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We reevaluate acute retinal pigment epitheliitis (ARPE) first described by Krill and Deutman in 1972, integrating a meticulous literature review with advanced multimodal imaging analyses. Our review included 98 eyes from 86 published cases diagnosed with ARPE. We scrutinized ARPE's clinical presentations, variability, and imaging characteristics, revealing that a large majority (90 %) of cases previously diagnosed as ARPE align more closely with other retinal disorders based on modern diagnostic criteria and imaging techniques. Only a small fraction (5 eyes) did not fit into any known categories, casting doubt on ARPE's distinct existence. This underscores the critical role of multimodal imaging in redefining our understanding of macular diseases and challenges the historical classification of ARPE as a unique clinical entity. [ABSTRACT FROM AUTHOR]

This study aimed to assess outer retinal layer (ORL), retinal pigment epithelium (RPE), choroid (Ch) and choriocapillaris (CC) modifications in adolescents with long-lasting (>10 years) type 1 diabetes (T1D) without (noDR) or with diabetic retinopathy (DR). ORL and RPE thickness were measured at optical coherence tomography (OCT) macular scans. Vascular parameters of Ch and CC were quantified after elaboration of macular OCT-angiography (OCTA) images. Insulin dose and auxological and metabolic parameters were correlated with OCT and OCTA findings in patients. ORL thickness was higher in DR eyes than in noDR and healthy controls (HC), and RPE thickness was higher in noDR and DR eyes than in HC, with statistical significance for some sectors in noDR versus HC. No OCTA parameters of CC and Ch differed among groups, and no significant correlation was observed with auxological and metabolic parameters. In conclusion, ORL and RPE were both increased in adolescents with long-lasting T1D. Such changes were not associated with insulin dose and glycemia control, nor to any choroid or choriocapillaris flow change clinically detectable at OCTA, and they could be potential imaging biomarkers of disease progression. [ABSTRACT FROM AUTHOR]

Purpose: To compare outer macular and retinal thickness in the circumpapillary area in unilateral advanced glaucomatous eyes to the normal or mild glaucomatous fellow eyes. Methods: Seventy-eight eyes of 39 patients with unilateral advanced glaucoma (mean deviation (MD) worse than –12.00 dB based on visual field 24-2) were included in this cross-sectional study as the cases. The healthy or mild glaucomatous fellow eyes were enrolled as the control group. All eyes underwent optical coherence tomography of the macula and circumpapillary retina by Topcon DRI Triton (Topcon, Tokyo, Japan). Ganglion cell layer 2+ was considered as the inner retina. Total retinal thickness minus the thickness of the inner retina was considered as the outer retina. Comparison between groups was done by paired-sample sign test. The correlation between structural and functional parameters was evaluated by a partial correlation coefficient. Results: Seventeen (43.6%), 15 (38.5%), and 7 (17.9%) patients had pseudoexfoliation, primary angle-closure, and primary open-angle glaucoma, respectively. The mean age was 62.69 ± 12.00 years. Thirty-three (84.6%) patients were male. The outer retinal thickness in the circumpapillary area was higher in temporal, superior, and inferior quadrants (p < 0.05). The outer macula in different parafoveal and perifoveal quadrants was also thicker (p < 0.05). Average outer parafoveal thickness in the case group had a significant negative correlation with MD (r = –0.339; p = 0.035). Conclusion: Advanced glaucomatous eyes had a thicker outer retina in the macula and circumpapillary area. There was a significant negative correlation between outer perifoveal thickness and MD. [ABSTRACT FROM AUTHOR]

The choroid supplies blood to the outer retina. We quantified outer retinal and choroidal parameters to understand better the pathogenesis of diabetic retinopathy (DR) and diabetic macular edema (DME). The retrospective cross-sectional single-center study included 210 eyes from 139 diabetic patients and 76 eyes from 52 healthy controls. Spectral-domain optical coherence tomography (OCT) was carried out with a Spectralis HRA + OCT imaging device. The outer retinal layer (ORL), outer nuclear layer (ONL), and choroidal thicknesses were assessed along with the choroidal vascularity index (CVI). The presence of DR, whether with DME or without, was associated with choroidal thinning (p < 0.001). Compared with the controls, patients with DR without DME presented with lower ORL and ONL thickness (p < 0.001), whereas those with DR and DME had higher values of both parameters (p < 0.001). Significant correlations between outer retinal and choroidal parameters were found only in patients with DR without DME (ORL with choroidal thickness: p = 0.003, rho = 0.34; ORL with CVI: p < 0.001, rho = 0.49, ONL with CVI: p < 0.027, rho = 0.25). No correlations between choroidal and outer retinal parameters were observed in the controls and patients with DR and concomitant DME. Aside from diabetic choroidopathy, other pathogenic mechanisms seem to predominate in the latter group. [ABSTRACT FROM AUTHOR]

