Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, concerning the immunofluorescence images shown in Fig. 2C on p. 855, the 'Blank/E‑cadherin' and 'TGF‑β2‑SIS3/E‑cadherin' data panels appeared to show the same data, albeit with different intensities of staining. In addition, in Fig. 3B on p. 856, the GAPDH blots shown for the '7 days' and '28 days' experiment gels were strikingly similar in appearance, in spite of different experiments being reported. After having asked the authors to explain the apparent anomalies in these figures, they realized that they had been assembled erroneously. Corrected versions of Figs. 2 and 3, now showing the correct data for the 'TGF‑β2‑SIS3/E‑cadherin' experiment in Fig. 2C and the GAPDH western blots for the '28 days' experiment in Fig. 3B, are shown opposite and on the next page. The errors made in assembling Figs. 2 and 3 did not grossly affect either the results or the conclusions reported in this paper. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to present this; moreover, the Editor and the authors apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 42: 851‑860, 2018; DOI: 10.3892/ijmm.2018.3662].
MicroRNAs (miRNAs) are a class of small endogenous gene regulators that play important roles in various developmental and pathological processes. However, little is known about the precise identity and functions of miR-26b in posterior capsule opacification (PCO). In this study, we report that the expression of miR-26b is decreased in human PCO-attached lens epithelial cells (LECs) and SRA01/04 cells in the presence of TGF-β2. Overexpression of miR-26b inhibited the proliferation of LECs based on MTT assays and BrdU incorporation assays. In addition, the overexpression of miR-26b inhibited the migration ability of LECs, as shown by wound-healing and transwell migration assays. The overexpression of miR-26b increased the level of the lens epithelial marker E-cadherin and reduced the levels of mesenchymal-related proteins, such as fibronectin, a-SMA, and type I collagen, in SRA01/04 cells in the presence of TGF-β2. Furthermore, the upregulation of E-cadherin and downregulation of mesenchymal-related proteins were induced in human PCO-attached LECs transfected with miR-26b mimics. We further demonstrated that Smad4 and COX-2 are targets of miR-26b in LECs using luciferase reporter assays. These data reveal that miR-26b can inhibit the proliferation, migration, and EMT of lens epithelial cells, and restoration of miRNA-26b may be a potential, novel therapeutic target for the prevention and treatment of posterior capsule opacification.
To evaluate the outcomes and complications of intravitreal injections of ranibizumab in patients during pars plana vitrectomy for treatment of diabetic vitreous hemorrhage. This retrospective, observational, comparative study included 103 patients (103 eyes) who underwent pars plana vitrectomy for treatment of diabetic vitreous hemorrhage. Sixty-six patients received an intravitreal injection of 0.05mg (0.05 cc) of ranibizumab at the end of surgery. Main outcome measures were the occurrence of recurrent early vitreous hemorrhage, reoperation, intraocular pressure, best corrected visual acuity. Mean follow-up time was 6 months. The rate of rebleeding in the intravitreal ranibizumab (IVR) group was 6.1% (4 eyes), which is significantly lower than the control group (24.3%, 9 eyes, P < .01). The incidence of postoperative diabetic vitreous hemorrhage (PDVH) was significantly lower in the IVR group than the control group, OR=0.26, 95% CI=(0.06, 0.95). Visual acuity 6 months after operation was better in IVR group (P<.01) There was no difference in mean intraocular pressure between the 2 groups (P=.56). The present clinical study suggests that intravitreal injection of ranibizumab is effective in the prevention of postoperative diabetic vitreous hemorrhage in eyes undergoing pars plana vitrectomy for the treatment of diabetic vitreous hemorrhage.
Transforming growth factor‑β (TGF‑β) is important in the development of posterior capsule opacification (PCO), and inhibition of the TGF‑β pathway may represent a novel method of treating PCO. Drosophila protein, mothers against decapentaplegic homolog 3 (Smad3) is a phosphorylated receptor‑activated Smad required for the transmission of TGF‑β signals. Smad3 knockout (KO) disturbs the activation of TGF‑β signaling, thus inhibiting the onset of PCO. In the present study, lens epithelial cell (LEC) damage induced by extracapsular cataract extraction was simulated by puncture of the anterior capsule using a 26‑gauge hypodermic needle. The effect of Smad3 in the trauma‑induced epithelial‑mesenchymal transition (EMT) of the lens epithelium in Smad3‑KO and wild‑type (WT) mice was then observed. The expression levels of EMT markers and extracellular matrix components were measured in the two groups by reverse transcription‑quantitative polymerase chain reaction analysis, western blot analysis and immunofluorescence staining. Apoptosis was also detected in the punctured anterior capsule. The Smad3‑KO mice exhibited lower expression levels of α‑smooth muscle actin, lumican, osteopontin, fibronectin and collagen, compared with the WT mice. Additionally, the Smad3‑KO mice exhibited a higher percentage of apoptotic cells than the WT mice. Smad3 signaling was associated with the induction of trauma‑induced EMT, and Smad3 KO interfered with TGF‑β signaling pathway activation, but did not completely inhibit the trauma‑induced EMT in LECs. Therefore, Smad3 may be a target in the treatment of PCO and other fibrosis‑related diseases.
