Pregabalin as a probable cause of central serous chorioretinopathy: Two case reports

Pregabalin is commonly used for the treatment of neuropathic pain and is attributed to adverse effects of peripheral vasodilation and peripheral edema. Central serous chorioretinopathy (CSCR) is characterized by choroidal fluid leaks from choroidal vessels under the retina, causing focal retinal detachment with macular vision loss. Herein, we report two cases admitted to our clinic with vision loss while under pregabalin treatment. Upon eye examination, both patients were diagnosed with acute CSCR. Pregabalin treatment was discontinued upon the diagnosis of CSCR. We consider that the use of pregabalin in the presented two cases may be the causal effect of the CSCR diagnosis, as pathophysiology of CSCR is in parallel with the edema-related adverse effects of pregabalin.

Quantitative Assessment of Three-Dimensional Choroidal Vascularity and Choriocapillaris Flow Signal Voids in Myopic Patients Using SS-OCTA

Purpose: To compare the choroidal vascularity of large- and middle-sized choroidal vessels and choriocapillaris (CC) perfusion in patients with different degrees of myopia using swept-source optical coherence tomography angiography (SS-OCTA). Methods: One hundred and thirteen people with myopia were enrolled. SS-OCTA was performed to analyze the choroidal vascularity and CC perfusion. Three-dimensional (3D) choroidal vascularity index (CVI) and choroidal luminal volumes (LV) were obtained by artificial intelligence segmentation of the choroidal lumen in Volume OCT images. CC perfusion was assessed by flow signal voids (FSVs). Results: In the macular, multiple linear regression model showed that choroidal thickness (CT), total choroidal volume, LV, and choroidal stromal volume were negatively correlated with axis length (AL), respectively (all p < 0.001). Three dimensional CVI was negatively associated with AL (p < 0.05). FSV% was positively correlated with age only (p < 0.001). Additionally, after adjustment for age and AL, FSV% had a significant negative correlation with CT (p < 0.05). Conclusion: Choroidal vascularity decreases gradually with increasing severity of myopia. The decrease of CC blood perfusion was related to a higher severity of myopia and the thinning of choroid.

Association between Vortex Vein Engorgement and Treatment Outcomes of Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy

Purpose: To investigate the influence of the number of engorged vortex veins on treatment outcomes in eyes with treatment-naïve polypoidal choroidal vasculopathy (PCV) undergoing intravitreal aflibercept monotherapy.Methods: The medical charts of 65 patients with PCV who underwent intravitreal aflibercept injection were reviewed retrospectively. The number of quadrants of vortex vein engorgement was evaluated in the middle phase of ultra-widefield indocyanine green angiography, which was classified as extended engorgement if the dilated choroidal vessels expanded the macula. Associations between treatment outcomes with age, subfoveal choroidal thickness (SFCT), central retinal thickness, and vortex vein engorgement were investigated using univariate and multivariate analyses.Results: There were no significant differences in best-corrected visual acuity (BCVA), SFCT, and central retinal thickness at baseline and 12 months, according to the number of vortex vein engorgement. However, an increase in the number of vortex vein engorgement extending to the macula was associated with a thick SFCT (p = 0.038), a greater number of injections (p = 0.041), low BCVA at 12 months (p = 0.038), and a less dry macula at 12 months (p = 0.026). In the multivariate analysis, the number of quadrants with vortex vein engorgement extending to the macula was significantly associated with BCVA changes at 12 months, total number of injections, and a dry macula at 12 months (p = 0.030, p = 0.030, p = 0.020, respectively).Conclusions: More quadrants with vortex vein engorgement extending to the macula in PCV was associated with unfavorable visual outcomes, a less dry macula at 12 months, and a greater number of injections at 1 year after intravitreal aflibercept injection. Clinicians should keep in mind that vortex vein engorgement extending to the macula may be a new biomarker in predicting treatment outcomes in PCV.

Cell Stiffening Contributes to Complement-mediated Injury of Choroidal Endothelial Cells in Early AMD

Age-related macular degeneration (AMD) is the leading cause of blindness in the aging population. Yet, no therapies exist for ~85% of all AMD patients who have the dry form that is marked by degeneration of the retinal pigment epithelium (RPE) and underlying choroidal vasculature. As the choroidal vessels are crucial for RPE development and maintenance, understanding how they degenerate may lead to effective therapies for dry AMD. One likely causative factor for choroidal vascular loss is the cytolytic membrane attack complex (MAC) of the complement pathway that is abundant on choroidal vessels of humans with early dry AMD. To examine this possibility, we studied the effect of complement activation on choroidal endothelial cells (ECs) isolated from a rhesus monkey model of early AMD that, we report, exhibits MAC deposition and choriocapillaris endothelial loss similar to that seen in human early AMD. Treatment of choroidal ECs from AMD eyes with complement-competent normal human serum caused extensive actin cytoskeletal injury that was significantly less pronounced in choroidal ECs from young normal monkey eyes. We further show that ECs from AMD eyes are significantly stiffer than their younger counterparts and exhibit peripheral actin organization that is distinct from the longitudinal stress fibers in young ECs. Finally, these differences in complement susceptibility and mechanostructural properties were found to be regulated by the differential activity of small GTPases Rac and Rho because Rac inhibition in AMD cells led to simultaneous reduction in stiffness and complement susceptibility while Rho inhibition in young cells exacerbated complement injury. Thus, by identifying cell stiffness and cytoskeletal regulators Rac and Rho as important determinants of complement susceptibility, the current findings offer a new mechanistic insight into choroidal vascular loss in early AMD that warrants further investigation for assessment of translational potential.

