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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]

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.

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.

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]

Purpose: To quantify the presence of early structural alterations in the outer retinal layer and choroid among healthy subjects and diabetic patients with no or mild diabetic retinopathy, and to establish the correlation between the measured structural parameters and retinal sensitivity., Methods: In total, 31 eyes from subjects with type 2 diabetes and 29 eyes from healthy subjects were enrolled. Optical coherence tomography was used to measure outer retina layers and choroid, while microperimetry was used to characterize the changes of visual function in a 6-mm diameter area at macula. Quantitative analysis of structural and functional changes was performed between groups and the structure-function correlations were determined., Results: The thickness of myoid and ellipsoid zone, choroid and the mean retinal sensitivity were significantly smaller in diabetic group than that in controls (all P values < 0.05). Besides, thinner choroid and outer retina was associated with the decreased retinal sensitivity，especially in diabetic patients ( r  = 0.377, P  = 0.048; r  = 0.401, P  = 0.034; respectively). Final multiple regression models showed the outer retinal thickness (ORT) ( P  = 0.033), choroidal thickness ( P  = 0.003) and the interaction between ORT and choroidal thickness ( P  = 0.001) were significant predictors to retinal sensitivity., Conclusions: Thinning of choroid and outer retina were significantly correlated with reduced retinal sensitivity, which indicate outer retina and choroid might be potential imaging markers for evaluation of visual function related to neural impairment in type 2 diabetic patients without or in the early stage of diabetic retinopathy., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: This study aimed to evaluate whether treatment with fingolimod (FTY) may induce functional changes on the macular pre-ganglionic retinal elements in patients affected by relapsing–remitting multiple sclerosis (RR-MS) without optic neuritis (ON). Methods: This case–control observational and retrospective study assessed multifocal electroretinogram (mfERG) responses from 35 healthy controls (mean age 43.58 ± 5.76 years), 41 patients with RR-MS without ON (mean age 40.64 ± 4.83 years, MS-noFTY group), and from 21 patients with RR-MS without ON (mean age 42.38 ± 12.34 years) and treated with fingolimod (Gilenya®, Novartis Europharm, 0.5 mg/day) (MS-FTY group). MfERG N1 and P1 implicit times (ITs), and N1–P1 response amplitude densities (RADs) were measured from concentric rings (R) with increasing foveal eccentricity: 0–5° (R1), 5–10° (R2), 10–15° (R3), 15–20° (R4), 20–25° (R5). We considered R1 and R2 as "central macular areas" and R3, R4 and R5 as "more eccentric retinal areas". In the MS-FTY group, mfERG recordings were performed between 6 and 12 months (mean 7.2 ± 1.5 months) from the start of FTY. Results: In the MS-FTY group, the mean values of mfERG N1 and P1 ITs and RADs detected in both central macular areas (R1 and R2) and in more eccentric retinal areas (R3, R4 and R5) were not significantly different (p > 0.01) with respect to those of control and MS-noFTY groups. Conclusions: Our mfERG results suggest that the chronic use of FTY does not induce a dysfunction of pre-ganglionic retinal elements located in the 0–25° of central retina. Since FTY does not cause any retinal functional abnormality, we suggest that FTY treatment could not produce any toxic effect on pre-ganglionic retinal elements even in the absence of macular oedema. [ABSTRACT FROM AUTHOR]

Christos Haritoglou,1 Ramin Tadayoni,2 Jean-Pierre Hubschman3 1Herzog Carl Theodor Eye Clinic, Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany; 2Department of Ophthalmology, Lariboisière Hospital, Assistance Publique-Hôpitaux de Paris, University Sorbonne Paris Cité, Paris, France; 3Retina Division, Stein Eye Institute, University of California Los Angeles, Los Angeles, CA, USA Abstract: 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. Keywords: lamellar macular hole, degenerative lamellar hole, tractional lamellar hole, outer retina, lamellar macular hole-associated epimacular proliferation, LHEP

