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The optical system of the human eye consists of three main components, i.e., the cornea, the crystalline lens and the iris. The iris controls the amount of light coming into the retina by regulating the diameter of the pupil. Therefore, the pupil of the eye acts as the aperture of the system. The optical axis of the eye (dotted grey line) is defined as the line joining the centers of curvature of all the optical surfaces. However, the appropriate and convenient axis that should be used for describing the optical system of the eye is the line of sight (dashed black line), which is defined as the ray that passes through the center of the entrance pupil and strikes the center of the fovea (i.e., the foveola).
Source publication
Adaptive optics (AO) is a technology used to improve the performance of optical systems by reducing the effects of optical aberrations. The direct visualization of the photoreceptor cells, capillaries and nerve fiber bundles represents the major benefit of adding AO to retinal imaging. Adaptive optics is opening a new frontier for clinical research...
Similar publications
Adaptive optics provides improved resolution in ophthalmic imaging when retinal microstructures need to be identified, counted, and mapped. In general, multiple images are averaged to improve the signal-to-noise ratio or analyzed for temporal dynamics. Image registration by cross-correlation is straightforward for small patches; however, larger ima...
Citations
... The direct visualization of retinal structures at a microscopic scale in vivo provided by AOSLO represents a major addition to retinal imaging and could allow for early detection of genetic retinal disease. [11][12][13] The mosaic of photoreceptor outer segments can be observed directly on confocal reflectance AOSLO images, 14 with cone inner segments visible on split-X. 15 In addition, hyalocytes and some inner retinal pathologies such as microcysts have been visualized on split-X AOSLO. ...
Purpose
Deep phenotyping of genetic retinal disease using multimodal adaptive optics ophthalmoscopy and protein structure variant analysis.
Observations
In a patient with extensive atrophy of the retinal pigment epithelium and yellow deposits in the retina, genetic testing identified two CYP4V2 variants: c.802-8_810delinsGC and c.1169G > A, p.Arg390His. AI-generated protein structures indicated loss of CYP4V2 function. Reflectance confocal and multiple-scattering Adaptive Optics Scanning Light Ophthalmoscopy (AOSLO) captured crystalline deposits throughout the retina as well as previously unreported cyst-like structures that were mainly independent from the crystalline deposits. Sequential AOSLO imaging was conducted and revealed anatomical and morphological changes in the cysts and surrounding cellular structures.
Conclusions and importance
Cyst-like changes may represent a new BCD degenerative feature. Characterizing retinal genetic disease variants with protein structural modeling and phenotyping with AOSLO represents an advanced approach for clinical diagnosis and may serve as a biomarker of disease progression.
... A microvascular structure evaluation was performed in retinal arterioles using an Rtx1e™ non-invasive adaptive optics camera (Imagine Eyes, Orsay, France). This camera enables the precise assessment of microvasculature with ultra-high resolution, at a near-histological scale [20][21][22][23]. This is made possible by the advanced space technology employed in Rtx1e™ which consists of three main components: a high-resolution fundus camera, a Shack-Hartmann wavefront sensor, and a deformable mirror for real-time correction of the aberrations of the ocular wavefront [20][21][22][23]. ...
... This camera enables the precise assessment of microvasculature with ultra-high resolution, at a near-histological scale [20][21][22][23]. This is made possible by the advanced space technology employed in Rtx1e™ which consists of three main components: a high-resolution fundus camera, a Shack-Hartmann wavefront sensor, and a deformable mirror for real-time correction of the aberrations of the ocular wavefront [20][21][22][23]. In short, when a beam of light enters the eye, a small amount is reflected to the optical system, and wavefront aberrations that arise within the eye are corrected by a deformable mirror, therefore the achieved image resolution is in the order of 1µm [20][21][22][23][24]. ...
... This is made possible by the advanced space technology employed in Rtx1e™ which consists of three main components: a high-resolution fundus camera, a Shack-Hartmann wavefront sensor, and a deformable mirror for real-time correction of the aberrations of the ocular wavefront [20][21][22][23]. In short, when a beam of light enters the eye, a small amount is reflected to the optical system, and wavefront aberrations that arise within the eye are corrected by a deformable mirror, therefore the achieved image resolution is in the order of 1µm [20][21][22][23][24]. The measurements were taken after 15 minutes of rest. ...
... In this study, we analyzed retinal photoreceptor (cone) features and vascular change with AOSLO in early DME patients, which has not been previously investigated 37,47,48 . Previous researches reported a significant decreased cone density in DM, moderate and severe NPDR, PDR patients when compared with healthy participants [49][50][51] . ...