Objectives: To study associations of established cardiovascular risk factors, inflammation and carotid artery intima-media thickness (CIMT) with oxidative stress in type 2 diabetes mellitus (T2DM). Methods: We recruited 343 T2DM subjects from the three main ethnic groups in Singapore (Chinese: 196, Indians: 106, Malays: 41; Age: 54.7±10.4 years; Males: 46%). Measurements: Demographics, BMI, blood pressure, HbA1c, glucose and lipids; CIMT and C-reactive protein (hsCRP). Derivatives of reactive oxygen metabolites (dROMS) and total anti-oxidant status (TAC) was estimated by the automated clinical chemistry analyser (Diacron, Italy). The total oxidative index (OXY) was calculated as the difference between standardised dROMS and TAC values. The relationship between OXY, dROMS and TAC as dependent variable and age, gender, ethnicity, BMI, blood pressure, HbA1c, fasting lipids, log CRP and CIMT as co-variates was assessed using multiple regression analysis. Associations with gender and ethnicity were assessed by student’s t test and Kruskal Wallis test respectively. Results: The mean OXY was higher in the females (0.2±1.3) compared to the males (0.2±1.0); p<0.001 and highest in the Indians (0.3±1.2) when compared to Chinese (-0.1±1.2) and Malays (-0.1±1.0); p=0.01. OXY exhibited a linear relationship with HbA1c (β=0.09, p=0.01), Non-HDL cholesterol ((β=0.28, p<0.001) and CRP (β=0.21, p<0.001). dROMS associated with HbA1c (β=5.3, p=0.04) and CRP (β=14.80, p<0.001) and TAC associated inversely with non-HDL-cholesterol (β= -121.4, p<0.001). No association with CIMT was seen. Conclusions: In T2DM, total oxidative stress is a function of HbA1c, non-HDL-Cholesterol and low-grade inflammation. HbA1c and inflammation increase reactive oxygen metabolites, whereas non-HDL cholesterol decreases the anti-oxidant potential. The mechanisms of oxidative stress generation, in particular in various ethnic groups, needs to be studied further. Disclosure R. Dalan: None. L. Goh: None. X. Tang: None. D.E.K. Chew: None. B. Boehm: None.
To explore the relationships between macular thickness and the plasma concentrations of homocysteine, vitamin B12, folate, and other known risk factors for patients with diabetes without diabetic macular edema (DME).
Background: We investigated whether increasing daily steps by 3000 improves glycemic indices (HbA1c and glycemic variability), cardiometabolic risk factors (BMI, blood pressure (BP) and lipids) and aortic stiffness in middle-aged Chinese men with type 2 diabetes mellitus (T2DM). Methods: In this 12 weeks, pre and post intervention, prospective study, 20 chinese men (40-70 years old; baseline HbA1c 7-10%) with T2DM were recruited. They were on stable therapeutic regime and had no preexisting macrovascular complications. Measurements included glycemic profile (HbA1c, CGMS (Medtronics iPro)), BMI, BP, fasting lipids, aortic BP and stiffness (SphygmoCor Xcel) and daily steps (pedometer). The intervention was to increase the daily step count by 3000/day. We compared group 1 who achieved an increase of >3000 steps/day (N=7) with group 2 who failed to achieve target (N=11). All comparisons were performed using Student’s independent t test. Results: We found that compared to Group 2, Group 1 had a significant improvement in BMI (-1.14 vs. +0.11), aortic systolic (-1.38 vs. +6.58mmHg) and diastolic (-4.63 vs. +4.08mmHg) BP(p<0.05). Interaction analysis showed that in patients who had an improvement in BMI, there was a significant improvement in HbA1c (β=0.57, p=0.041). Changes in indices of glycemic variability were not significantly different between the two groups. Conclusion: Increasing step counts by more than 3000 steps/day resulted in improvement in BMI and aortic BP with an interactive improvement in HbA1c in the long term. Further studies with a larger sample size and a longer follow-up are needed to confirm our findings. Disclosure C. Seow: None. L. Xia: None. J.S. Tan: None. X. Tang: None. B. Sun: None. R. Dalan: None.
