Diagnostic Yield of Vitreous Biopsy in Sarcoid Uveitis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00609687
First received: January 25, 2008
Last updated: April 9, 2013
Last verified: January 2008
  Purpose

The usefulness of diagnostic vitrectomy in patients with suspected sarcoidosis with posterior segment involvement (in whom a diagnosis cannot be determined by conventional methods) has not been well described. We hypothesized that diagnostic vitrectomy would help establish the diagnosis in these challenging cases. Herein, we evaluated the diagnostic yield of vitreous biopsy in patients with suspected sarcoidosis-associated uveitis that affected the posterior segment.This is a retrospective interventional case series. Cases of intermediate, posterior or panuveitis that could not be characterized by clinical examination, ancillary, and laboratory tests were considered for diagnostic pars plana vitrectomy. Retrospective chart review was conducted on consecutive eyes that underwent diagnostic, or diagnostic and therapeutic vitrectomy by a single surgeon from January 1989 to June 2006.


Condition Intervention
Sarcoidosis-associated Ocular Inflammation
Procedure: Diagnostic Vitrectomy

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Diagnostic Yield of Vitreous Biopsy in Sarcoid Uveitis

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • To determine the diagnostic yield of vitreous biopsy in patients with suspected sarcoid uveitis [ Time Frame: January 1989 to June 2006 ] [ Designated as safety issue: No ]

Enrollment: 150
Study Start Date: January 2007
Study Completion Date: January 2008
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A
Patients with suspected sarcoid-related posterior segment inflammation with inconclusive clinical exam findings, ancillary testing, and laboratory results
Procedure: Diagnostic Vitrectomy

Three-port, 20-gauge pars plana vitrectomy instrumentation was utilized. An infusion line was inserted into one sclerotomy and secured to the globe. A second sclerotomy was made, and a fiberoptic light pipe was immediately inserted to minimize vitreous egress. A third sclerotomy was created, and the vitreous cutter was inserted. To obtain an undiluted vitreous sample, the vitreous was cut mechanically with the vitreous cutter, while the assistant surgeon simultaneously manually aspirated the vitreous. After sufficient undiluted sample was obtained, infusion fluid was allowed to enter the eye and a diluted vitreous sample was obtained in a similar manner. The samples were personally carried to the clinical laboratories by the operating surgeon.

Vitreous fluid analysis was guided by clinical suspicion based on the pre-operative differential diagnosis and the intraoperative posterior segment appearance.


  Hide Detailed Description

Detailed Description:

We obtained approval to conduct this non-comparative, interventional, retrospective case series from the Duke University Institutional Review Board. We used an established database of patients with uveitis and the operative reports from a single surgeon (GJJ) to identify all consecutive patients who underwent diagnostic pars plana vitrectomy from January 1989 to June 2006. We excluded patients with acute postoperative or traumatic endophthalmitis from this study. Cases were included if intraocular vitreous specimens were obtained for diagnostic testing. After identifying 150 patients, we reviewed the medical records of these individuals as previously described.

Patient demographic data and clinical history were recorded at the time of initial visit. A complete ophthalmic history and examination were performed by a single examiner (GJJ). The examination included slit-lamp biomicroscopy and dilated fundus examination with indirect ophthalmoscopy. Anterior segment inflammation was graded using the system described by Hogan and colleagues. The system previously described by Nussenblatt et.al. was used to grade vitreous opacity. Fluorescein angiography, optical coherence tomography, and ultrasonography were performed as indicated. A differential diagnosis was compiled for each case, based on clinic findings. Additional laboratory tests were ordered depending on the constellation of clinical history, exam findings, and results of previous ancillary testing. Anti-inflammatory therapy was initiated in an empiric or diagnosis-specific manner, and the clinical response was followed carefully.

