Change of Optical Coherence Tomography Morphology and Associated Structural Outcome in Diabetic Macular Edema after Ranibizumab Treatment.

(1) Background: To investigate the correlation between therapeutic outcome and morphologic changes for diabetic macular edema (DME) after intravitreal injection of ranibizumab (IVIR). (2) Methods: This retrospective study included 228 eyes received IVIR for DME. Each participant was traced for two years after the initial IVIR, while the data of ophthalmic examination, optical coherence tomography (OCT) image, and systemic diseases were collected. The study population was categorized into different subgroups according to the existence of OCT morphologic change and the initial OCT morphologic pattern, including diffuse retinal thickening (DRT), cystoid macular edema (CME), serous retinal detachment (SRD), and vitreomacular interface abnormalities (VMIAs). The primary outcomes were the baseline best-corrected visual acuity (BCVA) and central macular thickness (CMT) during a two-year study period. The distribution of OCT morphologic change and its relation to primary outcome were analyzed. (3) Results: Comparing the 42 eyes (18.4%) with OCT morphological changes to another 186 eyes (81.6%) without such alteration, the former showed a poorer baseline BCVA (0.84 ± 0.39 vs. 0.71 ± 0.36, p = 0.035), worse final BCVA (0.99 ± 0.44 vs. 0.67 ± 0.30, p = 0.001), and thicker final CMT (354.21 ± 89.02 vs. 305.33 ± 83.05, p = 0.001). Moreover, the VMIA developed in 14.9% of all DME patients presenting the most common morphologic change among DRT, CME, and SRD. Besides, the presence of stroke was independently correlated to the morphologic change (adjusted odds ratio [aOR]: 6.381, 95% confidence interval (CI): 1.112-36.623, p = 0.038). (4) Conclusions: The change of OCT morphology in DME patients receiving IVIR was correlated to worse structural and visual outcome while the formation of VMIA most commonly occurred after initial treatment.

Ranibizumab reimbursement and treatment patterns for neovascular age-related macular degeneration in Taiwan - Results from the 12-month, observational RENOWNED study.

BACKGROUND: The RENOWNED study investigated the treatment patterns, real-world effectiveness and safety of ranibizumab in Taiwanese patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab 0.5 mg in accordance with the first reimbursement scheme effective from 2012 to 2014. METHODS: This study was a Phase IV, 12-month, open-label, prospective, observational study conducted in Taiwan. Patients with visual impairment due to nAMD initiating treatment with ranibizumab 0.5 mg were included. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from Baseline at Month 3. RESULTS: Overall, 202 patients with nAMD were included. Mean (standard deviation [SD]) BCVA Early Treatment Diabetic Retinopathy Study letters improved from Baseline (49.6 [21.5] letters) at Month 3 (+4.9 [11.8], P < 0.0001), and at Month 12 (+3.5 [14.1], P = 0.0043). The proportion of patients with nAMD who lost ≥5 letters at Months 3 and 12 was 13.6% (n = 27) and 26.6% (n = 37), respectively. Mean (SD) central retinal thickness decreased from Baseline (320.1 [127.2] µm) with a mean reduction of 49.1 (107.3) µm at Month 3 (P < 0.0001), but was not significant at Month 12 with a mean reduction of 11.6 (115.6) µm (P = 0.2861). Mean (SD) number of ranibizumab injections over 12 months was 3.1 (1.0). A mean treatment interval of 109.5 days was observed between the third and fourth injections. After limited reimbursed ranibizumab injections, 43.8% patients received other treatments. The safety findings are consistent with previous studies. CONCLUSION: Ranibizumab 0.5 mg treatment for 12 months under real-world settings improved visual outcomes in Taiwanese patients with nAMD.

Optical Coherence Tomographic Patterns as Predictors of Structural Outcome After Intravitreal Ranibizumab in Diabetic Macula Edema.

