The management of uveitis patients relies on in-depth history taking, physical exam, and imaging. The findings presented herein demonstrate that non-cystic or spongiform macular thickening is strongly correlated with the presence, severity, and extent of retinal vascular leakage on FA.
In uveitis, FA gives valuable information regarding the presence, extent and severity of retinal vascular leakage which cannot be obtained by examination especially in the absence of other suggestive signs such as cystoid macular edema. Regarding FA findings, there is no standardized scoring system. Therefore, we defined a scoring system which reflected our daily practice with FA of patients with uveitis10. With the progression of inflammation, the vascular leakage in peripheral becomes more extensive involving more quadrants and/or extends towards the posterior pole. Additionally, the intensity of leakage in periphery and posterior pole is a sign of severity of uveitis. Taking into account all these items, we defined our scoring system by grading these parameters. We found that the level of retinal thickening in the fovea and perifoveal area in OCT while the foveal contour is still preserved, can reliably predict the gradings in our FA scoring system. To validate the importance of peripheral vascular leakage in causing macular thickening, we performed a subgroup analysis with those lacking vascular leakage in posterior and macular area while peripheral leakage was present. Analysis showed that peripheral vascular leakage in isolation, have a significant correlation with thickening in OCT. Therefore, attention to the small thickenings in OCT map, may help monitoring the disease activity and reduce ordering FA which is invasive and time-consuming.
We also found that regarding the colors in the thickness map, the area between 1- and 3-mm circle is more frequently show red or orange color changes which are indicative of thickening, while the central macula and the area between 3- and 6-mm circle still preserve a color near the normal range. Therefore, attention to a doughnut between 1- and 3-mm circle can more readily guide us to the presence of peripheral vascular leakage.
Two previous studies investigated the correlation between perivascular thickening in OCT and retinal vascular leakage in FA and found it a useful noninvasive biomarker of inflammatory activity in birdshot retinochoroiditis3,4. However, these studies did not describe the severity, extension and location of retinal vascular leakage on FA and did not investigate the correlation of these parameters with OCT indices. We developed such scoring and demonstrated that with increasing the level of angiographic score, the level of macular thickening on OCT increases.
Increases in the volume of Muller cells are the first histopathologic findings in macular edema and correspond to spongiform macular edema on OCT. When cellular dysfunction occurs, fluid first accumulates inside retinal cells resulting in tissue swelling without cystic changes. As swelling progresses, cystic changes eventually form within the macula12. Prior studies have reported the presence of subclinical macular edema in uveitis patients including those with JIA patients or patients with anterior uveitis 13,14. As the development of cystoid macular edema and its magnitude obviously reflect the activity of uveitis most of the times, we included cases before development of macular edema or after resolution of macular edema. These are the cases in which the diagnosis of the presence of retinal vascular leakage is mostly dependent on performing an FA.
Patients in this study had thickening on OCT with preserved foveal contours and without cystoid macular edema. As such, they were in relatively earlier or milder stages of macular inflammation. Visual acuity and AV inflammation were not correlated with macular OCT parameters. This may be due to the fact that CMT that predicts visual acuity was near normal in our patients. Also, the score of AV cells in our cases were all small with a mean score of 0.5. All angiographic scores were significantly correlated with foveal and perifoveal thickness and volume. In fact, in a circle farther from the fovea, the correlation becomes stronger with inflammation indicators.
Although there is no standard scale for the measurement of vitreous cells, we graded the cells based on the method used in Multicenter Uveitis Steroid Treatment Trial9. We found a lower grade of inflammation in AC compared to AV. This may be because most cases in this series had posterior segment inflammation as their predominant feature. Also, administration of topical corticosteroids can suppress AC inflammation more than AV. Macular changes on OCT may help determine which patients with AV cells would benefit from a FA. Additionally, it is commonly difficult for clinicians to determine if AV cells are from intermediate uveitis or spill over cells from the AC. In these equivocal cases, macular changes on OCT may help point clinicians towards which cases of uveitis are predominantly posterior in nature.
This study demonstrates that non-cystic thickening on macular OCT, especially perifoveal area, strongly corresponds to retinal vascular leakage. Color maps on OCT can help highlight macular thickening and indicate the presence of retinal vascular leakage. A significant correlation was seen between peripheral vascular leakage and OCT changes, even in the absence of posterior vascular leakage on FA. This may be from inflammatory mediators which include intra-cellular inflammation. One of the limitations of the current study is lack of interobserver evaluation for scoring FA, however, in another study from our center, this scoring system was shown to have a high interclass correlation coefficient of 0.98610. Larger and prospective studies are necessary to support this correlation and determine which OCT features correspond to changes in retinal vascular leakage over time, especially with regards to treatment response. In addition, including uveitis patients with cystic macular edema in another study would be useful to evaluate the validity of our findings in this subcategory of patients