Photodynamic therapy combined with anti-vascular endothelial growth factor therapy for pachychoroid neovasculopathy.

This multicenter retrospective study was conducted to evaluate the 1-year treatment outcome of photodynamic therapy (PDT) combined with anti-vascular endothelial growth factor (VEGF) therapy for pachychoroid neovasculopathy (PNV). A total of 42 eyes of 42 patients with treatment-naïve PNV who were treated with PDT combined with intravitreal injections of an anti-VEGF agent (ranibizumab or aflibercept) for 1 year. All eyes showed exudative and/or hemorrhagic changes that affected the fovea at baseline. After the initial combination therapy, subfoveal choroidal thickness (SCT) and central retinal thickness (CRT) were significantly reduced and were maintained as such for 12 months (P < 0.01 in SCT and CRT). The best-corrected visual acuity (BCVA) (0.19 ± 0.30 at baseline) significantly improved at 3 months (0.15 ± 0.29, P < 0.05) and further improved at 12 months (0.10 ± 0.30, P < 0.01) when compared to that at baseline. After the initial combination therapy, 32 eyes (76.2%) required no additional treatments for 12 months. The mean number of additional PDT and intravitreal injections of anti-VEGF agents was 0.1 ± 0.3 and 0.9 ± 1.9, respectively. Of the 42 eyes included in this study, 22 eyes (52.4%) had polypoidal lesions at baseline. No significant differences in SCT, CRT, or BCVA were observed at any time points between eyes with and without polypoidal lesions. Of 20 eyes without polypoidal lesions, only 1 eye (5.0%) needed additional treatments. PNV, especially without polypoidal lesions, can be treated effectively with PDT combined with anti-VEGF therapy with few sessions.

Results of switchback from ranibizumab to aflibercept in patients with exudative age-related macular degeneration.

PURPOSE: Intravitreal injection of anti-VEGF drugs has become standard therapy for patients with exudative age-related macular degeneration (AMD). However, some patients do not exhibit sufficient response to the drugs for suppression of choroidal neovascularization activity. We investigated the efficacy of switchback from ranibizumab to aflibercept in patients with AMD who could not achieve further benefit beyond initial therapy of aflibercept injection. METHODS: Eleven eyes of eleven patients were included in this study. Two patients were nonresponders, and nine exhibited tachyphylaxis to aflibercept. All patients received three monthly injections of ranibizumab as an initial phase of switching and received aflibercept as a switchback drug. We investigated changes in injection interval, visual acuity, and central retinal thickness. RESULTS: In four patients (36.4%), injection interval was extended. The interval was 6.73 weeks before switch and 9.27 weeks after switchback (P=0.96). LogMAR visual acuity was 0.22 before switch and 0.24 after switchback (P=0.62). Central retinal thickness was 306.8 µm before switch and 256.1 after switchback (P=0.13). In all patients who were nonresponders to aflibercept, injection interval could not be extended. CONCLUSION: A switchback from ranibizumab to aflibercept may be beneficial in some patients with AMD who exhibit tachyphylaxis to aflibercept.

Three-year results of a modified photodynamic therapy procedure (Ironing PDT) for age-related macular degeneration patients with large lesions.

BACKGROUND: To evaluate the effect of photodynamic therapy (PDT) using a modified procedure on exudative age-related macular degeneration having been conventionally difficult to treat. METHODS: The medical records of eight consecutive patients (eight eyes) with age-related macular degeneration treated with modified PDT were reviewed retrospectively. Modified PDT was used for the lesions that could not be covered by conventional use of PDT, either because the lesion was too large or too close to the optic disc. A moving PDT laser spot at constant speed, for 83 seconds, was used to cover the entire lesion, and was named "Ironing PDT." This retrospective study was performed with informed patient consent. It was approved by the Institutional Review Board of Kansai Medical University. RESULTS: No exudation could be found 36 months after treatment in five eyes (62.5%). There was no significant difference between the best-corrected visual acuity before PDT (0.95 logMAR) and after PDT (1.09 logMAR). The logMAR best-corrected visual acuity was improved in one eye, maintained in five eyes, and deteriorated in two eyes. CONCLUSION: Ironing PDT decreased subfoveal fluid and preserved visual acuity in some patients with age-related macular degeneration difficult to treat with conventional therapy.

Initial non-responders to ranibizumab in the treatment of age-related macular degeneration (AMD).

