A correct diagnosis of uveitis is often challenging, given the wide range of possible underlying conditions and the lack of typical phenotypes. Management decisions may be difficult in view of the risk of visual loss with either inappropriate or delayed therapy. Analysis of the vitreous may therefore be used to provide the clinician with valuable information. In this paper, we describe the main clinical situations in which vitreous sampling is indicated and provide some guidance to clinicians for tailoring their requests. These situations include suspected intraocular infection and suspected intraocular malignancy. We describe the principal tests carried out on vitreous samples, including cultures, polymerase chain reaction-based testing, and cytokine analysis. Limitations of the tests used are likely to become less as more advanced testing methods are introduced. The importance of selecting the appropriate investigations to support a clinical suspicion is emphasised, as is the interpretation of test results within a clinical context. 1. Introduction The term “uveitis” encompasses a wide spectrum of conditions resulting in intraocular inflammation. Standardised uveitis nomenclature (SUN) defines uveitis depending on the predominant site of inflammation within the eye [1]. At the most severe end of the spectrum, uncontrolled or inadequately treated posterior uveitis may result in irreversible visual loss. Uveitis may be associated with an underlying systemic disease or may exclusively involve the eye [2]. There are a vast number of causes and conditions related to the development of uveitis; however, these may be broadly divided into infectious, autoinflammatory, and neoplastic causes. Extensive investigations are often carried out to establish one, as the clinical phenotype may not be specific for a diagnosis. Common investigations include angiography, blood tests, urinalysis, chest X-rays, and CT scans. In certain situations, incorrect treatment may be catastrophic for vision and could potentially threaten the patient’s life [3]. Hence, a rapid and accurate diagnosis based on intraocular sampling may be essential, mainly to exclude infection or malignancy before the introduction of powerful immunosuppressive or steroid therapy. The vitreous gel is amenable to sampling, either by vitreous tap, where a small amount of gel is aspirated with a needle or by a formal vitrectomy, where most or all of the vitreous gel is removed surgically [4]. In this paper, we describe the clinical situations in which vitreous sampling may become necessary, providing a guide
References
[1]
D. A. Jabs, R. B. Nussenblatt, and J. T. Rosenbaum, “Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop,” American Journal of Ophthalmology, vol. 140, no. 3, pp. 509–516, 2005.
[2]
T. Barisani-Asenbauer, S. Maca, L. Mejdoubi, W. Emminger, K. Machold, and H. Auer, “Uveitis—a rare disease often associated with systemic diseases and infections—a systematic review of 2619 patients,” Orphanet Journal of Rare Diseases, vol. 7, no. 1, p. 57, 2012.
[3]
A. Rothova, F. Ooijman, F. Kerkhoff, A. Van der Lelij, and H. M. Lokhorst, “Uveitis masquerade syndromes,” Ophthalmology, vol. 108, no. 2, pp. 386–399, 2001.
[4]
H. Manku and P. McCluskey, “Diagnostic vitreous biopsy in patients with uveitis: a useful investigation?” Clinical and Experimental Ophthalmology, vol. 33, no. 6, pp. 604–610, 2005.
[5]
A. Rothova, J. H. de Boer, N. H. ten Dam-van Loon et al., “Usefulness of aqueous humor analysis for the diagnosis of posterior uveitis,” Ophthalmology, vol. 115, no. 2, pp. 306–311, 2008.
[6]
D. Trivedi, A. K. Denniston, and P. I. Murray, “Safety profile of anterior chamber paracentesis performed at the slit lamp,” Clinical and Experimental Ophthalmology, vol. 39, no. 8, pp. 725–728, 2011.
[7]
J. Davis, D. Miller, and P. Ruiz, “Diagnostic testing of vitrectomy specimens,” American Journal of Ophthalmology, vol. 140, no. 5, pp. 822–829, 2005.
[8]
R. N. Van Gelder, “Applications of the polymerase chain reaction to diagnosis of ophthalmic disease,” Survey of Ophthalmology, vol. 46, no. 3, pp. 248–258, 2001.
[9]
K. Nandi, P. Ranjan, L. Therese, and J. Biswas, “Polymerase chain reaction in intraocular inflammation,” The Open Ophthalmology Journal, vol. 22, no. 2, pp. 141–145, 2008.
[10]
S. N. Yeung, A. Butler, and P. J. Mackenzie, “Applications of the polymerase chain reaction in clinical ophthalmology,” Canadian Journal of Ophthalmology, vol. 44, no. 1, pp. 23–30, 2009.
