Choroidal Histopathology

Nongranulomatous inflammation

Nongranulomatous uveal inflammations are the most common types of uveitis and usually present as iridocyclitis, characterized by an unspecific type of inflammatory reaction. The origin is frequently unknown. They can be suppurative or nonsuppurative. Suppurative nongranulomatous inflammation is an acute nongranulomatous purulent inflammatory reaction in which the predominant cell type is the polymorphonuclear leukocyte. It is usually secondary to bacterial infection. Nonsuppurative nongranulomatous inflammation can be either acute or chronic. In the acute inflammation, the predominant cell type is the neutrophil, and in chronic inflammation it is the lymphocyte and the plasma cell.

In histopathology, nongranulomatous processes can be defined as a predominantly exudative and alterative process. Contrary proliferative changes are subtle (i.e., granulomas, lymphoid aggregates, and exuberant granulation tissue). Plasma cells commonly predominate, and plasmacytoid cells and Russell’s bodies quite often are numerous. These cell types are particularly characteristic of nongranulomatous iritis, and since they are believed to be linked with antibody production, this form of uveitis may represent a local tissue response to antigenic stimulation.

As a sequelae of uveitis, the choroid may show focal or diffuse areas of atrophy or scarring. Retinochoroiditis or chorioretinitis may destroy Bruch’s membrane and the RPE, furthermore, the choroid and retina may become fused by fibrosis, and a chorioretinal scar or adhesion results.

Behçet’s disease

Behçet’s disease (syndrome) is characterized by retinal vasculitis, recurrent bilateral iridocyclitis with hypopyon, aphtous ulcers of the mouth and genitalia, dermatitis, arthralgia, thrombophlebitis, and neurologic disturbances. The disease is most common in men, especially between the ages of 20 years and 30 years. Also, men have more severe involvement and are at a greater risk of vision loss than women. Prevalence of Behçet’s disease worldwide ranges between 0.1/1000 and 1/10,000, with a significant presence in Asia. The lesions of the skin and mucous membrane most often appear before those of the eyes. Ocular inflammation occurs in about 70–80% of the patients. The etiology is unknown, and the disease appears to be more common in the Mediterranean countries.

Regarding ophthalmic examination, fluorescein angiography shows choroidal involvement. In addition, choroidal thickening has been shown using A-scan ecography, and more recently, enhanced depth imaging optical coherence tomography (EDI-OCT) has become an excellent tool to visualize choroidal layers and confirm its thickening in Behçet’s syndrome.

Pathological examination of the eyes diagnosed as Behçet’s disease shows a serohemorrhagic exudate containing polymorphonuclear leukocytes in the vitreous and in the anterior and posterior chambers. There are extensive areas of retinal necrosis. Depending on the stage of the disease, mononuclear and polymorphonuclear leukocytes can be found in the choroid. The choroidal infiltrate is predominantly composed of CD4 T lymphocytes, with some B lymphocytes and plasma cells ( Fig. 3.3 ).

Acute retinal necrosis

Acute retinal necrosis was first described in 1971 as an acute unilateral panuveitis with periarteritis that progressed to diffuse necrotizing retinitis. It is now known to be associated with the herpes family of viruses, most commonly varicella zoster virus and herpes simplex virus (HSV). HSV consists of linear double-stranded DNA packaged in an icosahedral capsid and covered by a lipid-containing membrane. HSV-1 is usually responsible for initial infections in children and for most herpetic eye infections in all ages. HSV-2, usually responsible for genital herpes, may rarely cause ocular disease in neonates, through contamination at birth by the mother’s genital herpes, or adults. Neonatal HSV most commonly causes a nonfollicular conjunctivitis followed by keratitis, but can also cause retinochoroiditis or chorioretinal scarring, iritis, cataracts, optic atrophy or neuritis, and microphthalmia. The differential diagnosis consists of the TORCH syndrome (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex).