BACKGROUND: Patients with exudative age-related macular degeneration (AMD) who did not respond to ranibizumab at the induction phase were assessed and referred to as initial non-responders. METHODS: We retrospectively reviewed the medical records of 215 patients (218 eyes) with exudative AMD. For the initial treatments, patients received three intravitreal injections of ranibizumab (IVR) every 4 weeks. Minimum follow-up period was 12 months. We defined patients with no improvement of best corrected logMAR visual acuity (BCVA), and with no decrease of central retinal thickness (CRT) at the end of the initial treatment, as initial non-responders. Patients who had previous treatment history prior to this investigation were included, but patients who had photodynamic therapy (PDT) with IVR were excluded. RESULTS: Twenty-two eyes (10.1%) were identified as initial non-responders. The mean BCVA of initial non-responders before IVR and after induction phase were 0.39 and 0.36, respectively. There was no significant difference between these values, however the mean BCVA decreased significantly to 0.55 at 12 months after the beginning of the induction phase (P = 0.021). The mean greatest linear dimension (GLD) of the lesion before IVR of initial non-responders was 4,121 µm. We found 16 eyes with typical AMD, and six eyes with polypoidal choroidal vasculopathy. One eye had predominantly classic choroidal neovascularization (CNV), and others had occult CNV of typical AMD. As additional treatments, twelve eyes received PDT, and in three of the eyes exudation remained after PDT. CONCLUSION: Initial non-responders were more prevalent in patients with occult CNV than in patients with other CNV types. Some of the initial non-responders did not respond to PDT. This study suggested possible involvement of other factors, in addition to vascular endothelial growth factor, in the occurrence of CNV in initial non-responder patients.

Characteristics of age-related macular degeneration in patients with diabetic retinopathy.

PURPOSE: The purpose of this study was to determine the clinical characteristics of age-related macular degeneration (AMD) in patients with diabetic retinopathy (DR). METHODS: Retrospective, consecutive case series. Twenty-six eyes of 25 Japanese patients were studied. All patients were diagnosed as having exudative AMD with DR. Patients with no apparent DR, dry AMD, neovascular maculopathy associated with high myopia, and age <50 years were excluded. The clinical characteristics of AMD in patients with DR, e.g., gender, age, stage of DR, and type of AMD were evaluated. RESULTS: In the 26 eyes, 2 eyes (7.7%) were classified as mild nonproliferative DR (NPDR), 7 (27.0%) with moderate NPDR, 16 (61.5%) with severe NPDR and 1 eye (3.8%) with PDR. Of the 26 eyes with exudative AMD, 21 eyes (80.8%) were classified as neovascular AMD, 4 (15.4%) as polypoidal choroidal vasculopathy and 1 eye (3.8%) as a retinal angiomatous proliferation. Among the eyes with neovascular AMD, 9 eyes (42.9%) were classified as predominantly classic choroidal neovascularization (CNV). CONCLUSIONS: There is a predominance of men, neovascular AMD and predominantly classic CNV in Japanese AMD patients with DR. The exudative AMD in patients with DR may have different clinical characteristics from those without DR.

Improvement of the topographic parameters of the optic discs after trabeculotomy in two patients with developmental glaucoma.

Changes in the optic discs before and after trabeculotomy were evaluated with the Heidelberg retina tomograph (Heidelberg Engineering GmbH, Heidelberg, Germany) in two patients with developmental glaucoma. The topographic parameters of each optic disc improved considerably compared with adult patients in previous reports. This improvement may have been the result of the elasticity of the histologic structure of the optic disc in younger patients.

Intraocular pressure (IOP) reduction by latanoprost in Japanese normal tension glaucoma patients over a five-year period stratified by presenting IOP.

