Scanning Laser Ophthalmoscope Research Articles

Retinal Artery Angles in High Axial Myopia and Its Relationship With Visual Function.

To evaluate the retinal artery angles in high axial myopia and assess the correlation with other morphometric and functional parameters. This cross-sectional study included 112 eyes of 112 patients with high axial myopia. Based on axial length (AL), the participants were divided into three groups: group 1 (26 ≤ AL < 28 mm), group 2 (28 ≤ AL < 31 mm), and group 3 (≥31 mm). Scanning laser ophthalmoscopy imaging was used to analyze the retinal artery angle (Yugami correlated angle [YCA]). Retinal vascular densities (VDs) in both superficial capillary plexuses (SCPs) and deep capillary plexuses were evaluated. Fixation behavior, including retinal mean sensitivity (MS), macular fovea 2°, 4° fixation rate (P1, P2), and 68.2% bivariate contour ellipse area, were analyzed by microperimetry. Finally, the correlation between YCAs and AL, VDs, best-corrected visual acuity (BCVA), and fixation behavior was assessed. The YCAs showed significant differences among the three groups (all P < 0.001, respectively). Compared to group 1, the YCA decreased in group 2 (P < 0.001) and continued to decrease in group 3 (P = 0.043). The correlation analysis revealed that smaller YCAs (YCA, YCA1/2, YCA1/4) were positively correlated with the longer AL (ρ = 0.580, 0.545, 0.448, P < 0.001) and lower VDs in any sector in SCPs (all P ≤ 0.05). Furthermore, smaller YCAs were positively correlated with decreased BCVA (ρ = 0.392, 0.387, 0.262; all P < 0.001) and reduced MS (ρ= 0.300, 0.269, 0.244; all P < 0.05). Smaller YCAs were correlated with longer AL, lower VD in SCP, decreased BCVA, and reduced MS. The YCAs might reflect vascular deformation caused by axial elongation and could potentially be useful in predicting visual function in high axial myopia. The quantitative analysis of YCAs in fundus photography holds potential clinical value in predicting visual function in high axial myopia.

Metabolic changes and retinal remodeling in Heterozygous CRX mutant cats (CRXRDY/+)

CRX is a transcription factor essential for normal photoreceptor development and survival. The CRXRdy cat has a naturally occurring truncating mutation in CRX and is a large animal model for dominant Leber congenital amaurosis. This study investigated retinal remodeling that occurs as photoreceptors degenerate. CRXRdy/+ cats from 6 weeks to 10 years of age were investigated. In vivo structural changes of retinas were analyzed by fundus examination, confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography. Histologic analyses included immunohistochemistry for computational molecular phenotyping with macromolecules and small molecules. Affected cats had a cone-led photoreceptor degeneration starting in the area centralis. Initially there was preservation of inner retinal cells such as bipolar, amacrine and horizontal cells but with time migration of the deafferented neurons occurred. Early in the process of degeneration glial activation occurs ultimately resulting in formation of a glial seal. With progression the macula-equivalent area centralis developed severe atrophy including loss of retinal pigmentary epithelium. Microneuroma formation occured in advanced stages as more marked retinal remodeling occurred. This study indicates that retinal degeneration in the CrxRdy/+ cat retina follows the progressive, phased revision of retina that have been previously described for retinal remodeling. These findings suggest that therapy dependent on targeting inner retinal cells may be useful in young adults with preserved inner retinas prior to advanced stages of retinal remodeling and neuronal cell loss.

Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and Development.