BACKGROUND/OBJECTIVES: The purpose of this study was to present an association between the treatment response of diabetic macular edema (DME) to intravitreal ranibizumab (IVR) injections and different morphology patterns using spectral domain optical coherence tomography (SD-OCT). SUBJECTS/METHODS: This retrospective study included 216 eyes of 142 subjects who received IVR for DME and were observed for at least 2 years. Medical charts and SD-OCT images of consecutive patients were reviewed at baseline, 1, 3, 6, 12, and 24 months after first IVR treatment. The OCT patterns were characterized as diffuse retinal thickening (DRT), cystoid macular edema (CME), serous retinal detachment (SRD), and vitreomacular interface abnormalities (VMIAs). All patients were classified into four groups based on the OCT findings. RESULTS: For a total of 216 eyes, 36 eyes were classified into the DRT group, 76 in the CME group, 42 in the SRD group, and 62 in the VMIA group. There were significant central macula thickness (CMT) improvements in all groups at the 1st month and the 2nd year, except for the DRT group at the 2nd year. Patients with OCT findings of hyperreflective dots (HRDs), metabolic parameters of hyperlipidemia, and coronary artery disease (CAD) had significantly less improvements in CMT at 2-year follow-up (P=0.029, 0.007, <0.001, respectively). CONCLUSION: A trend toward decreased effectiveness after long-term IVR treatment was observed in the DRT group. Consistent IVR treatment could still achieve favorable improvement in the reduction of CMT in 2-year follow-up in the VMIA group. Different OCT patterns in DME may affect the therapeutic role of anti-VEGF agents and predict the structure outcome.

The relationship between age, axial length and retinal nerve fiber layer thickness in the normal elderly population in Taiwan: The Chiayi eye study in Taiwan.

AIMS: To interpret how the thickness of the peripapillary retinal nerve fiber layer (RNFL) changes with increasing age, axial length, or anterior chamber depth as measured by spectral domain optical coherence tomography (OCT) in the normal elderly population in Taiwan. METHODS: A total of 82 volunteers (143 eyes) were enrolled. Generalized estimating equations were used to evaluate the correlation. RESULTS: The RNFL was significantly thinner in the superonasal (p = 0.004), inferotemporal (p = 0.046), and temporolower (p = 0.009) segments with age. The same trend was also observed in the superotemporal (p = 0.330) segment, although it was not statistically significant. The global RNFL thickness decreased by 4.97 µm per decade (ß = -0.497; p = 0.021), and thinning was significant in the superonasal (-9.90 µm per decade, p < 0.001) and temporolower (-6.78 µm per decade, p < 0.001) segments; the same trend showed borderline significance in the superotemporal (-6.96 µm per decade, p = 0.073) and inferotemporal (-7.23 µm per decade, p = 0.059) segments. In eyes with longer axial length, the RNFLs significantly decreased in the non-temporal segments. Global RNFL thickness decreased by 3.086 µm for each additional millimeter of axial length (ß = -3.086; p < 0.001). CONCLUSIONS: Changes in RNFL thickness were correlated with age in the superonasal, superotemporal, inferotemporal, and temporolower segments, and were correlated with axial length in the non-temporal segments. Anterior chamber depth was not correlated with RNFL thickness.

Myopia Prevention and Outdoor Light Intensity in a School-Based Cluster Randomized Trial.

PURPOSE: To investigate the effectiveness of a school-based program promoting outdoor activities in Taiwan for myopia prevention and to identify protective light intensities. DESIGN: Multi-area, cluster-randomized intervention controlled trial. PARTICIPANTS: A total 693 grade 1 schoolchildren in 16 schools participated. Two hundred sixty-seven schoolchildren were in the intervention group and 426 were in the control group. METHODS: Initially, 24 schools were randomized into the intervention and control groups, but 5 and 3 schools in the intervention and control groups, respectively, withdrew before enrollment. A school-based Recess Outside Classroom Trial was implemented in the intervention group, in which schoolchildren were encouraged to go outdoors for up to 11 hours weekly. Data collection included eye examinations, cycloplegic refraction, noncontact axial length measurements, light meter recorders, diary logs, and questionnaires. MAIN OUTCOME MEASURES: Change in spherical equivalent and axial length after 1 year and the intensity and duration of outdoor light exposures. RESULTS: The intervention group showed significantly less myopic shift and axial elongation compared with the control group (0.35 diopter [D] vs. 0.47 D; 0.28 vs. 0.33 mm; P = 0.002 and P = 0.003) and a 54% lower risk of rapid myopia progression (odds ratio, 0.46; 95% confidence interval [CI], 0.28-0.77; P = 0.003). The myopic protective effects were significant in both nonmyopic and myopic children compared with controls. Regarding spending outdoor time of at least 11 hours weekly with exposure to 1000 lux or more of light, the intervention group had significantly more participants compared with the control group (49.79% vs. 22.73%; P < 0.001). Schoolchildren with longer outdoor time in school (≥200 minutes) showed significantly less myopic shift (measured by light meters; ≥1000 lux: 0.14 D; 95% CI, 0.02-0.27; P = 0.02; ≥3000 lux: 0.16 D; 95% CI, 0.002-0.32; P = 0.048). CONCLUSIONS: The school-based outdoor promotion program effectively reduced the myopia change in both nonmyopic and myopic children. Outdoor activities with strong sunlight exposure may not be necessary for myopia prevention. Relatively lower outdoor light intensity activity with longer time outdoors, such as in hallways or under trees, also can be considered.

