Nongranulomatous Inflammation

Published on 20/03/2015 by admin

Filed under Pathology

Last modified 22/04/2025

Print this page

This article have been viewed 8555 times

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.

C. A history of cigarette smoking is a significant risk factor.

Fig. 3.5 Endogenous uveitis. A, Ciliary injection and constricted right pupil caused by chronic endogenous uveitis (“acute” iritis). B, Corneal epithelium shows edema of its basal layer. Lymphocytes, plasma cells, and pigment are seen on the posterior corneal surface (fine keratic precipitates). C, Chronic nongranulomatous inflammation of lymphocytes and plasma cells is present in iris root and ciliary body. Note early peripheral anterior synechia formation. D, Iris shows chronic nongranulomatous inflammation with lymphocytes, plasma cells, and Russell bodies (large, pink, globular structures).

Examples

I. Viral infections such as herpes simplex and zoster, Epstein–Barr virus (EBV), SSPE, rubella (see Chapter 2), and rubeola may cause an endogenous nonsuppurative, chronic nongranulomatous uveitis.

A. Herpes simplex virus (HSV; Fig. 3.6)

1. HSV consists of a linear, double-stranded DNA packaged in an icosahedral capsid and covered by a lipid-containing membrane.

a. HSV-1 is usually responsible for initial infections in children and for most herpetic eye infections in all ages.

b. HSV-2, usually responsible for genital herpes, may rarely cause ocular disease in neonates (contamination at birth by mother’s genital herpes) or adults.

2. Neonatal HSV most commonly causes a nonfollicular conjunctivitis followed by keratitis.

a. Other ocular findings include retinochoroiditis (or chorioretinal scarring), iritis, cataracts, optic atrophy or neuritis, and microphthalmia.

b. The differential diagnosis consists of the TORCH syndrome (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex).

3. Acquired HSV in children and adults is similar to that in neonates.

Children who have HSV keratitis may have bilateral involvement and are at risk for recurrent keratitis and amblyopia.

a. A mucocutaneous eruption is common.

b. HSV retinitis (a cause of the acute retinal necrosis syndrome) may occur in immunocompetent or immunodeficient people (e.g., in acquired immunodeficiency syndrome).

c. The most common ocular manifestation is keratitis (see Chapter 8).

4. Histologically, the infected area reveals both acute and chronic nongranulomatous inflammation.

a. Intranuclear inclusions (Cowdry type A) may be seen.

b. HSV can be detected by monoclonal antibodies, such as the avidin–biotin complex immunoperoxidase technique, and by in situ DNA hybridization method using viral genome segments.

Fig. 3.6 Congenital herpes simplex type 2 endophthalmitis. Infant died from effects of disseminated herpes simplex. A, Gross appearance of necrotic peripheral neural retina. B, Necrotic peripheral neural retina sharply demarcated from relatively normal retina. C, Complete capsids containing nucleoids, along with empty capsids, present in necrotic neural retina. D, Retinal pigment epithelium forms hyperplastic plaque under peripheral neural retina in area of neural retinal necrosis. (Adapted from Yanoff M, Allman MI, Fine BS: Congenital herpes simplex virus, type 2, bilateral endophthalmitis. Trans Am Ophthalmol Soc 75:325. © PubMed Central 1977.)

B. Epstein-Barr virus (EBV)

1. The EBV, a B-lymphotrophic virus that accounts for most cases of infectious mononucleosis, is associated with Burkitt’s lymphoma (see Chapter 14), and it is detected in up to 50% of B-cell malignancies encountered in immunosuppressed patients.

EBV, after infecting the host’s cells, can hide from the immune system by producing a protein that inhibits its own synthesis, thereby minimizing the amount that appears on the cell surface.

2. Ocular manifestations, most commonly a follicular conjunctivitis, usually occur in association with infectious mononucleosis.

3. X-linked lymphoproliferative syndrome (XLP), one of the reactive histiocytic disorders, is a disease in which a primary EBV infection results in a fatal outcome from infectious mononucleosis, aplastic anemia, malignant lymphoma, and hypogammaglobulinemia in most male patients who have the XLP gene.

Epithelial keratitis, episcleritis, iritis, uveitis, dacryoadenitis, cranial nerve palsies, Sjögren’s syndrome, and Parinaud’s oculoglandular syndrome (see Chapter 7) also may occur. The Fas (Apo1 and CD95) antigen, a cell surface receptor involved in apoptotic cell death, may be defective (through a deletion) in XLP, resulting in incomplete elimination of peripheral autoreactive cells.

