Reduced photoreceptor damage after photodynamic therapy through blockade of nitric oxide synthase in a model of choroidal neovascularization

PURPOSE: To investigate the role of nitric oxide synthase (NOS) in photoreceptor degeneration associated with photodynamic therapy (PDT) in a laser-induced model of choroidal neovascularization (CNV). METHODS: PDT was performed in monkey and Brown Norway rats with laser-induced CNV. L-NAME, a NOS inhibitor, or saline was injected intraperitoneally in rats with CNV. An NO donor, or saline, was injected intravitreously into normal rats. Photoreceptor apoptosis was evaluated by TUNEL and electron microscopy. NOS, ED-1, and cleaved-caspase-3 (c-casp-3) expression were determined by immunohistochemistry. CNV lesions were examined by fluorescence angiography and choroidal flat mount. RESULTS: TUNEL and electron microscopy showed photoreceptor apoptosis after PDT. In rats, there were significantly more TUNEL-positive cells in the photoreceptors 24 hours after PDT, whereas in the CNV lesions there were more TUNEL-positive cells 6 hours after PDT. C-casp-3 was detected in the CNV lesions but not in the photoreceptors after PDT. There was no difference in the numbers of ED-1-positive macrophages before and after PDT. However, inducible NOS (iNOS) was increased after PDT in macrophages. Intravitreous injection of the NO donor without PDT also induced substantial photoreceptor apoptosis. L-NAME-treated animals had significantly fewer TUNEL-positive cells in the photoreceptors than saline-treated animals after PDT (P < 0.05). There were no differences in CNV size and leakage between L-NAME- and saline-treated groups. CONCLUSIONS: iNOS expression in macrophages contributes to PDT-induced photoreceptor degeneration. NOS inhibition reduces PDT-induced photoreceptor degeneration without compromising the treatment effect of PDT in an experimental model of CNV.     

Phosphatidylinositol 3-kinase (PI-3K)/Akt but not PI-3K/p70 S6 kinase signaling mediates IGF-1-promoted lens epithelial cell survival

PURPOSE: To investigate the ability of insulin-like growth factor (IGF)-1 to prevent apoptosis in lens epithelial cells and the involvement of phosphatidylinositol 3-kinase (PI-3K)/Akt and PI-3K/p70 S6 kinase (p70 S6K) signaling in the cell-survival process. METHODS: Apoptosis in rabbit lens epithelial cell cultures was induced by staurosporine (10 ng/mL). Cellular apoptosis was detected by identifying the characteristic ladder-like fragmentation of genomic DNA in agarose gels and the intense blue fluorescence exhibited by apoptotic nuclei of cells in live cultures in the presence of Hoechst 33,258 dye. Proliferation of lens epithelial cells grown in culture was measured with a DNA-binding fluorescent dye. Overexpression of the constitutively active Akt (CA-Akt) in epithelial cells was achieved by the transfection of cells using Fugene 6 reagent with a plasmid carrying Akt cDNA. Western immunoblotting was performed to identify various proteins of interest. RESULTS: IGF-1 (5 to 50 nM) and insulin (100 to 400 nM) suppressed lens epithelial cell apoptosis in a dose-dependent manner, as determined by a significant inhibition of genomic DNA fragmentation and the decreased number of intense blue fluorescent Hoechst stain-positive apoptotic nuclei in live cultures. DNA degradation was almost completely inhibited in the presence of 50 nM IGF-1 or 400 nM insulin. PI-3K inhibitors wortmannin and LY294002 blocked the IGF-1 effect on cell survival. Stimulation of lens epithelial cells with IGF-1 for 10 minutes to 24 hours resulted in the sustained activation of both Akt and p70 S6K. IGF-1 also induced the phosphorylation of Bad (a pro-apoptotic protein of the Bcl-2 family), which was inhibited by PI-3K inhibitors, but not by the p70 S6K inhibitor rapamycin. Furthermore, activation of Akt but not p70 S6K signaling by IGF-1 resulted in the inhibition of caspase-3 endogenous substrate poly (ADP-ribose) polymerase (PARP) degradation and apoptosis. The overexpression of CA-Akt in lens epithelial cells inhibited PARP breakdown and suppressed apoptosis. Inhibition of p70 S6K activation by rapamycin blocked IGF-1-promoted lens epithelial cell proliferation but not the cell-survival effect. CONCLUSIONS: These studies demonstrated a role for IGF-1 in the prevention of the lens epithelial cell apoptosis process. Furthermore, these studies indicated that anti-apoptotic and proliferative signals from IGF-1 bifurcate downstream of PI-3K. Whereas IGF-1-mediated PI-3K/Akt signaling plays a pivotal role in cell survival by inactivating proapoptotic Bad protein and suppressing caspase activation, its stimulation of the PI-3K/p70 S6K cascade promotes proliferation.     