Purpose. To report the application of 25 MHz B-scan ultrasonography (MHzB) to determine the integrity of the posterior capsule (PC) in posterior polar cataract (PPC). Methods. Patients with whom PPC was clinically diagnosed using slit lamp microscopy who underwent 25 MHzB before phacoemulsification were retrospectively reviewed. The status of the PC was determined by 25 MHzB before phacoemulsification and confirmed during cataract surgery. Results. In total, 21 eyes in 14 clinically diagnosed PPC patients were enrolled in this study. Out of 25 MHzB images, 19 PCs were found to be intact, while 2 showed dehiscence before cataract surgery. During phacoemulsification, 17 PCs were observed to be intact, while 4 PCs showed posterior capsule rupture (PCR). These 4 PCR cases included the above 2 eyes, in which preexisting dehiscence was detected by 25 MHzB. The other 2 PCR cases showed high reflectivity between high echoes in posterior opacities and the PC, indicating synechia between the PPC and PC. Conclusion. This is the first report to show that 25 MHzB can be used to clearly visualize the status of the PC in PPC. These results, in turn, could be used to select the appropriate treatment and to thereby avoid further complications during PPC surgery.
Objectives. To objectively evaluate posterior capsular opacification (PCO) with RTVue-100 spectral domain-OCT and assess the agreement with the Pentacam system. Methods. Sixty-seven eyes diagnosed with PCO were included. RTVue-100 SD-OCT was used to scan the IOL outline and PCO at horizontal and vertical meridians. PCO was also imaged with a Pentacam and slit-lamp photography system. With RTVue-100 SD-OCT, the PCO area, thickness, density, and objective scores were recorded and used to evaluate the severity of PCO at 3 mm and 5 mm diameter ranges of the IOL optic region. We assessed the correlation of visual acuity, PCO characteristics, and PCO scores. PCO scores acquired from RTVue-100 SD-OCT images were also compared with those from the Pentacam. Differences between pear-type and fibrosis-type PCOs were also compared using RTVue-100 SD-OCT cross-sectional images. Results. The cross-sectional images of PCO acquired with RTVue-100 SD-OCT corresponded well to Pentacam and slit-lamp retroillumination images. IOL-posterior capsular space, area, thickness, and density of the proliferated and accumulated LECs could be clearly visualized and quantified with RTVue-100 SD-OCT. PCO scores were correlated with decreased visual acuity, which was in line with the outcomes using the Pentacam. Differences between the pear-type and fibrosis-type PCO were statistically significant; pear-type PCOs showed a wider and thicker opacification region with lower density compared with fibrosis-type PCOs. Conclusion. RTVue-100 SD-OCT could be a powerful tool in PCO objective evaluation and classification. OCT could be used to visualize the morphology and outline of PCO. Thus, it could discriminate and quantify differences between different types of PCO. PCO scores seem to be a useful factor that could reliably reflect PCO severity.
