Dual roles of the retinal pigment epithelium and lens in cavefish eye degeneration.

Astyanax mexicanus consists of two forms, a sighted surface dwelling form (surface fish) and a blind cave-dwelling form (cavefish). Embryonic eyes are initially formed in cavefish but they are subsequently arrested in growth and degenerate during larval development. Previous lens transplantation studies have shown that the lens plays a central role in cavefish eye loss. However, several lines of evidence suggest that additional factors, such as the retinal pigment epithelium (RPE), which is morphologically altered in cavefish, could also be involved in the eye regression process. To explore the role of the RPE in cavefish eye degeneration, we generated an albino eyed (AE) strain by artificial selection for hybrid individuals with large eyes and a depigmented RPE. The AE strain exhibited an RPE lacking pigment granules and showed reduced expression of the RPE specific enzyme retinol isomerase, allowing eye development to be studied by lens ablation in an RPE background resembling cavefish. We found that lens ablation in the AE strain had stronger negative effects on eye growth than in surface fish, suggesting that an intact RPE is required for normal eye development. We also found that the AE strain develops a cartilaginous sclera lacking boney ossicles, a trait similar to cavefish. Extrapolation of the results to cavefish suggests that the RPE and lens have dual roles in eye degeneration, and that deficiencies in the RPE may be associated with evolutionary changes in scleral ossification.

3D-Reconstructed Retinal Pigment Epithelial Cells Provide Insights into the Anatomy of the Outer Retina.

The retinal pigment epithelium (RPE) is located between the neuroretina and the choroid, and plays a critical role in vision. RPE cells internalise outer segments (OS) from overlying photoreceptors in the daily photoreceptor renewal. Changes to RPE structure are linked with age and retinopathy, which has been described in the past by conventional 2D electron microscopy. We used serial block face scanning electron microscopy (SBF-SEM) to reconstruct RPE cells from the central mouse retina. Three-dimensional-reconstructed OS revealed the RPE to support large numbers of photoreceptors (90-216 per RPE cell). Larger bi-nucleate RPE maintained more photoreceptors, although their cytoplasmic volume was comparable to smaller mono-nucleate RPE supporting fewer photoreceptors. Scrutiny of RPE microvilli and interdigitating OS revealed the angle and surface area of contact between RPE and photoreceptors. Bi-nucleate RPE contained more mitochondria compared to mono-nucleate RPE. Furthermore, bi-nucleate cells contained larger sub-RPE spaces, supporting a likely association with disease. Use of perfusion-fixed tissues ensured the highest possible standard of preservation, providing novel insights into the 3D RPE architecture and changes linked with retinopathy. This study serves as a benchmark for comparing retinal tissues from donor eyes with age-related macular degeneration (AMD) and other retinopathies.

Associations with Retinal Pigment Epithelium Thickness Measures in a Large Cohort: Results from the UK Biobank.