Verteporfin photodynamic therapy induced apoptosis in choroidal neovascular membranes

AIM: To evaluate the impact of verteporfin photodynamic therapy (PDT) on the induction of apoptosis in choroidal neovascular membranes (CNV) secondary to age related macular degeneration. METHODS: Retrospective review of 22 surgically excised CNV. 12 of these patients had been treated with PDT 3-146 days previously. Apoptotic cells were detected with the TUNEL technique and compared to the expression of CD34 (endothelial cells, EC), CD105 (activated endothelial cells), Ki-67 (proliferation marker), and cytokeratin18 (retinal pigment epithelial cells, RPE). RESULTS: CNV excised 3 days after PDT were characterised both by collapsed and patent vessels. The EC displayed a statistical significant positive TUNEL reaction when compared to the remaining treated CNV (p < 0.001) and untreated CNV (P = 0.002). The proliferative activity was reduced. CNV excised 1-5 months after PDT displayed a patent vascularisation and high proliferative activity. All membranes either treated or untreated disclosed only sporadic TUNEL positive cells within the stroma and the RPE. CONCLUSIONS: Verteporfin PDT leads to selective and effective damage of EC within CNV. Both patent and occluded vessels were lined by apoptotic EC. This finding and the increased expression of proliferation marker at later time points suggest that revascularisation after PDT is caused by angiogenesis rather than recanalisation.     

Verteporfin photodynamic therapy in the rat model of choroidal neovascularization: angiographic and histologic characterization

PURPOSE: To develop a model of verteporfin photodynamic therapy (PDT) for experimental choroidal neovascularization CNV in the rat. METHODS: A laser injury model was used to induce experimental CNV in rats. The transit and accumulation of the photosensitizer verteporfin was assessed angiographically in CNV lesions, to determine the optimal time for delivery of light energy. The CNV lesions were then treated with verteporfin PDT, with two doses of verteporfin (3.0 and 6.0 mg/m(2)) and four activating doses of light energy (10, 25, 50, and 100 J/cm(2)). Closure of the CNV was assessed both angiographically and histologically. Verteporfin PDT was also performed on areas of normal choroid and retina at the two verteporfin doses and four light energy doses. The effect of these treatments on these structures was also assessed angiographically and histologically. RESULTS: Peak verteporfin intensities in the CNV were detected at 15 to 20 minutes after intravenous injection. Rates of closure of the CNV varied as a function of the dose of verteporfin and of the activating light energy. Angiographic closure of the CNV correlated with damage to the neovascular complex, as seen with light and electron microscopy. Damage to areas of normal choroid and retina treated with verteporfin PDT also varied as a function of the verteporfin and light energy doses. CONCLUSIONS: Verteporfin PDT for experimental CNV in the rat is a feasible, effective, and reproducible model that can be used for testing the efficacy of adjunctive therapy to verteporfin PDT.     

