Abstract:Abstract AIM: To investigate the cytotoxic effect on human corneal epithelial cells (HCECs) and the ability to faciliate corneal epithelial wound healing of carboxymethylcellulose (CMC) and hyaluronic acid (HA). METHODS: HCECs were exposed to 0.5% CMC (Refresh plus?, Allergan, Irvine, California, USA) and 0.1% and 0.3% HA (Kynex?, Alcon, Seoul, Korea, and Hyalein mini?, Santen, Osaka, Japan) for the period of 30min, and 4, 12, and 24h. Methyl thiazolyl tetrazolium (MTT)-based calorimetric assay was performed to assess the metabolic activity of cellular proliferation and lactate dehydrogenase (LDH) leakage assay to assess the cytotoxicity. Apoptotic response was evaluated with flow cytometric analysis and fluorescence staining with Annexin V and propiodium iodide. Cellular morphology was evaluated by inverted phase-contrast light microscopy and electron microscopy. The wound widths were measured 24h after confluent HCECs were scratch wounded. RESULTS: The inhibitory effect of human corneal epithelial proliferation and cytotoxicity showed the time-dependent response but no significant effect. Apoptosis developed in flow cytometry and apoptotic cells were demonstrated in fluorescent micrograph. The damaged HCECs were detached from the bottom of the dish and showed the well-developed vacuole formations. Both CMC and HA stimulated reepithehlialization of HCECs scratched, which were more observed in CMC. CONCLUSION: CMC and HA, used in artificial tear formulation, could be utilized without any significant toxic effect on HCECs. Both significantly stimulated HCEC reepithelialization of corneal wounds.

Abstract:AIM: To investigate the expression of triggering receptor expressed on myeloid cells-1 (TREM-1) in the aberrant inflammation within the corneal epithelium at early period of fungal infection. METHODS: A total of 65 Wistar rats were randomly divided into control group, sham group and fungal keratitis (FK) group, in which the cornea was infected by Aspergillus fumigatus (A. fumigatus). After executed randomly at 8, 16, 24, 48 and 72h after experimental model being established, the severity of keratomycosis in rats was scored visually with the aid of a dissecting microscope and slit lamp. Then corneas in three groups were collected to assess the expression of TREM-1 through quantitative reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence technique and Western blot analysis. The correlation between FK inflammation and expression of TREM-1 was also analyzed. RESULTS: Corneal inflammation scores increased with time after fungal infection (F=49.74, P=0.000). The inflammation scores in FK group were obviously higher than those in sham group on the whole (F=137.78, P=0.000). Levels of TREM-1 in the infected rat corneal epithelium had elevated at 8h and peaked at 48h (P<0.001, compared with control group). Western blot analysis also showed an obviously elevated TREM-1 level in rat corneal epithelium at 24h and 48h after fungal infection. Immunofluorescence?technique showed that TREM-1 mainly existed in corneal epithelium and infected corneal stoma of rat. TREM-1 protein expression was enhanced after fungal infection. Moreover, severity of FK inflammation was significantly related to TREM-1 expression in FK (r=0.942, P=0.000). CONCLUSION: TREM-1 may contribute to amplify the inflammation in the cornea infected with A. fumigatus and play critical roles in the battle against A. fumigatus in the innate immune responses.

Abstract:AIM: To evaluate the therapeutic effect of netrin-4 on the early acute phase of inflammation in the alkali-burned eye. METHODS: Eye drops containing netrin-4 or phosphate buffered saline (PBS) were administered to a alkali-burn-induced corneal acute inflammatory model four times daily. The clinical evaluations, including fluorescein staining and inflammatory index, were performed on day 1, 4 and 7 using slit lamp microscopy. Global specimens were collected on day 7 and processed for immunofluorescent staining. The levels of inflammatory mediators in the corneas were determined by real-time polymerase chain reaction (PCR). RESULTS: Exogenous netrin-4 administered on rat ocular surfaces showed more improvements in decreasing fluorescein staining on day 4 and 7, and resolved alkali burn-induced corneal inflammation index on day 7 (P<0.01). The levels of IL-1β, IL-6, intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1) in corneas were decreased in netrin-4-treated groups (P<0.05). In addition, netrin-4 significantly reduced the expression of leukocyte common antigen 45 (CD45) in the alkali-burn cornea (P<0.001). CONCLUSION: Topical netrin-4 accelerated wound healing and reduced the inflammation on alkali-burn rat model, suggesting a potential as an anti-inflammatory agent in the clinical to treat the acute inflammation.

