Retinal Area Research Articles

Study of Nonperfusion Area Changes after Ranibizumab Intravitreal Injection for Diabetic Macular Edema by Means of Widefield OCT Angiography

Introduction: The aim of this study was to evaluate changes in retinal capillary nonperfusion areas (RCNPA) and the retinal capillary vessel density (RCVD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) using widefield optical coherence tomography angiography (WFOCTA) in patients with diabetic retinopathy (DR) and diabetic macular edema (DME) treated with intravitreal ranibizumab injection (IRI). Materials and Methods: Twenty-four eyes of 24 patients with DR and DME candidates to a loading dose of IRI were enrolled. All patients underwent WFOCTA with the PLEX Elite 9000 device with 15 × 9 mm scans centered on the foveal center at baseline (T0) and 1 month after each intravitreal injection at 30 days (T1), 60 days (T2), and 90 days (T3). In all patients, the variation of RCNPA and the RCVD of the SCP and DCP were calculated using automatic software written in MATLAB (MathWorks, Natick, MA, USA). Results: The SCP showed a significant longitudinal variation of RCNPA (p = 0.04). Post hoc analysis revealed a statistically significant reduction of RCNPA at T1 (p = 0.04) and a nonsignificant reduction at T2 (p = 0.18) and T3 (p = 0.96). The DCP showed longitudinal changes in the RCNPA that tended to statistical significance (p = 0.09). Post hoc analysis revealed a trend toward a statistically significant reduction of RCNPA at T3 (p = 0.09) not statistically significant at T1 (p = 0.17) and T2 (p = 0.75). The RCVD of SCP and DCP showed no significant changes at any of the time points. Conclusions: WFOCTA showed a decrease in RCNPA after IRI, probably related to the reperfusion of retinal capillaries.

Subretinal Implantation of Human Primary RPE Cells Cultured on Nanofibrous Membranes in Minipigs.

Purpose: The development of primary human retinal pigmented epithelium (hRPE) for clinical transplantation purposes on biodegradable scaffolds is indispensable. We hereby report the results of the subretinal implantation of hRPE cells on nanofibrous membranes in minipigs. Methods: The hRPEs were collected from human cadaver donor eyes and cultivated on ultrathin nanofibrous carriers prepared via the electrospinning of poly(L-lactide-co-DL-lactide) (PDLLA). “Libechov” minipigs (12–36 months old) were used in the study, supported by preoperative tacrolimus immunosuppressive therapy. The subretinal implantation of the hRPE-nanofibrous carrier was conducted using general anesthesia via a custom-made injector during standard three-port 23-gauge vitrectomy, followed by silicone oil endotamponade. The observational period lasted 1, 2, 6 and 8 weeks, and included in vivo optical coherence tomography (OCT) of the retina, as well as post mortem immunohistochemistry using the following antibodies: HNAA and STEM121 (human cell markers); Bestrophin and CRALBP (hRPE cell markers); peanut agglutining (PNA) (cone photoreceptor marker); PKCα (rod bipolar marker); Vimentin, GFAP (macroglial markers); and Iba1 (microglial marker). Results: The hRPEs assumed cobblestone morphology, persistent pigmentation and measurable trans-epithelial electrical resistance on the nanofibrous PDLLA carrier. The surgical delivery of the implants in the subretinal space of the immunosuppressed minipigs was successfully achieved and monitored by fundus imaging and OCT. The implanted hRPEs were positive for HNAA and STEM121 and were located between the minipig’s neuroretina and RPE layers at week 2 post-implantation, which was gradually attenuated until week 8. The neuroretina over the implants showed rosette or hypertrophic reaction at week 6. The implanted cells expressed the typical RPE marker bestrophin throughout the whole observation period, and a gradual diminishing of the CRALBP expression in the area of implantation at week 8 post-implantation was observed. The transplanted hRPEs appeared not to form a confluent layer and were less capable of keeping the inner and outer retinal segments intact. The cone photoreceptors adjacent to the implant scaffold were unchanged initially, but underwent a gradual change in structure after hRPE implantation; the retina above and below the implant appeared relatively healthy. The glial reaction of the transplanted and host retina showed Vimentin and GFAP positivity from week 1 onward. Microglial activation appeared in the retinal area of the transplant early after the surgery, which seemed to move into the transplant area over time. Conclusions: The differentiated hRPEs can serve as an alternative cell source for RPE replacement in animal studies. These cells can be cultivated on nanofibrous PDLLA and implanted subretinally into minipigs using standard 23-gauge vitrectomy and implantation injector. The hRPE-laden scaffolds demonstrated relatively good incorporation into the host retina over an eight-week observation period, with some indication of a gliotic scar formation, and a likely neuroinflammatory response in the transplanted area despite the use of immunosuppression.

