2020-06-08
59DEPARTMENT OF OPHTHALMOLOGY
Head of the Department Professor N.V. Ivanova
A lecture by the Department of Ophthalmology on the topic of uveitis is used to prepare this material Lecture theses
UVEITIS
Uveitis is a general term used to describe inflammation of the middle vascular tunic of the eye, the uvea.
The four main classifications are:
o anatomical
o clinical,
o aetiological
o pathological.
Classification of Uveitis
Anatomy
Anterior:
o Iritis
o Iridocyclitis
Middle:
o Cyclitis
o Pars planitis (peripheral uveitis, chronic cyclitis)
Posterior:
o Retinitis
o Retinochoroiditis
o Chorioretinitis
o Choroiditis
Diffuse:
o Diffuse uveitis
o Endophthalmitis
o Panuveitis
Pattern
o Focal
o Multifocal
o Disseminated
o Diffuse
o geographical
Chronology
o Acute
o Subacute
o Chronic
o Recurrent
Pathology
o Nongranulomatous
o Granulomatous
Age
o Child
o Young adult
o Adult
o Elderly
Demographic Factors
o Male/female
o Race/nationality
o Unilateral/bilateral/alternating
o Geographic factors
o Occupational factors
o Eating habits
o Pets
o Associated illnesses
o Associated events
o Personality factors
o Stress factors
o Drug use
o Smoking
Uveitis can also be divided anatomically into anterior, intermediate, posterior, and panuveitis
o Anterior uveitis includes iritis and iridocyclitis;
o intermediate uveitis includes cyclitis, vitritis, and pars planitis;
o posterior uveitis includes retinitis and choroiditis.
o The term panuveitis should be reserved for patients who have inflammation of all parts of the uvea—the choroid, ciliary body, and iris.
CLINICAL CLASSIFICATION
o Uveitis can be acute or chronic.
o Acute uveitis usually has a sudden symptomatic onset and persists for 6 weeks or less. If the inflammation recurs following the initial attack, it is referred to as recurrent acute.
o Chronic uveitis persists for months or years. Its onset is frequently insidious and may be asymptomatic, although occasionally acute or subacute exacerbations of inflammation may occur.
AETIOLOGICAL CLASSIFICATION
o Exogenous uveitis is caused by either external injury to the uvea or invasion of micro-organisms or other agents from outside.
o Endogenous uveitis is caused by micro-orgamsms or other agents from within the patient. The following are the main types:
1. Associated with systemic disease (e.g. ankylosing spondylitis).
2. Infections with bacteria (e.g. tuberculosis), fungi, viruses (e.g. herpes zoster), protozoans (e.g. toxoplasmosis) or roundworms (e.g. toxocariasis).
3. Idiopathic specific uveitis entities are a group of unrelated disorders which are not associated with an underlying systemic disease but have special characteristics of their own warranting a separate description (e.g. Fuchs’ uveitis syndrome).
4. Idiopathic non-specific uveitis entities which do not fall into any of the above categories.
Etiology of Posterior Uveitis and Panuveitis in ChildrenPosterior
Uveitis
o Toxoplasmosis (70%)
o Nematodiasis (10%-15%)
o Cytomegalovirus
o Tuberculosis
o Syphilis
o Rubella
o Subacute sclerosing panencephalitis
o Herpes simplex
o HIV
Panuveitis
o Sarcoidosis
o Sympathetic ophthalmia
o Vogt-Koyanagi-Harada syndrome
o Behcet's disease
o Ocular Lyme borreliosis
PATHOLOGICAL CLASSIFICATION
granulomatous uveitis if there are Busacca nodules in the iris stroma, large greasy "mutton-fat" keratic precipitates, large vitreous snowballs, or choroidal granulomas
2. non-granulomatous uveitis.
o Clinically, this distinction is not always useful because some types of granulomatous uveitis (e.g. sarcoid) may present with non-granulomatous features and, occasionally, non-granulomatous inflammation may have granulomatous characteristics (e.g. Fuchs’ uveitis syndrome).
