Introduction:
A multisystem inflammatory disease affecting the lungs, skin, heart, liver, spleen, central and peripheral nervous systems, salivary glands, and musculoskeletal system is known as sarcoidosis. The cause of the disease is unknown. It can lead to blindness, meningitis, kidney diseases, arthritis, dermatitis, or mortality. Sarcoidosis also affects the eyes and is called ocular sarcoidosis. It can affect any part of the eye, causing uveitis, scleritis, episcleritis, eyelid abnormalities, conjunctival granuloma, lacrimal gland enlargement, optic neuropathy, and orbital inflammation. Individuals with ocular sarcoidosis can have a lot of other manifestations; hence, a multi-disciplinary approach is needed for their treatment.
What Are the Clinical Features of Ocular Sarcoidosis?
Ocular sarcoidosis may lead to acute visual impairment. The granulomatous inflammation can affect any part of the eyes. However, uveitis, dry eyes, and conjunctival nodules are the most common ocular manifestations.
Intraocular Manifestations:
Uveitis - The common intraocular manifestation is uveitis. Uveitis is an inflammation of the uveal tissues comprising the iris, ciliary body, and choroid. It usually affects the tissues adjacent to the uvea, like the anterior chamber, vitreous humor, or retina. It can occur as anterior, intermediate, or panuveitis when associated with sarcoidosis. The most common is bilateral anterior uveitis without the involvement of the posterior segment.
Anterior uveitis is associated with photophobia, redness, and pain. Individuals can develop permanent eye damage from chronic inflammation before the treatment. The posterior part has bilateral involvement in sarcoid uveitis, but it can be asymmetric. Choroidal granulomas can lead to visual impairment and retinal detachment if they are significant.
In intermediate uveitis, people complain of floaters and blurred vision. It is often associated with vitreous opacities, snowballs - a group of inflammatory cells in the vitreous humor at the back of the lens, and snow banks - whitish exudates on the retinal wall.
Posterior uveitis includes peri phlebitis and candle wax drippings, yellowish-white perivascular retinal exudates along the retinal veins.
If left untreated, chronic uveitis can lead to cataracts, glaucoma, and cystoid macular edema, leading to vision loss in such individuals. Sarcoid uveitis can increase intraocular pressure and glaucoma due to edema. Certain individuals have been found to have trabecular meshwork nodules and tent-shaped peripheral anterior adhesions.
Manifestations on the Ocular Surface:
Ocular sarcoidosis can involve the conjunctiva, leading to conjunctival nodules, acute follicular conjunctivitis, and chronic cicatricial conjunctivitis. Conjunctival nodules are common and mostly asymptomatic. Scleritis is rarely seen and is usually found in older individuals. It can occur as anterior diffuse, anterior nodular, or posterior scleritis. Ocular sarcoidosis rarely involves the cornea but commonly presents as superficial punctate keratitis and peripheral ulcerative keratitis. Chronic inflammation and hypercalcemia can cause calcium deposition, leading to keratopathy.
Orbital Manifestations:
Ocular sarcoidosis rarely involves the eyelid. The lacrimal gland is the most common extraocular orbital tissue that gets affected by ocular sarcoidosis. Individuals can be asymptomatic or present with inflammatory symptoms. A condition known as keratoconjunctivitis sicca (KCS) is present with ocular sarcoidosis due to reduced tear production secondary to the inflammation of the salivary gland.
Epiphora is seen as a result of inflammation of the lacrimal drainage system. The extraocular muscles, orbital fat, and the optic nerve sheath can also get affected by ocular sarcoidosis, leading to swelling of the eyelids, ptosis, proptosis, and pain. These can mimic other systemic conditions, such as thyroid ophthalmopathy. If left untreated, the orbital masses could progress to central retinal artery occlusion and permanent blindness.
