Parafoveal cone function in choroideremia assessed with adaptive optics optoretinography.

Choroideremia (CHM) is an X-linked retinal degeneration leading to loss of the photoreceptors, retinal pigment epithelium (RPE), and choroid. Adaptive optics optoretinography is an emerging technique for noninvasive, objective assessment of photoreceptor function. Here, we investigate parafoveal cone function in CHM using adaptive optics optoretinography and compare with cone structure and clinical assessments of vision. Parafoveal cone mosaics of 10 CHM and four normal-sighted participants were imaged with an adaptive optics scanning light ophthalmoscope. While acquiring video sequences, a 2 s 550Δ10 nm, 450 nW/deg2 stimulus was presented. Videos were registered and the intensity of each cone in each frame was extracted, normalized, standardized, and aggregated to generate the population optoretinogram (ORG) over time. A gamma-pdf was fit to the ORG and the peak was extracted as ORG amplitude. CHM ORG amplitudes were compared to normal and were correlated with bound cone density, ellipsoid zone to RPE/Bruch's membrane (EZ-to-RPE/BrM) distance, and foveal sensitivity using Pearson correlation analysis. ORG amplitude was significantly reduced in CHM compared to normal (0.22 ± 0.15 vs. 1.34 ± 0.31). In addition, CHM ORG amplitude was positively correlated with cone density, EZ-to-RPE/BrM distance, and foveal sensitivity. Our results demonstrate promise for using ORG as a biomarker of photoreceptor function.

Fluorescence Lifetime Imaging of Human Retinal Pigment Epithelium in Pentosan Polysulfate Toxicity Using Adaptive Optics Scanning Light Ophthalmoscopy.

Purpose: Fluorescence lifetime ophthalmoscopy (FLIO) is an emerging clinical modality that could provide biomarkers of retinal health beyond fluorescence intensity. Adaptive optics (AO) ophthalmoscopy provides the confocality to measure fluorescence lifetime (FL) primarily from the retinal pigment epithelium (RPE) whereas clinical FLIO has greater influence from fluorophores in the inner retina and lens. Adaptive optics fluorescence lifetime ophthalmoscopy (AOFLIO) measures of FL in vivo could provide insight into RPE health at different stages of disease. In this study, we assess changes in pentosan polysulfate sodium (PPS) toxicity, a recently described toxicity that has clinical findings similar to advanced age-related macular degeneration. Methods: AOFLIO was performed on three subjects with PPS toxicity (57-67 years old) and six age-matched controls (50-64 years old). FL was analyzed with a double exponential decay curve fit and with phasor analysis. Regions of interest (ROIs) were subcategorized based on retinal features on optical coherence tomography (OCT) and compared to age-matched controls. Results: Twelve ROIs from PPS toxicity subjects met the threshold for analysis by curve fitting and 15 ROIs met the threshold for phasor analysis. Subjects with PPS toxicity had prolonged FL compared to age-matched controls. ROIs of RPE degeneration had the longest FLs, with individual pixels extending longer than 900 ps. Conclusions: Our study shows evidence that AOFLIO can provide meaningful information in outer retinal disease beyond what is obtainable from fluorescence intensity alone. More studies are needed to determine the prognostic value of AOFLIO.

Needs assessment for direct ophthalmoscopy training in neurology residency.