Serum response factor (SRF) controls the expression of muscle contraction and motility genes in mural cells (MCs) of the vasculature. In the retina, MC-SRF is important for correct angiogenesis during development and the continuing maintenance of the vascular tone. The purpose of this study was to provide further insights into the effects of MC SRF deficiency on the vasculature and function of the mature retina in SrfiMCKO mice that carry a MC-specific deletion of Srf. Retinal morphology and vascular integrity were analyzed in vivo via scanning laser ophthalmoscopy (SLO), angiography, and optical coherence tomography (OCT). Retinal function was evaluated with full-field electroretinography (ERG). We found that retinal blood vessels of these mutants exhibited different degrees of morphological and functional alterations. With increasing severity, we found vascular bulging, the formation of arteriovenous (AV) anastomoses, and ultimately, a retinal detachment (RD). The associated irregular retinal blood pressure and flow distribution eventually induced hypoxia, indicated by a negative ERG waveform shape. Further, the high frequency of interocular differences in the phenotype of individual SrfiMCKO mice points to a secondary nature of these developments far downstream of the genetic defect and rather dependent on the local retinal context.

THE WAY PATIENTS SEE FLOATERS: Widefield Dynamic Scanning Laser Ophthalmoscopy Imaging of Vitreous Abnormalities.

To investigate the use of dynamic widefield scanning laser ophthalmoscopy (SLO) and B-scan ultrasonography in imaging vitreous abnormalities in patients with complaints of floaters. Twenty-one patients underwent both dynamic SLO and B-scan ultrasonography to image their vitreous abnormalities. After reviewing these videos, patients graded each imaging technique on a scale of 1 to 10, based on how closely it represented their visual perception of floaters. The mean age of the patients (12 women and nine men) was 47.7 ± 18.5 years. The patients graded a median score of nine for SLO imaging (mean = 8.43) compared with a median score of 5 (mean = 4.95) for ultrasound ( P = 0.001). Widefield SLO imaging demonstrated three-dimensional interconnectivity within the condensations of the formed vitreous that exhibited translational and rotational movements with eye saccades. Floaters are a common complaint, but it is difficult to know whether imaging findings of the vitreous correlate to what patients perceive. Widefield SLO seems to image vitreous abnormalities related to how patients perceive their own floaters better than B-scan ultrasonography. Despite the term "floaters", the vitreous abnormalities in the videos seemed to be manifestations of a complex three-dimensional degeneration of the vitreous framework.

Spotlight on Lattice Degeneration Imaging Techniques.

Lattice degeneration (LD), routinely diagnosed with indirect ophthalmoscopy, is one of the most common and clinically significant peripheral retinal findings. In this review, we have summarized the data on currently available imaging techniques which help to improve diagnosis and our understanding of LD pathogenesis. Ultra-wide field imaging provides reliable color fundus capturing for the primary diagnosis of LD and may also be used as a screening tool. Wide-field imaging can be used for targeted documentation of LD lesions using true colors and with minimal optical distortions. Information on the status of the vitreoretinal interface, including detection of retinal holes, detachments, and vitreous tractions, can be obtained with peripheral structural optical coherence tomography (OCT) or scanning laser ophthalmoscopy in retro-mode. These techniques clarify the associated risks of rhegmatogenous retinal detachment. Fundus autofluorescence can provide details on atrophic changes. However, the risk of retinal detachment by means of this technique requires further investigation. OCT angiography may be successfully performed for some lesions. Taken together, OCT and OCT angiography demonstrate thinning of the choroid, alteration of local choroidal microcirculation, and, in severe lesions, involvement of the sclera. OCT angiography confirms loss of retinal microcirculation within LD lesion, which was previously shown with fluorescein angiography. In conclusion, despite relatively simple primary diagnosis, imaging of LD lesions remains challenging due to their peripheral localization. However, several new strategies, including ultra-wide field imaging, peripheral OCT, and scanning laser ophthalmoscopy, make LD imaging possible on a routine basis, improving diagnosis and understanding of LD pathogenesis.

Multimodal Deep Learning Classifier for Primary Open-angle Glaucoma Diagnosis Using Wide-field Optic Nerve Head Cube Scans in Eyes With and Without High Myopia.