4. Histologically, a chronic nongranulomatous inflammation is seen.

C. Subacute sclerosing panencephalitis (SSPE, Fig. 3.7)

1. SSPE, caused by measles slow virus infection, is a chronic, progressive disease of the central nervous system in children and young adults, which produces an intracellular infection of brain, retina, and lymphoid tissue.

2. The disease usually emerges 5–7 years after the child has had an uneventful measles (rubeola) infection. The ocular signs and symptoms may antedate those of the central nervous system by as long as two years.

a. Patients have high titers of measles antibody in their serum and cerebrospinal fluid.

b. Measles antigen can be demonstrated in brain tissue by immunofluorescence.

3. The ocular findings consist mainly of macular degeneration, optic atrophy, and peripheral retinochoroidal lesions.

4. Histologically, the neural retina is necrotic, is infiltrated by lymphocytes, and shows conglomerations of multinucleated cells. Intranuclear inclusion bodies in retinal cells can be seen.

Fig. 3.7 Subacute sclerosing panencephalitis (SSPE). Clinical (A) and light microscopic (B and C) appearance of necrotic macula (acute retinitis with foveal hole formation) in patient who had SSPE. D, Many intranuclear inclusions (myxoviruses) are present in the inner nuclear layer of the foveomacular neural retina. The nuclear chromatin is clumped in the peripheral nucleus. (Modified from Nelson DA, Weiner A, Yanoff M et al.: Retinal lesions in subacute sclerosing panencephalitis. Arch Ophthalmol 84:613, 1970, with permission. © American Medical Association 1970. All rights reserved.)

II. Local ocular (nonsystemic) syndromes such as pars planitis and Fuchs’ heterochromic iridocyclitis may cause a nonsuppurative, chronic nongranulomatous uveitis.

A. Pars planitis (intermediate uveitis, peripheral uveitis, chronic cyclitis)

1. Pars planitis, a chronic process usually of children and young adults, consists of vitreous opacities, exudation, and organization of the vitreous base (“snowbanking”) in the region of the pars plana, and neural retinal edema, especially of the posterior pole (cystoid macular edema).

A 36-kDa protein (p-36) is elevated in the blood of many patients with active pars planitis. A pars planitis-like picture may be seen in cat-scratch disease. A significant association also exists between pars planitis and serum HLA-DR15 (HLA-DR15 specificity has been associated with other entities such as multiple sclerosis, idiopathic optic neuritis, and narcolepsy). Cataract and cystoid macular edema are common complications. Uncommon complications include band keratopathy, glaucoma, neural retinal detachment, retinoschisis, vitreous hemorrhage, and neural retinal hemorrhage. A link may exist between pars planitis and multiple sclerosis, especially when retinal periphlebitis is present at the time of diagnosis of pars planitis (multiple sclerosis develops in perhaps 15% of patients with pars planitis when they are followed for at least 8 years).

2. Histologically, a chronic nongranulomatous inflammation of the vitreous base, retinal perivasculitis, and microcystoid degeneration of the macular retina are seen.

a. The snowbank noted clinically corresponds microscopically to a loose fibrovascular layer in a condensed vitreous, containing occasional fibrocyte-like cells and scattered mononuclear inflammatory cells adjacent to a hyperplastic, nonpigmented pars plana epithelium.

b. The layer appears continuous with similar preretinal fibroglial membranes.

B. Fuchs’ heterochromic iridocyclitis (FHI; also called Fuchs uveitic syndrome) (Figs 3.8 and 3.9)

1. FHI, a condition of unknown cause, consists of a unilateral, chronic, mild iridocyclitis with characteristic, translucent, stellate, relatively unchanging keratic precipitates; heterochromia iridum with the involved iris becoming the lighter iris; and cataract and glaucoma development in the hypochromic eye.

The hypochromia of the involved eye is caused by iris stromal atrophy with loss of stromal pigment. The iris stromal atrophy may become so severe that the iris pigment epithelium can be observed directly, resulting in a paradoxical heterochromia with the involved eye becoming the darker eye. The glaucoma is probably caused by a combination of neovascularization of the anterior chamber angle, a trabeculitis, and possibly an associated atrophy of the uveal portion of the drainage angle.

