Sarcoidosis and the Eye

Sarcoidosis is a multisystem disease with non-caseating granulomas. Eye involvement occurs in 25 to 60 percent of patients with systemic disease and may be the first or only presentation.

• It is more frequent and often more severe in people of African descent and in women, with peaks at 20 to 40 years and a second peak after 50 years.
• The commonest ocular manifestation is uveitis, which is bilateral in most, chronic or relapsing, and can affect any segment of the eye. The orbit, lacrimal gland, eyelids, conjunctiva and optic nerve can also be involved.
• Two characteristic syndromes exist: the combination of erythema nodosum, bilateral hilar lymphadenopathy, arthralgia and acute anterior uveitis (good prognosis, often self-limiting), and uveoparotid fever (uveitis, parotid enlargement, facial nerve palsy and fever).

• Anterior uveitis: granulomatous (large greasy mutton fat keratic precipitates), iris nodules at the pupil margin (Koeppe) or in the iris stroma (Busacca), trabecular meshwork nodules, tent shaped peripheral anterior synechiae, posterior synechiae, band keratopathy, cataract and secondary glaucoma. Onset may be acute or chronic.
• Intermediate uveitis: vitreous cells with snowball opacities (inferior vitreous) and snowbanking.
• Posterior segment: periphlebitis, with perivenous sheathing described as candle wax drippings, retinal macroaneurysms, peripheral neovascularisation with vitreous haemorrhage, choroidal granulomas, multifocal choroiditis, cystoid macular oedema and optic disc granuloma or oedema.
• Optic nerve: optic neuropathy from compressive granuloma or from infiltration, and papilloedema from neurosarcoidosis.
• Adnexal: lacrimal gland enlargement with dry eye, conjunctival follicular nodules, eyelid skin granulomas (lupus pernio on face and eyelids), orbital mass, extraocular muscle involvement and scleritis or episcleritis.
• Systemic clues: persistent cough and dyspnoea, skin nodules, arthropathy, hypercalcaemia, fatigue, cardiac arrhythmia, facial palsy.

• No single test is conclusive. The diagnosis is made on compatible clinical features, tissue showing non-caseating granulomas, and exclusion of infection.
• Chest radiograph and high resolution CT chest (hilar and mediastinal lymphadenopathy, perilymphatic nodules). Whole body PET-CT identifies accessible biopsy sites.
• Serum angiotensin converting enzyme (raised in about 60 percent, low specificity, falsely low on ACE inhibitors and physiologically raised in children), lysozyme, soluble interleukin-2 receptor, serum calcium, 24-hour urinary calcium, alkaline phosphatase, liver function, full blood count, creatinine.
• Biopsy: conjunctival nodule or blind conjunctival biopsy, lacrimal gland, skin lesion, or endobronchial ultrasound guided mediastinal lymph node biopsy showing non-caseating granulomas without organisms.
• Exclude infection: interferon gamma release assay (and chest imaging) for tuberculosis, treponemal serology for syphilis, HIV, fungal serology as appropriate. Granulomas in a patient with a positive TB test do not exclude tuberculosis.
• Eye investigations: slit lamp examination, gonioscopy, OCT macula (cystoid oedema), fluorescein angiography (periphlebitis, leakage, disc staining, neovascularisation), indocyanine green angiography (hypofluorescent choroidal spots), visual fields, B-scan.
• Cardiac (ECG, echocardiogram, cardiac MRI) and neurological (MRI brain with contrast) screening when symptoms or abnormal ECG.

• Asymptomatic or mild anterior uveitis: prednisolone acetate 1% hourly while awake, tapered over 6 to 8 weeks guided by cells, plus cyclopentolate 1% twice or three times daily to relieve ciliary spasm and prevent posterior synechiae. Elevated IOP: timolol 0.5% twice daily and brimonidine 0.2% three times daily, dorzolamide 2% three times daily as add on.
• Posterior or intermediate involvement, optic nerve involvement, or anterior disease not controlled by drops: prednisolone 1 mg/kg/day orally (maximum 80 mg), reducing by 10 mg every 1 to 2 weeks to 10 mg and then more slowly over 6 to 12 months, with calcium monitoring, bone protection (calcium and vitamin D only after serum calcium and urinary calcium are confirmed normal, because sarcoidosis raises 1,25-dihydroxyvitamin D), proton pump inhibitor when combined with NSAIDs, glucose and blood pressure monitoring.
• Local steroid options: posterior sub-Tenon triamcinolone 40 mg, intravitreal triamcinolone 4 mg, dexamethasone 0.7 mg intravitreal implant, or fluocinolone acetonide 0.19 mg intravitreal implant (3 years) in unilateral or asymmetric chronic disease or when systemic therapy is not tolerated.
• Optic neuropathy, neurosarcoidosis or sight threatening retinal vasculitis: intravenous methylprednisolone 1 g daily for 3 days, then oral prednisolone 1 mg/kg/day with early addition of a steroid sparing drug.
• Steroid sparing therapy when prednisolone above 10 mg daily is needed beyond 3 months or when steroid side effects appear: methotrexate 15 to 25 mg once weekly with folic acid 5 mg weekly (oral or subcutaneous), mycophenolate mofetil 1 g twice daily, or azathioprine 2 to 2.5 mg/kg/day after checking thiopurine methyltransferase activity.
• Refractory disease: adalimumab 80 mg subcutaneously then 40 mg every 2 weeks, or infliximab 5 mg/kg intravenously at weeks 0, 2 and 6 and every 4 to 8 weeks thereafter. Screen for latent tuberculosis, hepatitis B and C and HIV before biologic therapy.
• Complications: cystoid macular oedema (topical dorzolamide, periocular or intravitreal steroid, systemic therapy), cataract surgery with perioperative prednisolone 0.5 to 1 mg/kg for 1 week before and 2 to 4 weeks after surgery with the eye quiet for 3 months, neovascularisation (scatter laser to the ischaemic periphery), vitrectomy for persistent vitreous opacity or haemorrhage, glaucoma surgery for refractory secondary glaucoma.
• Dry eye from lacrimal gland infiltration: preservative free lubricant drops 4 to 8 times daily, ointment at night, punctal plugs.
• Systemic review in collaboration with a physician for pulmonary, cardiac, neurological and renal assessment, with ocular review every 3 to 6 months for at least 5 years because relapse is common.