Congenital hypertrophy of the retinal pigment epithelium (CHRPE): diagnosis and management = Hipertrofia congénita del epitelio pigmentario de la retina (HCEPR): diagnóstico y manejo

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ARCH. SOC. CANAR. OFTAL., 2020; 31: 12-17 CASO CLÍNICO
Congenital Hypertrophy of the
Retinal Pigment Epithelium (CHRPE):
diagnosis and management
Hipertrofia congénita del Epitelio Pigmentario de la
Retina (HCEPR): diagnóstico y manejo
GUEDES GUEDES II1, BERNAL MONTESDEOCA LI1, CABRERA LÓPEZ F2
ABSTRACT
Introduction: Grouped pigmentation of the RPE has aroused the interest of ophthalmologists
since it could be a manifestation of systemic diseases yet to be diagnosed.
Case Report: A 19-year-old woman visited the emergency department for ophthalmology con-sultation
after perceiving floaters for a month. Anterior segment was normal. A flat, pigmented
lesion with net edges was identified in the right eye, which had not been described previously.
Discussion: A descriptive morphological study is carried out in which the OCT shows a marked
retinal thinning and loss of photoreceptors. FA shows blockage of fluorescence and the auto-fluorescence
evidences lack of lipofuscin that helps to distinguish between other pigmented
lesions as nevus and choroidal melanoma. The importance of this case lies in its relevance
to identify this lesion and make the diagnosis of systemic pathology.
Key words: Congenital hypertrophy of the retinal pigment epithelium, familial adenomatous
polyposis, Gardner.
RESUMEN
Introducción: Las pigmentaciones agrupadas en el EPR han despertado el interés de los oftal-mólogos
ya que pueden ser la manifestación de enfermedades sistémicas que no han sido
diagnosticadas.
Caso clínico: Una joven de 19 años acude a urgencias oftalmológicas por miodesopsias desde
hace un mes. El segmento anterior es normal. En el ojo derecho objetivamos una lesión
plana, pigmentada y de bordes netos no descrita previamente.
Discusión: Se realiza un estudio descriptivo morfológico en el que la OCT de la lesión pre-senta
un marcado adelgazamiento retiniano y una pérdida de los fotorreceptores. La AGF
muestra un bloqueo de la fluorescencia y en la Autofluorescencia se evidencia un déficit de
lipofucsina que ayuda a descartar otras lesiones pigmentadas como el nevus y melanoma
de coroides. La importancia de este caso radica en su relevancia para identificar la lesión y
hacer un apropiado despistaje de patologías sistémicas asociadas.
Palabras Clave: Hipertrofia Congénita del Epitelio Pigmentario de la Retina, Poliposis Ade-nomatosa
Familiar, Gardner.
1 Licenciada en Medicina. Oftalmología. CHUIMI.
2 Doctor en Medicina. Oftalmología. CHUIMI.
Complejo Hospitalario Universitario Insular Materno Infantil de Las Palmas de Gran Canaria. Servicio de Oftalmología.
Correspondencia:
Isabel Inmaculada Guedes
isabel.guedes.oft@gmail.com
Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE): diagnosis and management
ARCH. SOC. CANAR. OFTAL., 2020; 31: 12-17 13
INTRODUCTION
Grouped pigmentation of the Retinal
Pigment Epithelium (RPE) has been known
for over 100 years, but it was not until 1911
when Hoeg used CHRPE to describe clus-ters
of pigment in the Retina. The entity has
also been called Melanosis Retinae, bear or
animal tracks (1), and naevoid pigmentation
of the fundus (2). Kurz and Zimmerman (3)
found on histopathology the Congenital Hy-pertrophy
of the RPE cells (CHRPE).
Solitary CHRPE is a well-known, common
fundus condition that has been the subject of
considerable attention in the ophthalmic liter-atura
because these pigmented lessions could
be related with systemic diseases like Adeno-matous
Polyposis Coli (APC) in the context
of Gardner’s disease, but it also may be re-lated
with neurological diseases.
The aim of these report is to explain the
characteristics of these pigmented lessions
and their relationship with systemic diseases.
CLINICAL CASE
A 19-year-old woman comes to the Oph-thalmologic
emergency due to myodesopsies
in right eye for a month. She denies photopsies
and other systemic antecedents. In the anam-nesis,
she only refers headaches since one year.
The ophthalmological examination re-veals
that her visual acuity was the unit in
both eyes. In the slit lamp examination we
checked that the cornea and anterior segment
were normal. At the funduscopic examination
we identified in the right eye, a flat pigment-ed,
subretinal lession, with well delimited
edges in midperipheral retina.