Background Multiple inflammatory factors in aqueous humor are indicated to be correlated with postoperative macular edema (ME) in type 2 diabetic patients who received phacoemulsification (Phcao) cataract surgery. To analyze the correlation of aqueous inflammatory factors and cytokines with postoperative ME in these patients is significant for the treatment. Objective This study was to ascertain whether cytokines in the aqueous humor can predict ME in type 2 diabetic patients following Phaco cataract surgery. Methods One hundred and thirty-six eyes of 136 consecutive patients with type 2 diabetes were included from January 2010 to April 2012 in Tianjin Eye Hospital. All the patients received Phaco cataract surgery and 0.1 ml aqueous fluid was collected from each eye during the surgery under the informed consent. Twenty-seven cytokines in aqueous humor samples were simultaneously assayed using multiplex bead immunoassay. Central foveal thickness was measured using OCT before and after surgery, and ME was defined as an 30% increase in foveal thickness after operation. The correlations of 27 aqueous cytokines with ME were analyzed. Results Phaco surgery was successfully performed in all the eyes, and 116 eyes completed the follow-up with the finishing rate 85.29%. ME occurred in 29.31% eyes (34/116) 4 weeks after surgery and were assigned to the ME (+) group; while 70.69% eyes (82/116) did not appear ME as the ME (-) group. The patients showed the matched demography between the two groups (all at P>0.05). The mean macular thickness value was (237.24±24.16) μm in the ME (+) group 4 weeks after operation, which was significantly higher than (162.41±21.33) μm before operation and (185.53±18.35) um in the ME (-) group (both at P<0.001). Compared to the ME(-) group, the concentrations of interleukin-1β (IL-1β), IL-6, IL-8, interferon-induced protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) in aqueous of the ME (+) patients were significantly elevated (all at P<0.01). In addition, these factors showed positive correlation with the postoperative central foveal thickness (r=0.288, P=0.005; r=0.345, P=0.008; r=0.256, P=0.016; r=0.377, P=0.007; r=0.423, P=0.001; r=0.279, P=0.012) . However, the aqueous levels of IL-10 and IL-12 before operation were significantly lower in the ME(+) group compared with the ME(-) group (P=0.003, 0.017), and showed negatively correlated with the postoperative central foveal thickness (r=-0.327, P=0.013; r=-0.264, P=0.036). Logistic regression analysis showed that higher glycosylated hemoglobin and above mentioned factors were risk factors of ME following Phaco cataract surgery (OR=1.25, P=0.026; OR=1.31, P=0.006; OR=3.62, P<0.001; OR=1.82, P=0.007; OR=1.58, P<0.001; OR=4.21, P<0.001; OR=5.36, P<0.001; OR=0.19, P=0.011; OR=0.31, P=0.013). Conclusions The increases of aqueous IL-1β, IL-6, IL-8, IP-10, MCP-1, VEGF and decreases of IL-10, IL-12 are associated with postoperative ME in type 2 diabetic patients following Phaco cataract surgery. Key words: Diabetes/complication; Retinopathy; Cytokine; Macular edema; Aqueous humor; Risk factors; Humans
目的 探讨视网膜分支静脉阻塞(branch retinal vein occlusion,BRVO)患者急性期及恢复期血浆同型半胱氨酸(homocysteine,Hcy)水平的变化.方法 连续收集42例BRVO患者作为观察对象,选择42名年龄、性别与观察对象相匹配的、无其他影响Hcy病史的非视网膜疾病患者作为对照组.BRVO发生后3d、1个月、3个月、6个月抽取BRVO患者的空腹静脉血,对照组抽取单次空腹血,采用高效液相色谱荧光检测法检测Hcy,用放射免疫法测定维生素B12、叶酸水平,C677T MTHFR基因多态性采用聚合酶链反应进行分析.结果 BRVO患者阻塞发生后3d Hcy水平(11.01±4.09) μmol·L-1与对照组(10.04±3.67) μmol·L-1相比,差异无统计学意义(P =0.257).BRVO患者的Hcy水平在发生阻塞后逐渐升高,BRVO发生后1个月Hcy达到高峰(13.27±5.81) μmol·L-1,6个月时下降到正常水平(11.17±4.36) μmol·L-1.同时,BRVO患者Hcy水平在BRVO发生后3 d(r =0.343)、1个月(r=0.381)、3个月(r=0.432)、6个月(r =0.360)都与黄斑区视网膜厚度呈显著的正相关(均为P<0.05).然而,BRVO患者Hcy水平的变化与维生素B12、叶酸水平以及C677T MTHFR基因多态性无关(均为P>0.05).结论 患者发生BRVO后Hcy水平一过性升高,本研究结果不支持Hcy是BRVO的独立危险因素的推测,然而Hcy水平的变化可能是疾病本身引起的.
