Wolf M. Harmening

Normal Perceptual Sensitivity Arising From Weakly Reflective Cone Photoreceptors.

PURPOSE To determine the light sensitivity of poorly reflective cones observed in retinas of normal subjects, and to establish a relationship between cone reflectivity and perceptual threshold. METHODS Five subjects (four male, one female) with normal vision were imaged longitudinally (7-26 imaging sessions, representing 82-896 days) using adaptive optics scanning laser ophthalmoscopy (AOSLO) to monitor cone reflectance. Ten cones with unusually low reflectivity, as well as 10 normally reflective cones serving as controls, were targeted for perceptual testing. Cone-sized stimuli were delivered to the targeted cones and luminance increment thresholds were quantified. Thresholds were measured three to five times per session for each cone in the 10 pairs, all located 2.2 to 3.3° from the center of gaze. RESULTS Compared with other cones in the same retinal area, three of 10 monitored dark cones were persistently poorly reflective, while seven occasionally manifested normal reflectance. Tested psychophysically, all 10 dark cones had thresholds comparable with those from normally reflecting cones measured concurrently (P = 0.49). The variation observed in dark cone thresholds also matched the wide variation seen in a large population (n = 56 cone pairs, six subjects) of normal cones; in the latter, no correlation was found between cone reflectivity and threshold (P = 0.0502). CONCLUSIONS Low cone reflectance cannot be used as a reliable indicator of cone sensitivity to light in normal retinas. To improve assessment of early retinal pathology, other diagnostic criteria should be employed along with imaging and cone-based microperimetry.

Benefits of retinal image motion at the limits of spatial vision

Even during fixation, our eyes are constantly in motion, creating an ever-changing signal in each photoreceptor. Neuronal processes can exploit such transient signals to serve spatial vision, but it is not known how our finest visual acuity—one that we use for deciphering small letters or identifying distant faces and objects—is maintained when confronted with such change. We used an adaptive optics scanning laser ophthalmoscope to precisely control the spatiotemporal input on a photoreceptor scale in human observers during a visual discrimination task under conditions with habitual, cancelled or otherwise manipulated retinal image motion. We found that when stimuli moved, acuities were about 25% better than when no motion occurred, regardless of whether that motion was self-induced, a playback of similar motion, or an external simulation. We argue that in our particular experimental condition, the visual system is able to synthesize a higher resolution percept from multiple views of a poorly resolved image, a hypothesis that might extend the current understanding of how fixational eye motion serves high acuity vision.

Test-Retest Reliability of Scotopic and Mesopic Fundus-Controlled Perimetry Using a Modified MAIA (Macular Integrity Assessment) in Normal Eyes

Purpose: To assess the intrasession test-retest reliability of scotopic cyan and scotopic red fundus-controlled perimetry (FCP) in normal subjects using a modified MAIA “microperimeter” (macular integrity assessment) device. Methods: Forty-seven normal eyes of 30 subjects (aged 33.8 years) underwent duplicate mesopic (achromatic stimuli, 400-800 nm), scotopic cyan (505 nm), and scotopic red (627 nm) FCP, using a grid of 49 stimuli over 14° of the central retina. Test-retest reliability for pointwise sensitivity (PWS), stability of fixation, reaction time and test duration were analyzed using mixed-effects models. Results: PWS test-retest reliability was good among all 3 types of retinal sensitivity assessments (coefficient of repeatability of 4.75 dB for mesopic, 5.26 dB for scotopic cyan, and 4.06 dB for scotopic red testing). While the mean sensitivity decreased with eccentricity for both mesopic and scotopic red testing, it was highest at 7° eccentricity for the scotopic cyan assessment (p < 0.001). Conclusions: The modified MAIA device allows for reliable scotopic FCP in normal subjects. Our findings suggest that testing of scotopic cyan sensitivity largely reflects rod function.

