Outer Choroid Research Articles

Aryl hydrocarbon receptor (AhR)-mediated immune responses to degeneration of the retinal pigment epithelium

Injuries to the retinal pigment epithelium (RPE) trigger immune responses, orchestrating interactions within the innate and adaptive immune systems in the outer retina and choroid. We previously reported that interleukin 17 (IL-17) is a pivotal signaling molecule originating from choroidal γδ T cells, exerting protective effects by mediating functional connections between the RPE and subretinal microglia. In this current study, we generated mice with aryl hydrocarbon receptor (AhR) knockout specifically in IL-17-producing cells. These animals had deficiency in IL-17 production from γδ T cells, and exhibited increased sensitivity to both acute and chronic insults targeting the RPE. These findings imply that IL-17 plays a crucial role as a signaling cytokine in preserving the homeostasis of the outer retina and choroid.

Outer retina and choroid as potential imaging markers for evaluation of neural impairment in early type 2 diabetic patients.

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. 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. 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. 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.

Visual functions and multimodal imaging of patients with idiopathic focal choroidal excavation

This study aimed to evaluate visual function and perform multimodal imaging on patients with focal choroidal excavation without any chorioretinal disease (idiopathic focal choroidal excavation [iFCE]). Seventeen eyes of 15 patients with iFCE (8 men, 7 women; mean ± standard deviation age, 56.0 ± 10.8 years) were assessed for visual function including visual acuity, metamorphopsia, aniseikonia, and retinal sensitivity. Multimodal imaging included optical coherence tomography (OCT), fundus autofluorescence (FAF), and OCT angiography. This study found that the maximum width and depth of the excavation were 597 ± 330 (238–1809) µm and 123 ± 45 (66–231) µm, respectively, and that FAF showed normal or hypoautofluorescence corresponding to iFCE. The fundus examination findings were stable during the follow-up period (96 ± 48 months). None of the eyes showed any abnormalities in central retinal sensitivity or aniseikonia. Metamorphopsia was detected using Amsler grid testing and M-CHARTS in two eyes. Therefore, this study is the first to quantitatively and qualitatively study metamorphopsia of patients with iFCE. Our results showed that most patients with iFCE did not have visual impairments, despite the presence of morphological changes in the outer retina and choroid.

A Case of Full Thickness Parafoveal Hole Associated with Chorio-Retinal Atrophy.

An idiopathic full-thickness parafoveal hole (PFH) in the absence of trauma or intraocular surgery is a rare finding. A 60-year-female who did not gain good vision following an uneventful phacoemulsification with intraocular lens (IOL) implantation in the right eye (RE) consulted a retina specialist, one year after her cataract surgery. There was no history of trauma, radiation exposure, reduced scotopic vision, or any other intraocular surgery. Her personal and family history were unremarkable for any systemic or ocular diseases. Routine blood investigations, an electrocardiogram, and a detailed ocular examination were done. She had the best corrected visual acuity (BCVA) of LogMAR 1.0 (20/200; 6/60) in the right eye. The right eye had an axial length (AL) of 23.50 mm and an intraocular lens power of 21.0 dioptres. The ultrawide field fundus examination saw parafoveal chorio-retinal atrophy without significant peripheral myopic degeneration. On optical coherence tomography (OCT), a central foveal thickness of 138 microns with foveal scarring was noticed. There was a full-thickness parafoveal hole between the fovea and optic disc having a height of 198 microns; base diameter of 240 microns; arm lengths of 203 microns and 206 microns; and a minimum linear dimension of 42 microns. The optical coherence tomography angiography scan showed a reduced vessel density in the superficial and deep retina; and increased visibility of choroidal vessels in outer retina chorio-capillaries, chorio-capillaries, and choroid slab at the parafoveal hole The ultrasound B scan was anechoic and there was no posterior vitreous detachment (PVD). The axial length, intraocular lens power and fundus examination did not indicate pathological myopia. As there was no preceding posterior vitreous detachment or retinal surgery, the underlying retinochoroidal atrophy most probably caused the full-thickness parafoveal hole.

