281

International Ophthalmology 18:281-285, 1995.

9 1995KluwerAcademicPublishers. Printedin theNetherlands.

Exudative retinopathy of adults: a late sequela of retinopathy of

prematurity *
Melissa M. Brown, Gary C. Brown, Jay S. Duker, William S. Tasman & James J. Augsburger
Retina Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA
Accepted 7 November 1994

Key words: retinal detachment, retinopathy of prematurity, hard exudate

Abstract
The cases of 11 patients with a unilateral, retinal detachment associated with hard exudate and other late sequelae
of retinopathy of prematurity are described. The abnormality was first noted in the second to fourth decades of life.
Ten of the patients were women and one was a man. The source of the hard exudate was thought to be telangiectatic
retinal vascular abnormalities. Among the ten treated eyes, four demonstrated an improvement in visual acuity. In
two cases a mass lesion was also noted in the fundus.
Introduction

Methods

Hard exudation in the fundus can occur secondary to

leakage of serum from the retinal, choroidal and/or
optic disc vessels. It is most frequently seen in association with diabetic retinopathy [1], but is encountered
with a number of other abnormalities, including malignant hypertension [2], retinal venous obstruction [3],
retinal arterial macroaneurysm [4], retinal telangiectasis [5], choroidal neovascularization [6], radiation
retinopathy [7], optic neuropathies [8], familial exudative vitreoretinopathy [9], and others.
Retinopathy of prematurity produces posterior segment changes that include extraretinal neovascularization, macular retinal dragging, and retinal detachment.
Retinal pigment epithelial changes can be seen in the
late stages of the disease, particularly at years following the resolution of retinal detachment [ 10]. Less well
emphasized is a form of exudative retinopathy that
seems to develop many years after the acute stages of
the disease during infancy. Described herein are the
cases of patients with exudative retinopathy occurring
as a late sequela of retinopathy of prematurity.

The records of adult patients seen on the Retina Service

at Wills Eye Hospital over a 14 year period, from 1975
through 1988, with hard exudate in the fundus in association with sequelae from retinopathy of prematurity
were reviewed. Among the inclusion criteria, were a
history of prematurity (at least four weeks or greater),
a birthweight of less than 1.800 grams, and a fundus
appearance characterized by straightening of the retinal vessels, dragging of the retina, and the presence of
hard exudate in the retina.
Exclusion criteria included the presence of diabetes
mellitus, retinal venous obstruction, severe systemic
arterial hypertension, choroidal neovascularization, a
family history of hereditary vitreoretinal disorders such
as familial exudative vitreoretiopathy, or other known
abnormalities that could potentially lead to an exudative response in the fundus.
No patient related a history of having retinal therapy as a neonate, during the acute phase of his or her
retinopathy of prematurity.

Results

* Supported in part by the Retina Research and Development

Fund, Philadelphia, and Research to Prevent Blindness, New York

Eleven patients met the inclusion criteria. Among these

were 10 women and one man. Their ages at the time of

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presentation ranged from 22 years to 39 years, with a
mean of 30 years and a median of 30 years. Although
sequelae of refinopathy of prematurity were present
bilaterally in each patient, the exudative responses
were routinely observed only unilaterally. Nevertheless, severe retinopathy of prematurity was present in
some contralateral eyes; four of the opposite eyes had
no lightperception due to sequelae of the disease. Most
patients related a history of recent decreasing vision in
the eye involved by exudate.
By history, the patients were born from one to three
months prematurely, with a mean of approximately
two months of prematurity. According to the patients,
birthweights ranged from less than 900 grams to almost
1800, with a mean of 1215 grams. Birth records were
unavailable to confirm gestational age or actual birthweight in any case.
Followup ranged from seven months to 14 years,
with a mean of 5.4 years. The median followup time
was five years.

Fig. 1. Localizedaccumulation of hard exudate in the temporal peripheryof a retinopathyof prematurityeye. Retinal pigment
epithelial hyperplasiais also present.