PURPOSE: We examined the effectiveness of latanoprost for reducing intraocular pressure (IOP) in Japanese patients with normal tension glaucoma (NTG) over a 5-year period. DESIGN: Prospective interventional case series. The patients were classified into 2 groups based on mean IOP. METHODS: A total of 38 patients with NTG were studied after being classified into the high-tension (mean IOP 16 mmHg or greater, n = 27) and low-tension (mean IOP lower than 15 mmHg, n = 11) groups. IOP was measured and Humphrey Field Analyzer (HFA) examinations were conducted at 6, 12, 24, 36, 48, and 60 months after beginning a daily administration of latanoprost. RESULTS: Mean IOP before administration was 17.6 mmHg in the high-tension group, which was reduced to 13.9, 14.6, 14.4, 14.1, 13.6, and 14.6 mmHg at 6, 12, 24, 36, 48, and 60 months, respectively, after beginning administration. That in the low-tension group was 13.6 mmHg before administration, and then was reduced to 12.2, 11.4, 11.5, 12.5, 10.5, and 11.5 mmHg, respectively, after beginning administration was noted. Mean deviation (MD) values in the HFA examinations were reduced by -4.27 and -1.49 dB after 5 years in the high- and low-tension groups, respectively. CONCLUSIONS: Latanoprost administration was effective in reducing IOP over a 5-year period in a range of 3.1-4.1 and 1.3-3.6 mmHg in NTG patients with high- and low-tension levels, respectively. In addition, our results indicate that latanoprost helped to prevent a decrease in MD values in both groups, as shown by the results of HFA examinations.

[Evaluation of cases of polypoidal choroidal vasculopathy showing classic choroidal neovascularization in their natural course].

BACKGROUND: Some cases of polypoidal choroidal vasculopathy (PCV) in their natural course develop into classic choroidal neovascularization(CNV) as shown by fluorescein angiography (FA) findings. SUBJECTS AND METHOD: We evaluated 8 eyes of 8 PCV patients showing classic CNV by FA findings, using indocyanine green angiography (IA) and optical coherence tomography(OCT). RESULT: All patients showed subretinal grayish exudates, which were considered fibrinous. Five cases were recognized as true subretinal CNV according to IA and OCT findings. The other 3 patients showed polypoidal dilatation with vascular networks by IA, and a moderately reflective mass considered fibrinous over the polypoidal elevation of retinal pigment epithelium (RPE) by OCT. CONCLUSION: Both true CNV and PCV with fibrin are present in PCV patients showing classic CNV. It requires care to determine proper treatment.

[Optical coherence tomographic findings of the retinal pigment epithelium tear in macular area preserving good visual acuity].

PURPOSE: It has been reported that the visual outcome of retinal pigment epithelial tear (RPE tear) in the fovea is worse than that of RPE tear sparing the fovea. We report optical coherence tomography (OCT) findings of 3 cases with RPE tear in the fovea who preserved good visual acuity. PATIENTS: All patients had serous retinal pigment epithelial detachment involving the macula. The RPE was torn and rolled RPE was observed in the fovea. In OCT findings, a fovea was observed on the RPE flap, and visual acuity was preserved after RPE tear repair. CONCLUSION: We considered that preservation of good visual acuity was due to the presence of a fovea on the RPE flap. We could precisely analyze the location of the fovea and RPE tear using OCT.

Retinopathy in monkeys with spontaneous type 2 diabetes.

PURPOSE: Type 2 diabetes occurs spontaneously in rhesus monkeys and shows an extraordinary similarity to human diabetes in clinical features and relative time course. The purpose of this study was to investigate clinically and histopathologically the ocular changes in these monkeys. METHODS: Ophthalmoscopic examinations were performed on aged normal and diabetic monkeys. Retinas from 16 diabetic monkeys and 6 nondiabetic monkeys were incubated postmortem for adenosine diphosphatase (ADPase) activity (labels viable retinal blood vessels) and flat-embedded in JB-4. Tissue sections were cut through areas of interest. RESULTS: Cotton-wool spots, intraretinal hemorrhages, and hard exudates in the macula were observed by ophthalmoscopy in some diabetic monkeys. Dot/blot hemorrhages, cotton-wool spots, and small nonperfused areas were the earliest histologically documented changes in the retinas. Large nonperfused areas extending from optic disc to midfovea were observed in four diabetic monkeys. Formation of small intraretinal microvascular abnormalities (IRMAs) and microaneurysms were associated with the areas of nonperfusion. There were apparent fluid-filled spaces in the outer plexiform layer in three of these maculas, suggesting macular edema. There was a significant correlation between the occurrence of retinopathy and hypertension (P = 0.037 for systolic pressure; P = 0.019 for diastolic pressure). In elastase-digested retinas, the ratio of pericytes to endothelial cells was 0.66:1 in diabetic and 0.64:1 in nondiabetic (P = 0.75) retinas. CONCLUSIONS: This is the first detailed analysis of retinopathy in a colony of spontaneous type 2 diabetic monkeys. Monkeys with type 2 diabetes have many of the angiopathic changes associated with human diabetic retinopathy. Hypertension correlates with the severity of the diabetic retinopathy.

