A new drug-screening procedure for photosensitizing agents used in photodynamic therapy for CNV.
(25/742)
PURPOSE: Because vascular occlusion has been observed as a consequence of photodynamic therapy (PDT), this method has been successfully used for the treatment of choroidal neovascularization (CNV) in age-related macular degeneration (AMD). However, most conventional photosensitizers, primarily developed for tumor PDT, lack selectivity for the targeting of neovascularization. An experimental model has been developed for drug screening of new photosensitizers for the treatment of CNV associated with AMD. It consists of intravenous (IV) injection of photosensitizers and fluorescent dyes into the chick's chorioallantoic membrane (CAM), followed by measurement of fluorescence pharmacokinetics, leakage from the vascular system, and photothrombic efficacy. METHODS: Fertilized chicken eggs were placed under a fluorescence microscope. After intravenous injection of different dyes, time-dependent fluorescence angiography was performed. The effect of PDT parameters was assessed by fluorescence angiography 24 hours after PDT. RESULTS: Although fluorescence of lipophilic benzoporphyrin derivative monoacid ring A (BPD-MA) remained intravascular during 2 hours, hydrophilic dyes tended to leak through the fenestrated neovascularization. By variation of PDT parameters, vascular damage could be directed toward closure of vessels with a diameter smaller than 10 microm, as measured 24 hours after PDT. High photosensitizer concentrations and high light doses resulted in blood flow stasis within 60 minutes, confirmed by fluorescence angiography. CONCLUSIONS: Fluorescence angiography and PDT after IV injection into the CAM showed strong similarities to results obtained in clinical tests of PDT in CNV associated with AMD. Thus, this model can provide valuable information about PDT mechanisms and can be used for drug-screening purposes in development of improved sensitizers for the PDT of CNV. (+info)
Manifest refraction versus autorefraction for patients with subfoveal choroidal neovascularization.
(26/742)
PURPOSE: To compare the results from manifest refraction using trial lenses and a standard visual acuity protocol to results from autorefraction for obtaining refractive error and best corrected visual acuity in patients enrolled in a randomized clinical trial. METHODS: During a 4-month period, 29 patients with subfoveal choroidal neovascularization (CNV), who were enrolled in the Submacular Surgery Trials (SSTs) Pilot Study at the Wilmer Ophthalmological Institute, gave verbal consent to participate in this study. Best corrected visual acuity was obtained using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts and standardized room lighting after performance of manifest refraction, according to the SST protocol, and autorefraction. Refractive error (spherical equivalent) and visual acuity scores were obtained in both eyes of all patients. RESULTS: On average, manifest refraction gave a spherical equivalent that was 1.04 D more plus than autorefraction (95% limits of agreement = 0.74, 1.34). On average, the visual acuity score was 1.5 letters better after manifest refraction than after autorefraction (95% limits of agreement = 0, 3.0). The comparison of the two methods of refraction was subdivided according to visual acuity level and eye disease (age-related macular degeneration or ocular histoplasmosis syndrome). CONCLUSIONS: Despite large differences in spherical equivalent between manifest refraction and autorefraction, the visual acuity scores were close (mean difference, 1.5 letters). Other studies comparing subjective refraction and autorefraction have shown similar results. Autorefraction in patients with subfoveal CNV may be a satisfactory alternative to manifest refraction in clinical trials and field studies in which best corrected visual acuity is of interest. (+info)
Transpupillary thermotherapy (TTT) for the treatment of choroidal neovascularisation.
(27/742)
AIM: To assess the effectiveness of transpupillary thermotherapy (TTT) for the treatment of classic and occult choroidal neovascularisation (CNV). METHOD: In a retrospective, case selected, open label trial 44 eyes of 42 patients with CNV secondary to age related macular degeneration (ARMD) were studied. 44 eyes with angiographically defined CNV were treated with diode laser (810 nm) TTT. Laser beam sizes ranged between 0.8 and 3.0 mm and power settings between 250-750 mW. Treatment was given in one area for 1 minute, the end point being no visible change, or a slight greying of the retina. Outcome was assessed with Snellen visual acuity and clinical examination; in 24/44 patients angiographic follow up was available. RESULTS: 12 predominantly classic CNV and 32 predominantly occult membranes were followed up for a mean of 6.1 months (range 2-19). Mean change in vision for classic membranes was -0.75 (SD 1.75) Snellen lines and occult membranes was -0.66 Snellen lines (2.1) (p>0.05). Predominantly classic membranes were closed in 75% (95% CI: 62.5-87.5) of eyes, remained persistent in 25% (95% CI: 12.5-37.5); no recurrences occurred. Predominantly occult membranes were closed in 78% (95% CI: 70.1-85.3) of eyes, remained persistent in 12.5% (95% CI: 6.6-18.5), and were recurrent in 5.1% (95% CI: 4.2-14.3). CONCLUSIONS: Transpupillary thermotherapy is a potential treatment for CNV. It is able to close choroidal neovascularisation while maintaining visual function in patients with classic and occult disease. Further trials of TTT are needed to compare this intervention with the natural history and other treatment modalities. (+info)
Relation between macular morphology and visual function in patients with choroidal neovascularisation of age related macular degeneration.