Photodynamic therapy using Lu-Tex induces apoptosis in vitro, and its effect is potentiated by angiostatin in retinal capillary endothelial cells

PURPOSE: To examine the effect of combining angiostatin with photodynamic therapy (PDT) using Lutetium Texaphyrin (Lu-Tex; Alcon, Fort Worth, TX) as a photosensitizer in bovine retinal capillary endothelial (BRCE) and retinal pigment epithelial (RPE) cells and to determine the mode of PDT-induced cell death in these cell lines. METHODS: Cultured BRCE and RPE cells were incubated with angiostatin (500 ng/ml) for 18 hours and subjected to Lu-Tex/PDT, using treatment parameters previously optimized (3 microgram/ml Lu-Tex for 30 minutes followed by timed irradiation at 732 nm). Cellular survival was assessed after a 1-week cellular proliferation. Data were analyzed using Student's t-test. Caspase 3 activity was monitored in cells after PDT using a fluorogenic substrate, (Asp-Glu-Val-Asp)-AFC (7-amino-4-trifluoromethyl coumarin) [DEVD-AFC], of caspase 3. After PDT, expression of Bcl-2, Bcl-x(L), Bax, and Bak was also examined in cell lysates by Western blot analysis. RESULTS: A synergistic cytotoxic effect of angiostatin and Lu-Tex/PDT was observed in BRCE cells at all fluences used (5, 10, and 20 J/cm(2); P 相似文献   

Photodynamic therapy with verteporfin for choroidal neovascularization in patients with diabetic retinopathy.

PURPOSE: To report the use of photodynamic therapy (PDT) with verteporfin in three patients with choroidal neovascularization (CNV) from age-related macular degeneration and underlying diabetic retinopathy. The level of diabetic retinopathy would have excluded these patients from participation in previously reported randomized clinical trials evaluating PDT with verteporfin due to a theoretic concern of damage to the overlying retinal vasculature. DESIGN: Retrospective interventional case series. METHODS: Three patients from a referral practice with at least severe nonproliferative diabetic retinopathy and a history of clinically significant macular edema developed loss of vision from concurrent choroidal neovascularization evaluated with fundus photography and fluorescein angiography before and after PDT with verteporfin to identify adverse retinal vascular events. RESULTS: Four eyes in three patients had PDT using verteporfin. Three eyes received two treatments. With short follow-up, visual acuity remained stable in two eyes, improved from 20/400 to 20/320 in one eye, and decreased from 20/200 to 20/400 in one eye. Fluorescein angiograms at intervals from 2 weeks to 3 months after PDT showed no damage to the retinal vasculature or progression of the diabetic retinopathy, but did show a decreased area of fluorescein leakage from CNV. One eye that had new subretinal hemorrhage following treatment appeared to show new vasculopathy on initial evaluation of the post-treatment angiogram. Retrospective review suggested that the subretinal hemorrhage provided increased contrast to more easily visualize vasculopathy that was present before the PDT. CONCLUSIONS: Three patients with diabetic retinopathy undergoing a total of seven PDT treatments with verteporfin in four eyes had no new retinal vascular abnormalities develop. No other atypical responses of CNV to PDT were noted except new subretinal hemorrhage, providing increased contrast of the overlying vasculature, which gave the false impression of the development of new vasculopathy in one eye. Patients with diabetic retinopathy who have concurrent CNV for which PDT with verteporfin is recommended should be cautioned regarding the theoretical concerns of harming the retinal vasculature. Periodic surveillance for such concerns seems warranted until more experience is obtained.     

Influence of treatment parameters on selectivity of verteporfin therapy

PURPOSE: To improve selectivity of verteporfin therapy (PDT) in neovascular age-related macular degeneration (AMD) using modified treatment parameters. METHODS: Nineteen consecutive patients with predominantly classic choroidal neovascularization (CNV) in AMD were treated with 6 mg/m2 verteporfin given as bolus infusion. Patients received PDT with a fluence of either 25 or 50 J/cm2. Choroidal perfusion changes were evaluated by indocyanine green angiography (ICGA) at baseline, day 1, week 1, week 4, and month 3. Secondary outcomes were CNV closure rate and therapy-induced leakage documented by fluorescein angiography (FA). The safety of the treatment was assessed with ETDRS visual acuity. RESULTS: Complete CNV closure was achieved in all patients at day 1. Choroidal hypoperfusion was minimal in eyes treated with a reduced fluence of 25 J/cm2. Most patients treated with 50 J/cm2 showed significant choriocapillary nonperfusion at week 1, lasting as long as 3 months. A transient PDT-induced increase in leakage area in FA at day 1 was found to be more extensive in the 50-J/cm2 group. CONCLUSIONS: Bolus administration of verteporfin combined with a reduced light dose achieved improved selectivity of photodynamic effects, avoiding collateral alteration of the physiologic choroid while obtaining complete CNV closure. An increased selectivity with decreased effect on the surrounding choroid should be of advantage in verteporfin monotherapy as well as in combination strategies.     

