Multimodal imaging in infectious and noninfectious intermediate, posterior and panuveitis.

PURPOSE OF REVIEW: Given the heterogeneity of uveitis, markers of inflammation vary from patient to patient. Multimodal imaging has proven itself to be critical for accurate evaluation for disease activity and treatment response in uveitis. RECENT FINDINGS: Ultra-widefield (UWF) fluorescein angiography and autofluorescence (AF) as well as optical coherence tomography angiography (OCTA) have provided insights into disease pathogenesis and monitoring not previously appreciated. In addition to structural retinal imaging, OCT can be used to assess the choroid, the posterior cortical vitreous and the retinal vasculature in eyes with uveitis. SUMMARY: Multimodal ocular imaging in eyes with uveitis is critical for disease diagnosis and assessing response to treatment. UWF fluorescein angiography can detect retinal vasculitis even in the absence of overt vascular sheathing. UWF AF can help detect more chorioretinal lesions than clinically visible. OCT can be used to assess the posterior cortical vitreous, retina, large retinal vessels and choroid in uveitis. The use of multimodal imaging will likely be needed to determine clinical trial endpoints in studies evaluating therapeutics for uveitis.

Local treatment of infectious and noninfectious intermediate, posterior, and panuveitis: current concepts and emerging therapeutics.

PURPOSE OF REVIEW: Local therapeutics play an important role in the management of infectious and noninfectious uveitis (NIU) as well as certain masquerade syndromes. This review highlights the established therapeutics and those under investigation for the management of uveitis. RECENT FINDINGS: An injectable long-acting fluocinolone acetonide insert was recently approved by the Food and Drug Administration for the treatment of NIU affecting the posterior segment. Intravitreal methotrexate, sirolimus, and anti-vascular endothelial growth factor (VEGF) agents are being evaluated for efficacy in NIU. Intravitreal foscarnet and ganciclovir are important adjuncts in the treatment of viral retinitis as are methotrexate and rituximab for the management of vitreoretinal lymphoma. SUMMARY: Local injectable steroids with greater durability are now available for NIU but comparative efficacy to other treatment modalities remains to be determined. Local steroid-sparing immunosuppressive agents are undergoing evaluation for efficacy in NIU as are anti-VEGF agents for uveitic macular edema. Local antivirals may improve outcomes in cases of viral retinitis. Local chemotherapeutics can help induce remission in vitreoretinal lymphoma.

Effect of an Injectable Fluocinolone Acetonide Insert on Recurrence Rates in Chronic Noninfectious Uveitis Affecting the Posterior Segment: Twelve-Month Results.

PURPOSE: To assess the safety and efficacy of an intravitreal fluocinolone acetonide (FA) insert to manage inflammation associated with chronic noninfectious posterior uveitis. DESIGN: Multicenter, randomized, prospective, doubled-masked, sham-controlled, 3-year phase 3 clinical trial. PARTICIPANTS: One hundred twenty-nine participants with recurrent noninfectious posterior uveitis were assigned randomly to FA insert (n = 87) or sham injection (n = 42). The more severely affected eye in participants with bilateral disease was designated as the study eye. METHODS: The insert (FA, 0.18 mg) was injected into the vitreous cavity; sham injection mimicked the insert delivery procedure. Ophthalmic examinations, OCT, and ocular tolerability and discomfort assessments were conducted; study visits were on days 7 and 28 and months 2, 3, 6, 9, and 12. Uveitis recurrence was treated as needed. The 6-month recurrence rate was the primary outcome measure. RESULTS: The 6-month (28% and 91%) and 12-month (38% and 98%) uveitis recurrence rates were significantly lower (P < 0.001) with FA insert vs. sham, respectively. Fewer recurrences per study eye (mean, 0.7 vs. 2.5), lower incidence of 15-letter or more decrease in best-corrected visual acuity (14% vs. 31%), and reduced systemic (19% vs. 40%) and local (7% vs. 62%) uveitis adjunctive treatments were observed with FA insert vs. sham, respectively. The FA insert group showed higher rates of cataract. Intraocular pressure-lowering treatment use was similar between groups. No deaths, treatment-related study discontinuations, or unanticipated safety signals were observed through 12 months. CONCLUSIONS: Chronic noninfectious posterior uveitis was managed successfully in this study population; FA insert eyes experienced fewer uveitis recurrence episodes, required fewer adjunctive treatments, and demonstrated less visual acuity loss compared with sham eyes. The FA insert treatment group showed higher rates of cataract; delivery by injection was not associated with an increase in ocular adverse events or any other safety measures not typically associated with local steroid use, suggesting the procedure is appropriate for an office setting.

