Outer Segment Tips Research Articles

Quantification of intrinsic optical signals in the outer human retina using optical coherence tomography.

Intrinsic optical signals constitute a noninvasive biomarker promising the objective assessment of retinal photoreceptor function. We employed a commercial optical coherence tomography (OCT) system and an OCT signal model for evaluation of optical path length (OPL) changes in the temporal outer retina of five healthy subjects during light adaptation. Data were acquired at 30 time points, in ambient light and during long duration stimulation with white light, and analyzed, employing a signal model based on the sum of seven Gaussian curves corresponding to all relevant anatomical structures of the outer retina. During light stimulation, mean OPL between rod outer segment tips (ROST) and the retinal pigment epithelium (RPE) decreased by 21.4 ± 3.5%. Further, OPL between the external‐limiting membrane (ELM) and the RPE decreased by 5.2 ± 0.9% versus baseline, while OPL between ELM and ROST showed an initial decrease by 2.1 ± 1.6% versus baseline and, thereafter, increased by 2.8 ± 2.1% versus baseline. Thus, the presented approach allowed for assess to dynamic changes in the outer retina in response to light. The change in the subretinal space occurring in the context of light adaptation could be measured using a standard OCT platform and a dedicated signal model.

OCT-based biomarkers for predicting treatment response in eyes with centre-involved diabetic macular oedema treated with anti-VEGF injections: a real-life retina clinic-based study

Background/aimsTo determine whether a combination of baseline and change in spectral domain-optical coherence tomography (SD-OCT)-based biomarkers can predict visual outcomes in eyes with diabetic macular oedema (DMO) treated with antivascular...

Optical Coherence Tomography Biomarkers Predicting Visual Acuity Change after Intravitreal Bevacizumab Injections for Macular Edema Secondary to Branch Retinal Vein Occlusion

Purpose: This study aimed to identify baseline optical coherence tomography (OCT) factors in branch retinal vein occlusion (BRVO) that predict response to bevacizumab injections. Methods: It is a retrospective case series of consecutive patients that underwent OCT at diagnosis, and the central macular thickness (CMT), extent of disorganized retinal inner layers, and outer retinal layers including external limiting membrane, ellipsoid zone (EZ), and cone outer segment tips (COST) were measured. Patients received 3 consecutive monthly injections of bevacizumab followed by pro re nata treatment. The main outcome measure was improvement in best-corrected visual acuity (BCVA) after 1 year. Results are expressed as mean ± SD, and p value <0.05 was considered statistically significant. Results: Overall, 66 eyes of 66 patients, with an average age of 68.5 ± 11.4 years, were included. The mean BCVA improved significantly from 0.68 logMAR at baseline to 0.50 logMAR at 1 year (p < 0.001). Baseline logMAR BCVA (r = 0.41, p < 0.001) and CMT (r = 0.23, p = 0.04) were associated with improvement while EZ (r = −0.24, p = 0.05) and COST (r = −0.32, p = 0.01) disruption with deterioration in BCVA. Conclusion: In patients with naïve BRVO treated with bevacizumab, BCVA improvement at 1 year can be predicted from baseline BCVA, CMT, extent of COST disruption, and EZ disruption.

Analyses of the effects of persistent subretinal fluid on visual/anatomic outcomes according to the type of macular neovascularization during the relaxed treat-and-extend protocol in age-related macular degeneration patients