Sequence of early vascular events after photodynamic therapy

PURPOSE: To identify early vascular changes in choroidal neovascularization (CNV) and in adjacent normal choroid, after photodynamic therapy (PDT). METHODS: In a prospective study, 40 patients with predominantly classic CNV due to age-related macular degeneration (AMD) were treated with PDT performed with verteporfin. Verteporfin was administered intravenously at a dose of 6 mg/m(2) body surface area. A near infrared laser light dose of 50 J/cm(2), an irradiance of 600 mW/cm(2) and a wavelength of 692 nm was applied. A scanning laser system was used to perform confocal fluorescein angiography (FA) and indocyanine green angiography (ICGA) before treatment and regularly at 5 hours, 1 day, 1 week, and 3 months after PDT. Images were analyzed for CNV size and leakage area as seen by FA and ICGA. Collateral damage within the surrounding choroid was documented based on the hypofluorescence in early- and late-phase ICGA. RESULTS: No immediate occlusion of the CNV complex was found angiographically, but a dynamic change over time was observed in the early perfusion patterns and late-phase hyper- and hypofluorescence. At 5 hours after treatment, large portions of the CNV lesion were still perfused. One day after PDT, CNV size in early FA and early ICGA reached its minimum, at 0.49 mm(2) (15.7%) and 0.78 mm(2) (31.1%) of the initial area, respectively. In late-phase FA and ICGA, however, an immediate massive exudation with a continuous increase in hyperfluorescence originated from the CNV and surrounding choroid, with a maximum in leakage area at 1 day. At 1 week PDT-induced exudation slowly resolved. Eyes in 36 patients showed some choroidal hypofluorescence by ICGA before treatment. A progressive increase of the hypofluorescent area surrounding the CNV was observed, which correlated with the size of the laser spot. Maximum hypofluorescence was noted at 1 week with an average size of 11.1 mm(2) in early- and late-phase ICGA. CONCLUSIONS: In contrast to findings in experimental animals, PDT in humans with classic CNV did not induce immediate thrombosis, but primarily caused a breakdown of vascular barriers. A characteristic sequence of vascular changes was observed with early, enhanced leakage from the CNV and normal choroid followed by nonperfusion later. Occlusion of the CNV lesions occurred 1 day after treatment, but closure of the adjacent choroidal vessels proceeded slowly over as long as 1 week.     

Photodynamic therapy in age-related macular degeneration--results of one year observation

PURPOSE: To evaluate the efficacy of photodynamic therapy (PDT) with verteporfin in reducing the vision loss and progression of choroidal neovascularization (CNV) in patients with subfoveal CNV due to age-related macular degeneration (AMD). MATERIALS AND METHODS: 46 eyes of 46 patients with subfoveal, predominantly classic CNV caused by AMD and best-corrected visual acuity of 5/50 to 5/10 were treated with photodynamic therapy with verteporfin (Visudyne, CIBA Vision). Verteporfin was administered via intravenous infusion over 10 minutes. Fifteen minutes after the start of the infusion, a diode laser light at 689 nm (Opal Photoactivator, Coherent) was delivered over 83 seconds. Visual acuity and fluorescein angiography were performed before and after the treatment at 7 days and 1, 3, 6, 9 and 12 months after the initial-treatment. Retreatment in the same manner was applied if at follow-up examination fluorescein leakage from CNV was seen. Outcomes were compared with those of control group which consisted of 38 eyes of 38 patients of the same condition of the disease, not treated with any method. RESULTS: The lost of visual acuity was significantly reduced in the verteporfin--treated eyes compared--with controls. At the 12 month 73.91% eyes of PDT group versus 36.84% of control group (p < 0.001) lost fewer than 3 Snellen lines. The vision loss appeared to be more rapid in first 6 months of the study. During the study growth of CNV was diminished in PDT group compared with control group. CONCLUSIONS: Results show, that photodynamic therapy may be an effective method of treatment for predominantly classic subfoveal choroidal neovascularization caused by AMD. Further studies are needed to find the best modes of PDT procedure.     