El espacio supracoroideo en pacientes afectados por retinosis pigmentaria

Background and objectiveThe suprachoroidal space (SCS) is a theoretical structure which can be demonstrated between the inner border of the sclera and the outer boundary of the choroid. SCS is being studied for its potential uses as a route for drug delivery and innovative surgical techniques for the treatment of many retinal diseases. Retinitis pigmentosa (RP) is a group of inherited eye disorders characterized by a gradual loss of photoreceptors, resulting in vision impairment, which typically presents as night blindness and progressive visual field loss. The purpose of the study is to define the morphology of outer choroidal margins by means of SS-OCT in RP. Material and methodThis is a retrospective observational study designed to evaluate the presence of SCS in RP. We performed swept source optical coherence tomography (SS-OCT) in a group of 55 patients affected by RP (26 males and 29 females, 110 eyes) with a mean age of 51.8±13.7 years. In the control group, we included 28 healthy subjects (6 males and 22 females, 56 eyes) with a mean age of 48.8±16.6 years. ResultsOCT scans allowed the outer choroidal margin and inner scleral margin to be delineated with certainty in all 110 eyes. In the RP group SCS was detected in 47 of 110 eyes (42.7%), in the control group SCS was detected in 11 eyes (19.6%).Subjects with SCS visible (RP group) had reduced retinal thickness (168.4μm) compared to those with not visible SCS (211.2μm, p=0.007). ConclusionsSS-OCT can be successfully applied to assess the presence of SCS in RP and the high rate of SCS found in the RP patients is encouraging when considering future innovative therapies.

The suprachoroidal space in patients affected by retinitis pigmentosa

Background and objectiveThe Suprachoroidal Space (SCS) is a theoretical structure which can be demonstrated between the inner border of the sclera and the outer boundary of the choroid. SCS is being studied for its potential uses as a route for drug delivery and innovative surgical techniques for the treatment of many retinal diseases.Retinitis pigmentosa (RP) is a group of inherited eye disorders characterized by a gradual loss of photoreceptors, resulting in vision impairment, which typically presents as night blindness and progressive visual field loss.The purpose of the study is to define the morphology of outer choroidal margins by means of SS-OCT in RP. Material and methodThis is a retrospective observational study designed to evaluate the presence of SCS in RP.We performed Swept Source optical coherence tomography (SS-OCT) in a group of 55 patients affected by RP (26 males and 29 females, 110 eyes) with a mean age of 51.8 ± 13.7 years. In the control group, we included 28 healthy subjects (6 males and 22 females, 56 eyes) with a mean age of 48,8 ± 16,6 years. ResultsOCT scans allowed the outer choroidal margin and inner scleral margin to be delineated with certainty in all 110 eyes. In the RP group SCS was detected in 47 of 110 eyes (42,7%), in the control group SCS was detected in 11 eyes (19,6%).Subjects with SCS visible (RP group) had reduced retinal thickness (168.4 µm) compared to those with not visible SCL (211.2 µm, P = .007). ConclusionsSS-OCT can be successfully applied to assess the presence of SCS in RP and the high rate of SCS found in the RP patients is encouraging when considering future innovative therapies.

Assessment of Outer Retina and Choroid Using Swept Source Optical Coherence Tomography and Angiography in Patients With Multiple Sclerosis.

For patients with multiple sclerosis (MS), both structure and microvasculature alterations in the inner retina have been investigated in several studies. However, little is known about the alterations in the outer retina and choroid. Hence, this study aimed to assess the outer retinal and choroidal changes in patients with MS with no history of optic neuritis (ON). Patients with MS and healthy control participants were enrolled in this cross-sectional study. Quantitative analyses were performed using swept source optical coherence tomography and swept source optical coherence tomography angiography images to assess outer retina thickness (ORT) and choroid thickness (CT), vessel density (VD) of choriocapillaris, and choroidal vascularity index (CVI), which were then compared between the groups. A total of 37 participants with MS (72 eyes) and 74 healthy control participants (148 eyes) were included in this study. Compared with healthy controls, patients with MS with no history of ON showed reduced VD of the choriocapillaris and CVI. There was no significant difference in ORT and CT between 2 groups. Meanwhile, in patients with MS, no correlation between OCTA parameters and expanded disability status scale score were found in this study. Our study indicates that patients with MS with no history of optical neuritis have reduced choriocapillaris vessel density and decreased choroidal vascularity index without detectable alteration in outer retina thickness and choroid thickness. The findings complement the outer retinal and choroidal component of MS, providing deeper insight into the pathophysiology of MS.