Objective: To quantitatively and qualitatively characterize the retinal optical coherence tomographic features of sudden acquired retinal degeneration syndrome (SARDS) and SARDS suspect dogs. Animals studied: Fourteen SARDS affected dogs, 11 age‐, breed‐, and sex‐matched control dogs, and two SARDS suspect dogs. Procedures: Spectral‐domain optical coherence tomography (OCT) images were used to evaluate the quantitative features, including thickness, intereye asymmetry, and longitudinal changes in retinal layer thickness and the qualitative features, including retinal architecture and vitreous haze. Results: Mean outer retinal layer thickness (ORT), outer nuclear layer thickness (ONL), and photoreceptor layer thickness (PRL) were significantly lower in the SARDS group, whereas mean inner retinal layer thickness was significantly higher in the SARDS group than in the control group. While thickness values of all retinal layers did not differ significantly between paired eyes in each group, the absolute intereye asymmetries in the ORT (p <.0001), ONL (p =.008), and PRL (p <.0001) were significantly higher in the SARDS group than in the control group. Some SARDS patients and SARDS suspects had a greater PRL than the control group, and serial OCT evaluation showed an increase in PRL in one SARDS suspect. Vitreous haze severity was greater in the SARDS group than in the control group (vitreous relative intensity, p =.030). Conclusions: We described the OCT features of SARDS patients and suspects. In particular, PRL thickening in the SARDS suspects might indicate an early change in SARDS. Although further studies are needed, this finding might provide new insights into the pathogenesis of SARDS. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the outer retinal band thickness and choriocapillaris (CC) visibility in four distinct retinal regions in dogs and cats imaged with spectral domain optical coherence tomography (SD‐OCT). To attempt delineation of a fovea‐like region in canine and feline SD‐OCT scans, aided by the identification of outer retinal thickness differences between retinal regions. Methods: Spectralis® HRA + OCT SD‐OCT scans from healthy, anesthetized dogs (n = 10) and cats (n = 12) were analyzed. Scanlines on which the CC was identifiable were counted and CC visibility was scored. Outer nuclear layer (ONL) thickness and the distances from external limiting membrane (ELM) to retinal pigment epithelium/Bruch's membrane complex (RPE/BM) and ELM to CC were measured in the area centralis (AC), a visually identified fovea‐like region, and in regions superior and inferior to the optic nerve head (ONH). Measurements were analyzed using a multilevel regression. Results: The CC was visible in over 90% of scanlines from dogs and cats. The ONL was consistently thinnest in the fovea‐like region. The outer retina (ELM‐RPE and ELM‐CC) was thickest within the AC compared with superior and inferior to the ONH in dogs and cats (p <.001 for all comparisons). Conclusions: The CC appears a valid, albeit less than ideal outer retinal boundary marker in tapetal species. The AC can be objectively differentiated from the surrounding retina on SD‐OCT images of dogs and cats; a fovea‐like region was identified in dogs and its presence was suggested in cats. These findings allow targeted imaging and image evaluation of these regions of retinal specialization. [ABSTRACT FROM AUTHOR]

