Subretinal fluid in macular edema secondary to branch retinal vein occlusion.

We identified characteristics of patients with subretinal fluid (SRF) in macular edema (ME) secondary to branch retinal vein occlusion (BRVO) and determined their clinical outcomes after anti-vascular endothelial growth factor (VEGF) treatment. Fifty-seven eyes of BRVO patients with ME were divided into two groups according to the presence or absence of SRF at diagnosis. We compared the aqueous profiles, ocular and systemic characteristics at baseline, and the clinical outcomes. The SRF group had significantly greater central subfield thickness (CST) values and poorer best-corrected visual acuity (BCVA) at baseline compared to the non-SRF group. The former group had significantly higher aqueous levels of interleukin-8, VEGF, and placental growth factor. CST reduction and BCVA improvement during treatment were significantly greater in the SRF group than in the non-SRF group. Consequently, CST values were significantly lower in the SRF group than in the non-SRF group at 12 months, when BCVA did not differ significantly between the two groups. The SRF group required more frequent anti-VEGF treatment over 12 months and exhibited a higher rate of macular atrophy. Based on the aqueous profiles and the number of treatments required, the presence of SRF in BRVO patients appears to be associated with higher disease activity.

Hypertension Likely Drives Arteriolar Wall Thickening in Preclinical Diabetic Retinopathy While Diabetes Drives Wall Thickness in Clinical Retinopathy.

Purpose: Both hypertension and diabetes are known to increase the wall-to-lumen ratio (WLR) of retinal arterioles, but the differential effects are unknown. Here, we study the timing and relative impact of hypertension versus diabetes on the WLR in diabetic retinopathy (DR) to address this unresolved question. Methods: This prospective cross-sectional study compared the retinal arteriolar WLR in 17 healthy eyes, 15 with diabetes but no apparent DR (DM no DR), and 8 with diabetic macular edema (DME) and either nonproliferative or proliferative DR. We imaged each arteriole using adaptive optics scanning laser ophthalmoscopy and measured the WLR using ImageJ. Multiple linear regression (MLR) was performed to estimate the effects of hypertension, diabetes, and age on the WLR. Results: Both subjects with DM no DR and subjects with DME had significantly higher WLR than healthy subjects (0.36 ± 0.08 and 0.42 ± 0.08 vs. 0.29 ± 0.07, 1-way ANOVA P = 0.0009). MLR in healthy subjects and subjects with DM no DR showed hypertension had the strongest effect (regression coefficient = 0.08, P = 0.009), whereas age and diabetes were not significantly correlated with WLR. MLR in all three groups together (healthy, DM no DR, and DME) showed diabetes had the strongest effect (regression coefficient = 0.05, P = 0.02), whereas age and hypertension were not significantly correlated with WLR. Conclusions: Hypertension may be an early driver of retinal arteriolar wall thickening in preclinical DR, independent of age or diabetes, whereas changes specific to DR may drive wall thickening in DME and later DR stages. Translational Relevance: We offer a framework for understanding the relative contributions of hypertension and diabetes on the vascular wall, and emphasize the importance of hypertension control early in diabetes even before DR onset.

Effect of topical bromfenac on intraretinal cystoid lesion in simultaneous cataract and idiopathic epiretinal membrane surgery.

PURPOSE: To investigate the effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs,) bromfenac on the intraretinal cystic lesions (IRC) when performing simultaneous cataract and idiopathic epiretinal membrane (iERM) surgery. METHODS: This study included patients with iERM who had been followed up for 6 months after vitrectomy, membrane removal, and concurrent cataract surgery. Eyes were treated with topical bromfenac or not. The baseline fluorescein angiography (FA) was obtained to assess the microvascular leakage (ML). Structural changes of macula, including IRC and central macular thickness (CMT) were assessed using optical coherence tomography (OCT). The main outcome measures were changes in IRCs and best-corrected visual acuity (BCVA) regarding FA findings. RESULTS: One hundred eighteen eyes were included. IRC and ML were observed in 51 eyes (43.2%) and 63 eyes (53.4%), respectively. The IRC did not show any association with the ML. Of total, 29 eyes (24.6%) were treated with topical bromfenac (Group A). Compared to Group B, topical bromfenac did not show beneficial effects in aspect of preventions for the newly developed IRC and treatment for pre-existed IRC. Whether the ML existed or not, topical bromfenac did not show any different effect on the changes in BCVA and IRC. CONCLUSION: When performing simultaneous cataract and ERM surgery, topical NSAIDs, bromfenac did not show beneficial effects on the preventions and treatment of IRC in both eyes with and without the ML.