The Association of Neovascularization With Optical Coherence Tomography Angiography Parameters in Proliferative Diabetic Retinopathy.

We aim to find an association between neovascularization (NVn) and optical coherence tomography angiography (OCTA) parameters in proliferative diabetic retinopathy (PDR). In a prospective study, 41 subjects including 28 (68%) males and 13 (32%) femaleshaving PDR were examined for neovascularization disc (NVD) and neovascularization elsewhere (NVE) clinically and with fundus fluorescein angiography (FFA). A total of 79 eyes were found to be involved. We examined OCTA parameters including foveal avascular zone (FAZ) size, perimeter and circularity, and vessel density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), outer retina (OR), outer retinal chorio-capillaries (ORCC), chorio-capillaries (CC), and choroid (C) in these subjects. In eyes with NVD, the central foveal thickness (CFT) (p=0.83) and sub-foveal choroidal thickness (SFCT) (p=0.08) were higher, the FAZ area was significantly larger (p=0.005), and the VD was lower in all retino-choroidal layers. However, it was significantly lower in SCP foveal (p=0.005) and ORCC foveal (p=0.05) than in eyes not having NVD. For NVE, the CFT (p=0.03) and SFCT (p=0.01) were more in affected eyes. The eyes without NVE had a better circularity index (p=0.07) and the highest VD in OR slab (p=0.02) than those eyes that had NVE < ½ disc area (DA) and NVE > ½ DA. On comparing eyes without NVE, NVE < ½ DA, and NVE > ½ DA, the latest had the highest VD in SCP (p=0.59) and lowest VD in DCP (p=0.43) and OR (p=0.02). The VD in ORCC, CC, and choroid was highest in the no NVE group, followed by the NVE > ½ DA and NVE < ½ DA groups in that order. The subjects having vitreous hemorrhage (VH) and intra-retinal microvascular abnormalities (IRMA) had higher values for CFT and SFCT than eyes without these. An increased CFT and SFCT are associated with the appearance of NVD, NVE, VH, and IRMA. The presence of NVD, VH, and IRMA is associated with a larger FAZ area, while that of IRMA and NVE is associated with reduced FAZ circularity. Eyes with NVD, VH, and IRMA had lesser VD in all the retino-choroidal layers. Eyes with NVE > ½ DA had the highest VD in SCP and lowest in DCP and OR; this pattern of VD foretells severer affection in NVE. IRMA was associated with a larger FAZ area, larger FAZ perimeter, and lesser circularity, indicating the presence of central ischemia.

Granzyme B Contributes to Choroidal Neovascularization and Age-Related Macular Degeneration Through Proteolysis of Thrombospondin-1

Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in the elderly. The pathology of neovascular age-related macular degeneration (nAMD), also known as wet AMD, is associated with an abnormal blood vessel growth in the eye and involves an imbalance of proangiogenic and antiangiogenic factors. Thrombospondin (TSP)-1 and TSP-2 are endogenous matricellular proteins that inhibit angiogenesis. TSP-1 is significantly diminished in eyes with AMD, although the mechanisms involved in its reduction are unknown. Granzyme B (GzmB) is a serine protease with an increased extracellular activity in the outer retina and choroid of human eyes with nAMD-related choroidal neovascularization (CNV). This study investigated whether TSP-1 and TSP-2 are GzmB substrates using in silico and cell-free cleavage assays and explored the relationship between GzmB and TSP-1 in human eyes with nAMD-related CNV and the effect of GzmB on TSP-1 in retinal pigment epithelial culture and an explant choroid sprouting assay (CSA). In this study, TSP-1 and TSP-2 were identified as GzmB substrates. Cell-free cleavage assays substantiated the GzmB proteolysis of TSP-1 and TSP-2 by showing dose-dependent and time-dependent cleavage products. TSP-1 and TSP-2 proteolysis were hindered by the inhibition of GzmB. In the retinal pigment epithelium and choroid of human eyes with CNV, we observed a significant inverse correlation between TSP-1 and GzmB, as indicated by lower TSP-1 and higher GzmB immunoreactivity. In CSA, the vascular sprouting area increased significantly with GzmB treatment and reduced significantly with TSP-1 treatment. Western blot showed significantly reduced expression of TSP-1 in GzmB-treated retinal pigment epithelial cell culture and CSA supernatant compared with that in controls. Together, our findings suggest that the proteolysis of antiangiogenic factors such as TSP-1 by extracellular GzmB might represent a mechanism through which GzmB may contribute to nAMD-related CNV. Future studies are needed to investigate whether pharmacologic inhibition of extracellular GzmB can mitigate nAMD-related CNV by preserving intact TSP-1.