PURPOSE:To analyse the demographic data, clinical characteristics, management and prognosis of patients with firework-related eye injuries.METHODS:A retrospective review was performed of patients with eye injuries related to fireworks referred to TianJin Eye Hospital in North China from 2008 to 2013. Demographic information, clinical features, management and visual outcome were analysed and prognosis factors were evaluated.RESULTS:Ninety-nine patients (86 men) with 118 eye injuries were enrolled in the study. The average age of the patients was 32.0±20.5 years; 70/99 (70.7%) were aged >20 years. Eighty-one of the patients had been lighting the fireworks while the rest were bystanders. The main ophthalmic manifestations were hyphaema, vitreous haemorrhage, corneal/sclera/corneoscleral open globe injury, eyelid laceration, traumatic cataract, retinal/choroid detachment, endophthalmitis and intraocular foreign body (IOFB). Ninety patients required surgical intervention including repair of open globe injury, vitrectomy, cataract extraction and enucleation. 56/118 eyes (47.5%) received multiple operations. After treatment, final best-corrected visual acuity (BCVA) significantly improved (p=0.015). Some factors were significantly correlated with better final BCVA, including initial BCVA (p=0.036), closed globe injury (p=0.031), absence of endophthalmitis (p=0.014), absence of IOFB (p=0.024) and absence of retinal detachment (p=0.046).CONCLUSIONS:Firework-related eye injuries mainly occur in adult men and result in severe visual damage. The most common clinical manifestations are hyphaema and vitreous haemorrhage. Better initial BCVA and closed globe injury have a better visual result while endophthalmitis, IOFB and retinal detachment have a negative visual outcome. Improved eye protection, along with enhanced public education and legal ban on fireworks, could reduce the incidence of eye injuries.
PURPOSE The purpose of this study was to characterize the inflammatory effect of amadori-glycated albumin (AGA) in cultured rat retinal ganglion cells (RGCs) and to further explore the potential mechanism of the anti-inflammatory effects of baicalein. METHODS Primary rat retinal neurons were separated and cultured. The levels of monocyte chemotactic protein-1 (MCP-1) mRNA and soluble MCP-1 produced by RGCs in response to AGA were measured with quantitative reverse transcription-PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). In addition, the expression of microRNA-124 (miR-124) and histone deacetylases (HDACs) were detected in cultured rat RGCs by qRT-PCR in the presence or absence of baicalein. Luciferase reporter assays were used to validate the regulation of a putative target of miR-124. RESULTS Amadori-glycated albumin stimulation increased the expression of MCP-1 and inhibited the expression of miR-124 in cultured rat RGCs. In addition, miR-124 directly controlled MCP-1 expression by binding directly to 3'-untranslated region (3'-UTR) of MCP-1. Next, we demonstrated that miR-124 expression was suppressed by HDACs and that treatment of RGCs with HDACs inhibitors increased miR-124 expression and decreased MCP-1 production. Furthermore, application of baicalein in RGCs attenuated AGA-induced MCP-1 expression and upregulated expression of miR-124 by controlling HDAC4 and HDAC5. CONCLUSIONS Collectively, these data suggest that baicalein inhibits AGA-induced MCP-1 expression in retinal ganglion cells via a microRNA-124-dependent mechanism.
PURPOSE:MicroRNA-181a (miR-181a) is thought to be involved in posterior capsule opacification (PCO). This study investigated the role of miR-181a in the proliferation, migration, and epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs).METHODS:The expression of miR-181a was detected in human PCO-attached LECs and LECs obtained from patients with anterior polar cataracts by quantitative RT-PCR (qRT-PCR). The proliferation of SRA01/04 cells transfected with miR-181a mimics was analyzed by MTT assays and bromodeoxyuridine (BrdU)-incorporation assays. The migration of SRA01/04 cells was evaluated by wound-healing assays and Transwell migration. Luciferase reporter assays were used to validate the regulation of a putative target of miR-181a.RESULTS:The expression of miR-181a is decreased in human PCO-attached LECs and LECs obtained from patients with anterior polar cataracts. A significant decrease in proliferation was observed in SRA01/04 cells transfected with miR-181a mimics. The overexpression of miR-181a inhibited the migration ability of LECs. Downregulation of fibronectin, Slug, and cyclooxygenase-2 (COX-2) expression and upregulation of E-cadherin expression were induced in human PCO-attached LECs transfected with miR-181a mimics and miR-181a-overexpressing LECs obtained from patients with anterior polar cataracts. Furthermore, luciferase assays using a reporter carrying a putative miR-181a target site in the 3' untranslated region of c-Met, Slug, and COX-2 revealed that miR-181a directly targets c-Met, Slug, and COX-2.CONCLUSIONS:These data reveal that miR-181a can inhibit the proliferation, migration, and EMT of LECs and suggest that the restoration of miRNA-181a expression may be a potential novel therapeutic target for the prevention and treatment of posterior capsule opacification.