Congenital simple hamartoma of the retinal pigment epithelium: 4 cases with multimodal imaging.

BACKGROUND: Congenital simple hamartoma of the retinal pigment epithelium is often identified as an incidental finding. One important issue is the differentiation of these benign lesions from other lesions which could be potentially sight-threatening. METHODS: This study describes 4 cases of congenital simple hamartoma of the retinal pigment epithelium that were referred to a university-based hospital. Multimodal imaging including fundus photo, multicolor fundus photo, fundus autofluorescence, optical coherence tomography (OCT), OCT angiography, fluorescein angiography and multifocal electroretinogram is provided. RESULTS: The first case is a young man with an incidental finding of this lesion. The second and third cases are diabetic patients with congenital simple hamartoma of the retinal pigment epithelium and diabetic macular edema and the fourth one is a case of congenital simple hamartoma of the retinal pigment epithelium with a full-thickness macular hole. CONCLUSIONS: Differentiation of congenital simple hamartoma of the retinal pigment epithelium from other potentially sight-threatening lesions is important. Multimodal imaging can be helpful regarding this issue. Besides typical findings described in the literature, unique features in our cases include concurrent diabetic macular edema and association with a full-thickness macular hole.

Systemic Inflammatory Mediator Levels in Non-Proliferative Diabetic Retinopathy Patients with Diabetic Macular Edema.

PURPOSE: To study the systemic inflammatory mediator levels in non-proliferative diabetic retinopathy (NPDR) patients with diabetic macular edema (DME) and explore the correlation between systemic inflammatory mediators and DME. METHODS: In this prospective study, we included 25 patients without diabetes (control group) and 75 patients with type 2 diabetes mellitus (diabetic group). According to fundus examination, the diabetic group patients were divided into: diabetic patients without diabetic retinopathy (DR) (Non-DR group), NPDR patients without DME (Non-DME group), and NPDR patients with DME (DME group). Serum levels of a broad panel of inflammatory mediators were analysed by multiplex protein quantitative detection technology based on a flow cytometry detection system. RESULTS: The interferon-γ (IFN-γ) levels were significantly higher in DME group and Non-DME group as compared to control group (p = 0.023 and p = 0.033) and Non-DR group (p = 0.009 and p = 0.015). Significantly higher values were obtained in DME group and Non-DME group as compared to control group for the interleukin-8 (IL-8) (p = 0.003 and p = 0.003). The IL-23 levels were significantly elevated in DME group and Non-DR group than in Non-DME group (p = 0.013 and p = 0.004). The diabetic group had significantly higher serum levels of IL-8 and IL-33 (p = 0.001 and p = 0.011), and lower serum levels of tumor necrosis factor-α (TNF-α) (p = 0.027) in comparison with control group. CONCLUSIONS: The changed levels of serum inflammatory mediators suggest that the systemic inflammatory mediators are involved in the pathogenesis of NPDR patients with DME. Such effects can guide clinical monitoring, diagnostic and therapeutic approaches for DME patients at an early stage.

Imaging the Retinal Vascular Mural Cells In Vivo: Elucidating the Timeline of Their Loss in Diabetic Retinopathy.

