EJO European

Journal of
Case report
Ophthalmology

European Journal of Ophthalmology

Dual corneal involvement
by endothelial 1 –4

© The Author(s) 2019

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and epithelial corneal
dystrophies in
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10.1177/1120672119872374 DOI:https://doi.org/10.1177/1120672119872374
Steinert’s disease: A case
of triple
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dystrophy

Amparo Gargallo-Benedicto , Vicente

Tomás Pérez-Torregrosa,
Rodrigo Clemente-Tomás and Antonio
Miguel Duch-Samper

Abstract
Introduction: A case of dual corneal involvement due to
Fuchs endothelial corneal dystrophy and epithelial basement
membrane corneal dystrophy in a patient with Steinert’s
myotonic dystrophy type 1 is described, and a literature review
on the triple association is made.
Case description: A 52-year-old male diagnosed with
myotonic dystrophy type 1 presented due to progressive
bilateral vision loss during the past year. A
full ophthalmological evaluation was made, with biomicroscopy,
funduscopy, anterior segment optical coherence tomography,
and endothelial cell count using specular microscopy.
Exploration revealed bilateral superior palpebral ptosis,
visual acuity 0.5 in the right eye and 0.3 in the left eye, and
with an intraocular pressure of 11 and 10 mmHg,
respectively. Biomicroscopy revealed map-dot-fingerprint lesions
characteristic of epithelial basement membrane corneal
dystrophy in both eyes, as well as abundant endothelial
guttae due to Fuchs endothelial corneal dystrophy (stage
II) and bilateral nuclear and posterior subcapsular cataracts.
Specular microscopy in turn showed cell loss and a
destructured endothelial map. Finally, anterior segment optical
coherence tomography revealed the accumulation of
epithelial basement membrane and hyperreflective endothelial
excrescences corresponding to guttae.
Conclusion: The association of Fuchs endothelial corneal
dystrophy with myotonic dystrophy has been described and
explained by a common genetic basis in the expansion of a
CTG trinucleotide repeat, though this is the first reported
case of the triple association of Fuchs endothelial corneal
dystrophy, epithelial basement membrane corneal dystrophy,
and myotonic dystrophy type 1. New mutations or still
unknown genetic alterations could possibly explain the triple
association reported in our case.

Keywords
Epithelial basement membrane corneal dystrophy, Fuchs
endothelial corneal dystrophy, myotonic dystrophy

Date received: 24 February 2019; accepted: 2 August 2019

Introduction
The most characteristic alterations are myotonia, fron-

tal alopecia, testicle atrophy, endocrine and immune disor-

Myotonic dystrophy type 1 or Steinert’s disease (DM1) is
ders, and ocular alterations in the form of “Christmas tree”
the most common hereditary muscle disease, with a preva-
cataracts, ptosis, orbicular muscle weakness blepharitis,
lence of 1:8000. It is an autosomal dominant disorder
attributable to the repeated expansion of the unstable CTG
triplet in the non-coding 3′ region of the myotonic dystro-
Hospital Clínico Universitario de Valencia, Valencia, Spain
phy protein kinase gene (DMPK) on chromosome 19. The
intranuclear accumulation of toxic RNA affects mRNA
Corresponding author:

Amparo Gargallo-Benedicto, Hospital Clínico Universitario de Valencia,

splicing and generates altered proteins that affect a range
Avenida Blasco Ibáñez, 17, Valencia 46010, Spain.
of tissues.1
Email: agargallobenedicto@gmail.com

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European Journal of Ophthalmology 00(0)
Figure 1. Diffuse map-dot subepithelial lesions in the entire cornea: (a) RE; (b,
c) LE; and (d) fingerprint peripheral lesion.

