British Journal of Ophthalmology, 1985, 69, 397-403

Retinal pigment epithelial detachments in the elderly:classification and outcomeA G CASSWELL, D KOHEN, AND A C BIRD

From Moorfields Eye Hospital, City Road, London EC]V 2PD

SUMMARY Sixty-four eyes of 57 elderly patients with pigment epithelial detachments (PEDs) werestudied with the aim of describing their morphological features and identifying prognostic factors.They were classified into four groups according to the following characteristics: (a) earlyfluorescence, (b) late fluorescence, (c) shallow detachment with limited fluorescence ('drusentype'), (d) irregular fluorescence. The following conclusions were drawn: (1) 30% developeddemonstrable subretinal new vessels; all groups except the drusen type were susceptible, theirregular group being particularly prone. (2) 10% developed retinal pigment epithelial tears, andthese occurred almost exclusively in the slow fluorescent group. (3) Flattening of PEDs was afeature of drusen type and early fluorescent groups. (4) Most patients lost vision. RPE tearsoccurred within a few months of presentation with immediate loss of vision; likewise rapid loss ofvision followed the development of demonstrable new vessels, though not necessarily in those withchanges thought to imply the presence of new vessels. Flattening after prolonged detachment wasassociated with pigment epithelial atrophy and invariable loss of vision. Visual acuity wasmaintained consistently only in those eyes with persistent detachment.

Pigment epithelial detachments (PEDs) are discrete,serous elevations of the retinal pigment epithelium.During fluorescein angiography the subpigmentepithelial space fills progressively with dye andremains hyperfluorescent long after dye transit. 'Recent behavioural studies have shown that thevisual prognosis may be determined by the size of thelesion and the age of the patient. Lewis2 has shownthat in younger patients (less than 55 years old) thevisual prognosis is good. Meredith et al.3 found thatelderly patients with small PEDs have a relativelybetter visual prognosis than those with large lesionsbut identified no other features as useful indicators ofprognosis.PEDs have a complex variety of appearances. The

nature of the different characteristics and the signific-ance of particular changes to visual prognosis havenot been defined. In particular it is acknowledgedthat the exclusion of subretinal new vessels can bedifficult, so that it may be impossible to be sure that alesion is 'avascular.' It has been considered that their

Correspondence to Mr A G Casswell, FRCS.

presence may be implied by the presence of focalhyperfluorescent spots within a PED, yellow sub-retinal deposits, and turbid fluid.

In the past it has been thought that PEDs causedsubretinal new vessels to develop and that this com-plication represented the principal threat to vision.Photocoagulation has been used to flatten the pig-ment epithelium with the aim of restoring vision andpreventing the development of disciform lesions, buta recent controlled trial of elderly patients treatedwith argon laser photocoagulation implies that thisform of therapy confers no visual benefit.4 Duringthis trial sight threatening complications other thanthe development of subretinal new vessels wereidentified.

It was the results of the trial and the observationsmade during the study which stimulated the presentreview to classify the morphological features of PEDsand to identify whether any particular characteristicshad prognostic significance. Information of this typemay help in identifying the expectations for vision ina patient and would also contribute to planning anyfurther trials of treatment for PEDs.

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Material and methods

We undertook a retrospective study of64 consecutiveuntreated patients older than 55 years with pigmentepithelial detachments who were referred to theRetinal Diagnostic Department at Moorfields EyeHospital from 1976 to 1981.The criteria for the diagnosis of a PED was elevation

of the retinal pigment epithelium with accumulationof fluorescein dye in the subpigment epithelial spaceduring angiography. Patients with identifiable sub-retinal new vessels, subretinal haemorrhage, unex-plained focal hyperfluorescent spots, or extensivesubretinal exudates were excluded. Those patientswith high myopia and any additional past or presenteye disease which could affect the visual acuity werealso excluded.The following were recorded: the age and sex of

the patient, duration of symptoms, corrected visualacuity, signs of age related macular changes (drusenetc.), the size, location, and ophthalmoscopicfeatures of the PEDs, together with the pattern offluorescence during angiography. At follow-up visitsthe visual acuity was recorded and colour photo-graphs and fluorescein angiography were repeated.

In the first part of the study we classified foveal andjuxtafoveal PEDs on the basis of their ophthalmo-scopic and fluorescein appearances. In the secondpart we recorded the outcome and visual acuity of allPEDs that had been observed for at least one year, orless if they developed a sight losing complicationwithin that time. All those patients who did not haveadequate follow-up were requested to attend again.The diagnosis of a disciform lesion was based on

the demonstration of new vessels or the presence ofsubretinal haemorrhage in the absence of a tear of theretinal pigment epithelium (RPE). The developmentof yellow subretinal exudates and the delayedappearance of fluorescence was not regarded asdiagnostic of subretinal neovascularisation.

