Nongranulomatous Inflammation

Uveitis, Endophthalmitis, Panophthalmitis, and Sequelae

Definition

I. Acute suppurative nongranulomatous inflammation

A. This is an acute, nongranulomatous (no epithelioid or giant cells), purulent inflammatory reaction in which the predominant cell type is the polymorphonuclear leukocyte.

B. The reaction usually has an acute onset and is characterized by suppuration (i.e., the formation of pus). It usually is secondary to infection with bacteria that cause a purulent (pus) inflammatory reaction, such as Staphylococcus aureus.

II. Nonsuppurative nongranulomatous inflammation

A. This may be an acute (e.g., cellulitis secondary to Streptococcus hemolyticus) or chronic (e.g., the common type of uveitis) inflammation. It may have an acute, subacute, or chronic course.

Streptococcal gangrene of the eyelids, caused by group A hemolytic Streptococcus (also called flesh-eating disease, necrotizing fasciitis, necrotizing erysipelas, and gangrenous erysipelas), although rare, is increasing in prevalence.

B. The predominant cell type in acute inflammation is the polymorphonuclear leukocyte, and in chronic inflammation it is the lymphocyte and the plasma cell.

Classification

Terminology

I. If a single tissue is involved, the inflammation is classified according to the involved tissue (e.g., cornea—keratitis; retina—retinitis; and uvea—uveitis).

If more than one tissue is involved but not an adjacent cavity (a most unusual occurrence), then the inflammation is classified by the tissues involved with the site of primary involvement first (e.g., retinochoroiditis in toxoplasmosis and chorioretinitis in tuberculosis).

II. Endophthalmitis (Fig. 3.1) is an inflammation of one or more coats of the eye and adjacent cavities.

By this definition, a corneal ulcer with a hypopyon or an iritis with aqueous cells and flare would be an endophthalmitis, but most clinicians require a vitritis before calling an ocular inflammation an endophthalmitis.

Fig. 3.1 Endophthalmitis. A, The patient contracted “sterile” endophthalmitis after undergoing extracapsular cataract extraction and a posterior-chamber lens implant. Note the hypopyon. B, Another patient contracted a suppurative bacterial endophthalmitis after intracapsular cataract extraction. The diffuse abscess seen filling the vitreous cavity is characteristic of bacterial infection (fungal infection usually causes multiple tiny abscesses). The neural retina and its adjacent cavity, the vitreous, are involved, but the choroid and sclera are not.

III. Panophthalmitis (Fig. 3.2) is an inflammation of all three coats of the eye (and adjacent cavities); it often starts as an endophthalmitis that then involves the sclera and spreads to orbital structures.

Fig. 3.2 Panophthalmitis. A, The patient had a regular measles infection; subsequently, pain and inflammation developed in the left eye that led to panophthalmitis and corneal perforation. B, Histologic section shows the vitreous body, adjacent retina, choroid, and sclera are all involved, and the inflammation extends through the coats of the eye into the episcleral tissue (l, lens; va, vitreous abscess; r, necrotic inflamed retina; c, inflamed choroid; b, fresh blood; on, optic nerve; s, thickened inflamed sclera and episclera). C, Increased magnification shows the corneal perforation and the inflammation involving all coats of the eye. (A, Courtesy of Dr. RE Shannon.)

Sources of Inflammation

I. Exogenous: Sources originate outside the eye and body [e.g., local ocular physical injury (surgical trauma, penetrating and perforating nonsurgical trauma, and radiant energy); chemical injuries (acid and alkali); and allergic reactions to external antigens (conjunctivitis secondary to pollen)].

II. Endogenous: Sources originate in the eye [e.g., inflammation secondary to cellular immunity (phacoanaphylactic endophthalmitis); spread from contiguous structures (the sinuses); hematogenous spread (virus, bacteria, fungus, and foreign particle); and conditions of unknown cause (sarcoidosis)].

Suppurative Endophthalmitis and Panophthalmitis

Clinical Features

I. Severe ocular congestion, chemosis, and haziness of the cornea, aqueous, and vitreous are characteristic. A purulent exudate, frequently visible as a hypopyon, may be present in the anterior chamber.

