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.     

Effectiveness of averaging strategies to reduce variance in retinal nerve fibre layer thickness measurements using spectral-domain optical coherence tomography

Background

Automated detection of subtle changes in peripapillary retinal nerve fibre layer thickness (RNFLT) over time using optical coherence tomography (OCT) is limited by inherent image quality before layer segmentation, stabilization of the scan on the peripapillary retina and its precise placement on repeated scans. The present study evaluates image quality and reproducibility of spectral domain (SD)-OCT comparing different rates of automatic real-time tracking (ART).

Methods

Peripapillary RNFLT was measured in 40 healthy eyes on six different days using SD-OCT with an eye-tracking system. Image brightness of OCT with unaveraged single frame B-scans was compared to images using ART of 16 B-scans and 100 averaged frames. Short-term and day-to-day reproducibility was evaluated by calculation of intraindividual coefficients of variation (CV) and intraclass correlation coefficients (ICC) for single measurements as well as for seven repeated measurements per study day.

Results

Image brightness, short-term reproducibility, and day-to-day reproducibility were significantly improved using ART of 100 frames compared to one and 16 frames. Short-term CV was reduced from 0.94?±?0.31 % and 0.91?±?0.54 % in scans of one and 16 frames to 0.56?±?0.42 % in scans of 100 averaged frames (P?≤?0.003 each). Day-to-day CV was reduced from 0.98?±?0.86 % and 0.78?±?0.56 % to 0.53?±?0.43 % (P?≤?0.022 each). The range of ICC was 0.94 to 0.99. Sample size calculations for detecting changes of RNFLT over time in the range of 2 to 5 μm were performed based on intraindividual variability.

Conclusion

Image quality and reproducibility of mean peripapillary RNFLT measurements using SD-OCT is improved by averaging OCT images with eye-tracking compared to unaveraged single frame images. Further improvement is achieved by increasing the amount of frames per measurement, and by averaging values of repeated measurements per session. These strategies may allow a more accurate evaluation of RNFLT reduction in clinical trials observing optic nerve degeneration.     

The role of choroidal hypoperfusion associated with photodynamic therapy in neovascular age-related macular degeneration and the consequences for combination strategies

The clinical benefits of verteporfin therapy have been documented in a wide variety of patients with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD), and there is encouraging evidence of improved outcomes when this angioocclusive modality is combined with antiangiogenic agents. Although the clinical benefits of verteporfin mono- and combination therapy are well established, there has been concern that treatment with verteporfin results in hypoperfusion in the treated area and that concomitant use of antiangiogenic agents could prolong this effect. However, despite well-documented occurrences of hypoperfusion on fluorescein and indocyanine green angiography, there is little evidence of associations with functional impairment or other adverse effects. It has also been suggested that hypoperfusion might actually help to reduce recanalization of CNV and permit neuronal recovery by decreasing exposure to oxygen and oxidative radicals. The reduced need for frequent retreatments clearly has a major appeal due to the lower costs associated with fewer interventions and reduced burden of clinical monitoring and diagnostic reevaluations. Ongoing evaluation in randomized clinical trials will provide further clarification on the effect of verteporfin plus ranibizumab compared with ranibizumab monotherapy in terms of visual acuity, anatomical outcomes, treatment frequency, and health economics. The results of these large-scale clinical trials will provide a strong basis for determining the benefits and risks of combination therapy.     

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.