Morphological versus functional photoreceptor viability of retinal pigment epithelium tears

Abstract

Editor, Retinal pigment epithelium tears (RPE tears) are a serious complication in patients with age-related macular degeneration (AMD) leading to a loss of photoreceptors. Previously, we have shown that the photoreceptors can be rescued and function restored by autologous transplantation of RPE and choroid in these patients (Caramoy et al. 2011a). We have also described previously that the morphological signs of viable photoreceptors can be seen in the area of pigment epithelium tears up to 325 days (Caramoy et al. 2011b), however little is known about the function of these photoreceptors in the area without retinal pigment epithelium. In a retrospective study, we examined the morphology of RPE tears using spectral-domain optical coherence tomography (SD-OCT) (Spectralis HRA + OCT; Heidelberg Engineering, Heidelberg, Germany) in relation to its function in microperimetry (MP1; Nidek Technologies, Padova, Italy). Mean age was 76 ± 7.9 years (range 63–85 years) and mean best corrected visual acuity was 0.54 ± 0.37 LogMAR. Among the seven patients, three were men and four were women. Four patients showed unstable fixation. Relatively unstable and stable fixations were seen in two patients and in one patient, respectively. In the patient with stable fixation, the fovea was still supported by pigment epithelium. The fixation stability (percentage of fixation within the central 2° and 4°) was 42 ± 29.65% and 75 ± 19.61%, respectively. Among these patients, morphological signs of viable photoreceptors were seen in four of seven patients, that is junction of inner and outer photoreceptor segments, external limiting membrane and nonatrophic outer nuclear layer. Time from RPE tear to OCT and microperimetry in these patients was <30 days in two patients, 21 and 109 days in the other two. These signs were not seen in three of seven patients because of retinal atrophy. Time from RPE tear to OCT and microperimetry in these three patients was <30 days in two patients and 717 days in one patient. Subretinal fluid was seen in the RPE denuded area in five of seven patients. Independent of these morphological signs of viable photoreceptors and independent of subretinal fluid presence, all patients showed an absolute scotoma in the RPE denuded area (Fig. 1). Mean retinal sensitivity among this region was 0.07 ± 0.1 dB. Microperimetry and spectral-domain optical coherence tomography of a pigment epithelium tear. A dense absolute scotoma is seen in the region without retinal pigment epithelium support in microperimetry (A). However, the corresponding spectral-domain optical coherence tomography shows signs of viable photoreceptors (B and C). Identifying signs of viable photoreceptors in the wrinkled RPE region was challenging. The retina in this region was thin; its anatomical layers could not be visualized closely. In this region, mean retinal sensitivity was 0.89 ± 1.20 dB. Unlike the RPE denuded area, which exhibited a dense absolute scotoma, the region of wrinkled RPE was more heterogenous. It consisted of areas of relative and absolute scotoma. The results from our study underlined the importance of the RPE regarding visual function. In normal retina, the RPE is essential in the visual cycle towards regenerating visual pigments in cones and rods. Kühne (1878) found in bleached frog retina that rhodopsin could only regenerate partially, if the retina was detached from the retinal pigment epithelium. Weinstein et al. (1967) have also shown that no rhodopsin regeneration is observed in rat retina perfused with enriched medium detached from retinal pigment epithelium. Photoreceptors lose their functions after separation from the pigment epithelium as shown by microperimetry. But they still show signs of viability in SD-OCT. These morphological signs seem to be correct as shown by the above-mentioned recovery of photoreceptors after transplantation of RPE and choroid. These findings emphasize the importance of RPE for photoreceptors towards regenerating visual pigments, which are crucial for the visual function.