Diagnosis of Eales disease from a macular epiretinal membrane

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Short communication

Diagnosis of Eales disease from a macular epiretinal membrane夽 J.L. Sánchez-Vicente a , A. Moruno-Rodríguez b , J. de las Morenas-Iglesias b,∗ , c ˜ , T. Rueda-Rueda d , F. López-Herrero e A. Munoz-Morales a

Sección de Retina Quirúrgica, Servicio de Oftalmología, Hospital Universitario Virgen del Rocío, Sevilla, Spain Sección General, Servicio de Oftalmología, Hospital Universitario Virgen del Rocío, Sevilla, Spain c Sección de Córnea, Servicio de Oftalmología, Hospital Universitario Virgen del Rocío, Sevilla, Spain d Sección de Uveítis, Servicio de Oftalmología, Hospital Universitario Virgen del Rocío, Sevilla, Spain e Sección de Retina Médica, Servicio de Oftalmología, Hospital Universitario Virgen del Rocío, Sevilla, Spain b

a r t i c l e

i n f o

a b s t r a c t

Article history:

Macular involvement is a common finding in patients with Eales disease. The purpose of this

Received 1 January 2019

communication is to describe the diagnosis of Eales disease from the finding of a macular

Accepted 6 June 2019

epiretinal membrane in a young patient.

Available online xxx

The case is presented of a 38-year-old man referred to this medical service unit with blurred vision developed over the past 3 months, and was associated with vitreoretinal trac-

Keywords:

tion and a macular epiretinal membrane. After an ophthalmological examination including

Eales disease

the retinal periphery, optical coherence tomography, tuberculin test, interferon gamma

Macular epiretinal membrane

release assay, and a systemic study, the patient was diagnosed with Eales disease.

Retinal vasculitis Tuberculosis

Macular oedema or epiretinal membranes due to Eales disease are relatively common. Sd-OCT is recommended in all patients with Eales Disease. On the other hand, the presence of epiretinal membranes in young patients usually suggests a non-idiopathic aetiology. ˜ ˜ S.L.U. All rights © 2019 Sociedad Espanola de Oftalmolog´ıa. Published by Elsevier Espana, reserved.

Diagnóstico de enfermedad de Eales a partir de una membrana epirretiniana r e s u m e n Palabras clave:

˜ Presentamos el caso de un varón de 38 anos, remitido a nuestro servicio por tracción vítreo-

Enfermedad de Eales

retiniana y membrana epirretiniana asociada a pérdida de visión de 3 meses de evolución.

Membrana epirretiniana macular

Tras una exploración oftalmológica que incluyó el examen de la periferia retiniana, tomo-

Vasculitis retiniana

grafía de coherencia óptica, prueba de tuberculina, IGRA y estudio sistémico se llegó al

Tuberculosis

diagnóstico de enfermedad de Eales.

夽 ˜ Please cite this article as: Sánchez-Vicente JL, Moruno-Rodríguez A, de las Morenas-Iglesias J, Munoz-Morales A, Rueda-Rueda T, López-Herrero F. Diagnóstico de enfermedad de Eales a partir de una membrana epirretiniana. Arch Soc Esp Oftalmol. 2019. https://doi.org/10.1016/j.oftal.2019.06.004 ∗ Corresponding author. E-mail address: [email protected] (J. de las Morenas-Iglesias). ˜ ˜ S.L.U. All rights reserved. 2173-5794/© 2019 Sociedad Espanola de Oftalmolog´ıa. Published by Elsevier Espana,

OFTALE-1529; No. of Pages 5

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La afectación macular en pacientes con enfermedad de Eales es un hallazgo común, ya sea en forma de edema macular o membrana epirretiniana. Por ello, es aconsejable realizar un estudio macular mediante OCT. Por otra parte, el hallazgo de una membrana epirretiniana en un paciente joven debe hacernos pensar en una posible etiología no idiopática. ˜ ˜ S.L.U. Todos de Oftalmolog´ıa. Publicado por Elsevier Espana, © 2019 Sociedad Espanola los derechos reservados.

Introduction Eales disease (ED) is an idiopathic inflammatory venous occlusion that affects the peripheral retina of young adults, constituting an exclusion diagnosis of other systemic and ocular diseases. The key finding of this disease is the presence of recurrent vitreous hemorrhages.1 ED usually affects healthy young adults, in their third or fourth decade of life. It is characterized by the presence of periphlebitis, areas of non-capillary perfusion, retinal neovascularization, vitreous hemorrhages and fibrovascular proliferation in an eye without inflammation.2 Usually, macular involvement in the disease is not a primary occurrence. Data on the frequency of macular involvement are scarce and vary according to the examination methods used. Thus, in a recent study by Goel et al.3 conducted using spectral domain optical coherence tomography (SD-OCT), macular damage was found in up to 58.2% of ED patients; the most frequent form of maculopathy being macular oedema, followed by epiretinal membrane (ERM) formation and macular thinning.3 A case of a young male patient referred from another center to evaluate vitreoretinal surgery by macular ERM is presented. The presence of ERM in a young patient should hint towards a search for a possible primary cause, in our case discovering

the existence of a peripheral retinal vasculitis that eventually led to the diagnosis of ED.