Anti-angiogenic effect of hexahydrocurcumin in rat corneal neovascularization.

AIM: This study was to investigate the anti-angiogenic effect of hexahydrocurcumin (HHC) to evaluate gene (p-basic fibroblast growth factor (bFGF)-SAINT-18 & p-vascular endothelial growth factor (VEGF)-SAINT-18 complex)-induced corneal neovascularization (CorNV) in rats. METHODS: CorNV was induced in 24 eyes of 24 rats. Four groups (Group A: 0 µg, B: 0.01 µg, C: 0.1 µg, and D: 1 µg) of HHC were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus at temporal side. The 1 µg of p-bFGF-SAINT-18 & p-VEGF-SAINT-18 complex were prepared and implanted into the rat corneal stroma 1.5 mm from the limbus at the same side. Inhibition of CorNV was observed and quantified from day 1 to day 60. bFGF and VEGF protein expression were analyzed by biomicroscopic examination, western blot analysis, and immunohistochemistry. RESULTS: Subconjunctival injection by 1 µg HHC successfully inhibited gene-induced CorNV in rats. bFGF and VEGF protein expression were reduced after 6 days. Meanwhile, the reduction of HLA-DR expression was detected. CONCLUSIONS: Our study showed that the HHC might provide an important anti-angiogenesis factor to inhibit CorNV development at the corneal experimental angiogenesis model.

ANGIOGRAPHIC SUBTYPES OF POLYPOIDAL CHOROIDAL VASCULOPATHY IN TAIWAN: A Prospective Multicenter Study.

PURPOSE: To determine the incidence and clinical characteristics of angiographic subtypes of polypoidal choroidal vasculopathy (PCV). METHODS: It is a prospective, multicenter, cross-sectional study. Patients with newly diagnosed exudative macular degeneration are classified into PCV, age-related macular degeneration (AMD), and retinal angiomatous proliferation. Polypoidal choroidal vasculopathy is further classified into two subtypes depending on the presence (Type 1: polypoidal choroidal neovascularization) or absence (Type 2: typical PCV) of feeder vessels on indocyanine green angiography. RESULTS: We enrolled 169 patients: 76 (45%) with PCV, 75 (44.4%) with AMD, and 14 (8.3%) with retinal angiomatous proliferation. Of the patients with PCV, 20 (26%) were classified as Type 1 PCV and 56 (74%) were classified as Type 2 PCV. The Type 1 PCV had a similar mean age compared to the AMD group (73.1 ± 9.6 vs. 75.6 ± 8.8 years, P = 0.281) and the Type 2 PCV (68.8 ± 9.6 years) was younger than the AMD group (P < 0.001). Type 1 PCV presented with worse visual acuity compared with the AMD. Both PCV subtypes had a higher incidence of hemorrhagic complications (85% and 75% respectively). CONCLUSION: Type 2 PCV is more common than Type 1 PCV in Taiwan. Our results support the hypothesis that polypoidal choroidal neovascularization and typical PCV may be distinct entities.

Deep vein thrombosis due to continuous prone positioning after retinal detachment surgery.