Abstract:AIM: To investigate anti-angiogenic effects of polysulfated heparin endostatin (PSH-ES) on alkali burn induced corneal neovascularization (NV) in rabbits. METHODS: An alkali burn was made on rabbit corneas to induce corneal NV in the right eye of 24 rabbits. One day after burn creation, a 0.2 mL subconjunctival injection of 50 μg/mL PSH-ES, 50 μg/mL recombinant endostatin (ES), or normal saline was administered every other day for a total of 14d (7 injections). Histology and immunohistochemisty were used to examine corneas. Corneal NV growth was evaluated as microvessel quantity and corneal vascular endothelial growth factor (VEGF) expression was measured by immunohistochemical assay. RESULTS: Subconjunctival injection of ES and PSH-ES resulted in significant corneal NV suppression, but PSH-ES had a more powerful anti-angiogenic effect than ES. Mean VEGF concentration in PSH-ES treated corneas was significantly lower than in ES treated and saline treated corneas. Histological examination showed that corneas treated with either PSH-ES or ES had significantly fewer microvessels than eyes treated with saline. Additionally corneas treated with PSH-ES had significantly fewer microvessels than corneas treated with ES. CONCLUSION: Both PSH-ES and recombinant ES effectively inhibit corneal NV induced by alkali burn. However, PSH-ES is a more powerful anti-angiogenic agent than ES. This research has the potential to provide a new treatment option for preventing and treating corneal NV.

Abstract:AIM: To evaluate the neuroprotective activity of systemically administered edaravone in early and late stage of experimental glaucoma in rats. METHODS: In this study, 60 Wistar albino rats were used. Experimental glaucoma model was created by injecting hyaluronic acid to the anterior chamber once a week for 6wk in 46 of 60 subjects. Fourteen subjects without any medication were included as control group. Edaravone administered intraperitoneally 3 mg/kg/d to the 15 of 30 subjects starting at the onset of glaucoma induction and also administered intraperitoneally 3 mg/kg/d to the other 15 subjects starting at three weeks after the onset of glaucoma induction. The other 16 subjects who underwent glaucoma induction was administered any therapy. Retinal ganglion cells (RGCs) have been marked with dextran tetramethylrhodamine (DTMR) retrograde at the end of the sixth week and after 48h, subjects were sacrificed by the method of cardiac perfusion. Alive RGC density was assessed in the whole-mount retina. Whole-mount retinal tissues homogenized and nitric oxide (NO), malondialdehyde (MDA) and total antioxidant capacity (TAC) values were measured biochemically. RESULTS: RGCs counted with Image-Pro Plus program, in the treatment group were found to be statistically significantly protected, compared to the glaucoma group (Bonferroni, P<0.05). The neuroprotective activity of edaravone was found to be more influential by administration at the start of the glaucoma process. Statistically significant lower NO levels were determined in the glaucoma group comparing treatment groups (Bonferroni, P<0.05). MDA levels were found to be highest in untreated glaucoma group, TAC levels were found to be lower in the glaucoma induction groups than the control group (Bonferroni, P<0.05). CONCLUSION: Systemic administration of Edaravone in experimental glaucoma showed potent neuroprotective activity. The role of oxidative stress causing RGC damage in glaucoma was supported by this study results.