II. Pain is prominent in both conditions but especially in panophthalmitis.

III. Extension into orbital tissue often results in congestion and edema of the lids and even exophthalmos.

IV. The cause may be infectious or noninfectious.

Classification

I. Exogenous

A. Infectious keratitis and corneal ulcers may cause a reflex sterile suppurative iridocyclitis and hypopyon.

B. Nonsurgical penetrating or perforating trauma may lead to the presence of a contaminated or sterile intraocular foreign body, producing a suppurative inflammation.

C. Postoperative suppurative inflammation in the first day or two after surgery is usually purulent, fulminating, and caused by bacteria.

1. Delayed (e.g., a month or two after intraocular surgery) endophthalmitis suggests a fungal infection.

2. A bacterial infection is also a possible cause of delayed endophthalmitis, especially with less virulent bacteria such as Staphylococcus epidermidis and Propionibacterium acnes (see Chapter 5).

II. Endogenous

A. Metastatic septic emboli, especially in children or debilitated persons, may occur in subacute bacterial endocarditis, meningococcemia, or other infections associated with a bacteremia, viremia, or fungemia.

B. Necrosis of an intraocular neoplasm, particularly retinoblastoma, may rarely result in a suppurative endophthalmitis or even panophthalmitis.

Histologically, necrosis of a malignant melanoma is more likely to induce an inflammatory reaction (usually lymphocytes and plasma cells) than is necrosis of a retinoblastoma. Clinically, however, inflammation is seen more frequently in retinoblastoma than in melanoma. In fact, retinoblastoma may clinically simulate inflammation in approximately 8% of retinoblastoma eyes.

C. Inflammation of contiguous or nearby structures (e.g., orbital abscess or cellulitis, meningitis, or a nasal phycomycosis) may rarely spread into the eye.

Histology

Suppurative inflammation is characterized by a polymorphonuclear leukocytic infiltrate (Figs. 3.3 and 3.4). Tissue necrosis causes a suppurative or purulent exudate (pus).

Fig. 3.3 Behçet’s disease. A, The patient has a hypopyon (h). Note the posterior synechiae (ps), a sign of the recurrent iridocyclitis in this patient (l, light reflexes; lr, lid reflexes). B, Anterior chamber contains exudate and polymorphonuclear leukocytes (hypopyon). C, A histologic section shows necrosis and perivasculitis of the neural retina. An organizing cyclitic membrane (c) has caused a detachment of the inflamed neural retina (r, detached, necrotic, inflamed retina). (Case shown in B reported by Green WR, Koo BS: Behçet’s disease: A report of the ocular histopathology on one case. Surv Ophthalmol 12:324. © Elsevier 1967; C, presented by Dr. TA Makley at the meeting of the Verhoeff Society, 1976.)

Fig. 3.4 Suppurative endophthalmitis (see also Fig. 3.1). A, Suppurative inflammation present in area of perforating corneal ulcer and in hypopyon in anterior chamber. Iris contains chronic nongranulomatous inflammatory infiltrate of lymphocytes and plasma cells. B, Polymorphonuclear leukocytes (PMNs) in hypopyon shown with increased magnification. C, Edge of corneal ulcer shown in A demonstrates corneal necrosis, PMNs seen as a lining-up of nuclear particles along stromal lamellae, and “smudgy” areas that represent bacterial colonies (seen as gram-positive cocci with special stain in D).

Examples

I. Behçet’s disease (see Fig. 3.3) is a chronic endogenous endophthalmitis.

A. It is a triple-symptom complex consisting of ocular inflammation (occurs in approximately 70% of patients), oral ulceration (aphthous stomatitis), and genital ulceration (conjunctival ulcers also may occur).

Eating English walnuts can exacerbate Behçet’s disease.

B. The disease is most common in men between the ages 20 and 30 years, who have a more severe involvement with a greater risk of vision loss than women. There is a 37% risk of visual loss at 10 years (24% risk of severe visual loss).

C. Arthritis or arthralgia, cutaneous lesions, thrombophlebitis, ulcerative colitis, encephalopathy, pancreatitis, central and peripheral neuropathy, vena caval obstruction, subungual infarctions, and malignant lymphomas may also be seen.

D. Plasminogen activator levels may be decreased.

E. A hypercoagulable or general vascular endothelial dysfunction is usually found.

F. S-antigen-responsive lymphocytes are increased in the peripheral blood during episodes of ocular inflammation.

G. To make the diagnosis of Behçet’s disease, patients must have at least three episodes of aphthous or herpetiform ulcerations in 12 months and two of the following four findings: recurrent genital ulceration, ocular signs (e.g., anterior or posterior uveitis, vitritis, or retinal vasculitis), skin lesions (e.g., erythema nodosum, pseudofolliculitis, or papulopustules), and positive pathergy test (sterile pustule developing within 24–48 hours at site of a cuticular needle puncture).