Reference database of total retinal vessel surface area derived from volume-rendered optical coherence tomography angiography

Optical coherence tomography angiography (OCTA) enables three-dimensional, high-resolution, depth-resolved flow to be distinguished from non-vessel tissue signals in the retina. Thus, it enables the quantification of the 3D surface area of the retinal vessel signal. Despite the widespread use of OCTA, no representative spatially rendered reference vessel surface area data are published. In this study, the OCTA vessel surface areas in 203 eyes of 107 healthy participants were measured in the 3D domain. A Generalized Linear Model (GLM) model analysis was performed to investigate the effects of sex, age, spherical equivalent, axial length, and visual acuity on the OCTA vessel surface area. The mean overall vessel surface area was 54.53 mm2 (range from 27.03 to 88.7 mm2). OCTA vessel surface area was slightly negatively correlated with age. However, the GLM model analysis identified axial length as having the strongest effect on OCTA vessel surface area. No significant correlations were found for sex or between left and right eyes. This is the first study to characterize three-dimensional vascular parameters in a population based on OCTA with respect to the vessel surface area.

NEW BIOMARKER QUANTIFYING THE EFFECT OF ANTI-VEGF THERAPY IN EYES WITH PROLIFERATIVE DIABETIC RETINOPATHY ON ULTRAWIDE FIELD FLUORESCEIN ANGIOGRAPHY: RECOVERY Study.

To quantify changes of the retinal vascular bed area (RVBA) in mm2 on stereographically projected ultrawide field fluorescein angiography images in eyes with proliferative diabetic retinopathy after antivascular endothelial growth factor injection. This is a prospective, observational study. The early-phase ultrawide field fluorescein angiography images (Optos 200Tx) of 40 eyes with proliferative diabetic retinopathy and significant nonperfusion obtained at baseline and after six months (NCT02863354) were stereographically projected by correcting peripheral distortion. The global retinal vasculature on ultrawide field fluorescein angiography was extracted for calculating RVBA by summing the real size (mm2) of all the pixels automatically. For the entire cohort, the global RVBA for the entire retina decreased from 67.1 ± 15.5 to 43.6 ± 18.8 mm2 after anti-VEGF treatment at six months (P < 0.001). In the subgroup receiving monthly anti-VEGF injections, the global RVBA decreased from 68.7 ± 16.2 to 33.9 ± 13.3 mm2 (P < 0.001). In the subgroup receiving anti-VEGF every three months, the global RVBA decreased from 65.6 ± 15.1 to 50.8 ± 19.3 mm2 (P = 0.004). RVBA seems to be a new biomarker to indicate efficiency of retinal vascular changes after anti-VEGF injection. Eyes with proliferative diabetic retinopathy and significant nonperfusion demonstrate reduced RVBA after anti-VEGF treatment.

Prospective, Longitudinal Study: Daily Self-Imaging with Home OCT for Neovascular Age-Related Macular Degeneration

