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  Vol. 122 No. 3, March 2004 TABLE OF CONTENTS
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Transretinal Pigment Migration: An Optical Coherence Tomographic Study

Arch Ophthalmol. 2004;122:406-408.

Cells of the retinal pigment epithelium (RPE) play an important role in the formation of epiretinal membranes after retinal detachment.1 The RPE cells may access the inner retinal surface through the retinal break that caused the detachment. Subsequent proliferation of these cells on the retinal surface then contributes to the formation of the epiretinal membranes, which typically consists of a variety of different cell types.

A second mechanism by which the RPE cells might access the inner retinal surface is by migration through the retina. The ability of proliferating RPE cells to migrate is well documented and can be altered by the cells' microenvironment.2-5 Proliferation of RPE cells occurs not infrequently after trauma and after retinal detachment repair.6-7 Experimental models of retinal detachment show that the RPE cell proliferation begins early in the course of the detachment and is confined to the region of the detachment.8-9 Translocation of RPE pigment into the retina occurs in some diseases such as retinitis pigmentosa ("bone spicula") as well as in experimental models of subretinal pigment clumping.10-11

The advent of optical coherence tomography (OCT) has provided an opportunity to obtain high-resolution, cross-sectional images of the retina and RPE in a variety of disease states. Optical coherence tomography provides an indirect image of the retina and RPE based on the reflective properties of the various cellular layers. The varying intensities seen on the OCT scan correlate well with the different levels of the retina and RPE.12 The RPE provides the most highly reflective surface, and usually appears as a bright orange-red layer on the OCT scan. In this article we report 2 cases of retinal detachment with subsequent migration of RPE cells into the retina. Optical coherence tomographic scans in both of these patients showed highly reflective material that was consistent with RPE proliferation and migration through the retina into the region of secondary epiretinal membranes. These findings suggest that the transretinal migration of proliferating RPE cells may have played a role in the formation of epiretinal membranes in these patients.

Report of Cases

Case 1

A 52-year-old man was initially seen with progressive loss of vision in the right eye over the previous 6 days. Ophthalmic examination was significant for visual acuity of counting fingers OD at 1 ft and 20/20 OS. Dilated fundus examination of the pseudophakic right eye showed a near-total retinal detachment with a single horseshoe retinal tear at the 12:30-o'clock position. The detachment was repaired with pars plana vitrectomy, retinotomy with internal drainage of subretinal fluid, endolaser photocoagulation, and a perfluoropropane fluid–air gas exchange (12%) followed by facedown positioning. At the 1-month postoperative visit, visual acuity was 20/200 OD and subretinal pigment clumping was evident in the macula. Three months after the retinal detachment repair, the visual acuity had improved to 20/40 OD. There was consolidation of the subretinal pigment clumps (Figure 1A). The OCT scan showed highly reflective spots emerging from the RPE and extending anteriorly into the retina (Figure 1B). These intraretinal spots had the same reflective intensity as the RPE and were found in the same location as the RPE pigment seen on the fundus photograph. Mild patches of glistening on the retinal surface suggested early epiretinal membrane formation.



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Figure 1. Case 1. A, Color fundus photograph taken 3 months after surgery. There has been consolidation of the pigment in the macula as well as development of a fine, patchy epiretinal membrane, not well visualized photographically. B, Horizontal optical coherence tomographic scan (5-mm scan length) through the central macula confirming the intraretinal location of the retinal pigment epithelial cell pigment.


Case 2

A 44-year-old man was initially seen in our clinic 6 weeks after primary repair of an open-globe injury with a nonclearing vitreous hemorrhage and retinal detachment. The patient underwent pars plana vitrectomy. During perfluoropropane fluid–air gas exchange, a large mobile pigment plaque was observed in the subretinal space in the superior midperiphery. Over the next 7 months, the patient developed an epiretinal membrane over the macula that extended well beyond the vascular arcades. During subsequent membrane peeling, it was noted that the posterior surface of the epiretinal membrane was focally pigmented where it was peeled from over the pigment plaque. Postoperatively, OCT of the area of pigmentation showed a highly reflective plane emerging from the RPE toward the retinal surface and ending at the point where the epiretinal membrane was separated (Figure 2).