BACKGROUND: Vascular mural cells (VMCs) are integral components of the retinal vasculature with critical homeostatic functions such as maintaining the inner blood-retinal barrier and vascular tone, as well as supporting the endothelial cells. Histopathologic donor eye studies have shown widespread loss of pericytes and smooth muscle cells, the 2 main VMC types, suggesting these cells are critical to the pathogenesis of diabetic retinopathy (DR). There remain, however, critical gaps in our knowledge regarding the timeline of VMC demise in human DR. METHODS: In this study, we address this gap using adaptive optics scanning laser ophthalmoscopy to quantify retinal VMC density in eyes with no retinal disease (healthy), subjects with diabetes without diabetic retinopathy, and those with clinical DR and diabetic macular edema. We also used optical coherence tomography angiography to quantify capillary density of the superficial and deep capillary plexuses in these eyes. RESULTS: Our results indicate significant VMC loss in retinal arterioles before the appearance of classic clinical signs of DR (diabetes without diabetic retinopathy versus healthy, 5.0±2.0 versus 6.5±2.0 smooth muscle cells per 100 µm; P<0.05), while a significant reduction in capillary VMC density (5.1±2.3 in diabetic macular edema versus 14.9±6.0 pericytes per 100 µm in diabetes without diabetic retinopathy; P=0.01) and capillary density (superficial capillary plexus vessel density, 37.6±3.8 in diabetic macular edema versus 45.5±2.4 in diabetes without diabetic retinopathy; P<0.0001) is associated with more advanced stages of clinical DR, particularly diabetic macular edema. CONCLUSIONS: Our results offer a new framework for understanding the pathophysiologic course of VMC compromise in DR, which may facilitate the development and monitoring of therapeutic strategies aimed at VMC preservation and potentially the prevention of clinical DR and its associated morbidity. Imaging retinal VMCs provides an unparalleled opportunity to visualize these cells in vivo and may have wider implications in a range of diseases where these cells are disrupted.

Quantification of dilated deep capillaries in diabetic retinopathy on optical coherence tomography angiography.

Morphological changes in capillaries are one of major clinical signs in diabetic retinopathy (DR). In this study, we quantified the dilated deep capillaries on optical coherence tomography angiography (OCTA) images. Central 3 × 3 mm en face images were obtained using a swept source OCTA device in 105 eyes of 99 patients with DR. Capillaries with a greater diameter in the deep layers were defined as the dilated deep capillaries, using stepwise image processing. The relative areas of automatically selected capillaries with a great diameter were calculated as the index of the dilated deep capillaries. Most eyes with DR had string-like or dot-like dilated deep capillaries in the OCTA images, which appeared to be dilated capillary segments or microaneurysms histologically. They were distributed more densely in the parafovea than in the central sector, while there were no differences between individual quadrants. The index of the dilated deep capillaries was higher in eyes with DR than in nondiabetic eyes. The index in the central subfield was modestly associated with visual acuity, diabetic macular edema, and proliferative diabetic retinopathy. The quantitative dilated deep capillaries are designated as a biomarker of vision-threatening DR.

Pushing Retinal Imaging Forward: Innovations and Their Clinical Meaning - The 2022 Ophthalmologica Lecture.

Retinal imaging has greatly expanded our understanding of various pathological conditions. This article presents a summary of the key points covered during the 2022 Ophthalmologica Lecture held at the Euretina Congress in Hamburg. The first part of the article focuses on the use of optical coherence tomography angiography to examine and comprehend the choroid in age-related macular degeneration (AMD). Subsequently, we delve into the discussion of the "postreceptor neuronal loss" theory in AMD, which was studied using en face structural optical coherence tomography (OCT). Following that, we explore pertinent findings obtained through cross-sectional OCT in retinal and optic nerve diseases, such as AMD, diabetic macular edema, pathologic myopia, central serous chorioretinopathy, and Leber's hereditary optic neuropathy.

The correlation between peripheral complete blood count parameters and diabetic macular edema in proliferative diabetic retinopathy patients: a cross-sectional study.

Background: Numerous studies have demonstrated that retinal chronic inflammation plays a critical role in the pathogenesis of diabetic macular edema (DME). However, studies about the association between peripheral complete blood count, an inexpensive and easily measurable laboratory index, and DME are limited. Research design and methods: The current study was a hospital-based, cross-sectional study. The participants were inpatients with type 2 diabetes who underwent vitrectomy for PDR, and the contralateral eyes in these PDR patients meeting the criteria were included in the study. Central macular thickness (CMT) was measured automatically and the DME was characterized as CMT ≥ 300 µm. Results: A total of 239 PDR participants were enrolled. The average age was 55.46 ± 10.08 years old, and the average CMT was 284.23 ± 122.09 µm. In the fully adjusted model, for CMT, the results revealed a significantly negative association between CMT and both white blood cell (WBC) count and neutrophil count (ß = -11.95, 95% CI: -22.08, -1.82; p = 0.0218; ß = -14.96, 95% CI: -28.02, -1.90; p = 0.0259, respectively); for DME, the results showed an inverse association between DME and WBC count, monocyte count, and eosinophil count (OR = 0.75, 95% CI: 0.59, 0.95; p = 0.0153; OR = 0.07, 95% CI: 0.00, 0.92; p = 0.0431; OR = 0.03, 95% CI: 0.00, 0.88; p = 0.0420, respectively). Conclusions: In conclusion, our results suggest that WBC and its subtypes in circulation may play an important role in the pathogenesis of DME in PDR patients.

