Response to Talks et al

Abstract

Sir, We would like to thank Talks et al1 for their interest in our article entitled ‘High-dose ranibizumab therapy for vascularized pigment epithelial detachment'2 and their letter to the editor that questions the presence of vascularized retinal pigment epithelial detachment (PED) in the three published cases. Although we understand their concern, we stand by our classification of PED in these three cases. Our study has incorporated strict inclusion and exclusion criteria as well as multi-modal imaging for patient enrollment and assessment of the fundus lesions throughout the study. The classification of PED is complicated and requires a historical overview. Serous PEDs are well circumscribed lesions that fill rapidly and homogeneously on fluorescein angiography (FA) and that fail to show any overt signs of CNV.3 Gass4 defined a vascularized serous PED as a serous PED with overt signs of CNV such as a hot spot or a notch. In Figures 1 and 2, a large serous PED component is certainly present but there is high suspicion for a CNV focus by virtue of the irregular fluorescence (which shows focal leakage and a hot spot in the late phase of the FA) present at the nasal edge of the PED in Figure 1 and the presence of a hot spot at the temporal edge of the serous PED in Figure 2. Moreover, the serous PED is large and irregular in each case and cystoid macular edema and subretinal fluid (SRF) are present with optical coherence tomography (OCT) imaging, consistent with the presence of an underlying CNV focus. The presence of a cluster of hard exudates along the temporal margin of the PED in Figure 2 further supports the presence of CNV underlying the PED in case 2. Thus, the findings of multi-modal imaging are consistent with the diagnosis of a vascularized serous PED for both cases 1 and 2. We further make the distinction of a vascularized serous PED vs a fibrovascular PED in which an RPE detachment is present but a distinct serous PED is not identified. A fibrovascular PED was defined during the course of the Macular Photocoagulation Study5 and the subsequent Treatment of Age-Related Macular Degeneration With Photodynamic Therapy Investigation and Verteporfin in Photodynamic Therapy Trial6 as an area of RPE elevation with stippled hyperfluorescence and late staining on FA.5 Indeed, in case 3 the authors were able to identify stippled filling of the PED with an obvious leaking ‘hot spot' on the FA (that likely represents a RAP lesion), and SRF was noted with the PED on OCT, all leading to the diagnosis of a fibrovascular PED associated with a RAP lesion for case 3. Please note that all PEDs were classified by the lead author. Each of these readings was then confirmed, independent of the original grade, by one of our co-authors (DS), who reanalyzed all FP, FA, indocyanine-green, and OCT images to ensure consistency. Any lesions with discordant readings were disqualified. Owing to the space limitation, we could only include a few selected images for the cases in our publication. In response to the letter by Talk et al, we have also obtained an independent review of our three cases by Dr Michael Ip at the Fundus Photograph Reading Center at the University of Wisconsin, who agreed with our classification and assessment of all three cases. Although these three cases of PED responded well to a high dose of ranibizumab, we do not wish to make any conclusions regarding the efficacy and safety of high-dose ranibizumab therapy until the results of our prospective study are released.