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Figure 2. Case 2. A, Color fundus photograph taken after epiretinal membrane peeling showing the densely pigmented patch in the superior midperiphery. B, Vertical optical coherence tomographic scan (left-right [inferior-superior]; 5-mm scan length) through the superior pigmented patch demonstrates transretinal migration of the retinal pigment epithelial cell pigment to the retinal surface.



Comment

The RPE cell migration has been proposed as a contributing factor in the formation of epiretinal membranes and proliferative vitreoretinopathy. Access to the inner retinal surface by the RPE cells in rhegmatogenous retinal detachments usually occurs through the retinal break. The RPE cell migration through the retina has been postulated to contribute to this process. The patients described earlier had pigment migration suspected on clinical examination and confirmed on OCT imaging. The migration of RPE cells occurred in temporal association with the formation of epiretinal membranes. The second patient, in particular, had a proven communication between the epiretinal membrane and a pigment patch that originated in the subretinal space. In both cases there were other mechanisms for RPE cell access to the inner retinal surface. However, the presence of pigment both in the subretinal space and within the retina strongly suggests migration of RPE cells into and across the retina. To our knowledge, this is the first clinical study to confirm RPE pigment migration in vivo using OCT. Although not proved by our cases, we postulate that this type of transretinal migration of RPE cells may be a contributing factor 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 from Research to Prevent Blindness Inc, New York, NY (Dr Zacks).


AUTHOR INFORMATION

David N. Zacks, MD, PhD; Mark W. Johnson, MD
Ann Arbor, Mich

Corresponding author: David N. Zacks, MD, PhD, Retina Service, Kellogg Eye Center, University of Michigan Medical School, 1000 Wall St, Ann Arbor, MI 48105 (e-mail: davzacks{at}umich.edu).


REFERENCES

1. Green WR, Sebag J. Vitreoretinal interface. In: Ryan SJ, Wilkinson CP III, eds. Retina. St Louis, Mo: Mosby–Year Book Inc; 2001:1882-1960.
2. Campochiaro PA, Jerdan JA, Glaser BM, Cardin A, Michels RG. Vitreous aspirates from patients with proliferative vitreoretinopathy stimulate retinal pigment epithelial cell migration. Arch Ophthalmol. 1985;103:1403-1405. FREE FULL TEXT
3. Nguyen-Tan JQ, Thompson JT. RPE cell migration into intact vitreous body. Retina. 1989;9:203-209. WEB OF SCIENCE | PUBMED
4. Lopez PF, Yan Q, Kohen L, et al. Retinal pigment epithelial wound healing in vivo. Arch Ophthalmol. 1995;113:1437-1446. FREE FULL TEXT
5. Hogg PA, Grierson I, Hiscott P. Direct comparison of the migration of three cell types involved in epiretinal membrane formation. Invest Ophthalmol Vis Sci. 2002;43:2749-2757. FREE FULL TEXT
6. Crouch ER, Apple DJ. Posttraumatic migration of retinal pigment epithelial melanin. Am J Ophthalmol. 1974;78:251-254. WEB OF SCIENCE | PUBMED
7. Hilton GF. Subretinal pigment migration: effects of cryosurgical retinal reattachment. Arch Ophthalmol. 1974;91:445-450. FREE FULL TEXT
8. Machemer R, LaQua H. Pigment epithelium proliferation in retinal detachment (massive periretinal proliferation). Am J Ophthalmol. 1975;80:1-23. WEB OF SCIENCE | PUBMED
9. Anderson DH, Stern WH, Fisher SK, Erickson PA, Borgula GA. The onset of pigment epithelial proliferation after retinal detachment. Invest Ophthalmol Vis Sci. 1981;21:10-16. FREE FULL TEXT
10. Li ZY, Possin DE, Milam AH. Histology of bone spicule pigmentation in retinitis pigmentosa. Ophthalmology. 1995;102:805-816. WEB OF SCIENCE | PUBMED
11. Crafoord S, Kopp ED, Seregard S, Algvere PV. Cellular migration into neural retina following implantation of melanin granules in the subretinal space. Graefes Arch Clin Exp Ophthalmol. 2000;238:682-689. FULL TEXT | WEB OF SCIENCE | PUBMED
12. Chauhan DS, Marshall J. The interpretation of optical coherence tomography images of the retina. Invest Ophthalmol Vis Sci. 1999;40:2332-2342. FREE FULL TEXT

SECTION EDITOR: W. RICHARD GREEN, MD



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