An OCT-based multimodal deep learning classification model including texture information is introduced that outperforms single-modal models and multimodal models without texture information for glaucoma diagnosis in eyes with and without high myopia. To evaluate the diagnostic accuracy of a multimodal deep learning (DL) classifier using wide optical coherence tomography (OCT) optic nerve head cube scans in eyes with and without axial high myopia. 371 primary open-angle glaucoma (POAG) eyes and 86 healthy eyes, all without axial high myopia (axial length AL≤26mm) and 92 POAG eyes and 44 healthy eyes, all with axial high myopia (AL>26mm) were included. The multimodal DL classifier combined features of 3 individual VGG-16 models: 1) texture-based en face image, 2) retinal nerve fiber layer (RNFL) thickness map image and 3) confocal scanning laser ophthalmoscope (cSLO) image. Age, AL, and disc area adjusted area under the receiver operating curves (AUROC) were used to compare model accuracy. Adjusted AUROC for the multimodal DL model was 0.91 (95% CI = 0.87, 0.95). This value was significantly higher than the values of individual models (0.83 [0.79, 0.86] for texture based en face image; 0.84 [0.81, 0.87] for RNFL thickness map; and 0.68 [0.61, 0.74] for cSLO image; all P≤0.05). Using only highly myopic eyes, the multimodal DL model showed significantly higher diagnostic accuracy (0.89 [0.86 , 0.92]) compared to texture en face image (0.83 [0.78 , 0.85]), RNFL (0.85 [0.81 , 0.86]) and cSLO image models (0.69 [0.63 , 0.76]) (all P≤0.05). Combining OCT-based RNFL thickness maps with texture based en face images showed better ability to discriminate between healthy and POAG than thickness maps alone, particularly in high axial myopic eyes.

Enhanced S-Cone Syndrome: Elevated Cone Counts Confer Supernormal Visual Acuity in the S-Cone Pathway.

To measure photoreceptor packing density and S-cone spatial resolution as a function of retinal eccentricity in patients with enhanced S-cone syndrome (ESCS) and to discuss the possible mechanisms supporting their supernormal S-cone acuity. We used an adaptive optics scanning laser ophthalmoscope (AOSLO) to characterize photoreceptor packing. A custom non-AO display channel was used to measure L/M- and S-cone-mediated visual acuity during AOSLO imaging. Acuity measurements were obtained using a four-alternative, forced-choice, tumbling E paradigm along the temporal meridian between the fovea and 4° eccentricity in five of six patients and in seven control subjects. L/M acuity was tested by presenting long-pass-filtered optotypes on a black background, excluding wavelengths to which S-cones are sensitive. S-cone isolation was achieved using a two-color, blue-on-yellow chromatic adaptation method that was validated on three control subjects. Inter-cone spacing measurements revealed a near-uniform cone density profile (ranging from 0.9-1.5 arcmin spacing) throughout the macula in ESCS. For comparison, normal cone density decreases by a factor of 14 from the fovea to 6°. Cone spacing of ESCS subjects was higher than normal in the fovea and subnormal beyond 2°. Compared to the control subjects (n = 7), S-cone-mediated acuities in patients with ESCS were normal near the fovea and became increasingly supernormal with retinal eccentricity. Beyond 2°, S-cone acuities were superior to L/M-cone-mediated acuity in the ESCS cohort, a reversal of the trend observed in normal retinas. Higher than normal parafoveal cone densities (presumably dominated by S-cones) confer better than normal S-cone-mediated acuity in ESCS subjects.

MULTIMODAL IMAGING IN NONEXUDATIVE CHOROIDAL NEOVASCULARIZATION: A Pilot Study of Status of Retinal Pigment Epithelium.

