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Purpose: Interface bonding with corneal crosslinking (CXL) after LASIK using two different photosensitizers was studied ex vivo., Methods: A LASIK flap was created in enucleated rabbit eyes using a femtosecond laser. After the dissection, CXL was performed to seal the interface. In one group interface CXL was performed using rose bengal and green light, whereas in a second group riboflavin and UV-A light was used. In both groups irradiance, radiant exposure, dye concentration, and imbibition time was varied. In a control group, LASIK only was performed. After the procedures, the maximal shear-force required to separate the flap from the stroma was measured. Additionally, corneal transmission spectra were recorded., Results: Optimized parameters for rose bengal/green-light bonding lead to a 2.1-fold increase in shear-force compared with untreated control eyes (P < 0.01). The optimal parameter combination was: irradiance of 180 mW/cm2 for 14 minutes (total radiant exposure 150 J/cm2), rose bengal concentration 0.1%, and an imbibition time of 2 minutes. Optimized riboflavin/UV-A light parameters were 0.5% for 2 minutes with a radiant exposure of 8.1 J/cm2 obtained by an irradiance of 30 mW/cm2 for 4.5 minutes. These optimized parameters lead to a 2-fold increase compared with untreated control eyes (P < 0.01). Optical transmission experiments suggest safety for more posterior structures., Conclusions: Based on ex-vivo results, interface bonding after LASIK using crosslinking with either rose bengal or riboflavin increases the adhesion between flap and stromal bed. In vivo trials are needed to evaluate the temporal evolution of the effect.

Purpose: Up to date several approaches have been undertaken to achieve an 'easy-to-handle' animal model of choroidal neovascularizations (CNVs) in rabbits; however, so far in none of the studies could healthy retinal tissue be maintained, which is mandatory to further investigate the effects of photodynamic therapy (PDT) or anti-vascular-endothelial-growth-factor treatments. It was our aim to reevaluate and verify the method of inducing experimental CNVs in rabbits using subretinally injected linoleic acid hydroperoxide (LHP) as proposed by Tamai et al. and to use it for experimental PDT., Material and Methods: In 33 eyes of Chinchilla breed rabbits LHP of two different concentrations (25 and 100 microg/50 microl) was injected into the subretinal space via a transvitreal approach under guidance of an operation microscope. Ophthalmoscopic and angiographic examinations were performed on days 3, 7, 14 and 28 after surgery. Preliminary PDT with different experimental parameter sets was performed in 3 eyes using the new photosensitizer Tookad., Results: Using LHP in the higher concentration, an angiographically determined CNV induction was observed in 27% of all injection sites (n = 34) on days 14 and 28 revealing early well-demarcated and progressive leakage. No CNV was detected at the lower LHP concentration (60 injection sites). Subretinal CNV was verified histologically revealing vessel formation above the retinal pigment epithelium level. Herein, a significant damage to the outer retinal layers was always observed; however, the general structure of the choriocapillary layer was maintained. Tookad PDT was clinically able to completely stop leakage in 1 case and reduce leakage in 2 cases. Histologically the choriocapillary layer was occluded., Conclusion: Subretinal injection of LHP induces angiographically well-demarcated classic CNVs in rabbits; however, the CNV rate was low, and histology revealed severe damage of the outer retinal layers but not of the choriocapillary layer, which is important for studying PDT interactions. Preliminary experimental PDT could clinically stop or reduce leakage from angiographic CNV. Due to the small CNV rate and the significant collateral retinal tissue damage, this model seems to be only of partial suitability for investigating new treatment modalities in CNV., ((c) 2008 S. Karger AG, Basel.)

