8.5Spectral Domain Optical Coherence Tomography in Geographic Atrophy

Spectral-domain optical coherence tomography (SD-OCT) has provided additional insights into the microstructural alterations associated with GA [37– 44]. SD-OCT imaging revealed a wide spectrum of morphological abnormalities, both in the surrounding retinal tissue and in the atrophic area. These alterations may reflect different disease stages or, alternatively, heterogeneity on a cellular and molecular level. Additionally, simultaneous recording of cSLO and SD-OCT images in one instrument with an exact topographic overlay during image acquisition allows for accurate orientation of cross sectional SD-OCT-scans at anatomic sites of interest, and, furthermore, serial examinations at the same location over time [38, 41]. Using this technology, the dynamic nature of development and progression of atrophy can be longitudinally analyzed in the same eye on a three-dimensional level. Microstructural changes such as the advancing loss of the RPE and photoreceptor bands at the GA border or the subsequent apposition of the outer plexiform layer

with Bruch’s membrane within the atrophic lesion have been recently described (Fig. 8.5). Of note, these observations can be made within a relatively short period of time [30]. This approach may be helpful both for monitoring the natural course of the disease and to elucidate pathogenetic mechanisms. In particular, the identification of structural risk factors reflecting disease activity and future GA progression may be important for prognosis and visual function. Furthermore, effects of pharmacological interventions on the border zone may be evaluated in the future.

8.6Quantification

of Atrophy Progression

Initial quantitative data on spread of atrophy were published by Schatz and McDonald in 1989 [45]. They showed in fundus photographs of 50 eyes an average growth rate of 139 mm/year in the horizontal direction.

To date, there are data from five large natural history studies exploring the progression of GA: the Geographic Atrophy Study (GAS) conducted by Janet Sunness and co-workers, the FAM-Study, the Beaver

OPL

ONL

ELM(1)

IPRL(2)

RPE/BM(4)

Baseline

OPL

ONL

ELM(1)

IPRL(2)

RPE/BM(4)

10 months

OPL

ONL

ELM(1)

IPRL(2)

RPE/BM(4)

14 months

Fig. 8.5 Progression of preexisting geographic atrophy (GA) visualized by serial spectral-domain OCT imaging (14 months follow-up). There is marked enlargement of the atrophic area over time with progressive loss of the RPE layer (inner part of band 4), IPRL (band 2,) and ELM (band 1), respectively, and thinning of ONL at the border of atrophy. Within the atrophic lesion, the remaining part of band 4 becomes more homogenous and the ONL progressively thins; subsequently, the OPL approaches the remaining part of band 4 (assumed Bruch’s membrane). OPL outer plexiform layer, ONL outer nuclear layer, ELM external limiting membrane (band 1), IPRL interface of the inner and outer segments of the photoreceptor layer (band 2), RPE/BM retinal pigment epithelium/Bruch’s membrane complex (band 4) (Copyright ARVO.org. Fleckenstein et al. [38])

Dam Eye Study, the ARED-Study, and the Natural History of Geographic Atrophy Progression (GAP) Study (Table 8.1).

Sunness et al. in 1999 [6] and 2007 [46, 47] reported GA progression rates based on serially acquired fundus photographs. The mean GA enlargement rate was 2.6 mm2/year (median 2.2 mm2/year) in 212 eyes (131 patients) over a median follow-up time of 4.3 years. There was a great difference and range in atrophy enlargement within the cohort, ranging from 0 to 13.8 mm2/year. Eyes were classified into five different groups according to the total size of atrophy at baseline and the enlargement rate of the atrophy increased with increasing baseline atrophy for up to 5 disc areas (DA) of baseline atrophy, leveled off for the 5–10 DA group and slightly decreased for the >10 DA group. They reported that the strongest predictor of subsequent growth of GA, however, is growth in the previous 2 years and that there is high correlation between the enlargement rates in the two eyes of patients with bilateral GA.

The FAM-Study reported a slower mean progression rate of 1.74 mm2/year (median 1.52 mm2/year) in 195 eyes (129 patients) over a median follow-up time of 1.8 years [33, 34]; these measurements were based on serial FAF images. It could be confirmed that the slowest atrophy progression was found to be in the eyes with a total baseline atrophy of <1 DA, but no statistical significant difference in atrophy enlargement was shown for the other DA groups. Hence, the great difference and range in atrophy enlargement that was also seen within their cohort could not be explained by baseline atrophy size alone. Interestingly, variable rates of GA progression were associated with specific phenotype of abnormal FAF pattern at baseline (see 8.4 [48]).

The Beaver Dam Eye Study in 2008 showed in fundus photographs of 53 eyes (32 patients) a mean progression rate of 1.3 mm2/year over a median fol- low-up time of 5 years [49], and in 2009, the AREDStudy reported, also based on fundus photographs, a median progression rate of 1.71 mm2/year over a median follow-up of 6 years [50].

The ARED-Study also found that baseline GA size is an important predictor of subsequent GA growth. Furthermore, it was shown that a linear model of GA growth is superior to a quadratic model. These results are in accordance to that reported by the FAM-Study [34, 51]: The linear model provides a better prediction of growth than nonlinear models, but the nonlinear model provides better agreement with assumptions.