Relationship Between Scleral Thickness and Choroidal Structure in Central Serous Chorioretinopathy.

Central serous chorioretinopathy (CSC) is a retinal disorder characterized by serous retinal detachment with or without pigment epithelial detachment in the posterior pole of the eye. We aimed to elucidate the relationship between scleral thickness and choroidal structure in CSC eyes. This single-center retrospective study included 111 eyes of 111 CSC patients. Using swept-source optical coherence tomography, the horizontal cross-sectional images of the posterior choroid were converted to binary images by semiautomated software. The luminal and stromal areas of the choroid were measured, and the luminal/stromal (L/S) ratios of the whole choroid (WC), inner choroid, and outer choroid (OC) at 1500 µm, 3000 µm, and 7500 µm ranges centered on the fovea were calculated. Correlations of L/S ratio and age, spherical equivalent, axial length, subfoveal choroidal thickness (SCT), and scleral thickness were determined. Scleral thickness was measured vertically, 6 mm posterior to the scleral spur in four directions. SCT and mean scleral thickness were significantly positively correlated with the L/S ratio in all ranges of WC and OC. Multiple regression analysis found that SCT and mean scleral thickness were significantly correlated with the L/S ratio, and the strength of correlation of mean scleral thickness (WC: 0.386, P < 0.001; OC: 0.391, P < 0.001) was greater than that of SCT (WC: 0.368, P < 0.001; OC: 0.383, P < 0.001) in 7500 µm range. Thick sclera appeared to play a role in an increase in the luminal component of the posterior choroid in CSC eyes.

Optical Coherence Tomography Angiography Parameters of the Retina in SARS-CoV-2 Recovered Subjects.

This study aims to evaluate retinochoroidal optical coherence tomography angiography (OCTA) parameters in patients recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This studywas an observational study that included 80 subjects being discharged after having negative reports on the reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 to evaluate OCTA parameters of the retina. The subjects underwent an ophthalmic evaluation that included best-corrected visual acuity (BCVA), intraocular pressure (IOP), color vision (CV), contrast sensitivity (CS), and optical coherence tomography (OCT) parameters. OCTA was done for all patients and was evaluated for foveal avascular zone (FAZ) area, perimeter, and circularity index, and vessel density (VD) in superficial capillary plexus (SCP), deep capillary plexus (DCP), outer retina (OR), outer retina chorio-capillaries (ORCC), chorio-capillaries (CC), and choroid (C) using 3 x 3 mm scans. The OCTA parameters were compared with normative data of the Indian population for various parameters in question. The subjects included 54/80 (67.5%) males and 26/80 (32.5%) females having a mean age of 52.40 ± 15.71 (18-60) years. The systemic evaluation revealed 38.75% of subjects had hypertension, 30% had diabetes, 20% had kidney disease, 5% had tuberculosis, and 3.75% had coronary artery disease.The mean distance BCVA was logarithm of the minimum angle of resolution (LogMAR) (1.17 ± 0.22), mean IOP was 17.0 ± 4.0 mmHg, mean CS was 2.13 ± 0.36, 50.62% of subjects had normal CV on Farnsworth test while 47% had tritanopia, and none of the subjects had red-green CV defect on Ishihara plates. The OCT scan was normal in 90% of eyes while the posterior vitreous detachment was seen in 4% of eyes, broad vitreomacular adhesion in 2.5% of eyes, and the globally adherent epiretinal membrane was seen in 2.5% of eyes. The mean central macular thickness (CMT) measured 245.14 ± 28.41 micrometers. The mean FAZ area measured 0.37 ± 0.15 mm2, the perimeter was 3.28 ± 1.08 mm, and the circularity index measured 0.41 ± 0.10. The average VD in SCP measured 16.06 ± 12.29, in DCPmeasured 9.11 ± 8.75, in ORmeasured 6.38 ± 7.37, in ORCC measured 42.53 ± 12.46, in CCmeasured 25.83 ± 16.31, and in C measured 25.52 ± 17.49. The VD in coronavirus disease 2019 (COVID-19) subjects was significantly lesser than that in the healthy Indian population in all layers except ORCC. The SARS-CoV-2 recovered subjects have a reduced VD in retinochoroidal layersfrom COVID-19, an underlying systemic disease, or both. The CS values fall within normal limits. Several subjects show tritanopia on the Farnsworth test but no red-green CV defect on Ishihara plates.