Purpose: To determine the efficacy of Tookad (WST09; Negma-Lerads, Magny-Les-Hameaux, France) photodynamic therapy (T-PDT) by evaluating the angiographic and histologic closure of choroidal vessels at different radiance exposures, drug dosages, and intervals between photosensitizer injection and laser application in a rabbit model., Methods: Chinchilla Bastard rabbits were injected intravenously with three different dye concentrations (2.5, 5, and 10 mg/kg) before application of light. In every group T-PDT was performed at four different times after injection: 5, 15, 30, and 60 minutes with different radiance exposures ranging from 200 to 3 J/cm2. Fundus photographs and fluorescein angiograms were obtained 90 minutes after injection. Follow-up angiographies were performed at days 1, 3, 7, and 14 after initial treatment. Histology was performed in selected cases immediately after treatment and on days 1, 3, and 7., Results: Immediately after irradiation, most of the visible lesions were angiographically hyperfluorescent due to damaged vessel endothelium and associated RPE damage. Lesions from high-radiance exposures revealed immediate hypofluorescence, indicating vessel closure. Hypofluorescent lesions appeared mainly during day 1 (all lesions angiographically visible, some hypofluorescent) to day 3 (all lesions hypofluorescent) after treatment. At day 7, ophthalmoscopically visible hyperpigmentation took place in all lesions. ED50 thresholds for angiographic hypofluorescence determined at day 3 after treatment with 2.5 mg/kg were 18.8 J/cm2 (5 minutes), 62.0 J/cm2 (15 minutes), and >100 J/cm2 (30 minutes); with 5 mg/kg, 8.4 J/cm2 (5 minutes), 22.8 J/cm2 (15 minutes), 54.5 J/cm2 (30 minutes), and >100 J/cm2 (60 minutes); and with 10 mg/kg, 11.7 J/cm2 (30 minutes) and 54.1 J/cm2 (60 minutes). Histology of the angiographically hypofluorescent lesions revealed vessel thrombosis in all groups 1 hour after PDT up to 7 days after treatment. Sparing of photoreceptors indicated selectivity of T-PDT; however, slight damage was partly observable. After 7 days, localized proliferation of the RPE cells was noted and was enhanced 14 days after treatment., Conclusions: T-PDT has the potential to achieve selective choroidal vessel occlusion with proper parameter selection, such as (1) 2.5 mg/kg, 5 minutes, 100 J/cm2; (2) 5 mg/kg, 5 minutes, 25 J/cm2; or (3) 5 mg/kg, 15 minutes, 50 J/cm2; however, slight damage to the photoreceptors cannot be ruled out. RPE proliferation indicates primary RPE damage due to PDT, also described with the use of all other photosensitizers.

Purpose: To evaluate the potential of liposomal Zinc(II)-phthalocyanine (ZnPc) to selectively target subretinal vasculature., Methods: Photodynamic therapy (PDT) with liposomal Zinc(II)-phtalocyanine was used to induce choroidal occlusion in eyes of pigmented rabbits. Drug doses of 0.16, 0.24, 0.32, and 0.4 mg/kg body weight were administered. Photosensitization was performed at a wavelength of 671 nm and an irradiance of 100 mW/cm2 applying fluences of 5, 10, 20, and 50 J/cm2., Results: Using liposomal ZnPc, occlusion of choroidal vessels was achieved without damage to the overlying neurosensory retina. A tight dose correlation was found with a drug dose of 0.32 mg/kg and a light dose of 10 J/cm2 inducing a selective thrombosis of the subretinal capillary layer. Histology revealed a selective intravascular alteration of the endothelial cells., Conclusions: PDT using liposomal ZnPc allows occlusion of subretinal vasculature with maintenance of neuroretina and RPE. The destructive effect on choroidal vascular endothelium is intensive.

Objective: To evaluate short-term safety and the effects on visual acuity and fluorescein angiography of single or multiple sessions of photodynamic therapy with verteporfin for choroidal neovascularization (CNV) not related to age-related macular degeneration (AMD), including pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes. Design: A nonrandomized, multicenter, open-label, doseescalation phase 1 and 2 clinical trial. Setting: Four ophthalmic centers in Europe and North America providing retinal care. Participants: Thirteen patients with subfoveal CNV due to pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, or idiopathic causes. Methods: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of photodynamic therapy treatments with verteporfin. Follow-up ranged from 12 weeks for patients who were treated once to 43 weeks for patients who were treated up to 4 times. Results: Verteporfin therapy was well tolerated in patients with CNV not related to AMD. No deterioration in visual acuity was observed; most patients gained at least 1 line of vision. Reduction in the size of leakage area from classic CNV was noted in all patients as early as 1 week after verteporfin therapy, with complete absence of leakage from classic CNV in almost half of the patients. Improvement in visual acuity after verteporfin therapy was greatest (+6, +8, and +9 lines) in 3 patients with relatively poor initial visual acuity (between 20/200 and 20/800). Up to 4 treatments were found to have short-term safety even with retreatment intervals as short as 4 weeks. Conclusions: Treatment of CNV not related to AMD with verteporfin therapy achieves short-term cessation of fluorescein leakage from CNV in a small number of patients without loss of vision. Further randomized clinical trials including a larger number of patients... [ABSTRACT FROM AUTHOR]