We completed the examination with a
Fluorescein Angiography (FA), Fundus Aut-ofluorescence
(FAF), OCT, Ultrasound and
Visual Field to confirm a CHRPE as diagno-sis
of presumption.
Due to the relationship of CHRPE with
Gardner’s disease we decided to refer the
patient to the Digestologist to study possible
signs of APC.
DISCUSSION
Solitary CHRPE is a well-known, com-mon
fundus condition that has been the sub-ject
of attention in the Ophthalmological lit-erature.
Due to it is believed to be congenital,
the median age at diagnosis is over 45 years
(4). Its asymptomatic character justifies the
late diagnosis despite mild visual field defects
can be detected in some cases (5).
CHRPE has been related with Gardner’s
síndrome (35). Multiple or bilateral CHRPE
may occur in Familial Adenomatous Poly-posis
(FAP), an autosomal dominant disease
caused by mutations in the Adenomatous
Polyposis Coli (APC) gene (6-11). This con-dition
is autosomal dominant (12). The glob-al
prevalence of CHRPE in individuals with
APC mutation is 19% (13), so CHRPE is
the most common and earliest extra colonic
manifestation among FAP populations which
may be present at birth (80%) (14). The prev-elance
of CHRPE in the normal population is
between 1,2% to 4,4% (15).
The Retinal Pigment Epithelium (RPE) is
a single layer of cuboidal epitelial cells that
constitutes the ourtermost layer of the retina.
The RPE is located between the highly vascu-lar
choriocapillaris and the outer segments of
photoreceptor cells. It has no photoreceptive
or neural function, but also RPE is essential
to the support and viability of photoreceptor
cells (16).
CHRPE appears clinically as a well-de-marcated
flat to minimally elevated fundus
plaque, usually with typi­cal
depigmented la-cunae
(17,18) (fig. 1) located in midperipher-al
or peripheral fundus. In the Optical Coher-ence
Tomography (OCT) (8,35) is typical the
overlying retinal thinning, loss of photore-
Fig. 1:
Funduscopic
characteristics
of CHRPE. Is
characteristic a
well-demarcated
flat to minimally
elevated fundus
plaque that ranges
from a black
homogeneous
lesion, usually
with depigmented
lacunae.
GUEDES GUEDES II, et al.
14 ARCH. SOC. CANAR. OFTAL., 2020; 31: 12-17
ceptors, and moderate relative shadowing of
the underly­ing
Choroid. Orduña-Azcona et al
(19) described the characteristics of CHRPE
in HD-OCT concordant to the exposed case
(fig. 2).
At CHPRE is typical that Fluorescein
Angiography (FA) shows blockage of flu-orescence
throughout most of the sequenc-es.
Characteristically, there is a persistent
hypofluores­cence
of the pigmented areas as
Fig. 2: OCT
characteristics of
CHRPE. Is very
characteristic
overlying retinal
thinning, loss of
photoreceptors
and moderate
relative shadowing
of the underlying
choroid.
Fig. 3: FA
characteristics
of CHRPE. It
shows a blockage
of fluorescence
throughtout most
of the sequences.
Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE): diagnosis and management
ARCH. SOC. CANAR. OFTAL., 2020; 31: 12-17 15
we could prove in this clinical case (figs. 3a
and 3b).
Touriño et al (20) developed a study to
determine which were the changes in the FA
in patients with CHRPE. Hypofluorescence
throughout the angiography was constant in
all cases. Certain authors (21) suggest that
these vascular changes are secondary to an
excessive concentration of oxygen in the in-ner
layers of the retina which would result in
vascular damage.
What is more the Fundus Autofluores-cence
(FAF) shows hypoautofluorescence
due to the decrease of lipofuscin within the
enlarged heavily and uniformily pigmented
RPE cells (22,23) (fig. 4). The Ultrasonogra-phy
(fig. 5) does not provide a clear diagno-sis,
but it shows the dimensions of the lession,
about 1,04 mm thickness. In the visual field
results range from a mild relative scotoma to
an absolute field defect, usually depending on
the size of the lesion. In this case, there are
no findings suggestive of any campimetric
alteration.
CHRPE is a benign lesion of the optic fun-dus,
which typically has no visual repercus-sion.
For this reason, the management consist
of periodic obser­vation.