BACKGROUND: Assessment of the ocular fundus, traditionally by direct ophthalmoscopy (DO), is essential to evaluate many neurologic diseases. However, the status of DO training in neurology residencies is unknown. We conducted a needs assessment to determine current attitudes, curricula, and gaps in DO training. METHODS: A survey was developed and administered to residents and program directors (PDs) at ACGME accredited neurology residencies in the United States. The survey assessed factors such as current DO curricula, perceived importance of DO, confidence of skills, and need for improvement. Data analysis was performed using the Mann Whitney U test and Fisher Exact Test. RESULTS: Nineteen PDs (11.6%) and 74 (41.1%) residents responded to the survey. 97.1% of residents and 100.0% of PDs believe DO is an important skill to learn. 29.4% of PDs expected graduating residents to have completed > 10 supervised DO exams, while 0.0% of graduating fourth year residents reported doing so (p = 0.03). 35.7% of graduating residents had never correctly identified an abnormal finding on DO. The number of times residents practiced DO unsupervised correlated with increasing confidence in all components of the DO exam (p < 0.05). Residents who felt their program emphasized DO were more likely to perform DO at least once a week compared to residents who did not perceive program emphasis (61.9% vs. 35.0%, p = 0.02) and were more confident in DO (p < 0.05). 66.7% of residents and 42.1% of PDs were not satisfied with current levels of DO training. 96.7% of residents and 78.9% of PDs felt it was important to improve curriculum for DO training. Supervised practice and practice skills sessions were identified as the most helpful interventions to improve DO training. CONCLUSIONS: The vast majority of neurology PDs and residents believe DO is an important skill to learn, are unsatisfied with the current level of DO training, and advocate for improvement in DO curricula. Current DO curricula have limited formal didactic training and supervised practice. The bulk of DO learning occurs through unsupervised practice, which is influenced by motivational factors such as perceived residency emphasis on DO learning.

Head stabilization apparatus for high-resolution ophthalmic imaging.

Head movement must be stabilized to enable high-quality data collection from optical instrumentation such as eye trackers and ophthalmic imaging devices. Though critically important for imaging, head stabilization is often an afterthought in the design of advanced ophthalmic imaging systems, and experimental devices often adapt used and/or discarded equipment from clinical devices for this purpose. Alternatively, those seeking the most stable solution possible, including many users of adaptive optics ophthalmoscopy systems, utilize bite bars. Bite bars can provide excellent stability but are time consuming to fabricate, decreasing imaging efficiency, and uncomfortable for many patients, especially the elderly and/or those with prosthodontics such as dentures who may refuse participation in a study that requires one. No commercial vendors specifically offer head mount solutions for experimental ophthalmic imaging devices, resulting in nearly every custom device having a different solution for this commonly encountered problem. Parallelizing the head stabilization apparatus across different custom devices may improve standardization of experimental imaging systems for clinical trials and other multicenter investigations. Here we introduce a head mount design for ophthalmic imaging that is modular, adjustable, and customizable to the constraints of different experimental imaging configurations. The three points of head contact in our solution provide excellent stabilization across a range of head sizes and shapes from small children to adults, and the ease of adjustment afforded by our design minimizes the time to get participants stabilized and comfortable.

FOVEAL PHENOTYPES IN CHOROIDEREMIA ON ADAPTIVE OPTICS SCANNING LIGHT OPHTHALMOSCOPY.

PURPOSE: Choroideremia is an X-linked inherited retinal degeneration involving the choriocapillaris, retinal pigment epithelium, and photoreceptors. Adaptive optics scanning light ophthalmoscopy allows visualization of retinal structure at the level of individual cells and is well poised to provide insight into the pathophysiologic mechanisms underpinning the retinal degeneration in choroideremia. METHODS: Foveal adaptive optics scanning light ophthalmoscopy images of 102 eyes of 54 individuals with choroideremia were analyzed. Measures were compared with those from standard clinical imaging. Visual acuity was also measured and compared with quantitative foveal metrics. RESULTS: The 3 distinct phenotypes observed were: relatively normal (5 eyes, 4 individuals), spiderweb (9 eyes, 7 individuals), and salt and pepper (87 eyes, 47 individuals). Peak cone density (86 eyes of 51 individuals) was significantly lower in choroideremia than in healthy retinas (P < 0.0001, range: 29,382-157,717 cones/mm2). Peak cone density was significantly related to extent of retained ellipsoid zone on en face optical coherence tomography (r2 = 0.47, P = 0.0009) and inversely related to visual acuity (r2 = 0.20, P = 0.001). CONCLUSION: Distinct phenotypes can be observed on adaptive optics scanning light ophthalmoscopy imaging in choroideremia that cannot always be discerned on standard clinical imaging. Quantitative measures on adaptive optics imaging are related to the structural and functional severity of disease.

Automated vertical cup-to-disc ratio determination from fundus images for glaucoma detection.

