Aim: To describe and classify patterns of abnormal fundus autofluorescence (FAF) in the junctional zone of geographic atrophy (GA) in patients with age related macular degeneration. Methods: Digital FAF images were recorded in 164 eyes of 107 patients using a confocal scanning laser ophthalmoscope (cSLO; excitation 488 nm, detection above 500 nm) as part of a prospective multicentre natural history study (FAM Study). FAF images were obtained in accordance with a standardised protocol for digital image acquisition and generation of mean images after automated alignment. Results: Image quality was sufficient for classification of FAF patterns in 149 eyes (90.9%) with lens opacities being the most common reason for insufficient image quality. Abnormal FAF outside GA in 149 eyes was classified into four patterns: focal (12.1%), banded (12.8%), patchy (2.0%), and diffuse (57.0%), whereby 12.1% had normal background FAF in the junctional zone. In 4% there was no predominant pattern. The diffuse pattern was subdivided into four groups including reticular (4.7%), branching (27.5%), fine granular (18.1%), and fine granular with peripheral punctate spots (6.7%). Conclusions: Different phenotypic patterns of abnormal FAF in the junctional zone of GA can be identified with cSLO FAF imaging. These distinct patterns may reflect heterogeneity at a cellular and molecular level in contrast with a non-specific ageing process. A refined phenotypic classification may be helpful to identify prognostic determinants for the spread of atrophy and visual loss, for identification of genetic risk factors as well as for the design of future interventional trials.

Background: Macular hole surgery including vitrectomy and peeling of epiretinal membranes and the internal limiting membrane (ILM) has become a standard procedure in retinal surgery. Poor visualization of epiretinal membranes and the ILM is an obstacle to successful surgery. Recently, indocyanine green (ICG) has been reported to be a helpful intraocular substance in identifying these membranes. Methods: In a case of stage IV macular hole, epiretinal membranes and ILM were intraoperatively stained with three drops of 1:9 diluted ICG. After 1 min incubation the vitreous cavity was rinsed with Ringer's lactate solution, and the membranes were peeled. Autologous thrombocytes were applied to the macular hole, and the eye was endotamponaded with 20% SF6 gas. Six weeks postoperatively, visual acuity was measured and fundus photographs and autofluorescence images, as well as a multifocal ERG, were obtained. Results: Intraoperatively, the ILM could be nicely visualized by ICG, which allowed immediate peeling. Six weeks after surgery, the visual acuity had improved from 0.1 to 0.7 and the macular hole was closed. Autofluorescence imaging at 795 nm revealed a strong signal. Multifocal ERG recording showed regular amplitudes. Conclusion: ICG as an intraocular tool for staining of the ILM is helpful in macular hole surgery. We did not observe any negative effect on retinal function; however, we were surprised to identify traces of ICG in retinal fluorescein angiography images 6 weeks postoperatively.

The high correlation of NIR fluorescence and reflectance indicated that part of the observed NIR fluorescence is pseudofluorescence, whereas gray-scale analysis indicated that both NIR autofluorescence and pseudofluorescence contribute to the NIR fluorescence images. Quantification of leakage of the imaging system indicated a significant part of the observed NIR fluorescence is NIR autofluorescence. As NIR fluorescence derives from pigmented lesions, melanin is a possible source if NIR reflectance is also increased. Comparison with blue-light-excited autofluorescence showed differences between AMD and patients with nevi. NIR autofluorescence was also detected in single cases of maculopathy without corresponding NIR reflectance.

BackgroundAge-related macular degeneration (AMD) is a prevalent cause of blindness in Western societies. Variants in the genes encoding complement factor H (CFH), complement component 3 (C3) and age-related maculopathy susceptibility 2 (ARMS2) have repeatedly been shown to confer significant risks for AMD; however, their role in disease progression and thus their potential relevance for interventional therapeutic approaches remains unknown.Methodology/Principal FindingsHere, we analyzed association between variants in CFH, C3 and ARMS2 and disease progression of geographic atrophy (GA) due to AMD. A quantitative phenotype of disease progression was computed based on longitudinal observations by fundus autofluorescence imaging. In a subset of 99 cases with pure bilateral GA, variants in CFH (Y402H), C3 (R102G), and ARMS2 (A69S) are associated with disease (P = 1.6×10−9, 3.2×10−3, and P = 2.6×10−12, respectively) when compared to 612 unrelated healthy control individuals. In cases, median progression rate of GA over a mean follow-up period of 3.0 years was 1.61 mm2/year with high concordance between fellow eyes. No association between the progression rate and any of the genetic risk variants at the three loci was observed (P>0.13).Conclusions/SignificanceThis study confirms that variants at CFH, C3, and ARMS2 confer significant risks for GA due to AMD. In contrast, our data indicate no association of these variants with disease progression which may have important implications for future treatment strategies. Other, as yet unknown susceptibilities may influence disease progression.

In our series rapid improvement of visual function was observed in one patient only, even if the macula appeared ophthalmoscopically and angiographically normal. Vitreoretinal complications occurred frequently during follow-up.