Photodynamic therapy with verteporfin for anterior segment neovascularizations in neovascular glaucoma

PURPOSE: To evaluate photodynamic therapy (PDT) with verteporfin for iris and angle neovascularization in eyes with neovascular glaucoma. DESIGN: Interventional case series. METHODS: A prospective, noncomparative case series included four patients (four eyes) with neovascular glaucoma. PDT was performed following the parameters of treatment of age-related macular degeneration with photodynamic therapy Study Group (TAP). The laser was directed at the anterior chamber angle and iris surface using a Goldmann three-mirror contact lens. Iris and angle neovascularization were quantified using the number of clock hours involved. Outcome measures were obliteration of neovascularization and decrease of intraocular pressure (IOP). RESULTS: One week after PDT, we registered complete obliteration of angle neovascularization and partial occlusion of iris neovascularization. Subsequent reopening of angle neovascularization was detectable at 1 month. Intraocular pressure diminished considerably after 1 week, with a subsequent tendency toward stabilization. CONCLUSIONS: Photodynamic therapy can be used safely and effectively in the early phases of neovascular glaucoma to achieve angle neovascularization obliteration and IOP reduction.     

Photodynamic therapy for posterior capsule neovascularization

We report a 71-year-old man with posterior capsule opacification with severe neovascularization who was treated with photodynamic therapy and neodymium:YAG capsulotomy. Treatment was performed using a diode laser at 692 nm, a light dose of 50 J/cm(2), and 6 mg/m(2) body surface area verteporfin. The initial visual acuity was hand motions; 6 months after therapy, the visual acuity was stable at 20/200. In 9 months of follow-up, there was no recurrence of neovascularization and the pupil area remained clear; no retreatment was needed. Photodynamic therapy provided safe and effective occlusion of neovascular vessels in the posterior capsule area.     

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.     

Treatment of rubeosis iridis with photodynamic therapy with verteporfin--A new therapeutic and prophylactic option for patients with the risk of neovascular glaucoma?

Patients with ischaemic retinopathy who show iris neovascularization despite panretinal laser photocoagulation (PRP) very often develop a neovascular glaucoma. Photodynamic therapy (PDT) has been shown to occlude neovascularization without damage to physiologic vessels or adjacent tissue in the treatment of choroidal neovascularization (CNV) and might also be of value for patients with neovascular glaucoma who did not benefit from the PRP. First results of a monocentre, open label, intra-individual controlled, pilot phase I/II, dose-finding study demonstrate that PDT with verteporfin is capable of occluding neovascular vessels for a defined period of time without damaging adjacent tissue or physiologic iris vessels. Whether this vessel occlusion will have an impact on the progression of rubeosis or neovascular glaucoma will be the subject of further investigation.     

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 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.     

Clinicopathologic studies of age-related macular degeneration with classic subfoveal choroidal neovascularization treated with photodynamic therapy

BACKGROUND: Photodynamic therapy (PDT) is a relatively new modality that is currently under clinical and experimental evaluation for treatment of subfoveal choroidal neovascularization (CNV). The authors report the case of an 82-year-old woman who underwent verteporfin-mediated PDT for classic subfoveal CNV. Fluorescein angiography performed 2 weeks after treatment disclosed reduction of the initial area of neovascularization and leakage by approximately 60%. Three weeks after PDT, however, the area of leakage was almost the same size as that before treatment. The patient underwent submacular membranectomy almost 4 weeks after treatment. The authors describe the ultrastructural vascular changes after PDT and a clinicopathologic study of classic CNV. METHODS: The submacular membrane was studied by light and electron microscopy and immunohistochemical techniques. RESULTS: Ultrastructural examination of the peripheral vessels showed evidence of endothelial cell degeneration with platelet aggregation and thrombus formation. Occasional occluded vessels were surrounded by macrophages, a phenomenon previously reported to describe the process of resorption of such blood vessels. The vessels in the center of the membrane were unremarkable. CONCLUSION: Photodynamic therapy causes endothelial cell damage, thrombus formation, and vascular occlusion of classic CNV in age-related macular degeneration.     

Immunohistopathologic evaluation of choroidal neovascular membranes following verteporfin-photodynamic therapy

