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.

Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 2: Guidelines for Initiating Antitubercular Therapy in Anterior Uveitis, Intermediate Uveitis, Panuveitis, and Retinal Vasculitis.

TOPIC: The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU). CLINICAL RELEVANCE: The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition. METHODS: Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process. RESULTS: Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive. DISCUSSION: The COTS consensus guidelines were generated based on the evidence from published literature, specialists' opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis.

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.

Supposed endogenous endophthalmitis caused by Serratia marcescens in a cat.

An 8-year-old male neutered domestic shorthair cat was presented for evaluation of acute respiratory distress. Respiratory auscultation revealed a diffuse and symmetric increase in bronchovesicular sounds. Thoracic radiographs showed a diffuse unstructured interstitial pulmonary pattern with multifocal alveolar foci. Despite an aggressive treatment with supportive care, including oxygenotherapy and systemic antibiotics, progressive respiratory distress increased. Three days after the presentation, acute anterior uveitis was noticed on left eye. Ophthalmic examination and ocular ultrasonography revealed unilateral panuveitis with ocular hypertension. The right eye examination was unremarkable. Cytological examination of aqueous humor revealed a suppurative inflammation. Serratia marcescens was identified from aqueous humor culture. Primary pulmonary infection was suspected but was not confirmed as owners declined bronchoalveolar lavage. Active uveitis resolved and cat's pulmonary status improved after appropriate systemic antibacterial therapy. Vision loss was permanent due to secondary mature cataract. To the best of authors' knowledge, this is the first report of endogenous bacterial endophthalmitis secondary to S. marcescens infection in a cat.

Combined Intravitreal and Systemic Antibiotic Therapy in a Patient with Syphilitic Uveitis.

PURPOSE: To report the novel use of combined intravitreal and systemic antibiotic therapy in a patient with syphilitic panuveitis and discuss the management of ocular syphilis. METHODS: Case report Results: A 45-year old heterosexual male with human immunodeficiency virus (HIV) presented with 1 month of blurry vision in both eyes. Clinical examination revealed a bilateral panuveitis. The patient denied history of genital lesions or rash, but did complain of difficulty hearing bilaterally. Treponemal EIA was positive, the RPR titer greater than 1:512 dilution, and CSF VDRL 1:4. A diagnosis of neurosyphilis and ocular syphilis was made based on the clinical and laboratory findings. The patient was admitted for systemic intravenous antibiotic therapy, but was noted to have a penicillin allergy. Intravitreal ceftazidime was promptly administered bilaterally to achieve treponemacidal levels of antibiotic therapy. After penicillin desensitization protocol, the patient received 14 days of intravenous penicillin with clinical resolution. CONCLUSIONS: There are increasing reports of ocular syphilis in the United States and delay in diagnosis and management can lead to severe visual impairment and blindness. We report the first case of adjunct intravitreal antibiotic therapy in a penicillin allergic patient. As ocular syphilis is a form of bacterial endophthalmitis, combination intravitreal and systemic antibiotics may be considered.

Panuveitis caused by Borrelia burgdorferi sensu lato infection.

A 13-year-old boy who presented with a red left eye, painful eye movement, blurred vision, photophobia and increased lacrimation, was diagnosed with 1-sided panuveitis with optic disk edema. Diagnostic work-up revealed borrelial antibodies in serum. Diagnosis of Lyme borreliosis was substantiated by demonstration of lymphocytic pleocytosis, intrathecal borrelial antibody synthesis, improvement after treatment with ceftriaxone and exclusion of other causes.

[Role of Chlamydia trachomatis and Chlamydophila pneumoniae in damage of eye posterior segment structures].

AIM: Study the ability of Chlamydia trachomatis and Chlamydophila pneumoniae to damage structures of eye posterior segment, features of development of such infectious process, its morphological and clinical characteristics. MATERIALS AND METHODS: 6 rabbits with confirmed absence of C. trachomatis, C. pneumoniae were used in the study. 3 animals were infected with C. trachomatis culture and 3 animals--with C. pneumoniae culture. Subconjunctival and intravitreal mode of infectious agent introduction were used, as well as instillation of its culture into conjunctival sac. Microbiological diagnostics included microscopy with direct immunofluorescence, culture method and determination of antibody titers. Infectious process was studied by using ophthalmologic methods and histological examination. Observation period was 4 months. RESULTS: In all the animals a development of infectious process at early stages after the infection was confirmed. Conjunctivitis symptoms, inflammatory exudation into vitreous humor, chorioretinal inflammation loci, disorders in transparency of optical media and detachment of retina were clinical manifestations. In 2 animals infected with C. trachomatis severe panuveitis was noted. In 4 animals infectious process assumed subclinical characteristics (infection with both C. trachomatis or C. pneumoniae). In pathomorphologic studies data on the ability of C. trachomatis and C. pneumoniae to cause damage to cells of retina, pigment epithelium and choroid were obtained. CONCLUSION: C. trachomatis and C. pneumoniae may play a significant role in pathology of vitreous humor, retina, pigment epithelium and choroid.

