USING RETeval SYSTEM FLICKER ELECTRORETINOGRAPHY FOR EVALUATION OF DENSE VITREOUS HEMORRHAGE.

PURPOSE: To determine whether the RETeval electroretinography (ERG) system can be used to evaluate eyes with dense vitreous hemorrhage (VH). METHODS: This retrospective case series study included 69 eyes of 69 patients with acute dense VH. Flicker ERGs were recorded by the RETeval system, an ERG device with adhesive skin electrodes. We evaluated the flicker ERG amplitudes in eyes with VH and the ratio of the VH eye amplitudes compared with the fellow eye amplitudes for each VH cause. RESULTS: In patients with rhegmatogenous retinal detachment, the amplitude ratios were extremely low (0.08 ± 0.03). To detect rhegmatogenous retinal detachment, the area under the receiver operating characteristic curve was 0.977 (95% confidence interval, 0.943-1.000) (best rhegmatogenous retinal detachment cutoff value, 0.14; sensitivity, 100.0%; and specificity, 95.4%). The flicker ERG amplitude was not significantly correlated with the initial visual acuity (ρ = -0.189, P = 0.120) but was positively correlated with the postoperative visual acuity in eyes with VH (ρ = -0.328, P = 0.006). CONCLUSION: The RETeval ERG system was found to be a useful diagnostic option in situations where dense VH precluded fundus examination or posterior vitreous detachment was indistinguishable from rhegmatogenous retinal detachment.

Changes in the Foveal Avascular Zone Area and Retinal Vessel Density after Anti-VEGF Therapy for Neovascular Age-Related Macular Degeneration.

PURPOSE: To investigate changes in the foveal avascular zone (FAZ) area and retinal vessel density (VD) in the macula of patients receiving multiple anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (N-AMD). METHODS: This study included 54 eyes of 54 treatment-naïve N-AMD patients. Thirty-three eyes were treated with intravitreal aflibercept injections, and 21 eyes were treated with intravitreal ranibizumab injections. Unaffected fellow eyes (54 eyes) were used as controls. All image scans were acquired after the macular architecture had recovered with drying up of the subretinal fluid/hemorrhage after treatment. RESULTS: Both the superficial and deep FAZ areas were significantly larger in the aflibercept group than in the control group. The VD was also significantly reduced in the aflibercept group. CONCLUSIONS: Prolonged and repeated anti-VEGF therapy may cause an increase in the FAZ area and a decrease in the VD in patients with N-AMD, indicating ischemic damage.

Comparison of Retinal Layer Thickness and Capillary Vessel Density in the Patients with Spontaneously Resolved Acute Central Serous Chorioretinopathy.

We investigate retinal layer thickness and capillary vessel density (VD) in the patients with central serous chorioretinopathy (CSC) who recovered spontaneously and evaluate the correlation between the changes in these values and visual outcomes using swept-source optical coherence tomography (SS-OCT) and OCT angiography (OCTA). This retrospective case-control study included 34 eyes of 34 patients with spontaneously resolved acute CSC. The changes in retinal layer thickness and capillary VD were examined using SS-OCT and OCTA after complete resolution of subretinal fluid (SRF). The fellow eyes and 34 healthy eyes were used as controls. In the eyes with CSC, the outer retinal layer was significantly thinner than in the eyes of fellow and healthy controls. The foveal avascular zone area and VDs in the superficial and deep capillary plexus in the eyes with CSC were not significantly different from those in the eyes of fellow and healthy controls. The VD of the choriocapillaris in the eyes with CSC was significantly lower than that in the eyes of fellow and healthy controls. Correlation analyses revealed that the outer retinal layer thickness and initial visual acuity were positively correlated with the final visual acuity. Furthermore, the initial SRF area and height were negatively correlated with the outer retinal layer thickness after SRF resolution. Attenuation of outer retinal layer thickness and decreased VD of the choriocapillaris were observed in the eyes with spontaneously resolved acute CSC. The outer retinal layer thickness could be an important visual predictor of CSC.