In March 2014, a 56-year-old woman without previous underlying disease underwent encircling scleral buckling, 20-gauge pars plana vitrectomy, cryotherapy around a retinal tear, and gas-fluid exchange with 15% perfluoropropane flush for upper rhegmatogenous retinal detachment of the left eye. However, she developed progressive left leg swelling, pain, warmth, and redness, associated with difficulty in elevating her left leg after continuously maintaining a prone head position when either lying down or sitting for 2 days. When she arrived at the emergency room, she had an elevated D-dimer level. After undergoing Doppler ultrasound imaging, she was diagnosed as having deep vein thrombosis of the left leg. She received anticoagulation therapy with enoxaparin and warfarin overlapping for 7 days. The edema, pain, and paresthesia of her left leg were relieved. However, because of the risk of bleeding with anti-coagulation drug usage, the patient needed to be monitored for 6 months. Prone positioning for gas tamponade is important for anatomic and functional success in retinal detachment surgery; however, timely walking and rest between periods of continuous prone positioning should be encouraged to prevent deep vein thrombosis and other impaired circulation-related complications.

Rapid regression of cystoid macular edema associated with cytomegalovirus retinitis in adult acute myeloid leukemia by intravitreal methotrexate combined with oral valganciclovir: A case report with comparison of binocular outcome.

Cytomegalovirus (CMV) retinitis is a late complication of organ and hematopoietic stem cell transplant, the risk of which depends on the degree of immunosuppression. With the institution of preemptive ganciclovir therapy early after transplant, most patients survive episodes of life-threatening CMV infection during the early months (usually the first 3 months) after transplant and hence late onset of CMV disease, such as CMV retinitis, is being recognized more frequently. Direct involvement of the macula or optic head remains the leading cause of visual loss in patients with CMV retinitis, but there are few studies investigating the management of this condition. Herein, we present the case of 28-year-old man who had acute myeloid leukemia and developed CMV retinitis with bilateral cystoid macular edema and optic swelling in the right eye 6 months after bone marrow transplant. He received treatment with intravitreal methotrexate in the right eye in combination with oral valganciclovir. Visual acuity improved 1 month after four weekly injections of intravitreal methotrexate 400 µg/0.1 mL. Resolved disc swelling and regression of macular edema were also observed. By comparing binocular outcome, we present our findings and discuss the possible efficacy and safety of this treatment with respect to regression of anatomical damage and improvement in visual acuity.

Cladosporium keratitis - a case report and literature review.

BACKGROUND: Fungal keratitis is one of the major causes of infectious keratitis in tropical countries. Symptoms of fungal keratitis consist of blurred vision, redness, tearing, photophobia, pain and foreign body sensation. If not treated effectively, it could lead to blindness. Common causes include Candida spp., Fusarium spp. and Aspergillus spp.. With the limited choices of topical antifungal agents, we were faced with Cladosporium keratitis, a rare cause of fungal keratitis. CASE PRESENTATION: A 62-year-old Asian male construction worker came to us with intense ocular pain, injection of the conjunctiva, blurred vision, and foreign body sensation in his left eye. His visual acuity was 20/40 OD and 20/400 OS. Slit-lamp exam revealed a corneal ulcer with feathery margin and Descemet's membrane folding. The culture yielded Cladosporium species.. The patient did not show improvements after applying topical natamycin (5 %), topical amphotericin B (1mg/ml), topical fluconazole (2mg/ml) and oral ketoconazole (200mg). After shifting the medical regimen to voriconazole via topical and systemic routes (1mg/ml and 200mg respectively), the keratitis was controlled. CONCLUSIONS: Fungal keratitis remains a challenge for ophthalmologists as there is no evidence suggesting any particular drug or combination of drugs is more effective than another. A review of common topical antifungal agents was done. Voriconazole could be a good choice for treating corneal infection by Cladosporium species.

Axial length and subfoveal choroidal thickness in individuals with age-related macular degeneration.