PURPOSE: To evaluate the vascularization and proliferative activity in choroidal neovascular membranes due to age-related macular degeneration after verteporfin photodynamic therapy and submacular removal. DESIGN: Interventional case series. METHODS: In a retrospective review of seven patients who underwent removal of subfoveal classic choroidal neovascular membranes after treatment with photodynamic therapy 3 to 146 days earlier, membranes were stained for CD 34, CD 105, and Ki-67 and correlated with clinical pictures and fluorescein angiography. RESULTS: Fluorescein angiography performed on the day of surgery disclosed nonperfusion of the treated area 3 days after photodynamic therapy, but perfusion and leakage were seen at greater post-photodynamic therapy intervals. Membranes excised 3 days after photodynamic therapy showed CD34 and CD105 positive, mostly occluded vessels. The endothelial cells appeared damaged. Ki-67 activity was low. In membranes excised 34 to 146 days after photodynamic therapy, all vessels appeared patent and were lined by healthy endothelial cells with strong expression of CD34 and CD105. Ki-67 expression was elevated after 34 days but decreased thereafter. CONCLUSION: Photodynamic therapy did not cause a general or complete occlusion of vessels within the choroidal neovascular membranes, as suggested by fluorescein angiography 3 days postintervention, but the endothelial cells appeared to be severely damaged. Proliferative activity within these specimens was reduced. At longer intervals after photodynamic therapy, the fibrovascular tissue seemed to recover; perfusion, hyperfluorescence, and leakage of the choroidal neovascular membranes could be detected by fluorescein angiography. The clinical appearance showed a correlation with the immunohistologic characteristics of an increased proliferative activity and patent vascularization.     

Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in central serous chorioretinopathy: case report

We report the use of photodynamic therapy with verteporfin for subfoveal choroidal neovacularization in central serous chorioretinopathy. Visual acuity improved (0.5 to 1.0) 30 days after the first session. After 141 days, the choroidal neovascularization reactivated and the patient was retreated. Again, visual acuity improved (0.5 to 1.0) 30 days afterwards. It remains stable after 20 months. Photodynamic therapy can be efficient in the treatment of choroidal neovascularization in central serous chorioretinopathy.     

Choriocapillaris photodynamic therapy using indocyanine green

PURPOSE: To evaluate the potential of photodynamic therapy using indocyanine green for occlusion of choroidal neovascularization, the authors studied efficiency and collateral damage of photodynamic therapy-induced photothrombosis in the rabbit choriocapillary layer. METHODS: Fundus photography, fluorescein angiography, and light and transmission electron microscopy were used to study the efficiency of photodynamic therapy-induced photothrombosis using indocyanine green as the photosensitizer, and to assess the resultant collateral damage. The delivery system consisted of a modified infrared diode laser tuned to 810 nm, near the maximum absorption peak of indocyanine green. RESULTS: Choriocapillary occlusion was achieved at indocyanine green doses of 10 and 20 mg/kg and a radiant as low as 6.3 J/cm(2). When photodynamic therapy was performed with indocyanine green doses of 10 mg/kg, damage to the neural retina was minimal. Only inner photoreceptor segments showed degeneration, probably secondary to choroidal ischemia. Bruch membrane remained intact. Retinal pigment epithelium was invariably damaged, as seen with other photosensitizers. Temporary occlusion of large choroidal vessels occurred at both dye doses. CONCLUSIONS: In this experimental study, photodynamic therapy using indocyanine green and 810-nm light irradiation produced endothelium-bound intraluminal photothrombosis, with preservation of the retinal architecture and minimal loss of visual cells. Membrane targetability, hydrophilic and fluorescent properties, and activation at 805 nm suggest indocyanine green as a potential photosensitizer for choroidal neovascularization. These combined considerations point toward further study of photodynamic therapy using indocyanine green for the treatment of choroidal vascular disease.     

Verteporfin photodynamic therapy for anterior segment neovascularization secondary to ischaemic central retinal vein occlusion

Purpose: To evaluate the efficacy of photodynamic therapy (PDT) with verteporfin for anterior segment neovascularizations (ASNVs) in patients affected by ischaemic form of central retinal vein occlusion (CRVO). Methods: Prospective non‐comparative case series including 10 consecutive patients (10 eyes) affected by ischaemic CRVO. Main outcome measure was the obliteration of ASNV. Results: One month after PDT, biomicroscopic examination showed partial obliteration of iris new vessels and complete closure of angle neovascularization. Iris fluorescein angiography performed 1 week after treatment showed partial closure of the iris new vessels with no evidence of leakage in the late phases. During the subsequent examinations, a partial reopening of the iris and angle new vessels in association with dye leakage on fluorescein angiography was evident. In any case, the fluorescein leakage turned out to be still reduced with respect to the baseline aspects. Conclusions: Our results show that PDT with verteporfin can partially obliterate ASNVs in eyes affected by ischaemic CRVO preventing from the evolution towards advanced stages of neovascular glaucoma, but is not effective in cases with complete angle synechial closure.     