Comparison of lamina cribrosa properties and the peripapillary vessel density between branch retinal vein occlusion and normal-tension glaucoma.

PURPOSE: To compare the properties of the lamina cribrosa (LC) and the peripapillary vessel density between branch retinal vein occlusion (BRVO) and normal-tension glaucoma (NTG), using swept-source optical coherence tomography and optical coherence tomography angiography. METHODS: This retrospective study included 21 eyes of 21 patients with BRVO and 43 eyes of 43 patients with NTG who were treated from June 2016 to September 2017. The anterior LC depth (ALCD) and LC thickness (LCT) at the mid-superior, central, and mid-inferior levels; the mean difference in ALCD; and the peripapillary vessel density in the superficial and deep capillary plexuses and the choriocapillaris were compared between groups. RESULTS: ALCD at the mid-superior, central, and mid-inferior levels was significantly greater in the NTG group (P < 0.05), while LCT was comparable between the groups. The mean difference in ALCD was significantly greater in the BRVO group (P = 0.03). The peripapillary vessel density in the superotemporal segment of the superficial capillary plexus was significantly lower in the BRVO group, while the density in all segments of the choriocapillaris was significantly lower in the NTG group (P < 0.05 for all). CONCLUSIONS: Our findings demonstrate that BRVO and NTG have different LC structures and peripapillary vessel densities.

Oxidative Stress-Induced Pentraxin 3 Expression Human Retinal Pigment Epithelial Cells is Involved in the Pathogenesis of Age-Related Macular Degeneration.

: (1) Background: Age-related macular degeneration (AMD) is closely related with retinal pigment epithelial (RPE) cell dysfunction. Although the exact pathogenesis of AMD remains largely unknown, oxidative stress-induced RPE damage is believed to be one of the primary causes. We investigated the molecular mechanisms of pentraxin 3 (PTX3) expression and its biological functions during oxidative injury. (2) Methods: Using enzyme-linked immunosorbent assays and real-time reverse transcription-polymerase chain reaction, we analyzed mRNA and protein levels of PTX3 in the presence or absence of oxidative stress inducer, sodium iodate (NaIO3), in primary human H-RPE and ARPE-19 cells. Furthermore, we assessed cell death, antioxidant enzyme expression, and AMD-associated gene expression to determine the biological functions of PTX3 under oxidative stress. (3) Results: NaIO3 increased PTX3 expression, in a dose- and time-dependent manner, in H-RPE and ARPE-19 cells. We found phosphorylated Akt, a downstream target of the PI3 kinase pathway, phosphor- mitogen-activated protein kinase kinase 1/2 (ERK), and intracellular reactive oxygen species (ROS) were predominantly induced by NaIO3. NaIO3-induced PTX3 expression was decreased in the presence of phosphoinositide 3 (PI3) kinase inhibitors, ERK inhibitors, and ROS scavengers. Furthermore, NaIO3 enhanced mRNA expression of antioxidant enzymes such as glucose-6-phosphate dehydrogenase (G6PDH), catalase (CAT), and glutathione S-reductase (GSR) in the control shRNA expressing RPE cells, but not in hPTX3 shRNA expressing RPE cells. Interestingly, NaIO3 did not induce mRNA expression of AMD marker genes, such as complement factor I (CFI), complement factor H (CFH), apolipoprotein E (APOE), and toll-like receptor 4 (TLR4) in hPTX3 shRNA expressing RPE cells. 4) Conclusions: These results suggest that PTX3 accelerates RPE cell death and might be involved in AMD development in the presence of oxidative stress.

Comparison of the Therapeutic Efficacies of Topical Rivoceranib and Topical Bevacizumab in a Murine Model of Corneal Neovascularization.

