Adaptive Optics Retinal Camera Research Articles

Retinal Microcirculation Measurements in Response to Endurance Exercises Analysed by Adaptive Optics Retinal Camera.

This study aimed to precisely investigate the effects of intensive physical exercise on retinal microvascular regulation in healthy volunteers through adaptive optics retinal camera (AO) measurement. We included healthy volunteers (11 men and 14 women) aged 20.6 ± 0.9. The heart rate (HR) and systolic and diastolic blood pressures (SBP, DBP) were recorded before and after a submaximal physical exertion of continuously riding a training ergometer. The superior temporal retinal artery measurements were captured using the AO-rtx1TM (Imagine Eyes, Orsay, France) without pupil dilation. We compared measures of vessel diameter (VD), lumen diameter (LD), two walls (Wall 1, 2), wall-to-lumen ratio (WLR), and wall cross-sectional analysis (WCSA) before and immediately after the cessation of exercise. Cardiovascular parameter results: After exercise, SBP, DBP, and HR changed significantly from 130.2 ± 13.2 to 159.7 ± 15.6 mm Hg, 81.2 ± 6.3 to 77.1 ± 8.2 mm Hg, and 80.8 ± 16.1 to 175.0 ± 6.2 bpm, respectively (p < 0.002). Retinal microcirculation analysis showed no significant decrease in LD, Wall 1 after exercise: from 96.0 ± 6.8 to 94.9 ± 6.7 (p = 0.258), from 11.0 ± 1.5 to 10.4 ± 1.5 (p = 0.107), respectively, and significant reduction in VD from 118.5 ± 8.3 to 115.9 ± 8.3 (p = 0.047), Wall 2 from 11.5 ± 1.0 to 10.7 ± 1.3 (p = 0.017), WLR from 0.234 ± 0.02 to 0.222 ± 0.010 (p = 0.046), WCSA from 3802.8 ± 577.6 to 3512.3 ± 535.3 (p = 0.016). The AO is a promising technique for investigating the effects of exercise on microcirculation, allowing for the tracking of changes throughout the observation. Intensive dynamic physical exertion increases blood pressure and heart rate and causes the vasoconstriction of small retinal arterioles due to the autoregulation mechanism.

Neurovascular coupling reflex from contralateral stimulation: System setup

Aims/Purpose: Neurovascular coupling (NVC) is the blood flow modulation in response to stimuli and has been extensively studied in the brain. Concerning the human retina, this behaviour has been only measured in the ipsilateral eye, where stimuli and observed effects involve the same eye. This work aims to set up the hardware to assess NVC in the contralateral eye and demonstrate its feasibility in edifying human retina‐retina or cortico‐retinal connections.Methods: Adaptive optics (AO) is a cutting‐edge technology in retinal fundus imaging, offering exceptional spatial resolution. The NVC effect was successfully assessed using the RTX1, an AO retinal camera capable of ipsilateral stimulation. The possible effects of contralateral stimulation can be readily assessed by providing RTX1 with an external flickering device. Furthermore, connecting the thread between previous fMRI results and photic stimulation in the ipsi‐ and contralateral retina can offer valuable information on uncharted interocular or brain‐retina neural pathways and lead to cost‐effective and non‐invasive biomarkers for neurodegenerative diseases or early brain vasculature impairment diagnosis.Results: Even though further optimization of flicker‐related parameters is necessary to investigate the contralateral NVC response, preliminary tests showed the successful integration of a fully operational contralateral stimulation prototype with the RTX1. The entire procedure has been documented, and all components have been thoroughly evaluated.Conclusions: These preliminary assessments precede a clinical study involving patients with type 1 Diabetes Mellitus and a control group of healthy individuals. It follows previous fMRI studies that showed impaired NVC in type 2 diabetic patients by measuring the BOLD (Blood Oxygen Level‐Dependent) response using block and event‐related optical stimuli. A comparative analysis of the findings aims to demonstrate the potential role of neurovascular uncoupling in the early pathogenesis of diabetic retinopathy.

Photoreceptor mosaic before and after macular hole surgery with RTX-1 adaptive optics retinal camera

Photoreceptor mosaic before and after macular hole surgery with RTX-1 adaptive optics retinal camera

Comprehensive automatic processing and analysis of adaptive optics flood illumination retinal images on healthy subjects.