exposure keratitis, reticular macular dystrophy, retinal pig- a common

physiopathological mechanism characterized
ment disorders, electroretinogram and dark adaptation by increased RNA
toxic function secondary to CTG trinu-
anomalies, or ocular hypotony.2
cleotide repeat (TNR) expansion.5–7
In the 1960s, a number of authors described different This
report describes the first case of dual corneal
corneal alterations in patients with myotonic dystrophy, involvement
due to FECD and epithelial basement mem-
such as recurrent superficial inflammatory lesions, and brane corneal
dystrophy (EBMCD) in a patient with DM1.
although their precise underlying etiology could not be
established, they were considered to be worsened by Case
description
alterations in palpebral function, reduced tear secretion,
and neurotrophic disturbances inherent to myotonic dys- A 52-year-old
male diagnosed with DM1 presented due to
trophy. In 1969, Eustace described a case of myotonic progressive
bilateral vision loss during the past year. The
dystrophy with bilateral corneal ulceration, vasculariza- best corrected
visual acuity was 0.5 in the right eye (RE)
tion, and scarring that required keratoplasty. Although and 0.3 in
the left eye (LE). The intraocular pressure was
the histological study was unable to establish the cause of 11 and 10 mmHg in
the RE and LE, respectively.
the lesions, a corneal epithelial dystrophic etiology was The
exploration revealed frontal alopecia and bilateral
suggested, involving the same process affecting the crys- palpebral
ptosis. Slit-lamp biomicroscopy showed the
talline lens, since both structures are characterized by an presence of
disperse subepithelial map-dot-fingerprint
ectodermal origin.3
corneal lesions in both eyes (Figure 1(a)–(d)) secondary
In 2014, Gattey et al.1 reported the first association of to
epithelial basement membrane dystrophy (EBMD).
Fuchs endothelial corneal dystrophy (FECD) to DM1 in a Numerous
predominantly central guttae were identified
series of four patients. Posteriorly, Heringer et al.4 on the
posterior endothelial surface, associated to bilat-
described another two cases in a family. Recently, Mootha eral subendothelial
pigment deposits (Figure 2(a)) with a
et al.5 and Winkler et al.6 reported a high prevalence of “beaten metal”
appearance characteristic of FECD. There
FECD in patients with DM1 (46% and 36%, respectively). was no epithelial
or stromal edema. Bilateral nuclear and
Different genetic studies have demonstrated a non-casual posterior
subcapsular cataracts were also identified.
association between both disease conditions, explained by (Figure 2(b)).

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Gargallo-Benedicto et al.
3

Figure 2. (a) Endothelial guttae in slit-lamp examination and specular microscopy

(inside); and (b) nuclear and subcapsular
posterior cataract RE.

Conclusion
FECD is an autosomal dominant hereditary disorder with

variable expression and penetrance that affects 4% of all

adults over 40 years of age. It is characterized by a gradual

loss of endothelial cells, corneal edema, and vision loss

and is the main indication of corneal transplantation.

Although mutations of different genes have been evi-

denced in FECD, the most common genetic cause in adults

Figure 3. AS-OCT. Irregular thickened epithelial basement (75% of all

cases) is non-coding CTG TNR expansion in

membrane and hyperreflective dots (arrowheads), with the third intron

of the TCF4 gene.6
undulation and elevation of the epithelium layer, corresponding The reported
prevalence of FECD in myotonic dystro-
to the map-dot-fingerprint corneal lesions in slit-lamp. Multiple phy is
significantly higher than in the general population
hyperreflective endothelial excrescences corresponding to (36%–46% vs 4%,
respectively)5,6 and FECD can be
guttae (arrows).
regarded as a frequent ocular manifestation in patients

with myotonic dystrophy.

Central corneal thickness (IOLMaster; ZEISS®) was Existing
evidence suggests a shared physiopathological
580 µm in the RE and 572 µm in the LE. Specular micros- mechanism underlying
FECD and myotonic dystrophy
copy in turn showed the presence of numerous guttae, with intranuclear
RNA toxicity secondary to CTG triplet
with a destructured endothelial map. Cell counting and expansion.
There have been reports of the presence of
the assessment of pleomorphism and polymegethism FECD in myotonic
dystrophy patients without TCF4
were not possible. No alterations of the ocular fundus expansion but
who do express the DMPK gene in the
were observed.
endothelial cells. In this respect, DMPK expansion could
Anterior segment optical coherence tomography contribute to
the global genetic burden of FECD, and the
(AS-OCT) (DRI OCT Triton; Topcon®) revealed the accu- pathogenic
contribution of CTG repeat expansion may be
mulation of epithelial basement membrane corresponding independent of the
location of the expansion within the
to the subepithelial lesions characteristic of EBMCD, as genome.5,6
well as multiple hyperreflective endothelial excrescences In our
patient, the clinical exploration and diagnostic
corresponding to guttae8,9 (Figure 3). tests
confirmed dual corneal involvement due to two dif-
There was no known family history of myotonic dystro- ferent
dystrophic conditions—FECD and EBMCD—in a
phy or ophthalmological diseases. The parents and the patient diagnosed
with DM1. The described molecular
only female sibling of the patient were healthy, with no bases would
explain the coexisting FECD–myotonic dys-
diagnosis of myotonic dystrophy. The exploration of the trophy
phenotype, though in this case we were unable to
female sibling of the patient revealed no ophthalmological complete the
study with a genetic analysis.
findings of corneal dystrophy. The patient and his sister However,
the presence of EBMCD constitutes an
did not have offspring.
added finding not previously described in association to

