Effect of Artesunate on Experimental Choroidal Neovascularization and Expression of HIF-1α and VEGF / 中国实验方剂学杂志

Objective:To observe the effects of artesunate （ART） on experimental choroidal neovascularization （CNV） and the expression of related proteins， and to explore the underlying mechanism. Method:Eighty BN rats were randomly divided into five groups： a normal group， a model group， a conbercept group， and low- （10.08 mg·kg^-1·d^-1） and high-dose （20.16 mg·kg^-1·d^-1） ART groups， with 16 rats in each group. A CNV model was established with 532 nm laser in rats of the groups except for the normal group. The rats in each group were treated with corresponding drugs by gavage for 14 days. The normal group， the model group， and the conbercept group received 1% CMC-Na solution at the same volume， while the conbercept group received an intravitreal injection （5 μL） once. On days 7 and 14， fundus fluorescein angiography （FFA） was used to evaluate the fluorescein leakage （gray value） of CNV. Hematoxylin-eosin （HE） staining was adopted to observe the histopathological changes of CNV. Western blot was employed to detect the protein expression levels of hypoxia-inducible factor-1<italic>α</italic> （HIF-1<italic>α</italic>） and vascular endothelial growth factor （VEGF） in the retina and choroid. Result:FFA results showed that compared with the normal group， other groups showed increased gray value on days 7 and 14 （<italic>P</italic><0.01）. On day 7， the gray value of the high-dose ART group and the conbercept group decreased compared with that in the model group （<italic>P</italic><0.01）. On day 14， the gray value of the ART groups and the conbercept group decreased in varying degrees compared with that in the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）. HE results showed that compared with the normal group， the model group showed increased thickness of CNV on days 7 and 14 （<italic>P</italic><0.01）. Compared with the model group， the ART groups and the conbercept group displayed decreased thickness of CNV （<italic>P</italic><0.01）. Western blot results revealed that the expression of HIF-1<italic>α</italic> and VEGF in the model group increased in varying degrees on the days 7 and 14 compared with that in the normal group （<italic>P</italic><0.05， <italic>P</italic><0.01）， while compared with the model group， the ART groups and the conbercept group showed decreased expression （<italic>P</italic><0.01）. Conclusion:ART can inhibit experimental CNV by down-regulating the expression of HIF-1<italic>α</italic> and VEGF in the early stage of experimental CNV formation.

A GO analysis of gene expression on the inhibitory effect of endostatin on mouse choroidal neovascularization / 西安交通大学学报(医学版)

Objective To study the gene expression on the inhibitory effect of endostatin on choroidal neovascularization in C57BL/6J mice and the mechanisms.Methods Photocoagulation using 532 nm diode laser was performed to establish a CNV model in mice’s eye.The mice were randomly divided into three groups:blank group (model group);endostatin group (experimental group),in which endostatin of 0.01 mg/2μL was given intravitreally;and saline group (control group),which received intravitreal injection of 2μL of 0.9 g/L saline.Four samples selected respectively from experimental group and control group were used to complete the gene expression profiling analysis.By comparing the differences of gene expression between the two groups,we selected the genes with expression difference ≥ 1.5 times and P ≤ 0.05. Results CD105 marking showed that choroidal neovascularization was significantly lower in endostatin group than in control group.The gene expression analysis showed that 1 1 6 genes were up-regulated and 1 0 6 genes were down-regulated in endostatin group compared with control group.GO analysis indicated that endostatin could inhibit cell activity and growth,but did not initiate the activity of the immune system,and even suppress it.Conclusion Endostatin can inhibit the activity and locomotion of endothelial cells and synergically inhibits the immune system,thus suppressing choroidal neovascular-ization.

Photodynamic Therapy of Choroidal Neovascularization in Age-Related Macular Degeneration with Verteporfin: An Analysis of 10 Years of Clinical Results

PURPOSE: To analyze the long-term results of photodynamic therapy (PDT) for exudative age-related macular degeneration (AMD). METHODS: The clinical data of patients treated with photodynamic therapy for exudative age-related macular degeneration between April 2000 and December 2000 were analyzed. Patients were followed-up for at least 10 years after PDT. RESULTS: Twenty-nine eyes of 29 patients were enrolled. Mean visual acuity on the logarithm of the minimum angle of resolution (log MAR) scale was 0.78 +/- 0.34 at baseline, 1.01 +/- 0.42 at 60 months, and 1.02 +/- 0.41 at 120 months. Predominantly classic, minimally classic, and occult without classic choroidal neovascularization was noted in 51.7%, 17.2%, and 31.1% of patients, respectively. Visual acuity was improved by 1 or more lines in 27.6% of patients and was unchanged in 20.7% of patients, while 51.7% of patients had lost 1 or more lines of visual acuity by 120 months. Baseline visual acuity and age were associated with the final visual prognosis (p < 0.05). Four patients developed neovascular AMD in the contralateral eye. CONCLUSIONS: PDT is safe and effective for neovascular AMD. However, AMD can recur at any time and thus patients should be followed-up for a long period of time.