X-linked retinoschisis (XLRS) is an early onset degenerative retinal disease characterized by cystic lesions in the middle layers of the retina. These structural changes are accompanied by a loss of visual acuity and decreased contrast sensitivity. XLRS is caused by mutations in the gene Rs1 which encodes the secreted protein Retinoschisin 1. Young Rs1 -mutant mouse models develop key hallmarks of XLRS including intraretinal schisis and abnormal electroretinograms. The electroretinogram (ERG) comprises activity of multiple cellular generators, and it is not known how and when each of these is impacted in Rs1 mutant mice. Here we use an ex vivo ERG system and pharmacological blockade to determine how ERG components generated by photoreceptors, ON-bipolar, and Müller glial cells are impacted in Rs1 mutants and to determine the time course of these changes. We report that ERG abnormalities begin near eye-opening and that all ERG components are involved. • X-linked retinoschisis (XLRS) visual response deficits appear near eye-opening. • Photoreceptors are the first cells with an observable XLRS phenotype. • XLRS has a top-down developmental progression mirroring photoreceptors deficits. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to generate baseline optical coherence tomography (OCT) measurements of retinal thickness in female Beagles and to determine how these are affected by meridian, eccentricity, and age. Methods: Twenty‐three female Beagles, including six puppies (<6 months old), six mature (1.8‐8.2 years old), and 11 elderly dogs (>11 years old) were studied. Both retinas of each dog were scanned (in 4 principal meridians) using the Heidelberg Spectralis following ophthalmic examination, refraction, and sedation. In each eye and each meridian, total retinal, outer retinal, and nerve fiber layer (NFL) thickness were measured from the disc rim up to 6 mm peripherally. Results: The canine retina is thickest dorsally and thinnest ventrally. Total retinal, outer retinal, and NFL thickness decrease progressively and significantly as a function of eccentricity. The greatest eccentricity‐dependent thinning occurs dorsally. This thinning is due mostly to NFL tapering, while the eccentricity‐dependent change in outer retinal thickness is more moderate, especially in the lateral meridian, possibly due to the presence of the visual streak. The retina is thickest in puppies, but there were no significant differences between mature and elderly dogs. Conclusions: Our results provide normative values for total, outer, and inner retinal thickness in female dogs and may facilitate OCT use in the diagnosis of canine glaucoma and inherited retinopathies. [ABSTRACT FROM AUTHOR]

Lamellar macular holes present distinct morphological features including tractional or non-tractional epimacular membranes, foveal tissue alterations, defects of the outer retinal layers, or a separation of the retinal layers. At present, degenerative lamellar holes are differentiated from tractional holes based on the morphological characteristics seen in OCT. The current treatment approach is based on this gross differentiation. Considering the recent developments in high-resolution imaging, this classification needs to be revisited since morphological features may present simultaneously, making it difficult to separate these entities. In addition, a revisited classification may be of value to better standardize the indication for surgical treatment. [ABSTRACT FROM AUTHOR]

Aims: To investigate the function of localized retinal areas in highly selected type 1 diabetes mellitus patients (DM1) with no or mild signs of diabetic retinopathy (NO DR and NPDR, respectively) and its correlation with age, diabetes duration and glycemic control.Methods: Multifocal electroretinograms (mfERG) were recorded in 35 eyes of 18 NO DR patients and 38 eyes of 19 NPDR patients. Thirty-one eyes of 17 normal subjects were enrolled as controls. N1-P1 response amplitude densities (RADs) and P1 implicit times (ITs) from isolated (R1: 0°-2.5°, R2: 2.5°-5°, R3: 5°-10°) and combined (R1 + R2, R2 + R3 and R1 + R2 + R3) annular rings and from four retinal sectors (nasal, N; temporal, T; superior, S and inferior, I) with increasing eccentricities up to 10° (S1, S2, S3, S1 + S2, S1 + S2 + S3) were measured. The statistical differences between DM1 groups and controls were tested by ANOVA. The electrophysiological data were correlated with age, duration of diabetes and glycated hemoglobin (HbA1c) level using the Pearson’s test.Results: MfERG RADs, but not ITs, from all isolated and combined rings and sectors up to 10° of foveal eccentricity were statistically different between DM1 groups compared to controls. No significant differences were found between NO DR and NPDR patients. The mfERG abnormalities of the central retinal areas were correlated significantly with age in both DM1 groups and with diabetes duration mainly in NPDR group.Conclusions: In DM1 patients, localized retinal dysfunction, described by reduced mfERG RAD, can be observed also in the absence of clinical signs of DR and it is related to aging. [ABSTRACT FROM AUTHOR]

To report a unique case of intraocular inflammation and outer retinal changes in a patient with coronavirus disease (COVID-19). A 57-year-old woman was seen 12 days after COVID-19 symptoms onset confirmed by positive IgM and IgG serological tests. No anterior chamber cells were seen. Color fundus photograph showed a yellowish lesion within the macular area, and fluorescein angiography revealed hyperfluorescence on the topography of the macular lesion in both eyes. Spectral-domain optical coherence tomography demonstrated hyperreflective pinpoints at the level of posterior vitreous hyaloid, corresponding to vitritis, hyperreflective lesions at the level of inner plexiform and ganglion cell layers, and disruption of the ellipsoid zone. COVID-19 is known to affect the inner retinal layers. The current case not only supports but also adds a vitreal and an outer retinal layer involvement that might also be caused by this infectious disease. [ABSTRACT FROM AUTHOR]