To study the status of retinal pigment epithelium in nonexudative and active choroidal neovascularization (CNV) in neovascular age-related macular degeneration. Only treatment-naïve neovascular age-related macular degeneration patients were enrolled in this prospective case-control study, including 17 eyes with nonexudative CNV (6 males and 11 females, 74.9 ± 10.0 years) and 28 eyes with active CNV (8 males and 20 females, 69.3 ± 6.8 years). All patients received a comprehensive ophthalmic examination, optical coherence tomography, dark-field scanning laser ophthalmoscopy, and fundus autofluorescence. The status of the retinal pigment epithelium was assessed with ImageJ software as the brightness of the CNV region on transillumination optical coherence tomography, dark-field scanning laser ophthalmoscopy, and fundus autofluorescence images. Choroidal neovascularization vessel density was measured based on optical coherence tomography angiography. The brightness of CNV region in nonexudative CNV was statistically significantly lower than in active CNV with both optical coherence tomography transillumination ( P = 0.004) and dark-field scanning laser ophthalmoscopy ( P = 0.0015). No difference in brightness of the CNV region between nonexudative and active CNV was found based on fundus autofluorescence ( P = 0.44). The vessel density of nonexudative CNV was statistically significantly higher than that of active CNV with a median value of 64.5% (95% confidential interval [CI] 53.4-79.0%) and 55.3% (95% CI 52.2-60.0%), respectively ( P = 0.05). Multimodal imaging revealed substantial alteration of the retinal pigment epithelium in active CNV but not in nonexudative CNV which correlates with the higher vessel density of nonexudative CNV.

Retinal Vessel Caliber Measurement Bias in Fundus Images in the Presence of the Central Light Reflex.

To investigate the agreement between a fundus camera and a scanning laser ophthalmoscope in retinal vessel caliber measurements and to identify whether the presence of the central light reflex (CLR) explains potential discrepancies. For this cross-sectional study, we obtained fundus camera and scanning laser ophthalmoscope images from 85 eyes of 85 healthy individuals (aged 50-65 years) with different blood pressure status. We measured the central retinal artery equivalent (CRAE) and central retinal artery vein equivalent (CRVE) with the Knudtson-Parr-Hubbard algorithm and assessed the CLR using a semiautomatic grading method. We used Bland-Altman plots, 95% limits of agreement, and the two-way mixed effects intraclass correlation coefficient for consistency [ICC(3,1)] to describe interdevice agreement. We used multivariable regression to identify factors associated with differences in between-device measurements. The between-device difference in CRAE (9.5 µm; 95% confidence interval, 8.0-11.1 µm) was larger than the between-device difference in CRVE (2.9 µm; 95% confidence interval, 1.3-4.5 µm), with the fundus camera yielding higher measurements (both P < 0.001). The 95% fundus camera-scanning laser ophthalmoscope limits of agreement were -4.8 to 23.9 µm for CRAE and -12.0 to 17.8 µm for CRVE. The corresponding ICCs(3,1) were 0.89 (95% confidence interval, 0.83-0.92) and 0.91 (95% confidence interval, 0.86-0.94). The between-device CRAE difference was positively associated with the presence of a CLR (P = 0.002). Fundus cameras and scanning laser ophthalmoscopes yield correlated but not interchangeable caliber measurements. The CLR induces bias in arteriolar caliber in fundus camera images, compared with scanning laser ophthalmoscope images. Refined measurements could yield better estimates of the association between retinal vessel caliber and ophthalmic or systemic disease.

Practical applications of vitreous imaging for the treatment of vitreous opacities with YAG vitreolysis.

To demonstrate the methodology and efficacy of using scanning laser ophthalmoscopy (SLO) and dynamic optical coherence tomography (OCT) to identify and treat symptomatic vitreous floaters using yttrium-aluminum garnet laser vitreolysis (YLV). This is a case series highlighted from a cross sectional retrospective study conducted at the Vitreous Retina Macula Specialists of Toronto. Forty eyes from thirty-five patients were treated with YLV between November 2018 and December 2020 for symptomatic floaters and imaged with SLO and dynamic OCT. Patients were re-treated with YLV if they reported ongoing significant vision symptoms during follow-up which correlated to visible opacities on exam and or imaging. Three cases will be highlighted to present the practical applications of SLO and dynamic OCT imaging for YLV treatment. Forty treated eyes were enrolled in this study, with twenty-six eyes (65%) requiring at least one repeat YLV treatment following the first treatment due to ongoing symptomatic floaters. Following the first YLV, there was a significant improvement in overall mean best corrected visual acuity compared to before treatment (0.11 ± 0.20 LogMAR units vs. 0.14 ± 0.20 LogMAR units, p = 0.02 (paired t test)). Case 1 demonstrates a dense, solitary vitreous opacity that has been localized with dynamic OCT imaging to track its movements and retinal shadowing with the patient's eye movements. Case 2 shows the utility of adjusting the fixation target to monitor the movement of vitreous opacities in real-time. Case 3 exhibits an association between decreased symptom burden and vitreous opacity density after YLV. Image-guided YLV facilitates the localization and confirmation of vitreous opacities. SLO and dynamic OCT of the vitreous can provide a real-time evaluation of floater size, movement, and morphology, to help clinicians target treatment and monitoring of symptomatic floaters.

