Ординатура / Офтальмология / Английские материалы / Practical Manual of Intraocular Inflammation_Dick, Okada, Forrester_2008

Box 5 Conditions Causing Predominant Choroidal White Lesions

With significant vitritis and/or anterior segment inflammation

always keep in mind the “phase” of the disease while examining the patient. In many conditions, the choroidal infiltrates begin near or actually extend from the optic disc (e.g., sarcoidosis, serpiginous choroidopathy, punctate inner choroiditis, and others) and as a result the normally circular optic nerve head can take on a “disfigured” or “moth-eaten” appearance (Fig. 8). In addition, this can produce an enlargement of the blind spot.

Serous Retinal Detachment

It is said that the hallmark of serous retinal detachment is the shifting nature of the subretinal fluid. However, small areas of serous retinal detachment, for example, confined to the posterior pole as seen in VKH disease (Fig. 9), will not shift. In all cases, a retinal break causing a rhegmatogenous retinal detachment or vitreous traction causing a tractional retinal detachment should be ruled out, as both can

Figure 6 Composite fundus color photographs of various white dot syndromes. (A) Multiple white dots at the level of the RPE were observed in the peripheral retina of this patient diagnosed with multifocal evanescent white dot syndrome. (B) Six days later, most of the white dots were found to have resolved. (C) Patient with characteristic choriocapillaris/RPE lesions of APMPPE and (D) patient with Vogt-Koyanagi-Harada disease had a posterior recurrence of inflammation during tapering of systemic corticosteroids in the form of multifocal choroiditis. Note the multiple white spots that are deep to the retina, particularly toward the top of the photograph. These white spots resolved after an increase in the dose of corticosteroids. Abbreviations: RPE, retinal pigment epithelium; APMPPE, acute posterior multifocal placoid pigment epitheliopathy.

also occur as a complication in eyes with chronic inflammation, such as due to sarcoidosis. However, once the feature of serous retinal detachment is confirmed, one needs to consider only a few specific diseases, all of which are noninfective (Box 6). Uveal effusion syndrome, not an intraocular inflammatory disease, is included only for the purposes of listing the most likely candidates to consider in the differential diagnosis. Uveal effusion syndrome should be suspected if there is no vitritis and/or anterior segment inflammation and no choroidal leakage on fluorescein angiography, particularly if the eye is nanophthalmic. Serous retinal detachment due to inflammatory disorders is generally indicative of active choroidal inflammation and will generally exhibit some fluorescein leakage at the choroid or retinal pigment epithelium (RPE) level on angiography.

Figure 9 Serous retinal detachments in Vogt-Koyanagi-Harada disease. (A) Multifocal areas of serous retinal detachment are observed in the posterior pole in this patient with Vogt-Koyanagi- Harada disease (arrow). (B) Corresponding dye leakage and pooling is observed on fluorescein angiography.

Box 6 Conditions Causing Predominant Serous Retinal Detachments

With significant vitritis and/or anterior segment inflammation

Without significant vitritis and/or anterior segment inflammation

Panuveitis

When both significant anterior segment intraocular inflammation and significant PSII are the predominant features of a clinical presentation, the most likely diseases are fairly limited (Box 7). Of course, all of the diseases are also given on other lists above. This particular list is divided into diseases with rapid onset occurring over a few days versus those with more indolent onset of signs and symptoms occurring over weeks to months.

Box 7 Conditions Causing Panuveitis

Rapid onset (over days)

Indolent onset (over weeks to months)

DESCRIPTIONS AND WORKUP FOR

SPECIFIC DISEASE ENTITIES

Once a list of differential diagnoses is determined based on the predominant feature(s), diagnoses on that list may be given higher or lower priority (or ruled out entirely) using additional information in the history, symptoms, review of systems, or anterior segment examination. This process is represented in the flow chart (Fig. 10). The clinician must then consider ancillary tests as appropriate for the particular patient to extract evidence that may support or refute a possible diagnosis. One should avoid a “shotgun” approach to diagnostic testing, as it leads to increased cost and morbidity for the patient as well as false-positive or incidentally positive results that often spark further rounds of testing of little or no clinical value. Furthermore, like the saying “the punishment should fit the crime,” one should probably not embark upon expensive and tedious ancillary tests for an ocular inflammatory condition that is mild, particularly in the absence of systemic manifestations.