Technical principles of OCT angiography

ZusammenfassungHintergrundDie OCT-Angiographie (OCT-A) ist eine neue klinische Untersuchungsmethode, die eine nichtinvasive dreidimensionale Darstellung der vaskulären Strukturen der Netzhaut und Aderhaut erlaubt. Technisch handelt es sich bei der OCT-A um eine Weiterentwicklung der optischen Kohärenztomographie (OCT). Durch leistungsfähigere Soft- und Hardware ermöglicht die OCT-A neben morphologischen Analysen auch eine dreidimensionale retinale und choroidale Perfusionsanalyse. Wir erläutern die Grundlagen sowie die Anwendung der OCT-A im Vergleich mit anderen nichtinvasiven Untersuchungsverfahren der retinalen und choroidalen Blutzirkulation.MethodenDer Arbeit liegen eine selektive Literaturrecherche und die Auswertung eigener Daten zugrunde.ErgebnisseVorteile der OCT-A bestehen in der einfachen Anwendung, die keiner Mydriasis oder intravenösen Fluoreszenzfarbstoffverabreichung bedarf. Sie gestattet eine exakte tiefensensitive Lokalisation vaskulärer Veränderungen. Bei retinalen Pathologien können Diskrepanzen zwischen softwareassistierter automatischer Segmentierung und realen Netzhautschichten bestehen, die bei der klinischen Interpretation zu beachten sind.SchlussfolgerungDie OCT-A ist von allen nichtinvasiven Perfusionsanalysen die einzige, die bereits in den klinischen Alltag implementiert werden kann. Mit diesem neuen bildgebenden Untersuchungsverfahren können vaskuläre retinale und choroidale Veränderungen tiefenselektiv und ohne Maskierungseffekt durch Pooling- oder Stainingphänomene detektiert werden.AbstractBackgroundOptical coherence tomography angiography (OCT-A) is a new diagnostic non-invasive method by which the vascular structures of the retina and choroid can be visualized three-dimensionally without need for using fluorescence dyes. The technology of OCT-A is an advancement of the OCT. By means of more powerful software and hardware used for OCT-A not only morphological but also retinal and choroidal vascular perfusion analyses can be performed. In this article, the principles and applications of OCT-A are discussed and compared to other non-invasive diagnostic devices for visualization of the retinal and choroidal blood circulation.MethodsThis article is based on a selective literature review and analyses of own data.ResultsThe advantages of OCT-A include easy application without the need for mydriasis or intravenous injection of fluorescence dyes and also the exact three-dimensional localization of vascular changes. In the case of retinal pathologies there is a considerable difference between software-assisted automatic segmentation and the real architecture of the retina, which must be taken into consideration in the clinical interpretation.ConclusionOf all noninvasive devices for visualization of the retinal and choroidal circulation, OCT-A is the only one which can already be implemented into the clinical routine. With this novel imaging device retinal and choroidal alterations can be visualized in a depth- selective manner and without masking affects, such as pooling or staining phenomena.BACKGROUND Optical coherence tomography angiography (OCT-A) is a new diagnostic non-invasive method by which the vascular structures of the retina and choroid can be visualized three-dimensionally without need for using fluorescence dyes. The technology of OCT-A is an advancement of the OCT. By means of more powerful software and hardware used for OCT-A not only morphological but also retinal and choroidal vascular perfusion analyses can be performed. In this article, the principles and applications of OCT-A are discussed and compared to other non-invasive diagnostic devices for visualization of the retinal and choroidal blood circulation. METHODS This article is based on a selective literature review and analyses of own data. RESULTS The advantages of OCT-A include easy application without the need for mydriasis or intravenous injection of fluorescence dyes and also the exact three-dimensional localization of vascular changes. In the case of retinal pathologies there is a considerable difference between software-assisted automatic segmentation and the real architecture of the retina, which must be taken into consideration in the clinical interpretation. CONCLUSION Of all noninvasive devices for visualization of the retinal and choroidal circulation, OCT-A is the only one which can already be implemented into the clinical routine. With this novel imaging device retinal and choroidal alterations can be visualized in a depth- selective manner and without masking affects, such as pooling or staining phenomena.

