The present study accrues useful additional clues in our understanding of the anatomical and functional repercussions of IU and its response to cortico-steroid treatment. Segregating patients with respect to the need for systemic treatment for CME and comparing anatomical and functional outcomes between patient sub-groups and with a group of healthy volunteers in a prospective study design allowed identifying the presence of subclinical retinal thickening in milder, not systemically treated cases as well as the clinical significance of this phenomenon. Re-affirming the established favorable prognosis to systemic treatment of CME secondary to IU, there was a statistically significant decrease in CFT after a period of 6 months in the sub-group of more severely affected patients, which translated into a significant, though slight, improvement in BCVA. Although in the group of patients that did not receive systemic treatment mean CFT was significantly inferior to that of the treated group, it was, nevertheless, significantly superior to that of the group of healthy volunteers. Despite this marginal retinal thickening in the group of untreated patients, retinal thickness did not increase further in the course of follow-up, nor was there a significant drop in visual acuity suggesting no clinical significance of subclinical retinal thickening in milder cases of IU. This slight, though statistically significant, macular thickening in the group of patients with mild disease, not necessitating systemic treatment, is a striking finding not previously identified in the context of IU. This patient sub-group presented sub-clinical macular thickening, as evidenced by the absence of visual acuity loss in these patients, compared to the group of normal volunteers. Few studies have tackled the issue of subclinical retinal thickening in other forms of intraocular inflammation, such as acute anterior uveitis (AAU) [
13,
14]. These include a retrospective study by Castellano [
13], demonstrating a statistically significant difference in retinal thickness between the study and fellow eye for all OCT subfields in patients with acute anterior uveitis and the prospective study by Balaskas et al. [
15] that offered a model of quantification of retinal thickness asymmetry between fellow eyes in the course of an episode of AAU. The identification of a critical value of retinal thickness beyond which systemic treatment is clearly indicated in patients with IU has yet to be determined, though it would constitute a powerful clinical tool. Although a precise CFT threshold for treatment cannot be envisaged in isolation, our post hoc analysis determined a cut-off value of 215.5 μm for commencing treatment in the present cohort. Clinical management decisions cannot be based on CFT values alone, however CFT should be taken into consideration when reaching management decisions alongside other qualitative morphological features on OCT, most importantly the presence of cystoid spaces. In the presence of cystic changes on OCT, however, determining a cut-off CFT value beyond which the risk-benefit ratio is tipped in favour of systemic treatment is of particular clinical relevance. When analysed against the actual presence or absence of severe disease requiring systemic treatment in our series, this cut-off value for CFT exhibited strong specificity, yet moderate sensitivity. This may indicate that cases requiring systemic treatment may occasionally be missed on the basis of this cut-off value if considered in isolation, while, on the other hand, this value is an accurate indicator of severe disease warranting systemic treatment in the vast majority of such cases. Taking into account that in a real-life scenario, clinical management decisions will be based on a multitude of factors rather than on CFT alone, the strong specificity of this cut-off value may offer a useful tool to clinicians as an additional argument in favour of systemic treatment in relevant cases that are more likely to benefit from it. Strong correlation between CFT thickness and mean logMAR visual acuity at baseline was observed in the present study. The issue of correlation between retinal thickness and visual acuity remains controversial with some studies reporting a high [
16] negative correlation and others failing to verify this finding [
17]. Several factors may play a role in the observed discrepancy, such as structural characteristics of macular edema, chronicity and underlying pathology. The high specificity of the identified CFT cut-off value for initiating systemic treatment in this study suggests that almost all cases deemed of sufficient severity to warrant systemic treatment in our practice, on the basis of various clinical indicators and not just OCT findings, had a CFT that exceeded the determined cut-off value. Although clinical application of this cut-off CFT value needs to be in conjunction with other clinical and imaging features rather than in isolation, its high specificity renders it a useful adjunct in the decision making process for commencing systemic treatment in IU. From a practical point of view, CFT values can be obtained on newer generation OCT technology as well and can be evaluated against the cut-off value suggested in this work employing conversion algorithms already reported in the literature, hence retaining their clinical relevance and usefulness [
18,
19]. The present study has certain limitations. Patients with advanced media opacities preventing clear visualization of the fundus and interfering with OCT measurements were excluded. The use of CFT as a marker of retinal thickness, although not uncommon in the literature, is a rather less frequently used clinical endpoint for research when compared to the more familiar central macular thickness (CMT) value. The choice of CFT in this work as clinical endpoint resides in the researcher’s reliance on this marker for clinical decision making in the era of the Stratus OCT. The age-matched group of healthy volunteers randomly selected may not be representative of the general population for determining normal CFT range, although very similar values for CFT in healthy eyes have been previously reported [
20].