Glaucoma is the leading cause of irreversible blindness worldwide. Often asymptomatic for years, this disease can progress significantly before patients become aware of the loss of visual function. Critical examination of the optic nerve through ophthalmoscopy or using fundus images is a crucial component of glaucoma detection before the onset of vision loss. The vertical cup-to-disc ratio (VCDR) is a key structural indicator for glaucoma, as thinning of the superior and inferior neuroretinal rim is a hallmark of the disease. However, manual assessment of fundus images is both time-consuming and subject to variability based on clinician expertise and interpretation. In this study, we develop a robust and accurate automated system employing deep learning (DL) techniques, specifically the YOLOv7 architecture, for the detection of optic disc and optic cup in fundus images and the subsequent calculation of VCDR. We also address the often-overlooked issue of adapting a DL model, initially trained on a specific population (e.g., European), for VCDR estimation in a different population. Our model was initially trained on ten publicly available datasets and subsequently fine-tuned on the REFUGE dataset, which comprises images collected from Chinese patients. The DL-derived VCDR displayed exceptional accuracy, achieving a Pearson correlation coefficient of 0.91 (P = 4.12 × 10-412) and a mean absolute error (MAE) of 0.0347 when compared to assessments by human experts. Our models also surpassed existing approaches on the REFUGE dataset, demonstrating higher Dice similarity coefficients and lower MAEs. Moreover, we developed an optimization approach capable of calibrating DL results for new populations. Our novel approaches for detecting optic discs and optic cups and calculating VCDR, offers clinicians a promising tool that significantly reduces manual workload in image assessment while improving both speed and accuracy. Most importantly, this automated method effectively differentiates between glaucoma and non-glaucoma cases, making it a valuable asset for glaucoma detection.

Design of ultra-wide-field scanning laser fundus imaging system with cascaded conicoid mirrors.

We propose and design a multi-stage cascaded scanning laser ophthalmoscope (SLO) for ultra-wide field (UWF), which uses conicoid mirrors, constructed by conjugation of pupil plane. The vergence uniformity and the angular magnification of a cascaded conicoid mirrors (CCM) system are analyzed recursively and optimized preliminarily to achieve high quality imaging with UWF, and the optimal system with the model eye are obtained by simulation and optimization. Two-stage and three-stage cascaded systems are designed with this method, and the formulas of beam vergence and angular magnification are obtained by theoretical derivation. As compared to the two-stage CCM system, the proposed three-stage cascaded UWF SLO has superior performance in imaging quality. Its average RMS radius of spot diagram is calculated to be 26.372 µm, close to the diffractive limit resolution. The image resolution of human retina can be up to 30 µm with 135° FOV in theory. The three-stage cascaded SLO is more suitable for UWF fundus imaging. This study will be helpful for early screening and accurate diagnosis of various diseases in the peripheral retina.

In vivo cone-photoreceptor density comparison between eyes with subretinal drusenoid deposits and healthy eyes using high magnification imaging.

PURPOSE: To compare photoreceptor density automated quantification in eyes with subretinal drusenoid deposits (SDD) and healthy controls using Heidelberg Spectralis High Magnification Module (HMM) imaging. METHODS: Twelve eyes of 6 patients with intermediate AMD, presenting with SDD were included, as well as twelve eyes of healthy controls. Individual dot SDD within the central 30° retina were examined with infrared confocal laser ophthalmoscopy, HMM, and spectral-domain optical coherence tomography (SD-OCT). Photoreceptor density analysis was performed on the best-quality image using the ImageJ Foci Picker plugin, after the removal of SDD from the HMM image. Correlations were made between the HMM quantified photoreceptor density, SD-OCT characteristics, stage, and number of SDD. RESULTS: Mean age was 75.17 ± 2.51 years in the SDD group (3 males, 3 females) versus 73.17 ± 3.15 years in the healthy control group (p = 0.2). Defects in the overlying ellipsoid zone were present on SD-OCT in 8/12 (66.66%) eyes. The mean ± standard deviation foci detected (i.e., cone photoreceptors) was 7123.75 ± 3683.32 foci/mm2 in the SDD group versus 13,253 ± 3331.00 foci/mm2 in the healthy control group (p = 0.0003). The number of SDD was associated with a reduction in foci density, p = 0.0055, r = - 0.7622. CONCLUSION: The decreased cone density in eyes with SDD may correlate with a decrease in retinal function in intermediate AMD eyes independent of neovascular complications or outer retinal pigment epithelial atrophy.