2. Characteristically, despite the chronic uveitis and iris neovascularization, anterior and posterior synechiae do not occur (even though a cataract forms). Intraocular surgery is tolerated well.

A subgroup of FHI has an association, which may be causal, with toxoplasmic retinochoroiditis, toxocariasis, and herpetic ocular infections. A high percentage of FHI cases show antibodies against the rubella virus.

3. White, opalescent iris nodules may develop in black patients.

4. Histologically, a chronic nongranulomatous inflammatory reaction is seen in the iris, ciliary body, and trabecular meshwork.

Plasma cells and Russell bodies are prominent in the iris stroma. The Russell bodies may be seen clinically with the slit lamp as subtle iris crystals.

a. Inflammatory membranes are common over the anterior surface of the iris and anterior face of the ciliary body.

b. A fine neovascularization of the anterior surface of the iris and anterior chamber angle may be present.

The iris neovascularization is quite fine and just within the anterior border layer of the iris. Anterior segment perfusion defects and iris vasculature leakage may be seen. Chronic anterior segment ischemia, therefore, may play a role in the development of iris neovascularization. Fine, translucent, stellate keratic precipitates, observed clinically, have their counterpart in small clumps of mononuclear cells, lymphocytes, and macrophages on the posterior surface of the cornea.

c. The iris stroma and the pigment epithelium show atrophy with loss of pigment, especially in the stroma and the posterior layer of pigment epithelium.

Fig. 3.8 Fuchs’ heterochromic iridocyclitis. A, Blue-green uninvolved right eye is darker than light-blue involved left eye, which also contained a cataractous lens. B, Anterior face of ciliary body and trabecular meshwork contain chronic nongranulomatous inflammation. C, High magnification of trabecular meshwork demonstrates chronic trabeculitis with infiltration by lymphocytes and plasma cells. D, Iris shows loss of dilator muscle, stromal atrophy, nodular and diffuse infiltration by lymphocytes and plasma cells, and a fine iris surface neovascularization. (B–D, Modified from Perry HD, Yanoff M, Scheie HG: Rubeosis in Fuchs’ heterochromic iridocyclitis. Arch Ophthalmol 93:337, 1975, with permission. © American Medical Association 1975. All rights reserved.)

Fig. 3.9 Fuchs’ heterochromic iridocyclitis. A, Slit-lamp examination shows typical stellate keratic precipitates (KPs), which tend to change very little over long periods. B, The KPs are composed of lymphocytes and histiocytes. (B, Modified from Perry HD, Yanoff M, Scheie HG: Rubeosis in Fuchs’ heterochromic iridocyclitis. Arch Ophthalmol 93:337, 1975, with permission. © American Medical Association 1975. All rights reserved.)

III. Systemic syndromes such as Reiter’s syndrome, rheumatoid arthritis, and Crohn’s disease

A. Reiter’s syndrome

1. The classic triad of nonbacterial urethritis, conjunctivitis or iridocyclitis, and arthritis characterize Reiter’s syndrome.

2. HLA-B27 is positive in a high percentage of patients.

3. Bilateral mucopurulent conjunctivitis is present in most cases, whereas iridocyclitis tends to be seen only in recurrent cases.

4. Histologically, edema and a lymphocytic and neutrophilic inflammatory infiltrate are noted in the conjunctiva.

B. Rheumatoid arthritis

1. Ankylosing spondylitis has a 10–15% prevalence of uveitis, and Still’s disease has a 15–20% prevalence.

2. Juvenile rheumatoid arthritis (JR) is the most common specific childhood entity associated with uveitis in children.

a. Risk factors for uveitis in children who have JR include female sex, pauciarticular onset of arthritis, circulating antinuclear antibodies, and HLA-DW5 and HLA-DPw2 antigens.

b. Approximately 12% of patients with JR in whom uveitis develops eventually become blind.

C. Crohn’s disease

1. Crohn’s disease is an idiopathic, chronic, inflammatory bowel disease that shows frequent extra-bowel inflammation in the eyes, eyelids, orbits, lungs, joints, and skin.

The cause is unknown. Genetic predisposition, dysfunctional immune system, early episodes of infection [e.g., with Mollicute-like organism, previously called mycoplasma-like organisms (i.e., a noncultivatable, cell wall-deficient bacterial pathogen)], and environmental factors have been proposed.

