Orbital Sarcoidosis

Description of Ophthalmic-Orbital Sarcoidosis

• Sarcoidosis is a disease of unknown aetiology characterized by chronic inflammation and granuloma formation across multiple systems of the body. Although it predominantly affects the lungs and eyes, it is seen to affect the skin, lymph nodes, liver, spleen, heart, central and peripheral nervous systems, musculoskeletal system, and salivary glands.

Pathophysiology of Ophthalmic-Orbital Sarcoidosis

• Histologically widespread noncaseating epithelioid granulomata in the presence of classic clinical and radiolologic findings aid the diagnosis of sarcoidosis. It commonly presents with complications such as blindness, meningitis, arthritis, kidney disease, skin disease, other systemic involvement and even death. A pulmonologist’s consultation might be the only way to support a diagnosis of ophthalmic or neurosarcoid using a bronchoscopic guided biopsy of concomitant chest lesions.

Symptoms and Signs of Ophthalmic-Orbital Sarcoidosis

• Sarcoidosis could present with isolated symptoms in specific systems, but more commonly it presents with a plethora of symptoms with varying severity and affecting multiple organ systems.
• Ophthalmologic involvement could affect the optic nerve pathways or various structures within the orbit producing the following symptoms and signs:

Neuro-ophthalmic involvement

Diplopia: Due to cranial nerve palsies

Reduced vision with or without scotoma: Due to oedema or infiltration of the optic nerve

Visual symptoms: Due to optic nerve damage caused by raised intraocular pressure

Orbital structure involvement

Uveitis results in blurring of vision, photophobia, floaters, scotomata and painful red eye.

Periocular lesions present with dry eye symptoms and disfigurement of adjacent structures

Mass lesion within the orbit causes bulging of the eyeballs and double vision

If it involves the orbital and adnexal structures, it can produce symptoms related to the lacrimal gland, lacrimal sac, eyelid and orbit.

Diagnosis of Ophthalmic-Orbital Sarcoidosis

Diagnosis of ophthalmic or orbital sarcoidosis is established through meticulous clinical examination and investigations.

Clinical examination reveals various manifestations of sarcoidosis in five different areas, namely:

1. Neuro-ophthalmic manifestations: Rare cases of diplopia and ptosis occur due to involvement of the cranial nerves – oculomotor, trochlear, or abducens nerve. 5-38% of patients with neurosarcoid affect the optic nerve with ensuing edema, increased vascularity, nerve head elevation, haemorrhage, or optic atrophy. Retrobulbar optic nerve involvement could present as a mass lesion requiring biopsy to confirm the diagnosis.
2. Ocular manifestations: 25-54% of patients with sarcoidosis present with ocular manifestations while almost all cases of ophthalmic sarcoidosis have systemic involvement.

Heerfordt Syndrome: Uveitis, parotid enlargement and occasionally papilledema.

Löfgren syndrome: Erythema nodosum, bilateral hilar adenopathy, arthralgias and uveitis.

Painless, bilateral, palpable swelling of the lacrimal gland is seen in some patients causing moderate to severe keratitis sicca.

• Anterior segment disease: The following findings are seen with involvement of the anterior segment of the eye.
• Granulomatous lesions in the conjunctiva
• Keratoconjunctivitis sicca
• Interstitial keratitis
• Band keratopathy
• Scleritis
• Cataract due to uveitis or corticosteroid-induced cataract
• Anterior uveitis is the most common manifestation with granulomatous or mutton-fat keratic precipitates, iris nodules, posterior synechiae and peripheral anterior synechiae
• Complications of uveitis can also be seen.
• Glaucoma is common. Gonioscopy should be done in all patients with raised intraocular pressure.

Posterior segment disease: Seen in 25-30% of patients with sarcoidosis. Findings include:

• Cellular infiltrates, “String of Pearls” opacities, haze, syneresis, posterior vitreous detachment, and hemorrhages in the vitreous cavity.
• Periphlebitis manifesting as perivenous exudates which look like candle-wax drippings or En taches de bougie. They resolve almost instantaneously with steroids.
• In retinal neovascularization with vitreous haemorrhage, ischemia, and retinal detachment, panretinal photocoagulation and/or vitrectomy could be advocated.
• Cystoid macular edema (CME) is the collection of extracellular fluid in the outer plexiform layer of the retina. Intravenous fluorescein angiography (IVFA) could assist in diagnosis by demonstrating leakage of dye in and around the fovea.
• Focal and discrete subretinal mottling on ophthalmoscopy
• Fibrinous exudates in the pars plana

Orbital disease: 20% of patients with ophthalmic manifestations of sarcoidosis involve the orbit or the lacrimal gland presenting as a mass lesion with bulging of the eyes, drooping of eyelids, enlarged lacrimal gland or ophthalmoplegia.