Scanning Laser Ophthalmoscopy Demonstrates Disc and Peripapillary Strain During Horizontal Eye Rotation in Adults

We used automated image analysis of scanning laser ophthalmoscopy (SLO) to investigate mechanical strains imposed on disc, and retinal and choroidal vessels during horizontal duction in adults. Deep learning analysis of optical images. The peripapillary region was imaged by SLO in central gaze, and 35° abduction and adduction, in younger and older healthy adults. Automated image registration was followed by deep learning-based optical flow analysis to track determine local tissue deformations quantified as horizontal, vertical, and shear strain maps relative to central gaze. Choroidal vessel displacements were observed when fundus pigment was light. Strains in the retina and disc could be quantified in 22 younger (mean ± SEM, 26 ± 5 years) and 19 older (64 ± 10 years) healthy volunteers. Strains were predominantly horizontal and greater for adduction than for abduction. During adduction, maximum horizontal strain was tensile in the nasal hemi-disc, and declined progressively with distance from it. Strain in the temporal hemi-retina during adduction was minimal, except for compressive strain on the disc of older subjects. In abduction, horizontal strains were less and largely confined to the disc, greater in older subjects, and generally tensile. Vertical and shear strains were small. Nasal to the disc, choroidal vessels shifted nasally relative to overlying peripapillary retinal vessels. Strain analysis during horizontal duction suggests that the optic nerve displaces the optic canal, choroid, and peripapillary sclera relative to the overlying disc and retina. This peripapillary shearing of the optic nerve relative to the choroid and sclera may be a driver of disc tilting and peripapillary atrophy.

ULTRA-WIDEFIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN MILD FAMILIAL EXUDATIVE VITREORETINOPATHY.

To investigate ultra-widefield optical coherence tomography angiography (UWF-OCTA) to detect and evaluate mild familial exudative vitreoretinopathy and compare the detective ratio of UWF-OCTA with ultra-widefield scanning laser ophthalmoscopy and ultra-widefield fluorescein angiography. The patients with familial exudative vitreoretinopathy were included in this study. UWF-OCTA, using a 24- × 20-mm montage, was performed for all patients. All images were independently tested for the presence of familial exudative vitreoretinopathy-associated lesions. Statistical analysis was performed with SPSS V.24.0. Forty-six eyes of 26 participants were included in the study. Ultra-widefield optical coherence tomography angiography was found to be greatly superior to ultra-widefield scanning laser ophthalmoscopy in detecting peripheral retinal vascular abnormality ( P < 0.001) and peripheral retinal avascular zone ( P < 0.001). The detection rates of peripheral retinal vascular abnormality, peripheral retinal avascular zone, retinal neovascularization, macular ectopia, and temporal midperipheral vitreoretinal interface abnormality were comparable with ultra-widefield fluorescein angiography images ( P > 0.05). Furthermore, vitreoretinal traction (17/46, 37%) and small foveal avascular zone (17/46, 37%) were detected effectively on UWF-OCTA. Ultra-widefield optical coherence tomography angiography is a reliable noninvasive tool to detect familial exudative vitreoretinopathy lesions, especially in mild patients or asymptomatic family members. The unique manifestation of UWF-OCTA offers an alternative to ultra-widefield fluorescein angiography for the screening and diagnosis of FEVR.