This work presents a novel fully automated method for retinal analysis in images acquired with a flood illuminated adaptive optics retinal camera (AO-FIO). The proposed processing pipeline consists of several steps: First, we register single AO-FIO images in a montage image capturing a larger retinal area. The registration is performed by combination of phase correlation and the scale-invariant feature transform method. A set of 200 AO-FIO images from 10 healthy subjects (10 images from left eye and 10 images from right eye) is processed into 20 montage images and mutually aligned according to the automatically detected fovea center. As a second step, the photoreceptors in the montage images are detected using a method based on regional maxima localization, where the detector parameters were determined with Bayesian optimization according to manually labeled photoreceptors by three evaluators. The detection assessment, based on Dice coefficient, ranges from 0.72 to 0.8. In the next step, the corresponding density maps are generated for each of the montage images. As a final step, representative averaged photoreceptor density maps are created for the left and right eye and thus enabling comprehensive analysis across the montage images and a straightforward comparison with available histological data and other published studies. Our proposed method and software thus enable us to generate AO-based photoreceptor density maps for all measured locations fully automatically, and thus it is suitable for large studies, as those are in pressing need for automated approaches. In addition, the application MATADOR (MATlab ADaptive Optics Retinal Image Analysis) that implements the described pipeline and the dataset with photoreceptor labels are made publicly available.

In vivo assessment of associations between photoreceptors structure and macular perfusion in type 1 diabetes

PurposeTo explore the potential relationships between macular vascular network and different adaptive optics (AO) metrics in patients with type 1 diabetes mellitus (DM1) with no signs (NoDR) or mild non-proliferative...

Evaluation of Morphological Changes in Retinal Vessels in Type 1 Diabetes Mellitus Patients with the Use of Adaptive Optics.

Introduction. Diabetes mellitus contributes to the development of microvascular complications in the eye. Moreover, it affects multiple end organs, including brain damage, leading to premature death. The use of adaptive optics technique allows to perform non-invasive in vivo assessment of retinal vessels and to identify changes in arterioles about 100 μm in diameter. The retinal vasculature may be a model of the cerebral vessels both morphologically and functionally. Aim. To evaluate morphological parameters of retinal arterioles in patients with type 1 diabetes mellitus (DM1). Material and methods. The study included 22 DM1 patients (13 females) aged 43.00 ± 9.45 years with a mean diabetes duration of 22.55 ± 10.05 years, and 23 healthy volunteers (10 females) aged 41.09 ± 10.99 years. Blood pressure, BMI, waist circumference, and metabolic control markers of diabetes were measured in both groups. Vascular examinations were performed using an rtx1 adaptive optics retinal camera (Imagine Eyes, Orsay, France); the vessel wall thickness (WT), lumen diameter (LD), wall-to-lumen ratio (WLR), and vascular wall cross-sectional area (WCSA) were assessed. Statistical analysis was performed with the application of IMB SPSS version 23 software. Results. The DM1 group did not differ significantly in age, BMI, waist circumference, blood pressure, or axial length of the eye compared to the control group. Intraocular pressure (IOP) in both groups was normal, but in the DM1 group it was significantly higher. The DM1 group had significantly higher WT, WLR, and WCSA. These parameters correlated significantly with the duration of diabetes, but not with IOP. Conclusions. The presented study demonstrates the presence of significant morphological changes in retinal vessels in DM1 patients without previously diagnosed diabetic retinopathy. Similar changes may occur in the brain and may be early indicators of cardiovascular risk, but further investigation is required to confirm that.

Hemodynamic and morphological changes of the central retinal artery in myopic eyes

Due to excessive elongation of the eyeball, myopia-related vascular abnormalities are frequently observed in the central retinal artery (CRA) and its intraretinal branches. In addition to inconsistency in previously reported findings, hemodynamic (reduced flow velocity, increased vascular resistance) and morphological changes (narrower vessel diameter) were usually studied separately. This cross-sectional study evaluated the hemodynamic and morphological characteristics concurrently in a large sample of healthy myopes, by using the color Doppler ultrasound and adaptive optics retinal camera. Results showed that the retrobulbar segment of CRA had a tendency of slightly reduced flow velocity in eyeballs with longer axial length, but the correlation was not significant after adjusting for the multiple correlations. Vascular resistance was not affected by the axial elongation. With respect to the intraretinal branches, no significant changes in longer eyes of total diameter or lumen diameter were observed, while both the wall thickness and the wall cross-sectional area were significantly increased, but only a marginally increase in the wall to lumen ratio was found with increasing axial length. This implies some potential small artery remodeling in the intraretinal CRA branches. Overall, blood supply of the inner retina in healthy young myopes is likely to be maintained. Additionally, morphological parameters of vascular microstructure could be potential biomarkers to monitor myopia progression and understand myopia-related vascular abnormalities in future studies.