Tuberculous Posterior Sclero-Uveitis with Features of Vogt-Koyanagi-Harada Uveitis: An Unusual Case.

BACKGROUND Ocular tuberculosis (TB) is a clinical entity that presents with a wide range of clinical manifestations. It is regarded as an extremely challenging condition from the point of view of diagnostic approach and calls for early diagnosis and prompt treatment, as it can potentially lead to blindness. CASE REPORT This is a case report of a 32-year-old male from southern India who has been living and working in Greece over the last 10 years and presented with 2-week history of pain and progressive visual impairment of his left eye. He underwent a thorough clinical ophthalmological examination and imaging of the fundus, and the findings were consistent with uveitis. However, the manifestations of the inflammation were complicated as they included features that could be attributed mainly to Vogt-Koyanagi-Harada (VKH) disease and tuberculous serpiginous-like uveitis. Therefore, a systemic evaluation, together with specific laboratory and paraclinical investigations, were carried out to define the etiology of the inflammation and develop an optimal therapeutic plan. Taking into account specific findings from the chest imaging, a positive purified protein derivative (PPD) skin test, and sputum cultures positive for Mycobacterium tuberculosis (MTB), we set a diagnosis of posterior sclero-uveitis and started our patient on anti-tuberculous treatment. CONCLUSIONS This case reveals an atypical manifestation of tuberculous sclero-uveitis imitating Vogt-Koyanagi-Harada disease together with a few characteristics of serpiginous-like tuberculous uveitis, emphasizing the fact that tuberculosis should always be included in the differential diagnosis of uveitis when there is no obvious underlying disease.

PRESUMED POSTERIOR UVEITIS RELATED TO EHRLICHIA EXPOSURE.

PURPOSE: To describe a case of posterior uveitis with retinal vasculitis related to Ehrlichia exposure. PATIENTS AND METHODS: Single case report of a 68-year-old woman with posterior uveitis, steroid-induced glaucoma, and retinal holes. RESULTS: Ehrlichia titers were elevated 4-fold (1:256; normal <1:64) with an otherwise normal laboratory workup. The patient's cystoid macular edema responded to sub-Tenon's triamcinolone and oral doxycycline. CONCLUSION: To our knowledge, this is the first case of posterior uveitis associated with Ehrlichia reported in humans.

Diagnostic pars plana vitrectomy and aqueous analyses in patients with uveitis of unknown cause.