Retinal pigment epithelial and choroidal atrophy in wet age-related macular degeneration treated with multiple transpupillary themotherapy:A case report / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To report a case of wet age-related macular degeneration (AMD) treat with multiple transpupillary themotherapy (TTT) and choroidal neovascularization (CNV) disappeared but retinal pigment epithelial(PRE) and choroidal atrophy occurred with a low vision at the end point.METHODS: Clinical data including fundus hotographs, fundus fluorescein angiography (FFA), indocyanine angiography (ICGA) and optical coherence tomography(OCT) was reviewed.RESULTS: A 72-year-old man complained about blurred vision of his left eye and FFA revealed polypoidal choroidal vasculopathy (PCV) in the macula. His left eye had stable vision of 0.1 for 6 years without any treatment of CNV. About 2 years later, his right eye presented a piece of CNV. During the period of 3 years, the lesion remained more (3×5 PD) and less (1×2PD) in size with remarkable exudates and bleeding, and 7 sessions of TTT were applied with 80-280mW, 2mm of spot, and 60 seconds exposure and with the interval of 3 months or more. The CNV lesion finally disappeared, but there left a white area in the macula and vision decreased from 0.3 to 0.04.CONCLUSION: Although CNV lesion can be eliminated by TTT, obvious atrophy of RPE cells and the choroids can happen and this may not be of help for patient vision. It suggests that the parameters of TTT will be lower than 120 mW/mm and limited less two sessions if applicable, especially for Asia people.

Photodynamic Therapy for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration

PURPOSE: To investigate the effects of repeated photodynamic therapy (PDT) for subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD) in Korean patients. METHODS: Clinical data of patients who were treated with repeated (3 times or more) PDT for subfoveal choroidal neovascularization secondary to AMD and followed up for more than 6 months were collected from 17 hospitals around the country. Visual outcomes at 12 and 24 months, follow-up were compared between subtypes of choroidal neovascularization. The factors related to final visual prognosis and PDT-related adverse effects were evaluated. RESULTS: 244 patients (244 eyes) were recruited (male: 60%, age: 67.7+/-9.1 years). The portion of patients with predominantly classic, minimally classic, and occult without classic choroidal neovascularization was 57%, 13%, and 24%, respectively and that of patients with visual improvements or less than moderate visual loss at 24 months follow-up were 28%, 38%, 30% and 47%, 56%, and 65%, respectively. Baseline visual acuity and age were significantly related to the final visual prognosis (p<0.05). PDT-related adverse events developed in 15 (6.1%) patients, but most were mild and transient. CONCLUSIONS: Repeated PDT for subfoveal choroidal neovascularization secondary to AMD has effects comparable to those of previous prospective, controlled trials without any significant safety concerns in Korea.

Indocyanine Green Angiographic Features of Myopic Subfoveal Choroidal Neovascularization as a Prognostic Factor after Photodynamic Therapy

PURPOSE: To determine the influence of clinical features and Indocyanine green (ICG) angiographic features on the visual outcome of patients with myopic sub-foveal choroidal neovascularization (CNV) who received photodynamic therapy (PDT). METHODS: Thirty-six consecutive patients (39 eyes) with myopic CNV who were followed up for more than one year after PDT were enrolled in this study. Clinical features included age, gender, refractive error, great linear dimension, and subretinal hemorrhage. ICG features included the lesion size, lacquer cracks, hypofluorescence surrounding the CNV (dark rim), peripapillary atrophy size, and visible prominent choroidal veins under the macula. Linear regression analysis was performed using the change in visual acuity (delta logMAR) as the dependent variable and the above factors as independent variables. RESULTS: At one-year follow-up after PDT, a younger age (p=0.002) and the presence of a dark rim (p=0.002) were significantly correlated with an improvement of visual acuity (decrement in logMAR) after PDT. Other factors had no significant influence on changes in visual acuity. CONCLUSIONS: Younger patients and patients with a dark rim on ICG angiography had a higher chance of visual improvement after PDT in myopic CNV.

Optical coherence tomography features of myopia / 中国康复理论与实践

@# ObjectiveTo explore the morphological features of macular subretina choroidal neovascularization (CNV) in high myopia with optical coherence tomography (OCT).Methods16 CNV cases (17 eyes) were examined with OCT, and compared with results of fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA).ResultsCNV appeared in space under sensory retinal anterior to the retinal pigment epithelium in 12 of 17 eyes. In 5 eyes, CNV appeared as a highly reflective fusiform or irregular mass at the level of retinal pigment epithelium and choriocapillaris. 9 of 17 eyes were associated with serous neurosensory retinal detachment, 11 eyes with hemorrhagic pigment epithelium detachment (PED) and 14 eyes with edema and thickening of sensory retina. 12 eyes regressed and its morphological features changed after photo dynamical therapy (PDT).ConclusionOCT can be used to confirm the morphological features, location and size of submacular CNV. CNV appears as a highly or moderately reflective round mass which protrudes from the retinal pigment epithelium in most cases. The morphology and the size of this mass may change after treatment and during follow-up.