BackgroundTo analyze the long-term effects of persistent subretinal fluid (SRF) on visual/anatomic outcomes according to the type of macular neovascularization (MNV) during relaxed treat-and-extend regimen with anti-vascular endothelial growth factor (anti-VEGF) agents in age-related macular degeneration (AMD) patients.MethodsPatients with fovea-involving type 1 or type 2 MNV, treated with a relaxed treat-and-extend regimen for 2 years were retrospectively reviewed. Eyes with SRF observed more than three times per year were defined as the ‘persistent SRF (+) group’. To exclude the effects of IRF as much as possible, the eyes with persistent IRF were excluded. The effects of persistent SRF on the best-corrected visual acuity (BCVA), central subfield retinal thickness (CST), and changes in the photoreceptor layer (PRL) thickness and outer retinal bands (external limiting membrane, ellipsoid zone, and cone outer segment tip line) after anti-VEGF injection were analyzed for each MNV type.ResultsSeventy-seven eyes with type 1 MNV (44 eyes with persistent SRF) and 53 eyes with type 2 MNV (18 eyes with persistent SRF) were enrolled. Following a relaxed treat-and-extend regimen with anti-VEGF agents, BCVA and CST improved for each MNV type. In comparison between persistent SRF (+) and persistent SRF (−) group, there were no differences in the amount of change in BCVA and CST between the two groups for each MNV type during 2-year follow-up periods. In addition, there were no differences in the amount of reduction in PRL thickness and state of the outer retinal bands between the two groups for each MNV type.ConclusionsUsing a relaxed treat-and-extend regimen with anti-VEGF agents, persistent SRF did not have additional effects on visual and anatomic outcomes by 2 years, regardless of the MNV type.

Autophagy in the retinal pigment epithelium: a new vision and future challenges.

The retinal pigment epithelium (RPE) is a highly specialized monolayer of polarized, pigmented epithelial cells that resides between the vessels of the choriocapillaris and the neural retina. The RPE is essential for the maintenance and survival of overlying light-sensitive photoreceptors, as it participates in the formation of the outer blood-retinal barrier, phagocytosis, degradation of photoreceptor outer segment (POS) tips, maintenance of the retinoid cycle, and protection against light and oxidative stress. Autophagy is an evolutionarily conserved 'self-eating' process, designed to maintain cellular homeostasis. The daily autophagy demands in the RPE require precise gene regulation for the digestion and recycling of intracellular and POS components in lysosomes in response to light and stress conditions. In this review, we discuss selective autophagy and focus on the recent advances in our understanding of the mechanism of cell clearance in the RPE for visual function. Understanding how this catabolic process is regulated by both transcriptional and post-transcriptional mechanisms in the RPE will promote the recognition of pathological pathways in genetic disease and shed light on potential therapeutic strategies to treat visual impairments in patients with retinal disorders associated with lysosomal dysfunction.

Assessment of a Small Molecule Synthetic Lignan in Enhancing Oxidative Balance and Decreasing Lipid Accumulation in Human Retinal Pigment Epithelia.

Visual function depends on the intimate structural, functional and metabolic interactions between the retinal pigment epithelium (RPE) and the neural retina. The daily phagocytosis of the photoreceptor outer segment tips by the overlaying RPE provides essential nutrients for the RPE itself and photoreceptors through intricate metabolic synergy. Age-related retinal changes are often characterized by metabolic dysregulation contributing to increased lipid accumulation and peroxidation as well as the release of proinflammatory cytokines. LGM2605 is a synthetic lignan secoisolariciresinol diglucoside (SDG) with free radical scavenging, antioxidant and anti-inflammatory properties demonstrated in diverse in vitro and in vivo inflammatory disease models. In these studies, we tested the hypothesis that LGM2605 may be an attractive small-scale therapeutic that protects RPE against inflammation and restores its metabolic capacity under lipid overload. Using an in vitro model in which loss of the autophagy protein, LC3B, results in defective phagosome degradation and metabolic dysregulation, we show that lipid overload results in increased gasdermin cleavage, IL-1 β release, lipid accumulation and decreased oxidative capacity. The addition of LGM2605 resulted in enhanced mitochondrial capacity, decreased lipid accumulation and amelioration of IL-1 β release in a model of defective lipid homeostasis. Collectively, these studies suggest that lipid overload decreases mitochondrial function and increases the inflammatory response, with LGM2605 acting as a protective agent.

Photoreceptor Disc Enclosure Is Tightly Controlled by Peripherin-2 Oligomerization.

