Abstract
Background/purpose
Vogt-Koyanagi-Harada (VKH) disease is a primary stromal choroiditis and a bilateral granulomatous panuveitis which, if not treated early and properly, could have a deleterious evolution. The purpose of our case report is to demonstrate that “so called” unilateral VKH disease should be investigated further with an Indocyanine Green Angiography (ICGA), in order to detect subclinical choroidal involvement of the other eye.
Case report
We present a case of 42-year old woman who came to see us for second opinion. She had consulted elsewhere for a left uveitis and had been treated with a periocular corticosteroid injection. At presentation she mentioned persistent headaches. Visual acuity on the Snellen scale was 1.0 OD and 0.5 OS. Slit-lamp examination showed granulomatous (rare mutton-fat KPs) signs in her left eye. Laser flare photometry showed a subclinical flare of 17.8 ph/ms OD and a flare of 66.4 ph/ms OS (normal values 3–6 ph/ms). Fundus examination showed left discoloration due to choroidal infiltration with a normal fundus aspect OD. ICGA showed a diffuse choroiditis also in the apparently normal right eye. Lumbar puncture confirmed the diagnosis of VKH and appropriate treatment was introduced.
Conclusion
VKH disease results from a generalized autoimmune process against melanocyte associated antigens starting in the choroidal stroma. It can be asymmetrical but is always bilateral, as long as investigations such as ICGA, able to detect subclinical choroiditis, are performed.
Introduction
Vogt-Koyanagi-Harada (VKH) disease is a primary stromal choroiditis caused by an autoimmune reaction against melanocyte associated proteins [1]. Ocular disease is associated with acute systemic manifestations including inflammation of the meninges (CSF mononuclear pleiocytosis) and auditory disturbances and later, if the disease is left to evolve, with integumentary changes (vitiligo, alopecia and poliosis). This is the way VKH is classically described in articles and textbooks and corresponds, actually to non-treated or undertreated disease evolving from acute to chronic disease [2]. The first comprehensive series was reported by Koyanagi in 1929, describing the natural course of the disease at a time when no treatment was available, not altering the natural course of the 16 reported cases which were all bilateral [3]. Likewise, in the report by Harada in 1926 on 5 cases with posterior findings of what is now called VKH disease, the involvement was bilateral [4]. This is how he described the time course: “The patients developed onset of visual disturbance in both eyes, either simultaneously or with a few days of delay from one eye to the other” [4].
It is important to be aware of the disease mechanism at the origin of VKH disease, namely a primary stromal choroiditis, generated by an autoimmune reaction against proteins associated with stromal melanocytes [1, 5]. This means that inflammation exclusively starts within the choroidal stroma and only secondarily spills over to involve the other compartments of the eye [6]. Until the mid-1950s no inflammation suppressive treatment was available. Since the mid-1950s corticosteroids started to be given, however usually with delay, as it was still an experimental treatment [7, 8]]. This explains why the reported cases until effective treatment became available, were always bilateral [9,10,11]. Indeed, lack of efficient management allowed asymmetrical cases to become bilateral.
“Unilateral” cases started to be described since efficient inflammation suppressive therapy such as corticosteroid therapy or other became available and was used early in the disease. In these cases, the typical clinical presentation in one eye led to prompt systemic treatment so that the subclinical involvement of the contralateral eye was suppressed and never emerged. Since the mid-1990s, precise investigation of choroidal inflammation has become possible thanks to ICGA, allowing to detect subclinical disease during initial onset disease and to monitor occult subclinical recurrence during follow-up. To a lesser extent this is also possible with Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) [12,13,14].
At least 11 cases of “unilateral” VKH disease in 8 articles were found in the literature (Table 1) [15,16,17,18,19,20,21,22]. None of them performed the investigations capable to show subclinical inflammatory involvement of the choroid in the other eye such as ICGA or EDI-OCT. [23, 24] We report a case of “so-called unilateral” VKH disease that in reality presented bilateral involvement, which was clinically apparent in one eye and subclinical in the contralateral eye with lesions only detected by ICGA.
Case report
A 42-year old woman consulted the Centre for Ophthalmic Specialised Care (COS) because of decreased visual acuity in her left eye. She had been seen several weeks earlier for photopsias. She had been investigated for uveitis but, allegedly, investigations were negative and a periocular corticosteroid injection had been administered on the left side.
