pathogenesis of tears of the pigment epithelium

British Journal of Ophthalmology, 1984, 68, 513-519

Pathogenesis of tears of the retinal pigmentepithelium *J. DONALD M. GASS

From the Department of Ophthalmology, Bascom Palmer Eye Institute, University ofMiami Medical School,Miami, Florida, USA

SUMMARY This report confirms a previous report that elderly patients with serous detachments ofthe pigment epithelium prior to and after developing a pigment epithelial tear at one borderpresent a characteristic ophthalmoscopic and fluorescein angiographic appearance. Evidence ispresented that subpigment epithelial choroidal neovascularisation and not irregular separation ofthe basement membrane from its pigment epithelium is the primary cause of the detachment andtear in the pigment epithelium.

In 1981 Hoskin et al. described the ophthalmoscopicand fluorescein angiographic features of (1) serousdetachments of the pigment epithelium that wereprone to develop a tear along their margin, and (2)the characteristic post-tear appearance of theselesions which occur in patients with senile maculardegeneration. ' They postulated that irregularseparation of the pigment epithelium from its base-ment membrane was responsible for the angiographicpicture and for determining the site of the pigmentepithelial tear. The purpose of this presentation is toconfirm their clinical observations and to suggest analternative explanation for the funduscopic andangiographic changes as well as the pathogenesis ofpigment epithelial tears.

Case reports

CASE 1An 85-year-old man developed metamorphopsia inhis right eye; He had lost central vision in his left eyepreviously because of senile disciform maculardegeneration. His visual acuity was 20/30 in the righteye and finger counting in the left eye. In the rightmacula there was a dome-shaped area of detachmentof the pigment epithelium (Fig. IA). The temporalhalf of the pigment epithelial detachment was slightlymore elevated than the nasal portion, where small

*Presentcd at the Intcrnational Symposium on Fluorcscein Angio-graphy, Coronado, California, USA, 24-3t) Octobcr, 1982.

drusen were present. There was no evidence ofsubretinal neovascularisation biomicroscopically.Fluorescein angiography revealed delayed and in-complete fluorescein staining of the nasal part of thepigment epithelial detachment (Fig. 1B). This wasinterpreted as evidence of the presence of fibro-vascular tissue and blood pigment lying beneath thenasal part of the pigment epithelial detachment. Hereturned five weeks later because of further reduction

Corrcspondence to J. Donald M. Gass, MD, Bascom Palmer Eye Fig. IA Case 1. 25 September1968. Pigment epithelialInstitute, PO Box 016880, Miami, Florida 331t)1, USA. detachment (arrows).

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Fig. 1 B Case 1. Note incomplete staining ofsubpigmentepithelial exudate nasally (arrows).

of visual acuity to 5/200. The temporal two-thirds ofthe previous pigment epithelial detachment wasreplaced by a sharply defined zone of what was inter-preted as atrophy of the pigment epithelium and thenasal one-third by a solid-appearing pigmentedmound (Fig. IC). Fluorescein angiography revealedmarked hyperfluorescence consistent with eithermarked attenuation or absence of the pigment epi-thelium temporally (Fig. 1D). There was irregularhyperfluorescence and late staining of the surface ofthe pigmented mound of tissue nasally (Figs. ID, E).Two months later there was subretinal blood aroundthe margins of the pigmented mound (Fig. IF). Oneyear later a large choroidal neovascular membraneextended throughout the centre of the macula.

1-i. 11)

F ig. I Ci Case/. 23 Uctober l Y68. Pigmented mound(arrows) and zone ofatrophic or missing pigment epitheliumindicative ofa previous tear in the pigment epithelium.

Comment. Colour stereophotographs of the pre-and post-tear appearance of this fundus lesion werepreviously published and interpreted as showinggeographic atrophy of the pigment epithelium causedby spontaneous reattachment of atrophic thinnedpigment epithelium adjacent to a zone of the sub-pigment epithelial fibrovascular proliferation .23 Ibelieve now, however, that Hoskin et al. are correctin assuming that this fundus change is usually caused

Fio. I E

Figs. ID and E Case l. Angiogram showing pinpoint areas offluorescence (arrows) and late staining indicative ofbloodvessels within the pigmented mound.

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Pathogenesis oftears ofthe retinalpigment epithelium

Fig. (Case 1. l9l)Dcemberti edge of]pigeine dlrledIo tId.

by a tear in the pigment epithelium. I still, however,interpret the pre- and post-tear angiogram as indicat-ing the presence offibrovascular tissue with or withoutblood pigment in the nasal portion of the detachment.In this case this interpretation was sustained by thesubsequent development of subretinal blood andangiographic evidence of unequivocal choroidal neo-vascularisation. If the pigmented mound of tissuenasally was composed solely of rolled-up and

Fig. 2A Case 2. 7July l979. Serous detachment ofthepigment epithelium (arrows).

retracted pigment epithelium, it should remain non-fluorescent throughout angiography.