PURPOSE:Transforming growth factor-β2 (TGF-β2) is a potent inducer of posterior capsular opacification (PCO), a critical Smad-dependent event. This study was conducted to investigate the contributions of Smad2 and Smad3 to PCO development based on selective over-expression of either Smad2 or Smad3.METHODS:We selectively activated the TGF-β/Smad pathway in cell lines transfected with expression plasmids containing Smad2 or Smad3. These cell lines were then analyzed to determine the individual contributions of Smad2 and Smad3 to TGF-β2 treatment response in an in vitro culture of HLE B-3 cells. The effects of Smad2 and Smad3 on cell viability were assessed by MTT and flow cytometry assay. A transwell assay was used to observe the role of Smad2 and Smad3 in the migration of HLE B-3 cells. Western blotting, real-time PCR, and immunocytofluorescence staining were performed to detect the accumulation of ECM proteins and EMT in response to selective Smad2 or Smad3 activation. The presence of soluble collagen I, and fibronectin in the culture medium supernatant were detected by ELISA.RESULTS:Selective Smad3 activation via gene transfection enhanced TGF-β2-responsive growth inhibition and apoptosis. Transwell assay results showed that TGF-β2-induced cell migration was Smad2 dependent and Smad3 independent. Analysis by Western blot, RT-PCR and ELISA demonstrated that the determinant factor in ECM secretion was Smad3 signaling rather than Smad2 signaling. Western blot and RT-PCR showed that the loss of E-Cadherin and acquisition of α-SMA, the hallmark of epithelial-mesenchymal transition (EMT), were both reliant on Smad2 signaling. Immunocytofluorescence staining confirmed the role of Smad2 in the accumulation of α-SMA.CONCLUSIONS:Smad2 and Smad3 are both necessary for the formation of PCO. The discovery of additional TGF-β2/Smad signaling mechanisms may provide potential therapeutic targets to help combat PCO.
AIMTo study the potential reasons of increased straylight in pseudophakic eyes.METHODSCross-sectional study. Seventy patients diagnosed as bilateral age-related cataract and implanted with Tecnis ZA9003, Sensar AR40e, SA60AT, XLSTABI ZO or Akeros AO intraocular lens (IOL) were enrolled in this research. Straylight was measured by a C-Quant straylight meter three to four weeks postoperatively. Five different modalities of IOL, including spherical/aspherical optics and hydrophobic/hydrophilic material were tested in this study. Normal as well as dilated pupils were used. The main outcome variable for straylight measurement was the logarithmic straylight parameter, log(s).RESULTSThe straylight parameter increased significantly after pupil dilation (P<0.05). Straylight of aspherical IOL was significantly higher after pupil dilation (P<0.05) compared to spherical IOL. In normal pupil, straylight of hydrophobic IOL was significant higher when compared with hydrophilic IOL (P<0.05).CONCLUSIONStraylight and visual acuity stand for the different aspects of visual function. Several factors including pupil diameter, optic material, aspherical design of IOL influence intraocular light scattering in pseudophakic eyes. Further investigation was needed to study the impact of optic material and optic surface design on pseudophakic straylight.
This study aims to ascertain whether cytokines in the aqueous humor can predict macular edema (ME) in diabetic patients following uncomplicated phacoemulsification cataract surgery. Undiluted aqueous humor samples were obtained from 136 consecutive type 2 diabetic patients who underwent cataract surgery. The concentrations of 27 cytokines were measured in aqueous humor using the multiplex bead immunoassay. At the final follow-up examination, 116 patients completed 4 weeks of follow-up, and the incidence of macular edema was 29.31% (34 patients) 4 weeks after cataract surgery. Compared to the ME (−) patients, the concentrations of interleukin-1β (IL-1β) (P<0.001), IL-6 (P<0.001), IL-8 (P<0.001), interferon-induced protein-10 (IP-10) (P=0.003), monocyte chemotactic protein-1 (MCP-1) (P<0.001), and vascular endothelial growth factor (VEGF) (P<0.001) in the ME (+) patients were significantly higher. In addition, the aqueous levels of IL-1β (r=0.288), IL-6 (r=0.345), IL-8 (r=0.256), IP-10 (r=0.377), MCP-1 (r=0.423), and VEGF (r=0.279) were positively correlated with the postoperative foveal center point thickness (FCPT). However, the aqueous levels of IL-10 (P=0.003) and IL-12 (P=0.017) were significantly lower in patients with ME. These results suggest IL-1β, IL-6, IL-8, IL-10, IL-12, IP-10, MCP-1, and VEGF may be potential predictors of postoperative macular thickness in patients with diabetes following uncomplicated phacoemulsification cataract surgery.