Multimodal Imaging of Choroidal Nodules in Neurofibromatosis Type I.

AIM: To clarify the possibilities and role of posterior segment imaging in patients with neurofibromatosis type I (NF1), and to show the prevalence of this disease in the pediatric population in Slovakia. MATERIAL AND METHODS: Until recently, ophthalmologic consultations in patients with NF1 were limited mainly to the observation of Lisch nodules of the iris and the presence of optic nerve glioma. However, advances in imaging capabilities have made it possible to investigate and describe new f indings concerning the ocular manifestations of this disease. Between October 2020 and November 2021, we examined the anterior and posterior segment of 76 eyes (38 children ­ 12 boys and 26 girls) with genetically confirmed NF1 gene mutation at our clinic. The age of the patients ranged from 4 to 18 years. The anterior segment was checked for the presence of Lisch nodules biomicroscopically with a slit lamp. On the posterior segment, the presence of choroidal nodules was checked by various imaging methods ­ fundus camera, infrared confocal selective laser ophthalmoscopy, MultiColor imaging, OCT, and OCT angiography. All the patients had magnetic resonance imaging performed in order to detect potential optic nerve gliomas for the purpose of diagnosis. We observed the correlation between the patients' age, presence of Lisch nodules and the presence of choroidal nodules. Eight patients also had other manifestations of the disease ­ optic nerve gliomas or microvascular changes (so-called "corkscrew" vessels). RESULTS: Out of 38 patients, Lisch iris nodules were present in 20 patients (53%) and choroidal nodules in 24 patients (63%). There was no positive correlation between the presence of these two manifestations within the same patient or eye, but there is a clear correlation between the presence of choroidal nodules and patient age. CONCLUSION: The results suggest that a previously unknown ocular manifestation of neurofibromatosis type I, namely choroidal nodules, has a higher prevalence than Lisch nodules also in the pediatric population and can be easily visualized using various imaging modalities. It will be important to include follow-up observation of this finding among the standard controls for ocular findings in NF1, and it will be very interesting to correlate this f inding with the exact NF1 mutation

Implementation of optical coherence tomography in retinopathy of prematurity screening.

PURPOSE OF REVIEW: In this review, we explore the investigational applications of optical coherence tomography (OCT) in retinopathy of prematurity (ROP), the insights they have delivered thus far, and key milestones for its integration into the standard of care. RECENT FINDINGS: While OCT has been widely integrated into clinical management of common retinal diseases, its use in pediatric contexts has been undermined by limitations in ergonomics, image acquisition time, and field of view. Recently, investigational handheld OCT devices have been reported with advancements including ultra-widefield view, noncontact use, and high-speed image capture permitting real-time en face visualization. These developments are compelling for OCT as a more objective alternative with reduced neonatal stress compared to indirect ophthalmoscopy and/or fundus photography as a means of classifying and monitoring ROP. SUMMARY: OCT may become a viable modality in management of ROP. Ongoing innovation surrounding handheld devices should aim to optimize patient comfort and image resolution in the retinal periphery. Future clinical investigations may seek to objectively characterize features of peripheral stage and explore novel biomarkers of disease activity.

Synchronous functional magnetic resonance eye imaging, video ophthalmoscopy, and eye surface imaging reveal the human brain and eye pulsation mechanisms.

The eye possesses a paravascular solute transport pathway that is driven by physiological pulsations, resembling the brain glymphatic pathway. We developed synchronous multimodal imaging tools aimed at measuring the driving pulsations of the human eye, using an eye-tracking functional eye camera (FEC) compatible with magnetic resonance imaging (MRI) for measuring eye surface pulsations. Special optics enabled integration of the FEC with MRI-compatible video ophthalmoscopy (MRcVO) for simultaneous retinal imaging along with functional eye MRI imaging (fMREye) of the BOLD (blood oxygen level dependent) contrast. Upon optimizing the fMREye parameters, we measured the power of the physiological (vasomotor, respiratory, and cardiac) eye and brain pulsations by fast Fourier transform (FFT) power analysis. The human eye pulsated in all three physiological pulse bands, most prominently in the respiratory band. The FFT power means of physiological pulsation for two adjacent slices was significantly higher than in one-slice scans (RESP1 vs. RESP2; df = 5, p = 0.045). FEC and MRcVO confirmed the respiratory pulsations at the eye surface and retina. We conclude that in addition to the known cardiovascular pulsation, the human eye also has respiratory and vasomotor pulsation mechanisms, which are now amenable to study using non-invasive multimodal imaging of eye fluidics.

