Potential role of CTSS in AMDImmune modulatory and anti-angiogenic effects of cathepsin S knockdown in ARPE-19 cells.

We aimed to determine the role of cathepsin S (CTSS) in modulating oxidative stress-induced immune and inflammatory reactions and angiogenesis in age-related macular degeneration. Human retinal pigment epithelium cells line ARPE-19 (immature) were maintained and treated with H2O2. The expression of CTSS, inflammatory cytokines, and complement factors induced by oxidative stress was compared between cells incubated without (control) and with CTSS knockdown (using small interfering ribonucleic acid; siRNA). To evaluate the role of CTSS in angiogenesis, we assayed tube formation using human umbilical vein endothelial cells and conditioned medium from ARPE-19 cells. We also used a mouse model of laser-induced choroidal neovascularization. CTSS levels were higher in ARPE-19 cells treated with H2O2 than in control cells. Oxidative stress-induced CTSS resulted in significantly elevated transcription of nuclear factor kappa B-dependent inflammatory cytokines, complement factors C3a and C5a, membrane attack complex (C5b-9), and C3a and C5a receptors. siRNA-mediated knockdown of CTSS reduced the number of inflammatory signals. Furthermore, oxidative stress-induced CTSS regulated the expression of peroxisome proliferator-activated receptor γ and vascular endothelial growth factor A/Akt serine/threonine kinase family signaling, which led to angiogenesis. Tube formation assays and mouse models of choroidal neovascularization revealed that CTSS knockdown ameliorated angiogenesis in vitro and in vivo. The present findings suggest that CTSS modulates the complement pathway, inflammatory reactions, and neovascularization, and that CTSS knockdown induces potent immunomodulatory effects. Hence, it could be a promising target for the prevention and treatment of early- and late-stage age-related macular degeneration.

Cathepsin S Knockdown Suppresses Endothelial Inflammation, Angiogenesis, and Complement Protein Activity under Hyperglycemic Conditions In Vitro by Inhibiting NF-κB Signaling.

Hyperglycemia plays a key role in the development of microvascular complications, endothelial dysfunction (ED), and inflammation. It has been demonstrated that cathepsin S (CTSS) is activated in hyperglycemia and is involved in inducing the release of inflammatory cytokines. We hypothesized that blocking CTSS might alleviate the inflammatory responses and reduce the microvascular complications and angiogenesis in hyperglycemic conditions. In this study, we treated human umbilical vein endothelial cells (HUVECs) with high glucose (HG; 30 mM) to induce hyperglycemia and measured the expression of inflammatory cytokines. When treated with glucose, hyperosmolarity could be linked to cathepsin S expression; however, many have mentioned the high expression of CTSS. Thus, we made an effort to concentrate on the immunomodulatory role of the CTSS knockdown in high glucose conditions. We validated that the HG treatment upregulated the expression of inflammatory cytokines and CTSS in HUVEC. Further, siRNA treatment significantly downregulated CTSS expression along with inflammatory marker levels by inhibiting the nuclear factor-kappa B (NF-κB) mediated signaling pathway. In addition, CTSS silencing led to the decreased expression of vascular endothelial markers and downregulated angiogenic activity in HUVECs, which was confirmed by a tube formation experiment. Concurrently, siRNA treatment reduced the activation of complement proteins C3a and C5a in HUVECs under hyperglycemic conditions. These findings show that CTSS silencing significantly reduces hyperglycemia-induced vascular inflammation. Hence, CTSS may be a novel target for preventing diabetes-induced microvascular complications.

Hyper- and hypo-perfusion of choriocapillaris in the eyes with pachychoroid pigment epitheliopathy.