Polypoidal choroidal vasculopathy: incidence, demographic features, and clinical characteristics.

OBJECTIVE: To clarify the incidence, demographic features, and clinical characteristics of polypoidal choroidal vasculopathy (PCV) in Japanese patients. METHODS: Consecutive patients with presumed neovascular age-related macular degeneration (AMD) who met the eligibility criteria were examined between January 1, 1999, and October 31, 2001. All patients underwent complete ophthalmologic examination and fluorescein and indocyanine green angiography. RESULTS: Among 471 eyes of 418 patients who met the criteria, 110 eyes (23%) of 100 patients were diagnosed as having PCV and 361 eyes (77%) of 318 patients as having neovascular AMD. Mean age of patients with PCV was 68.4 years, with a male preponderance (63% of patients); involvement was mostly unilateral (90% of patients), and polypoidal vascular lesions were located mainly in the macula (85% of eyes). Retinal manifestations of PCV were characterized by serous macular detachment (52% of eyes), submacular hemorrhage (30% of eyes), and retinal pigment epithelium degeneration (10% of eyes). There were few subretinal fibrovascular proliferations (7% of eyes). Mean visual acuity was 0.31 in eyes with PCV and 0.18 in eyes with AMD. The incidence of severe visual loss (0.2 or worse) was 35% in PCV and 53% in AMD. CONCLUSIONS: The incidence of PCV in Japanese patients is high, and the incidence and demographic features vary in different ethnic groups. The clinical manifestations of PCV and AMD resemble each other; however, PCV is characterized by low incidence of subretinal fibrovascular proliferation, slow progression of vascular abnormality, and minimal association with conventional choroidal neovascularization. These factors seem to lead to a more favorable visual outcome in PCV compared with neovascular AMD.

Immunohistochemical staining and morphometric analysis of the monkey choroidal vasculature.

The purpose of this study was to develop a method for staining non-human primate choroidal blood vessels for combined whole mount and histologic analysis. Ten monkey eyes were used in this study. Diabetic and non-diabetic aged rhesus monkeys ranging in age from 16 to 31 years were killed and eyes were obtained immediately after death. Anterior segments were removed and retinas dissected from the posterior eyecup. Eyecups were soaked in 0.1% EDTA for 1hr to remove the retinal pigment epithelium (RPE). The whole choroids were dissected from the sclera, fixed in 2% paraformaldehyde and processed for immunohistochemical demonstration of perlecan, a heparan sulfate proteoglycan, using a streptavidin alkaline phosphatase technique. The alkaline phosphatase reaction product was developed using Histomark Red. Following immunohistochemical staining, choroids were incubated for the enzyme histochemical demonstration of non-specific esterase to label granulocytes. Anti-perlecan was localized to the endothelial cells of viable choroidal blood vessels and provided excellent staining of the choriocapillaris in all regions. Morphometric measurements of choriocapillaris were made in wet preparations using digitized images and image analysis software. The staining was absent in degenerated choroidal capillaries (lacking endothelial cells), thus allowing for sites of pathology to be identified and analysed. The reaction product was retained within the tissue throughout the flat-embedding process and allowed for precise site-specific identification of angiopathic lesions en bloc during sectioning. This technique provides a method of staining monkey choroidal blood vessels in situ and allows for identification and analysis of pathologic changes associated with aging or diseases.

Quantifying changes in RPE and choroidal vasculature in eyes with age-related macular degeneration.

