Unmasking neurosarcoidosis in a patient with acute zonal occult outer retinopathy: a case report

Abstract

Background

We report a case of neurosarcoidosis in a patient with a prior history of acute zonal occult outer retinopathy (AZOOR), using multimodal imaging, including color fundus photography, spectral-domain optical coherence tomography, fluorescein and indocyanine green (ICG) angiography.

Case presentation

A 37-year-old female with a history of AZOOR presented with new-onset bilateral photopsia and a paracentral scotoma in the left eye. Examination revealed bilateral anterior chamber reaction, optic disc edema, vitreous cells, and choroiditis on ICG angiography. Given the presentation, AZOOR recurrence was deemed unlikely, and further workup for panuveitis was initiated. A week later, she developed multiple cranial neuropathies, and further systemic evaluation confirmed neurosarcoidosis. High-dose corticosteroids and methotrexate resolved both neurological and ophthalmic symptoms.

Conclusions

This case highlights the importance of carefully evaluating patients with inflammatory eye conditions, as new symptoms might suggest a different diagnosis rather than a recurrence of the preexisting condition. Prompt recognition and adequate treatment can significantly impact patient outcomes.

Background

Neurosarcoidosis (NS), a rare manifestation of systemic sarcoidosis, affects both the central and peripheral nervous systems [1]. Ocular involvement occurs in up to one-third of patients with NS, typically presenting as anterior uveitis in acute or chronic forms. Posterior segment involvement is less common and may include vitritis, periphlebitis with perivenous exudates, and multifocal choroiditis [2, 3]. Optic nerve dysfunction can manifest as anterior or retrobulbar optic neuropathy, granulomatous infiltration in severe intraocular inflammation, or papilledema due to increased intracranial pressure [4].

Case presentation

A 37-year-old Caucasian female presented to the emergency department with new-onset bilateral photopsia and a paracentral scotoma in her left eye. Her past medical history included acute zonal occult outer retinopathy (AZOOR) in the left eye, diagnosed 14 years ago, which resolved without recurrence following corticosteroid treatment. There was no other significant personal or family medical history, and no associated systemic complaints. On examination, her best-corrected visual acuity (BCVA) was 20/25 in the right eye and 20/32 in the left eye. Intraocular pressure was 18 mmHg in both eyes, measured using rebound tonometry (iCare Finland Oy, Vantaa, Finland). Pupils were symmetric, round, and reactive, with no afferent pupillary defect. Anterior segment evaluation revealed fine diffuse keratic precipitates, 0.5 + cells, and a 1 + faint flare bilaterally. Dilated fundus examination showed bilateral optic disc edema, more pronounced in the left eye, and vitreous haze (0.5 + in the right eye and 1 + in the left eye) without signs of vasculitis or retinitis (Fig. 1). The left eye exhibited atrophic and pigmentary changes in the nasal retina, consistent with previous AZOOR (Fig. 2).

Fig. 1.

Ocular fundus photographs at presentation, showing bilateral optic disc edema and an atrophic lesion in the nasal retina of the left eye

Fig. 2.

Fundus autofluorescence (A), infrared imaging (B), and optical coherence tomography scan (C) of the nasal retina in the left eye

Optical coherence tomography (OCT, Spectralis, Heidelberg Engineering Inc., Heidelberg, Germany) revealed increased peripapillary retinal fibre layer thickness (124 μm in the right eye and 163 μm in the left eye), normal macular topography in both eyes and hyperreflective vitreous dots, consistent with vitreous cells observed on fundoscopy. Fluorescein angiography demonstrated bilateral early papillary hyperfluorescence with diffusion (Fig. 3), while indocyanine green angiography revealed bilateral small hypofluorescent lesions, more evident in the superior and mid-peripheral retina, which did not persist into the late phases, consistent with choroiditis (Fig. 4).

Fig. 3.

Fundus fluorescein angiography demonstrating bilateral papillary diffusion

Fig. 4.

Indocyanine green angiography revealing bilateral small hypofluorescent lesions in the superior and mid-peripheral retina

Despite the prior diagnosis of AZOOR, a recurrence was considered unlikely with this presentation. The presence of bilateral panuveitis prompted further investigation for an alternative underlying condition. Given the presence of bilateral panuveitis and optic disc edema, cerebral and orbital MRI was performed to exclude optic nerve and central nervous system involvement. Results were normal. Blood tests were performed to investigate autoimmune and infectious causes of panuveitis and included complete blood count, C-reactive protein, erythrocyte sedimentation rate, angiotensin-converting enzyme, antinuclear antibodies, antineutrophil cytoplasmic antibodies, rheumatoid factor, and HLA-B27 typing. Infectious screening included serology for syphilis, human immunodeficiency virus, hepatitis B and C viruses, Toxoplasma gondii, and interferon-gamma release assay and Mantoux test for tuberculosis.

While awaiting the test results, the patient returned to the emergency department one week later with new-onset multiple cranial neuropathies, including involvement of the VII and VIII cranial nerves. This manifested as right peripheral facial palsy, vertigo, nausea, and vomiting. She was admitted for systemic work-up. Infectious screening results were negative and laboratory testing revealed elevated angiotensin-converting enzyme titers. High-resolution thoracic computed tomography showed multiple bilateral mediastinal and hilar adenopathies with parenchymal involvement (Fig. 5). Endobronchial ultrasound-guided transbronchial needle aspiration of enlarged lymph nodes revealed non-caseating granulomatous inflammation, consistent with sarcoidosis. Bronchoalveolar lavage fluid showed an increased number of lymphocytes with a high CD4/CD8 ratio.

Fig. 5.