Spatiochromatic Interactions between Individual Cone Photoreceptors in the Human Retina

A remarkable feature of human vision is that the retina and brain have evolved circuitry to extract useful spatial and spectral information from signals originating in a photoreceptor mosaic with trichromatic constituents that vary widely in their relative numbers and local spatial configurations. A critical early transformation applied to cone signals is horizontal-cell-mediated lateral inhibition, which imparts a spatially antagonistic surround to individual cone receptive fields, a signature inherited by downstream neurons and implicated in color signaling. In the peripheral retina, the functional connectivity of cone inputs to the circuitry that mediates lateral inhibition is not cone-type specific, but whether these wiring schemes are maintained closer to the fovea remains unsettled, in part because central retinal anatomy is not easily amenable to direct physiological assessment. Here, we demonstrate how the precise topography of the long (L)-, middle (M)-, and short (S)-wavelength-sensitive cones in the human parafovea (1.5° eccentricity) shapes perceptual sensitivity. We used adaptive optics microstimulation to measure psychophysical detection thresholds from individual cones with spectral types that had been classified independently by absorptance imaging. Measured against chromatic adapting backgrounds, the sensitivities of L and M cones were, on average, receptor-type specific, but individual cone thresholds varied systematically with the number of preferentially activated cones in the immediate neighborhood. The spatial and spectral patterns of these interactions suggest that interneurons mediating lateral inhibition in the central retina, likely horizontal cells, establish functional connections with L and M cones indiscriminately, implying that the cone-selective circuitry supporting red–green color vision emerges after the first retinal synapse. SIGNIFICANCE STATEMENT We present evidence for spatially antagonistic interactions between individual, spectrally typed cones in the central retina of human observers using adaptive optics. Using chromatic adapting fields to modulate the relative steady-state activity of long (L)- and middle (M)-wavelength-sensitive cones, we found that single-cone detection thresholds varied predictably with the spectral demographics of the surrounding cones. The spatial scale and spectral pattern of these photoreceptor interactions were consistent with lateral inhibition mediated by retinal horizontal cells that receive nonselective input from L and M cones. These results demonstrate a clear link between the neural architecture of the visual system inputs—cone photoreceptors—and visual perception and have implications for the neural locus of the cone-specific circuitry supporting color vision.

Perception of Haidinger Brushes in Macular Disease Depends on Macular Pigment Density and Visual Acuity

PURPOSE To optimize the perceptibility of Haidinger brushes (HB) and to investigate its association with visual acuity and macular pigment density. METHODS In this prospective cross-sectional study, each subject underwent best-corrected visual acuity (BCVA) testing, funduscopy, and assessment of macular pigment optical density (MPOD) using the two-wavelength fundus autofluorescence method. Haidinger brush visibility was tested with a rotating linear polarizer and a controllable three-color light-emitting diode (LED) panel as light source. A simple model of macular pigment absorption was used to predict HB visibility as a function of stimulus wavelength and MPOD. RESULTS All control eyes (n = 92) and 34% of the 198 eyes of subjects with macular disease (age-related macular degeneration, n = 40; macular telangiectasia type 2, n = 52; Stargardt disease, n = 58; other retinal dystrophies, n = 48) perceived HB when an optimized test setup (464-nm LED light) was applied. The degree of psychophysical perception and the dependency on different wavelengths were in accordance with the absorptance model. In eyes of subjects with macular disease, minimum thresholds of MPOD and BCVA required for HB perception were identified. Subjects with macular telangiectasia type 2 showed lowest values of MPOD and were mostly unable to perceive HB despite relatively preserved BCVA. CONCLUSIONS Macular pigment and a relatively preserved foveal function are necessary for the perception of HB. Haidinger brushes are usually not perceived by subjects with macular telangiectasia type 2, likely due to their characteristic foveal depletion of macular pigment.