The following is a disease-specific guide to clinical features and basic workup of patients, divided into the traditional categories of infectious diseases (viral, bacterial, fungal, and parasitic), presumed autoinflammatory diseases (with systemic manifestations and without systemic manifestations), and neoplastic disease.

Figure 10 The thinking process prior to ordering ancillary tests.

Infectious Diseases: Viral

Viral infections, particularly the herpes family of viruses, have a particular propensity for infecting the retina. In this era of readily available polymerase chain reaction (PCR) testing, most causative viruses can be identified; however, treatment outcomes depend greatly on the immune status of the patient.

Acute Retinal Necrosis

ARN usually occurs in otherwise healthy individuals and can be caused by either one of the HSVs (type 1 or type 2) or the VZV. Since the clinical features are virtually indistinguishable for these viruses, accurate diagnosis is based on PCR of aqueous or vitreous humor (2). The standard treatment of intravenous acyclovir is generally effective for ARN in terms of halting progression of the retinitis, which usually starts in the periphery. Timely treatment will limit involvement of the optic nerve and macula, and one main determinant of visual outcome is whether optic atrophy and/or macular atrophy develop. The other main determinant of visual outcome is whether retinal detachment occurs as a secondary complication. The retinal detachment in ARN is rhegmatogenous and often develops within a few weeks of the onset of posterior vitreous detachment. Close monitoring of the vitreous may be helpful in alerting one to the possibility

Table 1 American Uveitis Society Criteria for the Diagnosis of ARN Syndrome

Criteria for use of the term “acute retinal necrosis syndrome”

1.One or more foci of retinal necrosis with discrete borders located in the peripheral retina

2.Rapid progression of disease if antiviral therapy has not been given

3.Circumferential spread of disease

4.Evidence of occlusive vasculopathy, with arteriolar involvement

5.Prominent inflammatory reaction in the vitreous and anterior chamber

Characteristics that support, but are not required for, a diagnosis of ARN syndrome

1.Optic neuropathy/atrophy

2.Scleritis

3.Pain

Abbreviation: ARN, acute retinal necrosis.

Source: From Ref. 5.

of incipient retinal detachment. To improve visual outcomes for this disease, some physicians advocate prophylactic vitrectomy with barrier laser photocoagulation to the borders of healthy retina in eyes with significant vitreous inflammation but no retinal detachment. However, there are no randomized clinical trials as of yet to support such prophylactic surgery. Rarely a patient with ARN may have a history of herpetic encephalitis or recent cutaneous zoster, and ARN can occur in neonates. ARN can also occur in acquired immunodeficiency syndrome (AIDS) or other immunocompromised patients (e.g., patients on chronic systemic corticosteroids), and the disease may progress rapidly in these cases. ARN has been reported in rare instances to be due to CMV (3), and atypical toxoplasmosis may mimic ARN (4). The American Uveitis Society published a set of diagnostic criteria for ARN based solely on clinical characteristics and does not depend on identification of virus (Table 1) (5).

lOcular signs: Starts in one eye, but may eventually involve both eyes in one-third of patients, usually within a few weeks. Anterior: Moderate- to-severe granulomatous anterior segment inflammation, intraocular pressure frequently elevated in early phase of disease. Posterior: Progressively worsening vitritis, whitish yellow spots coalescing to patches of retinitis/retinal necrosis starting in the periphery and progressing toward the posterior pole (Fig. 7), prominent vasculitis with hemorrhage, macular edema, papillitis, optic atrophy, rhegmatogenous retinal detachment

lTreatment: Intravenous acyclovir followed by oral acyclovir or oral valacyclovir. Aspirin and systemic corticosteroids may be considered. Vitrectomy with laser photocoagulation, with or without silicone oil or gas tamponade, is performed for rhegmatogenous retinal detachment. The

utility of prophylactic surgery is unknown

lPrognosis: Varies depending on degree of posterior pole involvement and whether retinal detachment develops

