Infectious versus Non-Infectious Disease
Since many of the posterior uveitic conditions present with a somewhat restricted set of overlapping clinical signs and symptoms, the major clinical dilemma is to decide whether the disease is infectious or non-infectious (table 1). This has important therapeutic implications since many infectious diseases can be worsened by inappropriate use of immunosuppressants, while on the other
Table 1. Classification of posterior segment intraocular inflammation
Infectious Endophthalmitis Bacterial infections
Toxoplasmosis, toxocariasis, cysticercosis, diffuse unilateral subacute neuroretinitis Viral infections
Acute retinal necrosis (herpes simplex), herpes zoster (peripheral outer retinal necrosis), cytomegalovirus, HTLV-1, others Fungal (Candida, Aspergillus, others) Non-infectious Involving eye alone Pars planitis Idiopathic vitritis Idiopathic retinal vasculitis Idiopathic multifocal retinochoroiditis Sympathetic ophthalmia White dot syndromes Histoplasmosis-like disease Associated with systemic disease Behfet's disease Sarcoidosis
Vogt-Koyanagi-Harada disease Connective tissue diseases hand early control of non-infectious, immune-based uveitic disease can preserve vision. Examples of the former conditions include herpes simplex retinitis or cytomegalovirus retinitis, in which the use of immunosuppressants may sharply exacerbate the disease. In contrast, some infectious diseases may induce ocular tissue damage due to the associated immunological reaction and thus the correct treatment would be the combined use of antibiotics and immunosuppressants. Examples of this form of uveitic disease would be mil-iary tuberculosis and ocular toxoplasmosis.
Once the condition has been confirmed to be non-infectious, and is presumptively autoimmune or at least immune mediated, two major questions present themselves: what is the specific diagnosis and is there a significant threat to vision? In some cases these two questions are linked since the pattern of disease frequently will predict its course. For instance, some diseases such as bird-shot retinochoroidopathy (one of the white dot syndromes) carry a poor prognosis despite both the insidious nature of the disease and attempts to intervene with systemic immune suppression. Other disorders such as low-grade pars planitis have a good prognosis and merely require careful clinical observation provided there is no maculopathy. In other cases, the specific diagnosis may be difficult to identify and a careful assessment of the threat to vision is essential. This requires targeted investigation including fundus imaging, elec-trophysiology and other ocular function tests as well as systemic evaluation of general health to determine the risk of side effects from therapy should immunosuppression be required. These general principles are described in detail in recent monographs and guidelines [2, 3].
Non-Infectious Uveitis: Is Posterior Uveitis One or Several Diseases?
A question testing many ophthalmologists is whether the various clinical forms of non-infectious posterior uveitis represent discrete clinical entities or whether the condition is a single disease entity of varying severity reflecting the initial insult or inciting factors and the immune status of the patient at the time of disease onset. Most ophthalmologists adhere to the former view and recognize many disease entities, each with a site of origin in a specific ocular tissue component with a clear disease pattern and prognostic outcome. For example, pars planitis originates in the pars plana ciliaris and its hallmark is 'snow banking' in the retinal periphery. Snow banking is a clinical term for a dense amorphous exudate incorporating the vitreous base, retina and choroid and is composed of inflammatory cells, degenerating tissue debris and hyaline material [for review see ref. 4]. Sympathetic ophthalmia is a well-recognized condition of autoimmune inflammatory disease in which the second eye develops uveitis following penetrating injury to the first eye. It is characterized by granulomatous inflammation at the level of the outer retina (Dalen-Fuch's nodules) but is considered to spare the choriocapillaris layer [for review see ref. 4]. Serpiginous choroiditis is a spreading inflammation at the level of the retinal pigment epithelium which occurs in the apparent absence of significant inflammatory cell involvement in the vitreous. Recent indocyanine green studies of choroidal inflammatory diseases have allowed a new classification of ocular inflammatory disease, but lack definitive clinicopathological correlative evidence to support each disease entity .
In contrast, an alternative view has been proposed that the posterior segment of the eye has a limited set of responses to inflammatory insult, namely: [a] inflammatory cell infiltration of the vitreous (vitreous haze); [b] chorioretinal infiltration (granulomatous deposits, subretinal infiltrates of cells and/or neovascular membranes); [c] inflammation of the retinal vessels (retinal vas-culitis); and [d] edema, which is frequently focal and centered on the macula (macular edema) but may be extensive as in the localized detachments of VKH
or predominantly involve the optic nerve (optic nerve swelling) [1, 6, 7]. As indicated above, this view is based on data from experimental models using defined retinal autoantigens.
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