gms | German Medical Science

Reticular pseudodrusen (RPD) have been identified as a risk factor for late age-related macular degeneration (AMD) [1], [2], [3]. RPD can be visualized on blue-channel fundus photography and near infrared, red-free or autofluorescence images obtained with a scanning laser ophthalmoscope (SLO) [4]. On spectral domain optical coherence tomography (SDOCT), subretinal hyperreflective material is seen in those eyes. Histologically, RPD are corresponding to subretinal drusenoid deposits [5].

Choroidal thinning in eyes with RPD and early AMD as well as the localization of RPD related to choroidal watershed zones suggest involvement of the choroid and a possible influence of choroidal hypoxia for pathogenesis [6], [7].

Querques et al. recently analysed progression and fading of single RPD on SDOCT in eyes with dry AMD, suggesting that RPD are dynamic structures [8].

In our case series, we describe nearly complete disappearance of RPD on SDOCT and infrared images during long-term follow-up in AMD patients with and without choroidal neovascularisation (CNV), and demonstrate asymmetrical behaviour in both eyes.

SDOCT and infrared images of 4 patients with RPD, who were examined during retina clinic at the Department of Ophthalmology at the University of Cologne, were collected. The presence of RPD on infrared images as well as the presence of subretinal drusenoid deposits on SDOCT volume scans was evaluated on all available follow-up images. Ophthalmic history including history of intravitreal injections was reviewed. This study adhered to the tenets set forth in the Declaration of Helsinki.

A 79-year-old male presented with decrease in vision in his left eye due to neovascular AMD. His right eye showed dry AMD with RPD (Figure 1A [Fig. 1]), his left eye predominantly classic CNV and RPD (Figure 1B [Fig. 1]). Visual acuity was 20/25 in the right and 20/100 in the left eye. The left eye was treated with 13 intravitreal ranibizumab injections over 35 months. His right eye did not develop CNV during follow-up and did not receive any therapy. Twenty-five months after baseline, the subretinal deposits on SDOCT started to disappear in the right eye. After 35 months, nearly all RPD in the macular area had disappeared on the infrared image and the photoreceptor layer in this area appeared disturbed on SDOCT (Figure 1C [Fig. 1]). In the left eye, RPD appeared stable during follow-up (Figure 1D [Fig. 1]).

A 68-year-old female presented with neovascular AMD in her left eye. Her right eye showed dry AMD and few RPD (Figure 2A [Fig. 2]), her left eye occult CNV without RPD (Figure 2B [Fig. 2]). Visual acuity was 20/32 in the right and 20/400 in the left eye. After 23 months, the number of RPD had increased in the right eye (Figure 2C [Fig. 2]). One month later, the right eye developed occult CNV and was treated with intravitreal ranibizumab. At 29 months follow-up, the number of RPD had decreased. After 9 injections of ranibizumab, 43 months after baseline, no subretinal deposits were visible on SDOCT scans, only few RPD were present near the superior vascular arcade on infrared images (Figure 2E [Fig. 2]). The left eye was treated with a total of 10 injections and SDOCT scans did not show RPD during follow-up (Figure 2D, 2F [Fig. 2]).

A 80-year-old male presented with neovascular AMD with predominantly classic CNV and few RPD on his right eye (Figure 3A [Fig. 3]) and dry AMD and RPD in his left eye (Figure 3B [Fig. 3]). Visual acuity was 20/32 in the right and 20/50 in the left eye. The right eye received 22 intravitreal ranibizumab injections during 47 months follow-up, RPD remained stable (Figure 3C [Fig. 3]). Thirty-two months after baseline, the left eye developed predominantly classic CNV. At 43 months follow-up, after 5 injections of ranibizumab, RPD started to disappear. No further injections were required. After 47 months, RPD had nearly completely disappeared on infrared imaging and only few remaining subretinal deposits were visible on SDOCT (Figure 3D [Fig. 3]).

A 81-year-old female presented with dry AMD and RPD in her right eye (Figure 4A [Fig. 4]) and predominantly classic CNV and RPD in her left eye (Figure 4B [Fig. 4]). Visual acuity was 20/20 in the right and 20/40 in the left eye. RPD in the right eye remained approximately stable during follow-up (Figure 4C [Fig. 4]). The left eye showed a decrease of RPD at 22 months follow-up after 12 ranibizumab injections. After 47 months, following 25 intravitreal injections, progressive decrease of RPD and subretinal deposits was detected on infrared and SDOCT images (Figure 4D [Fig. 4]).

RPD were first described on color fundus photography in 1990 [9]. SDOCT imaging allows a more detailed analysis of pathological changes in eyes with RPD [10], leading to a new definition and staging system of the disease [5]. Pumariega et al. described fading of RPD on color fundus photographs in eyes with and without CNV over a three-year period [11]. Smith et al. detected fading of RPD in cases with CNV on infrared images using a SLO [2]. Querques et al. reported progression followed by fading of singular subretinal deposits on SDOCT images [8].

The reported changes suggest that RPD are dynamic structures. Progression and fading of single subretinal deposits may result in changes of the RPD-pattern on infrared images, however, complete disappearance of RPD may rather be explained by external influencing factors such as inflammatory stimuli following intravitreal injections or ophthalmic surgery as described for soft drusen [12].

In three of our 4 reported patients, RPD disappeared after CNV occurrence and treatment. One patient showed disappearance of RPD without CNV development or treatment for other ophthalmic diseases, indicating that CNV development, intravitreal injections or surgery may not fully explain this finding. In addition, all 4 cases show only unilateral disappearance of RPD.

Outer retinal atrophy with thinning of the photoreceptors and loss of the ellipsoid band has been described previously following regression of RPD [13]. In accordance with this, outer retinal alterations and thinning are visible in three of our cases after RPD regression.

A limitation of the detection of progression and regression of RPD on SDOCT is a possible misalignment of SDOCT scans during follow-up [14]. Fading of individual RPD may be misinterpreted, if e.g. RPD are located between two B-scans in the following SDOCT examination. However, it seems unlikely that all RPD visible on one visit are not captured on another visit. Further, a gradual decrease of subretinal deposits was detected over a long follow-up time corresponding to a decrease of RPD on infrared images. Therefore, fading of RPD in our cases is more likely than missing detection caused by misalignment of OCT scans.

In summary, high resolution SDOCT and infrared imaging allow to identify various stages of RPD and to follow their course over time. The reason for progression or fading or RPD as well as for the asymmetrical behaviour of these changes remains unclear. Careful attention to RPD in clinical practice and studies with a larger cohort of patients and long-term follow-up may help to understand reasons for progression and regression of RPD and to analyse their role in AMD.

Tina Schick received honoraria for presentations by Novartis Pharma, Germany. Lebriz Ersoy: none. Bernd Kirchhof: none. Sandra Liakopoulos served as a consultant for Novartis Pharma and received honoraria for presentations by Novartis Pharma and Heidelberg Engineering, Germany.

Supported in part by the Ilse Palm-Foundation, Germany.