Poststreptococcal syndrome uveitis in South African children.

OBJECTIVE: To describe the demographics, clinical features and management of the largest case series to date on poststreptococcal syndrome uveitis (PSU), a newly recognised immune-mediated response to group A ß-haemolytic streptococcus infection. METHODS: Case notes of all patients presenting to the Red Cross War Memorial Children's Hospital, Cape Town, with serologically confirmed PSU between 2004 and 2010, were retrospectively reviewed. RESULTS: A total of 22 cases were identified. Ages ranged from 4 to 12 years. 64% were black children and 64% were boys. Presenting visual acuities ranged from 6/6 to hand movements (median 6/24). 68% had bilateral disease. All had anterior uveitis (27% with posterior synechiae and 27% with hypopyon). 36% had vitritis and 23% had panuveitis. None had systemic illness or features of other poststreptococcal syndromes such as rheumatic fever, glomerulonephritis or polyarthritis. Anti-streptococcal titres (anti-streptolysin O and/or anti-deoxyribonuclease B) were significantly raised in all cases. Treatment comprised topical steroids and cycloplegic agents. Those with severe posterior segment involvement (41%) were treated with systemic corticosteroids. 55% received a course of oral penicillin. 82% had a single episode of uveitis. Four children had recurrences. Final visual acuities ranged from 6/6 to 6/36 (median 6/6). CONCLUSION: This case series significantly increases the evidence for PSU currently available in the world literature. The condition can manifest with the full spectrum of ocular inflammation, and most cases respond well to standard uveitis regimens. The role of antibiotic therapy remains unclear and requires further investigation.

Detection of Treponema pallidum in aqueous humor by real-time polymerase chain reaction.

PURPOSE: To report the additional clinical value of real-time Polymerase chain reaction (PCR) in the detection of Treponema pallidum in aqueous humor. METHODS: A real-time (RT) PCR assay targeting the polymerase 1 gene of Treponema pallidum was performed in aqueous humor samples collected in consecutive patients with ocular syphilis. RESULTS: Five patients presenting with optic neuritis (1), posterior placoid chorioretinitis (1), or panuveitis with retinitis (3) were tested. The PCR results were positive in the 3 cases of panuveitis and negative in the 2 other cases. CONCLUSION: RT-PCR for Treponema pallidum in aqueous humor is useful to confirm syphilitic panuveitis.

Syphilitic retinitis and panuveitis simulating acute retinal necrosis: case report.

Retinitis and panuveitis in immunocompetent patients is a rare and sight-threatening disease, of difficult diagnosis. A case of a 31-year-old male who presented with unilateral placoid retinitis and panuveitis, unsuccessfully treated as acute retinal necrosis, that in fact was syphilis, with neurosyphilis and excellent response to treatment is reported.

More to mutton than meets the eye.

A 64-year-old Mexican fisherman with a history of syphilis is diagnosed with panuveitis of the right eye after presenting with unilateral blurry vision, redness, and pain. A PPD was 35X30mm, and chest X-ray suggested tuberculosis. The patient's pain and vision improved with 4-drug anti-tuberculous therapy, topical steroids, and cycloplegic eye drops.

Syphilitic retinitis and panuveitis simulating acute retinal necrosis: case report / Retinite e panuveíte por sífilis simulando necrose aguda de retina: relato de caso

Retinitis and panuveitis in immunocompetent patients is a rare and sight-threatening disease, of difficult diagnosis. A case of a 31-year-old male who presented with unilateral placoid retinitis and panuveitis, unsuccessfully treated as acute retinal necrosis, that in fact was syphilis, with neurosyphilis and excellent response to treatment is reported.