To validate the performance of the Notal Vision Home OCT (NVHO) system for daily self-imaging at home and characterize the retinal fluid dynamics of patients with neovascular age-related macular degeneration (nAMD). Prospective observational study. Fifteen participants who had at least 1 eye with nAMD and underwent anti-VEGF treatments. The participants performed daily self-imaging at home using NVHO for 3 months. The scans were uploaded to the cloud, analyzed using the Notal OCT Analyzer (NOA), evaluated by human experts for fluid presence, and compared with in-office OCT scans. Weekly self-scan rate, image quality, scan duration, agreement between NOA and human expert grading for fluid presence, agreement between NVHO and in-office OCT scans for fluid presence, central subfield thickness (CST) and retinal fluid volume, and the characteristics of fluid dynamics during the study and in response to treatments. The mean weekly scan frequency was 5.7 ± 0.9 scans per week, and 93% of the scans were eligible for NOA analyses. The median scan time was 42 seconds. The NOA and human experts agreed on the fluid status in 83% of the scans, and discrepancies were limited to trace amounts of fluid. The NVHO scans analyzed using NOA and the in-office OCT scans graded by human experts agreed on the fluid status in 96% of the cases. The CST and retinal fluid volume measurements using the home OCT and in-office OCT scans demonstrated a Pearson correlation coefficient of r= 0.90 and r= 0.92, respectively. Novel parameters, such as retinal fluid volume and area under the curve (AUC) of retinal fluid volume, demonstrated wide variations in fluid exudation and fluid load over time among the patients. Parameters such as the rate of reduction in fluid volume in the first week after treatment and AUC between treatments captured the speed and duration of the response to anti-VEGF agents. Daily home OCT imaging is feasible among patients with nAMD. It demonstrated good agreement with human expert grading for retinal fluid identification and excellent agreement with the in-clinic OCT scans. Home OCT allows for detailed graphical and mathematical analyses of retinal fluid volume trajectories, including novel parameters to inform clinical decision making.

Image enhancement of color fundus photographs for age-related macular degeneration: the Shanghai Changfeng Study.

To develop and evaluate a new fundus image optimization software based on red, green, blue channels (RGB) for the evaluation of age-related macular degeneration (AMD) in the Chinese population. Fundus images that were diagnosed as AMD from the Shanghai Changfeng Study database were analyzed to develop a standardized optimization procedure. Image brightness, contrast, and color balance were measured. Differences between central lesion area and normal retinal area under different image brightness, contrast, and color balance were observed. The optimal optimization parameters were determined based on the visual system to avoid image distortion. A paired-sample diagnostic test was used to evaluate the enhancement software. Fundus optical coherence tomography (OCT) was used as the gold standard. Diagnostic performances were compared between original images and optimized images using McNemar's test. A fundus image optimization procedure was developed using 86 fundus images of 74 subjects diagnosed with AMD. By observing gray-scale images, choroid can be best displayed in red channel and retina in green channel was found. There was limited information in blue channel. Totally 104 participants were included in the paired sample diagnostic test to assess the performance of the optimization software. After the image enhancement, sensitivity increased from 74% to 88% (P=0.008), specificity decreased slightly from 88% to 84% (P=0.500), and Youden index increased by 0.11. The standardized image optimization software increases diagnostic sensitivity and may help ophthalmologists in AMD diagnosis and screening.

Retinal microvascular changes in white matter hyperintensities investigated by swept source optical coherence tomography angiography

BackgroTo assess the microvascular changes in the macular region and the foveal avascular zone (FAZ) area in participants with white matter hyperintensities (WMHs) using swept source optical coherence tomography angiography (SS OCTA).MethodsThis cross-sectional study included a total of 23 WMH participants (45 eyes) and 20 age-matched healthy participants (40 eyes). SS OCTA (VG200; SVision Imaging, Ltd., Luoyang, China) was used to assess the retinal vessel density (VD) and the FAZ area. VD was measured in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) within a 6 × 6-mm scan centred on the macula using a 5-mm Macula circle. The FAZ area was automatically measured on the inner retina layer within a 3 × 3-mm scan in the macular region.ResultsThere was no significant difference in VD in the SVP between the two groups. However, VD in both the ICP and DCP was significantly decreased in WMH participants (P = 0.028, P = 0.016). The FAZ area was significantly enlarged in WMH participants (P = 0.030). The signal quality was significantly lower in WMH participants (P < 0.001).ConclusionsThis study suggested that WMH participants have retinal microvascular and foveal avascular zone area changes compared with healthy controls. Further longitudinal studies with larger sample sizes are warranted to identify the value of our findings in the early evaluation of WMHs.

Topographical Relationship Between Acute Macular Neuroretinopathy and Choroidal Watershed Zone or Patchy Choroidal Filling.