Eight years follow‐up of two choroideremia patients with a new mutation of the choroideremia gene

AbstractPurpose: Choroideremia (CHM) is an inherited retinal dystrophy with an X‐linked inherited patron. It presents changes in the outer retina and choroid. CHM has a typical fundus appearance with preservation of the central retina, that progresses over the years. Fundus autofluorescence (FAF) shows the changes in the pigment distribution not only in patients but also in carriers. We present an 8‐year follow‐up of two boys affected by the disease.Methods: We studied a family with two cousins referring visual loss and nyctalopia and presented clinical findings of CHM at 11 and 10 years old. Their mothers referred that their deceased father had an important loss of visual acuity (VA) and that he had been diagnosed of Retinitis Pigmentosa. They were diagnosed of CHM with an undescribed mutation in the CHM gene c.1083_1084dupT (p.L362Sfs*56) at the Xp21.2 location. We present the patients and the carriers follow‐up.Results: During 8 years one of the patients had a progressive loss of VA. He presented a high myopic refraction and retinal changes that could be related to both conditions. His macular function decreased during the years with loss of retinal sensitivity evaluated by MAIA microperimetry, with Multifocal ERG showing a marked diminution on the central peak. His cousin has not presented important changes during the follow‐up time, preserving macular sensitivity and central visual field. Both mothers show a different AF pattern, with one geographic pattern and another sparse mottled on periphery. Carriers have not changed during these 8 years, neither in their retinal function nor in the anatomical findings.Conclusions: Evolution in CHM disease could differ in patients affected by the same mutation. Myopic defect may increase the retinal damage, with a more aggressive evolution.

MULTIMODAL IMAGING OF MULTIFOCAL CHOROIDITIS WITH ADAPTIVE OPTICS OPHTHALMOSCOPY.

To describe longitudinal, anatomical, and functional alterations caused by inflammatory and neovascular lesions of idiopathic multifocal choroiditis/punctate inner choroidopathy using adaptive optics imaging and microperimetry. Longitudinal case study using multiple imaging modalities, including spectral-domain optical coherence tomography, fluorescein angiography, indocyanine green angiography, optical coherence tomography angiography, flood illumination adaptive optics, and microperimetry. A 21-year-old myopic Asian man presented with blurred vision in the right eye. Clinical examination was notable for an isolated hypopigmented, perifoveal lesion in each eye. Multimodal imaging showed inflammatory lesions in the outer retina, retina pigment epithelium, and inner choroid lesions of both eyes. The right eye additionally exhibited active Type-2 macular neovascularization with loss of cone mosaic regularity that was associated with reduced sensitivity on microperimetry. The clinical picture was consistent with multifocal choroiditis/punctate inner choroidopathy. The patient was treated with oral steroids and three injections of intravitreal bevacizumab in the right eye. After therapy, imaging showed reestablishment of the cone mosaic on flood illumination adaptive optics and improvement in sensitivity on microperimetry. Adaptive optics imaging and microperimetry may detect biomarkers that help to characterize the nature and activity of multifocal choroiditis lesions and to help monitor response to therapy. With timely intervention, structural abnormalities in the outer retina and choroid can be treated, and anatomical improvements precede improvements in visual function.

Evaluating the Quantitative Foveal Avascular Zone and Retino-Choroidal Vessel Density Using Optical Coherence Tomography Angiography in a Healthy Indian Population.