Mutations in the PRPH2 gene encoding the photoreceptor-specific protein PRPH2 (also known as peripherin-2 or rds) cause a broad range of autosomal dominant retinal diseases. Most of these mutations affect the structure of the light-sensitive photoreceptor outer segment, which is composed of a stack of flattened "disc" membranes surrounded by the plasma membrane. The outer segment is renewed on a daily basis in a process whereby new discs are added at the outer segment base and old discs are shed at the outer segment tip. New discs are formed as serial membrane evaginations, which eventually enclose through a complex process of membrane remodeling (completely in rods and partially in cones). As disc enclosure proceeds, PRPH2 localizes to the rims of enclosed discs where it forms oligomers which fortify the highly curved membrane structure of these rims. In this study, we analyzed the outer segment phenotypes of mice of both sexes bearing a single copy of either the C150S or the Y141C PRPH2 mutation known to prevent or increase the degree of PRPH2 oligomerization, respectively. Strikingly, both mutations increased the number of newly forming, not-yet-enclosed discs, indicating that the precision of disc enclosure is regulated by PRPH2 oligomerization. Without tightly controlled enclosure, discs occasionally over-elongate and form large membranous "whorls" instead of disc stacks. These data show that the defects in outer segment structure arising from abnormal PRPH2 oligomerization are manifested at the stage of disc enclosure.SIGNIFICANCE STATEMENT The light-sensitive photoreceptor outer segment contains a stack of flattened "disc" membranes that are surrounded, or "enclosed," by the outer segment membrane. Disc enclosure is an adaptation increasing photoreceptor light sensitivity by facilitating the diffusion of the second messenger along the outer segment axes. However, the molecular mechanisms by which photoreceptor discs enclose within the outer segment membrane remain poorly understood. We now demonstrate that oligomers of the photoreceptor-specific protein peripherin-2, or PRPH2, play an active role in this process. We further propose that defects in disc enclosure because of abnormal PRPH2 oligomerization result in major structural abnormalities of the outer segment, ultimately leading to loss of visual function and cell degeneration in PRPH2 mutant models and human patients.

Degradation of Photoreceptor Outer Segments by the Retinal Pigment Epithelium Requires Pigment Epithelium-Derived Factor Receptor (PEDF-R).

PurposeTo examine the contribution of pigment epithelium-derived factor receptor (PEDF-R) to the phagocytosis process. Previously, we identified PEDF-R, the protein encoded by the PNPLA2 gene, as a phospholipase A2 in the retinal pigment epithelium (RPE). During phagocytosis, RPE cells ingest abundant phospholipids and protein in the form of photoreceptor outer segment (POS) tips, which are then hydrolyzed. The role of PEDF-R in RPE phagocytosis is not known.MethodsMice in which PNPLA2 was conditionally knocked out (cKO) in the RPE were generated. Mouse RPE/choroid explants were cultured. Human ARPE-19 cells were transfected with siPNPLA2 silencing duplexes. POSs were isolated from bovine retinas. The phospholipase A2 inhibitor bromoenol lactone was used. Transmission electron microscopy, immunofluorescence, lipid labeling, pulse–chase experiments, western blots, and free fatty acid and β-hydroxybutyrate assays were performed.ResultsThe RPE of the cKO mice accumulated lipids, as well as more abundant and larger rhodopsin particles, compared to littermate controls. Upon POS exposure, RPE explants from cKO mice released less β-hydroxybutyrate compared to controls. After POS ingestion during phagocytosis, rhodopsin degradation was stalled both in cells treated with bromoenol lactone and in PNPLA2-knocked-down cells relative to their corresponding controls. Phospholipase A2 inhibition lowered β-hydroxybutyrate release from phagocytic RPE cells. PNPLA2 knockdown also resulted in a decline in fatty acids and β-hydroxybutyrate release from phagocytic RPE cells.ConclusionsPEDF-R downregulation delayed POS digestion during phagocytosis. The findings imply that the efficiency of RPE phagocytosis depends on PEDF-R, thus identifying a novel contribution of this protein to POS degradation in the RPE.

Optical coherence tomography analyses based segmentation and relative intensity evaluation of outer retinal layers in patients affected with X-linked juvenile retinoschisis.

