To evaluate the feasibility of anterior segment optical coherence tomography (AS-OCT) for measuring anterior chamber (AC) cells in children with uveitis and to compare different AS-OCT acquisition modes.
Validity and reliability analysis.
We enrolled children younger than 18 years who had uveitis involving the anterior segment and children without eye disease as controls. All underwent clinical grading of AC cells. AC images of each eye were obtained using the Optovue Avanti RTVue XR AS-OCT. Two acquisition modes were used: a single cross-sectional line scan and an 8-line radial scan in an asterisk pattern. Two independent, masked graders counted cells manually on AS-OCT images. Rater agreement was assessed using intraclass correlation (ICC).
Included were 30 children (59 eyes) with uveitis (median age 13.0 years, range 3-17 years) and 20 control children (40 eyes, median age 10.5 years, range 4-17 years). The number of eyes assigned each clinical grade of cells were as follows: none, 32 (54%); 0.5+, 12 (20.3%); 1+, 5 (8.5%); 2+, 8 (13.6%); 3+, 2 (3.4%). ICC of graders for line and radial scan protocols were 0.87 and 0.90. There was no significant difference between acquisition modes for pooled grader results (95% CI for difference: –0.04 to 0.14). ICC of cell counts between line and radial scan protocols was 0.85 (95% CI: 0.69-0.90). No control eyes had cells on AS-OCT images.
Quantification of AC cell in children with uveitis is feasible with AS-OCT and has excellent reliability between different graders and acquisition modes.
Classification of uveitis is by the primary anatomic location of intraocular inflammation, the most common category being anterior uveitis, involving the iris and anterior ciliary body. Active anterior uveitis is recognized by the presence of cells (leukocytes) in the anterior chamber (AC) of the eye. The amount of AC cells is used to guide treatment with local or systemic corticosteroids or with systemic immunosuppression. Accurate quantification of cells is therefore critical in the management of anterior uveitis.
Currently, the standard for determining the severity of an AC cellular reaction involves slitlamp biomicroscopy, during which the examiner assigns a semiquantitative level to the amount of cells visualized in a 1 × 1-mm beam, as defined by the Standardization of Uveitis Nomenclature (SUN) Working Group. This grading system is operator dependent and requires patient cooperation. Even among uveitis specialists, there can be substantial variation in measurements using this system. Accurate assessment of cells can be particularly difficult in children, especially among young children who may be uncooperative for slitlamp biomicroscopy.
Children with uveitis represent a unique, at-risk population. They often have long disease courses, and children with chronic anterior uveitis are at high risk for ocular complications. Children are often asymptomatic at disease onset, and during exacerbations of inflammation, they may not report any symptoms until vision-limiting complications, such as cataracts, glaucoma, or band keratopathy, occur ; thus, frequent monitoring of the AC plays a central role in long-term preservation of vision. Children with uveitis may be evaluated by multiple clinicians who need to share clinical information, emphasizing the importance of accurate assessments.
To address the need for accurate and precise quantification of anterior segment inflammation, investigators have sought to develop objective image-based techniques to evaluate AC cells. Anterior segment adaptor modules are available for multiple optical coherence tomography (OCT) platforms, which allows for high-resolution imaging of the AC that should make AS-OCT widely available to clinicians who see children with uveitis. Studies have shown that anterior segment OCT (AS-OCT) can quantify AC cells, based on the number of hyperreflective dots in an AS-OCT image. Results correlate strongly with the SUN grading criteria. Multiple studies have evaluated the use of AS-OCT for quantifying AC cells in adults; in contrast, studies of children with uveitis, the population for which such techniques would be particularly useful, are limited. To understand the utility of AS-OCT for quantifying cells in children, investigations are needed that address the ability of children to cooperate sufficiently to detect cells consistently and reliably. One small, cross-sectional study suggested that use of AS-OCT for quantifying cells in children with uveitis was feasible, warranting additional studies.
Although AS-OCT can identify AC cells, the quantification of cells by this technique has not been standardized. Various studies have used different OCT platforms and varying protocols for image acquisition and processing, which limits the generalizability of individual reports. Before AS-OCT quantification of AC cell in children can be adopted widely in clinical practice, additional feasibility studies are needed, and a standardized approach must be developed. This study further evaluated the feasibility of AS-OCT for detecting AC cell in children of various ages who have anterior uveitis. It also compared different acquisition modes, to determine which mode is most suitable for children. Our ultimate goal is a more accurate and rapid, standard method for evaluating intraocular inflammation in children that can be used clinically.