Technische Grundlagen der OCT-Angiographie

ZusammenfassungHintergrundDie OCT-Angiographie (OCT-A) ist eine neue klinische Untersuchungsmethode, die eine nichtinvasive dreidimensionale Darstellung der vaskulären Strukturen der Netzhaut und Aderhaut erlaubt. Technisch handelt es sich bei der OCT-A um eine Weiterentwicklung der optischen Kohärenztomographie (OCT). Durch leistungsfähigere Soft- und Hardware ermöglicht die OCT-A neben morphologischen Analysen auch eine dreidimensionale retinale und choroidale Perfusionsanalyse. Wir erläutern die Grundlagen sowie die Anwendung der OCT-A im Vergleich mit anderen nichtinvasiven Untersuchungsverfahren der retinalen und choroidalen Blutzirkulation.MethodenDer Arbeit liegen eine selektive Literaturrecherche und die Auswertung eigener Daten zugrunde.ErgebnisseVorteile der OCT-A bestehen in der einfachen Anwendung, die keiner Mydriasis oder intravenösen Fluoreszenzfarbstoffverabreichung bedarf. Sie gestattet eine exakte tiefensensitive Lokalisation vaskulärer Veränderungen. Bei retinalen Pathologien können Diskrepanzen zwischen softwareassistierter automatischer Segmentierung und realen Netzhautschichten bestehen, die bei der klinischen Interpretation zu beachten sind.SchlussfolgerungDie OCT-A ist von allen nichtinvasiven Perfusionsanalysen die einzige, die bereits in den klinischen Alltag implementiert werden kann. Mit diesem neuen bildgebenden Untersuchungsverfahren können vaskuläre retinale und choroidale Veränderungen tiefenselektiv und ohne Maskierungseffekt durch Pooling- oder Stainingphänomene detektiert werden.AbstractBackgroundOptical coherence tomography angiography (OCT-A) is a new diagnostic non-invasive method by which the vascular structures of the retina and choroid can be visualized three-dimensionally without need for using fluorescence dyes. The technology of OCT-A is an advancement of the OCT. By means of more powerful software and hardware used for OCT-A not only morphological but also retinal and choroidal vascular perfusion analyses can be performed. In this article, the principles and applications of OCT-A are discussed and compared to other non-invasive diagnostic devices for visualization of the retinal and choroidal blood circulation.MethodsThis article is based on a selective literature review and analyses of own data.ResultsThe advantages of OCT-A include easy application without the need for mydriasis or intravenous injection of fluorescence dyes and also the exact three-dimensional localization of vascular changes. In the case of retinal pathologies there is a considerable difference between software-assisted automatic segmentation and the real architecture of the retina, which must be taken into consideration in the clinical interpretation.ConclusionOf all noninvasive devices for visualization of the retinal and choroidal circulation, OCT-A is the only one which can already be implemented into the clinical routine. With this novel imaging device retinal and choroidal alterations can be visualized in a depth- selective manner and without masking affects, such as pooling or staining phenomena.BACKGROUND Optical coherence tomography angiography (OCT-A) is a new diagnostic non-invasive method by which the vascular structures of the retina and choroid can be visualized three-dimensionally without need for using fluorescence dyes. The technology of OCT-A is an advancement of the OCT. By means of more powerful software and hardware used for OCT-A not only morphological but also retinal and choroidal vascular perfusion analyses can be performed. In this article, the principles and applications of OCT-A are discussed and compared to other non-invasive diagnostic devices for visualization of the retinal and choroidal blood circulation. METHODS This article is based on a selective literature review and analyses of own data. RESULTS The advantages of OCT-A include easy application without the need for mydriasis or intravenous injection of fluorescence dyes and also the exact three-dimensional localization of vascular changes. In the case of retinal pathologies there is a considerable difference between software-assisted automatic segmentation and the real architecture of the retina, which must be taken into consideration in the clinical interpretation. CONCLUSION Of all noninvasive devices for visualization of the retinal and choroidal circulation, OCT-A is the only one which can already be implemented into the clinical routine. With this novel imaging device retinal and choroidal alterations can be visualized in a depth- selective manner and without masking affects, such as pooling or staining phenomena.