PURPOSE: To describe associations of ocular and systemic factors with retinal pigment epithelium (RPE)-Bruch's membrane (BM) complex thickness as measured by spectral-domain (SD) optical coherence tomography (OCT). DESIGN: Multisite community-based study. This research has been conducted using the UK Biobank Resource. PARTICIPANTS: Sixty-seven thousand three hundred eighteen people 40 to 69 years old received questionnaires, physical examination, and eye examination, including macular SD OCT. Systematic selection process identified 34 652 eyes with high-quality SD OCT images from normal individuals for analysis. METHODS: We included people with no self-reported ocular disease, diabetes, or neurologic disorders; visual acuity of ≥20/25; refraction between -6 diopters (D) to 6 D, and IOP of 6 to 21 mmHg. Only high-quality, well-centered SD OCT images with central, stable fixation were included. Descriptive statistics, t tests, and regression analyses were performed. Multivariate regression modeling was used to adjust for covariates and to identify relationships between RPE-BM thickness and ocular and systemic features. MAIN OUTCOME MEASURES: Retinal pigment epithelium-BM thickness, as measured by SD OCT segmentation using Topcon Advanced Boundary Segmentation at 9 Early Treatment of Diabetic Retinopathy Study subfields. RESULTS: Mean RPE-BM thickness was 26.3 µm (standard deviation, 4.8 µm) at central subfield. Multivariate regression with age stratification showed that RPE thinning became apparent after age 45. Among those aged ≤45, RPE-BM was significantly thicker among those of black or mixed/other race (+3.61 and +1.77 µm vs. white, respectively; P < 0.001) and higher hyperopia (+0.4 µm/D; P < 0.001), but not for other variables considered. Among those age >45, RPE-BM was significantly thinner with older age (-0.10 µm/year; P < 0.001), Asian ethnicity (-0.45 µm vs. white; P = 0.02), taller height (-0.02 µm/cm; P < 0.001), higher IOP (-0.03 µm/mmHg; P < 0.001), and regular smoking (-0.27 µm vs. nonsmokers; P = 0.02). In contrast, RPE-BM was significantly thicker among black or mixed/other race (+3.29 µm and +0.81 µm vs. white, respectively; P < 0.001) and higher hyperopia (+0.28 µm/D; P < 0.001). There was no significant association with sex or Chinese ethnicity. CONCLUSIONS: We describe novel findings of RPE-BM thickness in normal individuals, a structure that varies with age, ethnicity, refraction, IOP, and smoking. The significant association with IOP is especially interesting and may have relevance for the etiology of glaucoma, while the association between age and smoking may have relevance for the etiology of age-related macular degeneration.

CHANGES OF OUTER RETINAL THICKNESS WITH INCREASING AGE IN NORMAL EYES AND IN NORMAL FELLOW EYES OF PATIENTS WITH UNILATERAL AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To test the hypothesis that the thickness of outer retinal layers will change with increasing age in normal eyes and in the normal fellow eyes of patients with unilateral age-related macular degeneration. METHODS: Spectral domain optical coherence tomography images of 127 normal eyes of 127 subjects and 58 normal fellow eyes of 58 patients with unilateral age-related macular degeneration were studied. The thickness between the retinal pigment epithelium line and the cone outer segment tips line, between the cone outer segment tips line and the photoreceptor inner segment/outer segment line, and between the inner segment/outer segment line and the external limiting membrane line were measured at the fovea in both groups. RESULTS: The thickness between retinal pigment epithelium line and the cone outer segment tips line, and between inner segment/outer segment line and the external limiting membrane line were significantly and negatively associated with age in the normal group. Cone outer segment tips line and the photoreceptor inner segment/outer segment thickness was not significantly associated with age. Retinal pigment epithelium line and the cone outer segment tips line was thinner in the fellow eyes of patients with unilateral age-related macular degeneration than in the age-matched normal eyes. Cone outer segment tips line and the photoreceptor inner segment/outer segment and inner segment/outer segment line and the external limiting membrane line thicknesses in the fellow eyes were not significantly different from that of normal eyes. CONCLUSION: The tissue between the retinal pigment epithelium line and the cone outer segment tips line may become atrophic in older eyes and in the normal fellow eyes of patients with unilateral age-related macular degeneration.

Conditional Ablation of Retinol Dehydrogenase 10 in the Retinal Pigmented Epithelium Causes Delayed Dark Adaption in Mice.