Neovascularization in the anterior segment of the rabbit eye by experimental anterior ischemia

PURPOSE: To investigate the effects of anterior ischemia accompanied by neither retinal nor choroidal ischemia on the anterior segment of the eye. METHODS: Both long posterior ciliary arteries in the right eye of 14 rabbits were directly cauterized with an electric coagulator. The eyes were enucleated 1, 2, 4, 7, 9 or 14 days after cauterization, then fixed with 4% paraformaldehyde. Semi-thin sections were studied by light microscopy. Several sections were stained with Griffonia simplicifolia lectin, which bound specifically to mammalian vascular endothelium. Other specimens were examined immunohistochemically for vascular endothelial growth factor (VEGF) protein. The tissue specimens of the first postoperative day were studied for expression of VEGF mRNA by in situ hybridization. RESULTS: Atrophy of the iris and ciliary body was seen after the second postoperative day. Corneal neovascularization appeared after 7 days. Neovascularization on the anterior surface of the iris and in the trabecular meshwork was detected after the ninth postoperative day. The proliferative tissues with newly formed vessels obstructed the iridocorneal angle 14 days after the treatment. There was no histological change in either the retina or choroid. Immunohistochemically, VEGF protein was detected in the epithelial and vascular cells of the iris on the first and fourth postoperative day. Expression of VEGF mRNA was detected in the epithelial cells of the ciliary body on the day following the treatment. CONCLUSIONS: Anterior segment ischemia, when unaccompanied by retinal ischemia, causes neovascularization in the cornea, iris and trabecular tissue.     

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.     

Effect of pan-retinal photocoagulation in iris neovascularization]

The authors were able to produce experimental rubeosis iridis in the rhesus monkey's eye on 5 days following occlusion of the major retinal vessels and persistent ocular hypotony. Histopathological examination revealed true neovascularization. This experiment attempted to see whether laser pan-retinal photocoagulation plays an inhibiting effect on the occurrence of rubeosis iridis or not. We first performed laser pan-retinal photocoagulation, and at the same time performed occlusion of the major retinal vessels and persistent hypotony to aid for rubeosis iridis. Clinically, rubeosis iridis appeared within 5 days. At 14 days, histological examination revealed vessels on the surface of the iris following pan-retinal photocoagulation treatment were covered by fibroblast and melanocyte, and their endothelial cells showed no fenestrations. This means that clinical rubeosis iridis is not true neovascularization, but dilatation of the iris vessels. Thus, it was confirmed that pan-retinal photocoagulation inhibits development of iris neovascularization.     

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。     

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.     

Morphological study of rubeosis iridis induced in animal eyes]

Rubeosis iridis was produced experimentally in rhesus monkey eyes, by means of occlusion of the major retinal vessels of the retina and persistent ocular hypotony. Clinically, rubeosis iridis was recognized 5 days after the procedure. Histopathologically, these vessels developed anteriorly to the iris surface and endothelial fenestrations showed evidence of iris neovascularization. Endothelial cells of the vessels projected toward the internal lumen and showed immaturity. Newly formed vessels originated from the stromal vessels in the iris. This method is an effective experimental model for the induction of rubeosis iridis.     

Successful photodynamic therapy with verteporfin for recurrent choroidal neovascularization beneath the new fovea after macular translocation surgery with 360-degree retinotomy

PURPOSE: To report a case of successfully treated recurrent choroidal neovascularization after macular translocation surgery with 360-degree retinotomy by photodynamic therapy with verteporfin. DESIGN: Interventional case report. METHODS: A 76-year-old man developed recurrent choroidal neovascularization at the new fovea after macular translocation surgery with 360-degree retinotomy. RESULTS: Two sessions of photodynamic therapy were applied, which resolved the choroidal neovascularization. Best-corrected visual acuity improved to 20/50 at the 6 and 12 months follow-up. CONCLUSION: Photodynamic therapy may be an option for treatment of recurrent choroidal neovascularization in the new subfoveal region after macular translocation surgery with 360-degree retinotomy.     

Treatment of angioid streaks with phothodynamic therapy

CLINICAL CASE: A patient had bilateral angioid streaks complicated by cicatricial degeneration in the left eye and subfoveal choroidal neovascularization in the right eye. Photodynamic therapy resulted in a favorable response with normalization of the visual acuity and angiographic resolution of the lesions. DISCUSSION: The most serious complication of angioid streaks is choroidal neovascularization. Today photodynamic therapy is an effective treatment of subfoveal choroidal neovascularization. It also appears useful in the treatment of choroidal neovascularization in angioid streaks.     

Photodynamic therapy for choroidal neovascularization after thermal laser photocoagulation for diabetic macular edema

PURPOSE: To report the use of photodynamic therapy for treating a choroidal neovascular membrane secondary to thermal laser photocoagulation. DESIGN: Interventional case report. METHODS: A 61-year-old man with a choroidal neovascular membrane secondary to thermal laser photocoagulation for diabetic macular edema was treated with photodynamic therapy. RESULTS: Subjective and objective improvement in visual acuity and improvement of fluorescein angiogram have been demonstrated for more than a year after treatment. CONCLUSIONS: Photodynamic therapy may be useful for treating patients with choroidal neovascularization secondary to thermal laser photocoagulation.