PURPOSE: To compare the yield of diagnostic pars plana vitrectomy (PPV) with the yield of aqueous analyses in patients with uveitis of unknown cause. METHODS: Seventy-five consecutive patients (84 eyes) with uveitis involving posterior eye segment who undergo a diagnostic PPV from 2005 through 2009 were retrospectively reviewed. Vitreous specimens were simultaneously analyzed by microbiological culture, flow cytometry, and cytology as well as by polymerase chain reaction and for intraocular antibody production by Goldmann-Witmer coefficient. In 53 eyes, both aqueous and vitreous samples were assessed. The primary outcome measure was the comparison between vitreous and aqueous analyses. RESULTS: Vitreous analysis was positive in 18 of 84 eyes (21%). Positive results indicated infectious uveitis in 12 of 18 cases (67%) and lymphoma in 6 of 18 (33%) cases. Of the 53 eyes with both aqueous and vitreous samples available, aqueous analysis revealed the diagnosis in 6 of 53 eyes and vitreous in 9 of 53 eyes. Unilateral uveitis (P = 0.022), panuveitis and uveitis posterior (P ≤ 0.001), preoperative immunosuppressive therapy (P = 0.004), and increasing age (P = 0.018) were associated with an increased diagnostic yield of PPV. Overall, 1 year after PPV, median visual acuity improved from 20/200 to 20/80 (Snellen, P ≤ 0.001). Of 18 patients who were on immunosuppressive treatment before PPV, 8 (44%) were able to stop immunosuppressive therapy during 1-year follow-up. The complications of PPV consisted predominantly of cataract development (33/65, 51%). CONCLUSION: Diagnostic PPV with the analysis of vitreous fluid by multiple laboratories for infectious and malignant disorders was useful in diagnosing uveitis of unknown cause. Previous aqueous analysis was especially valuable for the diagnosis of intraocular infections and may therefore decrease the number of patients who would otherwise undergo an invasive diagnostic PPV. Furthermore, PPV was associated with improved visual acuity and decreased use of immunosuppressive therapy.

Systematic analysis of wide-field fundus autofluorescence (FAF) imaging in posterior uveitis.

PURPOSE: To evaluate wide-field fundus autofluorescence (FAF) in patients with uveitis with retinal or chorioretinal involvement. MATERIALS AND METHODS: We included 78 study eyes in this prospective study. Best-corrected visual acuity, a full clinical examination, wide-field green-light FAF and composite color, green and red laser separation fundus imaging with Optomap SLO were performed. In a systematic analysis, the number, extension and margins of central and peripheral retinal or chorioretinal alterations, scars and infiltrates in infectious and non-infectious uveitic study eyes were evaluated. Wide-field FAF and color fundus imaging results were compared regarding their diagnostic properties. RESULTS: Nine out of 78 study eyes were diagnosed with infectious, 69 cases with non-infectious uveitis. Six infectious uveitic study eyes had changes of the peripheral fundus compared with 48 of 69 non-infectious uveitic eyes. In 33 (infectious versus non-infectious: 4 versus 29) cases, wide-field FAF images revealed more retinal or chorioretinal alterations or pathologies with a farther extended demarcation than wide-field composite color fundus imaging. Eleven out of 69 non-infectious study eyes were diagnosed with vasculitis which could be more precisely evaluated with wide-field FAF than wide-field composite color, green or red light filtered fundus imaging. CONCLUSIONS: Non-invasive wide-field FAF detects more retinal or chorioretinal involvement in patients with posterior uveitis than seen in color imaging and thus is useful in diagnosis and follow-up of uveitic patients.

The value of routine polymerase chain reaction analysis of intraocular fluid specimens in the diagnosis of infectious posterior uveitis.

OBJECTIVE: To assess the value of routine polymerase chain reaction (PCR) analysis on intraocular fluid from patients presenting with a first episode of suspected active infectious posterior uveitis in a population with a high prevalence of human immunodeficiency virus infection. DESIGN: Retrospective, interventional case series. Participants. 159 consecutive patients presenting at a tertiary care hospital over a five-year period. METHODS: PCR analysis was performed for cytomegalovirus, varicella zoster virus, herpes simplex virus types 1 and 2, Toxoplasma gondii, and Mycobacterium tuberculosis. RESULTS: PCR analysis confirmed the initial clinical diagnosis in 55 patients (35%) and altered the initial clinical diagnosis in 36 patients (23%). The clinical diagnosis prior to PCR testing was nonspecific (uncertain) in 51 patients (32%), with PCR providing a definitive final diagnosis in 20 of these patients (39%); necrotizing herpetic retinopathy and ocular toxoplasmosis were particularly difficult to diagnose correctly without the use of PCR analysis. CONCLUSION: The clinical phenotype alone was unreliable in diagnosing the underlying infectious cause in a quarter of patients in this study. Since the outcome of incorrectly treated infective uveitis can be blinding, PCR analysis of ocular fluids is recommended early in the disease even in resource poor settings.

Infectious causes of posterior uveitis.

