Photodynamic therapy with verteporfin for corneal neovascularization

PURPOSE: To investigate the efficacy of photodynamic therapy with verteporfin for the treatment of patients with corneal neovascularization. DESIGN: Prospective interventional case series. METHODS: Eighteen eyes of 18 patients with stable corneal neovascularization who were refractory to conventional treatment were treated with photodynamic therapy with verteporfin (6 mg/m(2)). Five patients were treated following penetrating keratoplasty (PK), and two patients were treated before PK. Anterior segment photography was performed before and after treatment. Best-corrected visual acuity (BCVA) and area of corneal neovascularization were measured. RESULTS: At the one-year follow-up, 14 eyes (77.8%) showed a decrease in corneal neovascularization, and nine eyes (50.0%) showed complete vascular occlusion. In five patients who had corneal allograft, complete or partial occlusion was achieved in all eyes. Two patients who underwent subsequent keratoplasty did not manifest allograft rejection or revascularization. Seventeen eyes (94.4%) had stable or improved vision. The mean area of corneal neovascularization significantly decreased from 25.5 +/- 14.2 mm(2) to 14.9 +/- 14.6 mm(2) (P < .01), respectively. No significant complications associated with photodynamic therapy were observed except mild stromal haze in one eye. CONCLUSION: Photodynamic therapy with verteporfin may be effective for the treatment of corneal neovascularization.     

角膜新生血管的药物治疗

临床上对角膜新生血管的治疗包括局部滴用糖皮质激素、非甾体类抗炎药物,对新生血管进行电凝、激光光凝、光动力疗法等,但临床效果不甚理想.目前抗血管内皮生长因子药物治疗角膜新生血管已用于临床,包括贝伐单抗、雷珠单抗、VEGF trap、干扰RNA等.多西环素、米诺环素等抗生素被证实对角膜新生血管有抑制作用.免疫抑制剂,如环孢素、雷帕霉素也被用于角膜新生血管的治疗.本文综述了角膜新生血管药物治疗的现状及未来可能的研发方向.     

角膜新生血管治疗的研究进展

多种病理因素可以导致角膜新生血管形成,新生血管化的角膜常导致视力严重下降、角膜移殖术失败。近年来,国内外对角膜新生血管的治疗在药物治疗、光动力疗法、眼表重建术等方面做了大量的研究,并取得迅猛发展。本文综述了角膜新生血管的治疗研究进展。     

Experimental inhibition of corneal neovascularization by photodynamic therapy with verteporfin

PURPOSE: To investigate the anti-angiogenic effects of photodynamic therapy with verteporfin in a rabbit model of corneal neovascularization. METHODS: One week after suturing, the localization of verteporfin in the neovascularized cornea was examined through fluorescent microscopy 1 hr after administration. Rabbits were treated with one or two times of photodynamic therapy with verteporfin at 1-week intervals. Analysis of corneal neovascularization was performed by biomicroscopic and histological examinations. RESULTS: Fluorescent microscopy showed green fluorescence in the vascular walls and interstitial tissue of the corneal stroma. The mean percentages of neovascularized corneal area at 3 days, 1 week, and 2 weeks after one time of photodynamic therapy were 90.3% +/- 3.5%, 71.6% +/- 6.2%, and 43.6% +/- 15.1% in treated eyes and 96.4% +/- 1.9% (p = 0.10), 88.6% +/- 4.6% (p = 0.01), and 76.8% +/- 4.4% (p < 0.01) in control eyes, respectively. The mean percentages 3 days, 1 week, and 2 weeks after two times of photodynamic therapy were also significantly lower in treated eyes compared with control eyes. In quantitative histological examination at 1 and 2 weeks after therapy, treated eyes showed significantly less neovascular area and number of vessels than control eyes. CONCLUSIONS: Photodynamic therapy with verteporfin is a safe and useful procedure to reduce experimental corneal neovascularization and can be used to inhibit angiogenesis in the cornea.     