When we saw the patient, she complained of persistent headaches and her visual acuity on the Snellen scale was 1.0 OD and 0.5 OS. At the slit-lamp there was no flare OD and a 1+ flare OS. Laser flare photometry showed a subclinical flare of 17.8 ph/ms OD and a flare of 66.4 ph/ms OS (normal values 3–6 ph/ms). On the left there were rare mutton-fat keratic precipitates and a few Koeppe nodules as well as 1+ of anterior vitreous cells. Fundus examination showed left yellow discoloration indicating choroidal infiltration while the right fundus was normal (Fig. 1).
Fluorescein angiography was normal in the right eye with the exception of a slightly hyperfluorescent disc, while on the right eye there was a pronounced disc hyperfluorescence and several areas of hyperfluorescence inferior-temporally (Fig. 2a & b). ICGA, however, showed bilateral hypofluorescent dark dots (HDDs) on both sides indicating bilateral diffuse choroiditis (Fig. 3a & b).
a ICGA OD of VKH case at presentation. ICGA shows numerous evenly distributed HDDs and loss of identification of choroidal vessels, while fundus picture and FA are normal, identifying subclinical diffuse choroiditis. b ICGA OS of VKH case at presentation. ICGA shows numerous evenly distributed HDDs and loss of identification of choroidal vessels and ICGA disc hyperfluorescence indicating sever inflammation
Anticipating vigorous dual steroidal and non-steroidal immunosuppression, in order to be sure of the diagnosis and to have the patient accept the therapy we performed a lumbar puncture showing a pleiocytosis of 243/3 lympho-monocytes in the cerebrospinal fluid. Dual corticosteroid and cyclosporin therapy was initiated at once. Two months later, under therapy, the colour of the fundus OS returned to normal (Fig. 4a & b), FA showed decrease of hyperfluorescence of the optic disc and temporal inferior area of hyperfluorescence and ICGA showed disappearance of HDDs and restoration of the choroidal vessels (Fig. 5a & b). No optical coherence tomography (OCT) data were available as the patient was seen in the pre-SD-OCT and pre-EDI-OCT era.
a ICGA OD of VKH case 2 months after dual steroidal and non-steroidal immunosuppression. ICGA shows disappearance of HDDs and clear visualisation of normalized choroidal vessels. b ICGA OS of VKH case 2 months after dual steroidal and non-steroidal immunosuppression. ICGA shows vanishing of HDDs and again clear visualisation of normal-appearing choroidal vessels
No clinically apparent disease developed on the right side. Unfortunately, after an attempt to taper therapy one year later, the disease recurred bilaterally and the patient had to be treated during the following 18 years with diverse combinations of inflammation suppressive therapies including anti-TNF agents.
Discussion
VKH disease results from a generalized autoimmune aggression of melanocyte related proteins starting in the choroidal stroma and extending anteriorly in the eye and to other sites if treatment is not introduced without delay [6]. Asymmetrical ocular involvement can happen and has been described, starting with Harada’s report [4]. In the ground-breaking report of Koyanagi in 1929, two of the 4 new cases reported had a delayed involvement of the second eye [3]. Lavezzo and coll. Indicate that there is a delay of involvement of the second eye in 30% of cases [25]. In the absence of inflammation suppressive therapy before the mid-1950s or thereafter, when corticosteroid therapy was usually applied with delay [7, 8], ultimately all cases developed bilaterality, even those cases with initially unilateral presentation. Introduction of rapid and efficient therapy was at the origin of the reports on apparently unilateral cases [26]. Indeed, prompt treatment following clinically apparent disease in one eye resolved uveitis in the affected eye but also suppressed the subclinical disease in the contralateral eye. The latter eye therefore never developed clinically apparent disease. In the “unilateral” cases reported, two patients were investigated by ICGA that showed bilateral ICGA signs, one of which showed discreet signs in the apparently uninvolved eye before full-blown ICGA signs appeared 2 months later [27]. An interesting report showed delayed involvement of the second eye after the first eye showed VKH signs [28]. Unfortunately no OCT data were available as the case was seen in the pre-EDI-OCT era. It would be interesting to find out whether this imaging modality would be able to uncover subclinical involvement in the fellow eye. Subsequent evolution of the cases was available in two articles. In the first one sunset glow fundus (SGF) developed in both eyes confirming involvement of the fellow eye [12]. In the 3 cases of the second article, the fellow eyes did not develop SGF, probably indicating that efficient therapy was introduced early enough to prevent depigmentation in the contralateral eye [13].