CASE 2A 76-year-old man complained of metamorphopsiain the right eye of four weeks' duration. His visualacuity was 20/200 in the right eye. He had a mildcataract and a large serous detachment of the pigment

Fig. 2B FiO. C(Figs. 2B and C Case 2. Delayed and incomplete staining ofsubretinal exudate.

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Fig. 2D Case2. 12 October1970. Post-tear appearancewith pigmented mound (arrows).

epithelium in the right macula (Fig. 2A), and multipledrusen in the left macula. Angiography confirmedthe presence of the detachment and revealed a delayin the overall fluorescein staining and incompletestaining of the nasal part of the detachment (Figs. 2B,C). Argon laser photocoagulation was placed alongthe margins of the detachment. Five weeks later thedetachment was unchanged. There was a smallamount of subretinal blood at the inferior margin ofthe detachment. Approximately eight weeks after

Fig. 3A Case3. Postpigment epithelial tear.

Fig. 2E Case2. Angiogram showing mottledfluoresceinstaining ofsurface ofpigmented mound (arrows).

treatment he noted a worsening of the vision in theright eye. Ten weeks after laser treatment the pigmentepithelial detachment was replaced by a large pig-ment epithelial defect temporally and an elevatedpigmented mass nasally (Fig. 2D). There was a serousdetachment of the retina overlying the pigmentepithelial defect. Circinate exudate was presentat the temporal margin of the pigmented mass.Angiography revealed marked hyperfluorescencecorresponding with the pigment epithelial defect andstaining of the nasal aspect of the pigmented mass(Fig. 2E).

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Fig. 3B Case 3. Notefaint areas ofstaining (arrows),indicative ofblood vessels within the subretinalpigmentedmass.

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_~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~.....'...Fig. 4A Postpigment epithelial tear. Note subretinalpigmented mound (large arrow), edge oftorn pigmentepithelium (small arrows) andsurrounding subretinalprecipitates in area ofresolving detachment.

Comment. Between five and 10 weeks after argonlaser treatment the patient probably developed a tearalong the temporal margin of the pigment epithelialdetachment. The subretinal blood noted just prior tothe tear and the circinate exudate afterwards areevidence that choroidal neovascularisation waspresent at the time of the tear.

CASE 3An 80-year-old man consulted his local ophthal-mologist because of recent loss of vision in the righteye. He had lost central vision in the left eye one yearpreviously. His physician noted serous maculardetachment in the right eye and a pigmented massthat he suspected might be a melanoma in the leftmacula. Examination at the Bascom Palmer EyeInstitute revealed bilateral senile macular disease anda left fundus picture typical of that following a tear inthe pigment epithelium (Fig. 3A). There was faintmottled fluorescein staining on the surface of thepigmented mound (Fig. 3B).

CASE 4A 68-year-old man noted an abrupt loss of centralvision in the left eye six weeks prior to examination.Visual acuity was 20/25 in the right eye, and 10/200 inthe left eye. He had drusen in the right macula and inthe left eye had ophthalmoscopic and angiographicevidence of having previously developed a pigmentepithelial tear (Figs. 4A, B).

Discussion

Hoskin et al. described the following three features ofthe pretear appearance of the pigment epithelial

Fig. 4B Staining (arrow) indicative ofblood vessels withinthe mound.

detachments which occurred in 8 of 12 patientsobserved prior to development of a tear: (1) unevenessof drusen distribution in the area of the pigmentepithelial detachment; (2) uneven hyperfluorescencein the area of most drusen; (3) greater elevationand more uniform hyperfluorescence of the drusen-free area of the detachment.' In four eyes the latefluorescein staining was uniform. The authorsdescribed the following features ofthe post-tearphaseof the lesion: (1) a zone of absent pigment epitheliumcaused by a tear occurring at the edge of that portionof the pigment epithelial detachment that wasuniformly fluorescent; (2) a pigmented mound, whichthey attributed solely to retracted and rolled-uppigment epithelium at one area of the bared area ofBruch's membrane; (3) non-fluorescence of thepigmented mound; and (4) no evidence of subretinalneovascularisation in spite of their observation ofsubretinal blood in five of 44 eyes.

