Cells of the retinal pigment epithelium (RPE) play an important rolein the formation of epiretinal membranes after retinal detachment.1 The RPE cells may access the inner retinal surfacethrough the retinal break that caused the detachment. Subsequent proliferationof these cells on the retinal surface then contributes to the formation ofthe epiretinal membranes, which typically consists of a variety of differentcell types.
A second mechanism by which the RPE cells might access the inner retinalsurface is by migration through the retina. The ability of proliferating RPEcells to migrate is well documented and can be altered by the cells' microenvironment.2-5 Proliferationof RPE cells occurs not infrequently after trauma and after retinal detachmentrepair.6,7 Experimentalmodels of retinal detachment show that the RPE cell proliferation begins earlyin the course of the detachment and is confined to the region of the detachment.8,9 Translocation of RPE pigmentinto the retina occurs in some diseases such as retinitis pigmentosa ("bonespicula") as well as in experimental models of subretinal pigment clumping.10,11
The advent of optical coherence tomography (OCT) has provided an opportunityto obtain high-resolution, cross-sectional images of the retina and RPE ina variety of disease states. Optical coherence tomography provides an indirectimage of the retina and RPE based on the reflective properties of the variouscellular layers. The varying intensities seen on the OCT scan correlate wellwith the different levels of the retina and RPE.12 TheRPE provides the most highly reflective surface, and usually appears as abright orange-red layer on the OCT scan. In this article we report 2 casesof retinal detachment with subsequent migration of RPE cells into the retina.Optical coherence tomographic scans in both of these patients showed highlyreflective material that was consistent with RPE proliferation and migrationthrough the retina into the region of secondary epiretinal membranes. Thesefindings suggest that the transretinal migration of proliferating RPE cellsmay have played a role in the formation of epiretinal membranes in these patients.
A 52-year-old man was initially seen with progressive loss of visionin the right eye over the previous 6 days. Ophthalmic examination was significantfor visual acuity of counting fingers OD at 1 ft and 20/20 OS. Dilated fundusexamination of the pseudophakic right eye showed a near-total retinal detachmentwith a single horseshoe retinal tear at the 12:30-o'clock position. The detachmentwas repaired with pars plana vitrectomy, retinotomy with internal drainageof subretinal fluid, endolaser photocoagulation, and a perfluoropropane fluid–airgas exchange (12%) followed by facedown positioning. At the 1-month postoperativevisit, visual acuity was 20/200 OD and subretinal pigment clumping was evidentin the macula. Three months after the retinal detachment repair, the visualacuity had improved to 20/40 OD. There was consolidation of the subretinalpigment clumps (Figure 1A). TheOCT scan showed highly reflective spots emerging from the RPE and extendinganteriorly into the retina (Figure 1B).These intraretinal spots had the same reflective intensity as the RPE andwere found in the same location as the RPE pigment seen on the fundus photograph.Mild patches of glistening on the retinal surface suggested early epiretinalmembrane formation.
A 44-year-old man was initially seen in our clinic 6 weeks after primaryrepair of an open-globe injury with a nonclearing vitreous hemorrhage andretinal detachment. The patient underwent pars plana vitrectomy. During perfluoropropanefluid–air gas exchange, a large mobile pigment plaque was observed inthe subretinal space in the superior midperiphery. Over the next 7 months,the patient developed an epiretinal membrane over the macula that extendedwell beyond the vascular arcades. During subsequent membrane peeling, it wasnoted that the posterior surface of the epiretinal membrane was focally pigmentedwhere it was peeled from over the pigment plaque. Postoperatively, OCT ofthe area of pigmentation showed a highly reflective plane emerging from theRPE toward the retinal surface and ending at the point where the epiretinalmembrane was separated (Figure 2).
The RPE cell migration has been proposed as a contributing factor inthe formation of epiretinal membranes and proliferative vitreoretinopathy.Access to the inner retinal surface by the RPE cells in rhegmatogenous retinaldetachments usually occurs through the retinal break. The RPE cell migrationthrough the retina has been postulated to contribute to this process. Thepatients described earlier had pigment migration suspected on clinical examinationand confirmed on OCT imaging. The migration of RPE cells occurred in temporalassociation with the formation of epiretinal membranes. The second patient,in particular, had a proven communication between the epiretinal membraneand a pigment patch that originated in the subretinal space. In both casesthere were other mechanisms for RPE cell access to the inner retinal surface.However, the presence of pigment both in the subretinal space and within theretina strongly suggests migration of RPE cells into and across the retina.To our knowledge, this is the first clinical study to confirm RPE pigmentmigration in vivo using OCT. Although not proved by our cases, we postulatethat this type of transretinal migration of RPE cells may be a contributingfactor in the formation of selected epiretinal membranes.
The authors have no relevant financial interest in this article.
This study was supported in part by a Career Development Award fromResearch to Prevent Blindness Inc, New York, NY (Dr Zacks).
Corresponding author: David N. Zacks, MD, PhD, Retina Service, KelloggEye Center, University of Michigan Medical School, 1000 Wall St, Ann Arbor,MI 48105 (e-mail: davzacks@umich.edu)
1.Green
WRSebag
J Vitreoretinal interface. Ryan
SJWilkinson
CP
IIIeds.
Retina. StLouis, Mo: Mosby– Year Book Inc2001;1882- 1960
Google Scholar 2.Campochiaro
PAJerdan
JAGlaser
BMCardin
AMichels
RG Vitreous aspirates from patients with proliferative vitreoretinopathystimulate retinal pigment epithelial cell migration.
Arch Ophthalmol. 1985;1031403- 1405
PubMedGoogle ScholarCrossref 5.Hogg
PAGrierson
IHiscott
P Direct comparison of the migration of three cell types involved inepiretinal membrane formation.
Invest Ophthalmol Vis Sci. 2002;432749- 2757
PubMedGoogle Scholar 6.Crouch
ERApple
DJ Posttraumatic migration of retinal pigment epithelial melanin.
Am J Ophthalmol. 1974;78251- 254
PubMedGoogle Scholar 8.Machemer
RLaQua
H Pigment epithelium proliferation in retinal detachment (massive periretinalproliferation).
Am J Ophthalmol. 1975;801- 23
PubMedGoogle Scholar 9.Anderson
DHStern
WHFisher
SKErickson
PABorgula
GA The onset of pigment epithelial proliferation after retinal detachment.
Invest Ophthalmol Vis Sci. 1981;2110- 16
PubMedGoogle Scholar 11.Crafoord
SKopp
EDSeregard
SAlgvere
PV Cellular migration into neural retina following implantation of melaningranules in the subretinal space.
Graefes Arch Clin Exp Ophthalmol. 2000;238682- 689
PubMedGoogle ScholarCrossref 12.Chauhan
DSMarshall
J The interpretation of optical coherence tomography images of the retina.
Invest Ophthalmol Vis Sci. 1999;402332- 2342
PubMedGoogle Scholar