Choroidal infarction in a glaucoma patient with Flammer syndrome: a case report with a long term follow-up
© The Author(s). 2017
Received: 27 August 2016
Accepted: 3 March 2017
Published: 14 March 2017
We present a long term follow-up of a young female patient with choroidal infarction, primary open angle glaucoma and Flammer syndrome. The patient had no classical risk factors for vascular occlusions, except for the presence of Flammer syndrome. The essential feature of this syndrome is primary vascular dysregulation, sometimes including vasospasm. The vessels of affected people respond more intensely to a number of stimuli, such as coldness or emotional stress. Any organ can be involved, including parts of the eye. The dense autonomic innervation of the choroidal vessels predisposes them particularly to vasospasms.
The patient was originally referred to our centre because of a deep unilateral paracentral scotoma with the presumptive diagnosis of a normal tension glaucoma. The discrepancy between the visual field defect and the optic nerve head morphology, however, led us to a vascular evaluation by a simultaneous fluorescein/indocyanine green angiography. This revealed an antecedent choroidal infarction that explained the visual field scotoma and the retinal nerve fibre layer defect in the corresponding area. During the follow-up period of 11 years, the patient also developed bilateral glaucomatous optic neuropathy despite a well-controlled intraocular pressure.
We hypothesise that in the patient presented here, the Flammer syndrome contributed to both the acute unilateral choroidal infarction and to the chronic development of bilateral glaucomatous optic neuropathy.
KeywordsChoroidal infarction Flammer syndrome Primary vascular dysregulation Glaucoma
Occlusions of ocular vessels are serious and sight threatening events. They occur particularly in elderly people with cardiovascular risk factors. However, such events can also occur, although much less frequently, in younger people without classical cardiovascular risk factors and in the absence of other diseases. Functional reversible vasoconstrictions (vasospasms) are considered possible mechanisms for such infarctions in younger people.
If vasospasms are present in several organs of the same subject, simultaneously or sequentially, the term vasospastic syndrome is used. The more general term vascular dysregulation encompasses not only spasms but any form of inappropriate constriction and dilatation. If vascular dysregulation is not caused by a disease, it is called primary vascular dysregulation (PVD). Subjects with PVD not only have vascular dysregulation but also other signs and symptoms, as summarized in a recent review [1, 2]. Therefore, the combination of PVD with this cluster of associated vascular and nonvascular signs and symptoms is called Flammer syndrome (FS) . The main vascular feature of FS is a predisposition to respond differently to a number of stimuli such as coldness or emotional stress [3, 4].
PVD can affect any organ, including the eye [1, 2], leading to a variety of effects depending on the intensity and duration of the resulting hypoxia. In subjects with PVD, vascular occlusions (including Susac syndrome, anterior ischemic optic neuropathy, and myocardial infarctions) can occur, though rarely, at a young age and in the absence of risk factors for arteriosclerosis. This is particularly true for retinal vein occlusions [1, 2]. Most often PVD is harmless. Unstable blood flow, however, increases local oxidative stress, contributing to the pathogenesis of glaucomatous damage [5–9]. Disturbed autoregulation and fluctuation of ocular perfusion pressure leads to an unstable oxygen supply and therefore to local mitochondrial oxidative stress.
Here we present a young female patient with classical FS who suffered from both an unilateral parapapillary choroidal infarction and a primary open angle glaucoma (POAG).
The patient and family history was negative for thrombotic disease or hypercoagulability. Classical risk factors for vascular occlusion were excluded: homocysteine and lipid serum levels were within normal limits, antinuclear antibodies levels in the blood were low and unspecific, and antibodies characteristic of antiphospholipid syndrome (anticardiolipin antibodies and antibodies against β-2-glicoprotein) in the blood were also negative.
As the VF defect was threatening fixation, we introduced an IOP-lowering treatment. First, a therapy with latanoprost was initiated, and later a fixed combination of latanoprost and timolol, but IOP did not diminish satisfactorily. On the latter therapy, IOP fluctuated between 15 to 19 mm Hg in the RE and between 12 to 15 mm Hg in the LE on the diurnal curve, with the highest values in the morning. Thus, the therapy was changed to a fixed combination of bimatoprost and timolol. Under this therapy, IOP measurements did not exceed 11–12 mm Hg in both eyes.
Discussion and Conclusions
We described here a young female patient with classical FS referred to our department with a suspicion of glaucomatous optic neuropathy. However, the deep local VF defect in the RE (Fig. 1) did not correspond to the morphology of the ONH. Both optic discs were only slightly and symmetrically excavated (Fig. 2). There was no notching, which could explain the deep, localized VF scotoma. The angiography revealed combined RPE/choriocapillaries atrophy (Fig. 3) corresponding to the VF defect (Fig. 1), indicating an antecedent choroidal infarction. The examination with GDx revealed reduced RNFL thickness in the corresponding region (Fig. 4).
The patient had no risk factors for arterial occlusions, except a classical FS, which likely predisposed the patient to choroidal infarction. Choroidal infarctions in the context of vasospasms have already been described in the literature. FS has been described to be a risk factor for both retinal arterial and vein occlusions , and choroidal infarction . The autoregulatory capacity of the choroid is less efficient than in the retina or ONH [5, 12]. The choroidal vessels are intensively innervated by the autonomic nervous system and are therefore prone to vasospasm. Increased choroidal vasoconstrictive response to sympathetic stimulation was reported in FS subjects . In addition, FS subjects have lower autoregulatory capacity of choroidal circulation than healthy controls [1, 12]. Diminished or even absent autoregulation in the peripapillary choroid has also been described in POAG patients . During the 11-year follow-up period, the patient also developed glaucomatous damage as demonstrated by HRT and GDx examinations (Figs. 2 and 4), in spite of a well-controlled IOP.