Fig. 5 is a diagram depicting their explanation forthe pre- and post-tear appearance of these lesions.They suggest that detachment of the pigment epi-thelium from its underlying basement membrane inthe area of greatest elevation is responsible for themore uniform area of hyperfluorescence and formaking the pigment epithelium more susceptible totearing.My observations of the pretear funduscopic and

angiographic appearance (Figs. 1 and 2) coincidewith that of Hoskin etal.,' although my interpretationof these findings is different. So far I have not seen atear develop in a pigment-epithelial detachment thatshowed early uniform fluorescein staining. As regardsthe post-tear lesion, I concur with their first twoobservations but not the last two. In my experience

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PRE-TEAR

POST-TEARFig. 5 Diagram ofHoskin et al. 's theory ofcause ofpigment epithelial tear. Arrows indicate portion ofbasementmembrane detachedfrom its overlyingpigment epithelium.

angiography ofthe post-tear lesions has shown streaksor spots of early fluorescence and small areas of stain-ing at the surface of the pigmented mound in mostcases (Figs. 1, 2, 3, and 4). I interpret these findings,as well as the delayed and non-uniform staining of thepre-tear lesions, as angiographic evidence ofprobablechoroidal neovascularisation. Since the mound offibrovascular tissue is partly covered by the retractedand rolled-under pigment epithelium, in some casesneither early nor late fluorescence will be evident.The hypothesis that separation of the pigment epi-

thelium from its basement membrane is responsiblefor the uniform fluorescence and for predisposing thepigment epithelium to tear is not supported byreported light microscopic, electron microscopic, orclinical findings. The basement membrane is tightlyadherent to the pigment epithelium, much more sothan to the collagenous portion of Bruch'smembrane.4 It is likely, therefore, that detachmentof the basement membrane from its pigment epi-thelium rarely, if ever, occurs. Electron microscopicstudies have shown that in the case of drusen thebasement membrane remains attached to the elevatedpigment epithelium.' In the case of one large serousdetachment of the pigment epithelium in an eyeenucleated because of suspected melanoma in anelderly woman, PAS stains revealed evidence thatthe basement membrane, as well as multiple smalldrusen, was detached along with the pigment epi-thelium.' Clinically, serous detachments of the pig-ment epithelium occurring in young as well as olderpatients characteristically show early uniform stainingwith fluorescein, which, if the authors were correct,would suggest that in most cases detached pigmentepithelium is separated from its basement membrane,a finding that to my knowledge has never beendemonstrated.

Fig. 6 depicts what I believe is a more plausible

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4Fig. 6 Diagram ofstages ofdevelopment oforganisedserous detachment ofpigment epithelium andpigmentepithelial tear. Stage 1: Occult choroidal neovascularisation.Stage 2: Secondary serous detachment ofpigment epitheliumand its basement membrane. Stage 3: Acute tear ofpigmentepithelium andsecondary retinal detachment. Stage 4: Post-tear regrowth ofhypopigmented pigment epithelium andreattachment ofretina.

hypothesis to explain the pathogenesis ofspontaneouspigment epithelial tears. In stage 1 new vessels invadeand grow through Bruch's membrane into the sub-pigment epithelial space. Over a period of weeks ormonths these vessels, together with fibrocytes, pro-liferate to form a progressively enlarging fibrovascularmound that gradually elevates the basementmembrane, drusen, pigment epithelium, and retina.Except for the elevation this may cause minimal or nochanges in the ophthalmoscopic, angiographic, orhistological appearance of the overlying retina andpigment epithelium, and it may produce nosymptoms. A rapid change in permeability of the newvessels within this occult lesion produces a serousdetachment of the adjacent pigment epithelium (stage2). This detachment is typically slightly broader andmore elevated than the area oforganised detachment.The normal granularity of the pigment epithelium

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and the drusen in the area of serous detachmenttypically disappear from biomicroscopic view. Thedrusen presumably dissolve within the serousexudate. The pigment epithelium remains anchoredby its attachment to one side of the organised mound.As the pressure of escaping serous fluid detaches thepigment epithelium away from the opposite side ofthe mound, a point is reached where the pigmentepithelial cells cannot withstand the pressure requiredto separate it from Bruch's merfmbrane, and a tearoccurs at the junction of the attached and detachedpigment epithelium (stage 3, Fig. 6). Serous fluidmoves from beneath the pigment epithelium into tthesubretinal space as the free edge of the tear retracts inan accordion-like fashion and rolls under toward theorganized mound. A localised serous detachment ofthe retina larger than the area of detached pigmentepithelium persists until the pigment epithelial cellsalong the margin of the tear slide and proliferate tocover the defect with hypopigmented cells. Weseldom have an opportunity to see stage 3, since itprobably lasts only a matter of days or a few weeks.Once re-epithelialisation occurs, the subretinalexudate disappears (stage 4, Fig. 6). In some cases

the defect is largely covered with a semitransparentgrey tissue that probably represents fibrous meta-plastic pigment epithelium.Uneven elevation of the pigment epithelial detach-

ment with preservation of the near normal granularityof the pigment epithelium and small drusen in the lesselevated organised portion of the detachment, theincomplete and uneven staining of the area of theorganisation, and the delay in staining of the adjacentsubpigment epithelial exudate, probably caused byits high protein and blood pigment content, are threeof the clues nearly always present in patients withdetachment destined to develop a tear in the pigmentepithelium.