Abstract:AIM: To investigate the effect of bevacizumab treatment on Notch signaling and the induction of epithelial-of-mesenchymal transition (EMT) in human retinal pigment epithelial cells (ARPE-19) in vitro. METHODS: In vitro cultivated ARPE-19 cells were treated with 0.25 mg/mL bevacizumab for 12, 24, and 48h. Cell morphology changes were observed under an inverted microscope. The expression of zonula occludens-1 (ZO-1), vimentin and Notch-1 intracellular domain (NICD) was examined by immunofluorescence. The mRNA levels of ZO-1, α-SMA, Notch-1, Notch-2, Notch-4, Dll4, Jagged-1, RBP-Jk and Hes-1 expression were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of α-SMA, NICD, Hes-1 and Dll-4 expression were examined with Western blot. RESULTS: Bevacizumab stimulation increased the expression of α-SMA and vimentin in ARPE-19 cells which changed into spindle-shaped fibroblast-like cells. Meanwhile, the mRNA expression of Hes-1 increased and the protein expression of Hes-1 and NICD also increased, which Notch signaling was activated. The mRNA expression of Notch-1, Jagged-1 and RBP-Jk increased at 48h, and while Dll4 mRNA and protein expression did not change after bevacizumab treatment. CONCLUSION: Jagged-1/Notch-1 signaling may play a critical role in bevacizumab-induced EMT in ARPE-19 cells, which provides a novel insight into the pathogenesis of intravitreal bevacizumab-associated complication.

Abstract:AIM: To determine the optimal concentration for inducing the differentiation of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) into neuron-like cells, although it is understood that all-trans retinoic acid (ATRA) regulates cell proliferation in the nervous system by modulating the balance between mitosis and apoptosis. METHODS: The abilities of ATRA to promote apoptosis as well as neural differentiation were assessed in cultured hUC-MSCs by morphological observation, MTT assay, annexin V-FITC/PI flow cytometry and immunocytochemistry. RESULTS: The data showed that low concentrations of ATRA (0.5 μmol, 0.25 μmol) had no effect on the number of cells. However, treatment with 1.0 μmol or 2.0 μmol ATRA induced a 24.16% and 52.67% reduction in cell number, respectively, compared with vehicle-treated cultures. Further, 4.0 μmol ATRA had a potent effect on cell number, with almost no adherent cells recovered after 24h. We further showed that 0.5 μmol ATRA caused these cells to express characteristic markers of neuronal progenitor cells. CONCLUSION: Taken together, we conclude that ATRA has a dose-dependent influence on the neural differentiation and apoptosis of hUC-MSCs. These findings have implications on the use of ATRA-differentiated hUC-MSCs for the study of neural degeneration diseases.

Abstract:AIM: To observe the effects of intravitreal injections of different concentrations of human umbilical mesenchymal stem cells on retinopathy in rats with diabetes mellitus. METHODS: Healthy and adult male Sprague-Dawley (SD) rats were randomly assigned to a normal control group (group A), a diabetic retinopathy (DR) blank control group (group B), a high-concentration transplantation group (group C), a low-concentration transplantation group (group D) and a placebo transplantation group (group E). The expression of nerve growth factor (NGF) protein in the retinal layers was detected by immunohistochemical staining at 2, 4, 6 and 8wk. RESULTS: The expression of NGF was positive in group A and most positive in the retinal ganglion cell layer. In groups B and E, the expression of NGF was positive 2wk after transplantation and showed an increase in all layers. However, the level of expression had decreased in all layers at 4wk and was significantly reduced at 8wk. In groups C and D, the expression of NGF had increased at 2wk and continued to increase up to 8wk. The level of expression in group C was much higher than that in group D. CONCLUSION: DR can be improved by intravitreal injection of human umbilical mesenchymal stem cells. High concentrations of human umbilical mesenchymal stem cells confer a better protective effect on DR than low concentrations.