Purpose: To determine the impact of metamorphopsia on quality of life after successful retinal detachment (RD) surgery and to determine which retinal changes are related to the most severe distortions. Design: This was a prospective, observational, consecutive study. Methods: The study included 58 eyes of 58 consecutive patients who underwent successful RD surgery. At 6 months postoperatively, the incidence and severity of metamorphopsia were assessed by a quality-of-life questionnaire. Microstructure retinal changes were studied with spectral domain optical coherence tomography (OCT). The questionnaire score was compared with pre- and postoperative OCT findings. Results: Overall, 20 patients (34.5%) had metamorphopsia. Outer retinal folds (ORFs) and the macular status before surgery, together with postoperative ORFs and decrease in ellipsoid and/or interdigitation photoreceptor zone reflectivity, were identified as risk factors of developing metamorphopsia (relative risk, 1.7–4.8). The most severe visual distortions were associated with ORFs. Conclusion: Metamorphopsia is a frequent occurrence after RD surgery and its impact on patients' quality of life appears to be limited. While it may be difficult to prevent photoreceptor loss occurring after surgery, limiting postoperative ORFs may be helpful in reducing their incidence. [ABSTRACT FROM AUTHOR]

Purpose: To investigate foveal avascular zone area, macular vascular density, choroidal thickness, and outer retina and choriocapillaris flow in myopic eyes by OCT angiography.Methods: Automated macular maps and flow calculations were retrospectively evaluated in 42 myopic and in 40 control eyes.Results: Myopic eyes presented lower whole superficial vessel density (46.4 ± 4.9 vs. 51.6 ± 3.6%, P < 0.0001) and higher flow area in the outer retina (1.3 ± 0.2 vs. 1.1 ± 0.3 mm2, P = 0.0012). Between the myopic and non-myopic eyes, no significant differences could be detected in the choriocapillaris perfusion area (1.9 ± 0.07 vs. 1.9 ± 0.05 mm2, respectively; P = 0.55) and in the foveal avascular zone area (0.23 ± 0.1 vs. 0.26 ± 0.1 mm2, respectively; P = 0.12). The spherical correction positively correlated with superficial vessel density and negatively correlated with outer retina perfusion (P ≤ 0.0021). The superficial vessel density and the local retinal thickness positively correlated at all macular locations (P < 0.005), especially in the foveal region (P < 0.0001).Conclusions: Eyes with high myopia present reduced superficial vascular density and increased outer retina flow. Superficial vascular density and retinal thickness appear to be significantly correlated. [ABSTRACT FROM AUTHOR]

The first synapse of the retina plays a fundamental role in the visual system. Due to its importance, it is critical that it encodes information from the outside world with the greatest accuracy and precision possible. Cone photoreceptor axon terminals contain many individual synaptic sites, each represented by a presynaptic structure called a 'ribbon'. These synapses are both highly sophisticated and conserved. Each ribbon relays the light signal to one ON cone bipolar cell and several OFF cone bipolar cells, while two dendritic processes from a GABAergic interneuron, the horizontal cell, modulate the cone output via parallel feedback mechanisms. The presence of these three partners within a single synapse has raised numerous questions, and its anatomical and functional complexity is still only partially understood. However, the understanding of this synapse has recently evolved, as a consequence of progress in understanding dendritic signal processing and its role in facilitating global versus local signalling. Indeed, for the downstream retinal network, dendritic processing in horizontal cells may be essential, as they must support important functional operations such as contrast enhancement, which requires spatial averaging of the photoreceptor array, while at the same time preserving accurate spatial information. Here, we review recent progress made towards a better understanding of the cone synapse, with an emphasis on horizontal cell function, and discuss why such complexity might be necessary for early visual processing. [ABSTRACT FROM AUTHOR]