Background and Objectives: Corneal neovasculariziation (CNV) is a serious vision-threatening complication; however, all therapeutics have their clinical limitations. The aim of this study is to investigate the efficacy of topical rivoceranib compared with topical bevacizumab in a murine model of corneal neovascularization (CNV). Materials and Methods: Murine CNV was induced by means of total de-epithelization and alkali burn. Mice were divided into five groups according to topical treatment: untreated control, phosphate-buffered saline (PBS), 0.1% and 0.5% rivoceranib, and 0.5% bevacizumab. CNV area and index were measured 7 and 14 days after treatment. After corneal tissues were excised at day 14, the blood and lymphatic vessels were quantified by cluster of differentiation 31 (CD31) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) immunofluorescence, respectively. Results: After 14 days, treatment groups with 0.1% and 0.5% rivoceranib and 0.5% bevacizumab showed a decrease in CNV area and index compared with the untreated and PBS groups (all p < 0.01). Blood and lymphatic vascularization significantly decreased in the 0.5% rivoceranib and 0.5% bevacizumab groups, as measured by CD31 and LYVE1 immunofluorescence. There was no significant difference of vascularization between the 0.5% rivoceranib and bevacizumab groups. Conclusions: Topical application of rivoceranib could effectively decrease CNV equivalent to topical bevacizumab in a murine model.

Retinal and Choroidal Changes after Anti Vascular Endothelial Growth Factor Therapy for Neovascular Age-related Macular Degeneration.

OBJECTIVE: To investigate changes in retinal nerve fiber layer, ganglion cell-inner plexiform layer, and choroidal thickness in the macular area in patients with neovascular age-related macular degeneration who received repeated intravitreal ranibizumab and aflibercept treatments. METHODS: This retrospective study included 90 eyes of 90 treatment-naive patients. Fifty eyes were treated with intravitreal injections of aflibercept, and 40 were treated with intravitreal injections of ranibizumab. Unaffected fellow eyes (71 eyes) were used as controls. The dosage was one injection per month for 3 consecutive months as an initial treatment. The patients were examined monthly for 6 months following the initial injection. Additional intravitreal injections were given reactively in an optical coherence tomography-guided "pro re nata" protocol. Measurements of the retinal nerve fiber layer, ganglion cell-inner plexiform layer, full retina, and choroidal thickness were simultaneously obtained via swept-source optical coherence tomography in the nine Early Treatment Diabetic Retinopathy Study subfields. RESULTS: The retinal nerve fiber layer thickness in the nine Early Treatment Diabetic Retinopathy Study subfields did not differ significantly among the three study groups (aflibercept vs. ranibizumab vs. control). The ganglion cell-inner plexiform layer thickness was significantly reduced in the aflibercept group, while the choroidal thickness was reduced in both the aflibercept and ranibizumab groups. CONCLUSION: Excessive long-term vascular endothelial growth factor inhibition by an anti-vascular endothelial growth factor agent that is trapped by neuronal and retinal pigment epithelium cells may adversely affect the function of physiological vascular endothelial growth factor and harm retinal cells and vessels.

Superficial foveal avascular zone area changes before and after idiopathic epiretinal membrane surgery.

To investigate the foveal morphological changes and foveal avascular zone (FAZ) area before and after epiretinal membrane (ERM) surgery. Twenty-two eyes with treatment-naive ERM were included in this retrospective study. The central foveal thickness (CFT) and FAZ area were measured via swept-source optical coherence tomography (SS-OCT) and OCT angiography pre- and postoperatively. The unaffected fellow eyes were used as controls. The preoperative superficial FAZ area was significantly smaller in patients (0.08±0.04 mm2) than in controls (0.33±0.09 mm2; P<0.001). The postoperative superficial FAZ (0.12±0.06 mm2) area was significantly greater than the preoperative area (P<0.001). The preoperative superficial FAZ area was strongly negatively correlated with CFT (P<0.001, rho=-0.763). ERM induced significant foveal morphological changes and reduction of the superficial FAZ area. Foveal thickness was restored and FAZ area increased postoperatively. However, the process is rather slow and the recovery is incomplete.

Foveal Avascular Zone Area Changes Analyzed Using OCT Angiography after Successful Rhegmatogenous Retinal Detachment Repair.