The Role of Müller Cells in Diabetic Macular Edema.

Diabetic macular edema (DME) is a common complication of diabetic retinopathy and is the leading cause of vision loss in diabetic patients. Various factors, such as metabolic disorders and inflammation caused by hyperglycemia, are involved in the occurrence and development of DME, but the specific mechanism is still unclear. Müller cells are a type of macroglial cell unique to the fundus, distributed throughout the retina, and they play a unique role in retinal homeostasis. This article reviews the role of Müller cells in the pathological process of DME and the research progress in the treatment of DME by targeting Müller cells through gene therapy.

The Disorganization of Retinal Inner Layers Is Correlated to Müller Cells Impairment in Diabetic Macular Edema: An Imaging and Omics Study.

The disorganization of retinal inner layers (DRIL) is an optical coherence tomography (OCT) biomarker strictly associated with visual outcomes in patients with diabetic macular edema (DME) whose pathophysiology is still unclear. The aim of this study was to characterize in vivo, using retinal imaging and liquid biopsy, DRIL in eyes with DME. This was an observational cross-sectional study. Patients affected by center-involved DME were enrolled. All patients underwent spectral domain optical coherence tomography (SD-OCT) and proteomic analysis of aqueous humor (AH). The presence of DRIL at OCT was analyzed by two masked retinal experts. Fifty-seven biochemical biomarkers were analyzed from AH samples. Nineteen eyes of nineteen DME patients were enrolled. DRIL was present in 10 patients (52.63%). No statistically significant difference was found between DME eyes with and without DRIL, considering the AH concentration of all the analyzed biomarkers except for glial fibrillary acidic protein (GFAP), a biomarker of Müller cells dysfunction (p = 0.02). In conclusion, DRIL, in DME eyes, seems to strictly depend on a major dysfunction of Müller cells, explaining its role not only as imaging biomarker, but also as visual function Müller cells-related parameter.

2022 Prentice Award Lecture: Advancing Retinal Imaging and Visual Function in Patient Management and Disease Mechanisms.

SIGNIFICANCE: Patient-based research plays a key role in probing basic visual mechanisms. Less-well recognized is the role of patient-based retinal imaging and visual function studies in elucidating disease mechanisms, which are accelerated by advances in imaging and function techniques and are most powerful when combined with the results from histology and animal models.A patient's visual complaints can be one key to patient management, but human data are also key to understanding disease mechanisms. Unfortunately, pathological changes can be difficult to detect. Before advanced retinal imaging, the measurement of visual function indicated the presence of pathological changes that were undetectable with existing clinical examination. Over the past few decades, advances in retinal imaging have increasingly revealed the unseen. This has led to great strides in the management of many diseases, particularly diabetic retinopathy and macular edema, and age-related macular degeneration. It is likely widely accepted that patient-based research, as in clinical trials, led to such positive outcomes. Both visual function measures and advanced retinal imaging have clearly demonstrated differences among retinal diseases. Contrary to initial thinking, sight-threatening damage in diabetes occurs to the outer retina and not only to the inner retina. This has been clearly indicated in patient results but has only gradually entered the clinical classifications and understanding of disease etiology. There is strikingly different pathophysiology for age-related macular degeneration compared with photoreceptor and retinal pigment epithelial genetic defects, yet research models and even some treatments confuse these. It is important to recognize the role that patient-based research plays in probing basic visual mechanisms and elucidating disease mechanisms, combining these findings with the concepts from histology and animal models. Thus, this article combines sample instrumentation from my laboratory and progress in the fields of retinal imaging and visual function.

Effect of peripheral laser photocoagulation retinopexy on macular morphology and optic nerve fiber layer thickness; a prospective case series.