The unconventional myosin VI, a member of the actin-based motor protein family of myosins, is expressed in the retina. Its deletion was previously shown to reduce amplitudes of the a- and b-waves of the electroretinogram. Analyzing wild-type and myosin VI-deficient Snell's Waltzer mice in more detail, the expression pattern of myosin VI in retinal pigment epithelium, outer limiting membrane, and outer plexiform layer could be linked with differential progressing ocular deficits. These encompassed reduced a-waves and b-waves and disturbed oscillatory potentials in the electroretinogram, photoreceptor cell death, retinal microglia infiltration, and formation of basal laminar deposits. A phenotype comprising features of glaucoma (neurodegeneration) and age-related macular degeneration could thus be uncovered that suggests dysfunction of myosin VI and its variable cargo adaptor proteins for membrane sorting and autophagy, as possible candidate mediators for both disease forms. [ABSTRACT FROM AUTHOR]

Purpose/aim: The aim of the study was to investigate the long-term functional changes that may occur in the retina and visual cortex in a rat ocular hypertension (OHT) model of glaucoma, used in our lab for treatment studies, using electroretinogram (ERG) and visual-evoked potential (VEP) cortical recordings in order to test the hypothesis that experimental glaucoma has differential retinal and central effects. Materials and methods: Experimental glaucoma was induced unilaterally in Dark Agouti rats using hypertonic saline injection into the episcleral veins. After 3, 8, 16 and 26 weeks, ERGs and VEPs were recorded under scotopic conditions using brief full-field white flashes (10 μcd s m−2 to 10.4 cd s m−2) and under photopic conditions using a rod-adapting background and white light flashes (0.13-10.4 cd s m−2). Results: At 16 and 26 weeks after OHT induction, there was a significant reduction in the amplitudes of the a- (50% and 30% of unoperated eye values, respectively) and b-waves (55% and 40%, respectively) of the scotopic ERG and the b-waves of the photopic ERG (55% and 45%, respectively) in the glaucomatous eyes. However, no significant changes in the VEPs simultaneously recorded over the visual cortex were seen at any of the time points. Conclusions: The reductions in ERG amplitudes suggest that this model of glaucoma not only causes retinal ganglion cell (RGC) degeneration but also degeneration of the outer retinal cells, and this was confirmed by histology showing a reduction in the outer retinal layers in the glaucomatous eyes. Cortical VEPs did not show detrimental effects suggesting that the retinal damage in this model was not extensive enough to be detected with the VEP methods used or that there could be central compensation in this model of glaucoma. [ABSTRACT FROM AUTHOR]

Background: Extramacular branch retinal vein occlusion (BRVO) occasionally causes serous macular detachment. We studied the movement of extravasated fluid from BRVO lesions to the submacular space. Methods: We examined nine eyes from nine patients with serous retinal detachment caused by extramacular BRVO. In addition to a comprehensive ophthalmic examination, optical coherence tomography was performed in all nine eyes. Six of the patients also underwent fluorescein angiography. Results: Visual acuity ranged from 0.03 to 0.9 (median 0.5). All nine eyes showed localized macular detachment and retinal edema which extended from the extramacular BRVO to the macula. Fluorescein angiography revealed dye leakage in the extramacular area but no macular leakage in the six eyes examined. Optical coherence tomography revealed serous retinal detachment in the macula and intraretinal swelling, with low reflectivity in the outer retina extending from the distant BRVO toward the detached macula in all nine eyes. Six eyes were treated with laser photocoagulation, covering the entire area of BRVO, and the other three eyes were treated with intravitreal bevacizumab. Serous retinal detachment and retinal swelling resolved within 3 months of treatment in all nine eyes. Conclusion: Distant retinal vascular leakage appears to diffuse through the outer retina to the macula, then permeate into the subretinal space. [ABSTRACT FROM AUTHOR]

The retina still poses many structural and computational questions. Structurally, for example, it is not yet clear how many distinct horizontal cell (HC) types the primate retina contains and what the exact patterns of connections between photoreceptors (PRs) and HCs consist of. Computationally, it is not yet clear, for instance, what functions are present and how they are being implemented. This paper proposes a model (a linear recurrent neural network defined by 31 parameters) of the outer retina and an optimization methodology that hopes to shed some light on these questions. This paper shows that a simplified model of the outer retina can implement several low-level visual functions involving the modulation of noise, brightness, contrast, saturation, and even color. The results demonstrate that contrast control functions can be implemented with a minimum of two HC types and that spectral specificity between PRs and HCs is a common and important feature. It is also shown that several different spectrally specific patterns can emerge in order to implement the same function. One interesting microcircuit that naturally emerged from our experiments involves nonblurry denoising via interchromatic gap junctions and compensatory resaturation via HC circuits, a strategy that we hypothesize to exist in some biological retinae. [ABSTRACT FROM PUBLISHER]