[11]
M. N. Muthiah, M. Michaelides, C. S. Child, and S. M. Mittchell, “Acute retinal necrosis: a national population-based study to assess the incidence, methods of diagnosis, treatment strategies and outcomes in the UK,” British Journal of Ophthalmology, vol. 91, no. 11, pp. 1452–1455, 2007.
[12]
J. L. Davis, “Diagnostic dilemmas in retinitis and endophthalmitis,” Eye, vol. 26, no. 2, pp. 194–201, 2012.
[13]
T. H. C. Tran, F. Rozenberg, N. Cassoux, N. A. Rao, P. LeHoang, and B. Bodaghi, “Polymerase chain reaction analysis of aqueous humour samples in necrotising retinitis,” British Journal of Ophthalmology, vol. 87, no. 1, pp. 79–83, 2003.
[14]
B. Balansard, B. Bodaghi, N. Cassoux et al., “Necrotising retinopathies simulating acute retinal necrosis syndrome,” British Journal of Ophthalmology, vol. 89, no. 1, pp. 96–101, 2005.
[15]
T. W. Harper, D. Miller, J. C. Schiffman, and J. L. Davis, “Polymerase chain reaction analysis of aqueous and vitreous specimens in the diagnosis of posterior segment infectious uveitis,” American Journal of Ophthalmology, vol. 147, no. 1, pp. 140–147.e2, 2009.
[16]
T. F. Cochrane, G. Silvestri, C. McDowell, B. Foot, and C. E. McAvoy, “Acute retinal necrosis in the United Kingdom: results of a prospective surveillance study,” Eye, vol. 26, quiz 378, no. 3, pp. 370–377, 2012.
[17]
J. R. Safneck, “Endophthalmitis: a review of recent trends,” Saudi Journal of Ophthalmology, vol. 26, no. 2, pp. 181–189, 2012.
[18]
L. A. Wittenberg, D. A. Maberley, P. E. Ma, N. K. Wade, H. Gill, and V. A. White, “Contribution of vitreous cytology to final clinical diagnosis fifteen-year review of vitreous cytology specimens from one institution,” Ophthalmology, vol. 115, no. 11, pp. 1944–1950, 2008.
[19]
C. Joseph, P. Lalitha, K. Sivaraman, K. Ramasamy, and U. Behera, “Real-time polymerase chain reaction in the diagnosis of acute postoperative endophthalmitis,” American Journal of Ophthalmology, vol. 153, no. 6, pp. 1031–1037, 2012.
[20]
P. J. M. Bispo, G. B. de Melo, A. L. Hofling-Lima, and A. C. C. Pignatari, “Detection and gram discrimination of bacterial pathogens from aqueous and vitreous humor using real-time PCR assays,” Investigative Ophthalmology and Visual Science, vol. 52, no. 2, pp. 873–881, 2011.
[21]
V. Schiedler, I. U. Scott, H. W. Flynn, J. L. Davis, M. S. Benz, and D. Miller, “Culture-proven endogenous endophthalmitis: clinical features and visual acuity outcomes,” American Journal of Ophthalmology, vol. 137, no. 4, pp. 725–731, 2004.
[22]
D. M. Meisler, A. G. Palestine, and D. W. Vastine, “Chronic Propionibacterium endophthalmitis after extracapsular cataract extraction and intraocular lens implantation,” American Journal of Ophthalmology, vol. 102, no. 6, pp. 733–739, 1986.
[23]
B. Bodaghi, V. Touitou, C. Fardeau, L. Paris, and P. LeHoang, “Toxoplasmosis: new challenges for an old disease,” Eye, vol. 26, no. 2, pp. 241–244, 2012.
[24]
J. G. Montoya, S. Parmley, O. Liesenfeld, G. J. Jaffe, and J. S. Remington, “Use of the polymerase chain reaction for diagnosis of ocular toxoplasmosis,” Ophthalmology, vol. 106, no. 8, pp. 1554–1563, 1999.
[25]
J. D. F. De Groot-Mijnes, A. Rothova, A. M. Van Loon et al., “Polymerase chain reaction and goldmann-witmer coefficient analysis are complimentary for the diagnosis of infectious uveitis,” American Journal of Ophthalmology, vol. 141, no. 2, pp. 313–318, 2006.
[26]
C. Fardeau, S. Romand, N. A. Rao et al., “Diagnosis of toxoplasmic retinochoroiditis with atypical clinical features,” American Journal of Ophthalmology, vol. 134, no. 2, pp. 196–203, 2002.