The differential diagnosis of posterior infectious uveitis is broad. There are, however, a few common infectious causes of posterior uveitis that should always be considered. The more common infectious causes of posterior uveitis include syphilis, toxoplasmosis, tuberculosis, endogenous endophthalmitis, and viral causes (including herpes simplex virus, herpes zoster virus, and cytomegalovirus). The clinical features, diagnostic tools, and treatment options for each of these are reviewed in this article.

New infectious etiologies for posterior uveitis.

Emergent and resurgent arthropod vector-borne diseases are major causes of systemic morbidity and death and expanding worldwide. Among them, viral and bacterial agents including West Nile virus, Dengue fever, Chikungunya, Rift Valley fever, and rickettsioses have been recently associated with an array of ocular manifestations. These include anterior uveitis, retinitis, chorioretinitis, retinal vasculitis and optic nerve involvement. Proper clinical diagnosis of any of these infectious diseases is based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. The diagnosis is usually confirmed by the detection of a specific antibody in serum. Ocular involvement associated with emergent infections usually has a self-limited course, but it can result in persistent visual impairment. There is currently no proven specific treatment for arboviral diseases, and therapy is mostly supportive. Vaccination for humans against these viruses is still in the research phase. Doxycycline is the treatment of choice for rickettsial diseases. Prevention, including public measures to reduce the number of mosquitoes and personal protection, remains the mainstay for arthropod vector disease control. Influenza A (H1N1) virus was responsible for a pandemic human influenza in 2009, and was recently associated with various posterior segment changes.

[Endogenous endophthalmitis as a first clinical manifestation of Klebsiella sepsis. The importance of an early diagnosis]. / Primera manifestación oftalmológica de una sepsis por Klebsiella. Importancia de la sospecha diagnóstica precoz.

CASE REPORT: A diabetic patient who developed a unilateral uveitis with a chorioretinitis patch in his right eye associated with decreased visual acuity and fever. Endogenous endophthalmitis was suspected and complementary tests were performed, finding hepatic abscesses with Klebsiella isolation in the biopsy. The ocular disorder slowly improved with intravenous therapy and guided percutaneous liver drainage. CONCLUSION: Endogenous Klebsiella endophthalmitis is an uncommon condition with severe complications. An early diagnosis and aggressive antibiotic therapy can ameliorate the final course but the visual outcome still remains poor.

Review for disease of the year: differential diagnosis of ocular toxoplasmosis.

The diagnosis of ocular toxoplasmosis is mainly clinical, based in the presence of focal necrotizing retinochoroiditis often associated with a preexistent chorioretinal scar, and variable involvement of the vitreous, retinal blood vessels, optic nerve, and anterior segment of the eye. Recognition of this clinical spectrum of toxoplasmic retinochoroiditis is crucial, but other infectious, noninfectious, and neoplastic entities should also be considered in the differential diagnosis. Investigations such as serological tests, polymerase chain reaction of ocular fluids, and assessment of intraocular antibody synthesis are helpful in uncertain cases. This article provides an overview of the differential diagnosis of ocular toxoplasmosis, focusing on the most important entities to be considered and emphasizing distinctive features of each one of them in the clinical setting. Ocular toxoplasmosis has multiple clinical manifestations, which partially overlap with those of other entities and these should be carefully considered when making the differential diagnosis, particularly in less typical cases.

[Clinical characteristics and treatment of syphilitic posterior uveitis].

OBJECTIVE: To study clinical characteristics, treatment and prognosis of syphilitic posterior uveitis. METHODS: A retrospective study was conducted in 26 patients with syphilitic posterior uveitis. The diagnosis was confirmed by clinical and laboratory tests. RESULTS: There were 26 patients, 16 males and 10 females, mean age was 40 years. Fourteen patients were bilateral. The symptoms included impaired vision and floaters. In 40 eyes, yellow-white lesions in the posterior pole were present in 8 eyes, 22 eyes showed mild congestion of optic discs and loss of reflex in the fovea, and 6 eyes showed significant congestion and swelling of the optic disc. Fluorescein angiography showed staining or hyperfluorescence of optic disc in 40 eyes, venous leakage in 26 eyes, retinal pigment epithelium damage with dye pooling in 6 eyes, and cystoid macular edema in 6 eyes. ICGA: squamous or disseminative hypofluorescence damage was present in all 40 eyes. After the treatment, 32 eyes had improved vision and fundus damage. CONCLUSIONS: Syphilitic posterior uveitis has typical symptoms and signs. This is a curable disease, early diagnosis and prompt treatment are important for the improvement of prognosis.