Histopathology shows that infected areas can have both acute and chronic nongranulomatous inflammation, and intranuclear inclusions may be seen. 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.

Subacute Sclerosing Panencephalitis

Subacute sclerosing panencephalitis is a chronic progressive disease of the central nervous system in children and young adults, which produces an intracellular infection of the brain, retina, and lymphoid tissue. The disease usually emerges 5–7 years after the child has had an uneventful measles infection. The ocular findings consist mainly of macular degeneration, optic atrophy, and peripheral retinochoroidal lesions.

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 with light and electron microscopy.

Tuberculosis

Tuberculosis is an infectious disease caused by the acid-fast bacilli Mycobacterium tuberculosis and is characterized pathologically by the formation of granulomas with a central area of caseous necrosis. The most frequent route through which the bacilli reaches the eye is the blood stream. Cyclitis is the most common form of ocular involvement, which could rapidly spread posteriorly to cause a choroiditis, and this may occur either in association with clinically apparent pulmonary tuberculosis or in isolation, with no clinical or laboratory evidence of pulmonary infection.

In tuberculous posterior uveitis, the ocular changes can be divided into four groups: choroidal tubercles, choroidal tuberculoma, subretinal abscess, and serpiginous-like choroiditis.

• 1.

  Choroidal tubercles: These are the most common intraocular manifestation of tubercular posterior uveitis. Clinically, the tubercles appear as small white to yellowish nodules with unlimited borders and could be uni- or bilateral ( Fig. 3.4 ). Usually there are no more than five tubercles; however, there may be many. They may be associated with serous detachment of the retina. When a tubercle continues to grow and becomes a solitary mass, it is called tuberculoma. When the infection resolves, the margins become sharp and the mass could turn yellow or white with pigmentation in the periphery.

  

• 2.

  Choroidal tuberculoma: This is less common than the tubercles and can happen anywhere in the choroid. It usually presents as a yellowish and large unique subretinal mass ranging from 4 to 14 mm, accompanied with an exudative retinal detachment. Neoplasias and infective abscess are the differential diagnosis.

• 3.

  Subretinal abscess: Multiplication of the bacilli inside the granuloma could cause a yellowish abscess formation. They can occur from liquefaction necrosis within a tubercular granuloma. If not treated, these abscesses can rupture into the vitreous and result in endophthalmitis.

• 4.

  Serpiginous-like choroiditis: The exact mechanism of serpiginous-like choroiditis in tuberculosis remains unknown. It may represent an immune-mediated hypersensitivity reaction in the presence of few acid-fast bacteria in the choroid or RPE. The lesions are usually multifocal, bilateral, noncontiguous to optic disc, and are commonly associated with mild vitreous inflammation. There are two distinct clinical patterns: discrete, multifocal choroiditis lesions that are initially noncontiguous but later progress to form diffuse lesions with an active edge, resembling serpiginous choroiditis; and less commonly, a solitary, plaque-like lesion.

Histopathology

The disease is characterized pathologically by the formation of one or multiple granulomas. The histology of the granuloma reveals central necrosis surrounded by histiocytes/epithelioid cells mixed with multinucleated giant cells—eosinophils, neutrophils, and Langhans giant cells ( Fig. 3.5 ).

These inflammatory phagocytes in turn are surrounded by lymphocytes. The necrotic area usually contains few bacteria, which can be visualized on Ziehl–Neelsen acid-fast stain as red rod-shaped organisms. However, several organisms can also be seen in the necrotic macrophages that line caseous necrosis. In some granulomas, the organisms can be seen in multinucleated giant cells ( Fig. 3.3 ) or they may not be detected by the histologic staining techniques. The development of granulomas reflects a T-cell-driven response to the organisms.

In the choroid, these tubercles/tuberculomas may involve all layers of the choroid. In the early stages, the overlying RPE remains normal but is disrupted during later stages as the tubercles increase in size. The surrounding choroid is essentially normal except for some lymphocytic infiltration.