Clinic case report Male, 38, with unremarkable history, referred by his specialty center due to the presence of macular ERM in the left eye (LE). In the initial examination, the patient exhibiteda corrected maximum visual acuity (CMVA) of 1.0 in right eye (RE) and 0.63 in LE. In anterior pole biomicroscopy (BMC), no inflammatory signs or media opacities were observed. Intraocular pressure (IOP) was 18 mmHg in both eyes (BE). In the left eye fundus examination (EF), the vitreous appeared clear, without vitritis or vitreous opacities. Optic disc (OD) was normal, well defined and with normal color. The presence of an ERM with tortuosity and vascular distortion was observed in the macula (Fig. 1). In the EF examination of the RE no alterations were found. OCT (DRI OCT Triton plus, Topcon Medical Systems, Inc., Tokyo, Japan) revealed the presence of an ERM that produced macular thickening, foveal profile loss and presence of cysts in the internal and external nuclear layers (Fig. 2). Given the patient’s age it was decided to explore the retinal periphery using a Goldmann lens, looking for a possible cause for the ERM expression. In the temporal periphery, an area of whitish retina with retinal hemorrhages, areas of capillary

Fig. 1 – Left eye (LE) and right eye (RE) posterior pole retinographies. In LE the presence of an epiretinal membrane (ERM) that produces an important vascular tortuosity secondary to traction is observed. Normal RE.

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OS(L)

91 mode: fine(2.0.7) TopQ image quality: Capture date: 02/05/2018 EVV:

Retinal thickness map ILM - OS/RPE / red-free

Retinal thickness ILM - OS/RPE (µm) ETDRS 337 388 N

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460 496 409

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494 417 373,8

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Fig. 2 – Left eye (LE) optical coherence tomography (OCT) showing the presence of an epiretinal membrane (ERM) that causes macular thickening, loss of the foveal profile and presence of cysts in the internal and external nuclear layers.

closure and possible retinal neovases were observed. The RE retinal periphery was normal. The presence of retinal peripheral abnormalities pointed towards an ERM secondary to an inflammatory or infectious process. Fluorescein angiography (FAG) confirmed the existence of a temporal peripheral periphlebitis with ischemic areas and presence of retinal neovessels (Fig. 3). The patient was referred to Internal Medicine to rule out an associated systemic disease. Blood count, coagulation study, antiphospholipid antibodies and biochemistry; C3, C4, rheumatoid factor and C-reactive protein were normal. Anticytoplasm and antinuclear antibodies were negative. Chest

radiology showed no signs of active or scar tuberculosis, nor of sarcoidosis. Angiotensin conversion enzyme (ACE), erythrocyte sedimentation rate (ESR) and tests to rule out syphilis were also negative. Mantoux and interferon gamma release assay (IGRA) were positive. Photocoagulation of the ischemic retinal areas was carried out and treatment with systemic corticosteroids (prednisolone 1 mg/kg/day) and isoniazid at a dose of 300 mg every 24 h orally for 9 months was initiated. The treatment had no effect on macular oedema, since the thickening and cysts were the result of the traction exerted by the ERM, so performing pars plana vitrectomy for membrane elimination was decided.

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Fig. 3 – Left eye (LE) fluorescein angiography (FAG). (A) Posterior pole FAG in late times. No diffusion of the dye can be observed; (B) FAG of the temporal periphery where periphlebitis, areas of retinal ischemia and vascular diffusion are observed from neovessels; (C) lower periphery of the LE.

Discussion Pathogenesis of ED is not well known. Currently, it constitutes a diagnosis of exclusion, in which other diseases associated with retinal vasculitis must be discarded.4 Many studies consider that ED is the product of an immune reaction triggered by an external agent.5,6 Most authors consider that the disease is a consequence of either tuberculosis or a hypersensitivity reaction to it.2 Even so, the presence of tuberculous mycobacteria in culture of samples obtained from the vitreous has not been demonstrated. Through studies performed with vitreous PCR, ERM extracted from patients with ED, Mycobacterium tuberculosisDNA has been detected. Therefore, individuals with ED may have non-viable organisms or DNA residues.5 On the other hand, a significantly high frequency of certain human leukocyte antigens (human leukocyte antigens [HLA]) has been demonstrated in the ED. Thus, it has been proposed that some individuals with certain HLA (preferably HLAB5, DR1 and DR4) may develop retinal vasculitis secondary to a cell-mediated immune reaction caused by mycobacterial antigens.7 Therefore, the main differential diagnosis of ED would be with tuberculous vasculitis, a generally bilateral picture, with