Ophthalmoscopic features
Each affected eye presented with some form of retinal detachment, either localized or extensive. In all
instances there was associated hard exudate. Eight eyes
had primarily an exudative retinal detachment, two also
had a rhegmatogenous component, and in one eye there
was a typical traction retinal detachment with a concave surface. In 10 of 11 (91%) eyes with an exudative
detachment there were noted to be telangiectatic retinal
vascular changes. These vascular abnormalities were
generally located within, or directly adjacent to, areas
of hard exudation. In one case, it was thought that there
was actual neovascularization of the retina, and accumulation of new vessels anterior to the internal limiting
membrane.
The exudate was predominantly located in the midperipheral or peripheral fundus in 10 of 11 (91%) eyes,
although lesser amounts usually extended more posteriorly. One case demonstrated primarily involvement
of the posterior pole. In most instances there were
areas of focal accumulation of hard exudate (Fig. 1), at
times congregated along the retinal arteries and veins
(Fig. 2). Areas of retinal pigment epithelial hyperplasia, to varying degrees, were encountered in most of
the eyes.
A mass lesion (Fig. 3) in the more peripheral retina
was noted in two eyes. These yellow orange elevations
were both approximately three millimeters in height
and appeared to have an intrinsic blood supply with

Fig. 2. Retinopathyof prematurity with temporaldragging of the

retina and hard exudate present along both the retinal arteries and
veins. Small foci of retinal pigmentepithelial hyperplasiacan also
be seen.

fluorescein angiography (Fig. 4). In the later phases

of the study there was diffuse leakage of dye from the
telangiectatic vessels within the mass lesion in each of
the two eyes.
Treatment
Varied treatment modalities were employed in 10 of 11
eyes. One patient, a 39-year-old woman with an exo-

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Fig. 3. Masslesion (large black arrow)in the inferiorperipheryin

an eye with retinopathyof prematurity.An areaof previouscryopexy
is also present (smallblack arrow), as is hard exudate(white arrow).

tion with additional cryotherapy and diathermy before

the subretinal fluid and exudate resolved. In the sixth
eye the hard exudate and serous detachment increased
despite revision of the buckle. The retina could not be
flattened and the eye subsequently required retrobulbar
alcohol for pain relief.
Two eyes were initially treated with vitrectomy for
vitreous traction. One also received a scleral buckle.
In each case the retina was successfully reattached and
the hard exudate resolved.
Laser therapy to the telangiectatic vascular abnormalities was applied in one eye with a low lying serous
retinal detachment. Despite three sessions of treatment,
with both argon green and yellow dye wave lengths,
it did not lead to regression of the subretinal fluid or
hard exudate. Subsequent cryotherapy was followed
by regression of the subretinal fluid and hard exudate.
Cryotherapy alone to a hemangiomatous lesion in the
tenth treated eye was effective in causing regression of
the associated serous retinal detachment and hard exudate. Overall, the exudate lessened spontaneously in
one untreated eye and after therapy in 9 of 10 eyes.
The visual acuity in affected eyes ranged from
20/40 to 20/200 at the time of initial presentation, with
a mean of 20/70. It should be noted, however, that
all eyes had some degree of nystagmus. The vision in
the one untreated eye remained 20/40 with one year of
followup. Among the treated eyes, considering a visual change to be at least two gradations on the Snellen
chart, four eyes improved, four were unchanged, and
two worsened. In spite of lessening of the hard exudate,
one of these latter eyes developed progressive retinal
traction in the posterior pole and experienced a change
in vision from 20/50 to 20/100. The second eye with
worsening vision eventually progressed from 20/200
to no light perception due to increasing subretinal fluid
and hard exudation.

Fig. 4. A. Huoresceinangiogramcorrespondingto the mass lesion

shown in Fig. 3 at 17 seconds after injection reveals telangiectatic

vesselsthat appearto be part of an intrinsic bloodsupply.The lesion
becamemarkedlyhyperfluorescentas the study progressed.

Discussion

phytic, peripheral hemangiomatous lesion and exudate,

was not treated. Over a one year period her exudate
spontaneously regressed; the visual acuity remained
20/40 throughout this time.
Among the 10 treated eyes, six initially received
cryopexy to the retinal break and or telangiectatic retinal vascular changes. This effectively decreased the
exudate and flattened the retina in four eyes. The fifth
patient required a scleral buckle revision in combina-

The cases described herein represent a group of eyes

that developed late sequelae of retinopathy of prematurity. The most prominent feature of this entity, which
seems to present most commonly in the third and fourth
decades of life, is an exudative retinal detachment.
The exudate and subretinal fluid most likely arise from
telangiectatic retinal vascular changes, but it is uncertain what is the precipitating cause for breakdown of the
blood-retinal barrier. Vitreoretinal traction is present in
many of these eyes and, similar to the case with dia-

