Part 2 • Diagnosis

Chapter 5 Diagnostic Testing

Box 5-2  Analysis of aqueous humor for antibody

A = Inverse titer of specific IgG in aqueous B = Total IgG in aqueous

X = Inverse titer of specific IgG in serum Y = Total IgG in serum

If (A/B)/(X/Y) > 1, then there is local antibody production within the eye, suggesting intraocular infection

example:

Aqueous titer to toxoplasmosis = 1:200; aqueous IgG = 0.1 g/dL Serum titer to toxoplasmosis = 1:400; serum IgG = 3 g/dL Therefore: A/B = 60, suggesting that uveitis is due to

toxoplasmosis

aqueous of half of patients with clinically confirmed herpes keratouveitis. Kaplan and colleagues24 found antibodies against either HSV or vesicular stomatitis virus in the aqueous of four of 20 patients with idiopathic uveitis. Samples may, however, become contaminated with peripheral serum. Further, local production of specific antibody may be related to a polyclonal B-cell activation totally unrelated to the virus in question. Clearly, these methods require further refinement, and only with continued attempts at such refinement can this technique help in the diagnosis of intraocular inflammatory disease. Although this approach is not generally used in the United States, it is commonly used by many specialists in Europe.25

Diagnostic vitrectomy is mostly used to evaluate the possibility of either infection or malignancy. Intraocular inflammation as a result of autoimmune disease may look similar to the inflammation after infection. In patients with a history of postsurgical uveitis, a diagnostic vitrectomy and anterior chamber tap are often warranted. Recently, a number of slow-growing bacteria have been identified as causes of chronic insidious postsurgical uveitis. One of these organisms, Propionibacterium acnes, is described in detail in the chapter on postsurgical uveitis (see Chapter 18) and the chapter on masquerade syndromes (see Chapter 30). Davis and colleagues26 reported on 84 eyes in 78 patients who underwent pars plana vitrectomy for diagnostic purposes. The preoperative diagnosis was either infection or malignancy. Vitreous testing led to a diagnosis in 48 of 78 patients. When the preoperative indication was compared with the final clinical diagnosis, the efficiency of the diagnostic procedure of cytologic evaluation, flow cytometry, and bacterial or fungal culture was 67%, 79%, and 96%, respectively. Margolis and colleagues27 reviewed 45 eyes of 44 consecutive patients with posterior segment inflammation who underwent pars plana vitrectomy for diagnostic purposes. The vitreous analysis, which included culture, cytologic analysis, and flow cytometry, identified a specific cause in nine (20%) of the 45 eyes. In addition, visual acuity improved in 60%.

Many clinicians routinely obtain samples for biopsy from the conjunctiva and lacrimal gland in the search for histologic evidence of sarcoidosis. Most studies, however, report disappointing results with random ‘blind biopsies’.28 We suggest obtaining a biopsy sample from the conjunctiva only if a specific lesion is noted, and of the lacrimal glands only if they are clinically enlarged or show increased uptake on a gallium scan. We have, however, found that biopsy of skin lesions can be extremely helpful to the clinician. We have

made the diagnosis of sarcoidosis in numerous patients on the basis of a noncaseating granuloma found on skin biopsy.

Finally, we have performed chorioretinal biopsy in patients with severe posterior uveitis that caused severe visual loss in one eye and threatened the other eye despite therapy. This technique is more fully described in the chapter on the role of surgery in the diagnosis and treatment of uveitis (see Chapter 8).

Ancillary ophthalmic tests

Electrophysiology

Electrophysiologic testing can help to determine the cause of visual loss in some patients with uveitis, but in general rarely leads to a specific diagnosis. Both the electroretinogram (ERG) and the electrooculogram (EOG) can be altered in many of the inflammatory disorders of the retina and choroid. Experiments in the 1960s showed that the ERG was altered in animals with experimental uveitis.29 Clinical studies also showed altered ERGs in patients with uveitis.30 Because of the general lack of specificity, the electroretinogram will only tell the observer if significant widespread damage has occurred, and to date we are not aware of changes noted on the electroretinogram or on the electro­ oculogram that are specific for entities within the broad category of posterior uveitis. Feurst and colleagues31 reported that the electroretinograms of patients with birdshot retinochoroidopathy show a loss of blue cone responses in the dark-adapted state (see Chapter 25). We have noted a loss of blue cone responses not only in birdshot retinochoroidopathy,32 but also in other posterior uveitis entities. This may reflect a general effect of the immune response on the retina’s electrophysiologic responsiveness. Because it is difficult to assess the clinical response to therapy in some patients with birdshot retinochoroidopathy, a number of uveitis specialists use ERG monitoring to assess the progression of disease and response to therapy.33–35

One problem with the use of electrophysiology in assessing some forms of uveitis is that the pathology is limited to the macula. As a result, the ERG may be relatively normal. The use of multifocal ERG allows the assessment of function in the central retina.36,37 The multifocal ERG may also be used to assess changes with therapy.38

Laser interferometry

Early in our therapeutic studies we wanted to know whether we could predict which patients with uveitis might improve with immunosuppressive therapy. We had noted that there was a discrepancy between the visual acuity obtained with the standard Snellen and later the Early Treatment Diabetic Retinopathy Study (ETDRS) eye charts and the laser interfero­ meter. The visual acuity obtained with the laser interfero­ meter is often better than that measured with eye charts. We hypothesized that these differences might be caused by potentially reversible macular changes as a result of the ongoing inflammatory disease. In a prospective study of 26 patients treated with ciclosporin for endogenous intermediate and posterior uveitis, we noted an improvement in 86% of patients in whom the laser interferometer predicted a