Children younger than 18 years with histories of uveitis involving the anterior segment were recruited from the practices of 3 uveitis specialists (E.T., S.S.M.F., G.N.H.) at the UCLA Stein Eye Institute, University of California, Los Angeles. Not included were patients with histories of intraocular surgery during the 90 days immediately preceding recruitment. Patients were included whether or not uveitis was active at the time of the study. In addition, children without histories of intraocular inflammation, intraocular surgery, or ocular trauma were recruited as controls. The study was approved by the UCLA Health Institutional Review Board. Written informed consent was obtained from a parent of all study participants, and an additional assent document was signed by all study participants aged ≥7 years. The study adhered to the tenets of the Declaration of Helsinki.
A comprehensive eye examination was performed on all study participants by one of 3 investigators (E.T., S.S.M.F., G.N.H.), during which AC cells were scored using the SUN grading system. Clinical grading was performed prior to AS-OCT imaging.
An experienced operator using the Optovue Avanti RTVue XR (Optovue, Inc) with the corneal adaptor module performed imaging on both eyes of all study participants. All AS-OCT images were acquired before pupillary dilation. AS-OCT scans were located in the central AC using 2 acquisition modes: a single 6-mm horizontal cross-sectional line B-scan and eight 6-mm cross-sectional line scans in a radial formation centered on the corneal apex (schematic shown in Figure 1 ). If scans were unclear because of poor focus or artifact from motion or the corneal reflex, scans were repeated.
DATA ANALYSIS AND STATISTICAL TECHNIQUES
AS-OCT B-scan images were deidentified and exported in JPEG format for manual assessment of AC cells. To assess interobserver agreement, 2 independent graders (E.T., J.L.C.), who were masked to the clinical cell grades assigned to each eye, counted cells on all images from both children with uveitis and controls. Graders used the same definition of an AC cell that has been reported in previous AS-OCT studies: hyperreflective dots in the AC that are brighter than the background noise or greater than 2 pixels in size. For the 8-line radial scan protocol, the mean number of cells for all 8 images was calculated.
Agreement between the 2 masked graders within the single line and radial scans were assessed using intraclass correlation (ICC). ICC was also used to assess agreement between the single line and radial scans across raters. ICC differences between counts from the single line and radial scan protocols were evaluated using a bias-corrected bootstrap 95% CI from 1000 resamplings. Linear regression analysis was used to compare AS-OCT cell counts to the clinically assigned SUN grades. Models were fit with clustered robust standard errors at the patient level. Statistical significance was defined as P <.05. All analyses were conducted in Stata, version 16.1 (Stata Corp LP, College Station, TX).
We enrolled 30 children with histories of uveitis (59 eyes) and 20 children without eye disease (40 eyes) as controls. Table 1 shows demographic and ophthalmic factors for study participants with uveitis and for controls. Figure 2 demonstrates representative AS-OCT images from line scans that correspond to each clinical grade of AC cells, as defined by the SUN Working Group. All control eyes of children without eye disease were determined clinically to have no AC cells. No control eyes were found to have cells on AS-OCT images by the 2 masked graders.
|Factor||Children With Uveitis||Controls|
|Individuals (n=30)||Eyes (n=59)||Individuals (n=20)||Eyes (n=40)|
|Mean ± SD||12.1 ± 3.7||10.9 ± 3.9|
|Median (range)||13.0 (3-17)||(4-17)|
|Median (IQR)||13.0 (10.3-15.0)||10.5 (7.8-14)|
|Diagnosis of uveitis, n (%)|
|No uveitis||—||—||20 (100)||40 (100)|
|Idiopathic anterior uveitis||7 (23.3)||14 (23.7)||—||—|
|Idiopathic anterior and intermediate uveitis||3 (10.0)||6 (10.2)||—||—|
|Idiopathic panuveitis||6 (20.0)||12 (20.3)||—||—|
|JIA-associated uveitis||11 (36.7)||22 (37.3)||—||—|
|HZO-associated anterior uveitis||1 (3.3)||1 (1.7)||—||—|
|Blau syndrome a||1 (3.3)||2 (3.4)||—||—|
|Tubulointerstitial nephritis and uveitis syndrome||1 (3.3)||2 (3.4)||—||—|
|Clinical grade of cells, b n (%)|
|None||—||32 (54.2)||20 (100)||40 (100)|