Brucellosis and uveitis.

A 30-year-old-lady, (Case 1) was found to have brucella uveitis in her left eye. Serum agglutination (SAT) and SAT/Coombs titers were positive at 1:320 and 1:160, respectively. In Case 2, a 12-year-old-girl diagnosis of left brucellosis uveitis was made. Both SAT and SAT/Coombs titers were positive at 1:1280. This report confirms that Brucellae organisms as a cause of uveitis.

Uveitis in a tertiary ophthalmology centre in Thailand.

PURPOSE: To determine the aetiology and clinical characteristics of patients with uveitis in a tertiary ophthalmology centre in northern Thailand. METHODS: Standard ophthalmological examination and laboratory screening blood tests were performed in 200 consecutive new patients with uveitis. Patients were classified according to the location and aetiology of the uveitis. Specific clinical characteristics were recorded. DESIGN: Prospective case series. RESULTS: The case series included 106 male and 94 female patients with a mean age of 38 years. HIV-associated uveitis was noted in 31% (62/200), and included mostly patients with cytomegalovirus retinitis (85%, 53/62). In the non-HIV group, the most common anatomical type was anterior uveitis (34%, 47/138). Infectious uveitis was diagnosed in 22% (30/138) of non-HIV patients, and toxoplasmosis was the most common infection (12/138, 8.7%). The most common non-infectious clinical entities were Vogt-Koyanagi-Harada disease (20%, 22/108) and HLA-B27-associated acute anterior uveitis (9%, 10/108). CONCLUSIONS: The spectrum of uveitis in northern Thailand included 27% of HIV-infected patients with cytomegalovirus retinitis. Causes of non-HIV uveitis were similar to those often observed in the Far East, but the specific prevalences of these disorders were distinct from that found in India and Japan.

Vitrectomy for the diagnosis and management of uveitis of unknown cause.

PURPOSE: To determine the diagnostic yield of tests commonly used for vitreous fluid analysis in eyes with suspected intraocular infection or malignancy. DESIGN: Noncomparative interventional case series. PARTICIPANTS: Forty-four consecutive patients (45 eyes) treated from 1998 through 2006 with posterior segment inflammation who underwent pars plana vitrectomy for diagnostic purposes. INTERVENTION: Vitreous specimens obtained via pars plana vitrectomy were analyzed by microbiologic culture, cytologic analysis, and flow cytometry. MAIN OUTCOME MEASURES: Diagnostic yield and sensitivity of each test performed on vitreous specimens and visual outcomes of eyes that underwent diagnostic vitrectomy (DVx). RESULTS: Preoperative diagnoses were infection in 15 eyes and malignancy in 30 eyes. Overall, vitreous analysis identified a specific cause in 9 (20%) of 45 eyes. The overall sensitivity of DVx was 63.6%. The sensitivities of individual tests were: culture, 50%; cytologic analysis, 66.7%; and flow cytometry, 83.3%. The yields of diagnostic tests were: culture, 5.7%; cytologic analysis, 14.3%; and flow cytometry, 20.6%. Final diagnoses were infection in 6 eyes, malignancy in 9 eyes, and idiopathic in 30 eyes. Mean visual acuity improved significantly in the first 6 months after DVx. Visual acuity improved in 60% of eyes, with 37.8% of eyes improving by 3 lines or more. CONCLUSIONS: Analysis of vitreous fluid by widely available tests is useful in identifying intraocular infection or malignancy. Most patients experienced a substantial improvement in vision.