Diagnostic vitrectomy was performed on eyes with intermediate, posterior, or panuveitis in which an etiology could not be characterized by clinical examination, laboratory, and/or ancillary testing. In addition, diagnostic vitrectomy was performed on eyes that did not adequately respond to empirical therapy, or those in which intraocular malignancy or infection was suspected. Therapeutic vitrectomy was performed in conjunction with diagnostic vitrectomy when clinically indicated, for example to repair retinal detachment, to remove epiretinal membranes, to decrease vitreous opacity, or to insert an intraocular sustained drug-delivery implant.

In this study, vitreous samples were collected in the operating room using a standardized technique which has been previously reported. Briefly, three-port, 20-gauge pars plana vitrectomy instrumentation was utilized. An infusion line was inserted into one sclerotomy and secured to the globe. A second sclerotomy was made, and a fiberoptic light pipe was immediately inserted to minimize vitreous egress. A third sclerotomy was created, and the vitreous cutter was inserted. To obtain an undiluted vitreous sample, the vitreous was cut mechanically with the vitreous cutter, while the assistant surgeon simultaneously manually aspirated the vitreous. The tip of the vitreous cutter was viewed at all times with the wide-field viewing system during the procedure. After sufficient undiluted sample was obtained, infusion fluid was allowed to enter the eye and a diluted vitreous sample was obtained in a similar manner. The samples were personally carried to the clinical laboratories by the operating surgeon. Vitreous fluid analysis was guided by clinical suspicion based on the pre-operative differential diagnosis and the intraoperative posterior segment appearance. Cytopathology was used to identify granulomatous inflammation or tumor cells. A thin-prep was prepared, processed through a membrane filter apparatus (Millipore Corp, Bedford, MA) and then stained with Papanicolaou stain. Gram stain, KOH preparation and culture were used to diagnose intraocular infection. Where appropriate, instructions were given to the clinical laboratory for specific sample processing (e.g., suspected slow-growing bacterium, such as Propionibacterium acnes or suspected fungal infection). Genomic amplification by polymerase chain reaction (PCR) was performed at the University of Colorado (Boulder, CO), or Texas Children's Hospital (Houston, TX) to test for the presence of Herpes simplex virus, Herpes zoster virus, and cytomegalovirus. PCR was performed for Toxoplasma gondii at the Palo Alto Medical Foundation (Palo Alto, CA) as previously described. Toxocara canis antibody levels were detected by enzyme-linked immunosorbent assay (ELISA) at the Centers for Disease Control and Prevention (Atlanta, GA). For Toxoplasma gondii and Toxocara canis, simultaneous serum samples were also collected and sent to the respective laboratories.

The final diagnosis was based upon the results of the directed diagnostic testing of the vitreous sample. A positive diagnostic vitrectomy result was based upon the identification of a specific etiologic agent through the testing modalities previously described. Sarcoidosis is a diagnosis of exclusion without a known etiologic agent. There are no definitive laboratory tests that unequivocally confirm a diagnosis of sarcoid. Therefore, a diagnostic specimen was deemed positive for sarcoid-related inflammation if the following criteria were satisfied: 1) if all other vitreous testing was negative 2) if the clinical features were such that sarcoidosis was included in the differential diagnosis based on pre-operative clinical appearance, and 3) if the cytopathology specimen was consistent with a pattern of sarcoid-related inflammation such as non-caseating granuloma formation, as established by the cytopathologist.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Cases were included if intraocular vitreous specimens were obtained for diagnostic testing.

Exclusion Criteria:

  • Patients with acute postoperative or traumatic endophthalmitis from this study were excluded.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00609687

Locations
United States, North Carolina
Duke University Eye Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: Glenn J Jaffe, MD Duke University Eye Center
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00609687     History of Changes
Other Study ID Numbers: Pro00014310
Study First Received: January 25, 2008
Last Updated: April 9, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
sarcoidosis
diagnostic vitrectomy
vitreous biopsy
sarcoidosis-associated ocular inflammation

Additional relevant MeSH terms:
Inflammation
Sarcoidosis
Pathologic Processes
Lymphoproliferative Disorders
Lymphatic Diseases

ClinicalTrials.gov processed this record on October 19, 2014