This study was intended to investigate the macular vascular and photoreceptor changes for diabetic macular edema (DME) at the early stage. A total of 255 eyes of 134 diabetes mellitus patients were enrolled and underwent an ophthalmological and systemic evaluation in this cross-sectional study. Early DME was characterized by central subfoveal thickness (CST) value between 250 and 325 μm, intact ellipsoid zone, and an external limiting membrane. While non-DME was characterized by CST < 250 μm with normal retinal morphology and structure. Foveal avascular zone (FAZ) area ≤ 0.3 mm² (P < 0.001, OR = 0.41, 95% CI 0.26–0.67 in the multivariate analysis) and HbA1c level ≤ 8% (P = 0.005, OR = 0.37, 95% CI 0.19–0.74 in multivariate analysis) were significantly associated with a higher risk of early DME. Meanwhile, no significant differences exist in cone parameters between non-DME and early DME eyes. Compared with non-DME eyes, vessel diameter, vessel wall thickness, wall-to-lumen ratio, the cross-sectional area of the vascular wall in the upper side were significantly decreased in the early DME eyes (P = 0.001, P < 0.001, P = 0.005, P = 0.003 respectively). This study suggested a vasospasm or vasoconstriction with limited further photoreceptor impairment at the early stage of DME formation. CST ≥ 250 μm and FAZ ≤ 0.3 mm² may be the indicator for early DME detection.
... Images taken by equipment indicate potential risks in the early stage of ophthalmic diseases, which provides eye doctors with an accurate treatment plan formulation. Due to the irregular optical pathways created by the passage of light through various ocular structures, including the cornea, crystalline lens, and vitreous body, aberrations in the wavefront images of the fundus can occur [3]. These aberrations distort the incoming wavefront, leading to imperfections in the imaging process. ...
This study presents a numerical simulation-based investigation of a MEMS (micro-electromechanical systems)technology-based deformable mirror employing a piezoelectric film for fundus examination in adaptive optics. Compared to the classical equal-area electrode arrangement model, we optimize the electrode array for higher-order aberrations. The optimized model centralizes electrodes around the mirror center, which realizes low-voltage driving with high-accuracy correction. The optimized models exhibited commendable correction abilities, achieving a unidirectional displacement of 5.74 μm with a driven voltage of 15 V. The voltage–displacement relationship demonstrated high linearity at 0.99. Furthermore, the deformable mirror’s influence matrix was computed, aligning with the Zernike standard surface shape of the order 1–3. To quantify aberration correction capabilities, fitting residuals for both models were calculated. The results indicate an average removal of 96.8% of aberrations to the human eye. This underscores that the optimized model outperforms the classical model in correcting high-order aberrations.
... A decrease in cone density has recently been noted in the presence of edema related to the macular telangiectasia type 2 and the diabetic macular edema in studies using adaptive optics (AO) fundus imaging [11,12]. Researchers have highlighted the potential value of AO for the non-invasive examination of photoreceptors at a resolution of up to 2 μm given its ability to reduce the effect of optical aberrations, yielding findings that cannot be obtained using conventional retinal imaging techniques [13]. The reflectance of the cone photoreceptor mosaic in AO images using a flood illuminated retinal fundus camera (rtx1 TM, Orsay, France) is substantially considered as a reflection of the outer segments of the photoreceptors or the interdigitation zone (IZ) in OCT images [14]. ...
Objective
Cystoid macular edema (CME) in retinitis pigmentosa (RP) is an important complication causing visual dysfunction. We investigated the effect of CME on photoreceptors in RP patients with previous or current CME, using an adaptive optics (AO) fundus camera.
Methods
We retrospectively observed the CME and ellipsoid zone (EZ) length (average of horizontal and vertical sections) by optical coherence tomography. The density and regularity of the arrangement of photoreceptor cells (Voronoi analysis) were examined at four points around 1.5° from superior to inferior and temporal to nasal. We also performed a multivariate analysis using CME duration, central macular thickness and transversal length of CME.
Results
We evaluated 18 patients with previous or current CME (18 eyes; age, 48.7 ± 15.6 years) and 24 patients without previous or current CME (24 eyes; age, 46.0 ± 14.5 years). There were no significant differences in age, logMAR visual acuity, or EZ length. In groups with and without CME, cell density was 11967 ± 3148 and 16239 ± 2935 cells/mm², and sequence regularity was 85.5 ± 3.4% and 88.5 ± 2.8%, respectively; both parameters were significantly different. The correlation between photoreceptor density and age was more negative in group with CME. The CME group tended toward greater reductions in duration of CME.