PURPOSE: To evaluate the changes in choriocapillaris vessel density (VD) in eyes with pachychoroid pigment epitheliopathy (PPE) using swept-source optical coherence tomography (OCT) angiography (OCTA). METHODS: This study included 83 eyes with PPE and 42 control eyes. We collected OCT and OCTA parameters, including central point thickness, subfoveal choroidal thickness (SFChT), and choriocapillaris VD of the fovea (CC fovea) and parafovea. The parafoveal area was divided into superior, nasal, inferior, and temporal choriocapillaris areas. Maximum (CC max) and minimum (CC min) choriocapillaris VD were defined as the highest and lowest values among the four parafoveal subfield VDs, respectively. We analyzed the average choriocapillaris VD, CC max, CC min, CC fovea, and the difference between CC max and CC min (CC delta) individually and compared all the parameters between PPE and control eyes. RESULTS: CC max (56.0% ± 1.7%) was significantly higher and CC min (50.9% ± 2.0%) significantly lower in eyes with PPE than in control eyes (CC max, 55.3% ± 1.0%, P = 0.006; CC min, 51.5% ± 1.3%, P = 0.046). The CC delta value (5.0% ± 2.1%) and SFChT (389.9 ± 129.9 µm) were also significantly higher in eyes with PPE than in the control group (3.7% ± 1.5%, P < 0.001; 268.2 ± 102.2 µm, P < 0.001; respectively). CONCLUSIONS: Choriocapillaris VD showed higher variability (hyperperfusion and hypoperfusion) in eyes with PPE than in control eyes. Choriocapillaris hypoperfusion may precede the development of PPE; however, choriocapillaris hyperperfusion is associated with projection artifacts.

Structural changes in the retina after implantation of subretinal three-dimensional implants in mini pigs.

The retinal structural changes after subretinal implantation of three-dimensional (3D) microelectrodes were investigated in a mini pig. Three types of electrode were implanted into the subretinal spaces of nine mini pigs: 75-µm-high 3D electrodes on a 200-µm-thick right-angled polydimethylsiloxane (PDMS) substrate (group 1); a 140-µm-thick sloped PDMS substrate without electrodes (group 2); and a 140-µm-thick sloped PDMS substrate with 20-µm-high 3D electrodes (group 3). One mini pig was used as a control. Spectral domain-optical coherence tomography (SD-OCT) images were obtained at baseline and 2, 6, and 12 weeks post-surgery. Retinal specimens were immunostained using a tissue-clearing method 3 months post-implantation. The 75-µm-high 3D electrodes progressively penetrated the inner nuclear layer (INL) and touched the inner plexiform layer (IPL) 2 weeks post-surgery. At 6 weeks post-operatively, the electrodes were in contact with the nerve-fiber layer, accompanied by a severe fibrous reaction. In the other groups, the implants remained in place without subretinal migration. Immunostaining showed that retinal ganglion and bipolar cells were preserved without fibrosis over the retinal implants in groups 2 and 3 during the 12-week implantation period. In summary, SD-OCT and immunohistology results showed differences in the extent of reactions, such as fibrosis over the implants and penetration of the electrodes into the inner retinal layer depending on different types of electrodes. A sloped substrate performed better than a right-angled substrate in terms of retinal preservation over the implanted electrodes. The 20-µm-high electrodes showed better structural compatibility than the 75-µm-high 3D electrodes. There was no significant difference between the results of sloped implants without electrodes and 20-µm-high 3D electrodes, indicating that the latter had no adverse effects on retinal tissue.

Differences in the incidence of aflibercept-related sterile endophthalmitis according to types of disposable syringes used.

PURPOSE: To evaluate the difference between the incidences of sterile endophthalmitis after administration of intravitreal aflibercept injection using two different types of syringes. METHODS: We administered a total of 498 intravitreal aflibercept injections between September 2017 and August 2021. The disposable syringe used was changed from a 1-mL disposable syringe (Profi syringe, Shinchang Medical., Ltd. Korea) to a 1-mL Becton Dickenson Luer-Lok syringe (BD, Franklin, NJ, USA) in September 2019. Thus, the patients who received injections before and after September 1, 2019, were classified into group 1 and group 2, respectively. The incidence of aflibercept-related sterile endophthalmitis between the two groups was compared. RESULTS: In group 1, six (2.791%) out of 215 cases were diagnosed with sterile endophthalmitis and prescribed topical or oral steroids. In group 2, one (0.353%) out of 283 cases was diagnosed with sterile endophthalmitis and prescribed a steroid eye drop. The incidence of sterile endophthalmitis was significantly different between the two groups (P = 0.046). CONCLUSION: The BD Luer-Lok syringe is associated with a lower incidence of aflibercept-related sterile endophthalmitis than the conventional polypropylene syringe. Differences in immunogenicity associated with silicone oil lubricants within the syringes might be one of the potential reasons behind the difference in the incidence of the sterile endophthalmitis.