Regeneration of the visual chromophore, 11-cis-retinal, is a crucial step in the visual cycle required to sustain vision. This cycle consists of sequential biochemical reactions that occur in photoreceptor cells and the retinal pigmented epithelium (RPE). Oxidation of 11-cis-retinol to 11-cis-retinal is accomplished by a family of enzymes termed 11-cis-retinol dehydrogenases, including RDH5 and RDH11. Double deletion of Rdh5 and Rdh11 does not limit the production of 11-cis-retinal in mice. Here we describe a third retinol dehydrogenase in the RPE, RDH10, which can produce 11-cis-retinal. Mice with a conditional knock-out of Rdh10 in RPE cells (Rdh10 cKO) displayed delayed 11-cis-retinal regeneration and dark adaption after bright light illumination. Retinal function measured by electroretinogram after light exposure was also delayed in Rdh10 cKO mice as compared with controls. Double deletion of Rdh5 and Rdh10 (cDKO) in mice caused elevated 11/13-cis-retinyl ester content also seen in Rdh5(-/-)Rdh11(-/-) mice as compared with Rdh5(-/-) mice. Normal retinal morphology was observed in 6-month-old Rdh10 cKO and cDKO mice, suggesting that loss of Rdh10 in the RPE does not negatively affect the health of the retina. Compensatory expression of other retinol dehydrogenases was observed in both Rdh5(-/-) and Rdh10 cKO mice. These results indicate that RDH10 acts in cooperation with other RDH isoforms to produce the 11-cis-retinal chromophore needed for vision.

OPTICAL COHERENCE TOMOGRAPHY EVIDENCE ON THE CORRELATION OF CHOROIDAL THICKNESS AND AGE WITH VASCULARIZED RETINAL LAYERS IN NORMAL EYES.

PURPOSE: To correlate choroidal thickness (CT) and age with vascularized retinal layer and outer retinal layer thickness in normal eyes. METHODS: This was a prospective, cross-sectional study. Complete ophthalmological examination, biometry, and enhanced depth imaging spectral domain optical coherence tomography were performed. Choroidal and individual retinal layer thickness measurements were obtained. Thickness maps for all layers were evaluated using the 1 mm, 3 mm, and 6 mm early treatment diabetic retinopathy study (ETDRS) macular grid areas. RESULTS: One hundred and twenty eyes were included. Choroidal thickness correlated negatively with age in all ETDRS areas. The ganglion cell layer (GCL) in the 1 mm; the GCL and inner plexiform layer (IPL) in the 3 mm and 6 mm; and the GCL, IPL, and inner nuclear layer in the 6 mm areas correlated negatively with age and positively with CT. Retinal nerve fiber layer thickness in the 6 mm area correlated negatively with age. The retinal pigment epithelium-photoreceptor layer in all areas correlated negatively with age and positively with CT. CONCLUSION: In normal subjects, vascularized retinal layer thicknesses and outer retinal layer thickness correlate positively with CT and negatively with age. The role of neuronal versus vascular components should be considered when evaluating individual retinal layer thicknesses.

CHOROIDAL THICKNESS IN RELATION TO ETHNICITY MEASURED USING ENHANCED DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To investigate the posterior choroidal thickness in healthy subjects of three different ethnicities. METHODS: In this prospective cross-sectional study, the choroidal thickness of 88 individuals (176 eyes) was measured using enhanced depth imaging-spectral domain optical coherence tomography. Subfoveal choroidal thickness was measured between the retinal pigment epithelium-Bruch membrane complex and chorioscleral interface. Nasal, temporal, superior, and inferior choroidal thicknesses at 0.5, 1.5, and 3.0 mm locations from the fovea were evaluated as well. RESULTS: Males and females were perfectly matched by number in all groups. The mean age of the entire study population was 27.43 ± 1 years. Mean subfoveal choroidal thicknesses of whites, Africans, Asians, and entire study population were 403.62 ± 37.4 µm, 372.47 ± 31.4 µm, 383.64 ± 40 µm, 386.64 ± 10.5 µm, respectively. Mean spherical error of the entire study population was -1.2685 diopter. Whites had the longest eyes on average 24.17 mm > 24.08 mm (Africans) > 23.86 mm (Asians), with the statistical mean of 24.04 mm for the entire study population. Subfoveal choroidal thickness was not significantly correlated with ethnicity in either ethnic group (P > 0.05). Subfoveal choroid thinned by 2.51 µm per 1 year increase in age (P = 0.282). Subfoveal choroidal thickness and sex were not significantly correlated to (P = 0.402). Subfoveal choroidal thickness was in strong negative correlation only with refractive error (P = 0.01) and axial length (P = 0.008). The intereye difference in subfoveal choroidal thickness was not statistically significant (P = 0.845). CONCLUSION: Enhanced depth imaging-spectral domain optical coherence tomography is a productive imaging method to study the choroidal thickness. Subfoveal choroidal thickness is not significantly correlated with ethnicity. The study reproduced previously found relations between thinner choroids and longer axial lengths, and increasing myopic refraction and showed no significant associations between subfoveal choroidal thickness and age and sex. Either the right or left eye can be used in future studies.