Photodynamic therapy of corneal neovascularization with verteporfin

PURPOSE: To describe the effect of photodynamic therapy (PDT) using verteporfin (Visudyne) on corneal neovascularization (CNV) in two patients. METHODS: Two patients with corneal neovascularization were treated with a nonthermal laser light at 689 nm delivered 15 min after an intravenous infusion of verteporfin. Postoperative outcome of neovascularization was followed clinically (inflammation, intraocular pressure, and visual acuity) and photographically [color photographs and corneal fluorescein and indocyanine green (ICG) angiography] for a minimum of 6 months. RESULTS: Successful photothrombosis of corneal neovascularization was obtained immediately after treatment in the two patients, and regression was verified by corneal fluorescein and ICG angiography. In one case, partial vessel recanalization was observed after 1 month, and treatment was repeated, with complete regression of new vessels. No relevant side effects were observed in our cases. CONCLUSIONS: PDT with verteporfin is an effective and safe procedure indicated for patients with corneal neovascularization; however, multiple sessions may be required.     

Retinal pigment epithelial tear after photodynamic therapy for choroidal neovascularization

PURPOSE: To report a case of retinal pigment epithelial tear after photodynamic therapy for choroidal neovascularization. METHODS: Case report. A 74-year-old woman with exudative age-related macular degeneration and classic subfoveal choroidal neovascularization RE underwent photodynamic therapy with verteporfin. RESULTS: Ophthalmoscopy and fluorescein angiography RE disclosed a retinal pigment epithelial tear in the area of photodynamic therapy. CONCLUSION: This case presents the first report of a retinal pigment epithelial tear after photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in age-related macular degeneration.     

Update on photodynamic therapy

Photodynamic therapy is a relatively selective form of treatment for choroidal neovascularization. Unlike standard laser photocoagulation, photodynamic therapy can close choroidal neovascularization with minimal or no detectable damage to surrounding tissues. Therefore, it allows the clinician to treat subfoveal choroidal neovascularization without immediately adversely affecting central visual function. Several dyes for photodynamic therapy have been under various stages of formal clinical investigation. There is now mounting evidence that shows that photodynamic therapy with at least one of these dyes can significantly reduce the risk of visual loss in eyes with subfoveal choroidal neovascularization from age-related macular degeneration. This form of treatment promises to have a major, favorable impact on public health in areas of the world in which age-related macular degeneration is common.     

Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization secondary to toxoplasmic chorioretinal scar

BACKGROUND: To assess the effect of photodynamic therapy in the treatment of subfoveal choroidal neovascularization consecutive to a toxoplasmic chorioretinal scar. HISTORY AND SIGNS: Three patients with a previous history of toxoplasmic chorioretinal scar noticed a decrease in visual acuity and metamorphopsia. Fundus examination and fluorescein angiography revealed the presence of subfoveal choroidal neovascularization at the edge of the toxoplasmic chorioretinal scar. THERAPY AND OUTCOME: The first patient, aged 78, was treated by photodynamic therapy followed by three subsequent treatments of feeder vessel by laser photocoagulation. Visual acuity decreased during follow-up in the presence of recurrence of choroidal neovascularization and subretinal fibrosis. The second patient, a 20-year-old lady, was treated with three sessions of photodynamic therapy for a subfoveal choroidal neovascularization related to a toxoplasmic scar. Visual acuity was stabilized on the last follow-up visit at 0.3. The third patient, aged 53, received four treatments with photodynamic therapy at an interval of 3 - 4 months. choroidal neovascularization was stabilized and the last visual acuity was 0.2. CONCLUSIONS: This preliminary report suggests that photodynamic therapy with verteporfine may be an effective therapeutic modality for subfoveal choroidal neovascularization related to a toxoplasmic chorioretinal scar. Further assessment is needed in order to confirm this preliminary findings.     