Changes in Plasma VEGF and PEDF Levels in Patients with Central Serous Chorioretinopathy

Background and Objectives: Retinal pigment epitheliopathy and hyperpermeability of choroidal vessels were postulated to be involved in the pathogenesis of central serous chorioretinopathy (CSC). Imbalanced levels of vascular endothelial growth factor (VEGF) and pigment-epithelium–derived factor (PEDF) were previously implicated in the development of chorioretinal diseases characterized by increased vascular permeability. We aimed to compare the plasma levels of proangiogenic VEGF and antiangiogenic PEDF for 26 patients with acute CSC, 26 patients with chronic CSC, and 19 controls. Materials and Methods: VEGF and PEDF levels were measured using a multiplex immunoassay or enzyme-linked immunosorbent assay. Correlations with disease duration were assessed. Results: VEGF levels differed between groups (p = 0.001). They were lower in patients with acute CSC (p = 0.042) and chronic CSC (p = 0.018) than in controls. PEDF levels were similar in all groups. The VEGF-to-PEDF ratio was lower in CSC patients than in controls (p = 0.04). A negative correlation with disease duration was noted only for PEDF levels in the group with chronic CSC (rho = −0.46, p = 0.017). Discussion: Our study confirmed that patients with CSC have imbalanced levels of VEGF and PEDF. This finding may have important implications for the pathogenesis of CSC. VEGF-independent arteriogenesis rather than angiogenesis may underlie vascular abnormalities in these patients.

Combination of Pigment Epithelium Derived Factor (PEDF) With Anti- Vascular Endothelial Growth Factor (VEGF) Therapy Protects the Retina From Ischemic Damage

BackgroundOcular ischemia is a vision-threatening disease, and is a medical condition associated with many ocular diseases. Anti-vascular endothelial growth factor (VEGF) therapy successfully prevents the progression of retinal neovascularization caused by ocular ischemia. Anti-VEGF therapy has limitations related to its side effects and suppression of physiological revascularization. Pigment epithelium derived factor (PEDF) has anti-angiogenesis and neurotrophic neuroprotective functions. It is a promising agent in the treatment of ischemia-induced retinal neurodegeneration. The purpose of this study is to investigate the effect of PEDF and anti-VEGF and the combined therapy on the ischemic rat eye model ex vivo.MethodsWe have previously established an ex vivo model of rat ocular ischemia by incubating the freshly enucleated eye in Dulbecco's modified eagle medium (DMEM) at 4 ℃ for 14 hours. This ex vivo eye model has already been confirmed as an ocular ischemia model. In this study, 36 eyes of 18 rats were used and each group included 6 eyes. The PEDF protein (10μg, 4μl), anti-VEGF drug (Avastin, 50μg, 4μl) or combined PEDF/Avastin (10μg PEDF + 50μg Avastin, 4μl) were intravitreally injected after eye enucleation. Fourteen hours later, eyes were fixed by formalin and immunohistochemical staining for VEGF, PEDF and glial fibrillary acidic protein (GFAP) was performed. The immunohistochemical staining intensity was analyzed for each group. Tunnel staining was used to determine the apoptosis of retinal neural cells.ResultsThe immunohistochemical staining intensity of VEGF and GFAP was significantly reduced in the neuroretina, the RPE cell layer and the choroidal vessels of the double treatment (PEDF/Anti-VEGF) eyes compared to the vehicle, PEDF, and anti-VEGF treatment alone. The intravitreally injected PEDF protein can penetrate the retina and locate in the neural retina, the RPE layer and the choroidal vessels. Compared to the vehicle-treated group, both the PEDF-treated and the double-treated groups showed significantly decreased number of TUNEL-positive nuclei, and the PEDF/Anti-VEGF treatment group had the least TUNEL-positive nuclei.ConclusionsPEDF/Anti-VEGF therapy shows a synergistic effect in the treatment of ischemic eye diseases. The combination of PEDF and anti-VEGF drug (Avastin) is a possible therapeutic strategy against ischemic retinal and choroidal diseases.