Progressive Outer Retinal Necrosis

PORN is a relatively rare variant on VZV-associated retinal infection that starts in the outer retina, giving a distinct pattern of whitening of large geographic areas of retina with initially little or no retinal edema, retinal hemorrhage, or vitritis. PORN has a predilection for individuals on immunosuppression and advanced AIDS patients, a characteristic that may play a role in the distinctive manifestation and pathogenesis of VZV infection in these patients. PORN will progress rapidly to full thickness retinal necrosis and optic atrophy, with poor visual outcomes in most cases despite treatment. Unfortunately, PORN usually starts in one eye at first, but eventually both eyes are involved in 70% of cases (7). Although rare, PORN may also be caused by other herpes family viruses such as HSV (8).

l Presenting symptoms: Decreased vision

lMedical history/demographic associations: Immunosuppression, AIDS, rarely a history of cutaneous zoster

lOcular signs: Bilateral in 70%. Anterior: Minimal-to-no anterior segment inflammation. Posterior: Minimal-to-no vitritis, progressively enlarging patches of retinal whitening in multifocal areas (Fig. 11), papillitis initially. Vitritis, vascular sheathing, vascular occlusion, optic atrophy, and rhegmatogenous retinal detachment may develop in later stages

lTreatment: Intravenous acyclovir or ganciclovir, with or without foscarnet, is commonly used but generally ineffective. Vitrectomy with

by secondary retinal detachment. Some patients on immunosuppressive treatment, who develop CMV retinitis, may experience spontaneous regression of their retinitis with reduction or discontinuation of their immunosuppressive regimen. CMV retinitis may also develop in newborn infants with systemic CMV infection, which may be fatal, or may result in severe central nervous system sequelae. In general, there are two distinct presentations of active CMV retinitis. The first involves an edematous retinitis with anywhere from mild to prominent retinal hemorrhages, usually in one or two areas either starting in the periphery or in the peripapillary region. The second involves more indolent disease with a granular appearance to the retinitis and minimal retinal edema or hemorrhage. The latter may be difficult to distinguish from regressing disease and therefore requires careful evaluation. Frosted branch angiitis and immune recovery uveitis (IRU), both immune phenomena which can be observed in patients with CMV retinitis are described in separate sections. Finally, it should be noted that CMV retinitis in AIDS patients can occur concomitantly with other opportunistic retinal infections, mainly toxoplasmosis retinochoroiditis, cryptococcal retinitis, and HSV retinitis.

l Presenting symptoms: Decreased vision, peripheral scotoma

lMedical history/demographic associations: AIDS, immunosuppressive treatment for autoinflammatory disease, cancer treatment, newborn infants with systemic CMV infection

lOcular signs: Bilateral in up to one-third of AIDS patients, although usually unilateral in patients on immunosuppressive therapy. Anterior: Minimal-to-no anterior segment inflammation. Posterior: Minimal-to-no vitritis, patchy retinal whitening and edema starting in the periphery or in the peripapillary area, commonly associated with retinal hemorrhages initially. Alternatively, a granular and somewhat faded pattern of retinitis starting in the periphery may be observed (Fig. 12). Without treatment, progressive enlargement and coalescence of lesions is observed over months. Vasculitis and papillitis are common features, particularly in later stages, with variable progression to vascular occlusion and optic atrophy

lSystemic signs: Fever, malaise, diarrhea, and abdominal pains (infective mononucleosis-like syndrome) may accompany acute systemic CMV

infection

lWorkup: PCR of aqueous or vitreous samples. If PCR is not available, Goldmann-Witmer coefficient may be calculated from intraocular antibody titers (6). If HIV status is unknown, HIV testing should be performed