Deficits in color detection in patients with Alzheimer disease.

Deficits in color vision and related retinal changes hold promise as early screening biomarkers in patients with Alzheimer's disease. This study aimed to determine a cut-off score that can screen for Alzheimer's dementia using a novel color vision threshold test named the red, green, and blue (RGB) modified color vision plate test (RGB-vision plate). We developed the RGB-vision plate consisting of 30 plates in which the red and green hues of Ishihara Plate No.22 were sequentially adjusted. A total of 108 older people participated in the mini-mental state examination (MMSE), Ishihara plate, and RGB-vision plate. For the analyses, the participants were divided into two groups: Alzheimer's dementia (n = 42) and healthy controls (n = 38). K-means cluster analysis and ROC curve analysis were performed to identify the most appropriate cut-off score. As a result, the cut-off screening score for Alzheimer's dementia on the RGB-vision plate was set at 25, with an area under the curve of 0.773 (p<0.001). Moreover, there was a negative correlation between the RGB-vision plate thresholds and MMSE scores (r = -0.36, p = 0.02). In conclusion, patients with Alzheimer's dementia had a deficit in color vision. The RGB-vision plate is a potential early biomarker that may adequately detect Alzheimer's dementia.

CORRELATION OF PHOTORECEPTOR INTEGRITY WITH RETINAL VESSEL DENSITY AND CHORIOCAPILLARIS IN EYES WITH DIABETIC RETINOPATHY.

PURPOSE: To investigate the correlation of foveal photoreceptor integrity with the vessel density (VD) of the retina and choriocapillaris using swept source optical coherence tomography angiography in eyes with diabetic retinopathy. METHODS: We retrospectively reviewed subjects having eyes with diabetic retinopathy, who underwent optical coherence tomography angiography using swept source optical coherence tomography (DRI OCT Triton; Topcon). We analyzed the area of the foveal avascular zone and VDs of the superficial capillary plexus, deep capillary plexus, and choriocapillaris. The length of the lateral extent of ellipsoid zone disruption, central subfield thickness, and subfoveal choroidal thickness were measured. Furthermore, we analyzed factors that were closely associated with the length of ellipsoid zone disruption. RESULTS: A total of 159 eyes with diabetic retinopathy and 30 healthy control eyes were included in this study. In all eyes, the lengths of ellipsoid zone disruption were positively correlated with the foveal avascular zone area (P = 0.009). However, they were negatively correlated with the parafoveal VD of the superficial capillary plexus (P = 0.049), the foveal VD of deep capillary plexus (P = 0.003), and that of the choriocapillaris (P = 0.036). CONCLUSION: The size of the foveal avascular zone and ischemia at the deep capillary plexus may play an important role in maintaining foveal photoreceptor integrity in eyes with diabetic retinopathy. Considering optical coherence tomography angiography artifacts, such as projection and shadowing, future studies are required to reveal the correlation between ellipsoid zone disruption and the VD of the choriocapillaris.

Correlation of Renal Profiles with Choroidal Vascularity Index in Eyes with Diabetic Retinopathy.

The vascular system is affected by systemic conditions, including diabetes, hypertension, and cardiovascular disease. The choroid is an important vascular tissue surrounding the sensory retina. However, the relationship between the choroid and systemic factors in patients with diabetes has rarely been investigated. Here, we assessed the correlation of renal profiles with choroidal vasculature in eyes with diabetic retinopathy (DR) using a retrospective study design. The study included 131 patients with diabetes who underwent swept-source optical coherence tomography and routine medical work-up within a 4-week period between 1 February 2016 and 30 October 2018. Consecutive patients with treatment-naïve DR who did not receive any subsequent treatment were included. The distribution of patients according to the DR stage was as follows: no DR, 32 patients; mild-to-moderate non-proliferative DR (NPDR), 33 patients; severe NPDR, 34 patients; and treatment-naïve proliferative DR, 32 patients. Multivariate regression analyses showed that the choroidal vascularity index (CVI) of naïve eyes with DR was negatively correlated with age (p = 0.013) and the serum levels of phosphorus (p = 0.002) and positively correlated with subfoveal choroidal thickness (p < 0.001). Taken together, our findings suggest that a lower CVI is associated with phosphorus retention in patients with chronic kidney disease.

The simply modified intrascleral fixation using round flange (SMURF) technique for intrascleral intraocular lens fixation.