Chronic choriocapillaris ischemia in dilated vortex vein region in pachychoroid neovasculopathy

We evaluated choroidal congestion using multimodal imaging in pachychoroid neovasculopathy (PNV). In a retrospective case series of 100 eyes of 99 treatment-naïve PNV patients, their clinical records were reviewed and the corresponding multimodal imaging studies were analyzed. We assessed areas of choriocapillaris filling delay which overlapped with dilated outer choroidal vessels, choroidal neovascularization (CNV), and retinal pigment epithelium (RPE) atrophy. The study subjects were 78 men (78.8%) and 21 women (21.2%). The mean patient age was 67.5 ± 10.5 years. On indocyanine green angiography, all eyes showed choriocapillaris filling delay in the early phase. Dilated outer choroidal vessels were demonstrated in all eyes by en face optical coherence tomography. The areas of choriocapillaris filling delay overlapped extensively with that of dilated outer choroidal vessels. All eyes showed CNV localized within the sites of choriocapillaris filling delay. RPE atrophy was noted in 71 eyes (71.0%), and 68 of these (95.8%) had RPE atrophy within the areas showing choriocapillaris filling delay. These findings indicate that chronic choriocapillaris ischemia secondary to vortex vein congestion may lead to CNV development as well as RPE atrophy in eyes with PNV.

Impact of large choroidal vessels on choriocapillaris flow deficit analyses in optical coherence tomography angiography

Purpose To investigate the impact of large choroidal vessels (LCV) on Choriocapillaris (CC) flow deficit (FD) analyses with swept-source optical coherence tomography angiography (SS-OCTA) Design Prospective, cross-sectional study. Methods Macular 6x6mm SS-OCTA scans were obtained from intermediate age-related macular degeneration (iAMD) and healthy eyes. Images were captured and processed according to most common standards and analyzed for percentage of flow-deficits (FD%) within four 1x1mm squares at the corners of each image. Choroidal thickness (CT), iris color and refraction error were considered as potential influential factors for LCV visibility. A linear mixed model and logistic regression models were calculated for statistical evaluation. Results Sixty-nine iAMD and 49 age-matched healthy eyes were enrolled. LCV were visible in at least one sector in 52% of iAMD and 47% of healthy eyes. Within the iAMD group FD% were significantly lower in areas containing LCV (p = 0.0029). Increasing CT resulted in an odds ratio decrease of LCV (OR: 0.94, p<0.0001). Below a CT value of ≤118μm LCV could be expected with a sensitivity of 86% and a specificity of 85%. Conclusions LCV can significantly affect CC FD analyses of SS-OCTA images. Their visibility is negatively associated with CT. The impact of LCV should be taken into account when performing CC FD assessments, especially in patients where reduced CT is to be expected and inclusion of affected areas should be considered carefully.

Choroidal microvasculature dropout is spatially associated with optic nerve head microvasculature loss in open-angle glaucoma

The presence of parapapillary choroidal microvasculature dropout (CMvD) may affect optic nerve head (ONH) perfusion in glaucoma patients, since parapapillary choroidal vessels provide vascular supply to the neighboring ONH. However, it remains to be determined whether the presence of parapapillary CMvD is associated with diminished perfusion in the nearby ONH. The present study investigated the spatial relationship between CMvD and ONH vessel density (ONH-VD) loss in open-angle glaucoma (OAG) eyes using optical coherence tomography angiography (OCT-A). This study included 48 OAG eyes with a single localized CMvD confined to the inferotemporal parapapillary sector and 48 OAG eyes without CMvD, matched for demographic and ocular characteristics. Global and regional ONH-VD values were compared between eyes with and without CMvD. The relationships between ONH-VD outcomes and clinical variables were assessed. ONH-VDs at the inferotemporal ONH sectors corresponding to the CMvD location were significantly lower in eyes with compared to those without CMvD. Multivariable linear regression analyses indicated that a lower inferotemporal ONH-VD was independently associated with CMvD presence and a greater CMvD angular extent (both P < 0.05). The localized presence of parapapillary CMvD in OAG eyes is significantly associated with ONH-VD loss in the neighboring ONH location, with a spatial correlation.

Choroidal shift in myopic eyes in the 10-year follow-up Beijing eye study

The aim of the study was to assess longitudinal changes in the spatial relationship of the choroidal vasculature to retinal vasculature in myopic eyes. In the population-based longitudinal Beijing Eye Study in 2001/2011, we examined all highly myopic eyes with assessable fundus photographs and a randomized group of non-highly myopic. Using fundus photographs, we qualitatively assessed changes in the location of major choroidal vessels in relationship to retinal vessels. The study consisted of 85 highly myopic eyes (58 participants;age:64.8 ± 9.4 years) and 85 randomly selected non-highly myopic eyes. A choroidal shift in relationship to the retinal vessels was detected more often in the highly myopic group than the non-highly myopic group (47/85 (55%) vs 6/85 (7%); P < 0.001). In the highly myopic group, the choroidal vessel shift occurring on the disc-fovea line in 39 (44%) eyes, was similar to, or smaller than, the enlargement in gamma zone width in 26 (67%) eyes and in 11 (28%) eyes respectively. The choroidal vessel shift was larger (P = 0.002) in eyes without choroidal vessels in gamma zone than in eyes with large choroidal vessels in gamma zone. In 14 (17%) eyes, a localized centrifugal choroidal shift was observed in association with an increase in the stage of myopic maculopathy. The results suggest that highly myopic eyes show a change in the position of large choroidal vessels in relationship to retinal vessels, in association with development or enlargement of gamma zone and an increase in the stage of myopic maculopathy.