Purpose.: Homocysteine is a potential risk factor for central retinal vein occlusion (CRVO), but this remains controversial. We measured fasting total plasma homocysteine (tHcy) concentrations immediately after CRVO and in the convalescent period to investigate this controversy. Methods.: We measured fasting tHcy concentrations in 36 consecutive patients with CRVO within three days; and at 1, 3, and 6 months after CRVO; and once in 36 control subjects. The vitamin B12 and folate levels, and the presence of C677T MTHFR polymorphisms, were analyzed in all patients and controls. Results.: Median tHcy concentrations were not significantly higher than in matched control subjects in the acute phase of CRVO (9.66 [10.75 ± 4.09] vs. 9.25 [9.96 ± 4.02] μmol/L, P = 0.371) and 1 month after CRVO (P = 0.119). However, tHcy levels increased significantly in the convalescent period and were significantly higher than in control subjects at 3 CRVO (P = 0.010) and 6 (P < 0.001) months after CRVO. Furthermore, tHcy levels of the ischemic CRVO patients at 6 months after CRVO were significantly higher than in nonischemic CRVO patients (P = 0.028). However, these observations did not appear to be explained by alteration in serum folate, vitamin B12 concentrations, and the MTHFR C677T genotype. Conclusions.: The tHcy levels are not immediately elevated after CRVO, but increase in the convalescent period. These data do not support the hypothesis that raised tHcy concentrations are independent risk factor for CRVO. Instead, it is possible that elevated tHcy levels may be caused by the disease process itself.
Endogenous endophthalmitis (EE) accounts for 2%-15% of endophthalmitis cases;1 EE may occur when microorganisms from remote infection site enter into the eye by crossing the blood-ocular barrier and reproduce in the eye. It is well known that EE often occurs secondary to systemic underlying condition, such as diabetes mellitus, extraocular infective foci, malignancy, and intravenous drug use (IVDU). Common pathogens of EE are bacteria and fungi. Gram-negative bacterial infections are gradually increasing in the Asian countries, in particular, Klebsiella pneumoniae. This is the first report referring to the case of endogenous Klebsiella pneumoniae panophthalmitis associated with IVDU in China. A 50-year-old male without any ocular and systemic disease presented a 3-day history of ocular pain and rapid visual decline in the right eye. General examination showed normal except for low fever (37.3°C) and tumid right submandibular lymph node. Ophthalmologic examination was performed; visual acuity was hand motion in the right eye and 10/10 in the left eye. Left eye examination found no abnormalities, while right eye examination demonstrated eyelid swelling, conjunctival hyperemia, and severe edema. Keratic precipitates were observed in the corneal endothelium, the anterior chamber had a 3-mm hypopyon, and the retina and optic nerve of the right eye could not be displayed due to moderated vitreous haze (Figure 1A). Intraocular pressure was 20 mmHg in both eyes. Ocular B-scan ultrasonography indicated serious vitreous opacity without choroidal lesion and retinal detachment (Figure 1B).Figure 1.: The patient's data. A: Photograph of right eye at admission: eyelid swelling, conjunctival hyperemia, and severe edema; the anterior chamber had a 3-mm hypopyon. B: Ocular B-scan ultrasonography at admission: serious vitreous opacity without choroidal lesion and retinal detachment. C: The second ocular ultrasonography before operation: more severe vitreous opacity and suspected choroidal detachment (arrow), which was identified as subretinal abscess after vitrectomy. D: Photograph of right eye after vitrectomy: anterior chamber with a large number of abscesses, pus discharged from the site of conjunctival perforation (arrow).The patient was immediately hospitalized due to diagnosis of EE. To determine the etiology, laboratory examination was performed. White blood cell (WBC) count was 13.9×109/L with 77% neutrophilia. Liver function test and urine analysis were normal. HIV was negative and hepatitis C virus was positive. Abdominal CT scan showed that liver, pancreas, kidney, and bladder were normal. No abnormalities were found by cardiac sonography. The infectious foci of EE were not found. The patient did not consent for vitrectomy and intravenous infusion therapy was performed. Meanwhile culture of aqueous specimen was taken and the result was negative. Intravenous cefoxitin (2 mg twice) and vancomycin (2 mg twice) were injected daily. In addition, topical tobramycin (0.3%) and levofloxacin (0.3%) eye drops were given hourly. Two days later, although the patient was afebrile, WBC count declined to 12.9×109/L; he complained of increased pain in the right eye and consented to ocular surgery. A second ocular ultrasonography was therefore performed prior to operation and the result showed more severe vitreous opacity and suspected choroidal detachment (Figure 