Thoracic computed tomography displaying multiple bilateral mediastinal and hilar adenopathies (C1-C6) consistent with sarcoidosis

The patient was treated with oral corticosteroids (1 mg/kg/day). After systemic evaluation, methotrexate was subsequently introduced at an initial dose of 7.5 mg/week, with stepwise dose escalation of 2.5 mg every 2–4 weeks under laboratory monitoring, reaching a dose of 12.5 mg/week. This resulted in significant clinical improvement, with resolution of neurological symptoms within two weeks. Ophthalmic signs, including optic disc edema and choroiditis lesions, progressively resolved, with recovery of BCVA to 20/20 bilaterally by two months (Fig. 6).

Fig. 6.

Ocular fundus photographs two months after presentation, showing resolution of bilateral optic disc edema following treatment

Discussion and conclusions

Sarcoidosis is a heterogeneous, multisystem granulomatous disorder with an elusive etiology. It typically presents with respiratory, dermatological, and ophthalmological manifestations but can affect any organ. Ocular sarcoidosis can occur without obvious systemic involvement and may be the primary site of the disease [5]. Neurologic complications occur in approximately 5–10% of patients with sarcoidosis [6]. Patients diagnosed with NS who also have ocular involvement are more likely to be female and of Caucasian origin, as observed in our case [2]. Diagnosing NS can be particularly challenging. It should be considered in any patient presenting with central or peripheral nervous system symptoms, especially if they have a known diagnosis of sarcoidosis. Even in patients without confirmed sarcoidosis, NS should remain a diagnostic consideration if their neurologic symptoms suggest the condition. Most patients with NS also exhibit signs of multisystem involvement, as seen in our case where pulmonary involvement was present. This multisystem involvement often aids in confirming the diagnosis of sarcoidosis, as obtaining nervous tissue for biopsy can be difficult [7].

Acute Zonal Occult Outer Retinopathy (AZOOR) is a rare inflammatory disease of unknown etiology characterized by outer retinal dysfunction. It typically presents with sudden visual impairment, often accompanied by scotomas and photopsia, and primarily affects young to middle-aged Caucasian women [8]. In the early stages, fundoscopic examination may appear normal, followed by the gradual development of retinal pigment epithelium atrophy, characterized by trizonal outer retinal changes on OCT. The condition is usually unilateral at onset, but late recurrence in the same eye or delayed involvement of the fellow eye can occur, with an average delay of 50 months [9]. AZOOR typically presents with minimal to no anterior segment inflammation, and vitreous cells are usually absent or minimal, often emerging weeks to months after disease onset. Vitreous cells, perivenous exudates, and optic disc edema have been reported to occur several weeks after AZOOR onset. These signs seem to correlate with the extent of the affected retinal zones and are likely due to an inflammatory response triggered by the death of retinal cells. AZOOR patients have been associated with a higher predisposition for autoimmune conditions [9]. To date, there are no reported associations between AZOOR and sarcoidosis.

We presented the case of a young woman with new-onset bilateral photopsia and left eye scotoma and a remote history of AZOOR in the left eye. She presented with bilateral anterior uveitis, vitreous cells, multifocal choroiditis lesions, and optic disc edema. Although the presentation with photopsia and scotoma could resemble AZOOR recurrence, there were several atypical factors making this unlikely, including the timing of a possible recurrence (14 years later), bilateral involvement, optic disc edema, and multifocal choroiditis lesions. These atypical findings should prompt a guided etiologic evaluation to search for autoimmune and infectious causes of panuveitis.

The subsequent presentation with peripheral facial palsy and vestibular dysfunction raised the suspicion for NS, even in a patient without a previous diagnosis of sarcoidosis. Cranial neuropathies are the most common manifestation of NS, with the majority of patients presenting with involvement of one or more cranial nerves. The facial and optic nerves are the most frequently affected. Optic nerve dysfunction has been reported as the second most affected cranial nerve, with various involvements including anterior or retrobulbar optic neuropathy, granulomatous infiltration, or papilledema. The eighth cranial nerve is involved in 3–10% of cases, which can lead to hearing and vestibular dysfunction [5, 10]. Neuroimaging with MRI is required to assess for inflammatory changes, including granulomatous involvement of brain parenchyma and the spinal cord. In our case, the MRI was normal. Interestingly, patients with neurological disease accompanied by intraocular inflammation are reportedly less likely to show compatible MRI findings [2].

In summary, we presented a case of NS manifesting as bilateral panuveitis in a patient with a prior diagnosis of AZOOR. Diagnosing these two conditions can be particularly challenging. This case underscores the importance of comprehensive evaluation in patients with inflammatory eye conditions, as new symptoms may point to a different diagnosis rather than a recurrence of the original condition. Early recognition and timely treatment are crucial for improving patient outcomes.

Abbreviations

AZOOR

Acute Zonal Occult Outer Retinopathy

BCVA

Best-corrected visual acuity

ICG

Indocyanine Green

MRI

Magnetic resonance imaging

NS

Neurosarcoidosis

OCT

Optical coherence tomography

Author contributions

I.C.C. prepared the manuscript draft and organized the clinical data. R.R. assisted in data collection and literature review and was a major contribution in writing the manuscript. A.R.S., S.P., and L.F. supervised the case management and critically revised the manuscript. S.T.C. contributed to the interpretation of findings and final approval of the manuscript. All authors read and approved the final manuscript.

Funding

This study was conducted without any funding or financial support.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

According to the policy of the Unidade Local de Saúde de São João, formal ethics committee approval is not required for single case reports. The study complied with the tenets of the Declaration of Helsinki. Written informed consent was obtained from the patient to participate in this report and clinical assessments as relevant to this publication.

Consent for publication

Written informed consent was obtained from the patient for the publication of this case report and any accompanying clinical images. A signed consent form is available upon request.

Competing interests

The authors declare no competing interests.