光动力学治疗角膜新生血管

介绍光动力学治疗（PDT）的机制、光敏剂的种类和PDT用于角膜新生血管的研究现状。PDT应用低能量的光作用于光敏剂，产生对靶组织有毒性的光化学反应。光敏剂易于聚积在肿瘤和新生血管处，被增殖性的细胞摄取，这些组织吸收激光能量，导致自身氧化作用和细胞膜、线粒体、溶酶体和核的直接损伤，最终导致靶组织的新生血管和肿瘤组织的细胞凋亡。临床常用的光敏剂多是卟啉和它的衍生物，包括：苯卟啉衍生物单酸、氯化铝酞花青磺酸盐（CASPc）、SnET2、SINc、菌绿素a等。血啉单醚是一种国产的较理想的单体光动力学治疗新药。国外研究应用ATX-S10和SnET 2等作为光敏剂治疗角膜新生血管，疗效显著。     

Micro-perimetric documentation of retinal function in photodynamic therapy of choroid neovascularizations

PURPOSE: Photodynamic therapy provides occlusion of choroidal neovascularization by intravascular endothelial damage. The photodynamic approach offers the potential to occlude choroidal neovascularization selectively without altering adjacent sensory retina and therefore to preserve visual acuity. To determine the selectivity of photodynamic therapy photoreceptor function was measured by microperimetry allowing topic mapping of retinal function. METHODS: A Rodenstock scanning laser ophthalmoscope was used to document preservation of central visual fields before and after photodynamic therapy. Single photodynamic therapy without known efficient parameters was performed in 13 patients and repeated photodynamic therapy using optimised light doses was performed in 10 patients with subfoveal choroidal neovascularization using benzoporphyrin derivate (verteporfin). Intensity and dimension of central scotomas were measured, using a grading system of stimuli ranging from 0-32 dB. Areas of absolute and relative defect were defined and fixation localisation was monitored. Perimetric testing was done pre photodynamic therapy, one week, one month and three months post photodynamic therapy. RESULTS: Postoperative scotomas after single photodynamic therapy were smaller in 8%, identical in 61% and larger in 31% compared with preoperative findings. After repeated photodynamic therapy postoperative scotomas were smaller in 70%, identical in 30% and larger in no case. The observed increase was less than 25% of the original size. Postoperative defects were always significantly smaller than the entire size of the irradiated area. No new scotomas were found after photodynamic therapy. Angiographically visible occlusion post photodynamic therapy was in general larger than scotoma size. CONCLUSION: Documentation of the retinal function by microperimetry after photodynamic therapy of subfoveal choroidal neovascularization shows no new scotoma in the treated area. This can also be documented in the hypofluorescent area around the lesion one week after the treatment. After repeated treatment a reduced scotoma size due to choroidal neovascularization could be seen in 2/3 of the patients after 3 months. No initial vision loss as seen in conventional photocoagulation could be documented after photodynamic therapy.     

Photodynamic therapy increases the eligibility for feeder vessel treatment of choroidal neovascularization caused by age-related macular degeneration

PURPOSE: To report angiographic observations about feeder vessel identification after photodynamic therapy in patients with choroidal neovascularization caused by age-related macular degeneration. DESIGN: Cohort study. METHODS: We analyzed fluorescein and indocyanine green dynamic angiography in 156 eyes of 145 patients before and after photodynamic therapy to identify the feeder vessels of the choroidal neovascular membrane. RESULTS: Before photodynamic therapy one or more feeder vessel could be detected in 35 (22.4%) out of 156 eyes with choroidal neovascularization. Three months after photodynamic therapy, a feeder vessel could be identified in 112 (84.2%) out of 133 eyes with persistent choroidal neovascularization. Among these, 16 eyes received direct laser photocoagulation of the feeder vessel and did not need any further photodynamic therapy. CONCLUSION: Previous photodynamic therapy improves the detection of the feeder vessel of the choroidal neovascularization. A sequential combined therapy (photodynamic and feeder vessel treatment) could be considered as an alternative to multiple photodynamic treatments.     

Experimental (in vivo) study of the capacities of use of radachlorine (chlorine E-6) for photodynamic therapy in ophthalmology

To study the capacities of ophthalmological application of the photosensitizer Radachlorine (0.35% solution for intravenous injection), the authors carried out a series of in vivo experiments on rabbits. They studied the time parameters of distribution of the agent in the chorioretinal complex and the reaction of newly formed vessels to photodynamic therapy. Radiation of a diode laser at a wavelength of 0.662 microm was used to stimulate the photosensitizer. A video micro-camera adapted to the ocular of a split lamp was applied to fluorescence fixation. Superficial corneal vascularization was used as a model of the neovascular membrane in response to the application of a non-penetrating silk suture. The findings suggest that photodynamic therapy using Radachlorine is safe and effective in treating ocular tissue neovascularization.     

