Indocyanine green angiography and retinal sensitivity after photodynamic therapy of subfoveal choroidal neovascularization

Photodynamic therapy (PDT) is currently being evaluated in clinical trials for the treatment of choroidal neovascularization (CNV). Preliminary results indicate that PDT achieves immediate absence of leakage from CNV while maintaining visual acuity. Indocyanine green angiography reveals a reduction in CNV size and a persistent decrease in leakage activity after PDT. PDT appears to be characteristically accompanied by choroidal perfusion changes that regularly resolve within 3 months. Microperimetry shows an improvement of the central visual field with a decrease in scotoma size and intensity. Repeated PDT applications do not cause additional damage to the treated area, but might further enhance the recovery of macular function. A placebo-controlled, multi-center trial (TAP trial) evaluating the benefit of repeated PDT treatments in 3-month intervals is currently underway.     

Topographic Distribution and Progression of Soft Drusen Volume in Age-Related Macular Degeneration Implicate Neurobiology of Fovea

PurposeTo refine estimates of macular soft drusen abundance in eyes with age-related macular degeneration (AMD) and evaluate hypotheses about drusen biogenesis, we investigated topographic distribution and growth rates of drusen by optical coherence tomography (OCT). We compared results to retinal features with similar topographies (cone density and macular pigment) in healthy eyes.MethodsIn a prospective study, distribution and growth rates of soft drusen in eyes with AMD were identified by human observers in OCT volumes and analyzed with computer-assistance. Published histologic data for macular cone densities (n = 12 eyes) and in vivo macular pigment optical density (MPOD) measurements in older adults with unremarkable maculae (n = 31; 62 paired eyes, averaged) were revisited. All values were normalized to Early Treatment Diabetic Retinopathy Study (ETDRS) subfield areas.ResultsSixty-two eyes of 44 patients were imaged for periods up to 78 months. Soft drusen volume per unit volume at baseline is 24.6-fold and 2.3-fold higher in the central ETDRS subfield than in outer and inner rings, respectively, and grows most prominently there. Corresponding ratios (central versus inner and central versus outer) for cone density in donor eyes is 13.3-fold and 5.1-fold and for MPOD, 24.6 and 23.9-fold, and 3.6 and 3.6-fold.ConclusionsNormalized soft drusen volume in AMD eyes as assessed by OCT is ≥ 20-fold higher in central ETDRS subfields than in outer rings, paralleling MPOD distribution in healthy eyes. Data on drusen volume support this metric for AMD risk assessment and clinical trial outcome measure. Alignment of different data modalities support the ETDRS grid for standardizing retinal topography in mechanistic studies of drusen biogenesis.     

Choroidal changes after photodynamic therapy (PDT). A two-year follow-up study of 38 patients

BACKGROUND: Photodynamic therapy is a new option for treatment of choroidal neovascularisation in patients with age-related macular degeneration. But choroidal changes and associated angiographic characteristics have not been further evaluated. PATIENTS: Indocyanine green angiography was used to follow 38 patients with subfoveal choroidal neovascularisation in age-related macular degeneration over up to two years. All patients were treated with the photosensitizer Benzoporphyrin Derivative-MA receiving either a single or triple treatment. RESULTS: Indocyanine green angiography shows two effects of photodynamic therapy. On the one hand a selective and lasting closure of choroidal neovascularisation was documented. Choroidal neovascularisation-size and leakage was significantly reduced in the entire treatment group to 20.7% and 28.3% one week after treatment, followed by a slow increase to 33.3% and 41.2% at up to two years longterm follow up. On the other hand photodynamic therapy causes typically a peri-lesional hypofluorescence in Indocyanine green angiography. This hypofluorescence is most likely due to choroidal hypoperfusion and vascular endothelial changes. A continuous increase in fluorescence was shown, reaching again 90% of the pretreatment intensity at 3 months, documenting a good recovery of the choroidal network. CONCLUSION: The results show that photodynamic therapy is an alternative treatment in age-related macular degeneration with choroidal, subfoveal neovascularisation. Indocyaningreen angiography reflects well choroidal changes associated with this therapy and may be helpful to choose treatment intervals.     

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 effects on choroidal neovascularization and physiological choroid

PURPOSE: To evaluate the effect of photodynamic therapy (PDT) on perfusion and vascular integrity of choroidal neovascularization (CNV) and collateral physiological choroid. METHODS: In a prospective clinical trial, patients with subfoveal CNV were treated with PDT and verteporfin. Indocyanine green angiography (ICG-A), using a confocal laser scanning system with tomographic sections, was performed continuously 1 week before and 1, 4, and 12 weeks after and a mean long-term follow-up of 16.5 months after the final PDT. Vascular changes were localized tomographically and quantified on the level of the CNV and collateral choroid according to early lesion size, late hyperfluorescence, and persistence or recurrence. Data were analyzed separately from 38 eyes in a single- and 12 eyes in a multiple-treatment regimen. RESULTS: CNV lesions were significantly reduced in size and late hyperfluorescence. However, 54% of lesions primarily demonstrated persistence, typically of the choroidal feeding complex, which was only detectable by ICG-A. Regrowth from the feeding vessel occurred regularly, but did not reach baseline dimensions. Collateral choroid exposed to photoactivation exhibited choriocapillary occlusion. Progressive recanalization was documented within 4 to 12 weeks after both single and multiple PDT. Residual changes in the choroidal filling pattern often persisted during long-term follow-up. CONCLUSIONS: Tomographic ICG-A after PDT reveals persistence of CNV and/or the feeder vessel and a reduction in perfusion within the entire photosensitized area, including the surrounding choroid. Repair mechanisms occur slowly in neovascular and normal choroidal structures.     

Veränderungen neovaskulärer Membranen und normaler Aderhautgefäße nach mehrfacher photodynamischer Therapie

PURPOSE: ICG angiography (ICGA) was used to document the effect of repeated PDT (verteporfin) on size and leakage of choroidal neovascularisation in age-related macular degeneration (AMD) and treatment-related side effects on the choroid. METHODS: Forty-two patients were followed over 24 months in a clinical trial for PDT in AMD. The ICGAs were performed every 3 months with a confocal laser scanning system. Patients received repeated verteporfin treatment. At each control visit, the patients were retreated if leakage was present in fluorescein angiography (FA). RESULTS: A continuous, highly significant reduction in CNV size and leakage area was found over 24 months. The initial CNV size dropped by 23% from 3.86 mm2 to 2.98 mm2. The leakage area in the late phase of the angiogram decreased by 30.3% from 5.0 mm2 to 3.5 mm2. A significant side effect of PDT on the choroid was documented by an increased hypofluorescent area in ICGA. The maximum size of the hypofluorescent area was reached after 12 months. At month 24, the choroidal fluorescence showed recovery in respect to area and intensity of fluorescence. But hypofluorescence surrounding the CNV lesion was already present in 40 out of 42 eyes before treatment. CONCLUSION: The ICGA confirms that repeated PDT treatments lead to a significant reduction in CNV size and leakage area over as long as 2 years. CNV lesions are surrounded by choriocapillary hypofluorescence in ICGA. PDT causes further hypoperfusion of the choroid but in the long-term significant recovery of choroidal perfusion was shown.