PURPOSE: To investigate foveal avascular zone (FAZ) area after surgery in patients with rhegmatogenous retinal detachment (RRD) that involved or uninvolved the macula, and to evaluate the correlation between FAZ area and visual outcomes using swept-source optical coherence tomography angiography (OCTA). MATERIALS AND METHODS: This retrospective case-control study included 34 eyes (34 patients) with recent onset RRD that were successfully repaired with a single, uncomplicated surgical procedure (pars plana vitrectomy with gas tamponade). The changes of FAZ area were examined by OCTA after surgery. The unaffected fellow eye was used as a control for additional comparison. RESULTS: Both superficial and deep FAZ area were significantly larger in the macula-off group (superficial: 0.374 ± 0.112, deep: 0.702 ± 0.193 mm2) than in the macula-on group (superficial: 0.282 ± 0.105, deep: 0.543 ± 0.114 mm2) following surgery. The deep FAZ area was also markedly larger in the macula-off group than in the control group (0.532 ± 0.124 mm2). Correlation analyses revealed that both superficial (ρ = 0.555, P = 0.015) and deep FAZ (ρ = 0.616, P = 0.005) areas were negatively correlated with postoperative best-corrected visual acuity in the macula-off RRD group. CONCLUSIONS: The FAZ area enlargement after successful surgical repair in macula-off RRD eyes may indicate that there is an ischemic damage to retinal capillary plexus in fovea.

Effects of Diabetic Macular Edema on Repeatability of Retinal Nerve Fiber Layer Thickness Measurements at the Macular and Peripapillary Area Using Swept-Source Optical Coherence Tomography.

PURPOSE: To investigate the repeatability of macular and peripapillary retinal nerve fiber layer (RNFL) thickness measurements made using swept-source optical coherence tomography (SS-OCT) and automated segmentation. Measurements were made in non-diabetic controls and in patients with diabetic retinopathy (DR) with or without diabetic macular edema (DME). MATERIALS AND METHODS: A total of 131 eyes of 131 participants were included. Fifty-one eyes with DR had no DME (DME[-]), 45 eyes with DR had DME (DME[+]), and 35 eyes were healthy. Measurements of RNFL and full retinal thickness were simultaneously obtained with SS-OCT in the peripapillary area and in the nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields using the wide three-dimensional mode. All measurements were made twice on the same day by a single examiner to test intra-observer repeatability. Intraclass correlation coefficients (ICCs) and coefficients of repeatability were examined to evaluate repeatability. RESULTS: Average macular and temporal peripapillary RNFL thickness values were greater in the DME[+] group (36.4 ± 13.2 and 83.8 ± 19.4 µm, respectively) than in the control (27.4 ± 3.5 and 73.5 ± 11.4 µm, respectively) and DME[-] (27.9 ± 3.4 µm and 70.3 ± 11.3 µm, respectively) groups (both P < 0.001). The ICCs of average macular (control: 0.982, DME[-]: 0.913, and DME[+]: 0.970) and peripapillary (control: 0.972, DME[-]: 0.973, and DME[+]: 0.958) RNFL thickness measurements indicated good repeatability in all three study groups. CONCLUSIONS: Although the ICCs of average RNFL thickness measurements were relatively lower in eyes with DR than in healthy controls, the intra-observer repeatability of SS-OCT RNFL and full retinal thickness measurements is sufficiently reliable for them to be clinically useful.

Tunicamycin-induced Endoplasmic Reticulum Stress Upregulates the Expression of Pentraxin 3 in Human Retinal Pigment Epithelial Cells.