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betic retinopathy [11], could play a role in inducing
vascular leakage.
Additional cases of retinal damage causing severe
visual loss, but unassociated with exudative retinal
detachment, have also been observed to occur in
retinopathy of prematurity survivors during the second
to fourth decades of life. Two patients with retinopathy of prematurity and not in the present series were
reported by Tasman and Brown [12]; both had severe
visual loss thought to develop secondary to photoreceptor damage. As in the patients described herein,
the underlying pathophysiologic process was unclear.
Nevertheless, the possibility of hyperoxemic retinal
necrosis [13], neuronal damage in the neonatal retina
secondary to oxygen, was theorized. This phenomenon
has been noted to cause karyorrhexis of retinal cells
within the posterior vascularized retina in neonates of
24 to 27 weeks gestation. It was thought that compensatory mechanisms that keep such damage under
control might eventually fail in retinopathy of prematurity eyes. We are unsure whether our cases represent
a similar phenomenon.
Hard exudation is seen with a number of other
posterior segment diseases, including retinopathies,
choroidopathies and optic neuropathies [1-8]. In most
instances the serum lipidlevels are unremarkable. Nevertheless, in some instances of severe exudation, such
as with diabetic retinopathy [14] and central retinal
vein obstruction [3] there can be an associated hyperlipidemia, particularly a hypertriglyceridemia. On the
other hand, with juvenile Coats' disease, in which there
is a marked exudative response, the serum lipid levels
are usually normal [5]. Although a marked exudative
response was observed in our patients, they were not
evaluated for concomitant hyperlipidemia.
The entity described in this paper resembles Coats'
disease [5, 15] in a number of ways. There is often a
severe hard exudative response in each, both are usually unilateral, serous retinal detachments can occur
with each, and with both diseases there appear to be
leaking retinal telangiectatic abnormalities. The fundus appearance differs in that with the retinopathy of
prematurity variant there is also usually some degree
of retinal dragging, an abnormality not commonly seen
with Coats' disease. More cases of Coats' disease occur
in patients under the age of 20 years, but they can occur
into the forties [15]. There is, therefore, an overlap in
age with the two abnormalities. In contrast to the cases
of exudative retinopathy, which were found predominantly in women, 85% of patients with marked Coats'
disease are male [15]. Nevertheless, Tasman [16] pre-

viously reported the cases of four males with fundus

abnormalities similar to ours.
Familial exudative vitreoretinopathy [9] can have
a fundus appearance similar to that of the patients
described herein. Although there was no family history of familial exudative vitreoretinopathy in any case,
family members of the patients were not routinely
available for fundus examination. It is therefore theoretically possible that one or more of the cases could
represent familial exudative retinopathy. Admittedly, a
birthweight of close to 1,800 grams, as occurred in one
patient is usually too great to be associated with severe
retinopathy of prematurity [17]. Nevertheless, it should
be emphasized that the birthweights in this study were
obtained by history from the patients as adults, rather
than by direct examination of birth records.
An angioma-like mass, similar to that seen in two
of the eyes in our series, has been previously described
in an eye with retinopathy of prematurity [18]. In this
prior report the authors thought the mass was comprised of a combination of neovascular tissue arising
from the retina and partially organized hemorrhage. It
was located in the mid-peripheral fundus at the border of perfused and nonperfused retina in a 13-year
old boy. Argon laser photocoagulation applied to the
lesion, as well as the surrounding fundus, produced
regression. Scars from cryotherapy were present in
the vicinity of the mass in the eye of one of our
patients (Fig. 3). Cryotherapy has been observed to
rarely lead to choroidal neovascularization, but it is
uncertain whether this mechanism played a role in our
case.
The role of treatment for exudative retinopathy of
prematurity is unclear. We believe that the natural
course is often one of progression of the serous or
rhegmatogenous detachment, but a definitive natural
history of the disease is lacking. Both vitrectomy and
scleral buckling, in combination with cryopexy, seem
to eradicate the retinal detachment and hard exudation
in most cases. Laser therapy to the telangiectatic abnormalities was applied to one eye, but was ineffective.
In summary, we report a series of patients with
retinopathy of prematurity who developed an exudative retinopathy in the third to fourth decades of life.
This abnormality, which we noted more frequently in
women than men, most likely occurs secondary to
breakdown of the blood retinal barrier. Treatment is
generally effective in ameliorating the retinal detachment and hard exudate, but the natural history of the
disease is uncertain.

285

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Address for correspondence: G.C. Brown, 910 E. Willow Grove

Avenue, Wyndmoor, PA 19118, USA