Objective: The foveal avascular zone (FAZ) is the round capillary-free zone within the macula and is supplied only by a single-layered parafoveal capillary arcade. This study aimed to evaluate the quantitative FAZ and retino-choroidal vessel density (VD) using optical coherence tomography angiography (OCTA) in a healthy Indian population.Methods: This was a cross-sectional observational study that was conducted for evaluating the quantitative FAZ and retino-choroidal VD of 200 eyes of 100 healthy Indian subjects, including 62 males and 38 females (age range 17-50 years) having the best-corrected visual acuity (BCVA) of logMAR 0 (20/20; 6/6) and spherical equivalent refractive error of not more than 1 D. The subjects were examined using OCTA automated software on spectral-domain OCT (SD-OCT; Nidek RS 3000 Advance 2; Nidek, Inc., Fremont, CA) on a 3 x 3 mm OCTA macular scan centred on the fovea. The FAZ size, perimeter and circularity index, VD in superficial, deep, and outer retina (OR), outer retinal chorio-capillaries (ORCC), chorio-capillaries (CC) and choroid (C) were analysed in the circular and quadrant-segmented zones. A correlation was found between the FAZ size, perimeter and circularity, and VD in retino-choroidal layers, and between BCVA, age, central foveal thickness (CFT) and sub-foveal choroidal thickness (SFCT), and OCTA parameters.Results: The FAZ and surrounding vascular arcades were intact in all eyes, showing either a vertical or horizontal oval-shaped symmetrical formation without gaps, holes or interruption of the capillary network. The mean value of CFT was 237.5±26.0 microns and SFCT was 269.6±53.0 microns. The mean FAZ area was 0.42±0.23 mm2, FAZ perimeter was 3.3±1.0 mm and FAZ circularity index was 0.46±0.1. The mean VD in superficial capillary plexus (SCP) was 23.87±10.66, in deep capillary plexus (DCP) was 16.03±9.90, in OR was 13.22± 12.27, in ORCC was 39.74±14.32, in CC was 37.02±16.43 and in choroid was 37.43±16.76. The increasing order of VD in different retino-choroidal layers was OR<DCP<SCP<CC<C<ORCC. The FAZ area and perimeter had a statistically significant (SS) negative correlation with the VD in SCP, DCP and OR, while the FAZ perimeter additionally had a SS negative correlation with the VD in the choroid. The FAZ circularity had a SS positive correlation with VD in SCP, DCP and OR. There was no SS correlation between the age of subjects and OCTA parameters. The BCVA had a SS correlation with only one parameter, i.e. ORCC foveal (r=-0.15; p=0.03). There was a SS negative correlation between CFT and FAZ area and perimeter, and a SS positive correlation between the CFT and VD in SCP, DCP and OR. There was a SS positive correlation between the SFCT and VD in different layers including SCP, DCP, ORCC, CC and choroid.Conclusions: VD is the highest in the ORCC and lowest in the OR segment. A better VD in SCP, DCP and OR is associated with a reduced FAZ area/FAZ perimeter and an increased FAZ circularity index. A lower VD in the ORCC is associated with worse BCVA. In a healthy subject, a relatively thicker foveal region is likely to have better vascularity of SCP, DCP and OR and a smaller FAZ area/FAZ perimeter. In the absence of diseases, relatively thicker sub-foveal choroid is expected to have better vascularity of SCP, DCP, ORCC, CC and choroid.