This case shows, a
follow up of 14 months that objectives sta-bility
of the visual acuity and the lesion. The
patient is awating for a colonoscopy in spite
of the probability of FAP is very low, due to
she only has one lesion.
In spite of CHRPE is a benign lesion,
the recent development of multiple or bi-lateral
CHRPE lesion are often associated
with FAP. At a minimum, these patients
should be referred for colonoscopy (24).
Colorectal examination is crucial for early
intervention and treatment, colon because
polyps progress to malignancy in near-ly
100% of cases. Multiple and bilateral
CHRPE in FAP is considered a clinical dis-ease
marker. CHRPE, has also been related
with isolated cases of microcephaly and hy-perreflexia
(25).
CHRPE has no malignant potential (26).
Recent reports have provided further infor-mation
about the potential of solitary CHRPE
to spawn a nodular growth pattern (1,27). The
nodule gradually acquires a retinal feeding
artery and draining vein and produces yellow
intraretinal exudation and exudative retinal
detachment (5).
The recommended management of sol-itary
CHRPE is periodic obser­vation.
If a
small nodular growth is dectected, it should
be observed for a period of time. Due to the
slow progression rate and extramacular lo-cation,
patients remains asymptomatic. The
prognosis for CHRPE is generally excellent.
Concerning differential diagnosis, soli-tary
CHRPE can appears similar to choroidal
melanoma (8) and nevus (table 1). Choroidal
melanomas have diffuse FAF pattern (28) in
contrast, CHRPE is hypoautofluorescence.
FA of choroidal melanomas, shows hypoflu-orescence
during the arterial phase and pro-gressive
hyperfluorescence during the subse-quent
phases (29). However, FA in CHRPE
shows blockage of fluorescence throughout
most of the sequences. In choroidal nevus,
FA shows hyporeflective mass with no signif-icant
deformity of choroidal vasculature and
an intact retinal pigment epithelium-Bruch’s
membrane complex (30).
Fig. 4:
Autofluorescence
of CHRPE.
Is typical the
absence of
autofluorescence
of CHRPE due
to de absence of
lipofuscin.
Fig. 5:
Ultrasonography.
It shows the
lession to be
about 1,04 mm
thickness.
GUEDES GUEDES II, et al.
16 ARCH. SOC. CANAR. OFTAL., 2020; 31: 12-17
CONCLUSIONS
Grouped pigmentation of the RPE has
aroused the interest of ophthalmologists due to
it could be a manifestation of systemic diseas-es.
In fact, it could be the first manifestation
of a pathology which has not been diagnosed.
The most frequently related pathology to
CHRPE is Gardner’s disease, but it also may
be related with neurological diseases. Fur-thermore,
concerning differential diagnosis,
solitary CHRPE can appear similar to choroi-dal
melanoma and nevus.
A meticulous anamnesis is convenient to
determine if CHRPE is related with congen-ital
or familiar diseases. Furthermore, all the
complementary tests should be done to deter-mine
the characteristics of the lesion and stab-lish
future tracking. In this patient, during the
follow up time of 14 months we did not find
signs of spread of the lesion and no new ones
were observed. The VA has remained at 1.
CHRPE has no malignant potencial, but
there are cases in which CHRPE spawn a nod-ular
growth pattern (1,31) that could produce
an intraretinal exudation and exudative retinal
detachment (5). The recommended manage-ment
of solitary CHRPE is periodic observa-tion
through diagnostics tests described and
the appropiate referral to the digestologist.
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Table 1. Differential diagnosis. The table shows the characteristics of CHRPE, Choroidal Nevus and Choroidal Melanoma in the different
complementary test carried out on the patient of the clinical case
Imaging technique CHRPE Choroidal nevus Choroidal melanoma
Fundus imaging
Well-demarcated flat that ranges
from a black homogeneous
lesion, usually with depigmented
lacunae
Round/oblong brown or coloured
mass undermeath the retina with
overlaying drusen.
Larger and thicker than nevus with
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SD-OCT EDI
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Similar appearance to nevus with
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Fluorescein angiography
Blockage of fluorescence
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Hyperfluorescent lesion in the
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Blockage of background choroidal
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Ultrasonography Flat lesion about 0.5mm to 1.5
mm thickness It cannot depict small nevus Hypo echoic round mass with smooth
anterior surface and choroidal excavation.
Fundus Autofluorescence Absence of autofluorescence due
to lack of lipofuscin.
Hipo-FAF due to chronic RPE
atrophy
Hyper-FAF due to overlaying lipofuscin
within the RPE.
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