FS is considered to be a risk factor for both occlusions of ocular vessels and glaucomatous optic neuropathy (particularly in normal tension glaucoma). The patient presented here had FS, a unilateral nonrecurring choroidal infarction, and a chronic progressive bilateral glaucomatous optic neuropathy. We hypothesise that vasospasms induced the choroidal infarction, and chronic unstable blood flow in the optic nerve head (due to disturbed autoregulation and low blood pressure) increased local oxidative stress and thereby contributed to the development of the glaucomatous optic neuropathy.
The pathogenesis of FS is still unclear. Vascular endothelial dysfunction as well as autonomic nervous system dysregulation could be involved [6–8]. The relationship between the FS and the FS related diseases needs to be established further, in order to promote early diagnosis and targeted prevention in groups at risk.
In summary, we present here a case of a young female patient with FS who experienced an unilateral choroidal infarction despite the absence of classical vascular risk factors, and a bilateral glaucomatous optic neuropathy despite a well-controlled IOP. FS is considered to be a risk factor for both occlusions of ocular vessels and glaucomatous optic neuropathy. The infarction could be induced by vasospasm. We hypothesize that FS also contributed to the development of glaucomatous optic neuropathy by disturbed autoregulation and instability of optic nerve blood flow.
Central corneal thickness
Indocyanine green angiography
Normal tension glaucoma
Optic nerve head
Primary open angle glaucoma
Primary vascular dysregulation
Retinal nerve fibre layer
Retinal pigment epithelium
Availability of data and materials
BTB provided conception and design of the paper, interpreted the data, participated in drafting the paper, reviewed literature. IGL critically reviewed the manuscript finally. APW collected and analyzed the data, reviewed the manuscript. KK participated in drafting the paper and critically reviewed the manuscript. All authors read and accepted the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Written informed consent was obtained from the patient for publication of the clinical details of this case report and accompanying clinical images.
Ethics approval and consent to participate
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Flammer J, Konieczka K, Flammer AJ. The primary vascular dysregulation syndrome: implications for eye diseases. EPMA J. 2013;4(1):14.View ArticlePubMedPubMed CentralGoogle Scholar
- Konieczka K, Ritch R, Traverso CE, Kim DM, Kook MS, Gallino A, Golubnitschaja O, Erb C, Reitsamer HA, Kida T, Kurysheva N, Yao K. Flammer syndrome. EPMA J. 2014;5(1):11.View ArticlePubMedPubMed CentralGoogle Scholar
- Saner H, Wurbel H, Mahler F, Flammer J, Gasser P. Microvasculatory evaluation of vasospastic syndromes. Adv Exp Med Biol. 1987;220:215–8.PubMedGoogle Scholar
- Guthauser U, Flammer J, Mahler F. The relationship between digital and ocular vasospasm. Graefe’s Arch Clin Exp Ophthalmol. 1988;226:224–226.
- Flammer J, Orgul S, Costa VP, Orzalesi N, Krieglstein GK, Metzner Serra L, Renard JP, Stefansson E. The impact of ocular blood flow in glaucoma. Progr Ret Eye Res. 2002;21:359–93.View ArticleGoogle Scholar
- Grieshaber M, Mozaffarieh M, Flammer J. What is the link between vascular dysregulation and glaucoma? Surv Ophthalmol. 2007;52 Suppl 2:144–54.View ArticleGoogle Scholar
- Nicolela TM. Clinical clues of vascular dysregulation and its association with glaucoma. Can J Ophthalmol. 2008;43:337–41.View ArticlePubMedGoogle Scholar
- Terelak-Borys B, Czechowicz-Janicka K. Investigation into the vasospastic mechanisms in glaucomatous neuropathy. Klin Oczna. 2011;113:201–8.PubMedGoogle Scholar
- Konieczka K, Fränkl S, Todorova MG, Henrich PB. Unstable oxygen supply and glaucoma. Klin Monbl Augenheilkd. 2014;231:121–6.View ArticlePubMedGoogle Scholar
- Flammer J. The concept of visual field indices. Graefes Arch Clin Exp Ophthalmol. 1986;224(5):389–92.View ArticlePubMedGoogle Scholar
- Flammer J, Pache M, Resink T. Vasospasm, its role in the pathogenesis of disease with particular reference to the eye. Progr Ret Eye Res. 2001;20:319–49.View ArticleGoogle Scholar
- Hasler PW, Orgul S, Gugleta K, Vogten H, Zhao X, Gherghel D, Flammer J. Vascular dysregulation in the choroid of subjects with acral vasospasm. Arch Ophthalmol. 2002;120:302–7.View ArticlePubMedGoogle Scholar
- Gugleta K, Orgul S, Hasler WP, Picornell T, Gherghel D, Flammer J. Choroidal vascular reaction to hand-grip stress in subjects with vasospasm and its relevance in glaucoma. Invest Ophthalmol Vis Sci. 2003;44:1573–80.View ArticlePubMedGoogle Scholar
- Ulrich A, Ulrich C, Barth T, Ulrich WD. Detection of disturbed autoregulation of the peripapillary choroid in primary open angle glaucoma. Ophthalmic Surg Lasers. 1996;27:746–57.PubMedGoogle Scholar