PurposeTo study the topographical relationship between acute macular neuroretinopathy (AMN) lesions and the choroidal watershed zone (CWZ) or patchy choroidal filling (PCF) using multimodal imaging.MethodsLesions in patients diagnosed with AMN were clinically examined using multimodal imaging, including fundus photography, near-infrared reflectance imaging, spectral-domain optical coherence tomography (OCT), fluorescein angiography, indocyanine green angiography, OCT angiography, and microperimetry. The topographical relationship between AMN and the CWZ or PCF was evaluated.ResultsSeven eyes of six patients were included in the study. The mean age of the patients was 35.8 ± 11.7 years. The AMN lesions were collocated with the CWZ in five eyes and the PCF in one eye. Among these eyes, three had complete patterns, and three had partial patterns. Only one eye showed no topographical relationship between AMN and the CWZ or PCF.ConclusionThe colocation of AMN and CWZ/PCF suggests that the AMN lesions were within an area with a dual-watershed zone: the watershed zone between the retinal deep capillary plexus and choriocapillaris, and the choroidal watershed zone or patchy choroidal filling. This retinal area was highly vulnerable to hypoperfusion. Our results suggest a novel pathophysiological mechanism for AMN.

Ocular microvascular alteration in Sjögren syndrome.

Sjögren syndrome (SjS) is a systemic disease affecting exocrine, including ocular lacrimal, glands. It is uncertain whether ocular microvascular alterations are associated with this disease. In this study, we evaluated retinal and conjunctival microvascular changes in SjS patients using optical coherence tomography angiography (OCTA). Twelve SjS patients (24 eyes) and 12 normal controls (24 eyes) were recruited to this study. Three-dimensional conjunctival and retinal OCTA images of each eye were captured and microvascular density was calculated. Each image was analyzed by retinal area based on the early treatment of diabetic retinopathy study method (R, S, L, and I) hemisphere segmentation method (SR, SL, IL, and IR); and central wheel division method (C1-C6). Correlation analyses were used to look for associations between retinal and conjunctival microvascular densities. Superficial and deep retinal layer microvascular density was decreased in SjS patients compared with normal controls (P<0.05). This significant difference was found in both superficial and deep layers in S, L, SL, IL and C1-C3 regions, and additionally in the I and SR regions in the superficial layer. Conversely, in the conjunctiva microvascular density was higher in SjS patients than in controls. In SjS patients, a significant negative correlation was found between conjunctival and both superficial (r=-0.641; P=0.025) and deep (r=-0.958; P<0.0001) microvascular densities. The changed microvascular densities measured in deep and superficial retinal layers and in the conjunctiva demonstrate that OCTA is a promising method in differentiating the eyes from those with SjS.

Effect of Accommodation on Peripheral Higher Order Aberrations

Knowledge of the effect of accommodation on image quality of peripheral retina is crucial for better understanding of the visual system, but only a few studies have been carried out in this area. This study was designed to evaluate the effect of accommodation on higher order aberrations from third to sixth Zernike polynomials in central and peripheral retina up to 23° off-axis. We used a Hartmann–Shack aberrometer to measure Zernike coefficients with both accommodated and non-accommodated eyes of 15 healthy subjects. Each Zernike coefficient, total higher order aberrations, spherical aberrations and astigmatism were compared between accommodated and non-accommodated status. Additionally, aberrations in the central retina were compared with the peripheral retina. Accommodation induced significant changes in the Zernike coefficients of vertical pentafoil C5−5 and secondary vertical tetrafoil C6−4 in central retina, secondary vertical astigmatism C4−2 on 23° of temporal retina, secondary vertical tetrafoil C6−4 and tertiary vertical astigmatism C6−2 on 10° of nasal retina, secondary vertical trefoil C5−3 and secondary vertical tetrafoil C6−4 on 23° of nasal retina, and horizontal tetrafoil C44, and secondary horizontal tetrafoil C64 on 23° of inferior retina (p &lt; 0.05). Total higher order aberration was lower in each retinal area examined with accommodation, but it was statistically significant only on 23° temporal retina and 11.5° and 23° of superior retina (p &lt; 0.05). Spherical aberration decreased with accommodation on 23° temporal retina (p = 0.036). Astigmatism was similar in non-accommodated and accommodated eyes. Overall, accommodation affected higher order aberration (HOA) asymmetrically in different peripheral retinal areas.