Third harmonic generation microscopy of a mouse retina.

PURPOSE: To demonstrate lipid-specific imaging of the retina through the use of third harmonic generation (THG), a multiphoton microscopic technique in which tissue contrast is generated from optical inhomogeneities. METHODS: A custom fiber laser and multiphoton microscope was constructed and optimized for simultaneous two-photon autofluorescence (TPAF) and THG retinal imaging. Imaging was performed using fixed-frozen sections of mouse eyes without the use of exogenous fluorescent dyes. In parallel experiments, a fluorescent nuclear stain was used to verify the location of the retinal cell nuclei. RESULTS: Simultaneous THG and TPAF images revealed all retinal layers with subcellular resolution. In BALB/c strains, the THG signal stems from the lipidic organelles of the cellular and nuclear membranes. In the C57BL/6 strain, the THG signal from the RPE cells originates from the pigmented granules. CONCLUSIONS: THG microscopy can be used to image structures of the mouse retina using contrast inherent to the tissue and without the use of a fluorescent dye or exogenously expressed recombinant protein.

Altered fundus appearance resulting from autofluorescence imaging with the confocal scanning laser ophthalmoscope (cSLO) in cats.

PURPOSE: This paper is to report that imaging the tapetal fundus of cats with the 488 nm laser of the Spectralis(®) HRA+OCT (Heidelberg Engineering Inc., Heidelberg, Germany) can result in a pale appearance of the imaged area. ANIMALS STUDIED AND PROCEDURES: Wild-type and Rdy kittens (CRX mutant heterozygotes-CRX(Rdy+/-) ) (8-20 weeks of age) and adult cats (1-4 years of age) were imaged by confocal scanning laser ophthalmoscope (cSLO) and spectral domain optical coherence tomography (SD-OCT) using the Spectralis(®) HRA+OCT. Color fundus photography (RetCam II(®) , Clarity Medical Systems, Inc., Pleasanton, CA) was performed after imaging using the Spectralis(®) HRA+OCT. RESULTS: Following retinal cSLO imaging using the 488 nm laser (autofluorescence imaging) in both wild-type kittens and adult cats, the imaged region appeared paler than the adjacent retina that had not been imaged. This change was probably due to retinal bleaching and was fully reversible. Imaging CRX(Rdy+/-) kittens or adults, which had very reduced levels of visual pigments, did not induce the altered fundus appearance. CONCLUSIONS: Those using autofluorescence imaging by cSLO should be aware that it can induce a characteristic pale appearance of the tapetal fundus in the imaged area of normal cats.

The fibrous tapetum of the horse eye.

The tapetum lucidum is a light-reflective tissue in the eyes of many animals. Many ungulates have a fibrous tapetum. The horse has one of the largest eyes of any living animal and also has excellent vision in low-light environments. This study aimed to clarify the macroscopic tapetal shape, relationship between the tapetal thickness and the degree of pigmentation of the retinal pigment epithelium (RPE), spatial relationship between the visual streak and the tapetum, and wavelength of the light reflected from the tapetum in the horse. Macroscopically, weak light revealed the tapetum as a horizontal band located dorsal to and away from the optic disc. The tapetum expanded dorsally as the illumination increased. The tapetal tissue consisted of lamellae of collagen fibrils running parallel to the retinal surface; these spread over almost the entire ocular fundus and were thicker in the horizontal band dorsal to the disc. Only the horizontal band of the tapetum was covered by unpigmented RPE, suggesting that this band reflects light and is responsible for mesopic and scotopic vision. The visual streak was located in the ventral part of the horizontal band, ventral to the thickest part of the tapetum. The wavelength of the light reflected from the horizontal band of the tapetum was estimated from the diameter and interfibrous distance of the collagen fibrils to be approximately 468 nm. Therefore, the light reflected from the tapetum should be more effectively absorbed by rods than by cones, and should not interfere with photopic vision.