Results

CLASSIFICATIONWe classified 64 PEDs of 57 patients into four groupsbased on the fundal appearance and fluoresceinangiograms.

Hyperpigmentation of the pigment epithelium(pigment figure) was a feature of many lesions andwas not used to differentiate one group from another.In several lesions a patch of hypofluorescence wasidentified which appeared to be due to obstruction offluorescein at the level of the pigment epitheliumwithout any corresponding lesions seen by ophthal-moscopy (Fig. 1).

1. Early hyperfluorescent group (17 eyes). A

Fig. 1 Fluorescein angiography ofapigment epithelialdetachmentshowing hypofluorescentpatches in its lowerpart(arrows). No ophthalmoscopic abnormalities werefound tocorrespond with these.

discrete dome-shaped elevation of the RPE is seenophthalmoscopically. During fluorescein angio-graphy the subpigment epithelial space fluorescesearly and progresses to an even hyperfluorescence inthe later stages of the transit (Figs. 1, 2). Thisappearance may be modified by small areas of

Fig. 2 Fluorescein angiography ofapigment epithelialdetachmentfilling early in the angiogram with evenhyperfluorescence.

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Retinalpigment epithelial detachments in the elderly: classification and outcome

hyperfluorescence which can be identified as corres-ponding to areas of pigment epithelial atrophy ordrusen that have become detached with the pigmentepithelium or occasionally round well-defined zonesof hypofluorescence that have no correspondingfeature ophthalmoscopically.

2. Late fluorescing group (14 eyes). Ophthalmo-scopically these cannot be differentiated from theearly hyperfluorescent PEDs. They are characterisedby the appearance of fluorescence after the arterio-venous phase (delayed appearance), which pro-gresses slowly to an even and featureless hyper-fluorescence (Figs. 3, 4). In some cases fluorescencemay appear first at the edges of the PED and spreadconcentrically inwards.

3. Drusen type (18 eyes). Multiple large confluentdrusen are seen in and surrounding these PEDs,which are usually shallow and irregular in outline. Onfluorescein angiography they fluoresce faintly duringthe transit and do not progress to the bright hyper-fluorescence seen in the lesions of other groups (Fig.5). The presence of underlying drusen modified theangiographic appearance of the lesion in that at thesite of the drusen the fluorescence was less markedthan elsewhere in the lesion.

4. Irregular fluorescence (10 eyes). Thoughophthalmoscopically indistinguishable from the firsttwo groups, angiography reveals an overall fineirregularity of fluorescence. Typically the irregularityof fluorescence comprises multiple areas of hypo- andhyperfluorescence over the whole detachment. The

Fig. 3A

hyperfluorescent areas increase in fluorescenceduring the study, whereas the hypofluorescent areasremain unchanged (Fig. 6).

5. Mixed group (5 eyes). There were five PEDswith two zones of different characteristics duringangiography, usually one area of irregular fluor-escence adjacent to a slowly filling hyperfluorescentarea. Typically the half with slow fluorescence wasthe more elevated of the two.Other characteristics did not serve to differentiate

between groups, the average age, age ranges, andpresenting visual acuities being similar (Table 1).Although size was variable within each group, therewas a tendency for the Drusen PEDs to be smaller(0-96 disc diameters, Fig. 5) and for the slowly fillingPEDs to be larger (2.1 disc diameters, Fig. 4).

OUTCOMEMorphologicalA variety of changes were identified during theperiod of review (Table 2). With few exceptionsspontaneous flattening occurred only after an inter-val of several years. In many there was persistence ofthe PED, though the characteristics changed insome. One drusen PED enlarged and became rapidlyfluorescent, and several PEDs became irregularlyfluorescent before either flattening or developingnew vessels. In four eyes subretinal exudatesdeveloped round the margins of the detachmentwithout demonstrable subretinal new vessels at anystage. In 30% a disciform lesion developed. In 10%

Fig. 31Fig. 3 Fluorescein angiography ofapigment epithelial detachment in theposteriorpole showingslow development ofhyperfluorescence, which is uniform.

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Fig. 4A Fig. 4B

Fig. 4 Fluorescein angiography ofa largepigment epithelial detachment showing slow acquisition ofhyperfluorescence,which is uniform.

there was a tear of the pigment epithelium, and ineach case this occurred within a few months ofpresentation. The true figure is probably higher than10%, as some patients presented with this earlycomplication and were excluded from the review.The characteristics of the lesion when the patient

was first seen were not an absolute determinant ofsubsequent behaviour, but certain complicationswere clearly more common in some types than others(Table 2). Subretinal neovascularisation was muchmore common in those with fine irregular hyper-fluorescence than in others, though this processbecame evident in all types except the shallow'drusen detachments.' All but one of the tearsoccurred in 'slow hyperfluorescent' lesions.