Retromode Scanning Laser Ophthalmoscopy for Choroidal Nevi: A Preliminary Study.

The purpose of the present study was to document pathological findings on retromode imaging in choroidal nevi and evaluate its diagnostic validity, using the confocal scanning laser ophthalmoscope Nidek Mirante (cSLO). A total of 41 choroidal nevi from 41 patients were included. All patients underwent multicolor fundus (mCF), infrared reflectance (IR), green fundus autofluorescence (FAF), dark-field (DF) and retromode (RM) imaging and optical coherence tomography (OCT) scans. We investigated retromode images to evaluate choroidal nevus features by comparing the results with those of mCF, IR, FAF, DF and OCT. In 100% of available images, retromode scanning laser ophthalmoscopy was able to detect choroidal nevi with a characteristic "hypo-retro-reflective" pattern, even the cases not visible on mCF, IR and FAF images. It also made it possible to delineate the margins of lesions with the highest rate of sharpness and accuracy among the imaging modalities examined. These findings seem to demonstrate how RM-SLO is an innovative diagnostic tool to detect and follow up choroidal nevi in a fast, reliable and non-invasive way.

It's not easy seeing green: The veridical perception of small spots.

When single cones are stimulated with spots of 543-nm light presented against a white background, subjects report percepts that vary between predominately red, white, and green. However, light of the same spectral composition viewed over a large field under normal viewing conditions looks invariably green and highly saturated. It remains unknown what stimulus parameters are most important for governing the color appearance in the transition between these two extreme cases. The current study varied the size, intensity and retinal motion of stimuli presented in an adaptive optics scanning laser ophthalmoscope. Stimuli were either stabilized on target locations or allowed to drift across the retina with the eye's natural motion. Increasing both stimulus size and intensity led to higher likelihoods that monochromatic spots of light were perceived as green, whereas only higher intensities led to increases in perceived saturation. The data also show an interaction between size and intensity, suggesting that the balance between magnocellular and parvocellular activation may be critical factors for color perception. Surprisingly, under the range of conditions tested, color appearance did not depend on whether stimuli were stabilized. Sequential activation of many cones does not appear to drive hue and saturation perception as effectively as simultaneous activation of many cones.

New Terminology and Methodology for the Assessment of the Vitreous, Its Floaters and Opacities, and Their Effect on Vision: Standardized and Kinetic Anatomical and Functional Testing of Vitreous Floaters and Opacities (SK VFO Test)

To introduce VFO and SK VFO Test: new, more representative terminology for symptoms of vitreous floaters/opacities (VFO) and new standardized kinetic (SK) anatomical-functional assessment. Eight eyes underwent before-after limited vitrectomy (LV): best-corrected visual acuity, low-luminance visual acuity, Minnesota Low Vision Reading Chart near visual acuity in logMAR, contrast sensitivity function (CV1000E), and straylight measurements (SM) (HDA/LDA/C-Quant). SK infrared confocal scanning laser ophthalmoscopy (SK IRcSLO) and swept-source widefield optical coherence tomography (SS-WF-OCT) identified VFO and posterior vitreous detachment (PVD). SK IRcSLO was performed with gaze directed towards the extreme superior, inferior, and lateral directions. Anatomical-functional results after LV improved in 7 eyes (87.5%): objective scatter index (27.34%), disturbance index (47.97%) and C-Quant Log units (2.26%). Pre-LV SK IRcSLO and SS-WFOCT imaging identified dynamic well-defined VFO and PVD status (100%). A residual asymptomatic anterior cortical vitreous-induced shadowing ripple effect was detected post-LV. This is the first objective-standardized test accounting for VFO kinesis and intermittent effect. There is potential for personalizing treatment and establishing best candidates for laser or surgery. [Ophthalmic Surg Lasers Imaging Retina 2023;54:306-315.].

Efficacy and accuracy of artificial intelligence to overlay multimodal images from different optical instruments in patients with retinitis pigmentosa.