We aim to provide a description of the optical coherence tomography findings in the outer macula hyperreflective bands of our patients with X-linked juvenile retinoschisis. Also to categorize these changes and to quantitatively and qualitatively correlate their reflectivity levels with visual function. We manually segmented the borders, and depicted relative intensity of the inner segment ellipsoid band, and quantified the volume of edema. The average relative intensity of the ellipsoid zone, ISe band, for the control subject was 14.864, our patient's, with the mild disease was, 28.238 and 34.943 in OD and OS, respectively, and for the patient with severe disease was, 44.442 and 40.154 for OD and OS respectively. Thresholding showed a significant difference in edema volume between mild disease (~20%), and severe form (~50%). Relative intensity analyses are indicative of homogeneity variability. High standard deviation value illustrates the high dispersion of data values and is a safe marker of ellipsoid zone homogeneity. Data suggested that both anatomic and functional characteristic of outer macula hyperreflective bands were notably associated with the pathogenesis cascade in the photoreceptor cells. External limiting membrane line disruption is initiated by the volume of macular edema and followed by disorganization of the three lines in a stepwise pattern, first at the ellipsoid zone, followed by the cone outer segment tips zone and finally at the External limiting membrane.

Three-dimensional composition of the photoreceptor cone layers in healthy eyes using adaptive-optics optical coherence tomography (AO-OCT).

To assess the signal composition of cone photoreceptors three-dimensionally in healthy retinas using adaptive optics optical coherence tomography (AO-OCT). Study population. Twenty healthy eyes of ten subjects (age 23 to 67). Procedures. After routine ophthalmological assessments, eyes were examined using AO-OCT. Three-dimensional volumes were acquired at 2.5° and 6.5° foveal eccentricity in four main meridians (superior, nasal, inferior, temporal). Cone densities and signal compositions were investigated in four different planes: the cone inner segment outer segment junction (IS/OS), the cone outer segment combined with the IS/OS (ISOS+), the cone outer segment tips (COST) and full en-face plane (FEF) combining signals from all mentioned cone layers. Additionally, reliability of a simple semi-automated approach for assessment of cone density was tested. Main outcome measures. Cone density of IS/OS, IS/OS+, COST and FEF. Qualitative depiction and composition of each cone layer. Inter-rater agreement of cone density measurements. Mean overall cone density at all eccentricities was highest at the FEF plane (21.160/mm2), followed by COST (20.450/mm2), IS/OS+ (19.920/mm2) and IS/OS (19.530/mm2). The different meridians and eccentricities had a significant impact on cone density, with lower eccentricity resulting in higher cone densities (p≤.001), which were highest at the nasal, then temporal, then inferior and then superior meridian. Depiction of the cone mosaic differed between all 4 layers regarding signal size and packing density. Therefore, different cone layers showed evident but not complete signal overlap. Using the semi-automated technique for counting of cone signals achieved high inter-rater reliability (ICC > .99). In healthy individuals qualitative and quantitative changes in cone signals are found not only in different eccentricities and meridians, but also within different photoreceptor layers. The variation between cone planes has to be considered when assessing the integrity of cone photoreceptors in healthy and diseased eyes using adaptive optics technology.

Factors Associated with the Clinical Course of Vitreomacular Traction.

Background To analyze the optical coherence tomography (OCT) characteristics as well as the clinical and demographic features to investigate their possible role to the course of vitreomacular traction syndrome. Methods The inclusion criteria were vitreomacular adhesion with traction causing distortion of the retinal architecture, with or without the presence of an epiretinal membrane, regardless of the size of the adhesion; age >18 years; follow-up of at least three months; and adequate quality OCT scan. Measurements of foveal thickness, average macular thickness, macular volume, maximum vertical and horizontal vitreomacular adhesion, nasal and temporal angles of traction, hyaloid hyperreflectivity, the presence of an epiretinal membrane (ERM), and cone outer segment tips detachment were obtained. Results 150 eyes were included in the analysis. 36 eyes (24%) developed complete resolution at the last visit, 19 eyes (12.7%) formed a full-thickness macular hole, and 95 eyes (63.3%) showed no resolution of the traction. Better BCVA at the first visit was associated with an increased likelihood of resolution of the VMT, but increasing age, CMT, and BCVA in the end of the follow-up was associated with a reduction in the likelihood of resolving. Of the other variables that were studied, no statistical significant predictors were identified. Conclusions Better BCVA in the first visit was associated with an increased likelihood of resolution of the VMT that occurred in 24% of our cases. Other factors such as the vertical area of adhesion and the angle of adhesion were not identified as prognostic factors affecting the clinical course of the disease.