We describe a simply modified intrascleral fixation using round flange (SMURF) technique and report the clinical outcomes of the surgery. Forty-one eyes of 41 consecutive patients, with intraocular lens (IOL) dislocation, crystalline lens subluxation, and zonular weakness, who underwent surgery using the SMURF technique were included. The modified technique included the use of a conventional 27-gauge needle, a non-bent needle, oblique sclerotomy, direct threading of the leading haptic, and simple placement of the following haptic. IOLs were successfully placed and showed good centring. There were no cases of wound leakage or hypotony during the early postoperative period. Postoperative complications included vitreous haemorrhage in one eye (2.4%), intraocular pressure elevation in one eye (2.4%), and iris capture in six eyes (14.6%). There were no cases of postoperative retinal detachment, cystoid macular oedema, endophthalmitis, or IOL dislocation during the follow-up period. We proposed a few modifications in the intrascleral flanged technique for IOL fixation. The modified technique is a simple, easy, and minimally invasive procedure for successful IOL intrascleral fixation.

An experimental pig model with outer retinal degeneration induced by temporary intravitreal loading of N-methyl-N-nitrosourea during vitrectomy.

We aimed to develop an outer retinal degeneration pig model induced by temporary intravitreal loading of N-methyl-N-nitrosourea (MNU) during vitrectomy. In a preliminary experiment involving 5 mini-pig cases to determine the appropriate concentration of MNU, the vitreous cavity of each eye was filled with 4, 8, 10, 12, or 16 mg/mL MNU for 10 min, which was then replaced with a balanced salt solution. Multimodal examinations including spectral-domain optical coherence tomography (OCT) images and full-field electroretinography (ffERG) were obtained at baseline and week 2, week 6, and week 12. The retinal degeneration was classified according to the amplitudes of a dark adaptive (DA) 10.0 a-wave amplitude. The degree of moderate retinal degeneration was defined as DA 10.0 a-wave amplitude ≥ 10% and < 60% of baseline amplitude. The degree of severe degeneration was defined as DA 10.0 a-wave amplitude < 10% of baseline amplitude, noise, or flat signal. Hematoxylin and eosin staining and immunohistochemistry were performed at week 12. The main experiments were conducted first with 10 cases of 5 mg/mL and later with 13 cases of 10 mg/mL. In the preliminary experiment, degree of outer retinal degeneration increased with MNU concentration. Use of 4, 8, 10, 12, and 16 mg/mL MNU showed no, moderate, severe, severe, and atrophic changes, respectively. In the main experiments, there were 9 cases of moderate retinal degeneration and 1 case of severe degeneration in 5 mg/mL MNU group. Two cases of moderate degeneration and 11 of severe degeneration were recorded in 10 mg/mL group. Mean thickness of total retina, inner nuclear layer, and outer nuclear layer decreased at week 2 in both groups. The mean amplitudes on ffERG decreased at week 2. The ffERG and OCT findings did not change from week 2 to week 6 or week 12. The results of staining supported those of ffERG and OCT. Temporal MNU loading in a vitrectomized pig-eye model induced customized outer retinal degeneration with changing the concentration of MNU.

Correlations between choroidal thickness and renal function in patients with retinal vein occlusion.

The purpose of this study was to analyze the correlation of renal function indices with sub-foveal choroidal thickness (SFChT) in treatment-naïve (naïve) eyes with retinal vein occlusion (RVO) using swept-source optical coherence tomography (SS-OCT) and systemic workup. Retrospective chart review was performed from Dec 2016 to Sep 2019 in patients newly diagnosed with treatment-naïve unilateral RVO. Ocular parameters, including SFChT, and systemic profiles, including renal function indices, were reviewed. Simple and multiple linear regression analyses were performed to check if there was a correlation between renal profiles and SFChT. A total of 56 patients were included in the study; 34 of them were branch RVO and 22 were central RVO patients. Multiple linear regression analysis revealed that SFChT was positively correlated with estimated glomerular filtration rate (eGFR) (P < 0.001). SFChT showed significant correlation with renal function indices. In addition, choroidal thickness may be considered as systemic biomarkers for renal function.

Carnosine Impedes PDGF-Stimulated Proliferation and Migration of Vascular Smooth Muscle Cells In Vitro and Sprout Outgrowth Ex Vivo.