Transthyretin proteoforms of intraocular origin in human subretinal fluid

Understanding the molecular composition of ocular tissues and fluids could inform new approaches to prevalent causes of blindness. Subretinal fluid accumulating between the photoreceptor outer segments and retinal pigment epithelium (RPE) is potentially a rich source of proteins and lipids normally cycling among outer retinal cells and choroid. Herein, intact post-translationally modified proteins (proteoforms) were extracted from subretinal fluids of five patients with rhegmatogenous retinal detachment (RRD), analyzed by tandem mass spectrometry, and compared to published data on these same proteins as synthesized by other organs. Single-nuclei transcriptomic data from non-diseased human retina/RPE were used to identify whether proteins in subretinal fluid were of potential ocular origin. Two human donor eyes with normal maculas were immunoprobed for transthyretin (TTR) with appropriate controls. The three most abundant proteins detected in subretinal fluid were albumin, TTR, and apolipoprotein A-I. Remarkably, TTR relative to the other proteins was more abundant than its serum counterpart, suggestive of TTR being synthesized predominantly locally. Six proteoforms of TTR were detected, with the relative amount of glutathionylated TTR being much higher in the subretinal fluid (12–43%) than values reported for serum (<5%) and cerebrospinal fluid (0.4–13%). Moreover, a putative glycosylated TTR dimer of 32,428 Da was detected as the fourth most abundant protein. The high abundance of TTR and putative TTR dimer in subretinal fluid was supported by analysis of available single-nuclei transcriptomic data, which showed strong and specific signal for TTR in RPE. Immunohistochemistry further showed strong diffuse TTR immunoreactivity in choroidal stroma that contrasted with vertically aligned signal in the outer segment zone of the subretinal space and negligible signal in RPE cell bodies. These results suggest that TTR in the retina is synthesized intraocularly, and glutathionylation is crucial for its normal function. Further studies on the composition, function, and quantities of TTR and other proteoforms in subretinal fluid could inform mechanisms, diagnostic methods, and treatment strategies for age-related macular degeneration, familial amyloidosis, and other retinal diseases involving dysregulation of physiologic lipid transfer and oxidative stress.

Variability in Retinal Neuron Populations and Associated Variations in Mass Transport Systems of the Retina in Health and Aging.

Aging is associated with a broad range of visual impairments that can have dramatic consequences on the quality of life of those impacted. These changes are driven by a complex series of alterations affecting interactions between multiple cellular and extracellular elements. The resilience of many of these interactions may be key to minimal loss of visual function in aging; yet many of them remain poorly understood. In this review, we focus on the relation between retinal neurons and their respective mass transport systems. These metabolite delivery systems include the retinal vasculature, which lies within the inner portion of the retina, and the choroidal vasculature located externally to the retinal tissue. A framework for investigation is proposed and applied to identify the structures and processes determining retinal mass transport at the cellular and tissue levels. Spatial variability in the structure of the retina and changes observed in aging are then harnessed to explore the relation between variations in neuron populations and those seen among retinal metabolite delivery systems. Existing data demonstrate that the relation between inner retinal neurons and their mass transport systems is different in nature from that observed between the outer retina and choroid. The most prominent structural changes observed across the eye and in aging are seen in Bruch’s membrane, which forms a selective barrier to mass transfers at the interface between the choroidal vasculature and the outer retina.

En face optical coherence tomography transillumination for evaluation of retinal pigment epithelium alteration in central serous chorioretinopathy: correlation with multimodal imaging.

To study optical coherence tomography (OCT) en face imaging approach to evaluate retinal pigment epithelium (RPE) alteration in central serous chorioretinopathy (CSC). Forty eyes with CSC were imaged with structural en face OCT, fluorescein angiography (FA), and fundus autofluorescence (FAF). Structural en face OCT projections were generated using a 200-µm slab with the inner limit at the outer choroid to register choroidal hypertransmission signal in transillumination manner. Two masked graders independently defined the area of RPE alteration on resultant images. Agreement between graders and correlation between imaging modalities was assessed by kappa coefficients (k) and intraclass correlation coefficients (ICC), respectively. The measurements derived from three methods were highly correlated with ICC of 0.99 (95% CI 0.99 to 1.0) for OCT and FA, 0.97 (95% CI 0.93 to 0.99) for OCT and FAF, and 0.98 (95% CI 0.95 to 0.99) for FA and FAF. For the measurement of the area of RPE alteration, kappa value for inter-grader agreement was 0.94 for OCT, 0.89 for FA, and 0.92 for FAF. En face OCT proved a reliable tool for the noninvasive evaluation of RPE status in CSC.

Short Axial Length Is Related to Asymmetric Vortex Veins in Central Serous Chorioretinopathy.