2. Ocular findings include, most commonly, acute episcleritis, scleritis, acute anterior uveitis, and marginal keratitis; less commonly, conjunctivitis, orbital inflammation, optic neuritis, ischemic optic neuropathy, and retinal vasculitis.

Similar ocular findings can occur in ulcerative colitis.

3. Histologically, a granulomatous process is most common, but a chronic nongranulomatous inflammation may also be found.

Sequelae of Uveitis, Endophthalmitis, and Panophthalmitis

Cornea

I. Corneal endothelial degeneration or glaucoma, or both, may result in chronic stromal and epithelial edema and ultimately in bullous keratopathy (Fig. 3.10).

A. Pannus degenerativus may follow bullous keratopathy.

B. Keratic precipitates of mononuclear cells (mainly lymphocytes and plasma cells) along with pigment (see Figs. 3.5B and 3.9B) may be found on the endothelium.

Fig. 3.10 Corneal edema. A, Epithelium shows basal epithelial edema (bedewing). B, The cornea is edematous and shows large bullous formation. The corneal edema and lymphocytes, plasma cells, and pigment on the posterior corneal surface, forming fine keratic precipitates, are secondary to chronic nongranulomatous uveitis.

II. Ruptured corneal bullae may become infected secondarily, leading to a corneal ulcer.

Corneal ulceration may lead to perforation. Perforation and the resultant abrupt decrease in intraocular pressure may cause a ciliary artery to rupture, producing an expulsive intraocular hemorrhage.

III. Band keratopathy (i.e., calcium deposition; see Figs. 8.23–8.25) is common beneath the corneal epithelium in chronically inflamed eyes, especially in children who have Still’s disease.

IV. Corneal vascularization (see Fig. 8.18)

Anterior Chamber

I. Products of inflammation or hemorrhage may become organized, resulting in cicatrization.

II. The cicatrization or iris neovascularization may obliterate the angle of the anterior chamber.

Iris

I. The iris may undergo atrophy and necrosis with loss of dilator muscle, stroma, and even sphincter muscle and pigment epithelium.

II. Chronic anterior uveitis may induce peripheral anterior synechiae formation (see Fig. 3.5C).

III. Neovascularization of the anterior surface of the iris (rubeosis iridis or red iris, as seen clinically) may cause secondary anterior chamber angle synechiae and secondary angle closure.
Shrinkage of the fibrovascular membrane on the anterior iris surface may evert the pupillary border of the iris, termed an ectropion uveae (Fig. 3.11; see Fig. 15.5).

Fig. 3.11 Ectropion uveae. A, The sphincter muscle and pigment epithelium (PE) of the iris are bowed forward, along with anterior proliferation of the PE. The iris is adherent to the underlying lens (posterior synechia), and neovascularization is arising from the posterior iris (shown with increased magnification in B).

IV. Inflammatory and fibrous iris membranes may attach the pupillary margin of the iris to an underlying lens, to a lens implant or lens capsule in pseudophakic eyes, or to the anterior surface of the vitreous in aphakic eyes, resulting in an immobile pupil, seclusio pupillae (Fig. 3.12).

Fig. 3.12 Seclusion and occlusion of pupil. A, A membrane has grown across the pupil (occlusion of the pupil) and has adhered to the underlying lens, preventing the pupil from moving (seclusion of the pupil). B, Aqueous in the posterior chamber has bowed the iris forward (iris bombé), resulting in peripheral anterior synechiae. C, Histologic section of another case shows iris bombé, posterior synechiae (ps) of the iris to the anterior surface of the lens, a cyclitic membrane (cm), and a neural retinal detachment (dr). All are the result of long-standing chronic uveitis (pas, peripheral, anterior synechia; l, lens; h, hemorrhage under retina). (A and B, Courtesy of Dr. GOH Naumann.)

The same membrane may grow over the pupil and cover or occlude the area completely, called occlusio pupillae (see Fig. 3.12).

The same membrane that binds the pupil down to surrounding structures usually grows across the pupil so that seclusio pupillae and occlusio pupillae are often found together. Also, shrinkage of the membrane between iris and lens may cause the pupillary border to become inverted, termed entropion uveae.

V. Total (i.e., 360°) posterior synechiae cause a complete pupillary block, preventing aqueous flow into the anterior chamber.

A. The pressure builds up in the posterior chamber, bowing the iris forward (iris bombé; see Fig. 3.12).

B. An iris bombé forces the anterior peripheral iris to touch the peripheral posterior cornea, resulting in peripheral anterior synechiae and, if aqueous secretion is adequate, secondary closed-angle glaucoma.