[27]
R. Singh, P. Toor, S. Parchand, K. Sharma, V. Gupta, and A. Gupta, “Quantitative polymerase chain reaction for Mycobacterium tuberculosis in so-called Eales' disease,” Ocular Immunology and Inflammation, vol. 20, no. 3, pp. 153–157, 2012.
[28]
V. Touitou, F. Fenollar, N. Cassoux et al., “Ocular whipple's disease: therapeutic strategy and long-term follow-up,” Ophthalmology, vol. 119, no. 7, pp. 1465–1469, 2012.
[29]
J. Péer, F. H. Hochberg, and C. S. Foster, “Clinical review: treatment of vitreoretinal lymphoma,” Ocular Immunology and Inflammation, vol. 17, no. 5, pp. 299–306, 2009.
[30]
S. E. Coupland, “The pathologist's perspective on vitreous opacities,” Eye, vol. 22, no. 10, pp. 1318–1329, 2008.
[31]
A. Karma, E. O. von Willebrand, P. V. Tommila, A. E. Paetau, P. S. Oskala, and I. J. Immonen, “Primary intraocular lymphoma: improving the diagnostic procedure,” Ophthalmology, vol. 114, no. 7, pp. 1372–1377, 2007.
[32]
S. E. Coupland, A. Perez-Canto, M. Hummel, H. Stein, and H. Heimann, “Assessment of HOPE fixation in vitrectomy specimens in patients with chronic bilateral uveitis (masquerade syndrome),” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 243, no. 9, pp. 847–852, 2005.
[33]
S. E. Coupland and B. Damato, “Understanding intraocular lymphomas,” Clinical and Experimental Ophthalmology, vol. 36, no. 6, pp. 564–578, 2008.
[34]
H. N. Sen, B. Bodaghi, P. L. Hoang, and R. Nussenblatt, “Primary intraocular lymphoma: diagnosis and differential diagnosis,” Ocular Immunology and Inflammation, vol. 17, no. 3, pp. 133–141, 2009.
[35]
K. Raparia, C. C. Chang, and P. Chévez-Barrios, “Intraocular lymphoma: diagnostic approach and immunophenotypic findings in vitrectomy specimens,” Archives of Pathology and Laboratory Medicine, vol. 133, no. 8, pp. 1233–1237, 2009.
[36]
K. G. J. Ooi, G. Galatowicz, V. L. Calder, and S. L. Lightman, “Cytokines and chemokines in uveitis—is there a correlation with clinical phenotype?” Clinical Medicine and Research, vol. 4, no. 4, pp. 294–309, 2006.
[37]
N. Cassoux, A. Giron, B. Bodaghi et al., “IL-10 measurement in aqueous humor for screening patients with suspicion of primary intraocular lymphoma,” Investigative Ophthalmology and Visual Science, vol. 48, no. 7, pp. 3253–3259, 2007.
[38]
J. M. Baehring, S. Androudi, J. J. Longtine et al., “Analysis of clonal immunoglobulin heavy chain rearrangements in ocular lymphoma,” Cancer, vol. 104, no. 3, pp. 591–597, 2005.
[39]
R. R. Caspi, P. B. Silver, D. Luger et al., “Mouse models of experimental autoimmune uveitis,” Ophthalmic Research, vol. 40, no. 3-4, pp. 169–174, 2008.
[40]
A. D. Dick, P. G. McMenamin, H. K？rner et al., “Inhibition of tumor necrosis factor activity minimizes target organ damage in experimental autoimmune uveoretinitis despite quantitatively normal activated T cell traffic to the retina,” European Journal of Immunology, vol. 26, no. 5, pp. 1018–1025, 1996.
[41]
E. B. Suhler, J. R. Smith, M. S. Wertheim et al., “A prospective trial of infliximab therapy for refractory uveitis: preliminary safety and efficacy outcomes,” Archives of Ophthalmology, vol. 123, no. 7, pp. 903–912, 2005.
[42]
A. D. Dick, J. V. Forrester, J. Liversidge, and A. P. Cope, “The role of tumour necrosis factor (TNF-α) in experimental autoimmune uveoretinitis (EAU),” Progress in Retinal and Eye Research, vol. 23, no. 6, pp. 617–637, 2004.
[43]
K. S. Nagata K, K. Maruyama, K. Uno et al., “Simultaneous analysis of multiple cytokines in the vitreous of patients with sarcoid uveitis,” Investigative Ophthalmology & Visual Science, vol. 53, no. 7, pp. 3827–3833, 2012.
[44]
A. Lobo and S. Lightman, “Vitreous aspiration needle tap in the diagnosis of intraocular inflammation,” Ophthalmology, vol. 110, no. 3, pp. 595–599, 2003.