PurposeTo investigate the clinical and morphologic factors related to asymmetric dilated vortex veins in central serous chorioretinopathy (CSC).DesignRetrospective, comparative study.ParticipantsOne hundred fifty-eight eyes of 158 patients with CSC.MethodsAll patients with CSC underwent ophthalmic examination and multimodal imaging, including measurements of axial length (AL), fluorescein angiography, indocyanine green angiography, swept-source OCT, and anterior segment OCT. Using en face OCT images at the level of the outer choroid, the eyes were divided into 2 groups: eyes with symmetric vortex veins (symmetry group) and those with asymmetric vortex veins (asymmetry group).Main Outcome MeasuresClinical and morphologic factors related to asymmetric vortex veins in CSC.ResultsOf the 158 eyes, 120 eyes (75.9%) were classified into the asymmetry group and 38 eyes (24.1%) were classified into the symmetry group. The asymmetry group showed significantly greater spherical equivalent (–0.32 ± 1.78 diopters [D] vs. –1.35 ± 2.64 D; P = 0.033), shorter AL (23.52 ± 0.86 mm vs. 24.10 ± 1.06 mm; P = 0.005), and greater subfoveal choroidal thickness (414.6 ± 105.3 μm vs. 360.4 ± 91.8 μm; P = 0.005) than the symmetry group. No significant differences existed between the 2 groups regarding age, sex, or all scleral thicknesses at the superior, temporal, inferior, and nasal points. In the multivariate analyses, shorter AL (odds ratio, 0.56; 95% confidence interval, 0.36–0.88; P = 0.011) was found to be significantly associated with the presence of asymmetric vortex veins.ConclusionsThe asymmetric dilated vortex vein is a common finding in patients with CSC. Our results suggest that certain biometric factors, such as short AL, may be associated with asymmetric dilated vortex veins developing in patients with CSC.

Assessment of the outer retina and choroid in white matter lesions participants using swept-source optical coherence tomography.

PurposeTo assess the three‐dimensional outer retina thickness and choroid in eyes with white matter lesions (WMLs) using swept‐source optical coherence tomography (SS‐OCT).MethodsParticipants without dementia and stroke with cerebral WMLs were enrolled in our study. Optical coherence tomography (OCT) and OCT angiography (OCTA) were used to image and evaluate the outer retinal layer, choroidal structure, and perfusion of the choriocapillaris, microvessels of the choroid, respectively. Measurement of the outer retinal thickness, choroidal thickness and perfusion of the choriocapillaris was done by the SS‐OCT tool.ResultsThirty‐one eyes from 16 WMLs and 40 eyes from 20 healthy controls were included in the data analyses. Outer retinal thickness was significantly reduced (P < .001) in WMLs participants when compared to healthy controls. Choroidal thickness was also significantly reduced (P < .001) in WMLs participants when compared to healthy controls. Choriocapillaris perfusion was significantly reduced (P = .002) in WMLs when compared to healthy controls. A significant correlation (Rho = .392, P = .032) was seen between the outer retinal thickness and choriocapillaris perfusion in WMLs participants.ConclusionsAssessing retinal thickness and choroidal changes with the SS‐OCTA as a proxy for WML could prove to be a potentially valuable tool for early detection of cognitive decline and other neurodegenerative diseases.

Regional Differences in Gene Expression of Proliferating Human Choroidal Endothelial Cells

Choroidal diseases including inflammation and neovascularization seem to have predilection for different vascular beds. In order to improve our understanding of human macular choroidal angiogenic diseases, we investigate the differences in gene expression between matched human macular and peripheral inner choroidal endothelial cells (CEC) and matched human macular inner and outer CEC. The gene expression profiles of matched, unpassaged human macular and peripheral inner CEC and matched human unpassaged macular inner and outer CEC were conducted using Affymetrix GeneChip arrays. Selected differences in gene expression were validated by real-time-PCR and immunohistochemistry. No differences in probeset expression were demonstrated between inner CECs compared with peripheral inner CECs. In comparison, there was a difference of 1.6% of probesets when matched, unpassaged proliferating human macular inner CEC and macular outer CEC from the same donors were compared. Macular inner CECs demonstrated up-regulation of probesets involved in nervous system development, growth factors, PLVAP, and collagen XVI, while macular outer CECs demonstrated up-regulation of probesets involved in immune function and intracellular signalling. There was a marked homogeneity of human macular and peripheral inner CECs. This suggests that gene expression differences in inner CECs are not responsible for the site specific selectivity of choroidal neovascularisation. Variability was noted, however, in the gene expression of matched macular inner and outer CECs. This could be explained by the differences in the roles and microenvironments of the inner and outer choroid.