Conclusion
In essence there is no such thing as unilateral VKH. All those VKH cases that were labelled as unilateral only because proper investigations to detect choroidal subclinical inflammation in the other eye were not performed.
Availability of data and materials
The data used during the current article are available from the corresponding author on reasonable request.
Abbreviations
- VKH:
-
Vogt-Koyanagi-Harada
- ICGA:
-
Indocyanine Green Angiography
- CSF:
-
Cerebrospinal Fluid
- HDDs:
-
Hypofluorescent dark dots
- EDI-OCT:
-
Enhanced Depth Imaging Optical Coherence Tomography
References
Gocho K, Kondo I, Yamaki K (2001) Identification of autoreactive T cells in Vogt-Koyanagi-Harada disease. Invest Ophthalmol Vis Sci 42(9):2004–2009
Attia S, Khochtali S, Kahloum R, Zouali S, Khairallah M (2012) Vogt-Koyanagi-Harada disease. Expert Rev Ophthalmol 7:565–585
Koyanagi Y (1929) Dysakusis, alopecia und poliosis bei schwerer uveitis nicht traumatischen ursprungs. Klin Monatsbl Augenheilkd 82:194–211
Harada E (1926) Beitrag zur klinischen Kenntnis von Michteitriger Choroiditis (choroiditis diffusa acta). Acta Soc Ophthalmol Jpn 30:356–378
Bouchenaki N, Herbort CP (2004) Stromal choroiditis. In: Pleyer U, Mondino B (eds) Essentials in Ophthalmology: Uveitis and Immunological Disorders. Springer, Berlin, Heidelberg, New York, pp 234–253
Herbort CP Jr, El Asrar AMA, Yamamoto JH, Pavesio CE, Gupta V, Khairallah M, Tugal-Tutkun I, Soheilian M, Takeuchi M, Papadia M (2017) Reappraisal of the management of Vogt-Koyanagi-Harada disease: sunset glow fundus is no more a fatality. Int Ophthalmol 37(6):1383–1395
Casey TA, Samman PD (1960) Two cases of Vogt Koyanagi-Harada disease. Proc R Soc Med 53:963–965
Reed H, Lindsay A, Silversides JL, Speakman J, Monckton G, Rees DL (1958) The uveo-encephalitic syndrome of Vogt-Koyanagi-Harada disease. Can Med Assoc 79:451–459
Vogt A (1906) Fruhzeitigers Ergrauen der Zilien und Bemerkungen uber den sogenannten plotlzichen Eintritt dieser Veranderung. Klin Monatsbl Augenheilkd 4:228–242
Babel J (1932) Syndrome de Vogt-Koyanagi (Uveite bilaterale, poliosis, alopecie, vitiligo et dysacousie). Schweiz Med Wochenschr Nr 44:1136–1140
Salus R (1932) Harada disease. Klin Monbl Augenheilk 89:84–87
Bouchenaki N, Herbort CP (2001) The contribution of indocyanine green angiography to the appraisal and management of Vogt-Koyanagi-Harada disease. Ophthalmology 108:54–64
Kawaguchi T, Horie S, Bouchenaki N, Ohno-Matsui K, Mochizuki M, Herbort CP (2010) Suboptimal therapy controls clinically apparent disease but not subclinical progression of Vogt-Koyanagi-Harada disease. Int Ophthalmol 30:41–50
Nakai K, Gomi F, Ikuno Y, Yasuno Y, Nouchi T, Ohguro N, Nishida K (2012) Choroidal observations in Vogt-Koyanagi-Harada disease using high-penetration optical coherence tomography. Graefes Arch Clin Exp Ophthalmol 250:1089–1095
Kouda N, Sasaki H, Harada S, Yamada Y, Takahashi N, Sasaki K (2002) Early manifestation of Vogt-Koyanagi-Harada disease as unilateral posterior scleritis. Jpn J Ophthalmol 46:590–593
Usui Y, Goto H, Sakai J, Takeuchi M, Usui M, Rao NA (2009) Presumed Vogt-Koyanagi-Harada disease with unilateral ocular involvement: report of 3 cases. Graefes Arch Clin Exp Ophthalmol 247:1127–1132