Three-dimensional assessment of para- and perifoveal photoreceptor densities and the impact of meridians and age in healthy eyes with adaptive-optics optical coherence tomography (AO-OCT).

An adaptive optics optical coherence tomography (AO-OCT) system is used to assess sixty healthy eyes of thirty subjects (age 22 to 75) to evaluate how the outer retinal layers, foveal eccentricity and age effect the mean cone density. The cone mosaics of different retinal planes (the cone inner segment outer segment junction (IS/OS), the cone outer segment combined with the IS/OS (ISOS+), the cone outer segment tips (COST), and the full en-face plane (FEF)) at four main meridians (superior, nasal, inferior, temporal) and para- and perifoveal eccentricities (ecc 2.5° and 6.5°) were analyzed quantitatively. The mean overall cone density was 19,892/mm2 at ecc 2.5° and 13,323/mm2 at ecc 6.5°. A significant impact on cone density was found for eccentricity (up to 6,700/mm2 between ecc 2.5° and 6.5°), meridian (up to 3,700/mm2 between nasal and superior meridian) and layer (up to 1,400/mm2 between FEF and IS/OS). Age showed only a weak negative effect. These factors as well as inter-individual variability have to be taken into account when comparing cone density measurements between healthy and pathologically changed eyes, as their combined effect on density can easily exceed several thousand cones per mm2 even in parafoveal regions.

Predicting response of ischemic central retinal vein occlusion to bevacizumab injections: 1year follow-up.

To identify baseline optical coherence tomography (OCT) factors in ischemic central retinal vein occlusion (CRVO) that predict response to bevacizumab injections. Patients underwent OCT at diagnosis and the central macular thickness, subretinal fluid width and height as well as the presence of intraretinal cysts were measured. The extent of disorganized retinal inner layers, outer plexiform layer (OPL), external limiting membrane, ellipsoid zone and cone outer segment tips (COST) was recorded. Patients received three consecutive monthly injections of bevacizumab followed by pro re nata treatment. Overall 32 eyes of 32 patients aging 69.4 ± 12.7years were included. In univariate correlational analyses baseline OPL disruption (- 41, p = 0.02), EZ disruption (r = - 0.36, p = 0.05) and COST disruption (r = - 0.37, p = 0.04) correlated with deterioration in BCVA at 1year. Partial least squares demonstrated that the factors most largely associated with deterioration in BCVA were COST disruption and OPL disruption followed by EZ disruption, while worst vision at baseline was associated with improvement in vision. In patients with ischemic CRVO treated with bevacizumab, BCVA improvement at 1year can be partially predicted from baseline OCT measurements by the extent of COST, OPL and EZ disruption.

Membrane trafficking in the retinal pigment epithelium at a glance.

The retinal pigment epithelium (RPE) is a highly specialised pigmented monolayer sandwiched between the choroid and the photoreceptors in the retina. Key functions of the RPE include transport of nutrients to the neural retina, removal of waste products and water from the retina to the blood, recycling of retinal chromophores, absorption of scattered light and phagocytosis of the tips of the photoreceptor outer segments. These functions place a considerable membrane trafficking burden on the RPE. In this Cell Science at a Glance article and the accompanying poster, we focus on RPE-specific adaptations of trafficking pathways. We outline mechanisms underlying the polarised expression of membrane proteins, melanosome biogenesis and movement, and endocytic trafficking, as well as photoreceptor outer segment phagocytosis and degradation. We also briefly discuss theories of how dysfunction in trafficking pathways contributes to retinal disease.

Comparison of SDOCT Scan Types for Grading Disorganization of Retinal Inner Layers and Other Morphologic Features of Diabetic Macular Edema.