Bilateral CNV associated with optic nerve drusen treated with photodynamic therapy with verteporfin

PURPOSE: To report a case of bilateral choroidal neovascularization (CNV) associated with optic nerve drusen (OND) treated with photodynamic therapy (PDT) with verteporfin. METHODS: A 10-year-old girl with juxtapapillary CNV in the right eye and juxtapapillary and juxtafoveal CNV in the left eye associated with OND underwent PDT with verteporfin in both eyes. RESULTS: Visual acuity increased from 20/160 to 20/25 in the right eye and from 20/1000 to 20/25 in the left eye after two sessions of PDT and 2 years of follow-up. CNV showed no leakage after two PDT sessions in both eyes and no recurrence was observed. CONCLUSIONS: Subfoveal CNV is an uncommon complication of OND and excellent anatomic and functional results can be obtained with PDT.     

Two years follow-up outcome of verteporfin therapy for subfoveal choroidal neovascularization in pathologic myopia in Indian eyes

Context:

In India, refractive errors are a major cause of treatable blindness. Population surveys in southern India have shown prevalence of high myopia to be 4.32-4.54%. Photodynamic therapy (PDT) for choroidal neovascularization (CNV) caused by pathologic myopia is beneficial.

Aims:

To report the 24 months outcome of PDT with verteporfin for subfoveal CNV caused by pathologic myopia in Indian eyes

Settings and Design:

Prospective case series

Materials and Methods:

Review of prospectively collected data of Indian patients with pathologic myopia and subfoveal CNV treated with verteporfin therapy between 2001 and 2005 using standard regimen for PDT.

Statistical Analysis Used:

Wilcoxon signed rank test was used to see the difference in the mean letter acuity at intervals compared to baseline. Kaplan Meier Survival analysis was done to estimate the success rate of verteporfin therapy for CNV caused by pathologic myopia.

Results:

Fifteen patients (15 eyes) treated with standard fluence PDT and who had completed 24 months follow-up were analyzed. The mean spherical equivalent was -13.36 ± 5.88 diopter. Five out of 15 eyes in six months, three out of 15 eyes at 12 months and four eyes out of 15 at 24 months had improved vision by > 10 letters. The mean number of treatment session was 2.2 in two years.

Conclusions:

PDT with verteporfin for subfoveal CNV caused by pathologic myopia in Indian eyes is effective.     

光动力疗法治疗病理性近视脉络膜新生血管的临床观察

目的 探讨光动力疗法(PDT)治疗病理性近视(PM)黄斑部脉络膜新生血管(cNV)短期的安全性和有效性.方法 回顾经临床眼底检查、FFA和/或ICGA检查及确诊的继发于PM的CNV患者19例(19只眼)行PDT治疗前后的临床资料,对比分析其最佳矫正视力、眼底像、眼底血管造影CNV渗漏、OCT及mf-ERG检查结果.光动力治疗方案参照TAP制定的标准.随访时间为3-6个月.结果 PDT治疗后全部患者视力改善或保持不变,无视力下降者.所有患眼底出血或渗出均减轻.FFA/ICGA检查显示:CNV停止渗漏11只眼,占57.89%;渗漏减少8只,占42.11%.OCT检查显示CNV明显变薄.PDT治疗后1个月mf-ERG3-5环N1、P1波波振幅密度值与治疗前均有显著提高(P＜0.05),3个月时3～4环N1、P1波振幅密度值与治疗前均有显著提高(P＜0.05).结论 病理性近视CNV经PDT治疗短期有效,安全性好,PDT治疗CNV的长期疗效有待进一步观察.     

