REVI EW Open Access

Spontaneous closure of macular holes secondary

to posterior uveitis: case series and a literature
review
Nicolas Bonnin
1*
, Pierre-Loc Cornut
2
, Florian Chaise
2
, Elodie Labeille
2
, Helene Janin Manificat
2
, Audrey Feldman
2
,
Laurent Perard
3
, Franck Bacin
1
, Frdric Chiambaretta
1
and Carole Burillon
2
Abstract
The occurrence of a macular hole due to posterior uveitis is infrequently reported. We report the evolution of three
cases of macular holes secondary to posterior segment inflammation. A complete inflammatory and infectious
assessment found one case of toxocariasis, one of sarcoidosis, and one of syphilis. After medical etiological
treatment, macular hole closure was rapidly obtained in all the cases and confirmed by spectral domain optic
coherence tomography, with visual acuity improvement. Fibrous scarring developed in two cases, and foveal
photoreceptor complex normalization was observed in the sarcoidosis case. These observations demonstrate that
macular holes secondary to posterior uveitis frequently resolve without surgical intervention and so could be
underdiagnosed if the patient is not evaluated at the time of onset before spontaneous hole closure.
Keywords: Posterior uveitis, Macular hole, Toxocara canis, Sarcoidosis, Syphilis
Review
Introduction
Ocular inflammatory diseases can cause sight loss by
macular impairment. Cystoid macular edema is the princi-
pal sight-threatening complication [1] in uveitis patients.
Among possible macular inflammatory alterations,
Nussenblatt describes macular hole occurrence as a
very rare complication [2], being more often idiopathic
or senile, postoperative or due to an epiretinal mem-
brane, but rarely to posterior segment inflammation.
Here we report three cases of macular hole secondary
to posterior uveitis that spontaneously resolved after
etiological treatment, and present a review of relevant
literature. Written informed consent was obtained from
all patients for publication of this report.
Case no. 1
A 58-year-old farmer presented for a sudden deterior-
ation of visual acuity in his left eye. His visual acuity was
20/40 in his right eye and counting fingers in his left
eye. Full examination of the right eye showed cataract.
In the left eye, slit-lamp examination showed a slight
Tyndall effect with small keratic precipitates. Ocular
pressure was normal, and fundus examination showed a
mild diffuse hyalitis with numerous vitreous aggregates
(at the top of the macula and along the vessels) overlying
a yellowish macular lesion estimated at two papillary
diameters. It was not pigmented (Figure 1A). Fluorescein
angiography showed a centripetal impregnation of the
macular lesion (Figure 1B,C) as seen in toxoplasmosis
infections [3], and a subclinical temporal hypofluores-
cent area in addition to the macular retinochoroidal
lesion. Indocyanine green (ICG) angiography showed a
late impregnation of the margins of the lesion. Spectral
domain optical coherence tomography (SD-OCT) as-
sessment showed a thickened hyper-reflective retina and
an inverted curvature of the posterior pole, showing
probable concomitant impairment of the choroid and
confirming the diagnosis of chorioretinitis (Figure 1D).
The Goldmann-Witmer coefficient was positive for
Toxocara canis, and albendazole was given to the patient
for 2 weeks. At the end of the treatment, the OCT
* Correspondence: nicoasmo@yahoo.fr
1
Service d'Ophtalmologie, Ple Mdecine Interne-Ophtalmologie-ORL, CHU
Clermont-Ferrand, Clermont-Ferrand 63003, France
Full list of author information is available at the end of the article
2013 Bonnin et al.; licensee Springer. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction
in any medium, provided the original work is properly cited.
Bonnin et al. Journal of Ophthalmic Inflammation and Infection 2013, 3:34
http://www.joii-journal.com/content/3/1/34
displayed the appearance of a stage III macular hole
(also evident at fundus examination), as the posterior
hyaloid was detached from the fovea (Figure 2A). After a
6-month follow-up, the macular hole had spontaneously
resolved, filled by fibrous scar tissue associated with an
epiretinal membrane (Figure 2B,C,D). The final visual
acuity in the left eye was 20/100 after a 3-year follow-up.
