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By Cheryl Guttman

Fort Lauderdale, FL — Fundus autofluorescence (AF) imaging shows promise as a prognostic tool in patients with both early and advanced age-related macular degeneration (AMD), according to preliminary reports presented at the annual meeting of the Association for Research in Vision and Ophthalmology.

AF imaging uses a confocal scanning laser ophthalmoscope (Heidelberg Engineering) to detect accumulations of lipofuscin granules in RPE cells. The technique is being used to characterise the spatial distribution and intensity of the lipofuscin-derived autofluorescence in vivo.

Preliminary results from ongoing studies suggested certain patterns of AF in eyes with early AMD might be associated with risks for progression to geographic atrophy or exudative choroidal neovascularisation, whereas AF subtypes in eyes with advanced atrophic AMD might be predictive of geographic atrophy progression rates.

“AF imaging gives information over and above conventional imaging techniques, such as fundus photography or fluorescence angiography. It allows visualisation of metabolic changes at the level of the RPE and identification of areas at high risk for development of functional loss,” said Frank G Holz MD, Co-ordinator of the Fundus Autofluorescence in Age-related Macular Degeneration (FAM) Study Group who is also Head of the Vitreoretinal Service at the Department of Ophthalmology, University of Heidelberg.

The study of eyes with early stage AMD included 65 patients aged 56 to 86 years who were followed at six-month intervals with AF images plus a detailed ophthalmological exam which included fundus photography and ETDRS visual acuity. Eligible eyes had large soft drusen, visual acuity 20/100 or better, and no previous laser treatment.
The AF images obtained at baseline were categorised by a pattern of disturbed AF into four groups: eyes with an annular pattern of increased AF, eyes with confluent patches of increased AF, eyes with central spots of increased AF, and diffusely increased AF.
AF imaging may help predict AMD

During the follow-up period, which ranged from six to 25 months, two patients developed geographic atrophy, and both eyes were noted at baseline to have diffuse increased AF. In addition, two patients developed an exudative AMD. Both of those eyes exhibited confluent patches at baseline.

“From these findings we suggest confluent patches may predict development of the exudative form of AMD and patients with pattern-like AF may be at risk from geographic atrophy.

“However, our follow-up is relatively short and we will continue to monitor this group to determine whether this technique truly has predictive value. Perhaps this might be a useful tool for defining risk factors for disease progression that could lead patients to earlier treatment and a better outcome,” said Wilma Einbock MD, University of Leipzig.

The study of patients with advanced atrophic AMD included 462 eyes from 277 patients who were classified into eight groups based on the AF phenotypic patterns in the junctional zone of geographic atrophy.

Five distinct patterns of AF were identified: none, focal, banded, patchy homogenous, and diffuse. The diffuse pattern included four subtypes: reticular, branching, fine granular, and fine granular with punctate peripheral spots.
At baseline, diffuse branching was the most common AF type (96 eyes), followed by banded (50 eyes) and fine granular (49 eyes). There were 26 eyes with no abnormal AF outside of the geographic atrophy area, while each of the other AF types was present in 15 or fewer eyes.

A total of 44 eyes were followed for increase in the area of atrophy over a period of one to five years. During that time, eyes with banded and focal AF displayed the slowest rate of size progression, 10% per year and 13% per year, respectively, while those with patchy homogenous AF showed the greatest increase in area of involvement at 343% per year.

No other group showed such a high annual progression rate. Among the eyes with diffuse fine granular AF, atrophy spread by about 30% per year, while in eyes with any of the other diffuse subtypes as well as those with focal AF, the relative annual progression rates ranged from 16% to 18%.

“Previous studies with AF show it is superior to fundus photography or angiography for delineating areas of geographic atrophy. In addition, we have found that eyes with AMD display variability in AF changes in the junctional zone and that increased AF may precede the development or spread of GA over time.

“Our current findings suggest some prognostic significance for predicting vision loss associated with different patterns of AF. Fundus AF in geography atrophy seems to be very interesting — not only for monitoring future therapies aimed to slow geographic atrophy progression, but also for giving prognostic significance,” said Steffen Schmitz-Valckenberg MD, Department of Ophthalmology, University of Heidelberg.

He added that among the various AF types, the patchy homogenous pattern is associated with the presence of the largest areas of increased AF. As lipofuscin is the fluorophore detected with AF, it seems to be a reasonable hypothesis that excessive lipofuscin accumulation might play an important role in the pathogenesis of RPE cell death in eyes with geographic atrophy related to AMD, said Dr Schmitz-Valckenberg.

None of the researchers mentioned in this article has any financial interest in Heidelberg Engineering.

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