Carnosine, a naturally producing dipeptide, exhibits various beneficial effects. However, the possible role of carnosine in vascular disorders associated with pathological conditions, including proliferation and migration of vascular smooth muscle cells (VSMCs), largely remains unrevealed. Here, we investigated the regulatory role and mechanism of carnosine in platelet-derived growth factor (PDGF)-induced VSMCs. Carnosine inhibited the proliferation of PDGF-induced VSMCs without any cytotoxic effects. Carnosine treatment also induced G1-phase cell cycle arrest by causing a p21WAF1-mediated reduction in the expression of both cyclin-dependent kinases (CDKs) and cyclins in PDGF-treated VSMCs. Carnosine treatment suppressed c-Jun N-terminal kinase (JNK) phosphorylation in PDGF-stimulated signaling. Additionally, carnosine significantly prevented the migration of VSMCs exposed to PDGF. Carnosine abolished matrix metalloproteinase (MMP)-9 activity via reduced transcriptional binding activity of NF-κB, Sp-1, and AP-1 motifs in PDGF-treated VSMCs. Moreover, using aortic assay ex vivo, it was observed that carnosine addition attenuated PDGF-stimulated sprout outgrowth of VSMCs. Taken together, these results demonstrated that carnosine impeded the proliferation and migration of PDGF-stimulated VSMCs by regulating cell cycle machinery, JNK signaling, and transcription factor-mediated MMP-9 activity as well as prevented ex vivo sprout outgrowth of blood vessels. Thus, carnosine may be a potential candidate for preventing vascular proliferative disease.

Effects of Systemic Profiles on Choroidal Thickness in Treatment-Naïve Eyes With Diabetic Retinopathy.

Purpose: The purpose of this study was to analyze the effects of systemic and ocular profiles on subfoveal choroidal thickness (SFChT) in treatment-naïve eyes with diabetic retinopathy (DR). Methods: This study included patients with treatment-naïve DR. They underwent routine laboratory evaluations, including complete blood cell count, liver function tests, kidney function tests, and urinalysis for macroalbuminuria. The systemic and ocular factors associated with the change in SFChT in DR were analyzed. Results: A total of 136 eyes from 136 patients with diabetes and 30 eyes from 30 age-matched healthy controls were recruited. Generalized linear model analyses showed that the SFChT in treatment-naïve eyes with DR was positively associated with the DR grade and estimated glomerular filtration rate (eGFR; P = 0.001) and negatively associated with age (P < 0.001) and serum phosphorus levels (P = 0.001). Treatment-naïve eyes with proliferative DR (PDR; 313.4 ± 9.0 µm) or severe nonproliferative DR (NPDR; 299.7 ± 9.7 µm) had thicker choroid than eyes with mild to moderate NPDR (251.7 ± 11.1 µm) or no DR (231.2 ± 14.5 µm) after adjusting for age, eGFR, and phosphorus levels. Conclusions: Choroid is affected by renal function and the grade of DR in patients with diabetes. Advanced retinopathy is associated with choroidal thickening, and the severity of concomitant renal disease is associated with choroidal thinning.

Strong Correlation of Renal Function with Choroidal Thickness in Patients with Type 2 Diabetes: Retrospective Cross-Sectional Study.

The purpose of this study was to analyze the correlation between renal function and subfoveal choroidal thickness (SFChT) in treatment-naïve proliferative diabetic retinopathy (PDR) patients. This study included 85 eyes of 52 treatment-naïve PDR patients who underwent kidney function testing and urinalysis and 42 eyes of 33 age-matched controls. Treatment-naïve eyes with PDR were categorized into pachychoroid and leptochoroid groups based on the SFChT of the control group. Kidney function profiles were compared between pachychoroid and leptochoroid groups; the relationship between kidney function profile and SFChT was evaluated using regression analysis. Compared with the pachychoroid group, the leptochoroid group had significantly higher serum creatinine (p = 0.026), cystatin C (p = 0.004), and phosphorus (p < 0.001) levels and a lower estimated glomerular filtration rate (eGFR) (p < 0.001). Multivariate linear regression analyses showed that SFChT was positively correlated with eGFR (Cystatin C) (p = 0.007) and negatively correlated with serum phosphorus (p = 0.001). SFChT of patients with eGFR < 30 mL/min/1.73 m2 and serum phosphorus level ≥4.0 mg/dL was less than that of patients with higher eGFR and lower serum phosphorus level. The choroidal thickness of treatment-naïve PDR patients is closely affected by renal function. Kidney function test should be considered if SFChT of patients with treatment-naïve PDR is reduced.