PurposeTo assess grading reproducibility of disorganization of the retinal inner layers (DRIL) and other morphologic features of diabetic macular edema (DME) across spectral domain optical coherence tomography (SDOCT) instruments and scan types.MethodsA cross-sectional study enrolled participants with current or recent center-involved DME. In group A (27 eyes), we obtained two Cirrus scans (512 × 128 macular cube [Cube] and high-definition five-line raster [HD 5-Line]) and two Spectralis scans (high-resolution [HR] and high-speed [HS]). In group B, 26 eyes underwent HR scans and Optovue AngioVue (OP) 3 × 3-mm scans. All scans were graded for type and extent of DRIL, intraretinal cysts, cone outer segment tip visibility, and subretinal fluid (SRF).ResultsIn the total cohort, mean central subfield thickness was 342.9 ± 83.4 µm. Intraclass correlations were high for DRIL extent across the four different imaging settings (HR vs. HS, r = 0.93; HR vs. Cube, r = 0.84, HR vs. HD 5-Line, r = 0.76, HR vs. OP, r = 0.87) and ranged from good to excellent for intraretinal cyst and SRF area. There were significantly smaller mean normalized differences between HR/HS scans versus HR and all other scan modalities (HR/HS vs. HR/Cube, P = 0.02; HR/HD 5-Line, P = 0.0005; HR/OP, P < 0.0001).ConclusionsOur data suggest that the reproducibility for SDOCT parameters of DRIL and intraretinal cysts was high across all five SDOCT scan types; thus, evaluation of DRIL is feasible using multiple SDOCT models in eyes with DME.Translational RelevanceDME morphological changes can be evaluated on multiple SDOCT devices with good reproducibility, allowing clinicians and researchers flexibility in DME assessment for clinical care and research.

Changes of outer retinal thickness with increasing age in normal eyes

AIM: To comprehensively investigate the relationship between outer retinal layer thickness and age in normal eyes. METHODS: One hundred normal eyes of 100 subjects who underwent spectral-domain optical coherence tomography (SD-OCT) were included in this retrospective study. The distances between the external limiting membrane (ELM) line and the photoreceptor inner segment/outer segment (IS/OS) line (ELM-IS/OS), the IS/OS line and the cone outer segment tips (COST) line (IS/OS-COST), the COST line and the retinal pigment epithelium (RPE) complex (COST-RPE) and the full retinal thickness (RT) were measured at the fovea and on four quarters. The relationship between thickness and age or sex was then analysed. CONCLUSION: In normal eyes, the RT thickness on the nasal quarter and the ELM-IS/OS thickness were significantly and negatively correlated with age. The IS/OS-COST and COST-RPE thicknesses were not significantly correlated with age or sex.

An anomalous foveal OCT-sign after posterior capsule rupture in cataract surgery: Complicated cataract surgery maculopathy.

To report a series of novel optical coherence tomography (SD-OCT) foveal abnormalities, that we called "T-sign," that were noticed after a complicated cataract surgery with posterior capsule rupture and vitreous loss. Retrospective case series of persistent foveal changes that incurred after anteroposterior vitreo-foveal traction secondary to phacoemulsification in presence of posterior capsule rupture. The study included three eyes of three patients that incurred in complicated cataract surgery and intraoperative vitreo-foveal traction. During 8-month follow-up period peculiar abnormalities in fundus examination and in OCT scans were reported in all cases. Phacoemulsification in presence of posterior capsule rupture could induce a vitreo-foveal strain that could be transmitted to the cone outer segment tips (COST line) and inner-outer segment (IS/OS) junction. This focal stress is liable for "T-sign," a persistent SD-OCT abnormality that induce a visual impairment and a slight metamorphopsia in the fixation point. All over the world, more than 9.5 million cataract surgeries are completed each year.1 During surgery, many intraoperative complications could occur, and capsule rupture with vitreous loss is a frequent event. Phacoemulsification in presence of a wide posterior capsule rupture and vitreo-macular adhesion could induce a typical modification of the foveal structure and a permanent visual impairment.

The cell biology of the retinal pigment epithelium.

The retinal pigment epithelium (RPE), a monolayer of post-mitotic polarized epithelial cells, strategically situated between the photoreceptors and the choroid, is the primary caretaker of photoreceptor health and function. Dysfunction of the RPE underlies many inherited and acquired diseases that cause permanent blindness. Decades of research have yielded valuable insight into the cell biology of the RPE. In recent years, new technologies such as live-cell imaging have resulted in major advancement in our understanding of areas such as the daily phagocytosis and clearance of photoreceptor outer segment tips, autophagy, endolysosome function, and the metabolic interplay between the RPE and photoreceptors. In this review, we aim to integrate these studies with an emphasis on appropriate models and techniques to investigate RPE cell biology and metabolism, and discuss how RPE cell biology informs our understanding of retinal disease.

