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.

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.

Krypton laser membranotomy for premacular hemorrhage.

BACKGROUND: To evaluate the safety and effectiveness of krypton laser membranotomy. METHODS: Eleven patients (12 eyes) with premacular hemorrhage were enrolled from April 1998 to November 2002. The causes of premacular hemorrhage were proliferative diabetic retinopathy (7 patients, 8 eyes), Valsalva retinopathy (3 patients) and leukemia (1 eye). Krypton laser was used to create a membranotomy on the sloping edge of the premacular hemorrhage. Five eyes with proliferative diabetic retinopathy were treated with inferior panretinal photocoagulation and laser membranotomy simultaneously. After intravitreal dispersion of premacular blood, fundus examinations were performed in all eyes and fluorescein angiography in 5 patients to evaluate the retinal damage. RESULTS: Vision was improved within 2 weeks after surgery in all eyes with premacular hemorrhage, which received krypton laser membranotomy. No retinal damage was seen at the site of membranotomy. No eye needed vitrectomy postoperatively during the follow-up (mean, 17 months). CONCLUSION: Krypton laser membranotomy appears to be a safe and simple alternative procedure for treating selected cases of premacular hemorrhage. Further trials are necessary to evaluate its benefit.

Significant prognostic factors for Vogt-Koyanagi-Harada disease in the early stage.

This study identified possible prognostic signs in the acute stage of Vogt-Koyanagi-Harada (VKH) disease in a retrospective chart review of all patients diagnosed with VKH disease between 1991 and 2001. Those who were diagnosed more than 1 month after the onset of ocular symptoms were excluded. Data recorded included age, sex, clinical features, systemic manifestations, recurrence, treatment, complications, and final visual acuity. Exudative retinal detachment was ranked into 3 grades (grade 1: within peripapillary 3 disc diameters and arcade; grade 2: larger than grade 1 but no inferior retinal detachment; grade 3: inferior or total retinal detachment). Of the 31 patients, 19 were males and 12 were females. Mean age at presentation was 38.55 +/- 10.63 years. The mean follow-up period was 33.09 months. Extraocular manifestations were present in 17 cases. Four patients had at least one complication, including cataract in seven eyes and glaucoma in one eye. Forty-nine eyes (79%) had a final visual acuity of 6/12 or better. Final visual acuity was significantly better in younger patients (p = 0.023) and those who had less extensive retinal detachment (p = 0.006), no pigmentary change (p = 0.008) and no complications (p = 0.030). The visual prognosis of VKH disease is variable, though generally favorable. In the acute stage, the extent of retinal detachment may be an important risk factor for visual outcome. Further study of this factor as an indicator for treatment is necessary.

Prognostic factors for Vogt-Koyanagi-Harada disease.

BACKGROUND: Vogt-Koyanagi-Harada disease is a chronic bilateral granulomatous panuveitis with involvement of the central nervous system, auditory and integumentary systems. The prognosis depends mostly on the development of complications or not. The purpose of this study was to identify the prognostic factors of Vogt-Koyanagi-Harada (VKH) disease. METHODS: Retrospective chart review of all the patients diagnosed with VKH disease between 1991 and 2000 was performed. Data recorded included age, sex, clinical features, systemic manifestations, recurrence, HLA typing, treatment, complications, and final visual acuity. Statistical analysis was performed using Statistical Products and Services Solutions. RESULTS: There were thirty-nine patients, the mean age at presentation was 39.82 +/- 12.38 years. The majority (46.2%) of patients were probable VKH disease, followed by incomplete type (43.5%), with only 10.3% complete type. Ten patients had at least one complication, including cataract in 19 eyes, glaucoma in 4 eyes and choroidal neovascularization in 3 eyes. Fifty eyes (64.1%) had final visual acuity of 6/12 or better. The interval between ocular symptom and treatment had significant effect on the development of complicaion (p = 0.022) and recurrence (p = 0.003), which were also significantly associated with the final visual acuity (p = 0.007). For patients who were diagnosed and treated within two weeks, the extent of exudative retinal detachment correlated significantly with final visual acuity (p = 0.001). CONCLUSIONS: The visual prognosis of VKH disease is generally favorable. The development of complications or recurrence was significantly associated with the visual outcome. Interval between development of ocular symptom and treatment seemed to be an important predictor in the early stage of VKH. It is important to start the treatment early even when the typical features of VKH disease have not completely appeared.

Inhibition of experimental angiogenesis of cornea by somatostatin.

BACKGROUND: This study evaluated the inhibitory activity of somatostatin 14 on the angiogenesis of cornea in vivo. METHODS: Corneal neovascularization was induced with a pellet containing 90 ng of basic fibroblast growth factor (bFGF) in a rat corneal pocket model. Three kinds of pellets were made containing bFGF plus somatostatin (SST) 0 ng, 20 ng and 200 ng for the control group, group 1 and group 2, respectively. Neovascularization was observed biomicroscopically from day 4 to day 8, and the corneas were then examined for changes in histology. Quantitation of angiogenesis in the cornea was accomplished by caliper and image analysis. RESULTS: The 200-ng dose of SST showed significant inhibition of both length and area of neovascularization on day 7 (0.62+/-0.11 mm vs 1.29+/-0.16 mm, 0.50+/-0.16 mm2 vs 1.35+/-0.29mm2, group 2 vs control; P<0.05). The 20 ng of somatostatin did not demonstrate any significant inhibition of neovascularization compared with the control group. CONCLUSION: Our study demonstrated that SST 14 can reduce bFGF-induced corneal angiogenesis. This shows the potential value of somatostatin in the treatment of corneal neovascularization.

Retinal capillary hemangiomas: clinical manifestations and visual prognosis.

BACKGROUND: To describe the clinical features, visual outcomes, and therapeutic complications of patients with retinal capillary hemangiomas. METHODS: A retrospective, non-comparative, observational case study of patients diagnosed with retinal capillary hemangiomas was conducted. Twelve patients (13 eyes) at Chang Gung Memorial Hospital of Kaohsiung from July 1987 to June 2001 were reviewed. Pre- and post-treatment visual acuity and ocular complications are described. RESULTS: One patient had bilateral and another had unilateral juxtapapillary hemangiomas. All of the other 10 patients were diagnosed with peripheral retinal capillary hemangiomas. More patients had retinal capillary hemangiomas located in the temporal peripheral retina and all had endophytic growth patterns. No patient met the diagnostic criteria of von Hippel-Lindau disease. Visual acuity levels of peripheral retinal hemangiomas without exudative retinal detachment often remained the same after focal laser treatment. Two patients received vitreoretinal surgery. Patients with juxtapapillary hemangiomas had variable visual outcomes and visual field defects during follow-up. CONCLUSION: Early diagnosis of capillary hemangiomas in the retinal periphery and treatment by focal laser produced good visual outcomes. If untreated, the tumors may eventually be complicated with exudative retinal detachment and have a worse visual prognosis even with vitreoretinal surgery.