Changes in confocal indocyanine green angiography through two years after photodynamic therapy with verteporfin

PURPOSE: To evaluate vascular changes documented by confocal indocyanine green angiography (ICGA) through 2 years after photodynamic therapy (PDT) with verteporfin of neovascular age-related macular degeneration (AMD). DESIGN: Single-center, 2-year, randomized, double-masked, interventional, placebo-controlled trial (subset from Treatment of AMD with PDT Study [TAP]). PARTICIPANTS: Sixty patients with subfoveal choroidal neovascularization (CNV) resulting from AMD. INTERVENTION: Patients were randomized in a ratio of 2:1 to a standard regimen using verteporfin therapy at a drug dose of 6 mg/m(2) body surface area and a light dose of 50 J/cm(2) or a sham treatment with placebo infusion and light exposure. Retreatments, if persistent fluorescein leakage from CNV was documented, were scheduled at 3-month intervals for up to 2 years. Confocal ICGA with tomographic sections was performed at baseline and continuously at the month 3, 6, 12, and 24 examinations using a standardized protocol. MAIN OUTCOME MEASURES: Analysis included the size of the neovascular net, the area of late hyperfluorescence, and choroidal hypofluorescence during early- and late-phase imaging. RESULTS: In the verteporfin-treated group, the mean size of the CNV and the mean area of late leakage consistent with active leakage or staining showed no further enlargement at month 12 and were reduced at month 24. In the placebo-treated group, new vessels grew threefold compared with baseline and exhibited persistent late hyperfluorescence resulting from leakage at 24 months. Associated choroidal hypofluorescence within the treated area was significantly increased in eyes treated with verteporfin PDT compared with the control group during the first year, persisted during all ICGA phases, and was irreversible during follow-up. Image analysis revealed choroidal hypoperfusion with choriocapillary dropout, which correlated with chorioretinal atrophy clinically. Progressive destruction of choroidal integrity by fibrosis in control eyes led to a similar extent of collateral hypofluorescence in both groups through the 24-month examination. CONCLUSIONS: Indocyanine green angiography is an important adjunct in the identification of vascular effects associated with verteporfin PDT. Repeated treatments effectively arrested CNV growth and reduced leakage activity. The collateral impairment of choroidal perfusion appears to influence the visual outcome of the treatment.     

Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization secondary to pathologic myopia: long-term study

PURPOSE: To assess the safety and effectiveness of photodynamic therapy (PDT) with verteporfin for subfoveal choroidal neovascularization (CNV) secondary to pathologic myopia (PM). METHODS: Sixty-two patients (62 eyes) with PM underwent PDT according to the guidelines of the Verteporfin in Photodynamic Therapy Study. Clinical evaluations performed at all study visits included measurement of best-corrected Snellen visual acuity, slit-lamp biomicroscopy, and fundus fluorescein angiography. Patients were followed up at 1 month and 3 months after treatment and thereafter at 3-month intervals. RESULTS: The final visual acuity of the study patients, after a median follow-up of 31 months, improved by >or=1 Snellen lines in 8 patients (13%), deteriorated in 20 (32%), and remained stable in 34 (55%). The baseline visual acuity was similar in the various study groups. The final mean visual acuity in group A (55 years of age or younger) was 20/80 and significantly (P=0.006) better than that (20/138) in group B (older than 55 years of age). The mean final visual acuity in eyes with higher refractive error at baseline (greater than -17 diopters) was significantly better (P=0.014) than that in eyes with lower refractive error (-6 to -10 diopters). CNV size did not affect visual outcomes. CONCLUSION: PDT preserves vision in patients with CNV associated with PM. Younger patients and eyes with higher refractive error appear more likely to benefit from PDT with verteporfin.     