(28/742)
AIM: To examine the relation between three measures of visual function (distance acuity, near acuity, and contrast sensitivity) and specific fluorescein angiographic characteristics of the macular lesion in patients with subfoveal choroidal neovascularisation (CNV) due to age related macular degeneration (AMD). METHODS: Visual evaluation and digital fundus fluorescein angiography were performed in 93 patients with subfoveal CNV. Standard morphometric techniques were used on two frames from the angiographic series closest to 30 seconds and 60 seconds respectively, to ascertain total lesion size (defined as the entire area of abnormal fluorescence), the size of the classic component, and the distance from the fovea to the closest point of healthy retina. Correlations were sought using Pearson's correlation coefficients. Stepwise regression was used to minimise multiple colinearity. RESULTS: When the study eye was the better eye of a patient's pair of eyes, the strongest correlation was between the size of the classic component and contrast sensitivity (r= 0.48, p <0.001) and was highly significant. When the study eye was the worse eye, significant correlations were observed between total lesion size and all three measures of visual function. The strongest correlation was observed between overall lesion size and contrast sensitivity (r = 0.52, p <0.001). CONCLUSIONS: This study has shown that the status of the study eye (that is, better or worse eye of a pair of eyes) influences the impact of macular pathology in AMD on visual function. The distance of the fovea from healthy retina was found to be an important factor in predicting visual function. (+info)
Feeder vessel laser photocoagulation of subfoveal choroidal neovascularization.
(29/742)
We performed laser photocoagulation for extrafoveal feeder vessels in a series of 10 eyes with subfoveal choroidal neovascular membranes (CNVMs) in which feeder vessels could be detected by means of indocyanine green angiography using scanning laser ophthalmoscope. On the follow up indocyanine green angiograms performed within one week after treatment, successful occlusion of the feeder vessels with nonperfusion of the corresponding CNVMs was observed in 8 eyes (80%). Four eyes showed improved visual acuities with resolution of the exudative manifestation. But within 3 months, recanalization of the feeder vessels or further proliferation of the CNVMs developed in 7 eyes. We confirmed the possibility of infarction and regression of the CNVM by feeder vessel photocoagulation, which could improve the visual acuity. But it was rarely possible to maintain them. (+info)
Influence of plasminogen activator inhibitor type 1 on choroidal neovascularization.
(30/742)
High levels of the plasminogen activators, but also their inhibitor, plasminogen activator inhibitor 1 (PAI-1), have been documented in neovascularization of severe ocular pathologies such as diabetic retinopathy or age-related macular degeneration (AMD). AMD is the primary cause of irreversible photoreceptors loss, and current therapies are limited. PAI-1 has recently been shown to be essential for tumoral angiogenesis. We report here that deficient PAI-1 expression in mice prevented the development of subretinal choroidal angiogenesis induced by laser photocoagulation. When systemic and local PAI-1 expression was achieved by intravenous injection of a replication-defective adenoviral vector expressing human PAI-1 cDNA, the wild-type pattern of choroidal angiogenesis was restored. These observations demonstrate the proangiogenic activity of PAI-1 not only in tumoral models, but also in choroidal experimental neovascularization sharing similarities with human AMD. They identify therefore PAI-1 as a potential target for therapeutic ocular anti-angiogenic strategies. (+info)
New approaches in the management of choroidal neovascular membrane in age-related macular degeneration.
(31/742)
Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly population. The prevalence is reported to be 1.2-1.4% in several population-based epidemiological studies. Currently 25-30 million people worldwide are blind due to AMD. With the aging world population it is bound to increase significantly, and could become a significant public health problem in next two decades, with serious socio-economic implications. Several strategies are today available to treat the wet form of AMD, which is responsible for significant visual loss. These were until recently confined to laser photocoagulation, and subretinal surgery, but today two other modalities, namely, radiation and photodynamic therapy, are available. These treatment modalities however, are aimed at preservation of vision only, and not at reversing the process of the disease. Further research on antiangiogenic drugs and gene therapy could significantly help AMD patients. (+info)
Angiopoietin-1 upregulation by vascular endothelial growth factor in human retinal pigment epithelial cells.
(32/742)
PURPOSE: To determine whether vascular endothelial growth factor (VEGF) regulates angiopoietin (Ang)-1 and -2 expression in retinal pigment epithelial (RPE) cells. METHODS: Expression of VEGF, Ang1, and Ang2 in surgically removed human choroidal neovascular membranes (CNVMs) was analyzed by double-label confocal immunofluorescence microscopy. Total RNA was extracted from cultured human RPE cells treated with VEGF for mRNA analysis. Northern blot analysis was performed to examine the time course and dose response of Ang1 and Ang2 mRNA expression. mRNA stability and nuclear run-on analyses were performed. Secreted Ang1 and Ang2 protein levels in conditioned media from RPE cells were examined by Western blot analysis. RESULTS: Ang1 and Ang2 immunostaining colocalized with VEGF-positive stromal cells in human CNVMS: Ang1 and Ang2 mRNAs were expressed by cultured serum-starved RPE cells. VEGF upregulated Ang1 mRNA in a time- and dose-dependent manner without a significant change in Ang2 mRNA. Ang1 and Ang2 mRNAs in RPE cells were as stable as that of S18. VEGF stimulation further increased the half-life of Ang1 mRNA, but did not alter its transcription rate. VEGF increased the amount of Ang1, but not Ang2, protein secreted into the medium. CONCLUSIONS: The colocalization of Ang1 and Ang2 with VEGF in CNVM stromal cells and the upregulation of Ang1 expression by VEGF in cultured RPE cells suggest that VEGF may selectively modulate Ang expression during CNV. (+info)