Complement Mediators in Development to Treat Age-Related Macular Degeneration.

Over recent years, great attention has been paid to the role of the complement system in the pathogenesis of age-related macular degeneration (AMD). In particular, several studies have highlighted a link between AMD development and complement dysregulation, which can probably be explained as a complement cascade hyperactivation resulting from the presence of a series of risk factors such as aging; smoking; obesity; alcohol consumption; exposure to pesticides, industrial chemicals, or pollution; and other causes of oxidative stress. This hypothesis has been mainly supported by the presence of complement mediators as constituents of drusen, representing one of the earliest and most characteristic signs of retinal damage in AMD. Additionally, activated complement mediators and some complement regulators, such as vitronectin, have been found not only in the drusen and adjacent retinal areas but also in the peripheral blood of patients with AMD. Therefore, we aim to provide a review of recently studied complement factors to highlight their role in the pathogenesis of AMD and to evaluate new potential therapeutic strategies.

Automated evaluation of retinal pigment epithelium disease area in eyes with age-related macular degeneration

The retinal pigment epithelium (RPE) is essential for the survival and function of retinal photoreceptor cells. RPE dysfunction causes various retinal diseases including age-related macular degeneration (AMD). Clinical studies on ES/iPS cell-derived RPE transplantation for RPE dysfunction-triggered diseases are currently underway. Quantification of the diseased RPE area is important to evaluate disease progression or the therapeutic effect of RPE transplantation. However, there are no standard protocols. To address this issue, we developed a 2-step software that enables objective and efficient quantification of RPE-disease area changes by analyzing the early-phase hyperfluorescent area in fluorescein angiography (FA) images. We extracted the Abnormal region. This extraction was based on deep learning-based discrimination. We scored the binarized extracted area using an automated program. Our program’s performance for the same eye from the serial image captures was within 3.1 ± 7.8% error. In progressive AMD, the trend was consistent with human assessment, even when FA images from two different visits were compared. This method was applicable to quantifying RPE-disease area changes over time, evaluating iPSC-RPE transplantation images, and a disease other than AMD. Our program may contribute to the assessment of the clinical course of RPE-disease areas in routine clinics and reduce the workload of researchers.

Ganglion Cell Topography and Retinal Resolution in an Irrawaddy Dolphin (Orcaella brevirostris)

The topographic distribution of retinal ganglion cells was investigated in a retinal wholemount of an Irrawaddy dolphin (Orcaella brevirostris). Two zones of increased concentration of ganglion cells were observed—one in the temporal segment and the other in the nasal segment of the retina. The maximal cell concentration was 250 cell/mm2 in the temporal area and 194 cell/mm2 in the nasal area. Based on the posterior nodal distance of 11 mm, the resolution was evaluated as 19.8 arc min in the temporal retinal area (the frontal visual field) and 22.4 arc min in the nasal retinal area (the temporal visual field). Among retinal ganglion cells, a group of giant cells that ranged from 42 to 52 µm in diameter were observed; these cells represented 8% of the total population. The obtained data allowed us to suggest that the presence of two areas of concentrated ganglion cells is characteristic of many delphinids inhabiting both clear oceanic waters or turbid river waters, whereas low ganglion cell density is associated with optic properties of the media.

Analysis of retinal vessel density and macular flow area in diabetic and healthy participants using optical coherence tomography angiography

Analysis of retinal vessel density and macular flow area in diabetic and healthy participants using optical coherence tomography angiography

Course of retinal ganglion cell loss and microglial activation in two models of neuronal degeneration

