Mircea Mujat

We developed a novel ophthalmic imaging platform that combines non-invasive measurements of retina/choroid structure and ocular blood flow based on optical coherence tomography (OCT) and wide-field semi-quantitative global flow visualization using line-scanning Doppler flowmetry. The combination of these two imaging modalities within the same imaging platform enables comprehensive assessment of blood flow in retina and choroid and provides efficient characterization of blood flow in hemodynamic studies both in human volunteers and in small animals. Our Doppler OCT procedure provides an absolute velocity measurement which is used to properly calibrate in vivo large-area Doppler flowmetry velocity maps.

(200/200) Purpose: Our aim was to evaluate structural alterations of retinal arterioles due to type 1 diabetes (T1D) and/or diabetic retinopathy (DR) under AOSLO imaging. Methods: Each study eye underwent mydriasis and AOSLO imaging in a single-visit study. The instrument’s arrangement of four offset aperture images provided two orthogonal split-detector images and enabled isotropic analysis of the arteriolar boundaries. For each arteriole, we calculated the wall-to-lumen ratio (WLR), mean wall thickness, and luminal and external diameters. Results: In total, we enrolled 5 (20.8%) healthy control eyes and 19 eyes of patients with T1D. The DR distribution was: four (16.7%) no-DR, nine (37.5%%) mild or moderate nonproliferative DR (NPDR), and six (25%) severe NPDR or proliferative DR. Mean wall thickness increased significantly in eyes with T1D compared to healthy controls (p = 0.0006) and in eyes with more advanced DR (p = 0.0004). The WLR was significantly higher in eyes with T1D (p = 0.002) or more severe DR (p = 0.004). There was no significant relationship between T1D status or DR severity and any of the arteriolar diameters. Conclusions: In this preliminary study, there appeared to be increases in the WLR and mean wall thickness in eyes with T1D and more severe DR than in the controls and eyes with no/less severe DR. Future studies may further elucidate the relationship between the retinal arteriolar structure and physiologic alterations in DR.

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.

Adaptive optics (AO) has been used in many applications, including astronomy, microscopy, and medical imaging. In retinal imaging, AO provides real-time correction of the aberrations introduced by the cornea and the lens to facilitate diffraction-limited imaging of retinal microstructures. Most importantly, AO-based retinal imagers provide cellular-level resolution and quantification of changes induced by retinal diseases and systemic diseases that manifest in the eye enabling disease diagnosis and monitoring of disease progression or the efficacy of treatments. In this paper, we present an overview of our team efforts over almost two decades to develop high-resolution retinal imagers suitable for clinical use. Several different types of imagers for human and small animal eye imaging are reviewed, and representative results from multiple studies using these instruments are shown. These examples demonstrate the extraordinary power of AO-based retinal imaging to reveal intricate details of morphological and functional characteristics of the retina and to help elucidate important aspects of vision and of the disruptions that affect delicate retinal tissue.

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.

We describe an imaging method and analysis procedure for characterization of the retinal vessel walls with cellular-level resolution. Segmentation of blood vessel walls provides quantitative measures of vessel and lumen diameters, wall thickness, and wall-to-lumen ratio.

Diseases such as diabetes affect the retinal vasculature and the health of the neural retina, leading to vision problems. We describe here an imaging method and analysis procedure that enables characterization of the retinal vessel walls with cellular-level resolution, potentially providing markers for eye diseases. Adaptive optics scanning laser ophthalmoscopy is used with a modified detection scheme to include four simultaneous offset aperture channels. The magnitude of the phase gradient derived from these offset images is used to visualize the structural characteristics of the vessels. The average standard deviation image provides motion contrast and enables segmentation of the vessel lumen. Segmentation of blood vessel walls provides quantitative measures of geometrical characteristics of the vessel walls, including vessel and lumen diameters, wall thickness, and wall-to-lumen ratio. Retinal diseases may affect the structural integrity of the vessel walls, their elasticity, their permeability, and their geometrical characteristics. The ability to measure these changes is valuable for understanding the vascular effects of retinal diseases, monitoring disease progression, and drug testing. In addition, loss of structural integrity of the blood vessel wall may result in microaneurysms, a hallmark lesion of diabetic retinopathy, which may rupture or leak and further create vision impairment. Early identification of such structural abnormalities may open new treatment avenues for disease management and vision preservation. Functional testing of retinal circuitry through high-resolution measurement of vasodilation as a response to controlled light stimulation of the retina (neurovascular coupling) is another application of our method and can provide an unbiased evaluation of one’s vision and enable early detection of retinal diseases and monitoring treatment results.

Adaptive optics provides improved resolution in ophthalmic imaging when retinal microstructures need to be identified, counted, and mapped. In general, multiple images are averaged to improve the signal-to-noise ratio or analyzed for temporal dynamics. Image registration by cross-correlation is straightforward for small patches; however, larger images require more sophisticated registration techniques. Strip-based registration has been used successfully for photoreceptor mosaic alignment in small patches; however, if the deformations along strips are not simple displacements, averaging can degrade the final image. We have applied a non-rigid registration technique that improves the quality of processed images for mapping cones over large image patches. In this approach, correction of local deformations compensates for local image stretching, compressing, bending, and twisting due to a number of causes. The main result of this procedure is improved definition of retinal microstructures that can be better identified and segmented. Derived metrics such as cone density, wall-to-lumen ratio, and quantification of structural modification of blood vessel walls have diagnostic value in many retinal diseases, including diabetic retinopathy and age-related macular degeneration, and their improved evaluations may facilitate early diagnostics of retinal diseases.

Simultaneous multi-channels offset imaging provides isotropic images of retinal microstructures free of directionality artifacts and enables phase imaging in the living eye with enhanced visualization contrast.

Simultaneous multi-channels offset imaging provides isotropic images of retinal microstructures free of directionality artifacts and enables phase imaging in the living eye with enhanced visualization contrast.