PURPOSE: To compare axial length (AL) and subfoveal choroidal thickness (SFCT) between individuals with age-related macular degeneration (AMD) and controls with no lesions. METHODS: This was a case-control study. In total, 853 eyes of 484 patients (>65 years), including 397 eyes at various AMD stages and 456 eyes with no fundus lesions (controls) were recruited. Using color fundus photography, eyes were grouped according to AMD degree. AL was automatically measured using IOL Master and SFCT was manually measured by two independent observers. The associations among age, AL, SFCT, and each AMD grade were analyzed. RESULTS: Out of 853 eyes, 456 had no lesions, 217 contained drusen only, 134 had early AMD, and 46 had late AMD. The eyes with late AMD were older (p = 0.007) and had longer AL (p ≥ 0.001) and thinner SFCT (p < 0.001) compared with groups of no fundus lesions, drusen only, and early AMD. SFCT in eyes with late AMD decreased by 19.20 µm (p = 0.049), 24.78 µm (p = 0.029), and 15.56 µm (p = 0.162) compared with groups of no fundus lesions, drusen only, and early AMD, respectively. SFCT decreased by 14.18 µm/mm increase in AL (p < 0.001). The odds ratio (OR) for late AMD by longer AL (≥25 mm) and thinner SFCT (<240 µm) was 4.54 (χ2 = 9.36; p = 0.002) and 4.86 (χ2 = 17.62; p < 0.001), respectively, and was 9.57 (χ2 = 18.07; p < 0.001) when both AL ≥ 25 ≥m and SFCT < 240 µm. CONCLUSION: Eyes with late AMD have distinct reduced SFCT and elongated AL. Eyes with thinner SFCT and longer AL showed high ORs for late AMD and even higher ORs when both factors were simultaneously present. These findings illustrate the crucial pathophysiological role of these two important ocular fac tors and arouse our attention to patients with both characteristics, especially in Asian countries where the prevalence of myopia are disturbingly high.

Inhibition of corneal neovascularization with the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18 (p-PEDF-SAINT-18) vector in a rat corneal experimental angiogenesis model.

Bevacizumab, a 149-kDa protein, is a recombinant humanized monoclonal antibody to VEGF. PEDF, a 50-kDa glycoprotein, has demonstrated anti-vasopermeability properties. In this study, we demonstrated that the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18(p-PEDF-SAINT-18) has a favorable antiangiogenic effect on corneal NV. Four groups(Group A: 0 µg + 0 µg, B: 0.1 µg + 0.1 µg, C: 1 µg + 1 µg, and D: 10 µg + 10 µg) of bevacizumab + p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus on the temporal side. Then, 1 µgof p-bFGF-SAINT-18 was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. The inhibition of NV was observed and quantified from days 1 to 60. Biomicroscopic examination, western blot analysis and immunohistochemistry were used to analyze the 18-kDa bFGF, 50-kDa PEDF and VEGF protein expression. No inhibition activity for normal limbal vessels was noted. Subconjunctival injection with the combination of bevacizumab and p-PEDF-SAINT-18 successfully inhibited corneal NV.The bFGF and PEDF genes were successfully expressed as shown by western blot analysis,and a mild immune response to HLA-DR was shown by immunohistochemistry. We concluded that the combination of bevacizumab and p-PEDF-SAINT-18 may have more potent and prolonged antiangiogenic effects, making it possible to reduce the frequency of subconjunctival bevacizumab administration combined with a relatively safe profile and low toxicity.

Review on pharmacological activities of Cinnamomum subavenium.

This review describes the morphological, phytochemical and pharmacological properties of Cinnamomum subavenium (Lauraceae). The plant grows wild in southern Mainland China, Burma, Cambodia, Taiwan, Malaysia and Indonesia. This plant is recorded as having long been used to treat carcinomatous swelling, stomach ache, chest pain, abdominal pain, hernia, diarrhoea, rheumatism, nausea and vomiting. This article enumerates an overview of phytochemical and pharmacological aspects that is useful to researchers for further exploration for the necessary development of this potential herb.

Cell cycle regulation by bevacizumab in ARPE-19 human retinal pigment epithelial cells.

Bevacizumab, a recombinant humanized monoclonal antibody, binds vascular endothelial growth factor (VEGF) and inhibits its interaction with receptors found on endothelial cells. Bevacizumab has been increasingly used as an off-label treatment for exudative age-related macular degeneration (AMD). Whether or not bevacizumab is capable of arresting the growth of human retinal pigment epithelial cells remains to be clarified. In this study, flow cytometry was used to evaluate whether bevacizumab markedly induced the G1/S phase arrest. The G1/S phase cycle-related protein analysis demonstrated that the expression of cyclin-dependent kinase (CDK)2, 4 and 6 and of cyclin D and E, as well as the phosphorylation of retinoblastoma tumor suppressor protein (ppRB) production were found to be markedly reduced by bevacizumab. By contrast, the protein levels of p53, p16, p21 and p27 were increased in bevacizumab-treated ARPE-19 cells (a human retinal pigment epithelial cell line). These events of G1/S arrest induced by bevacizumab in ARPE-19 cells suggest that a preventive effect of bevacizumab exists in AMD.