光动力疗法治疗湿性年龄相关性黄斑变性脉络膜新生血管膜的临床效果

目的探讨光动力疗法（PDT）对湿性年龄相关性黄斑变性（AMD）患者脉络膜新生血管（CNV）膜的临床疗效。方法回顾性分析2000年8月至2006年2月经PDT治疗后随访≥6个月的93例（98只眼）湿性AMD患者的临床效果,比较其治疗前后的视力、荧光素眼底血管造影（FFA）及吲哚氰绿眼底血管造影（ICGA）图像特征。结果PDT治疗后6个月,患者视力稳定不变的有59只眼（60．2％）,视力提高的有21只眼（21．4％）,视力下降的有18只眼（18．3％）。经FFA检查发现CNV复发且重复治疗者有54只眼（55．1％）;重复治疗时间：1个月者1只眼,3个月者24只眼,6个月者15只眼,9个月者6只眼,〉12个月者8只眼。54只眼重复治疗次数：2次40只眼,3次12只眼,4次2只眼,平均治疗次数为1．7次。随访时间：6—58个月,平均14个月。所有病例均未见严重的不良反应。结论PDT是治疗CNV的安全、有效方法,但需反复治疗。     

Verteporfin photodynamic therapy for extrafoveal choroidal neovascularisation secondary to age-related macular degeneration

PURPOSE: To report the results of verteporfin photodynamic therapy (PDT) of extrafoveal predominantly classic choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD). METHODS: In this retrospective study 20 consecutive patients (20 eyes) undergoing verteporfin PDT for extrafoveal predominantly classic CNV in AMD were examined. Colour photography of the fundus, fluorescein angiography and complete ophthalmic examination, including visual acuity assessment with ETDRS charts, were performed before treatment and at 3-month intervals thereafter. The primary outcome criterion was the change in visual acuity. The secondary outcome criterion was the extension of the CNV beneath the centre of the fovea during the follow-up period. RESULTS: Mean follow-up time of the patients was 24.2 months (range 12 to 58 months). Visual acuity at baseline varied from 20/200 to 20/20 (mean 20/50+/-2.3 lines). Final visual acuity ranged from 20/1000 to 20/20 (mean 20/200+/-5.1 lines) (P<0.001). In 85% (17/20) of the eyes visual acuity worsened. Visual acuity improved in 15% (3/20) of the eyes. During the course of the follow-up period, subfoveal extension of the CNV was detected in 80% (16/20) of the eyes. CONCLUSION: In 85% of the eyes with extrafoveal predominantly classic CNV secondary to AMD, visual acuity worsened after verteporfin PDT in an average follow-up time of 24 months. Subfoveal CNV was found in 80% of the eyes during follow-up. Even though verteporfin PDT can preserve visual acuity in selected cases, deterioration was seen in the majority of the patients.     

Dreidimensionale Darstellung photodynamischer Effekte und des Spontanverlaufs bei chorioidalen Neovaskularisationen

PURPOSE: Photodynamic therapy (PDT) induces occlusive and regenerative effects in choroidal neovascularization (CNV) and physiological choroid. The process of vascular alteration is documented quantitatively and qualitatively by three-dimensional angiography. METHOD: In a prospective, randomized trial 30 patients with subfoveal CNV due to age-related macular degeneration (AMD) were treated with PDT or placebo. Fluorescence series with 32 tomographic images over a 4-mm depth were analyzed topographically and reproduced in a three-dimensional display. RESULTS: At initial presentation CNV lesions were documented as a well-defined prominence in all patients. In the verteporfin group CNV height continuously decreased with each interval. In the placebo group CNV slightly increased in height during the first 6 months and remained stable at about 90% of the initial prominence at long-term follow-up. After 12 months 44% of the patients in the verteporfin group developed an additional choroidal defect. CONCLUSION: Three-dimensional angiography offers a reliable documentation of CNV progression and regression during PDT. A decrease in CNV size is associated with an increase in choroidal perfusion defects.     