PURPOSE: The goal of the research was to determine the incidence of microstructural alterations in the macula and optic nerve head (ONH) occurred in eyes treated with peripheral laser photocoagulation retinopexy. METHODS: Patients with retinal breaks, retinal holes, retinal dialysis, and lattice degenerations who required peripheral laser photocoagulation retinopexy were recruited in this prospective case series investigation. We performed preoperative and postoperative evaluations, including best corrected visual acuity (BCVA), slit lamp examination, intraocular pressure (IOP) measurement, funduscopic examination, and macular and ONH optical coherence tomography (OCT). RESULTS: Thirty-three eyes of the twenty-three patients enrolled in this study, 14 of which were female. The mean age of the sample was 45.12 ± 9.12 years. The mean refractive error was - 2.45 ± 1.12 Diopters (D). The most prevalent reason for peripheral laser photocoagulation retinopexy was retinal thinning with symptomatic lattice degeneration (90%), followed by retinal hole and break (7%) and retinal dialysis (3%). Between preoperative and postoperative (6-month) evaluation, there was no statistically significant difference in BCVA (P = 0.82), IOP (P = 0.54), central foveal thickness in macular OCT (P = 0.39), or global retinal nerve fiber layer (RNFL) thickness (P = 0.51). There was no association between changes in central foveal thickness and global RNFL thickness and total laser spot numbers (r = - 0.17 P = 0.21, r = 0.06 P = 0.60, respectively). None of patients developed cystoid macular edema (CME) or macular epiretinal membrane (ERM) . CONCLUSION: We found that OCT parameters were not significantly affected by laser retinopexy in patients with high-risk peripheral retinal lesions, also none of our patients had developed ERM, vitromacular traction or CME at 6 months follow up periods.

Potential impact of fluorescein angiography as a primary imaging modality in the management of diabetic retinopathy.

Purpose: To evaluate current practice patterns for Egyptian ophthalmologists in the diagnosis of diabetic retinopathy (DR) and explore potential implications of these approaches on management. Methods: Cross-sectional survey conducted in Egypt amongst practicing ophthalmologists. Results: The study had 203 responses (~6% of all Egyptian ophthalmologists). A majority of respondents were general ophthalmologists (78.2%), practicing for five to ten years (41.9%). In patients with DR and no diabetic macular edema (DME), 33.0% of respondents would use FA in patients with mild DR, 44.3% in patients with moderate DR and 51.2% in patients with severe non-proliferative diabetic retinopathy (NPDR). Color imaging (CI) was used by less than 1% as the sole imaging modality for any level of DR. Approximately 70% of respondents used fluorescein angiography (FA) to grade and base treatment decisions for DR, either alone or in conjunction with dilated eye exams and/or CI. Given the known more severe appearance of DR on FA than on standard color imaging upon which treatment guidelines are based, use of FA as the primary modality over a one-year period could result in PRP that would otherwise not be suggested in approximately 78,820 eyes at an additional cost of $10.1 million US dollars. These numbers are projected to double by 2045. Conclusion: Given that FA detects significantly greater pathology than CI, and that treatment and follow-up recommendations are based on CI, its use as the primary imaging modality in DR grading may result in apparently significantly higher DR severity, with subsequently increased procedures and associated costs.

Morphologic and Functional Changes of Macula and Optic Nerve Head in Adult Kidney Transplant Recipient.

AIM: To assess macular and optic nerve head characteristics in patients after kidney transplantation using noninvasive optical coherence tomography (OCT) imaging. METHODS: The study had a prospective character and was performed during period from November 2019 to November 2020 at the University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina, and included 59 patients with renal graft who underwent OCT. The obtained OCT images, pathologic changes on the fundus, including macula and optic nerve, were analyzed by reviewing nonparametric measures such as scanning laser ophthalmoscope, B-scan, 3D display, as well as parametric measurements such as central macular thickness, optic nerve head excavation, and retinal nerve thickness fiber (RNFL). RESULTS: There is a statistically significant difference in RNFL values (P = 0.031) and cup to disc (P = 0.002) ratio in relation to duration of graft. The highest average values of RNFL was in patients with creatinine clearance <30 mL/min, while average cup to disc ratio was lowest in patients with creatinine clearance >60 mL/min. Optic nerve head edema was bilateral in 9 and unilateral in 5 patients. Fundus examination also revealed changes on posterior segment, including retinal detachment (1 patient), bilateral macular edema (9 patients), unilateral macular edema (3 patients), central serous chorioretinopathy (2 patients), and macular pseudo hole (3 patients). CONCLUSIONS: Different retinal pathology is present in high incidence in patients secondary to renal transplant. Immunosuppressive therapy, older age, and comorbidities are the usual causes of these changes.

Comparison of hyperreflective foci in macular edema secondary to multiple etiologies with spectral-domain optical coherence tomography: An observational study.