Such eyes often have reduced aqueous flow, and hypotony may result even in the face of a completely closed angle.

Lens

I. Intraocular inflammation, especially posterior, frequently induces the lens epithelium to migrate posteriorly. The presence of the aberrant cells under the posterior lens capsule produces a posterior subcapsular cataract.

II. An anterior subcapsular cataract frequently results from an anterior uveitis (e.g., iritis or iridocyclitis), especially when posterior synechiae are present.

Ciliary Body

I. Ciliary processes or crests tend to become flattened and attenuated and their cores fibrosed (hyalinized).

II. Ciliary epithelium (nonpigmented, pigmented, or both) may proliferate, sometimes to a marked degree (i.e., massive proliferation of ciliary epithelium).

III. Intraocular inflammation may organize and fibrose behind the lens or lens implant (or behind the pupil in an aphakic eye) between portions of the pars plicata of the ciliary body. Such a fibrous membrane spanning the retrolental space and often incorporating proliferated ciliary epithelium and vitreous base is called a cyclitic membrane (see Fig. 3.12C; Fig. 3.13).

When a cyclitic membrane shrinks, the vitreous base, ciliary body pars plana, and peripheral neural retina are drawn inward to cause a total ciliary body and neural retinal detachment (see Fig. 3.13). Ciliary body degeneration diminishes aqueous production and leads to hypotony.

Fig. 3.13 Shrinkage of a cyclitic membrane, a fibrous membrane that spans the retrolental space and incorporates proliferated ciliary epithelium and vitreous base, has caused a neural retinal detachment. Massive ciliary body edema (“detachment”), posterior synechiae of iris to lens, and iris bombé are also present.

Permanent vascular sheathing results from organization and cicatrization of a perivascular inflammatory infiltrate or from involution of the blood vessels and thickening of their walls.

II. Intraocular inflammation, especially involving the peripheral neural retina or ciliary body, may be accompanied by fluid in the macular retina (i.e., cystoid macular edema).

III. Retinochoroiditis or chorioretinitis may result in chorioretinal scarring.

IV. The neural retina may become detached secondary to subneural retinal exudation or hemorrhage or to organization and formation of vitreal fibrous membranes or a cyclitic membrane.

V. The retinal pigment epithelium is a very reactive tissue and may undergo massive hyperplasia after inflammation. It also may show alternating areas of mild hyperplasia and atrophy, or it may be associated with intraocular ossification.

Glaucoma

I. Glaucoma may result from inflammatory cells and debris clogging an open anterior chamber angle; from peripheral anterior synechiae and secondary angle closure; from posterior synechiae, pupillary block, iris bombé, and secondary angle closure; or from trabecular damage (inflammation; i.e., trabeculitis and scarring).

II. The proper combination of factors must be present for glaucoma to develop; for example, peripheral anterior synechiae may be present, but if the inflammation damages the capacity for the ciliary body to secrete aqueous, glaucoma does not develop; in fact, hypotony may result.

When hypotony or a normal intraocular pressure is present in an eye with iris bombé and complete closure of the anterior chamber angle, aqueous is not being secreted. Intraocular surgery in such an eye often hastens the development of phthisis bulbi.

End Stage of Diffuse Ocular Diseases

I. Atrophy without shrinkage

A. Atrophy of intraocular structures such as the retina and uvea in a normal-size or even enlarged eye (e.g., buphthalmos).

B. The best example is the diffuse atrophy with long-standing glaucoma.

II. Atrophy with shrinkage (atrophia bulbi; Fig. 3.14)

A. This refers to atrophy of intraocular structures, which remain recognizable, plus atrophy of the globe so that it is smaller than normal.

B. The best example is chronic, long-standing uveitis (especially when it starts in childhood) that goes on to hypotony in the presence of an anterior chamber angle closed by peripheral anterior synechiae.

Clinically, the eye is soft and partially collapsed. The pull of the horizontal and vertical rectus muscles causes the shrunken eye to appear cuboid (“squared-off”) instead of spherical when viewed with the lids widely separated. A soft, squared-off atrophic eye when seen clinically is called a phthisical eye or a phthisis bulbi. Histologically, however, the eye does not usually show phthisis bulbi (see later) but, rather, atrophia bulbi.