retinal microstructures such as blood vessel wall components, not available with other imaging modalities, is provided with unprecedented details by dark-field imaging configurations; however, the interpretation of such images alone is sometimes difficult since multiple structural disturbances may be [...] Read more.
The cellular-level visualization of retinal microstructures such as blood vessel wall components, not available with other imaging modalities, is provided with unprecedented details by dark-field imaging configurations; however, the interpretation of such images alone is sometimes difficult since multiple structural disturbances may be present in the same time. Particularly in eyes with retinal pathology, microstructures may appear in high-resolution retinal images with a wide range of sizes, sharpnesses, and brightnesses. In this paper we show that motion contrast and phase gradient imaging modalities, as well as the simultaneous acquisition of depth-resolved optical coherence tomography (OCT) images, provide additional insight to help understand the retinal neural and vascular structures seen in dark-field images and may enable improved diagnostic and treatment plans. Full article
(This article belongs to the Special Issue High-Resolution Retinal Imaging: Hot Topics and Recent Developments)
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