High-speed retinal imaging with polarization-sensitive OCT at 1040 nm.

PURPOSE: To demonstrate the ability of a new high-speed polarization-sensitive optical coherence tomography (PS-OCT) system for retinal imaging at 1040 nm. METHODS: A new polarization-sensitive swept source OCT system in the 1 µm wavelength range is used to image the retina of healthy volunteers. The instrument is operated at an A-scan rate of 100 kHz which is about three times faster than previously reported PS-OCT instruments in this wavelength region. The increased imaging speed can be used to record densely sampled volumes of the retina. Moreover, it enables averaging of several B-scans recorded at the same location to obtain high-definition B-scans without the use of an eye tracker. RESULTS: Polarization-sensitive images of healthy volunteers clearly show the retinal pigment epithelium as a depolarizing layer. In addition, the good tissue penetration of the system allows the visualization of the sclera, which is highly birefringent and therefore shows increased image contrast with PS-OCT. CONCLUSIONS: PS-OCT in the 1 µm wavelength region shows similar polarization effects as in the 840 nm wavelength range. The high speed enables averaging of several B-scans to obtain high-definition polarization-sensitive images. The new system provides excellent penetration depth into the choroid and sclera.

Intensity-based modified Doppler variance algorithm: application to phase instable and phase stable optical coherence tomography systems.

The traditional phase-resolved Doppler method demonstrates great success for in-vivo imaging of blood flow and blood vessels. However, the phase-resolved method always requires high phase stability of the system. In phase instable situations, the performance of the phase-resolved methods will be degraded. We propose a modified Doppler variance algorithm that is based on the intensity or amplitude value. Performances of the proposed algorithm are compared with traditional phase-resolved Doppler variance and color Doppler methods for both phase stable and phase instable systems. For the phase instable situation, the proposed algorithm demonstrates images without phase instability induced artifacts. In-vivo imaging of window-chamber hamster skin is demonstrated for phase instable situation with a spectrometer-based Fourier domain OCT system. A microelectromechanical systems (MEMS) based swept source OCT (SSOCT) system is also used to demonstrate the performance of the proposed method in a phase instable situation. The phase stability of the SSOCT system is analyzed. In-vivo imaging of the blood vessel of human skin is demonstrated with the proposed method and the SSOCT system. For the phase stable situation, the proposed algorithm also demonstrates comparable performance with traditional phase-resolved methods. In-vivo imaging of the human choroidal blood vessel network is demonstrated with the proposed method under the phase stable situation. Depth-resolved fine choroidal blood vessel networks are shown.

Anatomical correlates to the bands seen in the outer retina by optical coherence tomography: literature review and model.

PURPOSE: To evaluate the validity of commonly used anatomical designations for the four hyperreflective outer retinal bands seen in current-generation optical coherence tomography, a scale model of outer retinal morphology was created using published information for direct comparison with optical coherence tomography scans. METHODS: Articles and books concerning histology of the outer retina from 1900 until 2009 were evaluated, and data were used to create a scale model drawing. Boundaries between outer retinal tissue compartments described by the model were compared with intensity variations of representative spectral-domain optical coherence tomography scans using longitudinal reflectance profiles to determine the region of origin of the hyperreflective outer retinal bands. RESULTS: This analysis showed a high likelihood that the spectral-domain optical coherence tomography bands attributed to the external limiting membrane (the first, innermost band) and to the retinal pigment epithelium (the fourth, outermost band) are correctly attributed. Comparative analysis showed that the second band, often attributed to the boundary between inner and outer segments of the photoreceptors, actually aligns with the ellipsoid portion of the inner segments. The third band corresponded to an ensheathment of the cone outer segments by apical processes of the retinal pigment epithelium in a structure known as the contact cylinder. CONCLUSION: Anatomical attributions and subsequent pathophysiologic assessments pertaining to the second and third outer retinal hyperreflective bands may not be correct. This analysis has identified testable hypotheses for the actual correlates of the second and third bands. Nonretinal pigment epithelium contributions to the fourth band (e.g., Bruch membrane) remain to be determined.