Case no. 2
A 28-year-old woman presented for sight loss in her left
eye. Her visual acuity was 20/20 in her right eye and 20/100
in her left eye. Anterior chamber examination showed
granulomatous keratic precipitates in the left eye but
no Tyndall effect. Fundus examination showed bilateral
optic disc edema and a macular hole on the left.
Figure 1 Case 1, eye examination results before treatment. (A) Retinophotography of the right eye: mild diffuse vitritis, vitreous aggregates
(at the top of the macula and along the vessels), and macular chorioretinitis focus. (B, C) Fluorescein angiography of the right eye: centripetal
impregnation of the macular lsion and temporal subclinical hypofluorescent area. (D) SD-OCT of the right eye: thickened hyper-reflective retina
and inverted curvature of the posterior pole showing choroid impairment.
Figure 2 Case 1, eye examination results after treatment. (A) SD-OCT of the right eye: stage III macular hole. (B) Retinophotography of the
right eye: a fibrous closure associated with an epiretinal membrane, spontaneously developed. (C) Red-free photography showing large macular
fold due to fibrosis. (D) SD-OCT of the right eye: closure of the macular hole, filled with fibrosis.
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Fluorescein angiography confirmed the bilateral optic
nerve head diffusion and showed bilateral phlebitis
(Figure 3A,B). Both fluorescein angiography and ICG
angiography show hypofluorescent linear lesions in the
macular area (Figure 3C). SD-OCT confirmed the pres-
ence of a pseudo macular hole (Figure 3D).The
diagnosis workup was positive for sarcoidosis: increase
in the angiotensin-converting enzyme to 160 U/L, me-
diastinal adenopathies on the computed tomography,
increased rate of CD4/CD8 lymphocyte level in
broncho-alveolar lavage, and multiple epithelioid and
gigantocellular granuloma without caseous necrosis in
Figure 3 Case 2, eye examination results before treatment. (A, B) Fluorescein angiography of both eyes: bilateral optic disc edema and
phlebitis (arrows). (C) Both fluorescein angiography and ICG angiography show hypofluorescent linear lesions in the macular area. (D) Macular
SD-OCT of the left eye: pseudohole.
Figure 4 Case 2, eye examination results after treatment. (A, B) Fluorescein angiography of the left eye: healing of the optic disc edema and
vascularitis. (C) Macular SD-OCT of the left fundus: closure of the macular hole promoted by the posterior hyaloid release and development of an
epiretinal membrane.
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Figure 5 Case 3, eye examination results before treatment. (A, B) Fluorescein angiography of the left eye: macular window effect.
(C) Indocyanine green angiography of the left eye: multiple hypofluorescent parafoveolar chorioretinitis foci. (D) Macular SD-OCT of the left eye:
macular hole.
Figure 6 Case 3, eye examination results after treatment. (A, B) Fluorescein angiography of the left eye: macular RPE alterations. (C)
Indocyanine green angiography of the left eye: healing of the chorioretinitis foci. (D) Macular SD-OCT of the left fundus: closure of hole with
some cystoid alterations remaining.
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analysis of bronchial biopsies. A prednisolone treatment
at 1 mg/kg was given. After a 3-month follow-up, the
visual acuity had increased to 20/25 in the left eye. Fun-
dus examination and fluorescein angiography showed
bilateral healing of the optic disc edema and vascularitis
(Figure 4A,B). SD-OCT showed closure of the macular
hole with normalization of the foveal photoreceptor
layer and the development of an epiretinal membrane
(Figure 4C). Examination remained stable after a 3-year
follow-up.
Case no. 3
A 39-year-old man was referred for a 2-day loss of visual
acuity in his left eye. This patient had a medical history
of hepatitis C infection, human immunodeficiency infec-
tion with normal T lymphocyte count and undetectable
viral load, and a known evolutive syphilis infection.