Neuro-ophthalmic Manifestations:
Depending on the areas of the nervous system involved, neurosarcoidosis causes several symptoms. Cranial neuropathy of the facial and optic nerves is one of the most common manifestations. This can affect any of the cranial nerves. The cranial nerves get affected by direct infiltration by the sarcoid tissue or compression from the lesions. Neurosarcoidosis can also lead to nystagmus, papilledema, and other visual defects.
How Is Ocular Sarcoidosis Diagnosed?
Ocular sarcoidosis is a condition that may involve several ocular tissues. Such individuals may have acute anterior uveitis with lacrimal gland enlargement, bilateral multifocal choroiditis, conjunctivital nodules, or peripheral ulcerative keratitis with orbital inflammation. The following are the diagnostic modalities for ocular sarcoidosis:
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Biopsy - It is a procedure in which the tissue is scraped out to be microscopically examined. Most commonly, the samples are taken from the lungs, skin, lymph nodes, conjunctiva, lacrimal glands, or orbital tissues.
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Neuroimaging - Retrieving a tissue from a suspected lesion is not always possible, so additional diagnostic procedures are carried out. Imaging studies like chest CT scans, X-rays, and Gallium scintigraphy may help diagnose the condition.
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Vitreous Fluid Analysis - Vitreous tap and immunologic analysis is carried out in individuals with vitreous inflammation. A CD4/CD8 ratio of vitreous-infiltrating lymphocytes of more than 3.5 gives a diagnosis of ocular sarcoidosis.
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Laboratory Investigations - Certain individuals may have increased calcium serum levels, angiotensin-converting enzyme (ACE), or lysozyme.
How Is Ocular Sarcoidosis Treated?
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Topical Corticosteroid - The common topical corticosteroid for anterior uveitis is Prednisolone acetate. The dose of the medicine is calculated based on the inflammation of the anterior chamber from once daily to hourly. Another potent medication is Difluprednate which is given four times daily to treat anterior uveitis.
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Topical Cycloplegics - Topical cycloplegic eye drops help to relieve pain from ciliary spasms to the posterior adhesions commonly seen in individuals with severe anterior chamber inflammation. In acute cases, medications like Cyclopentolate are used, whereas, in chronic anterior chamber inflammation, longer-acting agents like Atropine are used.
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Regional Corticosteroid Injections and Implants - Regional corticosteroid injections and implants can be used in uveitis of the posterior segment or when the individual is not responding to topical corticosteroids. These injections can be given periocularly or intravitreally.
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Systemic Corticosteroids - Systemic corticosteroids are given to individuals with severe bilateral uveitis when topical therapy cannot control inflammation. Systemic corticosteroid therapy is very effective in such cases. Prednisone is the commonly used oral corticosteroid. Its dose is gradually tapered to avoid relapse. Sometimes, short-term methylprednisolone is given in individuals with retinal or optical nerve lesions, followed by oral Prednisone.
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Systemic Immunosuppressive Agents - It is indicated in corticosteroid-dependent or intolerant individuals. A 5 mg dose of Prednisone is usually given. Anti-metabolites and calcineurin inhibitors are being studied to treat sarcoid-related inflammation of the eye. Common drugs used to treat ocular sarcoidosis are Methotrexate, Mycophenolate, Mofetil, Azathioprine, and Cyclosporine.
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Biologic Agents - Certain biologic agents are used for treating refractory noninfectious uveitis. Such agents include tumor necrosis factor-alpha inhibitors, like Infliximab, Adalimumab, Etanercept, and Golimumab.
Conclusion:
Ocular sarcoidosis is a condition that can involve any part of the eyes and their structures. The common manifestations include uveitis, dry eyes, and conjunctival nodules. A multi-disciplinary approach is needed to achieve a good outcome for both the ocular and systemic manifestations. A proper treatment leads to a good prognosis. Educating the individual about the chronic nature of ocular inflammation is essential. Long-term medication and follow-up are needed for the success of the treatment to prevent permanent loss of vision.