Adaptive Optics Ophthalmoscopy in Diabetic Retinopathy

Abstract Diabetic retinopathy is the leading cause of visual loss and blindness in working-age adults and represents the most common microvascular complication of diabetes mellitus. The current research assesses the retinal arterioles status in healthy volunteers and diabetic patients, in order to detect early retinal changes by using adaptive optics ophthalmoscopy (AOO), a cutting edge, noninvasive imaging technique. Our patients were evaluated between 2021-2022 in the Retina Clinic Bucharest, Romania. All of them underwent a complete ophthalmologic examination. By using rtx1™ adaptive optics retinal camera (Imagine Eyes, Orsay, France) together with the manufacturer’s software (AO detect artery, Imagine Eyes, France), several vascular parameters of the retinal arteriole were calculated, including wall to lumen ratio (WLR), vessel diameter (VD), lumen diameter (LD), mean wall thickness (WT) and cross-sectional area of the vascular wall (WCSA). All five studied vascular parameters were found to have higher values in diabetic patients, when compared to healthy volunteers. The differences were statistically significant for WT, WLR and WCSA (p values under 0.05). Adaptive optics ophthalmoscopy represents a cutting-edge technique, opening a new era in the medical retina field. It provides useful data regarding the retinal vascular status, in a non-invasive manner, being a promising tool in the diagnosis, staging and follow-up of diabetic retinal disease.

Solar retinopathy-correlation between adaptive optics and spectral domain optical coherence tomography with visual acuity.

To study the characteristics of photoreceptors on adaptive optics (AO) in patients of solar retinopathy and its correlation to changes in spectral domain optical coherence tomography (SDOCT) and visual acuity. This is a cross-sectional observational study of six eyes of five patients with clinically diagnosed solar retinopathy. Five age-matched controls were included for comparison. A flood-illuminated adaptive optics retinal camera (AO; rtx1, Imagine Eyes, Orsay, France) was used to image the photoreceptors and a spectral domain optical coherence tomography (SDOCT; Spectralis™ Heidelberg Engineering, Germany) was used to study the retinal layers in these patients. The corrected distance visual acuity (CDVA) was assessed using Snellen's chart. Defects on the SDOCT were smaller (0.25 to 0.75°) at the fovea compared with AO (more than 1°). The cone mosaic was preserved beyond 1°. The cone count from the foveal center at 0.75, 1, 2, and 3° was decreased in all patients of solar retinopathy (mean value 5352) compared with age-matched controls (mean value 15693). A corresponding increase in spacing (mean value 19.13) compared with controls (mean value 9.34) was also observed. The CDVA ranged from 20/30 to 20/80. There was no statistically significant relationship between cone density, at any of the eccentricities measured, with CDVA or OCT defect (p > 0.05, for all). Adaptive optics is a sensitive and accurate tool to analyze photoreceptor damage in solar maculopathy. It can be used as an adjunct for better understanding of the pathology and to observe or predict changes in these patients.

Association Between Alterations of the Choriocapillaris Microcirculation and Visual Function and Cone Photoreceptors in Patients With Diabetes.

PurposeThe purpose of this study was to investigate the association between the choriocapillaris microcirculation and the visual function and cone photoreceptor structure in patients with diabetes.MethodsThirteen control subjects and 26 patients with type 2 diabetes were recruited. The patients with diabetes were divided into three groups based on the grade of diabetic retinopathy (DR). The retinal sensitivity (RS) was evaluated using microperimetry. Cone photoreceptor mosaics were imaged using an adaptive optics retinal camera, and the cone heterogeneity packing index (HPi) was calculated. Optical coherence tomography angiography (OCTA) images of the choriocapillaris were obtained using spectral-domain OCTA, and the area of flow deficit (FD) was evaluated. All parameters were evaluated in the foveal and parafoveal areas.ResultsThe study included four patients with diabetes without retinopathy, 12 patients with nonproliferative diabetic retinopathy (NPDR), and 10 patients with proliferative diabetic retinopathy (PDR). The foveal and parafoveal FDs were correlated significantly (fovea, r = −0.58; P = 0.046 and r = −0.82; P = 0.003; parafovea, r = −0.59; P = 0.044 and r = −0.72; and P = 0.019, respectively) with the RS in patients with NPDR and PDR, but not in control and no diabetic retinopathy (NDR) groups. There were no differences in the foveal HPi among the groups.ConclusionsImpaired choriocapillaris microcirculation is associated with impaired visual function but not cone photoreceptor integrity in eyes with DR.