Changes in choroidal thickness in advanced diabetic retinopathy treated with pan-retinal photocoagulation using a pattern scanning laser versus a conventional laser.

BACKGROUND: To compare the effect of pan-retinal photocoagulation (PRP) using pattern scanning or conventional laser on subfoveal choroidal thickness (SFChT). METHODS: Thirty-eight patients (64 eyes) with advanced diabetic retinopathy (DR) who underwent PRP using pattern scanning or conventional laser were included. Changes in SFChT were compared with baseline values at 1, 3, 6, and 12 months after PRP using swept-source optical coherence tomography. RESULTS: The conventional laser group showed a statistically significant decrease in SFChT at 1, 3, 6, and 12 months after PRP (P < 0.001). SFChT was significantly decreased at 3 (P = 0.025), 6 (P = 0.004), and 12 (P < 0.001) months after treatment in the pattern laser group. CONCLUSION: Eyes with advanced DR showed a significant reduction in SFChT over 12 months regardless of the type of laser used; however, the reduction was sooner after conventional laser than after pattern laser.

PERSISTENT REMNANTS OF DEXAMETHASONE INTRAVITREAL IMPLANT (OZURDEX).

PURPOSE: To describe persistent remnants of dexamethasone intravitreal implant (DEX implant) and evaluate the risk factors for remnant persistence in patients who received a DEX implant. METHODS: This retrospective observational study involved a retrospective chart review of 133 eyes from 129 patients who received DEX implant injection. RESULTS: Seventeen eyes of 17 patients (12.78%) exhibited remnant persistence >1 year after DEX implant injection; eight eyes (13.33%) were diagnosed with branching retinal vein occlusion, three eyes (14.28%) were diagnosed with central retinal vein occlusion, and six eyes (35.3%) were diagnosed with diabetic macular edema. The number of intravitreal DEX implant injections and triamcinolone acetonide injections administered to eyes with remnant persistence was significantly higher than that administered to the eyes without remnant persistence (P < 0.001 and P = 0.024, respectively). Remnants caused symptomatic floaters in 11.7% (2/17 eyes) of the patients with remnants and in 1.5% (2/133) of the entire patient cohort. CONCLUSION: DEX implant was not completely dissolved in the eyes that received multiple DEX implant or triamcinolone acetonide injections.

The Anti-Inflammatory Effects of Angiogenin in an Endotoxin Induced Uveitis in Rats.

Angiogenin (ANG) is involved in the innate immune system and inflammatory disease. The aim of this study is to evaluate the anti-inflammatory effects of ANG in an endotoxin induced uveitis (EIU) rat model and the pathways involved. EIU rats were treated with balanced salt solution (BSS), a non-functional mutant ANG (mANG), or wild-type ANG (ANG). The integrity of the blood-aqueous barrier was evaluated by the infiltrating cell and protein concentrations in aqueous humor. Histopathology, Western blot, and real-time qRT-PCR of aqueous humor and ocular tissue were performed to analyze inflammatory cytokines and transcription factors. EIU treated with ANG had decreased inflammatory cells and protein concentrations in the anterior chamber. Compared to BSS and mANG, ANG treatment showed reduced expression of IL-1ß, IL-8, TNF-α, and Myd88, while the expression of IL-4 and IL-10 was increased. Western blot of ANG treatment showed decreased expression of IL-6, inducible nitric oxide synthase (iNOS), IL-1ß, TNF-α, and phosphorylated NF-κB and increased expression of IL-10. In conclusion, ANG seems to reduce effectively immune mediated inflammation in the EIU rat model by reducing the expression of proinflammatory cytokines, while increasing the expression of anti-inflammatory cytokines through pathways related to NF-κB. Therefore, ANG shows potential for effectively suppressing immune-inflammatory responses in vivo.

Changes in choroidal vascular parameters following pan-retinal photocoagulation using swept-source optical coherence tomography.