Investigations form the basis of confirming a diagnosis of sarcoidosis due to the wide variety of eye disorders that mimic its manifestations. The various investigations that could lead to a diagnosis of sarcoidosis include:

1. Neuroimaging: Magnetic Resonance Imaging (MRI) is more useful than Computed Tomography (CT). Lesions detected on MRI are multiple white matter lesions, meningeal enhancement, optic nerve enhancement and mass lesions in the brain parenchyma.
2. Nuclear Studies: Gallium-67 citrate scanning helps in identifying potential biopsy sites to aid tissue diagnosis.
3. Vitreous Fluid Analysis: Tapping of vitreous for immunological analysis provides supportive evidence for a diagnosis of sarcoidosis.
4. Biopsy: Most cases of sarcoidosis require a biopsy from the most accessible tissues to confirm the diagnosis.

• Biopsy of the conjunctiva should be done as it is readily accessible and associated with low morbidity.
• A transconjunctival lacrimal gland biopsy might confirm a diagnosis suspected during a gallium scan.
• Salivary gland biopsy could be considered in cases where sarcoid uveitis is suspected

Treatment of Ophthalmic-Orbital Sarcoidosis

Oophthalmicor orbital sarcoidosis is treated using both medications and surgery.

Pharmacologic Therapy could include topical or systemic steroids, cycloplegics, topical nonsteroidal anti-inflammatory agents and corticosteroid-sparing agents.

• Corticosteroids: They are the mainstay of treatment of ophthalmic and orbital sarcoidosis. Routes of administration include topical application, depot periocular injections, oral corticosteroids, and injectable corticosteroids. Immunosuppression and other adverse effects due to systemic corticosteroids should be discussed with the patient.
  • The treatment of choice for anterior uveitis is topical corticosteroids and could be used with cycloplegics.
  • Predinisolone acetate 1% is the standard topical steroid. Prednisolone phosphate is of lesser potency.
  • Newer corticosteroids such as loteprednol etabonate are effective maintenance drugs having lesser incidence of steroid-induced glaucoma.
  • It is important to monitor improvement or progress of the disease with readjustments of steroid dosages to meet the requirements.
• Retrobulbar Corticosteroid Injections: Depot or sub-Tenon corticosteroid injections subvert the inaccessibility to topical steroids in cases of intermediate and posterior uveitis. They are given weekly, bi-weekly, or monthly, up to 3 or 4 times.
• Oral Corticosteroids: They are preferred in uveitis with optic nerve involvement; intermediate uveitis, posterior uveitis, and panuveitis; bilateral disease; and coexisting threshold systemic disease.
• Cycloplegics: They are indicated to relieve ciliary spasm due to the severe inflammatory process and to prevent the formation of posterior synechiae.
• Topical Non-Steroidal Anti-inflammatory Agents: These could be used when the risk for steroid-induced cataract formation or steroid-induced glaucoma is high.
• Corticosteroid-Sparing Agents: These agents help when there is intolerance to steroids or treatment failure.
  • Cyclosporine A
  • Methotrexate in recalcitrant uveitis
  • Oral monoclonal antibody therapy and interferon is being tried for nonresponsive uveitis
  • Anti-tumor necrosis factor-alpha (TNF-alpha) therapy (ie, infliximab, etanercept, adalimumab) are used in recalcitrant sarcoid uveitis
  • Intravitreal vascular endothelial growth factor (VEGF) agents (bevacizumab) is used in cases of choroidal or retinal neovascularization

Surgical treatment includes cataract surgery, vitrectomy or trabeculectomy.

• Cataract surgery is done only with complete control or resolution of ocular inflammation
• vitreous opacification requires vitrectomy
• Trabeculectomy or glaucoma drainage device implant procedures are needed when medical therapy fails to treat glaucoma.