PURPOSE: To investigate the production of long pentraxin 3 (PTX3) in response to tunicamycin-induced endoplasmic reticulum (ER) stress and its role in ER stress-associated cell death, PTX3 expression was evaluated in the human retinal pigment epithelial cell line, ARPE-19. METHODS: PTX3 production in ARPE-19 cells was analyzed in the absence or presence of tunicamycin treatment by enzyme-linked immunosorbent assay. PTX3 protein and mRNA levels were estimated using western blot analysis and real-time reverse transcription-polymerase chain reaction, respectively. Protein and mRNA levels of CCAAT-enhancer-binding protein homologous protein (CHOP) and ARPE-19 cell viability were measured in the presence of tunicamycin-induced ER stress in control or PTX3 small hairpin RNA (shRNA)-transfected ARPE-19 cells. RESULTS: The protein and mRNA levels of PTX3 were found to be significantly increased by tunicamycin treatment. PTX3 production was significantly decreased in inositol-requiring enzyme 1α shRNA-transfected ARPE-19 cells compared to control shRNA-transfected cells. Furthermore, pretreatment with the NF-κB inhibitor abolished tunicamycin-induced PTX3 production. Decreased cell viability and prolonged protein and mRNA expression of CHOP were observed under tunicamycin-induced ER stress in PTX3 shRNA transfected ARPE-19 cells. CONCLUSIONS: These results suggest that PTX3 production increased in the presence of tunicamycin-induced ER stress. Therefore, PTX3 could be an important protector of ER stress-induced cell death in human retinal pigment epithelial cells. Inositol-requiring enzyme 1α and the NF-κB signaling pathway may serve as potential targets for regulation of PTX3 expression in the retina. Therefore, their role in PTX3 expression needs to be further investigated.

The Wound Healing Effects of Adiponectin Eye Drops after Corneal Alkali Burn.

PURPOSE: To investigate the wound healing effect of adiponectin eye drops following corneal alkali burn. MATERIALS AND METHODS: A chemical burn was induced using 0.1 M NaOH in both adenovirus 12-SV40 hybrid-transformed human corneal epithelial (HCE-2) cells and C57BL/6 mice. The injured HCE-2 and mice were then treated using either 0.1% hyaluronic acid (HA) or adiponectin at 0.0001%, 0.001%, or 0.01% concentration. The viability of the HCE-2 cells was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The wound healing rate of the HCE-2 cells was evaluated using a migration assay 4, 8, 12, 24, and 48 h after chemical injury. In mice, corneal epithelial defects and degree of haze were analyzed 6 h and 1, 2, 3, 6, and 7 days after chemical injury. Seven days after injury, the concentrations of IL-1ß and transforming growth factor-ß (TGF-ß) in the cornea were measured using enzyme-linked immunosorbent assay, and histological analysis was also performed. RESULTS: The viability of HCE-2 cells was not affected by adiponectin at any of the concentrations used. In HCE-2 cells treated using either 0.001% or 0.01% adiponectin, the wound healing rate after 4 h was significantly faster than in the control and HA-treated groups. With regard to mice, the 0.001% and 0.01% adiponectin-treated groups showed a significant improvement in epithelial defect parameters and haze scores at 3, 5, and 7 days after chemical injury. A significant decrease in IL-1ß and TGF-ß levels was observed in the 0.001% and 0.01% adiponectin-treated groups compared to the other groups. Histologically, corneal thickness and the inflammatory cells were also decreased in the adiponectin-treated groups. CONCLUSIONS: Topical adiponectin (both 0.001% and 0.01%) increased epithelial migration and improved clinical signs and inflammation on the ocular surface after alkali burn, suggesting that adiponectin can promote wound healing in the cornea.

Elevated Plasma Pentraxin3 Levels and Its Association with Neovascular Age-related Macular Degeneration.

PURPOSE: To evaluate pentraxin3 (PTX3) levels in patients with neovascular age-related macular degeneration (N-ARMD) and to investigate its role as a predictive biomarker. METHODS: Thirty individuals with N-ARMD and 30 controls without N-ARMD were studied. Plasma concentrations of C-reactive protein (CRP) and PTX3 were measured in frozen samples using an enzyme-linked immunosorbent assay kit. RESULTS: PTX3 concentration was 1341 ± 625 pg/mL (mean ± standard deviation) in N-ARMD patients, which was significantly higher than in control subjects (887 ± 478, p = 0.003). The mean CRP level was also significantly higher in N-ARMD (2121 ± 2300) than in control (748 ± 618, p = 0.004). Pearson's correlation analysis showed a significant positive correlation between PTX3 and CRP (r = 0.407, p = 0.002). CONCLUSIONS: Our data support the role of chronic inflammation in the development of ARMD. They also show PTX3 may contribute to efforts to understand pathogenesis of N-ARMD.