Yokoi R, Asami T, Kachi S, Ito Y, Nakamura M, Terasaki H (2010) Acute retinal necrosis after corticosteroid pulse therapy for unilateral Vogt-Koyanagi-Harada disease. Retin Cases Brief Rep 4:51–54
Agrawal A, Biswas J (2011) Unilateral Vogt-Koyanagi-Harada disease: report of two cases. Middle East Afr J Ophthalmol 18:82–84
Neves A, Cardoso A, Almeida M, Campos J, Campos A (2015) Unilateral Vogt-Koyanagi-Harada disease: a clinical case report. Case Rep Ophthalmol 6:361–365
Valenzuela RM, Keung B, Pula JH, Kattah JC. A Rare Case of Unilateral Progressive Vision Loss and Pachymeningitis. Neuroophthalmology. 2016;40(5):237–42. https://doi.org/10.1080/01658107.2016.1212079.
Tsui E, Bottini A, Ghadiali Q, Balaratnasingam C, Barbazetto I (2018) Unilateral ocular manifestations of Vogt-Koyanagi-Harada disease. Ocul Immunol Inflamm 26:1297–1300
Pellegrini F, Interlandi E, Prosdocimo G (2018) Vogt-Koyanagi-Harada disease presenting as unilateral neuroretinitis. Neuroophthalmology 42:11–16
Abouammoh MA, Gupta V, Hemachandran S, Herbort CP, Abu El-Asrar AM (2016) Indocyanine green angiographic findings in initial-onset acute Vogt-Koyanagi-Harada disese. Acta Ophthalmol 94:573–578
Miyanaga M, Kawaguchi T, Miyata K, Horie S, Mochizuki M, Herbort CP (2010) Indocyanine green angiography findings in initial acute pretreatment Vogt-Koyanagi-Harada disease in Japanese patients. Jpn J Ophthalmol 54:377–382
Lavezzo MM, Sakata VM, Morita C, Rodriguez EE, Abdallah SF, da Silva FT, Hirata CE, Yamamoto JH (2016) Vogt-Koyanagi-Harada disease: review of a rare autoimmune disease targeting antigens of melanocytes. Orphanet J Rare Dis 11:29
Abu EL-Asrar AM, Dosari M, Hemachandran S, Hikandi PW, Al-Muamar A. (2017) Mycophenolate mofetil combined with systemic corticosteroids prevents progression to chronic recurrent inflammation and development of “sunset glow fundus” in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease. Acta Ophthalmol 95:85–90
Hosseini SM, Dourandish M, Mazouchi M (2020) Unilateral presentation of Vogt-Koyanagi-Harada syndrome: a case report. J Ophthalmic Vis Res 15:99–103
Khochtali S, Abroug N, Hani MS, Khairallah-Ksiaa I, Jelliti B, Khairallah M (2015) Concurrent acute Vogt-Koyanagi-Harada disease in one eye and chronic disease in the fellow eye. J Ophthalmic Inflamm Infect, Doi (1):57. https://doi.org/10.1186/s12348-015-0057-9 Epub 2015 Sep 3
Acknowledgements
Not applicable.
Funding
Not applicable.
Author information
Authors and Affiliations
Contributions
IP contribute in acquisition, analyse and interpretation of the data. He contributed in writing and reviewing of the manuscript. CHP was the major reviewer of the manuscript. He also contributed in writing. All authors read and approved the final manuscript.
Authors’ information
Not applicable.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
There is no financial disclosure.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Papasavvas, I., Herbort, C.P. Vogt-Koyanagi-Harada disease is always bilateral: reports of unilateral cases failed to use choroidal investigations showing subclinical involvement of the fellow eye. J Ophthal Inflamm Infect 11, 6 (2021). https://doi.org/10.1186/s12348-021-00237-3
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s12348-021-00237-3