Bone spicule pigments (BSP) are a hallmark of retinitis pigmentosa (RP). In this study, we examined the process of BSP formation in the rhodopsin knockout ( rho -/-) mouse, a murine model for human RP. In rho -/- mice from 2 to 16 months of age, representing the range from early to late stages of degeneration, retinal sections and whole mounts were examined morphologically by light and electron microscopy. The results were compared to scanning laser ophthalmoscopy of BSP degeneration in human RP. After the loss of all photoreceptor cells in rho-/- mice, the outer retina successively degenerated, leading to approximation and finally a direct contact of inner retinal vessels and the retinal pigment epithelium (RPE). We could show that it was the event of proximity of retinal vessel and RPE that triggered migration of RPE cells along the contacting vessels towards the inner retina. Ultrastructurally, these mislocalized RPE cells partially sealed the vessels by tight junction linkage and deposited extracellular matrix perivascularly. Also, the vascular endothelium developed fenestrations similar to the RPE-choroid interface. In whole mounts, the pigmented cell clusters outlining retinal capillaries correlated well with BSPs in human RP. The structure of the inner retina remained well preserved, even in late stages. The Rho -/- mouse is the first animal model that depicts all major pathological changes, even in the late stages of RP. Using the rho -/- mouse model we were able to analyze the complete dynamic process of BSP formation. Therefore we conclude that: (1) In rho -/- retinas, BSPs only form in areas devoid of photoreceptors; (2) Direct contact between inner retinal vessels and RPE appears to be a major trigger for migration of RPE cells; (3) The distribution of the RPE cells in BSPs reflects the vascular network at the time of formation. The similarity of the disease process between mouse and human and the possibility to study all consecutive steps of the course of the disease makes the rho -/- mouse valuable for further insights in the dynamics of BSP formation in human RP. [ABSTRACT FROM AUTHOR]

Abstract: We tested whether calcium-induced calcium release (CICR) contributes to synaptic release from rods in mammalian retina. Electron micrographs and immunofluorescent double labeling for the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2) and synaptic ribbon protein, ribeye, showed a close association between ER and synaptic ribbons in mouse rod terminals. Stimulating CICR with 10 μM ryanodine evoked Ca2+ increases in rod terminals from mouse retinal slices visualized using confocal microscopy with the Ca2+-sensitive dye, Fluo-4. Ryanodine also stimulated membrane depolarization of individual mouse rods. Inhibiting CICR with a high concentration of ryanodine (100 μM) reduced the electroretinogram (ERG) b-wave but not a-wave consistent with inhibition of synaptic transmission from rods. Ryanodine (100 μM) also inhibited light-evoked voltage responses of individual rod bipolar cells (RBCs) and presumptive horizontal cells recorded with perforated patch recording techniques. A presynaptic site of action for ryanodine''s effects is further indicated by the finding that ryanodine (100 μM) did not alter currents evoked in voltage-clamped RBCs by puffing the mGluR6 antagonist, (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG), onto bipolar cell dendrites in the presence of the mGluR6 agonist l-(+)-2-amino-4-phosphonobutyric acid (l-AP4). Ryanodine (100 μM) also inhibited glutamatergic outward currents in RBCs evoked by electrical stimulation of rods using electrodes placed in the outer segment layer. Together, these results indicate that, like amphibian retina, CICR contributes to synaptic release from mammalian (mouse) rods. By boosting synaptic release in darkness, CICR may improve the detection of small luminance changes by post-synaptic neurons. [Copyright &y& Elsevier]

Purpose: To investigate the safety of the thrombolytic agent, Tenecteplase to the outer retina in pig eyes. Methods: Tenecteplase (50 µg) was injected into the subretinal space in one eye while the fellow eye received balanced salt solution. At 24 h, 1 week and 9 weeks the eyes were examined by indirect ophthalmoscopy and photographed. Animals were killed at 9 weeks, eyes enucleated and processed for light and transmission electron microscopy. Three locations within the area of the injection bleb were analysed. Results: Retinal pigment epithelial defects, which appeared to be iatrogenic and confined to the injection site, were seen in most of the treated and control eyes. There was no significant difference in the degree of retinal damage between the two groups of eyes at the three sites examined ( P > 0.05). Conclusion: Fifty micrograms of Tenecteplase appears to be a safe dose with no evidence of toxicity to the outer retina and may have a potential role in the treatment of submacular haemorrhage. [ABSTRACT FROM AUTHOR]