Retinite com panuveíte em pacientes imunocompetentes é um condição rara e ameaçadora para a visão, e de difícil diagnóstico. É relatado um caso de um paciente do sexo masculino com 31 anos de idade, que se apresentou com retinite em placas e panuveíte, inicialmente tratado sem sucesso como necrose aguda de retina, que na verdade era um caso de sífilis ocular, com afecção do sistema nervoso central e ótima resposta ao tratamento sistêmico para sífilis.

Very severe HLA B27-associated panuveitis mimicking endophthalmitis: a case series.

PURPOSE: To report rare but important instances of very severe, hyperacute HLA B27-associated panuveitis, mimicking infective endophthalmitis and providing challenges to both diagnosis and management. DESIGN: Retrospective case review. METHODS: Four patient records were reviewed. Demographic features, clinical findings, course of uveitis, diagnostic/therapeutic measures, and outcomes are reported. RESULTS: All cases presented with severe panuveitis with visual acuities below 6/60 and poor fundal views. Three patients underwent intraocular fluid sampling for microbiology. All required systemic high-dose corticosteroid treatment, and two also needed oral immunosuppression. All eventually required cataract extraction. Final visual acuity varied from 6/12 to 6/6. CONCLUSIONS: HLA B27-associated uveitis may be unusually severe and may cause a panuveitis, mimicking infective endophthalmitis. The course may be prolonged and difficult with frequent complications including cataract.

Involvement of intraocular structures in disseminated histoplasmosis.

PURPOSE: To describe ocular involvement and response to treatment in a patient with human immunodeficiency virus (HIV) infection with severe progressive disseminated histoplasmosis (PDH). METHODS: We report a 35-year-old HIV-infected patient seen in our clinics over a period of 4 years. During antiretroviral treatment (ART), the HIV load became undetectable at 3 months; however, CD4 T-cell count increased slowly and rose to 100 cells/microl. Histoplasma capsulatum was cultured from skin pustules, cerebrospinal fluid (CF) and aqueous humour. RESULTS: The patient developed central nervous system (CNS) involvement 2 months and panuveitis in both eyes 4 months after the initiation of ART. With intravenous liposomal amphotericin B followed by oral voricanozole, the chorioretinal lesions of the right eye (RE) became inactivated and magnetic resonance imaging (MRI) lesions of CNS disappeared. Relapse of the inflammation in the anterior segment of the left eye (LE) resulted in a total closure of the chamber angle and severe glaucoma. Despite medical therapy, two cyclophotocoagulations, total vitrectomy and repeated intravitreal amphotericin B injections, LE became blind. Histoplasma capsulatum was cultured from the aqueous humour after antifungal therapy of 16 months' duration. CONCLUSION: PDH with intraocular and CNS manifestations was probably manifested by an enhanced immune response against a previous subclinical disseminated infection. It seems difficult to eradicate H. capsulatum from the anterior segment of the eye in an immunocompromised patient.

Ocular involvement in brucellosis.

OBJECTIVE: To report the ocular findings associated with brucellosis. DESIGN: Cohort study. PARTICIPANTS: One hundred thirty-two patients with the diagnosis of brucellosis. METHODS: Ocular manifestations of 132 patients with brucellosis admitted to the Uveitis-Behçet Service of Ophthalmology Department at the Ankara Education and Research Hospital in Turkey between May 1992 and May 2006 were evaluated prospectively. The diagnosis of brucellosis was based on clinical signs, Brucella agglutination tests, and blood cultures. RESULTS: Ocular involvement was detected in 21% of brucellosis patients. The most frequent manifestations were anterior uveitis (41%) and choroiditis (32%), followed by panuveitis (9%), papilledema (9%), and retinal hemorrhages (9%). Forty-one percent of these patients were in the acute stage and 59% were in the chronic stage of brucellosis. Interestingly, all the patients with anterior uveitis were in the acute stage and all the other patients with choroiditis, papilledema, and retinal hemorrhages were in the chronic stage. All patients responded well to systemic antibiotic treatment along with topical or systemic corticosteroid treatment. No recurrence of ocular manifestations was detected during the follow-up period, after completion of a 2-month systemic antibiotic treatment. CONCLUSIONS: Because ocular involvement of brucellosis is frequent in endemic regions, detailed ophthalmic examination of all patients with brucellosis should be done routinely. Ocular brucellosis should be considered in the differential diagnosis of all forms of uveitis or choroiditis in endemic regions, and these patients should undergo serologic screening for brucellosis.