Treatment of juxtafoveal choroidal neovascularization with photodynamic therapy using verteporfin in eyes with age-related macular degeneration.

To report the results of treating juxtafoveal choroidal neovascularization with photodynamic therapy using verteporfin in eyes with age-related macular degeneration. Seven patients with predominantly classic juxtafoveal choroidal neovascularization were treated by photodynamic therapy using verteporfin. Three of the 7 patients had a gain in visual acuity and 2 had a stabilization of vision. The remaining 2 patients had a decrease in visual acuity. Subfoveal extension of the choroidal neovascularization was not observed in any patient and all choroidal neovascularization lesions after treatment were found to be nonperfused on fluorescein angiography. The encouraging results based on this small pilot study suggest that photodynamic therapy should be considered for treatment of select juxtafoveal choroidal neovascularization due to age-related macular degeneration.     

Corneal neovascularization

Corneal neovascularization (NV) is a sight-threatening condition usually associated with inflammatory or infectious disorders of the ocular surface. It has been shown in the field of cancer angiogenesis research that a balance exists between angiogenic factors (such as fibroblast growth factor and vascular endothelial growth factor) and anti-angiogenic molecules (such as angiostatin, endostatin, or pigment epithelium derived factor) in the cornea. Several inflammatory, infectious, degenerative, and traumatic disorders are associated with corneal NV, in which the balance is tilted towards angiogenesis. The pathogenesis of corneal NV may be influenced by matrix metalloproteinases and other proteolytic enzymes. New medical and surgical treatments, including angiostatic steroids, nonsteroidal inflammatory agents, argon laser photocoagulation, and photodynamic therapy have been effective in animal models to inhibit corneal NV and transiently restore corneal "angiogenic privilege."     

Photodynamic therapy for corneal neovascularization using polymeric micelles encapsulating dendrimer porphyrins

PURPOSE: To investigate the accumulation of new photosensitizers (PSs), dendrimer porphyrin (DP, free DP), and DP encapsulation into polymeric micelles (DP-micelle) and the efficacy of photodynamic therapy (PDT) in an experimental corneal neovascularization model in mice. METHODS: Corneal neovascularization was induced by suturing 10-0 nylon 1 mm away from the limbal vessel in C57BL6/J mice. To determine the accumulation of free DP and DP-micelle, 10 mg/kg free DP or DP-micelle was administered by intravenous injection 4 days after suture placement. Mice were killed 1, 4, 24, and 168 hours after the injection of PS. Twenty-four hours after the administration of free DP or DP-micelle, mice were treated with a diode laser of 438-nm wavelength at 10 or 50 J/cm(2). Fluorescein angiography was performed before and 7 days after irradiation, and the area of corneal neovascularization was quantified. RESULTS: Free DP and DP-micelle accumulated in the neovascularized area 1 hour to 24 hours after administration. Fluorescence of DP was weaker than that of DP-micelle. Neither DP-micelle nor DP could be detected in normal limbal vasculature. In the PDT experiments using PS, mean residual rates of corneal neovascularization were 10.1% in the mice treated with DP-micelle and 21.6% in the mice treated with free DP at 10 J/cm(2) (P < 0.01). At 50 J/cm(2), mean residual rates of corneal neovascularization were 10.6% in the mice treated with DP-micelle and 13.7% in the mice treated with free DP (P > 0.05). Although corneal neovascularization in PDT-treated mice exhibited significant regression compared with the control group, significant energy-related vessel regression with increasing laser energy could not be observed. CONCLUSIONS: PDT with DP-micelle and free DP can provide efficacious treatment of corneal neovascularization.     

