Assessment of local sensitivity in incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) lesions in intermediate age-related macular degeneration (iAMD).

Lesions of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) are associated with disease progression in age-related macular degeneration. However, the corresponding functional impact of these precursor lesions is unknown.We present a cross-sectional study of four patients employing clinical-grade MAIA (stimulus size: 0.43°, ~125 µm) and adaptive optics scanning light ophthalmoscope (AOSLO, stimulus size 0.07°, ~20 µm) based microperimetry (MP) to assess the specific impact of iRORA lesions on retinal sensitivity.AOSLO imaging showed overall reduced photoreceptor reflectivity and patches of hyporeflective regions at drusen with interspersed hyper-reflective foci in iRORA regions. MAIA-MP yielded an average retinal sensitivity loss of -7.3±3.1 dB at iRORA lesions compared with the in-eye control. With AOSLO-MP, the corresponding sensitivity loss was 20.1±4.8 dB.We demonstrated that iRORA lesions are associated with a severe impairment in retinal sensitivity. Larger cohort studies will be necessary to validate our findings.

Retinal Arteriolar Wall Remodeling in Diabetes Captured With AOSLO.

Purpose: Adaptive optics scanning laser ophthalmoscopy (AOSLO) enables the visualization and measurement of the retinal microvasculature structure in humans. We investigated the hypothesis that diabetes mellitus (DM) induces remodeling to the wall structure in small retinal arterioles. These alterations may allow better understanding of vascular remodeling in DM. Methods: We imaged retinal arterioles in one eye of 48 participants (26 with DM and 22 healthy controls) with an AOSLO. Structural metrics of 274 arteriole segments (203 with DM and 71 healthy controls) ≤ 50 µm in outer diameter (OD) were quantified and we compared differences in wall thickness (WT), wall-to-lumen ratio (WLR), inner diameter (ID), OD, and arteriolar index ratio (AIR) between controls and participants with DM. We also compared the individual AIR (iAIR) in groups of individuals. Results: The WLR, WT, and AIRs were significantly different in the arteriole segments of DM participants (P < 0.001). The iAIR was significantly deviated in the DM group (P < 0.001) and further division of the participants with DM into groups revealed that there was an effect of the presence of diabetic retinopathy (DR) on the iAIR (P < 0.001). Conclusions: DM induces remodeling of wall structure in small retinal arterioles and in groups of individuals. The use of AIR allows us to assess remodeling independently of vessel size in the retina and to compute an index for each individual subject. Translational Relevance: High-resolution retinal imaging allows noninvasive assessment of small retinal vessel remodeling in DM that can improve our understanding of DM and DR in living humans.

Imaging fine structures of the human trabecular meshwork in vivo using a custom design goniolens and OCT gonioscopy.

The trabecular meshwork (TM), located within the iridocorneal angle, is a target for many glaucoma treatments aimed at controlling intraocular pressure. However, structural variations between individuals are poorly understood. We propose a newly designed gonioscopic lens optimized for high-resolution imaging to image fine structures of the human TM in vivo. The body of the new lens is index-matched to the human cornea and includes a choice of two gonioscopic mirrors (59° and 63°) and matching air-spaced doublets placed on the anterior surface of the goniolens. The new design allows a diffraction-limited image plane at the iridocorneal angle structures. The goniolens design was built and then placed on the subjects eyes coupled to the cornea with goniogel and a 3D adjustable mount. Images were obtained using a commercially available OCT device (Heidelberg Spectralis). The optical resolution was measured in a model eye as 40.32 and 45.25 cy/mm respectively for each mirror angle. In humans, dense OCT scans with minimum spacing oriented tangential to the iris and ICA were performed on 7 healthy subjects (23-73 yrs). The TM was successfully imaged in all subjects. The custom goniolens improved the contrast of the uveoscleral meshwork structures and corneoscleral meshwork revealing limbus parallel striations, not visible with previous goniolens designs. Transverse OCT images were constructed along the segmentation line, providing an enface image of the TM structures including corneoscleral beams, previously only imaged in vivo using custom adaptive optics systems.

Characterization of the human iridocorneal angle in vivo using a custom design goniolens with OCT gonioscopy.

Intraocular pressure (IOP) is the only modifiable risk factor for glaucoma progression, and many treatments target the trabecular meshwork (TM). Imaging this region in vivo is challenging due to optical limitations of imaging through the cornea at high angles. We propose a gonioscopic OCT approach using a custom goniolens and a commercially available OCT device to improve imaging of the TM, Schlemm's canal (SC) and adjacent structures within the iridocorneal angle (ICA). The goniolens is modified with a plano-convex focusing lens and placed on the eye optically mated with goniogel and aided by a 3D adjustable mount. Gonioscopic OCT volume scans are acquired to image SC. Transverse enface images allowed measurements of SC over a 45° section of the ICA for the first time and revealed locations of SC narrowing. The band of extracanalicular limbal lamina and corneoscleral bands were imaged in most subjects and these bands were confirmed using exterior OCT imaging. The polarization dependence of the visibility of these structures is studied by polarization rotation the OCT beam with a half-wave plate, allowing increased contrast of SC. Gonioscopic OCT has successfully been used to image the human ICA in 3D in vivo. This approach provides more detailed characterization of the TM and SC, enhancing their contrast against their birefringent backgrounds.

Measuring Temporal and Spatial Variability of Red Blood Cell Velocity in Human Retinal Vessels.