Abstract:AIM: To investigate the effects of selenium in rat retinal ischemia reperfusion (IR) model and compare pre-treatment and post-treatment use. METHODS: Selenium pre-treatment group (n=8) was treated with intraperitoneal (i.p.) selenium 0.5 mg/kg for 7d and terminated 24h after the IR injury. Selenium post-treatment group (n=8) was treated with i.p. selenium 0.5 mg/kg for 7d after the IR injury with termination at the end of the 7d period. Sham group (n=8) received i.p. saline injections identical to the selenium volume for 7d with termination 24h after the IR injury. Control group (n=8) received no intervention. Main outcome measures were retina superoxide dismutase (SOD), glutathione (GSH), total antioxidant status (TAS), malondialdehyde (MDA), DNA fragmentation levels, and immunohistological apoptosis evaluation. RESULTS: Compared to the Sham group, selenium pre-treatment had a statistical difference in all parameters except SOD. Post-treatment selenium also resulted in statistical differences in all parameters except the MDA levels. When comparing selenium groups, the pre-treatment selenium group had a statistically higher success in reduction of markers of cell damage such as MDA and DNA fragmentation. In contrast, the post-selenium treatment group had resulted in statistically higher levels of GSH. Histologically both selenium groups succeeded to limit retinal thickening and apoptosis. Pre-treatment use was statistically more successful in decreasing apoptosis in ganglion cell layer compared to post-treatment use. CONCLUSION: Selenium was successful in retinal protection in IR injuries. Pre-treatment efficacy was superior in terms of prevention of tissue damage and apoptosis.

Abstract:AIM: To identify and understand the relationship between co-expression pattern and clinic traits in uveal melanoma, weighted gene co-expression network analysis (WGCNA) is applied to investigate the gene expression levels and patient clinic features. Uveal melanoma is the most common primary eye tumor in adults. Although many studies have identified some important genes and pathways that were relevant to progress of uveal melanoma, the relationship between co-expression and clinic traits in systems level of uveal melanoma is unclear yet. We employ WGCNA to investigate the relationship underlying molecular and phenotype in this study. METHODS: Gene expression profile of uveal melanoma and patient clinic traits were collected from the Gene Expression Omnibus (GEO) database. The gene co-expression is calculated by WGCNA that is the R package software. The package is used to analyze the correlation between pairs of expression levels of genes. The function of the genes were annotated by gene ontology (GO). RESULTS: In this study, we identified four co-expression modules significantly correlated with clinic traits. Module blue positively correlated with radiotherapy treatment. Module purple positively correlates with tumor location (sclera) and negatively correlates with patient age. Module red positively correlates with sclera and negatively correlates with thickness of tumor. Module black positively correlates with the largest tumor diameter (LTD). Additionally, we identified the hug gene (top connectivity with other genes) in each module. The hub gene RPS15A, PTGDS, CD53 and MSI2 might play a vital role in progress of uveal melanoma. CONCLUSION: From WGCNA analysis and hub gene calculation, we identified RPS15A, PTGDS, CD53 and MSI2 might be target or diagnosis for uveal melanoma.

Abstract:AIM: To compare the anterior segment measurements obtained by rotating Scheimpflug camera (Pentacam) and Scanning-slit topography (Orbscan IIz) in keratoconic eyes. METHODS: A total of 121 patients, 71 males (58.7%) and 50 females (41.3%) (214 eyes) with the diagnosis of keratoconus (KC) were enrolled in this study. Following diagnosis of KC by slit-lamp biomicroscopic examination, central corneal thickness (CCT), thinnest corneal thickness (TCT), anterior chamber depth (ACD), and pupil diameter (PD) were measured by a single examiner using successive instrumentation by Pentacam and Orbscan. RESULTS: There was no significant difference between the two instruments for the measurement of CCT and TCT. In contrast, scanning-slit topography measured ACD (3.46±0.40 mm vs. 3.38±0.33 mm, P=0.019) and PD (4.97±1.26 mm vs 4.08±1.19 mm, P<0.001) significantly larger than rotating Scheimpflug camera. The two devices made similar measurements for CCT (95% CI: -2.94 to 5.06, P=0.602). However, the mean difference for TCT was -6.28 (95% CI: -10.51 to -2.06, P=0.004) showing a thinner measurement by Orbscan than by Pentacam. In terms of the ACD, the mean difference was 0.08 mm (95% CI: 0.04 to 0.12, P<0.001) with Orbscan giving a slightly larger value than Pentacam. Similarly, Orbscan measurement for PD was longer than Pentacam (95% CI: 0.68 to 1.08, P<0.001). CONCLUSION: A good agreement was found between Pentacam and Orbscan concerning CCT measurement while comparing scanning-slit topography and rotating Scheimpflug camera there was an underestimation for TCT and overestimation for ACD and PD.