Elevated plasma pentraxin 3 and its association with retinal vein occlusion.

PURPOSE: To evaluate plasma pentraxin 3 (PTX3) in patients with retinal vein occlusion (RVO), and investigate the possibility of its role as a predictive biomarker. METHODS: Nested case-control study. The study included 57 patients with RVO and 45 age- and gender-matched subjects without RVO as controls. Plasma PTX3 and C-reactive protein concentration were measured in both groups a posteriori from frozen samples by using an enzyme-linked immunosorbent assay kit. RESULTS: The measured PTX3 value for the RVO group was 1,508 ± 1,183 pg/mL (mean ± standard deviation) and 833 ± 422 pg/mL for the controls (p < 0.001). There was no significant difference in PTX3 levels between patients with central retinal vein occlusion and branched retinal vein occlusion (1,468 ± 1,300 vs. 1,533 ± 1,121 pg/mL; p = 0.818). CONCLUSIONS: Our data seems to support the role of chronic inflammation and ischemia in the development of RVO. It is possible that PTX3 can be used as a diagnostic biomarker of RVO.

Elevated plasma pentraxin 3 levels are associated with development and progression of diabetic retinopathy in Korean patients with type 2 diabetes mellitus.

PURPOSE: To evaluate the association between elevated levels of plasma pentraxin 3 (PTX3) and the development and/or progression of diabetic retinopathy (DR). METHODS: In this case-control study, 92 diabetic patients with DR (group 3), 30 diabetic patients without DR (group 2), and 41 normal subjects (group 1) were enrolled. Log-transformed values of plasma PTX3 and high-sensitivity C-reactive protein (hsCRP) concentrations were measured and used in our analysis. For subgroup analysis, group 3 was divided into four subgroups: mild, moderate, severe nonproliferative, and proliferative DR. RESULTS: In our 163 participants, average plasma PTX3 levels were 916.1 ± 532.2, 1093.7 ± 1034.2, and 1817.9 ± 1776.9 pg/mL for groups 1, 2, and 3, respectively. The duration of diabetic mellitus (DM), glycated hemoglobin (HbA1c), log hsCRP, and log PTX3 were significantly different between the three groups (P = 0.008, P < 0.001, P = 0.046, and P < 0.001, respectively). In subgroup analysis, plasma log PTX3 levels increased in correlation with the severity of DR (R = 0.372, P < 0.001). Multivariate logistic analysis showed that the correlation between DR development and duration of DM and log PTX3 values was significant (P = 0.014 and P = 0.025, respectively), whereas correlation with log hsCRP values was not significant in univariate analysis (P = 0.129). The receiver operating characteristic curves of DR development were plotted using log PTX3 and log hsCRP values, and the area under the curves was found to be 0.721 (P = 0.001) and 0.614 (P = 0.087), respectively. CONCLUSIONS: Plasma PTX3 is positively associated with DR development and progression, and may be a more accurate predictor of DR development than hsCRP.

Human retinal pigment epithelial cells express the long pentraxin PTX3.