SYMPTOMS
PAIN
o The pain of iritis is primarily related to ciliary spasm (cycloplegia). Pain caused by inflammation of ciliary body may therefore radiate to the periorbital region and to the eye. Because branches of the trigeminal nerve supply the cornea and iris, inflammation of these areas can cause a retrograde reflex with vascular dilation and swelling in the ciliary body, the so-called axon reflex.
PHOTOPHOBIA (pain caused by light exposure), lacrimation and blepharospasm
o Photophobia is a prominent symptom in patients with inflammation of the iris or ciliary body and in patients with keratitis and scleritis because of the axon reflex. Again, cycloplegia may lessen photophobia and pain.
BLURRED VISION
o Blurred vision may be caused by cloudy media, although vision is often surprisingly good in the presence of dense inflammatory reaction in the anterior chamber and vitreous. Macular edema, which frequently occurs with both anterior and posterior uveitis, can produce blurred vision, micropsia, and metamorphopsia.
RADNESS
SIGNS
CILIARY INJECTION
o Ciliary injection, or "ciliary flush," is manifest by a ring of dilated episcleral vessels radiating from the limbus.
PUPILLARY MIOSIS OR IRREGULARITY
o The pupil is typically small in patients with iritis because iris inflammation results in a release of prostaglandins, which constrict the pupil. One exception is patients with herpetic uveitis, who may present with a dilated pupil. The pupil in patients with anterior uveitis often becomes irregular and fixed because of the development of posterior synechiae.
BAND KERATOPATHY
o Long-standing chronic iridocyclitis, may result in calcific band keratopathy, the deposition of calcium hydroxyapatite in the cornea at the level of Bowman's membrane. Band keratopathy usually begins as grayish-white opacities at the periphery of the interpalpebral region. The opacification may spread centrally and in time may form a complete band within the interpalpebral zone. A lucid interval is noted between the band and the limbus because Bowman's layer does not extend to the absolute limbus. Small clear areas are noted in the opacity, representing the location where corneal nerves penetrate Bowman's layer. These holes impart a "Swiss cheese" appearance to band keratopathy. Band keratopathy should be distinguished from Vogt's limbal girdle and spheroidal degeneration. Occasionally, band keratopathy is atypical and starts centrally. Rarely, it forms a reticular pattern resembling lattice dystrophy called superficial reticular degeneration of Koby.
KERATIC PRECIPITATES
o Clusters of inflammatory cells deposited on the endothelial surface of the cornea are known as keratic precipitates. The cells, which have been deposited from the aqueous humor, are often found inferiorly on the cornea in a linear vertical formation (Turk's line) or in the form of a base-down triangle (Arlt's triangle).
o Small KP are characteristic of herpes zoster and Fuchs’ uveitis syndrome.
o Medium KP occur in most types of acute and chronic anterior uveitis.
o Large KP are usually of the ‘mutton fat’ variety and have a greasy waxy appearance. They typically occur in granulomatous uveitis.
o Fresh KP tend to be white and round. With age, they shrink, fade and become pigmented. Fading ‘mutton fat’ KP usually take on a ‘ground-glass’ (hyalinized) appearance.
Keratic precipitates are characterized as follows:
o Pigmented: Often old and inactive
o White or yellow: Recently or currently active
o Granulomatous: Larger and frequently "greasy" in appearance
o Nongranulomatous: Smaller
o Stellate: Often distributed over the entire endothelial surface; occur most commonly with herpes simplex and zoster uveitis, Fuchs' heterochromic iridocyclitis, toxoplasmosis, and sarcoidosis
ANTERIOR CHAMBER FLARE
o Normal aqueous humor is optically empty. If the slit-lamp beam is seen in the anterior chamber, it is termed "flare" and represents breakdown of the blood-aqueous barrier with exudation of protein. Flare is still graded according to the scheme proposed by Hogan. The light intensity of the slit lamp is turned to maximum, a short 1- to 2-mm slit is used, and the ray of light is directed at an oblique angle to the plane of the iris. Flare may also be measured using a laser flare meter or flare-cell meter, which quantifies anterior chamber protein by measuring light scattering of a helium-neon laser beam in the anterior chamber.