ATTENUATION OUTER RETINAL BANDS ON OPTICAL COHERENCE TOMOGRAPHY FOLLOWING MACULAR EDEMA: A Possible Manifestation of Photoreceptor Misalignment.

Macular edema is a common retinal disease which may leave important anatomical and functional sequelaes. Directional fundus imaging consists of comparing on- and off-axis images to reveal angle-dependent reflectance properties of fundus structures, which may be related to misaligned photoreceptors. Here, we analyzed directional optical coherence tomography (OCT) and flood-illumination adaptive optics ophthalmoscopy images to detect evidence of misaligned photoreceptors following macular edema. Transversal, observational study. Nine patients having recovered a normal macular profile after macular edema due to retinal vein occlusion were included. For each patient, a reference OCT scan (i.e., with the incident beam normal to the fovea) was acquired, and off-axis scans were then acquired by laterally shifting the entry pupil. In addition, in four of these eyes, directional adaptive optics ophthalmoscopy documented the directional variations of cone metrics. Included patients comprised two women and seven men (age range, 19-76 years). Reference OCT scans showed patchy attenuation of the cone outer segment tips and to a lesser extent of the inner segment/outer segment lines in all, but two eyes; these. Increased intensity of the cone outer segment tips and inner segment/outer segment lines could be observed on off-axis scans. Accordingly, fusion images showed 66% average reduction of the length of cone outer segment tips attenuation. In two cases, although reference scans showed continuity of outer bands, focal attenuation was evidenced in off-axis images. Directional adaptive optics ophthalmoscopy imaging showed a strong directional variability of cone counts in these areas, ranging from near absence to roughly two-third of reference values. In each case, directional variations of cone counts paralleled those of the reflectance of outer bands. After macular edema, focal attenuations of the inner segment/outer segment and of the cone outer segment tips lines may be present on OCT. These areas may show a strong directional variability by both OCT and adaptive optics ophthalmoscopy, suggesting that misaligned photoreceptor outer segments contribute to such features. The evaluation of outer retinal damage following macular edema should therefore take into account the optical Stiles-Crawford effect to disambiguate missing from misaligned cones.

Interpretation of OCT and OCTA images from a histological approach: Clinical and experimental implications.

Optical coherence tomography (OCT) and OCT angiography (OCTA) have been a technological breakthrough in the diagnosis, treatment, and follow-up of many retinal diseases, thanks to its resolution and its ability to inform of the retinal state in seconds, which gives relevant information about retinal degeneration. In this review, we present an immunohistochemical description of the human and mice retina and we correlate it with the OCT bands in health and pathological conditions. Here, we propose an interpretation of the four outer hyperreflective OCT bands with a correspondence to retinal histology: the first and innermost band as the external limiting membrane (ELM), the second band as the cone ellipsoid zone (EZ), the third band as the outer segment tips phagocytosed by the pigment epithelium (PhaZ), and the fourth band as the mitochondria in the basal portion of the RPE (RPEmitZ). The integrity of these bands would reflect the health of photoreceptors and retinal pigment epithelium. Moreover, we describe how the vascular plexuses vary in different regions of the healthy human and mice retina, using OCTA and immunohistochemistry. In humans, four, three, two or one plexuses can be observed depending on the distance from the fovea. Also, specific structures such as vascular loops in the intermediate capillary plexus, or spider-like structures of interconnected capillaries in the deep capillary plexus are found. In mice, three vascular plexuses occupy the whole retina, except in the most peripheral retina where only two plexuses are found. These morphological issues should be considered when assessing a pathology, as some retinal diseases are associated with structural changes in blood vessels. Therefore, the analysis of OCT bands and OCTA vascular plexuses may be complementary for the diagnosis and prognosis of retinal degenerative processes, useful to assess therapeutic approaches, and it is usually correlated to visual acuity.