Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00609687 |
| Other study ID # |
Pro00014310 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
January 25, 2008 |
| Last updated |
April 9, 2013 |
| Start date |
January 2007 |
| Est. completion date |
January 2008 |
Study information
| Verified date |
January 2008 |
| Source |
Duke University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Institutional Review Board |
| Study type |
Interventional
|
Clinical Trial Summary
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.
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.