AbstractPurposeOrganotypic retinal cultures (COR) are inherently a model of retinal axotomy and detachment. In vivo, optic nerve axotomy causes degeneration of retinal ganglion cells (RGCs). Our objective is to evaluate and compare the time course of RGC death and the activation of microglial cells (MCs) in vivo and in vitro.MethodsC57/Bl6 mice were used. For the in vitro model, retinas were dissected and cultured in supplemented medium, and axotomy in vivo was done to the left optic nerve. In both models, retinas were analyzed from 24 hours to 9 days. RGCs were immunodetected with Brn3a, MCs with Iba1 and the density in the medial retinal area was quantified for both populations.ResultsThe loss of RGCs was similar in vivo and in vitro during the first days, but from 5 days onwards RGC loss is quicker and more abrupt in vitro than in vivo. MC morphology differs between both models and their density is smaller in vitro than in vivo at all time points.ConclusionsRGCs loss in vitro and in vivo follows the same kinetics at early time points. Morphologically, MCs seem to be differently activated in both models, and because their density is lower in vitro than in vivo, it is possible that in vivo either MCs or circulating macrophages invade the retina to cope with RGC degeneration.

Diagnosis of Alzheimer's disease by analyzing the roughness of the retinal layers

AbstractPurposeAlzheimer’s Disease (AD) is the most common cause of dementia. Retinal thickness changes had been reported in different stages of the disease, being these changes a biomarker of AD progression. There is increasing evidence that thinned and thickened regions are interspersed throughout the retinal layers of AD patients, resulting in the roughness of their bounding surfaces and thickness maps. The aim of this work is to prove the roughness of retinal layers, as assessed by the fractal dimension (FD) of their thickness maps, is an early biomarker of AD.MethodsA complete ophthalmological exam and cognitive test (Mini Mental State Examination) was carried out in 24 healthy volunteers and 19 patients with mild AD. Total retinal thickness and retinal layers thickness were studied by optical coherence tomography (OCT) and thickness retinal maps were obtained. From the whole retinal area scanned on each subject only a central square region available from all sample subjects was kept for roughness analysis. In this square, the FD of the thickness map of each retinal layer was calculated as an index of its roughness.ResultsThe FD of retinal layers is significantly higher (p &lt; 0.05) in the AD group, compared to the healthy group. The correlation of FD with cognitive score, visual acuity and age reaches statistical significance in 7 layers. Nearly all (44 out of 45) FD correlations among layers are positive and half of them (23) reached statistical significance (p &lt; 0.05). Factor analysis revealed two groups of retinal layers whose roughness evolves independently: the first includes two layers related to the outer segments and may be influenced by dysregulation of the choroidal vascular network; and the second includes the remaining layers, and may be associated with the inflammatory process of the retina.ConclusionsRoughness is a holistic feature of retinal layers that can be assessed by FD of their thickness maps and is an early biomarker of AD.

The potential of physiotherapy technologies in the rehabilitation of patients with non-exudative form of age-related macular degeneration (drusen)

Evaluation of the effectiveness of rehabilitation complex involving physiotherapy in the form of infrared and magnetic stimulation of the retina, aerogenation with Heliox21 and dry needling in patients with non-exudative AMD (drusen). The study included 84 patients (168 eyes), among them 50 men and 74 women with stage 1 non-exudative AMD, aged 60 to 70 years old (average age 60±3.7 years), who were divided into 2 groups with comparable clinical and functional characteristics. Group 1 included 42 patients (84 eyes) who underwent ophthalmic neurostimulation consisting of daily infrared-magnetic stimulation of the retina for 10 days, 10 procedures of daily aerogenation with Heliox21 and 10 daily procedures of acupuncture. Group 2 included 42 patients (84 eyes) who received only basic parenteral therapy (Nutrof forte 1 tablet per day during the entire observation period), which was also the medication background in the main group. Visual acuity (VA), retinal OCT parameters, local photosensitivity and bioelectrical potential indices were assessed with mfERG. The control time points were before therapy, after 2 weeks, 3 months, 6 months and 12 months. After undergoing therapy with the described physiotherapeutic regimen, a positive effect on functional characteristics was noted - the level of light sensitivity of the central zone of the retina and the amplitude of the electrical biopotential have improved. The indicators of maximally corrected visual acuity and the structure of the ellipsoidal zone of the retina and the choroid did not change during the entire observation period. In patients with non-exudative form of AMD the developed ophthalmic rehabilitation complex involving infrared-magnetic stimulation of the retina, aerogenation with Heliox21 and dry needling promotes improvement of functional characteristics of the central retina in the form of increased maximal light sensitivity of the central retinal area and increased amplitude of bio-electrical potential.