1C). Pars plana vitrectomy and lensectomy were performed; the retina appeared necrotic; subretinal abscess was found and drained; cultures of intraoperative vitreous fluid and abscess were carried out, but contained no organism. Despite the continuation of systemic and ocular therapies after operation, the patient still complained of pain and vision loss in the right eye. Slit lamp examination of the right eye demonstrated severe eyelid swelling, edema of conjunctiva, anterior chamber filled with abscess, and proptosis. The ocular condition confirmed that inflammation was not under control and it even developed to panophthalmitis. Because of aggravation of ocular inflammation, ceftazidime (2 mg twice) and vancomycin (2 mg twice) were administered. Two days later, the right eye perforated at the inferior conjunctiva and there was an outflow of pus from the perforated site (Figure 1D). Subsequently, the patient felt comfortable and the eyelid swelling gradually disappeared. The material of pus grew Klebsiella pneumoniae ssp. pneumoniae. On day 10, WBC count decreased to normal (6.6×109/L), and the patient was discharged with no light perception vision. Before being discharged, the patient unconsciously admitted to drug use. EE is an uncommon infectious disease that can severely damage the eyesight. Many previous researches have reported that most patients with EE have preexisting systemic condition or infective foci, such as diabetes mellitus, malignancy, immunosuppressive therapy, cortisone therapy, liver abscess, chest and urinary tract infection, endocarditis, hemodialysis, prolonged catheter, and IVDU, and all these conditions may increase the risk of infection. In this case, we did not find the possible infective source of EE that we have mentioned above. The patient has no history of any predisposing conditions except intravenous drug abuse. We thus speculated that contaminated needle or cutaneous infection of injecting site might be the possible source of EE. Previous literatures showed that in Europe the major pathogen found in EE was fungi.1 This result was different from those found in Asia, where Gram-negative bacteria were considered as the major causative microorganism, particularly, Klebsiella pneumoniae. Case studies showed that hepatobiliary infection has a relatively high prevalence in Asia which might be the reason for the differences. Recently, it was reported that EE caused by Klebsiella pneumoniae has increased from 54% to 61% in Asia. 2 However, it was documented that patients with IVDU mainly suffered from fungal infection. Our study is the first to point out that Klebsiella pneumoniae should be considered as a pathogen of EE in patients with IVDU in China. Major clinical manifestations of EE include blurred vision, ocular pain, eyelid swelling, conjunctival edema, inflammation of anterior chamber, hypopyon, and vitreous haze. Previous documents concluded that in endogenous Klebsiella pneumoniae endophthalmitis, the appearance of hypopyon leads to poor visual outcome,3 and this association was also observed in this case. Topical, intravitreal, and systemic antibiotics and vitrectomy are the main treatment options of EE. Because the blood-ocular barrier prevents the entry of antibiotics, the effect of topical and systemic antibiotics administration is limited. Although intravitreal injection can increase antibiotic concentration to reach therapeutical level in vitreous cavity, it can also result in severe complications, such as retinal detachment and lens lesion. Vitrectomy, as the most important treatment method so far, can reduce the chance of enucleation by the removal of pathogen, inflammatory response cells, and contaminated vitreous body. There is still a possibility to achieve better final vision if vitrectomy is performed within 48 hours of presentation of EE.4 Although specimen culture (intraocular tap, blood urine, etc.) can confirm the diagnosis of EE, positive culture rate of intraocular specimen is not high which only occupies 36%-73% of the overall ocular fluid results.5 In this article, the samples of aqueous humor and vitreous tap in early stage were all found to be culture false-negative; besides the patient refused surgery and treatment was therefore delayed. We thus concluded that empirical treatment with combination of vancomycin and ceftazidime was valid and important before culture results. Recently, polymerase chain reaction (PCR) technique has been applied to the diagnosis of EE; however, it has drawback on sensitivity identification and may also present false positive results. After its onset, EE becomes a very aggressive disorder progressing rapidly, despite proper treatment, resulting in a poor visual outcome and even turning into a life-threatening one. Thorough understanding of the patient's medical history and finding out the causes rapidly are critically important for effective treatment. When no obvious cause of EE is found, ophthalmologists should consider drug use as the cause.