Grading of Anterior Chamber Flare
Flare Description
o 0 Complete absence
o 1+ Faint flare (barely detectable)
o 2+ Moderate flare (iris and lens details clear)
o 3+ Marked flare (iris and lens details hazy)
o 4+ Intense flare (fixed, coagulated aqueous humor with considerable fibrin)
ANTERIOR CHAMBER CELLS
o Cells in the aqueous humor usually result from active inflammation of the iris and ciliary body. T lymphocytes are the most common cell type overall, and polymorphonuclear leukocytes are common in hypopyon uveitis. Inflammatory anterior chamber cells are usually white and should be distinguished from pigmented cells, which may not indicate active inflammation.
o Cells in the anterior chamber are counted using the wide beam with a 1- to 2-mm long slit and graded according the method of Hogan and coworkers. If the cells seem to be suspended rather than moving, there is probably extensive fibrin in the aqueous. Leukocytes may precipitate out of the anterior chamber to form a hypopyon, and erythrocytes may layer out in a hyphema.
Grading of Cells
o Grade Cells per Field
o 0 No cells
o Rare 1—2
o Occasional 3—7
o 1+ 7—10
o 2+ 10—20
o 3+ 20—50
o 4+ 50 or more
CELLS IN THE ANTERIOR VITREOUS
o The density of cells in the anterior vitreous (retrolental space) should be estimated after pupillary dilation and compared with the density of the cells in the anterior chamber. A diagram indicating the density of the cells in these two locations is a useful method of documentation
IRIS ABNORMALITIES
o Some iris nodules are analogous to keratic precipitates in representing cells that have precipitated out of the aqueous humor. Other nodules may represent inflammatory foci on or within the iris.
o Iris nodules may be gray or white and translucent and are often covered with pigment. Masses at the pupillary border are called Koeppe nodules, whereas those on the anterior surface of the iris are called Busacca nodules. Busacca nodules are evidence of granulomatous inflammation, and Koeppe nodules are often located in areas that subsequently develop posterior synechiae. The presence and location of nodules should be carefully diagrammed, and every effort must be made to keep the pupil moving, thereby preventing the development of permanent iridolenticular adhesions.
o Posterior synechiae may also develop without nodule formation because fibrin in the aqueous can induce adhesions to the lens. If posterior synechia formation proceeds unchecked, pupillary block glaucoma may develop. Peripheral anterior synechiae (PAS) in the anterior chamber angle may result from chronic shallowing of the anterior chamber because of posterior synechiae and pupillary block. They may also result from fibrous organization of inflammatory exudates and precipitates in the angle. Rubeosis may also occur in severe long-standing uveitis and lead to PAS.
o In cases of chronic iritis, tiny refractile crystals may be seen on the surface of the iris, probably representing Russell bodies. These congested normal vessels must be distinguished from neovascular rubeotic vessels, which tend to arborize at random.
o The iris often becomes atrophic in patients with chronic iridocyclitis. Atrophy of the posterior pigmented epithelium of the iris is more common in herpetic uveitis and may result in iris transillumination defects. Anterior stromal atrophy is more characteristic of Fuchs' iridocyclitis and often results in heterochromia. The irides should therefore be examined by external inspection with the room lights on to document any heterochromia and at the slit lamp to document transillumination defects.
LENS OPACITIES
o Chronic or recurrent acute iridocyclitis may lead to posterior subcapsular cataract formation. Lysophosphatidyl choline, which is elevated in the anterior chamber during inflammation, may contribute to cataract formation. Steroids also contribute to the development of cataract in uveitis patients. Fibrinous membranes may develop over the surface of the lens in some cases of iridocyclitis. The underlying lens may be clear but the epilenticular membrane prevents a clear view of the lens and decreases vision.
VITREOUS OPACITIES AND HAZE
o Inflammatory posterior vitreous opacities have historically been graded by direct ophthalmoscopy. The method most commonly used is that described by Nussenblatt and associates, which uses the indirect ophthalmoscope.