Topical Ketotifen Fumarate Inhibits Choroidal Mast Cell Degranulation and Loss of Retinal Pigment Epithelial Cells in Rat Model for Geographic Atrophy.

PurposeThis study evaluates whether topical ketotifen fumarate (KTF) can prevent geographic atrophy (GA)-like phenotypes in a rat model.MethodsPharmacokinetics (PKs) of KTF after topical administration twice daily for 5 days was analyzed in rat retina, retinal pigment epithelium (RPE)/choroid/sclera, and in plasma by an liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Rats were then given hydrogel implants +/- 48/80 in the superior subconjunctival space and topically treated with 1% and 0.25% of KTF or phosphate buffer saline (PBS) twice daily. Rats were euthanized at 1, 2, 4, and 8 weeks postinjection. Choroidal mast cells (MCs) were stained with nonspecific esterase and the RPE monolayer was labeled with RPE65 and ZO-1 in whole mount choroids. Retinal and choroidal areas were determined in cryosections stained with picrosirius red. Dark-adapted electroretinogram (ERG) was also performed to evaluate retinal function.ResultsPK results showed the highest level of KTF (average 5.6 nM/mg) in the RPE/choroid/sclera in rats given topical 1% KTF. Topical 1% KTF significantly reduced choroidal MC degranulation at 1 week and 2 weeks (both P < 0.001) and RPE loss at 4 weeks (P < 0.001) as well as retinal and choroidal thinning (both P < 0.001) and reduction in ERG amplitude at 8 weeks (P < 0.05) compared to PBS. Similar results were obtained with 0.25% KTF.ConclusionsBoth 1% and 0.25% KTF eye drops effectively reduced MC degranulation, RPE loss, and retinal and choroidal thinning while preventing the decline of ERG amplitude in a GA-like rat model. These data suggest that topical KTF might be a new therapeutic drug for treating GA.Translational RelevanceThe results of this study demonstrate that topical KTF successfully reduced GA-like phenotypes in a rat model and may provide a novel therapy for GA.

Multiple arteriectomies in a case of juvenile retinoschisis with rhegmatogenous retinal detachment

A16-year-old Caucasian boy presented himself with a sudden visual loss in his RE due to a pre-retinal haemorrhage involving the macula. A wide portion of the inferior retina ballooned into the vitreous cavity, extending from the temporal arcades to the ora serrata. Fundoscopy and B-scan ultrasound were compatible with pre-existing retinoschisis, combined with a limited area of probable full-thickness retinal detachment. X-linked retinoschisis was clinically suspected based on the presence of a circumscribed inner retinal elevation area in the inferior-temporal mid periphery of the fellow eye (siblings not available for examination because living outside the European borders).

Quantitative analysis of retinal vasculature in normal eyes using ultra-widefield fluorescein angiography.

To quantify the area and density of retinal vascularity by ultra-widefield fluorescein angiography (UWFA). In a retrospective study, UWFA images were obtained using an ultra-widefield imaging device in 42 normal eyes of 42 patients. Central and peripheral steered images were used to define the edge of retinal vasculature by a certified grader. The length from the center of the optic disc to the edge of retinal vascularity (RVL) in each quadrant and the total retinal vascular perfusion area (RVPA) were determined by the grader using OptosAdvance software. The density of retinal vascularity (RVD) was quantified in different zones of central-steered images using Image J software. Among 42 healthy eyes, the values for mean RVL in each quadrant were 19.007±0.781 mm (superior), 18.467±0.869 mm (inferior), 17.738±0.622 mm (nasal) and 24.241±1.336 mm (temporal). The mean RVPA was 1140.117±73.825 mm2. The mean RVD of the total retina was 4.850%±0.638%. RVD varied significantly between different retina zones (P<0.001), and significant differences existed in the RVD values for total retinal area in patients over 50 years old compared to those under 50 years old (P=0.033). No gender difference was found. The UWFA device can be a promising tool for analyzing the overall retinal vasculature and may provide a better understanding of retinal vascular morphology in normal eyes. Aging may be related to lower RVD.