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European Journal of Ophthalmology 00(0)

the aforementioned disorders. Also known as map-dot- Funding

fingerprint dystrophy or Cogan’s microcystic dystrophy, The author(s)
received no financial support for the research,
EBMCD is a frequent bilateral corneal dystrophy. authorship,
and/or publication of this article.
Although in a minority of cases mutations of the TGFBI
gene have been identified, the latest IC3D revision of ORCID iD
corneal dystrophies establishes that most cases of Amparo
Gargallo-Benedicto https://orcid.org/0000-0003-1357
EBMCD have no documented hereditary pattern and are -7944
considered to be of degenerative or posttraumatic ori-
gin.10 As a result, genetic studies are generally not made References
in this type of dystrophy. However, a study published in
2016 revealed two mew TGFBI mutations in the context 1. Gattey D, Zhu
AY, Stagner A, et al. Fuchs endothelial cor-

neal dystrophy in patients with myotonic dystrophy: a case

of EBMCD, different from the two previously known series.
Cornea 2014; 33(1): 96–98.
mutations.11
2. Burian HM and Burns CA. Ocular changes in myotonic dys-
A case has been published involving the association of trophy.
Am J Ophthalmol 1967; 63: 22–34.
FECD and EBMD in a patient who moreover presented 3. Eustace P.
Corneal lesions in myotonic dystrophy. Br J
with keratoconus,12 though there have been no descrip- Ophthalmol
1969; 53: 633–637.
tions of the association of myotonic dystrophy and EBMD 4. Heringer JF,
Santo RM, Barbosa LJ, et al. Corneal endothe-
or of the triple association myotonic dystrophy–FECD– lial
dystrophy associated with myotonic dystrophy: a report
EBMCD seen in our patient.
of 2 cases. Cornea 2017; 36(10): e24–e25.
Based on the literature review and the physiopatho- 5. Mootha
VV, Hansen B, Rong Z, et al. Fuchs’ endothelial
logical mechanisms of the three diseases, it could be corneal
dystrophy and RNA foci in patients with myotonic

postulated that the described triple association, with the

dystrophy. Invest Ophthalmol Vis Sci 2017; 58: 4579–4585.

6. Winkler NS, Milone M, Martinez-Thompson JM, et al.

added finding of EBMCD, is a mere coincidence with no Fuchs’
endothelial corneal dystrophy in patients with myo-
causal relationship, since such corneal disorders are tonic
dystrophy, type 1. Invest Ophthalmol Vis Sci 2018;
common. However, corneal dystrophies—more cor- 59(7): 3053–
3057.
rectly referred to as genetic corneal diseases—are char- 7. Wieben ED,
Aleff RA, Tosakulwong N, et al. A common
acterized by genetic heterogeneity and are open to new
trinucleotide repeat expansion within the transcription fac-
future genetic findings.10 Although most cases of adult tor 4
(TCF4, E2–2) gene predicts Fuchs corneal dystrophy.
FECD involve alterations of the TCF4 gene, other genes PLoS ONE
2012; 7(11): e49083.
have also been implicated (SLC4A11, LOXHD2, TCF8, 8. El Sanharawi M,
Sandali O, Basli E, et al. Fourier-domain
KANK4, LAMC1, ATP1B1, ZEB1).5,7 Likewise, if optical
coherence tomography imaging in corneal epithelial
EBMCD is a true dystrophy and not a degenerative dis- basement
membrane dystrophy: a structural analysis. Am J

order, a genetic basis would be present in most cases, in Ophthalmol

2015; 159(4): 755–763.

9. Siebelmann S, Scholz P, Sonnenschein S, et al. Anterior

the same way that TGFBI mutations occur in only a segment
optical coherence tomography for the diagnosis of
minority of cases.
corneal dystrophies according to the IC3D classification.
Genetic studies have established a common molecu- Surv
Ophthalmol 2018; 63(3): 365–380.
lar mechanism explaining the high prevalence of the 10. Weiss JS,
Moller HU, Aldave AJ, et al. IC3D classifica-
FECD–myotonic dystrophy phenotype. In the same tion of
corneal dystrophies—edition 2. Cornea 2015; 34(2):
way, genome-wide studies involving a large series of 117–159.
patients with the three described diseases may discover 11. Evans CJ,
Davidson AE, Carnt N, et al. Genotype-phenotype
new mutations or still unknown genetic alterations that
correlation for TGFBI corneal dystrophies identifies
could explain the triple association described in our p.
(G623D) as a novel cause of epithelial basement mem-
case.
brane dystrophy. Invest Ophthalmol Vis Sci 2016; 57(13):

5407–5414.

12. Mazzotta C, Traversi C, Raiskup F, et al. First identification

Declaration of conflicting interests
of a triple corneal dystrophy association: keratoconus, epi-
The author(s) declared no potential conflicts of interest with thelial
basement membrane corneal dystrophy and Fuchs’
respect to the research, authorship, and/or publication of this
endothelial corneal dystrophy. Case Rep Ophthalmol 2014;
article.
5(3): 281–288.