PURPOSE: An image-analysis technique was developed to quantify changes in the retinal pigment epithelium (RPE) and choriocapillaris in eyes of deceased donors with age-related macular degeneration (AMD). METHODS: Both eyes of two donors with AMD and of one normal control donor were used to develop this technique. After removal of the anterior segments, the eyecups were hemisected through the macula, with the disc included in one half of the eyecup. The choroid with RPE cells was dissected from the sclera and incubated for alkaline phosphatase (APase) activity, and the pigment was partially bleached with H2O2. The APase-incubated choroid was flat embedded and sectioned after image and morphometric analyses. Quantitative computer-assisted morphometric analyses of the two AMD-affected eyes (cases 1 and 2) were compared with analysis of the normal eye of a 70-year-old control subject (case 3). RESULTS: The right eye in case 1 had geographic atrophy (GA) and demonstrated a large area in the posterior pole with very few RPE cells (90% loss of RPE), but the border of the area of RPE atrophy was not well defined. The density of choroidal blood vessels in this area was reduced 30% to 50%, compared with the same regions in the control eye. No area was completely devoid of choriocapillaris. Clinically undetected choroidal neovascularization (CNV) was observed in the right eye in case 1 in both the periphery and the macula and was generally associated with surviving RPE cells. The right eye in case 2 had GA (areolar RPE atrophy) and demonstrated a reduction in vascular density in the area from disc to macula that was even greater than that in the eye in case 1 (53% reduction in the submacular region). RPE atrophy between the disc and macula was almost complete. The border of the RPE defect was clearly delineated and coincided closely with the area of decreased choroidal vascular density. Surviving choriocapillaris in the area of RPE atrophy was significantly narrower than choriocapillaris in the control subject and in normal areas of the eyes with GA (P < 0.0001). CONCLUSIONS: In these eyes with GA, RPE atrophy was more severe than loss of choriocapillaris. Surviving choriocapillaris in areas with complete RPE loss was highly constricted. The association of surviving RPE cells with CNV suggests that RPE cells may furnish a stimulus for new vessel formation or stabilization.

Expression of pigment epithelium-derived factor in normal adult rat eye and experimental choroidal neovascularization.

PURPOSE: Pigment epithelium-derived factor (PEDF) is a protein produced by the retinal pigment epithelial (RPE) cells. Recent studies have implicated PEDF in activities that are inhibitory to angiogenesis. In this study, the expression of PEDF was investigated in normal rat eyes and in eyes with experimentally induced choroidal neovascularization and compared with the expression of vascular endothelial growth factor (VEGF). METHODS: Choroidal neovascularization was induced by laser photocoagulation in rat eyes. At intervals of up to 2 weeks after photocoagulation, the eyes were removed and prepared for in situ hybridization and immunohistochemical study. In situ hybridization was performed with digoxigenin-labeled PEDF riboprobes. Protein expression of PEDF and VEGF was studied immunohistochemically. RESULTS: In normal adult rat eyes, PEDF mRNA was observed mainly in the corneal epithelial and endothelial cells, lens epithelial cells, ciliary epithelial cells, retinal ganglion cells, and the RPE cells. During the development of choroidal neovascularization, PEDF mRNA, PEDF protein, and VEGF protein were strongly detected in many cells within the laser lesions at 3 days after photocoagulation, after which levels gradually declined. However, PEDF was still expressed in the RPE cells that proliferated and covered the neovascular tissues at 2 weeks, whereas VEGF protein was weakly expressed in endothelial cells in choroidal neovascularization. CONCLUSIONS: PEDF is expressed in different cell types of normal rat eyes. The expression of PEDF was detected in the choroidal neovascular tissues induced by photocoagulation, and these findings suggest that PEDF may modulate the process of choroidal neovascularization.

Pathologic features of vascular endothelial growth factor-induced retinopathy in the nonhuman primate.

PURPOSE: Vascular endothelial growth factor (VEGF) is a potent ischemia-upregulated angiogenic protein that has been implicated in diabetic retinopathy. Intravitreal VEGF injections have not previously been shown to produce preretinal neovascularization. The purpose of this study was to further characterize the angiopathic changes that occur after intravitreal injections in a nonhuman primate and determine if preretinal neovascularization develops. DESIGN: Experimental animal study. METHODS: Vascular endothelial growth factor 165 was injected into the eyes of normal cynomolgus monkeys at regular intervals. As a control, normal eyes were injected with phosphate buffered saline. Color photography and fluorescein angiography were performed at regular intervals. The retinas were incubated for adenosine diphosphatase (ADPase) activity to visualize retinal vessels. The retinas were flat-embedded and areas of potential preretinal neovascularization were identified en bloc and serially sectioned. RESULTS: Areas of capillary nonperfusion and vessel dilation and tortuousity were seen by angiography. In serial sections, the nonperfused areas were found to be associated with endothelial cell hyperplasia in vessel lumens. Preretinal neovascularization originating only from superficial veins and venules was observed throughout peripheral retina, but was not seen in the posterior pole. Lacunae-like veins were subdivided by the process of intussusception and endothelial cell bridging. Arterioles demonstrated endothelial cell hyperplasia and microaneurysms. CONCLUSION: Intraocular injections of VEGF were sufficient to produce preretinal neovascularization in the nonhuman primate. Most vasculopathic structures were associated with endothelial cell hyperplasia. These results demonstrate that VEGF alone can produce many features of both nonproliferative and proliferative diabetic retinopathy including the previously undescribed development of preretinal neovascularization. This well-characterized VEGF-induced primate model of retinal neovascularization may be useful as a means of testing new treatments for retinal neovascularization.