Photodynamic therapy with verteporfin in a rabbit model of corneal neovascularization

PURPOSE: To determine the efficacy of photodynamic therapy (PDT) with verteporfin (Visudyne; Novartis AG, Basel, Switzerland) for treatment of corneal neovascularization in a rabbit eye model. METHODS: Corneal neovascularization was induced in Dutch belted rabbits by placing an intrastromal silk suture near the limbus. Verteporfin was administered by intravenous injection at a dose of 1.5 mg/kg, and the pharmacokinetics of verteporfin distribution in the anterior segment or PDT-induced (laser energy levels 17, 50, and 150 J/cm(2)) regression of corneal blood vessels were then determined. To assess PDT-induced toxicity of the anterior segment, corneal and iris/ciliary body histology, and IOP were evaluated after PDT. RESULTS: Verteporfin accumulation in vascularized regions of the cornea and the iris/ciliary body tissue were time dependent and maximum levels achieved at 60 minutes after injection. In rabbits, PDT of corneal vessels using laser energy of 17 or 50 J/cm(2) resulted in 30% to 50% regression of corneal neovascularization; however, in these animals, a rapid regrowth of new blood vessels occurred between 3 and 5 days. In the rabbits receiving PDT using laser energies of 150 J/cm(2), the mean vessel regression was 56%. During the nine days of the laser therapy follow-up period, no vessel regrowth was observed in these rabbits. Histologic examination of the anterior segment after PDT (150 J/cm(2)) showed localized degeneration of the corneal blood vessels without observable change in other anterior segment structures. CONCLUSIONS: These results provide evidence that PDT can produce significant regression of neovascular corneal vessels with no observable toxicity to the anterior segments. However, the optimal laser energy necessary to induce long-term regression (150 J/cm(2)) was three times that used to treat choroidal neovascularization.     

角膜新生血管的药物治疗进展

角膜在病理因素的作用下产生新生血管。角膜新生血管不但严重影响视力,而且导致角膜移植手术的失败。近年来,国内外对角膜新生血管的治疗取得迅猛发展,但角膜新生血管依然是目前最常见的致盲原因之一。本文综述了近年来角膜新生血管的药物治疗进展。     

Photodynamic therapy for the treatment of choroidal neovascularization secondary to rubella retinopathy

PURPOSE: To describe a patient for whom photodynamic therapy was used to treat subfoveal choroidal neovascularization secondary to rubella retinopathy. DESIGN: Interventional case report.METHODS: A 36-year-old man with subfoveal choroidal neovascularization secondary to rubella retinopathy was treated with photodynamic therapy using verteporfin. Outcome was followed up with subsequent fundus examinations, fluorescein angiography, and evaluations of best-corrected visual acuity. RESULTS: Two treatments of photodynamic therapy using verteporfin resulted in involution of the neovascular membrane, resolution of subretinal hemorrhage, and improvement in best-corrected visual acuity from 20/200 to 20/60 2 months after the second treatment. Owing to recurrence of active choroidal neovascularization, the patient required two more treatments of photodynamic therapy in the next 6 months, after which his best-corrected visual acuity was restored to 20/60. CONCLUSION: Photodynamic therapy may be an effective treatment for subfoveal choroidal neovascularization secondary to rubella retinopathy.     

Photodynamic therapy for choroidal neovascularization secondary to choroidal nevus

PURPOSE: To describe a patient treated with photodynamic therapy for subfoveal choroidal neovascularization secondary to choroidal nevus. DESIGN: Interventional case report. METHODS: A 61-year-old woman presented with subfoveal choroidal neovascularization secondary to choroidal nevus and best-corrected visual acuity of 20/50. The choroidal neovascularization was treated with two verteporfin photodynamic therapy sessions, separated by 3 months. RESULTS: The choroidal neovascularization was occluded after two sessions. Best-corrected visual acuity improved to 20/25 and remained stable throughout an 18-month follow-up. CONCLUSION: Photodynamic therapy seems to be an effective treatment for subfoveal choroidal neovascularization secondary to choroidal nevus.     

抑制角膜新生血管生长的研究进展

角膜新生血管(CNV)多见于感染、炎症、外伤或角膜手术后。CNV是眼表疾病的显著特征之一,血管化的角膜不但严重影响视力,而且是角膜移植失败的主要原因。近年来,随着对CNV的深入研究,在血管的形成机制和治疗方面取得了一些成果,主要就CNV治疗的新进展作一综述。