Being allergic to penicillin, he had been treated using
oral tetracycline for several months with no decrease in
serum Treponema pallidum hemagglutination assay-
Venereal Disease Research Laboratory (TPHA-VDRL).
His visual acuity was 20/20 in his right eye and counting
fingers in his left eye. Slit-lamp examination showed a
mild Tyndall effect in the anterior chamber and a macular
hole (Figure 5A,B). Fluorescein angiography showed the
macular hole; indocyanine green angiography revealed
multiple hypofluorescent parafoveolar chorioretinitis foci
(Figure 5C), and SD-OCTconfirmed the hole (Figure 5D).
A complete inflammatory and infectious assessment
found only increased serum TPHA-VDRL. The patient
was treated by intravenous ceftriaxone at 2 g/day for 1
week and then at 1 g/day for a further week. One month
after treatment, the angiography showed healing of the
chorioretinitis foci (Figure 6A,B,C). After a 2-year follow-
up, visual acuity had increased to 20/40, and the OCT
showed a subtotal closure of the macular hole with some
cystoid alterations remaining (Figure 6D).
Discussion
Intraocular inflammatory diseases have long been described
as a major cause of blindness [1]. In all kinds of uveitis,
bilateral legal blindness develops in 4% of patients, uni-
lateral blindness in 14%, bilateral visual impairment in
6%, unilateral impairment in 11%, and unilateral im-
pairment with blindness of the other eye in 4% to 5%.
The occurrence of a macular hole in a context of uve-
itis is an unusual, little-described complication.
In 1986, Nussenblatt [2] studying macular alterations
in uveitic patients described this evolution as uncom-
mon. Later, in a retrospective study of 582 patients with
uveitis [1], no macular hole was described. Neither
prevalence nor incidence of macular holes linked to pos-
terior segment inflammation can be established from the
literature, cases or short series being too scant.
Table 1 Review of the literature of macular holes in a
context of intraocular inflammation
Etiology Number of cases Study
Behcet's disease 35 [5-11]
Idiopathic intermediate uveitis 4 [9,12]
Idiopathic posterior uveitis 2 [9]
Bartonella henselae 2 [13,14]
Toxoplasmosis 2 [15,16]
Vogt-Koyanagi-Harada 2 [17]
CMV retinitis 1 [9]
HLA B27 1 [18]
Bilateral idiopathic anterior uveitis of
unknown etiology
1 [19]
Serpiginous choroiditis 1 [20]
Fungal endophthalmitis 1 [21]
T/NK lymphoma 1 [22]
Presumed histoplasmosis 1 [23]
Immune recovery uveitis in AIDS patients
with CMV retinitis
1 [24]
Figure 7 Physiopathology of (A) iodiopathic macular holes compared with (B) macular holes in circumstances of inflammation.
Bonnin et al. Journal of Ophthalmic Inflammation and Infection 2013, 3:34 Page 5 of 7
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On the other hand, in a histopathological study of 17
lamellar and 18 full-thickness macular holes [4], mild to
moderate choroiditis was present in six eyes in the
macular area. One of these cases was suspected of being
an incidental finding because the choriocapillaris, Bruch's
membrane, and the retinal pigment epithelium (RPE) were
intact. This study gives us an approximate figure for the
proportion of macular holes linked to posterior uveitis in
all macular holes. However, there is a selection bias: the
eyes of this study were obtained from enucleations or
post-mortem, so the results do not reflect the general epi-
demiology of the disease.
The literature reports 55 cases of macular hole sec-
ondary to posterior uveitis (Table 1): 35 Behcet's disease
[5-11], 3 idiopathic intermediate uveitis [9], 2 idiopathic
posterior uveitis [9], 1 bilateral intermediate uveitis [12],
2 Bartonella henselae [13,14], 2 toxoplasmosis [15,16], 2
Vogt-Koyanagi-Harada [17], 1 cytomegalovirus (CMV)
retinitis [9], 1 HLA B27 uveitis [18], 1 bilateral anterior
uveitis [19], 1 serpiginous choroiditis [20], 1 fungal
endophthalmitis [21], 1 T/natural killer (NK) lymphoma
[22], 1 presumed histoplasmosis [23], and 1 immune re-
covery uveitis in an AIDS patient after CMV retinitis [24].
