The mechanism by which the vitreous becomes involved is not known with certainty. Because amyloid deposits are found within the walls of retinal vessels and in the RPE, amyloid may gain access to the vitreous through these tissues. In addition, because transthyretin is a blood protein, it may gain access to the vitreous by crossing the blood–aqueous or blood–retina barrier.

Neoplasia

Intraocular Lymphoma

Primary neoplastic involvement of the vitreous is uncommon because of the relatively acellular nature of the vitreous. However, the vitreous can be the site of primary involvement in cases of B-cell lymphoma. This type of lymphoma has been referred to as primary intraocular/central nervous system lymphoma, large cell lymphoma, and vitreoretinal/retinal lymphoma. Immunohistochemical and molecular genetic studies have confirmed that this entity is typically a B-cell lymphoma; however, T-cell lymphomas may occur in rare instances.

Clinically, primary intraocular lymphoma (PIOL) presents most commonly as a vitritis. Some patients have sub-RPE infiltrates (Fig 10-14) with a very characteristic speckled pigmentation overlying tumor detachments of the RPE. The sub-RPE infiltrates are present in a minority of patients with intraocular lymphoma. Recent evidence suggests that the lymphoma cells may be attracted to the RPE by B-cell chemokines and subsequently migrate from the sub-RPE space into the vitreous. More than half of patients presenting with ocular findings have or will develop involvement of the central nervous system.

The diagnosis of intraocular lymphoma is made by cytologic analysis of vitrectomy specimens. Immunohistochemical study of cell markers, flow cytometry, or gene amplification studies can be performed on vitreous specimens, although the standard method of diagnosis is cytology.

Cytologically, the vitreous infiltrate in intraocular lymphoma is heterogeneous. The atypical cells are large lymphoid cells, frequently with a convoluted nuclear membrane and multiple, conspicuous nucleoli. An accompanying infiltrate of small lymphocytes almost always appears, and the normal cells may obscure the neoplastic cell population. These small round lymphocytes are mostly reactive T cells. Numerous cell ghosts are usually present, and this feature is very suggestive of a diagnosis of intraocular lymphoma (Fig 10-15). Immunohistochemically, the viable tumor cells can be labeled as a monoclonal population of B cells. Flow cytometry is helpful in demonstrating a monoclonal population. Other laboratory tests that may be useful in the diagnosis and follow-up of patients with intraocular lymphoma are determination of the interleukin-10 to interleukin-6 ratio and the use of microdissection and polymerase chain reaction (PCR) for the detection of immunoglobulin gene rearrangement and translocation.

The subretinal/sub-RPE infiltrates are composed of neoplastic lymphoid cells (Fig 10-16). With or without treatment, the subretinal infiltrates may resolve, leaving a focal area of RPE atrophy. Optic nerve and retinal infiltration may also be present. Infiltrates in these locations tend to be perivascular and may lead to ischemic retinal or optic nerve damage. The choroid is most often free of lymphoma cells; however, secondary chronic inflammation may be present in the choroid. In the setting of systemic lymphoma with ocular involvement, the choroid (rather than the vitreous, retina, or subretinal space) is the primary site of involvement.

Coupland SE, Hummel M, Müller HH, Stein H. Molecular analysis of immunoglobulin genes in primary intraocular lymphoma.

Invest Ophthalmol Vis Sci. 2005;46(10):3507–3514.