Purpose: To investigate on the morphology of the macular inner (IR) and outer (OR) layers in multiple sclerosis (MS) patients with and without history of optic neuritis (ON), followed by good or poor recovery of best corrected visual acuity (BCVA).Methods: Thirty-five normal control subjects and 93 relapsing remitting MS patients were enrolled. Of this, 40 MS patients without ON (MS-noON, 40 eyes), 27 with history of ON and good BCVA recovery (MS-ON-G, 27 eyes), and 26 with history of ON and poor BCVA recovery (MS-ON-P, 26 eyes) were studied. Controls and MS patients underwent an extensive ophthalmological examination including spectral-domain optical coherence tomography evaluating in 3 localized macular areas (0–1 mm, Area 1; 1–3 mm, Area 2; 3- 6 mm, Area 3), volumes (MV), and thicknesses (MT) of the whole retina (WR), further segmented in IR and OR. The differences of MV and MT between the groups were tested by ANOVA. In the MS-ON-P group, the correlations between MV and MT and BCVA were evaluated by Pearson's test.Results: When compared to controls, the MS-noON group showed not significantly (p > 0.01) different MVs, whereas MTs were significantly (p < 0.01) reduced in the evaluation of WR and IR. In the MS-ON-G group, a significant (p < 0.01) reduction of WR and IR MVs and MTs was found in Areas 2 and 3; OR MVs and MTs were similar (p > 0.01) to controls. In the MS-ON-P group a significant (p < 0.01) reduction of WR, IR, and OR MVs and MTs was detected in all areas; the BCVA reduction was significantly (p < 0.01) correlated with WR and IR MVs and MTs.Conclusions: In MS without history of ON or when ON is followed by a good BCVA recovery, the neurodegenerative process is limited to IR macular layers; in the presence of ON, with a poor BCVA recovery, a morphological impairment of both IR and OR macular layers occurs.

Abstract 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.

Purpose: To investigate on the morphology of the macular inner (IR) and outer (OR) layers in multiple sclerosis (MS) patients with and without history of optic neuritis (ON), followed by good or poor recovery of best corrected visual acuity (BCVA). Methods: Thirty-five normal control subjects and 93 relapsing remitting MS patients were enrolled. Of this, 40 MS patients without ON (MS-noON, 40 eyes), 27 with history of ON and good BCVA recovery (MS-ON-G, 27 eyes), and 26 with history of ON and poor BCVA recovery (MS-ON-P, 26 eyes) were studied. Controls and MS patients underwent an extensive ophthalmological examination including spectral-domain optical coherence tomography evaluating in 3 localized macular areas (0–1 mm, Area 1; 1–3 mm, Area 2; 3- 6 mm, Area 3), volumes (MV), and thicknesses (MT) of the whole retina (WR), further segmented in IR and OR. The differences of MV and MT between the groups were tested by ANOVA. In the MS-ON-P group, the correlations between MV and MT and BCVA were evaluated by Pearson's test. Results: When compared to controls, the MS-noON group showed not significantly (p > 0.01) different MVs, whereas MTs were significantly (p < 0.01) reduced in the evaluation of WR and IR. In the MS-ON-G group, a significant (p < 0.01) reduction of WR and IR MVs and MTs was found in Areas 2 and 3; OR MVs and MTs were similar (p > 0.01) to controls. In the MS-ON-P group a significant (p < 0.01) reduction of WR, IR, and OR MVs and MTs was detected in all areas; the BCVA reduction was significantly (p < 0.01) correlated with WR and IR MVs and MTs. Conclusions: In MS without history of ON or when ON is followed by a good BCVA recovery, the neurodegenerative process is limited to IR macular layers; in the presence of ON, with a poor BCVA recovery, a morphological impairment of both IR and OR macular layers occurs. [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]

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.