Conclusion
Complications of CME in RP patients may lead to a decrease in photoreceptor density and regularity. Additionally, a longer duration of CME may result in a greater reduction in photoreceptor density.
... The history of the use of AO in ophthalmology is more than 20 years old -it was first used in 1997 by Liang to obtain high-quality retinal images [3]. The AO system consists of 3 basic elements -a wave-front sensor, a wave-front corrector, and a control system -which are used to identify the eye's optical aberrations and then correct them [4]. A wave-front sensor measures the aberrations of the eye. ...
... A wave-front corrector compensates for the aberrations measured by the SHS. The most commonly used type of wave-front corrector is the deformable mirror, which works by changing the shape of the surface [4,5]. A series of electric actuators connected to the mirror deform its surface to modify the light beam and thus effectively remove optical distortion in real-time [2,4]. ...
... The most commonly used type of wave-front corrector is the deformable mirror, which works by changing the shape of the surface [4,5]. A series of electric actuators connected to the mirror deform its surface to modify the light beam and thus effectively remove optical distortion in real-time [2,4]. The control system aims to connect the first 2 elements: a wave-front sensor and a wavefront corrector [2]. ...
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).
... The examined position can be selected (e.g., 2°superior, inferior, temporal, or nasal-as in our study). The image acquisition in a single position lasts 2-4 s, during which 40 individual images are acquired [13,[23][24][25]. The Rtx1™ software provides two programs for data evaluation: AO Detect for the analysis of photoreceptors parameters and AO Detect Artery for the analysis of vessel parameters. ...
Inherited retinal dystrophies (IRDs) are bilateral genetic conditions of the retina, leading to irreversible vision loss. This study included 55 eyes afflicted with IRDs affecting the macula. The diseases examined encompassed Stargardt disease (STGD), cone dystrophy (CD), and cone–rod dystrophy (CRD) using adaptive optics (Rtx1™; Imagine Eyes, Orsay, France). Adaptive optics facilitate high-quality visualisation of retinal microstructures, including cones. Cone parameters, such as cone density (DM), cone spacing (SM), and regularity (REG), were analysed. The best corrected visual acuity (BCVA) was assessed as well. Examinations were performed twice over a 6-year observation period. A significant change was observed in DM (1282.73/mm2 vs. 10,073.42/mm2, p< 0.001) and SM (9.83 μm vs. 12.16 μm, p< 0.001) during the follow-up. BCVA deterioration was also significant (0.16 vs. 0.12, p = 0.001), albeit uncorrelated with the change in cone parameters. No significant difference in REG was detected between the initial examination and the follow-up (p = 0.089).
... The wavefront sensor and corrector measure these aberrations. The control system then interprets the data collected by the sensor and orchestrates the interaction between the sensor and corrector [41,44]. There are two main AO technologies used in visualizing retinal photoreceptors: split detector (SD-AOSLO) and confocal (cSLO). ...
... Both confocal and spectral images can be taken simultaneously. Some AO imaging devices capture three channels simultaneously (confocal, split detection, and dark-field), each highlighting different retinal structures [18,44,45]. ...
... Research on its application in IRDs is emerging, as existing diagnostic techniques (SD-OCT, FAF, FA, and microperimetry) are not sufficiently precise for comprehensive assessments. Several studies confirm that IRDs can present morphological changes detectable by AO preceding functional vision loss, which could greatly impact IRDs' diagnostic processes [36,39,44]. ...
