ABSTRACT

In this study, we present a case of bilateral optic neuropathy and macular ischemia in the right eye associated with neurosarcoidosis. A 26-year-old woman presented to our clinic with complaints of bilateral blurred vision. Bilateral granulomatous anterior uveitis, vitritis, optic neuropathy, and macular ischemia were detected in the right eye in slit-lamp examination. She also reported complaints of fever, weakness, sweating, arthralgia, and headache for 2 months. She was referred to the pulmonary diseases unit of our hospital due to hilar lymphadenopathy seen in her chest x-ray, and biopsies were taken for diagnostic purposes. Histological analysis of the mediastinal lymph node biopsies revealed chronic, non-caseating, granulomatous inflammation. Furthermore, the patient was referred to a neurologist due to concomitant complaint of intense headaches. She was diagnosed with neurosarcoidosis supported by findings on cranial magnetic resonance imaging and lumbar puncture. She received a 3-day course of high-dose (1 g/day) intravenous steroid treatment (methylprednisolone) followed by a tapering dose of oral prednisone. The patient began receiving oral methotrexate 15 mg/week as a steroid-sparing agent. Significant improvement in neurological and ophthalmological symptoms occurred in the first week of treatment. In this case report, we emphasized that neurosarcoidosis should be included in the differential diagnosis of patients with both bilateral optic neuropathy and macular ischemia. Furthermore, early diagnosis and timely treatment of neurosarcoidosis are important for favorable visual outcomes.

Introduction

Sarcoidosis can affect multiple organs and is histologically characterized by non-caseified granulomas.¹ Ocular involvement is observed in 25-50% of patients with systemic sarcoidosis.² The most common findings are uveitis and conjunctival nodules.^3,4

Neurosarcoidosis is found in 5-15% of those with systemic disease.^5,6 In patients with neurosarcoidosis, ophthalmic symptoms are mostly associated with cranial nerve involvement and uveitis. The facial, trigeminal, oculomotor, and optic nerves are the most commonly involved cranial nerves.⁷

Presented herein is a patient with bilateral uveitis, unilateral macular ischemia, bilateral optic disc involvement, and a biopsy-confirmed diagnosis of pulmonary sarcoidosis. This case report emphasizes that optic disc involvement may be a sign of neurosarcoidosis in patients with sarcoidosis and that macular ischemia may develop due to reduced flow in the retinal artery resulting from inflammation.

Discussion

Although the lungs are most commonly affected, sarcoidosis can manifest with extrapulmonary involvement including dermal, ocular, neurological, cardiac, renal, and gastrointestinal involvement.⁸ Neurological involvement is uncommon in sarcoidosis. Neurosarcoidosis is seen in 5-15% of patients with systemic sarcoidosis.^5,6

Turner et al.⁹ reported that the central nervous system is also involved in 37% of patients with intraocular sarcoidosis. In a study by Menezo et al.⁷, it was found that 7.4% of patients with neurosarcoidosis had optic nerve involvement. In a series of 19 patients with systemic sarcoidosis, optic neuropathy was accompanied by granulomatous anterior uveitis in 10 patients, retinal vasculitis and cotton-wool spots in 2 patients each, and isolated vitritis, panuveitis, isolated choroidal involvement, macular exudates, and episcleritis in 1 patient each.¹⁰ In our case, the patient had systemic sarcoidosis with ocular involvement manifesting as bilateral anterior uveitis, vitritis, and macular ischemia in the right eye. When the patient underwent neurological evaluation for bilateral optic nerve involvement and headaches, we found that she also had neurosarcoidosis.

Yu and Yannuzzi¹¹ associated bilateral decreased vision in a patient who had pulmonary neurosarcoidosis and neurosarcoidosis with findings of avascular zone enlargement on FFA and cystic changes in the macula on OCT. The patient was found to have bilateral perifoveal ischemia, which was presented as a rare finding of sarcoidosis involvement. Sarcoidosis usually causes non-ischemic retinal vasculitis.¹² The macular ischemia in the right eye of our patient and the soft exudate in the lower temporal part of the optic disc may be attributable to reduced flow in the retinal artery due to inflammation. The macular ischemia and exudate regressed within the first week of treatment. Due to the poor general condition of the patient, OCT and FFA were not done during this period.

Unlike pulmonary sarcoidosis, spontaneous resolution of neurosarcoidosis is uncommon. Neurosarcoidosis-related morbidity and mortality are minimized with treatment.¹³ Although corticosteroids appear to be the first choice for the treatment of neurosarcoidosis, response rates to treatment with corticosteroids alone are lower in patients with neurosarcoidosis compared to patients with pulmonary sarcoidosis.^14,15 In the long-term treatment of neurosarcoidosis, reactivation has been reported when the corticosteroid dose is reduced to 20-25 mg.¹⁵ The addition of immunosuppressive agents such as methotrexate,¹⁴ azathioprine,¹⁶ mycophenolate mofetil,¹⁶ and chlorambucil¹⁷ to corticosteroid therapy has been reported in case reports. There are also studies in which the anti-TNF inhibitor infliximab has been used as a biological agent.¹⁸ In one report, a 61% remission rate was achieved in neurosarcoidosis by discontinuing corticosteroids and treating with methotrexate.¹⁴ In the present case, full remission with no recurrence during the 15-month follow-up period was achieved with methotrexate treatment.

In conclusion, neurosarcoidosis should be included in the differential diagnosis of patients with bilateral optic neuropathy and uveitis. Although macular ischemia is a rare finding of sarcoidosis, we should bear in mind that it may arise as a result of reduced flow in the retinal artery due to inflammation. Early diagnosis and treatment improve the prognosis of the disease and of ocular involvement if present. Sarcoidosis requires a multidisciplinary approach, and ophthalmologists play a key role in diagnosis and treatment planning.