Classification of Vitreous Haze
o Grade Description
o 0 No haze
o Trace Slight blurring of optic disc margin
o 1+ Slightly blurred optic nerve and vessels
o 2+ Moderately blurred optic nerve and vessels
o 3+ Optic nerve head border blurry but visible
o 4+ Optic nerve head obscured
Posterior vitreous opacities are best studied with contact or noncontact (78 diopter, 90 diopter, or superfield lens) slit-lamp biomicroscopy. Exudates or clumps of inflammatory cells may be seen anywhere in the vitreous. They may line the posterior surface of a posterior vitreous detachment, forming so-called vitreous precipitates, which are analogous to keratic precipitates and are common in toxoplasmosis. They may also be seen within the vitreous or on the retinal surface. Large clumps of vitreous cells are often termed "snowballs". Traction bands may form in the vitreous and result in the development of vitreous hemorrhage or retinal detachment.
FUNDUS ABNORMALITIES
o Every patient with uveitis requires a complete fundus examination. Posterior foci inflammation or infection may be missed if one examines the anterior chamber only. Indirect ophthalmoscopy is necessary to see the peripheral retina. Cystoid macular edema is a frequent cause of decreased vision in patients with anterior, intermediate, and posterior inflammation. Other causes of decreased visual acuity in patients with uveitis include epiretinal membranes and subretinal neovascularization.
o Disc edema or hyperemia is frequent in uveitis patients, often preceding the development of macular edema. Neovascularization of the disc is another abnormality that may develop in patients with severe uveitis. The optic nerve head may also be a site of granuloma formation
o The retinal vessels should be examined for evidence of vasculitis, noting whether the vasculitis affects primarily the veins (phlebitis) or the arteries (arteritis). Patients with sarcoid uveitis commonly have extensive periphlebitis, whereas patients with Behcet's disease may have more of an arteritic picture. Patients with herpetic retinitis may have extensive arteritis and phlebitis, which produce the appearance of "frosted branch angiitis“
o Examination of the fundus also includes an evaluation of the choroid because choroidal lesions are seen in many infectious and noninfectious uveitides. They may range in size from small Dalen-Fuchs–like nodules to large patches of choroidal infiltration, as seen in large-cell lymphoma. Choroidal granulomas may resolve, leaving "punched-out" atrophic lesions, such as the peripheral spots seen in the ocular histoplasmosis syndrome.
Entity Anatomy Chronology Granul./Nongranulom. Male/Female Unilateral/Bilateral Laboratory Test*
Syndromes
o Reiter's syndrome is a clinical syndrome usually described as arthritis, conjunctivitis, or iridocyclitis and nonbacterial urethritis or cervicitis.
o Behchet's disease is a clinical syndrome characterized by acute-onset iridocyclitis with hypopyon, posterior intraocular inflammation, recurrent aphthous stomatitis, genital aphthous ulceration, and multiple systemic manifestations, including arthropathy, gastrointestinal disease, subcutaneous nodules, erythema nodosum, cutaneous vasculitis, neurologic involvement, thrombophlebitis, and other areas of vasculitis, both arterial and venous.
o VOGT-KOYANAGI-HARADA SYNDROME
Patients may present with both acute iridocyclitis and meningeal symptoms of headache and neck stiffness. Posterior inflammatory changes include exudative retinal detachment and macular edema, vitreous inflammation, and optic nerve edema. Poliosis, alopecia, vitiligo, and auditory symptoms are frequently encountered, but are usually part of the longer term course of the disease.
Sarcoidosis
Treatment of uveitis
o The aims of treating uveitis are:
1. To prevent vision-threatening complications.
2. To relieve the patient’s discomfort.
3. If possible, to treat the underlying cause
o The four groups of drugs currently used in the treatment of uveitis are: mydriatrics, steroids, cytotoxic drugs and cyclosporin/
o Patient with uveitis caused by infections should be treated with the appropriate antimicrobial or antiviral agent
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SYMPATHETIC OPHTHALMIA
Patients with sympathetic ophthalmia may present with acute symptoms and findings of an acute iridocyclitis. The history of trauma or injury to one eye and later onset of inflammation in the other eye should alert one to the possibility of this diagnosis.
Thank you for your attention!