Optical coherence tomographic patterns in diabetic macula edema can predict the effects of intravitreal bevacizumab injection as primary treatment.

PURPOSE: To identify optical coherence tomography (OCT) patterns in diabetic macular edema (DME) that were predictive of visual outcomes after intravitreal bevacizumab (IVB) injection. METHODS: This was a retrospective study. We examined 31 eyes (24 patients) with clinically significant macular edema that received IVB injections along with macular OCT data. The eyes were categorized into 4 groups by using OCT features: diffuse retinal thickening (DRT), cystoid macular edema (CME), serous retinal detachment (SRD), and vitreomacular interface abnormalities (VMIAs). Changes in retinal thickness, retinal volume, and visual acuity (VA) after IVB injection were compared on the basis of OCT patterns. RESULTS: After IVB injections, changes in VA logarithm of the minimum angle of resolution were -0.06±0.36, -0.26±0.26, 0.09±0.13, and -0.08±0.15, respectively, for DRT, CME, SRD, and VMIA patterns. Central macular thickness decreased by 70.5±105.5, 110.67±97.28, 181±125.87, and 24.25±77.12 µm for the DRT, CME, SRD, and VMIA patterns, respectively. The CME group was associated with a greater reduction in retinal thickness (P=0.009) and volume (P=0.027) with superior VA improvement (P=0.012) as compared with the DRT, SRD, and VMIA groups. CONCLUSIONS: Patients with CME gained greater improvement in visual acuity and macular thickness and volume after IVB injection had been administered as the primary treatment for DME, as compared with other patients. The OCT patterns of DME may indicate the appropriate treatment; we consider these patterns to be prognostic of the response to IVB injection for macular edema.

Role of redox signaling regulation in propyl gallate-induced apoptosis of human leukemia cells.

Propyl gallate (PG) is a synthetic antioxidant that has been used in processed food and medicinal preparations. The anti-cancer effect of PG in leukemia is unclear. In the present study, we demonstrate that PG reduced cell viability in THP-1, Jurkat, and HL-60 leukemia cells and induced apoptosis in THP-1 cells. PG activated caspases 3, 8, and 9 and increased the levels of p53, Bax, Fas, and Fas ligand. PG activated mitogen-activated protein kinases (MAPKs), inhibited nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf-2) and induced intracellular glutathione (GSH) depletion. In addition, PG increased superoxide dismutase-1 expression and decreased intracellular levels of reactive oxygen species. Our data show for the first time that an early event of PG-induced apoptosis is MAPKs/Nrf-2-mediated GSH depletion and that PG induced apoptosis via multiple pathways in human leukemia. PG might serve as a potential chemotherapeutic agent or food supplement for human leukemia patients.

Inhibition of corneal neovascularization with plasmid pigment epithelium-derived factor (p-PEDF) delivered by synthetic amphiphile INTeraction-18 (SAINT-18) vector in an experimental model of rat corneal angiogenesis.

The use of Synthetic Amphiphile INTeraction-18 (SAINT-18) carrying plasmid pigment epithelium-derived factor (p-PEDF) as an anti-angiogenesis strategy to treat corneal neovascularization in a rat model was evaluated. Four partially dried forms (Group A: 0 microg, B: 0.1 microg, C: 1 microg, D: 10 microg) of a p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus at the temporal side. The 1 microg of plasmid-basic fibroblast growth factor--SAINT-18 (p-bFGF-SAINT-18) (1 microg) was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. Inhibition of neovascularization was observed and quantified from day 1 to day 60. PEDF (50-kDa) and bFGF (18-kDa) protein expression were analyzed by biomicroscopic examination, Western blot analysis, and immunohistochemistry. Gene expression in corneal and conjunctival tissue was observed as early as 3 days after gene transfer and stably lasted for over 3 months with minimal immune reaction. Subconjunctival injection of a highly efficient p-PEDF-SAINT-18 successfully inhibited corneal neovascularization. Successful gene expression of bFGF, PEDF and a mild immune response of HLA-DR were shown by immunohistochemistry staining. We concluded that SAINT-18 was capable of directly delivering genes to the ocular surface by way of subconjunctival injection, and delivered sustained, high levels of gene expression in vivo to inhibit angiogenesis.