Abstract: Nitric oxide (NO) can play either a neuroprotective or a neurotoxic role in diverse neurodegenerative conditions. This study investigated the differential expression of neuronal nitric oxide synthase (nNOS) in the streptozotocin-induced diabetic rat retina to clarify the involvement of NO produced from neurons in the early pathogenesis of diabetic retinopathy. A decrease in thickness of the outer retina was evident at 12 and 24 weeks after onset of diabetes. nNOS was immunolocalized in two subtypes of amacrine cells, displaced amacrine cells and in some bipolar cells in the normal retinas. The densities of each type of nNOS-expressing neuron showed no significant differences in the diabetic retinas with the exception of the bipolar cells. The numbers of nNOS bipolar cells at 12 weeks of diabetes increased threefold, showing dendritic polarity of nNOS expression. Protein levels of nNOS increased throughout the diabetic retinas reaching a peak value at 24 weeks of diabetes. Thus, diabetes up-regulates the expression of nNOS in bipolar cells, and NO from these cells may aggravate the degeneration of the outer retina in the diabetic retinas. [Copyright &y& Elsevier]

A variety of disease processes can affect the retina and/or the optic nerve, including vascular or ischemic disease, inflammatory or infectious disease, and degenerative disease. These disease processes may selectively damage certain parts of the retina or optic nerve, and the specific areas that are damaged may have implications for the design of potential therapeutic visual prosthetic devices. Outer retinal diseases include age-related macular degeneration, pathologic myopia, and retinitis pigmentosa. Although the retinal photoreceptors may be lost, the inner retina is relatively well-preserved in these diseases and may be a target for retinal prosthetic devices. Inner retinal diseases include retinal vascular diseases such as diabetic retinopathy, retinal venous occlusive disease, and retinopathy of prematurity. Other retinal diseases such as ocular infections (retinitis, endophthalmitis) may affect all retinal layers. Because the inner retinal cells, including the retinal ganglion cells, may be destroyed in these diseases (inner retinal or whole retinal), prosthetic devices that stimulate the inner retina may not be effective. Common optic nerve diseases include glaucoma, optic neuritis, and ischemic optic neuropathy. Because the ganglion cell nerve fibers themselves are damaged, visual prosthetics for these diseases will need to target more distal portions of the visual pathway, such as the visual cortex. Clearly, a sound understanding of retinal and optic nerve disease pathophysiology is critical for designing and choosing the optimal visual prosthetic device. [ABSTRACT FROM AUTHOR]

Large animal model of optic nerve crush (ONC) plays an important role in translating novel therapeutic strategies developed in rodent model to clinical application. Due to the poor accessibility of the optic nerve (ON) in humans and large animals, lateral orbitotomy is needed to expose the retrobulbar ON. This study was to explore the effects of ONC and ON exposure with lateral orbitotomy (sham surgery) on the outer retinal function and structure in goats by using standard flash electroretinogram (FERG) and spectral-domain optical coherence tomography (SD-OCT). We found that ONC led to a transient reduction in FERG amplitudes at 1 week post injury (wpi), which recovered gradually over 2 months afterwards. Sham surgery alone also caused a similar pattern of amplitude reduction in FERG, although not as significantly as ONC did. Transient outer retinal thickening following ONC occurred at 4 wpi (when progressive thinning of the ganglion cell complex began), peaked at 8 wpi, then recovered gradually at 12 wpi. In contrast, outer retinal thickness remained unchanged statistically 3 months after sham surgery. Fundus fluorescein angiography showed that neither ONC nor ON exposure with lateral orbitotomy significantly caused any significant delay or absence of central retinal vascular filling. In summary, ONC with lateral orbitotomy affects outer retinal function and structure transiently. • Outer retinal function and structure were evaluated after retrobulbar optic nerve crush (ONC) in goats. • Transient FERG amplitude reduction was observed following ONC. • The thickness of outer retina measured by OCT underwent a transient increment following ONC. • FFA test revealed that the central retinal vasculature remained normal following ONC. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a leading cause of blindness. It has long been regarded as vascular disease, but work in the past years has shown abnormalities also in the neural retina. Unfortunately, research on the vascular and neural abnormalities have remained largely separate, instead of being integrated into a comprehensive view of DR that includes both the neural and vascular components. Recent evidence suggests that the most predominant neural cell in the retina (photoreceptors) and the adjacent retinal pigment epithelium (RPE) play an important role in the development of vascular lesions characteristic of DR. This review summarizes evidence that the outer retina is altered in diabetes, and that photoreceptors and RPE contribute to retinal vascular alterations in the early stages of the retinopathy. The possible molecular mechanisms by which cells of the outer retina might contribute to retinal vascular damage in diabetes also are discussed. Diabetes-induced alterations in the outer retina represent a novel therapeutic target to inhibit DR. [ABSTRACT FROM AUTHOR]