Abstract:AIM: To evaluate the effect of torsional mode phacoemulsification on central corneal thickness, corneal endothelial cell density, and morphology in eyes with/without pseudoexfoliation (PEX) syndrome. METHODS: Fourty-two consecutive patients with and 42 patients without PEX as a control group scheduled for cataract surgery was studied. Phacoemulsification, using OZiL IP system, was performed with quick chop technique. Using noncontact specular microscopy, the central endothelial cell density (ECD), coefficient of variation, percentage of hexagonal cells, and the central corneal thickness (CCT) were evaluated preoperatively and postoperatively at 1, 7 and 30d. RESULTS: The ECD in PEX syndrome was statistically significantly lower than that in the control group preoperatively and postoperatively (P≤0.001). Percentage change in ECD was statistically significantly higher in PEX than that in control group after surgery follow up (P≤0.04). There was no statistically significant difference between both groups comparing percentage of hexagonal cells and coefficient of variation in the cell size before and after the surgery. At 1 and 7d after surgery, percentage change in CCT was statistically significantly higher in PEX group than that in the control group (P≤0.041). CONCLUSION: Although torsional mode phacoemulsification and intraocular lens (IOL) implantation provided a safe and favorable surgical outcome in patients with/without PEX, torsional phacoemulsification led to significantly higher ECD loss in the PEX group than that in the control group during the whole follow up period. In addition, more corneal swelling in the PEX group than that in the control group during the early postoperative period has indicated that the corneal endothelium, in presence of PEX endotheliopathy, seems to be more susceptible to the effects of phacoemulsification surgery in eyes with PEX. The increased risk of anterior chamber manipulations in patients with PEX should be taken into account for an increased risk of bullous keratopathy.

Abstract:AIM: To evaluate the outcome of laser iridotomy using 532-nm Nd: YAG laser (PASCAL) with short pulse duration and Nd: YAG laser compared to conventional combined laser iridotomy. METHODS: Retrospective, nonrandomized, comparative case series. Forty-five eyes of 34 patients underwent laser iridotomy. Twenty-two eyes underwent iridotomy using short duration PASCAL and Nd: YAG laser, and 23 eyes underwent iridotomy using conventional combined laser method. The average settings of PASCAL were 60 μm and 700-900 mW with a short duration of 0.01s to reduce the total applied energy. The conventional laser was 50 μm and 700-900 mW for 0.1s. After photocoagulation with these laser, the Nd: YAG laser was added in each group. Endothelial cell counts of pre-iridotomy and 2mo after iridotomy were measured and compared. RESULTS: All eyes completed iridotomy successfully. The total energy used in the PASCAL group was 1.85±1.17 J. Compared to conventional laser 13.25±1.67 J, the energy used was very small due to the short exposure time of PASCAL. Endothelial cell counts were reduced by 0.88% in the PASCAL group and 6.72% in the conventional laser group (P=0.044). The change in corneal endothelial cell counts before and after iridotomy was significant in conventional combined laser iridotomy group (P=0.004). CONCLUSION: Combined PASCAL and Nd:YAG laser iridotomy is an effective and safe technique in the dark brown irides of Asians. Furthermore, the short duration of exposure in PASCAL offers the advantages of reducing the total energy used and minimizing the corneal damage.