Mechanisms for sickle red blood cell retention in choroid.

PURPOSE: Although sickle (SS) red cell-mediated vaso-occlusion in retina and resultant retinopathy is well documented, the effects of SS red cells on choroidal vasculature are poorly understood. The intent of this study was to determine, using a rat model, the conditions under which retention of sickle erythrocytes in choroid occur and if that retention can be inhibited. METHODS: Sickle red cells were density separated into high density (SS4) or normal density, reticulocyte-enriched fractions (SS2). Red cells were labeled with FITC and administered IV to anesthetized Sprague Dawley rats. Rats were made either hypoxic or were given TNF-alpha intraperitoneally 5 hours before intravenous administration of red cells. Five minutes after administration of red cells, rats were exsanguinated, the retinas removed, and choroids prepared as flatmounts. The number of red cells retained in five high power fields of choroid was then determined. In other experiments, SS red cells were preincubated with the cyclic peptide TBC772 [inhibits binding of alpha4beta1 (VLA-4) and alpha4beta7 to their ligands], a control peptide TBC1194, or a VLA-4 neutralizing antibody before administration to the rat or antibodies against VLA-4 ligands were delivered IV before administration of SS red cells. RESULTS: Hypoxic conditions before administration of SS red cells significantly stimulated retention of SS4 cells (P = 0.0003), but did not significantly increase retention of SS2 cells. Administration of TNF-alpha significantly increased retention of all types of SS red cells (P < 0.001). Preincubation of cells with anti-VLA-4 or TBC 772 inhibited retention of SS red cells in choriocapillaris of TNF-alpha-treated rats (P < 0.0001). Complete inhibition of cytokine-stimulated retention was also accomplished by IV administration of monoclonal antibodies against fibronectin or its CS-1 domain, a ligand for VLA-4. CONCLUSIONS: The mechanisms for retention of SS red cells in retina and choroid appear identical: hypoxia-mediated retention of dense red cells and adherence of red cells in reticulocyte-rich fractions after cytokine stimulation. TNF-alpha-stimulated retention of SS red cells in choroid appears to be mediated by VLA-4, presumably on the surface of some reticulocytes. This increased retention was inhibited by a VLA-4 antagonist (TBC772), a VLA-4 neutralizing antibody or by blocking one of VLA-4's ligands, the CS-1 portion of fibronectin.

Effective transfection of a cis element "decoy" of the nuclear factor-kappaB binding site into the experimental choroidal neovascularization.

PURPOSE: To evaluate the efficacy of the gene transfer of a double-stranded phosphorothioate oligonucleotides (ODNs), called a "decoy", against the NF-kappaB binding site into cells of an experimentally-induced choroidal neovascularization. METHODS: FITC-labeled decoy was injected into the subretinal space of rat eyes by the HVJ-liposome delivery system, and 3 days later, choroidal neovascularization was induced by laser photocoagulation. The eyes were removed and the transfected cells were detected by fluorescence microscopy and also detected by immunohistochemistry. The degree of neovascularization was evaluated by fluorescein angiography. RESULTS: The decoy was transfected into the retinal pigment epithelial (RPE) cells, inner and outer segment of the photoreceptors at 3 days after the injection. When choroidal neovascularization was induced, highly effective transfection of the decoy was observed 3 to 14 days after photocoagulation, after which the level decreased. Decoys were transfected into the RPE cells and macrophages in the choroidal neovascularization. The eyes transfected with NF-kappaB decoy showed a weaker leakage in fluorescein angiograms than that of the control eyes transfected with scrambled decoy. CONCLUSIONS: A decoy can be transfected into retinal cells and cells within a choroidal neovascularization by the HVJ-liposome method. The transferred NF-kappaB decoy reduced the degree of choroidal neovascularization. Decoy targeted against NF-kappaB may be considered as a potential therapy for neovascularization.