BACKGROUND: Hyperreflective foci (HRF) features in macular edema associated with different etiologies may indicate the disease pathogenesis and help to choose proper treatment. The goal of this study is to investigate the retinal microstructural features of macular edema (ME) secondary to multiple etiologies with spectral-domain optical coherence tomography (SD-OCT) and analyze the origin of HRF in ME. METHODS: This was a retrospective study. SD-OCT images were reviewed to investigate macular microstructural features such as the number and distribution of HRF and hard exudates and the internal reflectivity of the cysts. The differences in microstructural features between groups and the correlations between the number of HRF and other parameters were analyzed. RESULTS: A total of 101 eyes with ME from 86 diabetic (diabetic macular edema, DME) patients, 51 eyes from 51 patients with ME secondary to branch retinal vein occlusion (branch retinal vein occlusion-macular edema, BRVO-ME), 59 eyes from 58 central retinal vein occlusion (central retinal vein occlusion-macular edema, CRVO-ME) patients, and 26 eyes from 22 uveitis (uveitic macular edema, UME) patients were included in this study. The number of HRF, the frequency of hard exudates and the enhanced internal reflectivity of the cysts were significantly different among the groups. The number of HRF in the DME group was significantly higher than that in the other groups (all P < 0.05). The frequency of hard exudates and enhanced internal reflectivity of the cysts in the DME group were significantly higher than ME secondary to other etiologies (all P < 0.001). Within the DME group, the number of HRF in the patients with hard exudates was significantly higher than that in the patients without hard exudates (P < 0.001). CONCLUSION: HRF detected with SD-OCT were more frequent in DME patients than in BRVO-ME, CRVO-ME, or UME patients. The occurrence of HRF was correlated with the frequency of hard exudates. HRF may result from the deposition of macromolecular exudates in the retina, which is speculated to be a precursor of hard exudates.

Regional Variety of Reduction in Retinal Thickness of Diabetic Macular Edema after Anti-VEGF Treatment.

Background and Objectives: The presence of refractory cases resistant to anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) is a problem in clinical practice. This study aimed to explore the less responsive area of optical coherence tomography (OCT) 3D map the characteristics of naïve DME cases after their first anti-VEGF. Materials and Methods: In 46 patients with DME who received an intravitreal injection of anti-VEGF agents, retinal thickness in 100 sections of the macular area was measured by 3D-mapping mode using OCT before and 1 month after injection. The density of the microaneurysm (MA) was calculated using merged images of the OCT map and fluorescein angiography. Results: One month after injection, the central retinal thickness significantly decreased (p < 0.0001). In severe edema (retinal thickness more than 500 µm), the area percentages with a reduction rate of the retinal thickness greater than 30% and less than 5% were 6.4 ± 6.6% and 10.1 ± 4.6%, respectively. The reduction rate of the retinal thickness varied from section to section. The mutual distance between the areas of maximum thickness before and after the injection averaged 1.22 ± 0.62 mm apart. The reduction rate of retinal thickness in the thickest region before injection was significantly higher (p = 0.02), and that in the thickest region after injection was lower (p = 0.001) than in the other regions. MA density in the residual edema was significantly higher than in the edema-absorbed area (p = 0.03). Conclusion: DME has areas that show low response to the reduction in retinal thickness with anti-VEGF therapy. A high density of MA may be associated with this pathogenesis.

Clinical significance of metabolic quantification for retinal nonperfusion in diabetic retinopathy.

Diabetic retinopathy (DR) is characterized by microvascular changes including ischemia. Degradation and metabolic changes of various retinal cells occur during ischemia. Ischemic region containing more cells will lead to greater metabolic impairment. We analyzed the non-perfusion region (NPR) by integrating histologic mapping with ultra-widefield fluorescein angiography (UWF FA) images. We also investigated the correlations of the weighted ischemic index (ISI) considering the regional distribution of retinal cells with cytokines, macular edema (ME), and neovascularization (NV). In this study, 32 patients with treatment-naïve DR and 21 age-matched control participants were included. The difference between the non-weighted and weighted ISI of NPR with leakage was greatest at the posterior region. The weighted ISI of NPR with leakage was correlated with MCP-1, IL-8, IL-6, PlGF, and VEGF-A levels, while the non-weighted ISI of NPR with leakage was correlated with IL-8 and IL-6 levels. The presence of baseline ME or NV in patients with DR was associated with the weighted ISI, with a stronger association when cones and rods were weighted. The weighted ISI reflecting both metabolic activity and cell distribution demonstrated a better correlation with clinical features and was more valuable in NPR with leakage than non-weighted ISI, which previous studies conventionally used.