Abstract:AIM: To evaluate the visual outcome and factors influencing visual outcome of manual small incision cataract surgery (MSICS) in the rural area in the Xianfeng County. METHODS: Eighty-two eyes of 82 patients who underwent cataract surgery performed by using MSICS technique were identified. Data collected included each patient’s age, gender, the level of education. Uncorrected and corrected distance visual acuity (UDVA and CDVA) at presentation and at 1, 6, 8wk postoperatively, pre-existing eye disease, operative findings and complications, the risk factors were evaluated. RESULTS: In 82 patients, the average age was 69.6±0.6y, illiterate were 52 (63.4%). Of 82 eyes, pseudophakia was present in 77 eyes (93.9%). At 1wk postoperatively, 47 eyes (57.3%) had the UDVA of ≥6/18, and 52 eyes (63.4%) had the CDVA of ≥6/18. At 6 to 8wk postoperatively, 50 eyes (61.0%) had UDVA of ≥6/18, and 57 eyes (69.5%) had the CDVA of ≥6/18. Postoperative visual status was significantly related to the co-morbidities, such as corneal pathology, glaucoma (P<0.001). Operative complications, such as posterior capsule opacity and cystoid macular edema were main operative cause for the poor visual outcome. CONCLUSION: MSICS provides a good visual recovery in our study but the vision outcome did not fulfill the standards proposed by WHO, which highlights the need for an improvement in local socioeconomic understanding, population education and surgery quality.

Abstract:AIM: To compare the intraocular pressure (IOP) measurements obtained with the rebound tonometry (RT), dynamic contour tonometry (DCT) and Goldmann applanation tonometry (GAT) in normal and glaucomatous eyes and investigate the effects of central corneal thickness (CCT) and corneal curvature (CC) on IOP measurements. METHODS: One hundred and twenty-four eyes of 124 subjects were enrolled in this cross-sectional study. Fifty-six of participants were healthy individuals and 68 of them were glaucomatous patients. IOP was measured on each subject always in the same order, ICare RT-Pascal DCT-GAT, after a minimum interval of 10min between measurements. CCT and CC were measured using a rotating Scheimpflug camera before the IOP measurements in all subjects. One way repeated measures ANOVA, Pearson correlation coefficient and regression analysis, and Bland-Altman analysis was used for the statistical assessment. RESULTS: Mean IOP for all enrolled eyes was 16.00±3.80 mm Hg for GAT, 16.99±4.91 mm Hg for RT, and 20.40±4.44 mm Hg for DCT. Mean differences between GAT and RT was -1.75±3.41 mm Hg in normal (P<0.001) and -0.37±3.00 mm Hg in glaucomatous eyes (P=0.563). Mean differences between GAT and DCT was -4.06±3.42 mm Hg in normal (P<0.001) and -4.67±3.12 mm Hg in glaucomatous eyes (P<0.001). GAT and RT were significantly positive correlated with CCT in normal (r=0.317, P=0.017 and r=0.576, P<0.001, respectively) and glaucomatous eyes (r=0.290, P=0.016 and r=0.351, P=0.003, respectively). DCT was also significantly positive correlated with CCT in normal eyes (r=0.424, P=0.001) but not in glaucomatous eyes (r=0.170, P=0.165). All tonometers were unaffected by CC. CONCLUSION: IOP measurements by RT and DCT were significantly higher than GAT. DCT has highest IOP measurements among these tonometers. RT was most influenced tonometer from CCT although all tonometers were significantly positive correlated with CCT except DCT in glaucomatous eyes. CC did not influence IOP measurements.

Abstract:AIM: To assess the relation between central retinal artery (CRA) resistive index (RI) and retinal nerve fiber thickness measured by optical coherence tomography (OCT) in assessment of disease progress in cases of open angle glaucoma. METHODS: Twenty-three patients with diagnosed open angle glaucoma were included in this study. They were examined by colored duplex ultrasonography of CRA with estimation of RI of CRA and ophthalmic artery (OA) with estimation of CRA/OA RI ratio as well as OCT measurement of the average retinal nerve fiber layer (RNFL) thickness in order to assess the disease progress. RESULTS: There was strong inverse relation between the increased RI in CRA as well as the increased CRA/OA RI ratio and the decrease in average RNFL thickness in cases of open angle glaucoma. CONCLUSION: Assessment of CRA RI can indirectly assess the vascular changes associated with glaucoma and can assess the degree of retinal atrophy helping in evaluating prognosis thus guiding the choice of treatment.