If the above hypothesis is correct, it has importanttherapeutic implications. Any attempt to flattena partly organised pigment epithelial detachmentby photocoagulation along the margin of the detach-ment7` will not only fail in flattening the area ofdetachment but may increase the risk of a tear. Theuse of a grid pattern of laser to the surface of theorganised portion of the detachment"" may increase

the permeability of the new vessels, the subpigmentepithelial hydrostatic pressure, and the risk of a tear.Conversely, if that portion of the pre-tear lesion thatstains incompletely lies outside the foveal avascularzone, moderately intense laser treatment to the entirearea of neovascular complex may be successful in

flattening the adjacent areas of serous detachment ofthe pigment epithelium.

Varying results of photocoagulation of serousdetachment of the pigment epithelium have been

reported."'3 One of the reasons for this variabilityhas been the lack of uniformity in the recognition ofthe many subtle clues to the presence of new vesselsbeneath the pigment epithelium."'"'Two recent reports have also suggested the unlikeli-

hood that detachment of the pigment epithelium fromits basement membrane is the cause of pigment epi-thelial tears.'7 "l One report noted evidence ofchoroidal neovascularisation in five of six patientswith a tear. The others noted subretinal and subpig-ment epithelial blood following development of alarge tear with a visible rolled margin; however, thiswas attributed to mechanical disruption of the chorio-capillaris at the site of the tear. ",

This investigation was supported in part by Public Health ServiecResearch Grant 5R1( EY02549, Department of Health and HumanServices, National Institutes of Health, National Eye Institute,Bethesda, Maryland.

References

I Hoskin A, Bird AC, Schmi K. Tears of detached retinal pigmentepithelium. Br J Ophthalmol 1981; 65: 417-22.

2 Gass JDM. Stereoscopic atlas of mnacular diseases. St Louis:Mosby, 197t): 39.

3 Gass JDM. Stereoscopic atlas of inacular diseases. 2nd ed. StLouis: Mosby, 1977: 73.

4 Goldbaum MH, Madden K. A new perspective on Bruch'smembrane and the retinal pigment epithelium. BrJ Ophthalmol1982; 66: 17-25.

5 Hogan MJ, Alvarado J. Studies of the human macula. IV. Agingchanges in Bruch's membrane. Arch Ophthalmol 1967; 77: 410-20).

6 Gass JDM. Pathogenesis of disciform detachment of the neuro-epithelium. 111. Senile disciform macular degeneration. Am JOphthalmol 1967; 63: 617-44.

7 Gass JDM. Stereoscopic atlas of inacular diseases. 2nd ed. StLouis: Mosby, 1977: 390-1.

8 Jepson CN, Wetzig PC. Photocoagulation in disciform maculardegeneration. Am J Ophthalmol 1969; 67: 920-30.

9 Gass JDM. Drusen and disciform macular detachment anddegeneration. Arch Ophthalmol 1973; 90: 2t)6-17.

1) Bird AC. Treatment of senile macular degeneration by photo-coagulation. Br J Ophthalmol 1974; 58: 367-76.

11 The Moorfields Macular Study Group. Retinal pigment epithelialdetachments in the elderly: a controlled trial of argon laserphotocoagulation. BrJ Ophthalmol 1982; 66: 1-16.

12 Braunstein RA, Gass JDM. Serous detachments of the retinalpigment epithelium in patients with senile macular disease. Am JOphthalmol 1979; 88: 652-60.

13 Meredith TA, Braley RE, Aaberg TM. Natural history of serousdetachments of the pigment epithelium. Am J Ophthalmol 1979;88: 643-51.

14 Gass JDM. Stereoscopic atlas of inacular diseases. 2nd ed. StLouis: Mosby, 1977: 392.

15 Gass JDM. Radial chorioretinal folds. A sign of choroidal neo-vascularization. Arch Ophthalmol 1981; 99: 1016-8.

16 Gass JDM. Serous retinal pigment epithelial detachment with a,notch': a sign of choroidal neovascularization. Retina in press.

17 Cantrill HL, Ramsay RC, Knobloch WH. Rips in the pigmentepithelium. Arc h Ophthalmol 1983; 101: 1t)74-9.

18 Green SW, Yarian D. Acute tear of the retinal pigment epi-thelium. Retina 1983; 3: 16-2t).

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