Photodynamic Therapy in Practice: A Review of Experiences with Myopic CNV in Korean Patients

PURPOSE: To evaluate the effects of photodynamic therapy with verteporfin on visual acuity and fluorescein angiography in choroidal neovascularization (CNV) associated with pathologic myopia and to determine if this treatment could reproduce the results achieved in the Verteporfin in Photodynamic Therapy (VIP) Trial in Korean patients. METHODS: Forty-two eyes of 39 patients with CNV secondary to pathologic myopia were included. A retrospective review of their clinical records and fluorescein angiography was done. The patients underwent photodynamic therapy with verteporfin and were followed up for more than 6 months after the therapy. The change in best corrected visual acuity (BCVA) and leakage in fluorescein angiography were evaluated. RESULTS: The mean age of the patients was 39.6 and mean follow-up period was 23.5 months. The BCVA of the patients improved in 22 (52.4%) eyes, was unchanged in 13 (30.9%), and worsened in 7 (16.7%). The leakage in fluorescein angiography decreased in 25 (59.5%) eyes. CONCLUSIONS: Photodynamic therapy with verteporfin for myopic CNV in Korean patients appeared to be effective in stabilization of the lesions and improvement of visual acuity.

Result of Photodynamic Therapy for Idiopathic Subfoveal Choroidal Neovascularization

PURPOSE: To investigate the factors that affect final vision following photodynamic therapy (PDT) for idiopathic subfoveal choroidal neovascularization (CNV). METHODS: A retrospective review of 16 patients whose eyes were diagnosed as idiopathic subfoveal CNV and were followed up for a minimum of 9 months. Statistical analysis was performed to investigate relationships between sex, age, size of the lesion, and initial vision compared to final vision. RESULTS: In the PDT group (10 eyes), the mean age of the patients was 34 years, mean size of the lesion was 1300 micrometer, mean initial vision was 20/60, and 7 of the 10 patients (70%) showed more than a two-line improvement in vision. Factors affecting final vision were sex (p=0.049), initial vision (p=0.0455), and size of the lesion (p=0.006). In the observation group (6 eyes), the mean age of the patients was 39 years, mean size of the lesion was 575 micrometer, mean initial vision was 20/32, and 5 of the 6 patients (83%) showed more than a two-line improvement in vision. CONCLUSIONS: The prognosis of idiopathic CNV was favorable as was reported in other studies. In the PDT group, statistically significant factors affecting final vision were initial vision, size of the lesion, and sex. However, since the number of patients sampled was insufficient and the average size of the lesions in the female patients was smaller, the size of the lesion seems to be the most important factor.

Therapeutic Effect of Photodynamic Therapy with Indocyanine Green Dye in the Treatment of Choroidal Neovascularization

PURPOSE: To determine experimentally the effectiveness of photodynamic therapy (PDT) with indocyanine green (ICG) dye in the treatment of choroidal neovascularization. METHODS: Following the creation of choroidal neovascularization in the retina of 18 pigmented rats (36 eyes), and ICG dye injection (10 mg/kg) in 18 of the eyes, the authors performed PDT, at intensity of 60 mW, spot size of 2.0 mm, and duration of 20 seconds within 2 minutes after ICG dye injection. 0ne, 4, 6, and 8 weeks after PDT, the authors examined the retina for any signs of regression through angiogram and light microscope. RESULTS: When authors conducted PDT after injecting ICG dye into pigmented rats, there was no significant damage to retina when the intensity was set at 60mW with duration of 10 or 20 seconds. Choroidal neovascularization was found in 18 eyes after argon laser photocoagulation, and regression of neovascularization was confirmed through angiogram and pathologic examination after PDT was performed with ICG dye. Pathologic views revealed significant fibrosis and fibrinoid necrosis. The control group consisting of 18 eyes in which no diode laser photocoagulation was performed, showed no regression of choroidal neovascularization. CONCLUSIONS: PDT with ICG dye was found to be quite effective in the treatment of choroidal neovascularization.

The Role of VEGF and Bruch's Membrane in the Development Choroidal Neovascularization

A major cause of blindness in elderly people is choroidal neovascularizapathogenesis and stimulating factor of CNV is not clearly understood. Vascular endothelial growth factor(VEGF)is a major stimulating factor for retinal neovascularization in ischemic retinopathy such as diabetic retinopathy, retinopathy of prematurity. But it is not known if VEGF is a stimulating factor for CNV. In this study, we have treated VEGF transgenic mice and C57BL/6 mice with laser. Different laser parameter for damage to retina pigment epithelium(RPE)only and for break of Bruch's membrane were used each. We were not able to induce CNV with only RPE damage. CNV wes induced when the break of Bruch's membrane was made and there was profuse CNV in VEGF transgenic mice rather than C57BL/6. These data suggest that the damage of Bruch's membrane may be the prerequisition for CNV formation and VEGF is the important stimulating factor for CNV.