Functional Imaging of Cone Photoreceptors

Color pervades our visual sensory world, yet our understanding of the neural basis of color perception, starting with the retina and on through the multiple cortical areas that subserve vision, is still incomplete. The L, M, and S cone photoreceptors, being the cellular entry point for trichromatic vision in humans and primates, have been studied in a variety of ways to reveal their relative numbers, their spatial arrangement, and their anatomical connectivity. We review work in these species that has linked mapped cone mosaics directly to functional properties such as single neuron responses in the retina and color percepts arising from cone-targeted microstimulation. Technical issues that constrain access to single cone photoreceptors for functional studies are also considered.

Ultra-high contrast retinal display system for single photoreceptor psychophysics

Due to the enormous dynamic range of human photoreceptors in response to light, studying their visual function in the intact retina challenges the stimulation hardware, specifically with regard to the displayable luminance contrast. The adaptive optics scanning laser ophthalmoscope (AOSLO) is an optical platform that focuses light to extremely small retinal extents, approaching the size of single photoreceptor cells. However, the current light modulation techniques produce spurious visible backgrounds which fundamentally limit experimental options. To remove unwanted background light and to improve contrast for high dynamic range visual stimulation in an AOSLO, we cascaded two commercial fiber-coupled acousto-optic modulators (AOMs) and measured their combined optical contrast. By compensating for zero-point differences in the individual AOMs, we demonstrate a multiplicative extinction ratio in the cascade that was in accordance with the extinction ratios of both single AOMs. When latency differences in the AOM response functions were individually corrected, single switch events as short as 50 ns with radiant power contrasts up to 1:1010 were achieved. This is the highest visual contrast reported for any display system so far. We show psychophysically that this contrast ratio is sufficient to stimulate single foveal photoreceptor cells with small and bright enough visible targets that do not contain a detectable background. Background-free stimulation will enable photoreceptor testing with custom adaptation lights. Furthermore, a larger dynamic range in displayable light levels can drive photoreceptor responses in cones as well as in rods.

Retinal injury following laser pointer exposure

BACKGROUND Recent years have seen a marked increase in laser-pointerrelated injuries, which sometimes involve severe retinal damage and irreversible visual impairment. These injuries are often caused by untested or incorrectly classified devices that are freely available over the Internet. METHODS We reviewed pertinent publications retrieved by a systematic search in the PubMed and Web of Science databases and present our own series of clinical cases. RESULTS We identified 48 publications describing a total of 111 patients in whom both acute and permanent damage due to laser pointers was documented. The spectrum of damage ranged from focal photoreceptor defects to macular foramina and retinal hemorrhages associated with loss of visual acuity and central scotoma. On initial presentation, the best corrected visual acuity (BCVA) was less than 20/40 (Snellen equivalent) in 55% of the affected eyes and 20/20 or better in 9% of the affected eyes. Treatment options after laserpointer- induced ocular trauma are limited. Macular foramina and extensive hemorrhages can be treated surgically. In our series of 7 cases, we documented impaired visual acuity, central visual field defects, circumscribed and sometimes complex changes of retinal reflectivity, and intraretinal fluid. Over time, visual acuity tended to improve, and scotoma subjectively decreased in size. CONCLUSION Laser pointers can cause persistent retinal damage and visual impairment. In view of the practically unimpeded access to laser pointers (even high-performance ones) over the Internet, society at large now needs to be more aware of the danger posed by these devices, particularly to children and adolescents.