Correction Method for Optical Scaling of Fundoscopy Images: Development, Validation, and First Implementation.

Purpose: Although fundus photography is extensively used in ophthalmology, refraction prevents accurate distance measurement on fundus images, as the resulting scaling differs between subjects due to varying ocular anatomy. We propose a PARaxial Optical fundus Scaling (PAROS) method to correct for this variation using commonly available clinical data. Methods: The complete optics of the eye and fundus camera were modeled using ray transfer matrix formalism to obtain fundus image magnification. The subject's ocular geometry was personalized using biometry, spherical equivalent of refraction (RSE), keratometry, and/or corneal topography data. The PAROS method was validated using 41 different eye phantoms and subsequently evaluated in 44 healthy phakic subjects (of whom 11 had phakic intraocular lenses [pIOLs]), 29 pseudophakic subjects, and 21 patients with uveal melanoma. Results: Validation of the PAROS method showed small differences between model and actual image magnification (maximum 3.3%). Relative to the average eye, large differences in fundus magnification were observed, ranging from 0.79 to 1.48. Magnification was strongly inversely related to RSE (R2 = 0.67). In phakic subjects, magnification was directly proportional to axial length (R2 = 0.34). The inverse relation was seen in pIOL (R2 = 0.79) and pseudophakic (R2 = 0.12) subjects. RSE was a strong contributor to magnification differences (1%-83%). As this effect is not considered in the commonly used Bennett-Littmann method, statistically significant differences up to 40% (mean absolute 9%) were observed compared to the PAROS method (P < 0.001). Conclusions: The significant differences in fundus image scaling observed among subjects can be accurately accounted for with the PAROS method, enabling more accurate quantitative assessment of fundus photography.

Fluorescence Lifetime Imaging Ophthalmoscopy of Mouse Models of Age-related Macular Degeneration.

Purpose: To investigate fluorescence lifetime of mouse models of age-related macular degeneration (AMD) by fluorescence lifetime imaging ophthalmoscopy (FLIO). Methods: Two AMD mouse models, apolipoprotein E knockout (ApoE-/-) mice and NF-E2-related factor-2 knockout (Nrf2-/-) mice, and their wild-type mice underwent monthly ophthalmic examinations including FLIO from 3 months of age. After euthanasia at the age of 6 or 11 months, blood plasma was collected to determine total antioxidant capacity and eyes were enucleated for Oil red O (ORO) lipid staining of chorioretinal tissue. Results: In FLIO, the mean fluorescence lifetime (τm) of wild type shortened with age in both spectral channels. In short spectral channel, τm shortening was observed in both AMD models as well, but its rate was more pronounced in ApoE-/- mice and significantly different from the other strains as months of age progressed. In contrast, in long spectral channel, both model strains showed completely opposite trends, with τm becoming shorter in ApoE-/- and longer in Nrf2-/- mice than the others. Oil red O staining at Bruch's membrane was significantly stronger in ApoE-/- mice at 11 months than the other strains. Plasma total antioxidant capacity was highest in ApoE-/- mice at both 6 and 11 months. Conclusions: The two AMD mouse models exhibited largely different fundus fluorescence lifetime, which might be related to the different systemic metabolic state. FLIO might be able to indicate different metabolic states of eyes at risk for AMD. Translational Relevance: This animal study may provide new insights into the relationship between early AMD-associated metabolic changes and FLIO findings.

Scanning Laser Ophthalmoscopy Demonstrates Pediatric Optic Disc and Peripapillary Strain During Horizontal Eye Rotation.