VisualThe visual outcome was also correlated to someextent with the initial classification. The irregular andslow fluorescent PEDs had worse final vision than theother types, and the shallow drusen types fared bestof the groups.As might have been predicted, the final visual

acuity was poor in those patients who developed tearsof the retinal pigment epithelium or subretinal newvessels (Table 3). The visual outcome was also bad inthose lesions in which there was spontaneous flatten-ing of the pigment epithelium. The only lesionsassociated with consistently good vision at the end ofthe review period were those with persistent detach-ment.

Discussion

INTERPRETATION OF APPEARANCECertain determinants of behaviour of PEDs duringfluorescein angiography might be predicted on thebasis of theoretical considerations together with thelimited knowledge of the structural changes occur-ring within the lesion derived from histopathologicalstudies. It is generally assumed that the hyper-fluorescence of PEDs is due to the increased thick-ness of the fluorescing medium due to dye accumula-tion in the subpigment epithelial space, the fluor-escein being derived from the choroid having passedinto subretinal space by diffusion through Bruch'smembrane. Unequal rates of dye accumulation mightbe predicted if there were variation of the lipidcontent within Bruch's membrane or the sub-epithelial fluid from one lesion to another or within asingle lesion. This would influence the speed ofdiffusion, since fluorescein-sodium is highly solublein water but not in lipid. It is well recognised thatmaterial accumulating within and on the inner sur-face of Bruch's membrane with age contains bothlipid and protein, but the results of a systematicanalysis of this material in man do not exist.The appearance of fluorescence may also be modi-

fied by the transparency of the subpigment epithelialfluid and the detached structures; this is well illus-trated by the light absorption by luteal pigment andpigment figures. Clinical evidence implies that pig-ment epithelium may become detached, with drusen

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Fig. 5 Fluorescein angiography ofa shallowpigmentepithelial detachment associated with drusen.

on its under surface in some lesions but not in others.That there should be a similar disparity in thebehaviour of pigment epithelial basement membranehas been postulated by Hoskin et al.5 Such variationin the distribution of material would predictablyinfluence the appearance of the lesion clinically andduring angiography, and this could account for thetwo different zones of a 'mixed PED.'The slow appearance of fluorescence in some

lesions may be accounted for by slow diffusion of dyeinto the subretinal space due to high lipid contentwithin the subpigment epithelial fluid or in Bruch'smembrane, or by the presence of blue/green absorb-ing material within the subpigment epithelial fluid, sothat fluorescence is not recorded until the dye hasdiffused as far as the detached pigment epithelium.The latter would explain the appearance of fluor-escein at the periphery of the lesion in the early stagesof the study, a feature common to many lesions.These two situations may coexist, since lipofuscin,which absorbs blue light well, is the most likely lipid

Fig. 6 Fluorescein angiography ofapigmentepithelialdetachment with irregular hyperfluorescence.

to accumulate at these sites. By contrast in thosePEDs which become rapidly and evenly fluorescent itis unlikely that there is a high lipid content withineither Bruch's membrane or the subretinal fluid orthat the detached tissues contain large amounts ofblue/green absorbing pigments.The diffuse irregular fluorescence in the irregular

masking group suggests irregular transmission oflight by the detached tissues due to material on theouter aspect of the detached retinal pigment epi-thelium. While the origin of such a material isunknown, it could result from deposition of phago-somal debris, thickening of pigment epithelial base-ment membrane, or possibly the product of unde-tected new vessels.The focal and increasing fluorescence which

corresponds with large dFusen seen on the under-surface of Bruch's membrane is probably due todisplacement of pigment within the detached pig-ment epithelium and accumulation of dye in thedrusen. The areas of hypofluorescence seen without

Table 1 Pigment epithelial detachments at presentation

Type No. Age Size VA VA (mean)(worse

Mean Range than 6124)

Early 17 65 70 (56-75) 1-90 3 6/12Late 14 69-9 (57-79) 2-10 1 6/12'Drusen' 18 65 3 (57-78) 0-96 0 6/12Irregular 10 67-27 (64-79) 1-70 1 6/12Mixed 5 70 (67-74) 2 45 0 6/12

Size measured in disc diameters.

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Table 2 Outcome ofpigment epithelial detachments with afollow-up ofone year or more

Type No. Outcome VA VA (mean)(worse

Flat PED Disc Tear than 6124)

Typical 16 3 6 6 1 9 6/24Late 11 0 4 3 4 5 6/36'Drusen' 15 6 9 0 0 5 6/12Irregular 8 0 2 6 0 4 6/48Mixed 3 0 0 2 1 1 6/36

Flat=PEDs that spontaneously flatten.PED=pigment epithelium remaining detached.Disc=development of a disciform lesion.Tear=pigment epithelial tear.