Idiopathic macular holes can be explained by a triple
constraint [25]: (1) an antero-posterior traction, often
effected by the posterior vitreous detachment; (2) a tan-
gential traction especially when there is an epiretinal
membrane or a lateral shifting of vitreoretinal adher-
ence; and (3) an intraretinal constraint that weakens the
inner retinal surface by inducing cystic changes and con-
tributes to the macular hole (Figure 7A). A parallel can
be done in circumstances of posterior segment inflam-
mation: the inflammation often induces changes or
liquefaction of the vitreous body and contributes to the
posterior vitreous detachment which realizes the first
constraint. The development of an epiretinal membrane
is classical in uveitis [26], responsible of a tangential
traction, as seen in the cases 1 and 2. Finally, chorioreti-
nitis foci or cystoid macular edema cause the third con-
straint, fragilizing the retinal tissue (Figure 7B). This
explains why treating the inflammation can relieve these
constraints or tractions and produce spontaneous heal-
ing of the macular hole. The report of Halkiadakis et al.
[18] on a spontaneous macular hole closure after peri-
bulbar steroid injection in the case of a HLA B27 uveitis
demonstrates this well.
The relatively old references on the low prevalence of
macular hole in uveitic patients could be explained by the
fact that OCT is a recent tool. Our cases also show the im-
portance of the SD-OCT in uveitis to confirm cystoid
macular edema, the principal sight-threatening effect in
uveitis [1]. OCT can also be a diagnostic criterion in some
etiologies such as intermediate uveitis or a poor-prognosis
marker as in Birdshot retinochoroidopathy, indicating a
specific care requirement. OCT is necessary during follow-
up after resolution of active inflammation to seek the cause
of any unexplained sight loss and may reveal a closed
macular hole filled by fibrosis.
SD-OCT is useful for the preoperative evaluation of
the inflammatory secondary epiretinal membrane to
evaluate the benefits of the procedure: in our first case,
in which an epiretinal membrane developed, there was a
partial posterior vitreous detachment, and so there is a
persistent risk of macular hole recurrence in a such
damaged and weakened retina, with very small hope of
visual improvement.
Conclusion
The occurrence of a macular hole linked to posterior
uveitis is an uncommon but possibly underestimated
cause of sight loss. Etiological treatment seems to lead
to macular hole closure in most such cases. SD-OCT is
very useful for assessing the evolution of these cases and
should be performed whenever there is a posterior in-
volvement or unexplained sight loss in uveitis patients.
Competing interest
The authors declare that they have no competing interests.
Authors contributions
NB wrote the manuscript, synthetized the cases, and made the literature
review. PLC was the co-author; he corrected and directed the redaction of
the manuscript and followed the cases. FC, EL, HJM, AF, and LP participated
to the management of the cases and the diagnosis. FC, FB, and CB
participated in the design of the study and its coordination. All authors read
and approved the final manuscript.
Acknowledgments
This paper was presented at the SFO (Socit Franaise d'Ophtalmologie)
2011 Congress. We are grateful to ATT Medical Society for proofreading the
manuscript.
Author details
1
Service d'Ophtalmologie, Ple Mdecine Interne-Ophtalmologie-ORL, CHU
Clermont-Ferrand, Clermont-Ferrand 63003, France.
2
Department of
Ophthalmology, Hospices Civils de Lyon, University Hospital, Claude Bernard
Lyon I University, Lyon 69008, France.
3
Department of Internal Medicine,
Edouard-Herriot Hospital, place d'Arsonval, Lyon 69008, France.
Received: 31 August 2012 Accepted: 25 January 2013
Published: 11 February 2013
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doi:10.1186/1869-5760-3-34
Cite this article as: Bonnin et al.: Spontaneous closure of macular holes
secondary to posterior uveitis: case series and a literature review.
Journal of Ophthalmic Inflammation and Infection 2013 3:34.
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