The Changes of Irisin and Inflammatory Cytokines in the Age-Related Macular Degeneration and Retinal Vein Occlusion.

Purpose: Age-related macular degeneration (AMD) and retinal vein occlusion (RVO) are irreversible chorioretinal diseases, which might induce severe damage in visual function. The metabolic factor and inflammatory factors might play important roles in the pathogenesis of AMD and RVO. The levels of irisin and 14 cytokines were analyzed in aqueous humor of AMD and RVO eyes to evaluate the roles of irisin and inflammatory factors. Methods: We collected aqueous humor samples from patients with AMD (n = 27), RVO (n = 30), and cataract (as control, n = 23) eyes. Samples were assayed using ELISA kit for irisin and a multiplex immunoassay kit for 14 cytokines. The macular thickness (MT) was measured with OCT in all included eyes. Results: MT in the RVO group is significantly higher than that in the AMD or control group. Irisin levels in the aqueous samples of AMD and RVO eyes were both significantly lower than that in the control. Furthermore, a positive correlation was found between irisin and MT in the RVO. Compared with the controls, AMD eyes had significantly higher levels of BDNF, VEGF-A, VEGF-R1, VEGF-R2, IL-10, TNF-α, VCAM-1, IP-10, and MCP-1. Similarly, RVO eyes had significantly higher levels of BDNF, VEGF-A, VEGF-R1, VEGF-R2, IL-6, IL-8, IL-10, TNF-α, ICAM-1, VCAM-1, IP-10, and MCP-1. However, there was no significant difference between the levels of PDGF-BB or TNF-ß in these three groups. A negative correlation was found between VEGF-A and MT in AMD, as well as in control. Furthermore, a positive correlation was found between IL-6 and MT in the 80 included eyes, as well as in RVO. A positive correlation was found between ICAM-1 and MT in the 80 included eyes, as well as in RVO. Conclusions: The metabolic factor, irisin levels in the aqueous humor are decreased in AMD and RVO eyes and show a positive correlation between irisin and MT in RVO eyes, prompting researchers to explore the relationship between irisin and macular edema. We also identified the higher expression of vascular growth factors (VEGF-A, VEGF-R1, and PDGF-BB), inflammatory cytokines (IL-6, IL-8, IL-10, and TNF-α), and chemokines (ICAM-1, VCAM-1, IP-10, and MCP-1) in AMD and RVO eyes.

SYSTEMATIC CORRELATION OF CENTRAL SUBFIELD THICKNESS WITH RETINAL FLUID VOLUMES QUANTIFIED BY DEEP LEARNING IN THE MAJOR EXUDATIVE MACULAR DISEASES.

PURPOSE: To investigate the correlation of volumetric measurements of intraretinal (IRF) and subretinal fluid obtained by deep learning and central retinal subfield thickness (CSFT) based on optical coherence tomography in retinal vein occlusion, diabetic macular edema, and neovascular age-related macular degeneration. METHODS: A previously validated deep learning-based approach was used for automated segmentation of IRF and subretinal fluid in spectral domain optical coherence tomography images. Optical coherence tomography volumes of 2.433 patients obtained from multicenter studies were analyzed. Fluid volumes were measured at baseline and under antivascular endothelial growth factor therapy in the central 1, 3, and 6 mm. RESULTS: Patients with neovascular age-related macular degeneration generally demonstrated the weakest association between CSFT and fluid volume measurements in the central 1 mm (0.107-0.569). In patients with diabetic macular edema, IRF correlated moderately with CSFT (0.668-0.797). In patients with retinal vein occlusion, IRF volumes showed a moderate correlation with CSFT (0.603-0.704). CONCLUSION: The correlation of CSFT and fluid volumes depends on the underlying pathology. Although the amount of central IRF seems to partly drive CSFT in diabetic macular edema and retinal vein occlusion, it has only a limited impact on patients with neovascular age-related macular degeneration. Our findings do not support the use of CSFT as a primary or secondary outcome measure for the quantification of exudative activity or treatment guidance.