vitritis, snowball opacities, neovascularization, retinal hemorrhages, focal neuroretinitis and focal choroiditis.8 On the contrary, ED would be characterized by recurrent vitreous hemorrhages in a young adult, in an eye with no signs of intraocular inflammation. The presence of choroidal lesions would point to tuberculosis or sarcoidosis.2 Typically, the main cause of vision loss in ED is vitreous hemorrhage and its sequelae. Primary involvement of the macula is rare. This allows VA preservation. Data on macular involvement in ED is scarce. In a retrospective study conducted in patients with ED between 1989 and 1997, macular involvement was found in 28% of cases. The patients were studied by posterior pole BMC and FAG. The same authors reported 32% of cases with macular involvement in patients with ED in a retrospective analysis to assess visual outcomes in the disease. Through the use of SD-OCT, up to 58.2% of macular involvement was found. Macular involvement is a relatively frequent finding in ED, with macular oedema being the most frequently found alteration (35.4%). The presence of ERM (11.4%) and macular thinning (11.4%) are next in frequency. Other findings are: hard exudates (6.3%), macular hemorrhages (5%), internal retina or limiting internal membrane folds (3.8%), premacular hemorrhages (2.5%) and macular holes (1.2%).3

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In an ERM study of patients under 40 years of age that included 142 eyes from 140 patients, 64.79% of the membranes were secondary to various etiologies, the most frequent cause of ERM in this group of patients being intraocular inflammation (uveitis, vasculitis, toxocara) with 27.5%, followed by eye trauma (17.6%), eye surgery (surgery, laser, cryotherapy) (13.2%), retinal vascular diseases (ED, Coats, familial exudative vitreoretinopathy) (6.6%), intraocular tumors (hamartomas, retinal hemangioblastoma, retinal vasoproliferative tumors) (6%) and retinal tears (3.3%).9 In conclusion, a possible cause should be sought in every young patient with ERM, the most frequent being intraocular inflammatory processes. As in the case of idiopathic ERM, in cases associated with macular alterations produced by traction exerted by the membrane, its elimination by pars plana vitrectomy should be a therapeutic option to consider. On the other hand, macular involvement in ED is common. Therefore, it is advisable to routinely perform an OCT in all patients with this disease, given the frequency and the functional impact it implies. Lastly, it should be noted that none of the current studies can distinguish between ED and tuberculous vasculitis. Several studies in India, where the disease prevalence is high, support a strong relationship between this type of occlusive vasculitis and tuberculosis. Thus, according to some authors, it would be better to call ED a presumed tuberculous retinal periphlebitis.5

Conflict of interests The authors declare the absence of conflict of interests of any kind and state they have not received any financial support.

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references

1. Das T, Pathengay A, Hussain N, Biswas J. Eales’ disease: diagnosis and management. Eye (Lond). 2010;24:472–82, http://dx.doi.org/10.1038/eye.2009.315. 2. Gupta V, Gupta A, Rao NA. Intraocular tuberculosis–an update. Surv Ophthalmol. 2007;52:561–87, http://dx.doi.org/10.1016/j.survophthal.2007.08.015. 3. Goel N, Kumar V, Arora S, Jain P, Ghosh B. Spectral domain optical coherence tomography evaluation of macular changes in Eales disease. Indian J Ophthalmol. 2018;66:433–8, http://dx.doi.org/10.4103/ijo.IJO 845 17. 4. Majji AB, Vemuganti GK, Shah VA, Singh S, Das T, Jalali S. A comparative study of epiretinal membranes associated with Eales’ disease: a clinicopathologic evaluation. Eye (Lond). 2006;20:46–54, http://dx.doi.org/10.1038/sj.eye.6701788. 5. Biswas J, Ravi RK, Naryanasamy A, Kulandai LT, Madhavan HN. Eales’ disease - current concepts in diagnosis and management. J Ophthalmic Inflamm Infect. 2013;3:11, http://dx.doi.org/10.1186/1869-5760-3-11. 6. Saxena S, Rajasingh J, Biswas S, Kumar D, Shinohara T, Singh VK. Cellular immune response to retinal S-antigen and interphotoreceptor retinoid-binding protein fragments in Eales’ disease patients. Pathobiology. 1999;67:39–44, http://dx.doi.org/10.1159/000028049. 7. Ishaq M, Karamat S, Niazi MK. HLA typing in patients of Eales disease. J Coll Physicians Surg Pak. 2005;15:288–90. 8. Gupta A, Gupta V, Arora S, Dogra MR, Bambery P. PCR-positive tubercular retinal vasculitis: clinical characteristics and management. Retina. 2001;21:435–44. 9. Chen W, Shen X, Zhang P, Xu G, Jiang R, Huang X, et al. Clinical characteristics, long-term surgical outcomes, and prognostic factors of epiretinal membrane in young patients. Retina. 2018, http://dx.doi.org/10.1097/IAE.0000000000002202.