Retinitis pigmentosa (RP) represents a group of progressive, genetically heterogenous blinding diseases. Recently, relationships between measures of retinal function and structure are needed to help identify outcome measures or biomarkers for clinical trials. The ability to align retinal multimodal images, taken on different platforms, will allow better understanding of this relationship. We investigate the efficacy of artificial intelligence (AI) in overlaying different multimodal retinal images in RP patients. We overlayed infrared images from microperimetry on near-infra-red images from scanning laser ophthalmoscope and spectral domain optical coherence tomography in RP patients using manual alignment and AI. The AI adopted a two-step framework and was trained on a separate dataset. Manual alignment was performed using in-house software that allowed labelling of six key points located at vessel bifurcations. Manual overlay was considered successful if the distance between same key points on the overlayed images was ≤1/2°. Fifty-seven eyes of 32 patients were included in the analysis. AI was significantly more accurate and successful in aligning images compared to manual alignment as confirmed by linear mixed-effects modelling (p < 0.001). A receiver operating characteristic analysis, used to compute the area under the curve of the AI (0.991) and manual (0.835) Dice coefficients in relation to their respective 'truth' values, found AI significantly more accurate in the overlay (p < 0.001). AI was significantly more accurate than manual alignment in overlaying multimodal retinal imaging in RP patients and showed the potential to use AI algorithms for future multimodal clinical and research applications.

Insights Into PROM1-Macular Disease Using Multimodal Imaging.

To describe the features of genetically confirmed PROM1-macular dystrophy in multimodal images. Thirty-six (36) eyes of 18 patients (5-66 years; mean age, 42.4 years) were prospectively studied by clinical examination and multimodal imaging. Short-wavelength autofluorescence (SW-AF) and quantitative fundus autofluorescence (qAF) images were acquired with a scanning laser ophthalmoscope (HRA+OCT, Heidelberg Engineering) modified by insertion of an internal autofluorescent reference. Further clinical testing included near-infrared autofluorescence (NIR-AF; HRA2, Heidelberg Engineering) with semiquantitative analysis, spectral domain-optical coherence tomography (HRA+OCT) and full-field electroretinography. All patients were genetically confirmed by exome sequencing. All 18 patients presented with varying degrees of maculopathy. One family with individuals affected across two generations exhibited granular fleck-like deposits across the posterior pole. Areas of granular deposition in SW-AF and NIR-AF corresponded to intermittent loss of the ellipsoid zone, whereas discrete regions of hypoautofluorescence corresponded with a loss of outer retinal layers in spectral-domain optical coherence tomography scans. For 18 of the 20 eyes, qAF levels within the macula were within the 95% confidence intervals of healthy age-matched individuals; nor was the mean NIR-AF signal increased relative to healthy eyes. Although PROM1-macular dystrophy (Stargardt disease 4) can exhibit phenotypic overlap with recessive Stargardt disease, significantly increased SW-AF levels were not detected. As such, elevated bisretinoid lipofuscin may not be a feature of the pathophysiology of PROM1 disease. The qAF approach could serve as a method of early differential diagnosis and may help to identify appropriate disease targets as therapeutics become available to treat inherited retinal disease.

The fundus of the eye as a target organ in hypertension: a literature review

This review discusses the current understanding of hypertensive retinopathy. It describes the pathomorphology of hypertensive retinopathy according to its grade. The main approaches to classification and elements of pathophysiology are briefly considered, and the clinical significance of hypertensive changes in the fundus is examined. The characteristics of traditional and innovative methods of assessing the retina, and their accuracy in predicting the course of hypertension is discussed. Data from our investigations with scanning laser ophthalmoscopy and optical coherence tomographic angiography are presented. Our data show that uncomplicated hypertension in middle-aged men and women is accompanied by a distinct reduction in the diameter of the retinal arterioles and an expansion of the foveal avascular zone at the level of the superficial capillary plexus of the retina. We review the literature and present the results of our observations, demonstrating the retinoprotective benefits of antihypertensive therapy.