Purpose: We employed automated analysis of scanning laser ophthalmoscopy (SLO) to determine if mechanical strains imposed on disc, and retinal and choroidal vessels during horizontal duction in children differ from those of adults.Methods: Thirty-one children aged 11.3 ± 2.7 (standard deviation) years underwent SLO in central gaze, and 35° ab- and adduction. Automated registration with deep learning-based optical flow analysis quantified vessel deformations as horizontal, vertical, shear, and equivalent strains. Choroidal vessel displacements in lightly pigmented fundi, and central disc vessel displacements, were also observed.Results: As in adults, strain in vessels during horizontal duction was greatest at the disc and decreased with distance from it. Strain in the pediatric disc was similar to published values in young adults,1 but in the peripapillary region was greater and propagated significantly more peripherally to at least three disc radii from it. During adduction in children, the nasal disc was compressed and disc vessels distorted, but the temporal half experienced tensile strain, while peripapillary tissues were compressed. The pattern was similar but strains were less in abduction (p < .001). Choroidal vessels were visualized in 24 of the 62 eyes and shifted directionally opposite overlying retinal vessels.Conclusions: Horizontal duction deforms the normal pediatric optic disc, central retinal vessels, peripapillary retina, and choroid, shearing the inner retina over the choroid. These mechanical effects occur at the sites of remodeling of the disc, sclera, and choroid associated with typical adult features that later emerge later, including optic cup enlargement, temporal disc tilting, and peripapillary atrophy.

EVALUATING ULTRA-WIDEFIELD IMAGING UTILITY IN THE DETECTION OF TREATMENT-REQUIRING PERIPHERAL RETINAL TEARS AND HOLES.

PURPOSE: To determine the utility of ultra-widefield (UWF) imaging in detecting pathologic peripheral retinal tears and holes. METHODS: This was a retrospective, observational study. One-hundred ninety-eight eyes of 198 patients diagnosed with acute posterior vitreous detachment were included. Eyes were divided into two groups: 89 eyes with peripheral retinal holes and tears treated with laser retinopexy (treatment group) and 109 control eyes. Patients underwent UWF imaging and indirect ophthalmoscopy with scleral depression. UWF images from both groups were reviewed by two blinded graders and then compared with funduscopic examination and medical records. RESULTS: UWF imaging identified 60 of the 89 eyes (sensitivity of 67.4%) found to have treatment-requiring peripheral retinal lesions and 107 of the 109 control eyes (specificity of 98.2%).The distribution of misses based on octant location did reach statistical significance ( P = 0.004). Lesions anterior to the equator were more likely to be missed (21/41 eyes, 51.2%) compared with those located posterior to the equator (4/20 eyes, 25.0%) and at the equator (4/28, 14.3%), P = 0.002. The combined discordance rate between graders in the entire cohort was 12.1% (24/198 eyes) yielding an interrater agreement of 87.9%. CONCLUSION: UWF imaging showed a moderate sensitivity and high specificity in detecting treatment-requiring retinal tears and holes, with high interrater agreement. Given there is only a moderate sensitivity in identifying treatment-requiring retinal tears and holes, UWF imaging can assist with clinical examination, but a 360-degree scleral depressed examination should remain the gold standard.

Peak Cone Density Predicted from Outer Segment Length Measured on Optical Coherence Tomography.

PURPOSE: To compare peak cone density predicted from outer segment length measured on optical coherence tomography with direct measures of peak cone density from adaptive optics scanning light ophthalmoscopy. METHODS: Data from 42 healthy participants with direct peak cone density measures and optical coherence tomography line scans available were used in this study. Longitudinal reflectivity profiles were analyzed using two methods of identifying the boundaries of the ellipsoid and interdigitation zones to estimate maximum outer segment length: peak-to-peak and the slope method. These maximum outer segment length values were then used to predict peak cone density using a previously described geometrical model. A comparison between predicted and direct peak cone density measures was then performed. RESULTS: The mean bias between observers for estimating maximum outer segment length across methods was less than 2 µm. Cone density predicted from the peak-to-peak method against direct cone density measures showed a mean bias of 6,812 cones/mm2 with 50% of participants displaying a 10% difference or less between predicted and direct cone density values. Cone density derived from the slope method showed a mean bias of -17,929 cones/mm2 relative to direct cone density measures, with only 41% of participants demonstrating less than a 10% difference between direct and predicted cone density values. CONCLUSION: Predicted foveal cone density derived from peak-to-peak outer segment length measurements using commercial optical coherence tomography show modest agreement with direct measures of peak cone density from adaptive optics scanning light ophthalmoscopy. The methods used here are imperfect predictors of cone density, however, further exploration of this relationship could reveal a clinically relevant marker of cone structure.