BACKGROUND: To assess the effect of pan-retinal photocoagulation (PRP) on choroidal vascular parameters in eyes with advanced diabetic retinopathy (DR). METHODS: Forty patients (65 eyes) with severe nonproliferative DR or proliferative DR who underwent PRP were included. Changes in choroidal vascular parameters were assessed at 3, 6, and 12 months after PRP by using swept-source optical coherence tomography (OCT) and OCT angiography and were compared with baseline values. RESULTS: Choroidal vascularity index (CVI) significantly decreased from 66.27% ± 1.55% at baseline to 65.85% ± 1.61%, 65.77% ± 1.29%, and 65.74% ± 1.60% at 3, 6, and 12 months after PRP, respectively. The ratio of luminal area to stromal area (L/S ratio) also significantly decreased from 1.98 ± 0.15 at baseline to 1.94 ± 0.14, 1.95 ± 0.13, and 1.93 ± 0.14 at 3, 6, and 12 months after PRP, respectively. The subfoveal choroidal thickness (SFCT) similarly showed a significant decrease from 319.50 ± 56.64 µm at baseline to 299. 07 ± 51.14 µm, 294.70 ± 58.96 µm, and 280.93 ± 53.57 µm at 3, 6, and 12 months after PRP, respectively. However, the choriocapillaris vessel density in both the fovea and parafovea showed no significant differences following PRP. CONCLUSION: Eyes with advanced DR showed a significant reduction in CVI, L/S ratio, and SFCT over 12 months after PRP treatment.

Comparison of Vessel Density Reduction in the Deep and Superficial Capillary Plexuses in Branch Retinal Vein Occlusion.

PURPOSE: To quantify the susceptibility of the deep capillary plexus (DCP) in comparison with that of the superficial capillary plexus (SCP) in eyes with branch retinal vein occlusion (BRVO) using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: SS-OCTA (TritonTM; Topcon, Tokyo, Japan) scans (3 × 3 mm) of 41 patients with BRVO were retrospectively analyzed. The mean vessel densities (VDs) of the SCP and the DCP were calculated in eyes with BRVO using the ImageJ program (National Institutes of Health, Bethesda, MD, USA) and compared with those in the normal fellow eye without any morbidity or unaffected sector in the BRVO eye. RESULTS: The reduction rate of mean VD in SCP and DCP between the affected and unaffected sector of eyes with BRVO was 13.88 and 24.60%, respectively. Additionally, the reduction rate of mean VD in the SCP and DCP in the affected sector of BRVO eyes versus the corresponding sector of fellow eyes was 13.31 and 24.49%, respectively. CONCLUSION: The DCP was 1.77-1.84 times more affected than the SCP by ischemic damage in eyes with BRVO.

SCF (Stem Cell Factor) and cKIT Modulate Pathological Ocular Neovascularization.

OBJECTIVE: Aberrant neovascularization is a leading cause of blindness in several eye diseases, including age-related macular degeneration and proliferative diabetic retinopathy. The identification of key regulators of pathological ocular neovascularization has been a subject of extensive research and great therapeutic interest. Here, we explored the previously unrecognized role of cKIT and its ligand, SCF (stem cell factor), in the pathological ocular neovascularization process. Approach and Results: Compared with normoxia, hypoxia, a crucial driver of neovascularization, caused cKIT to be highly upregulated in endothelial cells, which significantly enhanced the angiogenic response of endothelial cells to SCF. In murine models of pathological ocular neovascularization, such as oxygen-induced retinopathy and laser-induced choroidal neovascularization models, cKIT and SCF expression was significantly increased in ocular tissues, and blockade of cKIT and SCF using cKit mutant mice and anti-SCF neutralizing IgG substantially suppressed pathological ocular neovascularization. Mechanistically, SCF/cKIT signaling induced neovascularization through phosphorylation of glycogen synthase kinase-3ß and enhancement of the nuclear translocation of ß-catenin and the transcription of ß-catenin target genes related to angiogenesis. Inhibition of ß-catenin-mediated transcription using chemical inhibitors blocked SCF-induced in vitro angiogenesis in hypoxia, and injection of a ß-catenin agonist into cKit mutant mice with oxygen-induced retinopathy significantly enhanced pathological neovascularization in the retina. Conclusions; Our data reveal that SCF and cKIT are promising novel therapeutic targets for treating vision-threatening ocular neovascular diseases.