Multimodal Imaging of Quiescent Choroidal Neovascularization: Status of Retinal Pigment Epithelium

Purpose: to study the status of retinal pigment epithelium (RPE) over the area of quiescent choroidal neovascularization (CNV) in comparison with active CNV in neovascular age-related macular degeneration (nAMD).Patients and methods: This study included 17 patients with quiescent CNV (6 males and 11 females, mean age 74.9 ± 10.0 years) and 28 patients with active CNV (8 males and 20 females, average age 69.3 ± 6.8 years). All participants received a standard ophthalmological examination, including spectral optical coherence tomography (OCT), dark-field scanning laser ophthalmoscopy (DF-SLO) and autofluorescence. Using ImageJ, the brightness of the image in the projection of the CNV was evaluated. The vascular density of the membrane was assessed using OCT angiography.Results: The vascular density of quiescent CNV was statistically significantly higher than that of active CNV with a median value of 64.5 % (95 % confidence interval (CI) 53.4–79.0 %) and 55.3 % (95 % CI 52.2–60.0 %) (p = 0.05). Image brightness in the silent membrane region was significantly lower by compared with active CNV, both according to OCT transillumination data (p = 0.004) and according to DF-SLO data (p = 0.0015). There were no differences in autofluorescence indices between active and quiescent CNV (p = 0.44).Conclusion: Multimodal imaging indicates significant loss of integrity of RPE over active CNV, which corresponds to their lower vascular density according to OCT angiography.

A comparison of optophysiological biomarkers of photoreceptor stress and phototoxicity in BALB/cJ, B6 (Cg)-Tyrc-2J/J, and C57Bl/6J mouse strains.

Ophthalmic imaging instruments, including the confocal scanning laser ophthalmoscope and spectral-domain optical coherence tomography system, originally intended for revealing ocular microstructures in the human eye, have been deployed by vision researchers to evaluate the eyes of numerous small and large animal species for more than two decades. In this study, we have used these two instruments to obtain imaging data sequentially from the retinas of three prominent, widely used experimental mouse models to document changes induced by two contrasting vivarium lighting conditions. Mice studied include albino BALB/cJ and B6(Cg)-Tyrc-2J/J and pigmented C57Bl/6J. Mice were reared under dim light conditions until ~8 weeks of age where they underwent baseline imaging. Following, mice were returned to the dim vivarium or relocated to the top rack cage position in a standard vivarium. Mice were then followed for several months by ocular imaging to catalog the retinal dynamics as a function of long-term dim vs. elevated, standard vivarium lighting exposure levels. Upon exposure to elevated light levels, B6(Cg)-Tyrc-2J/J underwent similar changes as BALB/cJ in regard to photoreceptor outer segment shortening, photoreceptor layer proximal aspect hyperreflective changes, and the development of retinal infoldings and autofluorescent sub-retinal inflammatory monocyte infiltrate. Noteworthy, however, is that infoldings and infiltrate occurred at a slower rate of progression in B6(Cg)-Tyrc-2J/J vs. BALB/cJ. The photoreceptor outer nuclear layer thickness of BALB/cJ degenerated steadily following elevated light onset. In contrast, B6(Cg)-Tyrc-2J/J degeneration was unremarkable for many weeks before experiencing a noticeable change in the rate of degeneration that was concomitant with a plateau and decreasing trend in number of retinal infoldings and monocyte infiltrate. Pathological changes in C57Bl/6J mice were unremarkable for all imaging biomarkers assessed with exception to autofluorescent sub-retinal inflammatory monocyte infiltrate, which showed significant accumulation in dim vs. elevated light exposed mice following ~1 year of observation. These data were evaluated using Spearman's correlation and Predictive Power Score matrices to determine the best imaging optophysiological biomarkers for indicating vivarium light stress and light-induced photoreceptor degeneration. This study suggests that changes in proximal aspect hyperreflectivity, outer segment shortening, retinal infoldings and autofluorescent sub-retinal inflammatory monocyte infiltrate are excellent indicators of light stress and light-induced degeneration in albino B6(Cg)-Tyrc-2J/J and BALB/cJ mouse strains.