体外光动力疗法致血管内皮细胞和视网膜色素上皮细胞凋亡的研究

目的 研究体外光动力疗法（PDT）诱导的血管内皮细胞和视网膜色素上皮（RPE）细胞凋亡情况。 方法 将体外培养的血管内皮细胞和人RPE细胞与血药浓度（1.0 μg/ml）相当的光敏剂verteporfin共同孵育，根据孵育时间的不同，每种细胞分成6组：0、5、15、30、60、120 min组。孵育至上述时间后，分别用光敏剂最大吸收波长光照（689 nm、功率密度为600 mW/cm2的二极管激光），能量密度为2.4 J/cm2，光照时间为83 s。用流式细胞仪检测3 h后各组细胞凋亡比例，实验重复进行3次。 结果 PDT后3 h，血管内皮细胞在6组的凋亡比例分别为：0.01±0.01、0.25±0.02、0.32±0.02、0.41±0.04、0.49±0.03和0.61±0.02；RPE细胞各组的凋亡比例分别为：0.02±0.01、0.22±0.01、0.31±0.02、0.38±0.03、0.47±0.05和0.58±0.03；两种细胞的凋亡比例均随细胞与光敏剂孵育时间的延长而增加；两种细胞在相同时间组的凋亡比例经t检验差异均无统计学意义(P>0.05)。 结论 PDT可致RPE细胞和血管内皮细胞快速凋亡，在相同的体外环境下，PDT对两种细胞所诱导的凋亡反应无明显选择性。 (中华眼底病杂志, 2006, 22: 253-255)     

Photodynamic therapy for subfoveal choroidal neovascularisation in Vogt-Koyanagi-Harada disease

AIM: To assess the effects of photodynamic therapy (PDT) with verteporfin in the treatment of subfoveal choroidal neovascularisation (CNV) secondary to Vogt-Koyanagi-Harada disease (VKH). METHODS: Six eyes of six patients with VKH who developed subfoveal CNV underwent standard PDT. Repeated treatments were performed at 3 month intervals for persistent leakage. Charts and angiographic data were analysed retrospectively. RESULTS: Age of patients ranged between 17 years and 27 years. Five CNV lesions were recent and classic (greatest lesion diameter was 1100-3100 microm). One CNV was chronic and partially scarred. Mean visual acuity (VA) at presentation was 20/200. Five patients had more than 1 year of follow up. In five eyes there was active inflammation and CNV. Of these eyes, the first three required one PDT each. The final CNV scar was smaller/stable with improvement of VA in two eyes. The third developed a larger CNV scar with loss of two lines of VA. Submacular fibrosis developed in all three. In the fourth eye, mild CNV leakage persisted after one PDT but hazy media precluded a second PDT. At 18 months the CNV scar and VA were stable. The fifth case, with mild inflammation, required three PDT. The CNV leakage became minimal, the lesion became smaller, and VA improved significantly. The sixth eye with CNV had no inflammation and needed two PDT sessions to halt the CNV leakage. The final lesion was smaller and vision was stable. There were no PDT related complications in our series. CONCLUSION: Photodynamic therapy with verteporfin appears to be a safe and viable treatment option for subfoveal CNV secondary to VKH. It offers a chance for stabilisation or even improvement of vision. Further study is warranted.     

A preliminary assessment of macular function by MF-ERG in myopic eyes with CNV with complete response to photodynamic therapy

PURPOSE: To evaluate by multifocal electroretinogram (MF-ERG) macular function before and after photodynamic therapy (PDT) in myopic eyes with choroidal neovascularization (CNV). PATIENTS AND METHODS: Ten eyes with classic subfoveal CNV due to pathologic myopia were studied with MF-ERG before and after PDT in order to evaluate the results of PDT with verteporfin. The post-treatment follow-up was 6 months. Visual acuity testing, ophthalmic examinations, fluorescein and indocyanine green angiograms, and MF-ERG recordings were used to evaluate the results of PDT with verteporfin. The post-treatment period was 6 months. RESULTS: Before treatment, the electrical response densities in the foveal and perifoveal areas were apparently decreased in all patients. Six months after treatment, the mean retinal response densities in the same areas were found to be higher than before treatment. CONCLUSIONS: MF-ERG evaluates objectively the macular function in myopic eyes with CNV. After successful PDT, the electrical activity of the foveal and parafoveal areas is higher than before treatment. This finding postulates the efficacy of PDT in the treatment of CNV.