Plasma exchange, by removing immune complexes from the circulation, may be an alternative treatment for severe cases of Behçet’s disease.

H. The ocular inflammation is characterized by recurrent iridocyclitis and hypopyon (often motile), usually involving both eyes but not necessarily simultaneously.

1. In addition, macular edema, retinal pigmentary changes and periphlebitis, vitritis, periarteritis, and retinal and vitreal hemorrhages may occur (even when visual complaints are not present, fluorescein angiography shows leakage from superficial optic nerve capillaries and venules and peripheral retinal capillaries).

2. Small patches of retinal whitening are characteristic.

3. Secondary posterior synechiae may lead to iris bombé, peripheral anterior synechiae, and secondary angle-closure glaucoma.

4. Rarely, a bilateral immune corneal ring (Wessely ring) may occur.

I. Biopsy of mucocutaneous lesions shows vasculitis.

J. The serum may show variable increases in polyclonal immunoglobulins and anticytoplasmic antibodies. Serum and aqueous humor sialic acid levels are elevated during the active and remission phases of Behçet’s disease.

K. Human leukocyte antigen (HLA)-B51 is the most strongly associated genetic marker on Behçet’s disease over many ethnic groups.

L. Histologically, the main process appears to be a small or moderate-sized blood vessel obliterative and necrotizing vasculitis.

1. Retinal perivasculitis, vasculitis, hemorrhagic infarction, and detachment, along with a chronic nongranulomatous uveitis, may be seen.

2. An acute, suppurative inflammatory infiltrate with neutrophils occurs in the anterior chamber (hypopyon).

3. A secondary chronic nongranulomatous inflammatory infiltrate is frequently noted in adjacent tissues (see Fig. 3.4).

The choroidal infiltrate is predominantly CD4⁺ T lymphocyte, and some B lymphocytes and plasma cells. Spontaneous rupture of the lens can cause phacoanoaphylactic endopthalmitis.

Nonsuppurative, Chronic Nongranulomatous Uveitis and Endophthalmitis

Clinical Features

I. Anterior involvement often causes a severe, acute, “plastic” or exudative recurrent iridocyclitis, whereas posterior involvement produces a choroiditis or chorioretinitis.

II. A chronic nongranulomatous uveitis of unknown cause characterizes the “garden-variety” type of uveitis.

Classification

I. Exogenous: The inflammation is usually secondary to trauma.

A. The most common type is the iridocyclitis (traumatic iridocyclitis) that follows blunt ocular trauma or intraocular surgery.

B. Penetrating or perforating ocular injuries may produce a sterile, chronic nongranulomatous inflammation, resulting from multiple, tiny foreign bodies, degenerating blood, necrotic uvea, and so forth.

II. Endogenous (Fig. 3.5)

A. Idiopathic inflammation (i.e., “garden-variety” anterior uveitis) is the most common form of endogenous uveitis.

Rhegmatogenous retinal detachment may occur in approximately 3% of cases of uveitis. A close association exists with the HLA-B27 antigen. In addition, the anterior uveitis may follow, and be related to, infection with a variety of gram-negative bacteria (e.g., Yersinia species and Chlamydia trachomatis) or with Mollicutes (see discussion of Crohn’s disease, later).

B. The inflammation may be associated with viral infections such as rubella and subacute sclerosing panencephalitis (SSPE); bacterial infections such as syphilis; local ocular (nonsystemic) entities such as pars planitis, Fuchs’ heterochromic iridocyclitis, uveal effusion (see Chapter 9), and glaucomatocyclitic crisis (Posner–Schlossman syndrome; see Chapter 16); and systemic diseases such as Reiter’s syndrome, Behçet’s disease (see earlier), Kawasaki’s disease (mucocutaneous lymph node syndrome), phacoanaphylactic endophthalmitis (the uvea usually shows a chronic, nongranulomatous uveitis; see Chapter 4), collagen vascular disease (including rheumatoid arthritis), Crohn’s disease (regional enteritis; see later in this chapter), ulcerative colitis, and Whipple’s disease (see Chapter 12); and atopy.