Abstract:AIM: To examine eplerenone (Inspra, Pfizer), a mineralocorticoid receptor antagonist, as a treatment option for chronic central serous chorioretinopathy (CSCR). METHODS: A retrospective consecutive case series was conducted for patients receiving oral eplerenone for chronic CSCR. At baseline and each follow-up visit, spectral domain optical coherence tomography (SD-OCT) imaging was performed, including manual measurements of the height and diameter size of subretinal fluid. The primary outcome measure was the reduction in subretinal fluid following initiation of therapy. RESULTS: A total of 17 eyes of 13 patients treated with 25 and 50 mg of oral eplerenone per day were identified. Subretinal fluid (SRF) decreased over time following eplerenone therapy (P= 0.007 and P = 0.002, diameter and height respectively). Maximum SRF height decreased from a mean of 131.5 μm at baseline to 15.3 μm at day 181+. SRF diameter decreased from an average of 2174.4 μm at baseline to 46.9 μm at day 181+. LogMAR visual acuity improved from 0.42 (Snellen equivalent: 20/53) at baseline to 0.29 (Snellen equivalent: 20/39) at day 181+ (P = 0.024). Central subfield thickness (CST) decreased from 339.5 μm at baseline to 270.3 μm at day 181+ (P = 0.029). CONCLUSION: Eplerenone therapy resulted in significant anatomic and visual improvements in eyes with chronic CSCR.

Abstract:AIM: To evaluate the efficacy and safety of three consecutive monthly injections of intravitreal ranibizumab for the treatment of polypoidal choroidal vasculopathy (PCV) in Korea. METHODS: A retrospective chart review of 25 patients (27 eyes) with PCV was conducted. Patients received three initial monthly intravitreal injections (0.5 mg) of ranibizumab and were monitored monthly for 12mo between January 2010 and October 2011. Reinjection of ranibizumab after three initial monthly loading was administered on an as-needed basis, guided by the optical coherence tomography (OCT), fluorescein angiography (FA) and indocyanine green angiography (ICGA). The main outcomes were the changes of the mean best corrected Snellen visual acuity (VA), central macular thickness (CMT) by OCT, the changes of polyps and branching vascular network by FA and ICGA, and total number of injections received by patients during the 12mo. RESULTS: The mean best corrected Snellen visual acuities at baseline, 1, 3, 6 and 12mo after primary injection were 0.77±0.59, 0.76±0.53, 0.70±0.47, 0.63±0.43, 0.61±0.43, 0.62±0.42 logMAR, respectively, and showed significant improvement at 3, 6, 12mo (P=0.003, P=0.002, P=0.018, Wilcoxon signed-rank test). The mean CMT at baseline, 1, 2, 3, 6, and 12mo was 312.41±66.38 μm, 244.59±71.47 μm, 232.32±69.41 μm, 226.69±69.03 μm, 228.62±37.07 μm, 227.59±51.01 μm respectively, and showed significant reduction (all P<0.001, Wilcoxon signed-rank test). Polypoidal lesions resolved on ICGA in 3 eyes (11.1%) and a branching vascular network remained in all 24 eyes (88.9%). A total of 106 injections were given in the 12-month period, which equaled to a mean of 3.92 (range, 3-6) times. Sixteen of the 27 treated eyes had additional 1.56±0.91 injections. The others (11 eyes) had just 3 consecutive injections. CONCLUSION: An initial loading dose of three monthly ranibizumab injections is a safe and effective method in treating PCV, with visual and anatomical improvement over one year follow-up.