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]

Prolonged hyperglycemia can alter retinal function, ultimately resulting in blindness. Adult zebrafish adults exposed to alternating conditions of 2% glucose/0% glucose display a 3× increase in blood sugar levels. After 4 weeks of treatment, electroretinograms (ERGs) were recorded from isolated, perfused, in vitro eyecups. Control animals were exposed to alternating 2% mannitol/0% mannitol (osmotic control) or to alternating water (0% glucose/0% glucose; handling control). Two types of ERGs were recorded: (1) native ERGs measured using white-light stimuli and medium without synaptic blockers; and (2) spectral ERGs measured with an AMPA/kainate receptor antagonist, isolating photoreceptor-to-ON-bipolar-cell synapses, and a spectral protocol that separated red (R), green (G), blue (B) and UV cone signals. Retinas were evaluated for changes in layer thickness and for the inflammatory markers GFAP and Nf-κB (RelA or p65). In native ERGs, hyperglycemic b- and d-waves were lower in amplitude than the b- and d-waves of mannitol controls. Alteration of waveshape became severe, with b-waves becoming more transient and ERG responses showing more PIII-like (a-wave) characteristics. For spectral ERGs, waveshape appeared similar in all treatment groups. However, a1- and b2-wave implicit times were significantly longer, and amplitudes were significantly reduced, in response to hyperglycemic treatment, owing to the functional reduction in signals from R, G and B cones. Nf-κB increased significantly in hyperglycemic retinas, but the increase in GFAP was not significant and retinal layer thickness was unaffected. Thus, prolonged hyperglycemia triggers an inflammatory response and functional deficits localized to specific cone types, indicating the rapid onset of neural complications in the zebrafish model of diabetic retinopathy.

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]

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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 outer retina consists of the light-sensitive photoreceptors, the pigmented epithelium, and the choroid, which interact in a complex manner to sustain homeostasis. The organisation and function of these cellular layers are mediated by the extracellular matrix compartment named Bruch's membrane, situated between the retinal epithelium and the choroid. Like many tissues, the retina experiences age-related structural and metabolic changes, which are relevant for understanding major blinding diseases of the elderly, such as age-related macular degeneration. Compared with other tissues, the retina mainly comprises postmitotic cells, making it less able to maintain its mechanical homeostasis over the years functionally. Aspects of retinal ageing, like the structural and morphometric changes of the pigment epithelium and the heterogenous remodelling of the Bruch's membrane, imply changes in tissue mechanics and may affect functional integrity. In recent years, findings in the field of mechanobiology and bioengineering highlighted the importance of mechanical changes in tissues for understanding physiological and pathological processes. Here, we review the current knowledge of age-related changes in the outer retina from a mechanobiological perspective, aiming to generate food for thought for future mechanobiology studies in the outer retina., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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.

During neuronal degenerative diseases, microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. This can be particularly well observed in the retina, where photoreceptor degeneration triggers rewiring of connections in the retina's first synaptic layer (e.g., Strettoi et al., 2003; Haq et al., 2014), while the synaptic organization of inner retinal circuits appears to be little affected (O'Brien et al., 2014; Figures 1A,B). Remodeling of (outer) retinal circuits and diminishing light-driven activity due to the loss of functional photoreceptors lead to spontaneous activity that can be observed at different retinal levels (Figure 1C), including the retinal ganglion cells, which display rhythmic spiking activity in the degenerative retina (Margolis et al., 2008; Stasheff, 2008; Menzler and Zeck, 2011; Stasheff et al., 2011). Two networks have been suggested to drive the oscillatory activity in the degenerating retina: a network of remnant cone photoreceptors, rod bipolar cells (RBCs) and horizontal cells in the outer retina (Haq et al., 2014), and the AII amacrine cell-cone bipolar cell network in the inner retina (Borowska et al., 2011). Notably, spontaneous rhythmic activity in the inner retinal network can be triggered in the absence of synaptic remodeling in the outer retina, for example, in the healthy retina after photo-bleaching (Menzler et al., 2014). In addition, the two networks show remarkable differences in their dominant oscillation frequency range as well as in the types and numbers of involved cells (Menzler and Zeck, 2011; Haq et al., 2014). Taken together this suggests that the two networks are self-sustained and can be active independently from each other. However, it is not known if and how they modulate each other. In this mini review, we will discuss: (i) commonalities and differences between these two oscillatory networks as well as possible interaction pathways; (ii) how multiple self-sustained networks may hamper visual restoration strategies employing, for example, microelectronic implants, optogenetics or stem cells, and briefly; and (iii) how the finding of diverse (independent) networks in the degenerative retina may relate to other parts of the neurodegenerative central nervous system. [ABSTRACT FROM AUTHOR]