PURPOSE: To determine whether the long pentraxin 3 (PTX3) is expressed in human retinal pigment epithelial cells and is induced by inflammatory cytokines, interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ), expression of PTX3 was investigated in the human retinal pigment epithelial cell line, ARPE-19 cells. METHODS: In ARPE-19 cells, we first analyzed PTX3 production in the presence or absence of inflammatory cytokines, IL-1ß, TNF-α, and IFN-γ, dose- and time-dependently using enzyme-linked immunosorbent assay. Protein and mRNA expression of PTX3 was measured with western blotting analysis and real-time reverse transcription-polymerase chain reaction. Specific inhibitors were used to determine the signaling pathways of inflammatory cytokine-induced PTX3 expression. RESULTS: In this study, production of PTX3 was induced by IL-1ß and TNF-α dose- and time-dependently, but not by IFN-γ in ARPE-19 cells. Protein and mRNA expression of PTX3 was significantly upregulated in the presence of IL-1ß and TNF-α. Furthermore, pretreatment with extracellular signal-regulated kinase1/2 and nuclear factor kappa-light-chain-enhancer of activated B cells specific inhibitor abolished IL-1ß and TNF-α-induced PTX3 production, but the other inhibitors had no effect. CONCLUSIONS: These results suggested that human retinal pigment epithelial cells may be a major source of PTX3 production in the presence of proinflammatory cytokines, IL-1ß and TNF-α, and could be an important mediator for host defense and inflammatory response in the retina. The importance of the mitogen-activated protein kinase/extracellular signal-regulated kinase1/2 and nuclear factor kappa-light-chain-enhancer of activated B cells pathways for regulated PTX3 expression may be a potential target for PTX3 regulation in the retina.

Acute vision loss associated with retinal circulatory disturbances after intravitreal injection of bevacizumab.

PURPOSE: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), specifically binds to VEGF protein, and inhibits angiogenesis. Intravitreal/intracameral injection of bevacizumab has been reported as another treatment option for patients with various ocular ischemic conditions. However, we report 4 cases of acute vision loss after bevacizumab intravitreal injection. METHODS: Intravitreal bevacizumab injections were administrated to 2 ocular ischemic syndrome (OIS) patients and 2 central retinal vein occlusion (CRVO) patients. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), funduscopic findings, and fluorescein angiography were evaluated before and after the treatments. RESULTS: All 4 cases presented with acute vision loss within 1 week after bevacizumab injection, before its clearance from the eye, and showed that microcirculatory disturbances occurred in the retina. CONCLUSIONS: We believe that intravitreal injection of bevacizumab should be undertaken with extreme caution in patients with a history of cerebral infarction, especially with OIS or nonischemic CRVO, and with diabetic retinopathy and vitrectomized eye with pseudophakia.

Therapeutic effect of topical adiponectin in a mouse model of desiccating stress-induced dry eye.

PURPOSE: To investigate the therapeutic effect of topical adiponectin in a mouse model of experimental dry eye (EDE). METHODS: EDE was created by desiccating stress in 6- to 8-week old female C57BL/6 mice. Eye drops consisting of 0.0001%, 0.001%, or 0.01% adiponectin, or balanced salt solution (BSS), were applied in EDE. Tear volume and corneal irregularity score were measured at 5 and 10 days after treatment. Levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and monokine induced by interferon-γ (MIG) were measured in the conjunctiva and lacrimal gland using a multiplex immunobead assay at 10 days. Periodic acid-Schiff staining, immunohistochemistry, and flow cytometry were also performed. RESULTS: Mice treated with 0.001% or 0.01% adiponectin showed a significant improvement in tear volume and corneal irregularity compared with the EDE control and BSS-treated groups. A significant decrease in the levels of IL-1ß, IL-6, TNF-α, IFN-γ, and MIG and staining intensity of TNF-α was observed in the 0.001% and 0.01% adiponectin-treated groups, compared with the other groups, in the conjunctiva and lacrimal gland. In the 0.001% and 0.01% adiponectin-treated groups, the density of conjunctival goblet cells was higher and the number of CD4+CXCR3+ T cells was lower than in the other groups. However, there were no significant differences in all parameters between the 0.0001% adiponectin and control groups. CONCLUSIONS: Topical application of adiponectin can markedly improve clinical signs and decrease inflammation in the ocular surface and lacrimal gland of EDE, suggesting that adiponectin eye drops may be used as a therapeutic agent for dry eye disease.