Adaptive optics imaging in inherited retinal diseases: A scoping review of the clinical literature.

Adaptive optics (AO) imaging enables direct, objective assessments of retinal cells. Applications of AO show great promise in advancing our understanding of the etiology of inherited retinal disease (IRDs) and discovering new imaging biomarkers. This scoping review systematically identifies and summarizes clinical studies evaluating AO imaging in IRDs. Ovid MEDLINE and EMBASE were searched on February 6, 2023. Studies describing AO imaging in monogenic IRDs were included. Study screening and data extraction were performed by 2 reviewers independently. This review presents (1) a broad overview of the dominant areas of research; (2) a summary of IRD characteristics revealed by AO imaging; and (3) a discussion of methodological considerations relating to AO imaging in IRDs. From 140 studies with AO outcomes, including 2 following subretinal gene therapy treatments, 75% included fewer than 10 participants with AO imaging data. Of 100 studies that included participants' genetic diagnoses, the most common IRD genes with AO outcomes are CNGA3, CNGB3, CHM, USH2A, and ABCA4. Confocal reflectance AO scanning laser ophthalmoscopy was the most reported imaging modality, followed by flood-illuminated AO and split-detector AO. The most common outcome was cone density, reported quantitatively in 56% of studies. Future research areas include guidelines to reduce variability in the reporting of AO methodology and a focus on functional AO techniques to guide the development of therapeutic interventions.

Clinical Application of Adaptive Optics Imaging in Diagnosis, Management, and Monitoring of Ophthalmological Diseases: A Narrative Review.

Visualization of the retinal structure is crucial for understanding the pathophysiology of ophthalmic diseases, as well as for monitoring their course and treatment effects. Until recently, evaluation of the retina at the cellular level was only possible using histological methods, because the available retinal imaging technology had insufficient resolution due to aberrations caused by the optics of the eye. Adaptive optics (AO) technology improved the resolution of optical systems to 2 µm by correcting optical wave-front aberrations, thereby revolutionizing methods for studying eye structures in vivo. Within 25 years of its first application in ophthalmology, AO has been integrated into almost all existing retinal imaging devices, such as the fundus camera (FC), scanning laser ophthalmoscopy (SLO), and optical coherence tomography (OCT). Numerous studies have evaluated individual retinal structures, such as photoreceptors, blood vessels, nerve fibers, ganglion cells, lamina cribrosa, and trabeculum. AO technology has been applied in imaging structures in healthy eyes and in various ocular diseases. This article aims to review the roles of AO imaging in the diagnosis, management, and monitoring of age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, hypertensive retinopathy (HR), central serous chorioretinopathy (CSCR), and inherited retinal diseases (IRDs).

Cone Density Is Correlated to Outer Segment Length and Retinal Thickness in the Human Foveola.

Purpose: Assessment of the relationship between in vivo foveolar cone density, cone outer segment length (OSL), and foveal retinal thickness (RT). Methods: Foveolar cone density maps covering the central ±300 µm of the retina were derived from adaptive optics scanning laser ophthalmoscopy images. The corresponding maps of foveal cone OSL and RT were derived from high-resolution optical coherence tomography volume scans. Alignment of the two-dimensional maps containing OSL and RT with the cone density map was achieved by placing the location of maximum OSL on the cone density centroid (CDC). Results: Across 10 participants (27 ± 9 years; 6 female), cone density at the CDC was found to be between 147,038 and 215,681 cones/mm². The maximum OSL and minimum RT were found to lie between 31 and 40, and 193 and 226 µm, respectively. A significant correlation was observed between cone density at the CDC and maximum OSL (P = 0.001), as well as the minimal RT (P < 0.05). Across all participants, the best fit for the relationship between normalized cone density and normalized OSL within the central 300 µm was given by a quadratic function. Conclusions: Using optical coherence tomography-derived measurements of OSL enables to estimate CDC cone density and two-dimensional foveal cone density maps for example in patient eyes unsuitable for adaptive optics imaging. Furthermore, the observation of a fixed relationship between the normalized OSL and cone density points to a conserved mechanism shaping the foveal pit.