Objectives: To evaluate safety and short-term visual acuity and fluorescein angiographic effects of photodynamic therapy (PDT) after retreatments with verteporfin for choroidal neovascularization (CNV) in agerelated macular degeneration (AMD) that demonstrated fluorescein leakage after at least 1 course of PDT. Design: Nonrandomized, multicenter, open-label phase 1 and 2 clinical trial using 2 different retreatment dosage regimens. Setting: Four ophthalmic centers in Europe and North America providing retinal care. Methods: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of multiple PDT treatments. Two regimens (regimens 2 and 4) for treatment and retreatment were chosen from 5 used in a single-treatment study. Both regimens used a verteporfin dose of 6 mg/m² infused for 10 minutes. However, regimen 2 used a light dose of 100 J/cm² applied 20 minutes after the start of the verteporfin infusion, whereas regimen 4 used a light dose of 50, 75, or 100 J/cm² applied 15 minutes after infusion commenced. Posttreatment evaluations were planned in 31 participants up to 3 months after up to 2 retreatments given at 2- or 4-week intervals after initial PDT treatment. Similar posttreatment evaluations were planned after retreatments in 5 additional participants who were reenrolled some time more than 12 weeks after an initial PDT treatment. the initial treatment and a follow-up examination 16 to 20 weeks after the initial treatment was 0.2 lines (range, -4 to 4 lines) in regimen 2 and -1.0 line (range, -5 to 3 lines) in regimen 4. Similar outcomes were noted in the 5 reenrolled participants. Cessation of fluorescein leakage from classic CNV for at least 1 to 4 weeks could be achieved without loss of visual acuity after at least 2 treatments in 2 (6.5%) of 31 patients. Similar to single-treatment effects, the disappearance of leakage was documented... [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety and short-term visual and fluorescein angiographic effects of a single photodynamic therapy treatment with verteporfin with the use of different dosage regimens in patients with choroidal neovascularization (CNV) from age-related macular degeneration. Design: Nonrandomized, multicenter, open-label, clinical trial using 5 dosage regimens. Setting: Four ophthalmic centers in North America and Europe providing retinal care. Participants: Patients with subfoveal CNV caused by age-related macular degeneration. Methods: Standardized protocol refraction, visual acuity testing, ophthalmic examination, color photographs, and fluorescein angiograms were used to evaluate the effects of a single treatment of photodynamic therapy with verteporfin. Follow-up was planned through 3 months in 97 patients and for less than 3 months in 31 other patients. Results: The mean visual acuity change (and range of change) from baseline at the follow-up examination at week 12 after a single treatment with regimens 1 through 5 was -0.2 (-3 to +2), -0.9 (-9 to +5),-1.6 (-9 to +2), +0.4 (-8 to +7), and +0.1 (-8 to +9) lines, respectively. Only the highest light dose (150 J/cm²) in regimens 2 and 3, which produced angiographic nonperfusion of neurosensory retinal vessels, caused marked vision loss. Some cessation of fluorescein leakage from CNV was achieved without loss of vision when the light dose used was less than 150J/cm². Systemic adverse events were rare. Cessation of fluorescein leakage from CNV was noted in all regimens by 1 week after photodynamic therapy. Fluorescein leakage from at least a portion of the CNV reappeared by 4 to 12 weeks after treatment in almost all cases. Progression of classic CNV beyond the area of CNV identified before treatment was noted in 42 (51%) of the 83 eyes with classic CNV followed up for 3 months after a single treatment. Eyes in which the area of any CNV leakage at 12 weeks was less than at baseline had a... [ABSTRACT FROM AUTHOR]