Effect of pterygium surgery on refractive spherocylinder power and corneal topography.

BACKGROUND AND OBJECTIVE: To evaluate the effect of pterygium surgery on refractive spherocylinder power and corneal topography. PATIENTS AND METHODS: Twenty-four patients (27 eyes) undergoing pterygium surgery from January to December 2006 were retrospectively identified. Visual acuity, refractive spherocylinder power, and corneal topography were measured preoperatively and postoperatively. RESULTS: Improvement of visual acuity, decreases of refractive spherocylinder power, and significant differences of 3-mm topographic irregularity and 3-mm topographic astigmatism postoperatively were found. Differences of refractive spherocylinder power preoperatively and postoperatively correlated significantly with differences of 3-mm topographic irregularity (spherical, r = 0.828, P = .000; cylinder, r = -0.805, P= .000) and of 3-mm topographic astigmatism (spherical, r = 0.673, P= .000; cylinder, r = -0.811, P = .000) preoperatively and postoperatively. CONCLUSION: Pterygium surgery produces improvements in visual acuity, decreases of refractive spherocylinder power, topographic irregularity, and topographic astigmatism. Three-millimeter topographic irregularity and astigmatism have a close correlation with refractive spherocylinder power.

A novel vector system for gene transfer into the cornea using a partially dried plasmid expressing 18 basic fibroblast growth factor-synthetic amphiphile INTeraction-18 (SAINT-18) complex.

PURPOSE: We describe a novel vector system of nonviral gene transfer into the cornea using a partially dried form of a plasmid expressing 18-kDa basic fibroblast growth factor (p-bFGF)-synthetic amphiphile INTeraction-18 (SAINT-18) complex. METHODS: Corneal neovascularization (NV) was evaluated in 48 eyes of Sprague-Dawley rats after implantation of SAINT-18 containing 2 micro g of plasmid-expressing green fluorescent protein (p-GFP; control group), 0.2 micro g, 2 micro g, or 20 micro g of p-bFGF from day 0 to day 60. bFGF protein expression was analyzed by Western blotting and immunohistochemistry. RESULTS: The p-bFGF-SAINT-18 complex induced dose-dependent corneal neovascularization, which reached a maximum on days 15-21 in the 20-micro g p-bFGF group, days 12-18 in the 2-micro g p-bFGF group, and on days 9-15 in the 0.2-micro g p-bFGF group, and then regressed progressively. No NV was observed in the p-GFP group. CONCLUSIONS: This noninflammatory corneal transfection model using partially dried p-bFGF-SAINT-18 complex allows precise localization of tranfection reagents for producing corneal neovascularization.

Effect of insulin on the expression of intraocular vascular endothelial growth factor in diabetic rats.

BACKGROUND: To investigate the long-term effect of insulin on vascular endothelial growth factor (VEGF) of streptozotocin (STZ)-induced diabetic rats. METHODS: Male Sprague-Dawley rats received intraperitoneal injections of STZ (60 mg/kg) to induce diabetes. The diabetic rats were divided into two groups: the poorly controlled diabetic group (4 U of Ultratard week) and the insulin-controlled group (2-8 U of Ultratard per day according to blood glucose level). The animals were sacrificed 4 months after diabetes induction. The intraocular fluids of four eyes from two rats were pooled together as one sample. VEGF was checked using an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: There were eight rats in the poorly controlled diabetic group, 13 in the insulin-controlled group and 10 in the healthy group. The concentration of VEGF ranged from 70.72-164.89 pg/ml (mean, 99.60 +/- 31.37 pg/ml) in the poorly controlled diabetic group, 65.17-124.33 pg/ml (mean, 79.05 +/- 21.50 pg/ml) in the insulin-controlled group and 50.6-67.6 pg/ml (mean, 58.07 +/- 6.49 pg/ml) in the healthy group. There were statistical differences between groups (ANOVA, p < 0.001). The mean difference between the poorly controlled diabetic group and the insulin-controlled group was 20.55 +/- 9.61 pg/ml (p = 0.041). CONCLUSION: The concentrations of VEGF in the two diabetic rat groups were higher than that in the healthy rat group. Insulin control reduced the rise of VEGF.