Purpose: The retinal circulation regulates blood flow through various internal and external factors; however, it is unclear how locally these factors act within the retinal microcirculation. We measured the temporal and spatial variability of blood velocity in small retinal vessels using a dual-beam adaptive optics scanning laser ophthalmoscope. Methods: In young healthy subjects (n = 3), temporal blood velocity variability was measured in a local vascular region consisting of an arteriole, capillary, and venule repeatedly over 2 days. Data consisted of 10 imaging periods separated into two sessions: (1) five 6-minute image acquisition periods with 30-minute breaks, and (2) five 6-minute image acquisition periods with 10-minute breaks. In another group of young healthy subjects (n = 5), spatial distribution of velocity variability was measured by imaging three capillary segments during three 2-minute conditions: (1) baseline imaging condition (no flicker), (2) full-field flicker, and (3) no flicker condition again. Results: Blood velocities were measurable in all subjects with a reliability of about 2%. The coefficient of variation (CV) was used as an estimate of the physiological variability of each vessel. Over 2 days, the average CV in arterioles was 7% (±2%); in capillaries, it was 19% (±6%); and, in venules, it was 8% (±2%). During flicker stimulation, the average capillary CV was 16% during baseline, 15% during flicker stimulation, and 18% after flicker stimulation. Conclusions: Capillaries in the human retina exhibit spatial and temporal variations in blood velocity. This inherent variation in blood velocity places limits on studying the vascular regulation of individual capillaries, and the study presented here serves as a foundation for future endeavors.

Measuring Ocular Aberrations Sequentially Using a Digital Micromirror Device.

The Hartmann⁻Shack wavefront sensor is widely used to measure aberrations in both astronomy and ophthalmology. Yet, the dynamic range of the sensor is limited by cross-talk between adjacent lenslets. In this study, we explore ocular aberration measurements with a recently-proposed variant of the sensor that makes use of a digital micromirror device for sequential aperture scanning of the pupil, thereby avoiding the use of a lenslet array. We report on results with the sensor using two different detectors, a lateral position sensor and a charge-coupled device (CCD) scientific camera, and explore the pros and cons of both. Wavefront measurements of a highly aberrated artificial eye and of five real eyes, including a highly myopic subject, are demonstrated, and the role of pupil sampling density, CCD pixel binning, and scanning speed are explored. We find that the lateral position sensor is mostly suited for high-power applications, whereas the CCD camera with pixel binning performs consistently well both with the artificial eye and for real-eye measurements, and can outperform a commonly-used wavefront sensor with highly aberrated wavefronts.

Hartmann-Shack wavefront sensing without a lenslet array using a digital micromirror device.

The common Hartmann-Shack wavefront sensor makes use of a lenslet array to sample in-parallel optical wavefronts. Here, we introduce a Hartmann-Shack wavefront sensor that employs a digital micromirror device in combination with a single lens for serial sampling by scanning. Sensing is analyzed numerically and validated experimentally using a deformable mirror operated in closed-loop adaptive optics with a conventional Hartmann-Shack wavefront sensor, as well as with a set of ophthalmic trial lenses, to generate controllable amounts of monochromatic aberrations. The new sensor is free of crosstalk and can potentially operate at kilohertz speed. It offers a reconfigurable aperture that can exclude unwanted parts of the wavefront.

Analysing the impact of myopia on the Stiles-Crawford effect of the first kind using a digital micromirror device.

PURPOSE: Photoreceptor light acceptance is closely tied to the Stiles-Crawford effect of the first kind (SCE-I). Whether the SCE-I plays a role in myopic development remains unclear although a reduction in directionality has been predicted for high myopia. The purpose of this study is to analyse the relationship between foveal SCE-I directionality, axial eye length, and defocus for emmetropic subjects wearing ophthalmic trial lenses during psychophysical measurements and for myopic subjects with their natural correction. METHOD: A novel uniaxial flicker system has been implemented making use of a Digital Micromirror Device (DMD) to flicker between a 2.3 visual degrees circular reference and a set of circular test patterns in a monocular Maxwellian view at 0.5 Hz. The brightness of the test is adjusted by the duty cycle of the projected light to an upper limit of 22 727 Hz. The wavelength and bandwidth are set by a tuneable liquid-crystal filter centred at 550 nm. A total of four measurement series for 11 pupil entrance points have been realized for the right eye of 6 emmetropic and 10 myopic subjects whose pupils were dilated with tropicamide. Five of the emmetropic subjects wore ophthalmic trial lenses in the range of -3 to +9 dioptres to mimic hyperopic to highly myopic vision and resulting visibility plots have been fitted to a Gaussian SCE-I function. In turn, the myopic subjects wore their natural correction during the analysis of the SCE-I. All subjects had their axial eye length determined with an ultrasound device. RESULTS: A SCE-I directionality parameter in the range of 0.03 to 0.06/mm2 was found for the emmetropic subjects with corrected vision in fair agreement to values in the literature. The results also revealed a marked reduction in directionality in the range from 16% to 30% with every 3 dioptre increase of simulated myopia, as well as a 10% increased directionality in simulated hyperopic eyes. For both emmetropic and myopic subjects, a decrease in directionality with increase in axial length was found in agreement with theoretical expectations. CONCLUSION: The study confirms a clear link between SCE-I directionality, uncorrected defocus, and axial eye length. This may play a role for emmetropization and thus myopic progression as cone photoreceptors capture light from a wider pupil area in elongated eyes due to a geometrical scaling.