(1) Background: We aimed to reveal the relationship between the choroid and the outer retina with optical coherence tomography (OCT) in patients with diabetes mellitus (DM) with mild or no diabetic retinopathy (DR) in order to find early biomarkers for progressing retinopathy. (2) Methods: We performed a prospective study including 61 eyes of patients with type 1 or type 2 DM and 36 eyes of healthy controls. All subjects were imaged with Spectralis OCT. The choroid was assesseed using enhanced depth imaging OCT (EDI-OCT). Binarization of subfoveal choroidal images was done with public domain software, ImageJ (version 1.53a; National Institutes of Health, Bethesda, Maryland, USA). (3) Results: Luminal area, stromal area and total choroidal area were significantly decreased in diabetic patients compared to control: 0.23 ± 0.07 vs. 0.28 ± 0.08, p = 0.012; 0.08 ± 0.03 vs. 0.10 ± 0.04, p = 0.026; 0.31 ± 0.09 vs. 0.38 ± 0.11, p = 0.008. The thickness of retinal pigment epithelium (RPE) correlated positively with the choroidal vascularity index (CVI). The correlations between outer nuclear layer (ONL), photoreceptors (PR) and foveal choroidal thickness (FChT) were moderately negative. (4) Conclusion: Thicker RPE and a thinner PR layer may be assigned the role of early biomarkers signaling the conversion time to progressing retinopathy. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the thickness of all inner and outer macular layers between ocular hypertension (OHT) and early primary open-angle glaucoma (POAG) using spectral domain optical coherence tomography (SD-OCT) 8 × 8 posterior pole algorithm (8 × 8 PPA). Fifty-seven eyes of 57 OHT individuals and fifty-seven eyes of 57 early POAG patients were included. The thickness of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform and nuclear layer, photoreceptor layer (PRL) and retinal pigment epithelium were obtained in 64 cells for each macular layer and mean thickness of superior and inferior hemispheres was also calculated. Thinning of superior and inferior hemisphere mean thickness in mRNFL, GCL and IPL and thickening of superior and inferior hemisphere mean thickness in PRL and inferior hemisphere in INL were found in early GPAA group. Otherwise, heatmaps representing cell-to-cell comparisons showed thinning patterns in inner retinal layers (except for INL) and thickening patterns in outer retinal layers in GPAA group. We found that 8 × 8 PPA not only allows the detection of significant thinning patterns in inner retinal layers, but also thickening patterns in outer retinal layers when comparing early POAG eyes to OHT eyes. [ABSTRACT FROM AUTHOR]

Background: Swept-source optical coherence tomography (SS-OCT) has a higher scanning rate and longer wavelength in comparison with spectral-domain OCT (SD-OCT), allowing an improved imaging of retinal vascular plexuses and choriocapillaris. The present two patients diagnosed with multiple evanescent white dot syndrome (MEWDS) underwent fundus autofluorescence (FAF), en-face SS-OCT, and SS-OCT angiography (OCTA) imaging, and its features were described and correlated.Results: The clinical and imaging findings of both cases were consistent with the diagnosis of MEWDS. Color fundus photograph revealed subtle deep retinal white spots in the posterior pole and around the optic disk. FAF showed several hyperautofluorescent lesions corresponding topographically to the subtle deep retinal white lesions observed on color fundus photographs. Cross-sectional SS-OCT showed disruption of the ellipsoid zone (EZ) within the macular area in all study patients. En-face SS-OCT at the level of the outer retina showed lower reflectivity correspondent to the diffuse attenuation due to the EZ disruption on cross-sectional OCT. SS-OCTA demonstrated flow preservation within the retinal vasculature and choriocapillaris.Conclusions: SS-OCT imaging allows a better visualization of the choriocapillaris, and its normal appearance in MEWDS may suggest that the outer retina and photoreceptors represent the primary site of inflammation. [ABSTRACT FROM AUTHOR]