Inherited retinal dystrophies (IRDs) are genetic disorders that lead to the bilateral degeneration of the retina, causing irreversible vision loss. These conditions often manifest during the first and second decades of life, and their primary symptoms can be non-specific. Diagnostic processes encompass assessments of best-corrected visual acuity, fundoscopy, optical coherence tomography, fundus autofluorescence, fluorescein angiography, electrophysiological tests, and genetic testing. This study focuses on the application of adaptive optics (AO), a non-invasive retinal examination, for the assessment of patients with IRDs. AO facilitates the high-quality, detailed observation of retinal photoreceptor structures (cones and rods) and enables the quantitative analysis of parameters such as cone density (DM), cone spacing (SM), cone regularity (REG), and Voronoi analysis (N%6). AO examinations were conducted on eyes diagnosed with Stargardt disease (STGD, N=36), cone dystrophy (CD, N=9), and cone-rod dystrophy (CRD, N=8), and on healthy eyes (N=14). There were significant differences in the DM, SM, REG, and N%6 parameters between the healthy and IRD-affected eyes (p<0.001 for DM, SM, and REG; p=0.008 for N%6). The mean DM in the CD, CRD, and STGD groups was 8900.39/mm2, 9296.32/mm2, and 16,209.66/mm2, respectively, with a significant inter-group difference (p=0.006). The mean SM in the CD, CRD, and STGD groups was 12.37 μm, 14.82 μm, and 9.65 μm, respectively, with a significant difference observed between groups (p=0.002). However, no significant difference was found in REG and N%6 among the CD, CRD, and STGD groups. Significant differences were found in SM and DM between CD and STGD (p=0.014 for SM; p=0.003 for DM) and between CRD and STGD (p=0.027 for SM; p=0.003 for DM). Our findings suggest that AO holds significant potential as an impactful diagnostic tool for IRDs.
... Applied to the human eye, AO allows direct visualisation of individual rod and cone photoreceptor mosaic, RPE cells, and white blood cells [138][139][140]. This technology allows for optical resolutions of less than 2 μm, which is sufficient for measurements of cellular and subcellular details of normal retina to be made; thus, AO has the potential to detect very early signs of HCQ retinopathy ( Figure 11) [141]. ...
... Applied to the human eye, AO allows direct visualisation of individual rod and cone photoreceptor mosaic, RPE cells, and white blood cells [138][139][140]. This technology allows for optical resolutions of less than 2 µm, which is sufficient for measurements of cellular and subcellular details of normal retina to be made; thus, AO has the potential to detect very early signs of HCQ retinopathy ( Figure 11) [141]. In a pilot study of 23 patients, Debellemanièree et al. reported that parafoveal cone metric changes may represent the earliest sign of HCQ macular toxicity. ...
This review provides an overview of conventional and novel retinal imaging modalities for hydroxychloroquine (HCQ) retinopathy. HCQ retinopathy is a form of toxic retinopathy resulting from HCQ use for a variety of autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Each imaging modality detects a different aspect of HCQ retinopathy and shows a unique complement of structural changes. Conventionally, spectral-domain optical coherence tomography (SD-OCT), which shows loss or attenuation of the outer retina and/or retinal pigment epithelium–Bruch’s membrane complex, and fundus autofluorescence (FAF), which shows parafoveal or pericentral abnormalities, are used to assess HCQ retinopathy. Additionally, several variations of OCT (retinal and choroidal thickness measurements, choroidal vascularity index, widefield OCT, en face imaging, minimum intensity analysis, and artificial intelligence techniques) and FAF techniques (quantitative FAF, near-infrared FAF, fluorescence lifetime imaging ophthalmoscopy, and widefield FAF) have been applied to assess HCQ retinopathy. Other novel retinal imaging techniques that are being studied for early detection of HCQ retinopathy include OCT angiography, multicolour imaging, adaptive optics, and retromode imaging, although further testing is required for validation.
... The two gratings have the same period. If the phase object is placed in front of the first grating, the light deflected by the object yields the shifted Fourier images, and the resultant Moiré fringes show the deflection mapping [71]. The distortion of the fringe pattern reflects the local tilt of the wavefront. ...
... two gratings have the same period. If the phase object is placed in front of the first grating, the light deflected by the object yields the shifted Fourier images, and the resultant Moiré fringes show the deflection mapping[71]. ...
Adaptive optics (AO) is employed for the continuous measurement and correction of ocular aberrations. Human eye refractive errors (lower-order aberrations such as myopia and astigmatism) are corrected with contact lenses and excimer laser surgery. Under twilight vision conditions, when the pupil of the human eye dilates to 5–7 mm in diameter, higher-order aberrations affect the visual acuity. The combined use of wavefront (WF) technology and AO systems allows the pre-operative evaluation of refractive surgical procedures to compensate for the higher-order optical aberrations of the human eye, guiding the surgeon in choosing the procedure parameters. Here, we report a brief history of AO, starting from the description of the Shack–Hartmann method, which allowed the first in vivo measurement of the eye’s wave aberration, the wavefront sensing technologies (WSTs), and their principles. Then, the limitations of the ocular wavefront ascribed to the IOL polymeric materials and design, as well as future perspectives on improving patient vision quality and meeting clinical requests, are described.