High-resolution Imaging of Central Retinal Artery Occlusion using Adaptive Optics Retinal Camera

High-resolution Imaging of Central Retinal Artery Occlusion using Adaptive Optics Retinal Camera

Optyka adaptywna – nowa technologia w diagnostyce obrazowej

Technologia optyki adaptywnej (AO, adaptive optics) stała się w ostatnim czasie cennym narzędziem diagnostycznym w badaniach nad mikrostrukturą i funkcją siatkówki. Wykorzystując światło z zakresu bliskiej podczerwieni, kamera optyki adaptywnej umożliwia nieinwazyjne obrazowanie fotoreceptorów (głównie czopków), ściany i światła naczyń siatkówki, włókien nerwowych oraz struktur blaszki sitowej, które trudno uwidocznić za pomocą innych, stosowanych obecnie technik. Technologia AO może dostarczyć informacji o patologicznych zmianach w siatkówce, nawet gdy brakuje jakichkolwiek odchyleń od normy w obrazowych badaniach strukturalnych lub funkcjonalnych. Obecnie aparat rtx1TM (Imagine Eyes, Francja) jest jedynym urządzeniem z kamerą optyki adaptywnej dopuszczonym do badań okulistycznych w wielu krajach. W niniejszym artykule przedstawiamy krótki przegląd rozwoju technologii optyki adaptywnej oraz stale zmieniające się możliwości jej zastosowania w diagnostyce okulistycznej.

Cone mosaic characteristics in red-green colour deficiency: a comparative study

ObjectiveTo compare photoreceptor cone characteristics using adaptive optics (AO) technology between congenital colour blind patients and healthy age-matched controls. DesignCross-sectional. Participants21 eyes (21 cases) with congenital red-green colour blindness and 21 eyes of age-matched controls (21 controls), all having a best-corrected visual acuity of 20/20 and normal ophthalmological examination, were recruited. MethodsColour vision testing was done using the Farnsworth–Munsell 100-Hue test and Nagel anomaloscope. Imaging of fovea was done using rtx1 AO retinal camera with a sampling window size of 4° × 4°. Peak cone density, intercone spacing, cone regularity, and cone dispersion were determined using AOdetect Mosaic software. ResultsOverall, mean cone characteristics at 2° off fixation in cases and controls, respectively, were density 26 587 ± 1328/26 448 ± 687 cells/mm2 (p = 0.67), spacing 6.69 ± 0.17/6.75 ± 0.11 μm (p = 0.19), regularity 94.36 ± 2.56/94.83 ± 1.28% (p = 0.46), dispersion 10.22 ± 1.21/11.68 ± 0.79% (p = 0.0001), and hexagonality 50.62 ± 4.21/49.52 ± 2.45% (p = 0.31). No significant difference was noted in various cone metrics except dispersion, which was markedly decreased in colour-deficient individuals. At 4° off fixation, the cone characteristics were not significantly different between cases and controls: density 16 521 ± 1230/16 930 ± 678 cells/mm2 (p = 0.37), spacing 8.60 ± 0.29/8.46 ± 0.17 μm (p = 0.19), regularity 92.68 ± 2.83/92.6 ± 3.05% (p = 0.95), dispersion 13.43 ± 3.48/13.65 ± 2.38% (p = 0.87), and hexagonality 45.22 ± 3.8/45.21 ± 5.5% (p = 0.99). A significant reduction in cone density, regularity, and hexagonality was associated with corresponding increase in spacing and dispersion as we moved from 2° to 4° off fixation in both cases and controls. ConclusionCone photoreceptor characteristics are anatomically well preserved in young colour-deficient individuals except cone dispersion.

Effect of A Multinutrient Complex on Retinal Microcirculation in Diabetic Patients Investigated Using an Adaptive Optics Retinal Camera.

Alimentary supplements may have beneficial effects on retinal microvasculature in diabetic patients. State-of-the-art imaging techniques were used to assess retinal microcirculation in diabetic patients in an observational study before and after 3 months treatment with a multinutrient complex including resveratrol, vitamins D3, C, E, essential fatty acids, trace elements (zinc and copper) and macular pigments (lutein and zeaxanthin)-Resvega. Fifteen subjects were included in this study. Adaptive optics ophthalmoscopy was used to measure the parameters of temporal retinal arterioles. Optical coherence tomography angiography was employed to assess foveal avascular zone and vessel densities of the superficial capillary plexus, deep capillary plexus and choricapillary plexus. After 3 months of treatment, there was a statistically significant median decrease in wall-to-lumen ratio (p=0.0001). The same tendencies were noticed for wall thickness values (p=0.008) and wall cross sectional area values (p=0.001). On the other side, no significant changes were noticed concerning the OCTA parameters. Resvega seems to have a beneficial effect on the retinal arterioles in diabetic patients.

Cone photoreceptor density in type I diabetic patients measured with an adaptive optics retinal camera

Purpose: To assess the variation in cone photoreceptor density on the basis of age compatibility between healthy subjects, on one side, and type 1 diabetic patients with no diabetic retinopathy, on the other. Methods: A high resolution adaptive optics retinal camera in flood illumination regime was employed to image cones of 15 type I diabetic patients and 16 healthy controls. For each subject we scanned the cone mosaic in 4 perifoveal areas (nasally, temporally, superiorly and inferiorly) at 2, 3 and 4 degrees eccentricity. The impact of diabetes duration, gender and age were evaluated. Results: In the type I diabetic group we found a meaningful lower cone density (p<0.05), except for the temporal meridian at 2 and 4 degrees eccentricity. Moreover, a significant asymmetry of cone photoreceptor densities was proved between the horizontal and vertical meridians in both diabetic and control groups. Conclusion: The rtx1 retinal image evaluation demonstrated photoreceptors loss in DM1 diabetic patients prior to any clinical changes. Abbreviations: AO = adaptive optics, SS = swept source, OCT = optical coherence tomography, BCVA= best corrected visual acuity, DM = diabetes mellitus, DR = diabetic retinopathy.

High-resolution imaging of diabetic retinopathy lesions using an adaptive optics retinal camera

Purpose. Adaptive optics (AO) imaging is a promising high-resolution investigation technique in ophthalmology that can bring new information about the pathophysiology of diabetic retinopathy. Material and methods. Seven patients previously diagnosed with diabetic retinopathy were investigated with optical coherence tomography (OCT) scanning, OCT angiography, fundus photo, and AO retinal camera (rtx1TM, Imagine Eyes, Orsay, France). Results. The red lesions on fundus photos appeared on AO imaging as hyporeflective lesions. OCT angiography helped us to differentiate between microaneurysms and hemorrhages. Hard exudates had a heterogeneous granular appearance. Retinal oedema was proved to have a blurring effect on the AO images. In addition to this, cystic spaces were identified to have a hyporeflective demarcation line. Conclusions. AO imaging is offering a fine documentation of retinal lesions and might become an important instrument for early diagnosis of diabetic retinopathy and for explaining its pathophysiological mechanisms. Abbreviations: AO = adaptive optics, AOO = adaptive optics ophthalmoscopy, SS = swept source, OCT =optical coherence tomography, SLO = scanning laser ophthalmoscope.

Adaptive Optics (rtx1) High-Resolution Imaging of Photoreceptors and Retinal Arteries in Patients with Diabetic Retinopathy.

Background Diabetic retinopathy (DR) is the leading cause of impaired vision in patients with diabetes mellitus. An adaptive optics retinal camera (rtx1™; Imagine Eyes, France) was used to capture images of cones and retinal arteries from patients with DR. Objective Cone parameters (density, interphotoreceptor distance, and regularity) and retinal artery parameters (wall thickness, lumen diameter, WLR, and WCSA) were analyzed in 36 patients with nonproliferative DR (NPDR; 22 with mild NPDR and 14 with moderate NPDR) and in 20 healthy volunteers (the control group). Results Cone density at 2° eccentricities was significantly lower in the DR compared to the control group (19822 ± 4342 cells/mm2 vs. 24722 ± 3507 cells/mm2, respectively). Cone density and regularity decreased with increasing severity of DR. The artery walls were significantly thicker in the DR group. The WLR and WCSA differed significantly between the DR and the control groups (WLR 0.339 ± 0.06 vs. 0.254 ± 0.04; WCSA 5567 ± 1140 vs. 4178 ± 944, respectively). Conclusions Decreased cone regularity and density are seen in patients with mild and moderate NPDR. Abnormalities of retinal arterioles show signs of arteriolar dysfunction in DR. Retinal image analysis with the rtx1 offers a novel noninvasive measurement of early changes in the neural cells and retina vasculature in diabetic eyes.

RETINAL MICROCIRCULATION INVESTIGATION IN TYPE I AND II DIABETIC PATIENTS WITHOUT RETINOPATHY USING AN ADAPTIVE OPTICS RETINAL CAMERA.

State of art imaging techniques might be a useful tool to early detect the retinal vessels lesions in diabetes. This analytical observational study investigates the retinal microcirculation changes in type I and II diabetic patients without retinopathy using adaptive optics ophthalmoscopy (AOO) and optical coherence ophthalmoscopy angiography (OCTA). Fifty-five subjects were included in this study and were divided in three groups: type I diabetic group (n=16), type II diabetic group (n=19) and control group (n=20). An adaptive optics retinal camera was used to assess the parameters of the temporal superior retinal arterioles. Moreover, vessel density of the superficial capillary plexus across the parafoveal area was measured with OCT-A. All cases were investigated once, in a cross-sectional design. Diabetic patients from both groups had a higher wall-to-lumen-ratio compared to the controls (p=0.01 and 0.01, respectively). Interestingly, no significant differences were found between the two diabetic groups (p=0.69). Moreover, the vessel density was smaller in the type I diabetic group than in the control group (p=0.001). AOO might be a useful tool to detect early retinal vascular changes in diabetes before any clinical signs and together with OCTA it might bring important information on the prognostic and pathophysiology of the disease.

Morphometric analysis of retinal arterioles in control and hypertensive population using adaptive optics imaging.

Purpose:To measure the wall-to-lumen ratio (WLR) and the vascular wall cross-sectional area (WCSA) of retinal arterioles by an Adaptive Optics (AO) retinal camera using semi-automated software and comparing them between control and hypertensive population.Methods:This was a cross-sectional observational study including a hypertensive group and a control group. Subjects were examined and their medical history recorded. Retinal arteriolar morphometry was assessed by rtx1 AO retinal camera using AOdetect Artery semiautomated software. Main Outcome Measures: WLR and WCSA were measured on the basis of retinal arteriolar wall thickness (W1, W2), lumen diameter (LD) and vessel diameter (VD). Influence of age and arterial hypertension on the WLR and WCSA were examined.Results:A total of 150 human subjects were included out of which 110 were controls and 40 were hypertensives under treatment. There was statistically significant difference in the age, systolic and diastolic blood pressures between the control and hypertensive groups (P < 0.01). We found no significant correlation between age and WLR (R2 = 0.049, P > 0.05) or age and WCSA (R2 = 0.045, P > 0.05). We observed a significant difference in WLR and WCSA measurements between control and hypertensive groups (P < 0.01). On measuring intra-observer variability (IOV) we found excellent consistency.Conclusion:AO retinal imaging allows a direct measurement of the retinal vessel wall and LD with excellent IOV. WLR and WCSA reflect the remodelling process and can be used to further aid the early detection and monitoring of systemic hypertension.

High-resolution imaging of photoreceptors in healthy human eyes using an adaptive optics retinal camera.

To determine the effects of age on perifoveal cone density in healthy subjects using adaptive optics. Healthy subjects of various ages were imaged using an adaptive optics retinal camera (RTX-1® Imagine Eyes, Orsay, France). All patients underwent a comprehensive ophthalmologic examination and retinal imaging using spectral-domain optical coherence tomography (Spectralis®, Heidelberg Engineering, Heidelberg, Germany). Cone density together with cone spacing and cone mosaic packing were measured in the nasal and temporal area 450 µm from the fovea. A multivariate analysis was performed to determine which of the following parameters were related to a decrease in cone density: age, axial length, central macular thickness, and retrofoveal choroidal thickness. One hundred and sixty-seven eyes of 101 subjects aged 6-78 years were studied. Perifoveal cone density significantly decreased with age (R2 = 0.17, p<0.01). Inversely, cone spacing increased with age (R2=0.18, p<0.01). There was no change in the cone packing mosaic (p>0.05). The mean coefficient of variation between fellow eyes was 3.9%. Age and axial length were related to a cone density decrease, while choroidal and retinal thicknesses did not affect cone metrics in healthy subjects. A moderate perifoveal cone loss occurs with age. The precise consequences of these findings on visual function should be investigated. In addition to a better understanding of normal retinal anatomy, these results could act as a comparative database for further studies on normal and diseased retinas.