Table 3 Visual change ofPEDs in terms of their outcome

Outcome No. Age Size Initial VA Follow-up Final VA Worse(DD) (mean) (months) (mean) than 6/24

Flat 9 64 1-5 6/13 49 6/30 7PED 21 65-1 1-23 6/10 29*5 6/15 4Disciform 15 67-4 2 25 6/13 14-5 6/24 8Tears 6 70 3-04 6/21 7 6/36 4

Follow-up=mean time between presentation and event. DD=disc diameter.

corresponding ophthalmoscopic changes appear tobe due to transmission change at the level of thepigment epithelium, which might be caused byaccumulation of a blue/green absorbing pigmentother than melanin, which may be intra- or extra-cellular. Collections of lipofuscin-containing macro-phages or RPE cells growing on the outer surface ofthe detached RPE would account for such an appear-ance.Drusen PEDs are small, shallow, and surrounded

by and containing large drusen. The large drusencontained within the PED fluoresce faintly towardsthe end of the transit, and because they occupy mostof the sub-RPE space there is relatively little sub-RPE fluid to accumulate fluorescein, thus limitingfluorescence. The difficulty differentiating some ofthese ophthalmoscopically from confluent drusensuggests that they may develop as a direct result ofaccumulation ofconfluent drusen rather than indicat-ing the onset of a new process.

OUTCOMEIf the variation in the appearance of retinal pigmentepithelial detachments is due to different distributionof cellular and non-cellular material within thelesion, correlation might be expected between theclinical characteristics of the lesion and its subse-quent behaviour.Hoskin has postulated that the features of 'slow

filling' lesions implied that the retinal pigment epi-thelium may be detached without a normal basement

membrane and that the lack of physical supportwithin the detached tissue would increase the risk oftearing. The results of this study support the conclu-sion concerning the risk of this complication occur-ring in this type of lesion, though the conclusionsconcerning pathogenesis have not been tested. Thelarger size of these lesions may also be important inthe pathogenesis of the tear. While disciform lesionsoccurred within this group, four patients had noevidence of subretinal new vessels at the end of thereview period. This means that turbidity of thesubpigment epithelial fluid does not necessarily implythe inevitable presence of neovascularisation. It isclear, however, that in such cases new vessels mayhave been present on the inner surface of Bruch'smembrane when the patient was first seen and maynot have been identified on angiography. Thisphenomenon has been identified in the past,4 and itwas shown that blood vessels at this level may notinvolve the detached pigment epithelium and do notnecessarily cause loss of visual acuity.

Disciform lesions were common in the lesions withfinely irregular hyperfluorescence. This may berelated to the presence of debris on the under surfaceof the detached tissues, which may stimulate neo-vascularisation and in particular cause the newvessels to grow at the level of the pigment epitheliumrather on the inner surface of Bruch's membrane.Few sight threatening complications were seen in

the 'drusen RPE detachments.' This may be aconsequence of their small size and the shallow

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detachment; there is little evidence that the largedrusen would suppress the development of newvessels.

It was not surprising that severe visual loss was

common in patients with tears of the retinal pigmentepithelium or vascular disciform lesions. However,the explanation for the poor vision in those lesionswhich flattened spontaneously is not evident. It ispossible that flattening caused function to be lost or

that tissue failure caused both the loss of vision andthe resolution of the detachment, the secondexplanation being the most attractive of the two.Some useful prognostic information can be gained

from the morphological appearance of PEDs. PEDsof all groups except the drusen group are at risk ofdeveloping disciform lesions, and those with irregu-lar fluorescence were the worst affected. Nearly allthe RPE tears were in the slow fluorescing group.The visual prognosis is poor for all groups. RPE tearsare followed by visual loss within days of occurrence.

The development ofnew vessels was accompanied byvisual loss within a few months, and those thatflattened after several years had atrophy of the RPEand visual loss. These results should be useful in theplanning of any future trial of the treatment ofpigment epithelial detachments.

References

1 Donald J, Gass M. Pathogenesis of disciform detachment of theneuroepithelium. Am J Ophthalmol 1976; 63: 617-44.

2 Lewis ML. Idiopathic serous detachment of the pigment epi-thelium. Arch Ophthalmol 1978; 96: 620-4.

3 Meredith TA, Braley RE, Aaberg TM. Natural history of serous- detachments of the retinal pigment epithelium. Am J Ophthalmol

1979; 88: 643-51.4 Moorfields Macular Study Group. Retinal pigment epithelial

detachments in the elderly: a controlled trial of laser. Br JOphthalmol 1982; 66: 1-16.

5 Hoskin A, Bird AC, Schmi K. Tears of the detached retinalpigment epithelium. BrJ Ophthalmol 1981; 65: 417-22.

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