Assessment of the pigeon (Columba livia) retina with spectral domain optical coherence tomography.

BACKGROUND: To assess the normal retina of the pigeon eye using spectral domain optical coherence tomography (SD-OCT) and establish a normative reference. METHODS: Twelve eyes of six ophthalmologically normal pigeons (Columba livia) were included. SD-OCT images were taken with dilated pupils under sedation. Four meridians, including the fovea, optic disc, red field, and yellow field, were obtained in each eye. The layers, including full thickness (FT), ganglion cell complex (GCC), thickness from the retinal pigmented epithelium to the outer nuclear layer (RPE-ONL), and from the retinal pigmented epithelium to the inner nuclear layer (RPE-INL), were manually measured. RESULTS: The average FT values were significantly different among the four meridians (p < 0.05), with the optic disc meridian being the thickest (294.0 ± 13.9 µm). The average GCC was thickest in the optic disc (105.3 ± 27.1 µm) and thinnest in the fovea meridian (42.8 ± 15.3 µm). The average RPE-INL of the fovea meridian (165.5 ± 18.3 µm) was significantly thicker than that of the other meridians (p < 0.05). The average RPE-ONL of the fovea, optic disc, yellow field, and red field were 91.2 ± 5.2 µm, 87.7 ± 5.3 µm, 87.6 ± 6.5 µm, and 91.4 ± 3.9 µm, respectively. RPE-INL and RPE-ONL thickness of the red field meridian did not change significantly with measurement location (p > 0.05). CONCLUSIONS: Measured data could be used as normative references for diagnosing pigeon retinopathies and further research on avian fundus structure.

Macular thickness varies with age-related macular degeneration genetic risk variants in the UK Biobank cohort.

To evaluate the influence AMD risk genomic variants have on macular thickness in the normal population. UK Biobank participants with no significant ocular history were included using the UK Biobank Resource (project 2112). Spectral-domain optical coherence tomography (SD-OCT) images were taken and segmented to define retinal layers. The influence of AMD risk single-nucleotide polymorphisms (SNP) on retinal layer thickness was analysed. AMD risk associated SNPs were strongly associated with outer-retinal layer thickness. The inner-segment outer segment (ISOS)-retinal pigment epithelium (RPE) thickness measurement, representing photoreceptor outer segments was most significantly associated with the cumulative polygenic risk score, composed of 33 AMD-associated variants, resulting in a decreased thickness (p = 1.37 × 10-67). Gene-gene interactions involving the NPLOC4-TSPAN10 SNP rs6565597 were associated with significant changes in outer retinal thickness. Thickness of outer retinal layers is highly associated with the presence of risk AMD SNPs. Specifically, the ISOS-RPE measurement. Changes to ISOS-RPE thickness are seen in clinically normal individuals with AMD risk SNPs suggesting structural changes occur at the macula prior to the onset of disease symptoms or overt clinical signs.

Interpretation of anatomic correlates of outer retinal bands in optical coherence tomography.

By providing the sectioning capability to differentiate individual retinal layers, optical coherence tomography (OCT) is revolutionizing eye disease diagnosis and treatment evaluation. A better understanding of the hyper- and hypo-reflective bands in retinal OCT is essential for accurate interpretation of clinical outcomes. In this article, we summarize the interpretations of clinical OCT and adaptive optics (AO) OCT (AO-OCT) of the outer retina in the human eye, and briefly review OCT investigation of the outer retina in animal models. Quantitative analysis of outer retinal OCT bands is compared to established parameters of retinal histology. The literature review and comparative analysis support that both inner/outer segment (IS/OS) junction and IS ellipsoid zone nonexclusively contribute to the second band; and OS, OS tips, and retinal pigment epithelium apical processes contribute to the third band in conventional OCT. In contrast, AO-OCT might predominantly detect the IS/OS junction and OS tip signals at the second and third bands due to its improved sectioning capability and possible AO effect on the sensitivities for recording ballistic and diffusive photons from different regions of the outer retina.

Relationship between distribution of tapetum fibrosum and retinal pigment epithelium in the sheep eye.

The tapetum lucidum is a light-reflective device improving visual sensitivity in mesopic vision. There have been few studies on tapetal distribution and its relationship with degree of pigmentation in the retinal pigment epithelium (RPE). In the present study, sheep's eyes were used for macroscopical observation of the tapetum, and then histological sections of the posterior eyecups were made to analyze the distribution of tapetal thickness and degree of pigmentation in the RPE. Macroscopically, with available light, the tapetum was located in the dorsal eye fundus to the optic disc and showed an L-shape with the horizontally elongated nasal part and the dorsally expanded temporal part. In photographs with a flash, the tapetal area expanded and showed a more triangular shape. The tapetum histologically consisted of layers of dense collagen fibers and was thicker in the temporal part than in the nasal part. The maximum tapetal thickness was approximately 70 microm. The histological tapetal area was similar to the tapetal shape with a flash light. The pigmentation of the RPE was divided into three types, nonpigmented, transitional, and pigmented areas. The nonpigmented area was similar to the tapetal shape with available light. It is suggested that approximately 55% of the histological tapetal area is covered with the nonpigmented area and is functional under a natural light condition. The functional tapetal area was similar to the L-shaped high-density area of retinal ganglion cells.

Analysis of the outer retina reconstructed by high-resolution, three-dimensional spectral domain optical coherence tomography.

BACKGROUND AND OBJECTIVE: A retrospective cross-sectional study was conducted to demonstrate an analysis of an outer retinal layer reconstructed by the three-dimensional and high-speed spectral domain optical coherence tomography (SD-OCT) instrument. PATIENTS AND METHODS: New measurement protocols for SD-OCT and methods of analysis and visualization of the individual segmented retinal layer reconstructed by SD-OCT were proposed. Three contour maps representing mutual distances between the basal part of the retinal pigment epithelium, the junction between the inner and outer segments of photoreceptors, and a reference contour representing the shape of a healthy retina were introduced. RESULTS: The analysis of the outer retina was performed on pathological eyes. Three cases of central serous chorioretinopathy, age-related macular degeneration, and acute zonal occult outer retinopathy are demonstrated. CONCLUSION: Three contour maps reconstructed for clinical cases demonstrate high variability of observed patterns depending on analyzed pathology. The authors believe this can help to present OCT data simultaneously in a more comprehensive and convenient way to assist in everyday clinical diagnosis.

Automatic choroidal segmentation in OCT images using supervised deep learning methods.

The analysis of the choroid in the eye is crucial for our understanding of a range of ocular diseases and physiological processes. Optical coherence tomography (OCT) imaging provides the ability to capture highly detailed cross-sectional images of the choroid yet only a very limited number of commercial OCT instruments provide methods for automatic segmentation of choroidal tissue. Manual annotation of the choroidal boundaries is often performed but this is impractical due to the lengthy time taken to analyse large volumes of images. Therefore, there is a pressing need for reliable and accurate methods to automatically segment choroidal tissue boundaries in OCT images. In this work, a variety of patch-based and fully-convolutional deep learning methods are proposed to accurately determine the location of the choroidal boundaries of interest. The effect of network architecture, patch-size and contrast enhancement methods was tested to better understand the optimal architecture and approach to maximize performance. The results are compared with manual boundary segmentation used as a ground-truth, as well as with a standard image analysis technique. Results of total retinal layer segmentation are also presented for comparison purposes. The findings presented here demonstrate the benefit of deep learning methods for segmentation of the chorio-retinal boundary analysis in OCT images.

Associations with photoreceptor thickness measures in the UK Biobank.

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness.