Inflammation of the anterior segment causes changes in the corneal endothelium that, if severe, can compromise the integrity of the cornea; these changes have been observed in some studies using AS-OCT [7]. Some authors [7] have proposed that corneal thickness is an indicator of endothelial function and suggested that this response can be clinically assessed via central corneal thickness OCT measurement. Agra et al. [8] have studied these changes in uveitis and have demonstrated endothelial changes induced by inflammation, which include defects in the endothelium associated to the deposition of precipitates on the posterior surface of the cornea and other defects similar to guttata and not associated with the precipitates. Moreover, in most patients, these alterations tended to disappear completely, together with other signs of acute inflammation, without changes in cell count, and were significantly correlated with the increase in corneal thickness during the inflammatory period of the disease. Despite these anomalies, the majority of cases of uveitis in most series did not progress to permanent corneal decompensation, and OCT central corneal thickness values returned to normal by the end of the inflammatory crisis.

In the three studies that analyze cornea by means of OCT in uveitis patients [8–10], the participants exhibited a significant reduction in mean central corneal thickness measured by OCT between the initial period of the disease and following the control of ocular inflammation (564.2 ± 44.3 μm to 529.50 ± 33.1 μm, respectively). None of the authors reported any edema of the cornea on clinical examination. The patients in these studies did not exhibit a significant change in IOP during the disease.

Ophthalmologists are trained to evaluate the severity of anterior segment inflammation by examining the aqueous humor by slit-lamp biomicroscopy. Various systems have been reported to quantify the cell number and estimate the amount of protein in the anterior chamber [11]. The number of visible cells in the anterior chamber are counted and graded on a scale of 0–4 based on the Standardization of Uveitis Nomenclature (SUN) Working Group [11]. This allows for a standardized method for comparing the degree of inflammation in clinical trials. However, this method relies on the subjective evaluation of the number of cells by a trained observer and thus is susceptible to interobserver variation. The wide range of cells per high-power field in grade 3+ (26–50 cells/high-power field) and grade 4+ (greater than 50 cells/high-power field) limits the ability to accurately determine a small change within these higher grades of inflammation. Moreover, slit-lamp assessment may be difficult in eyes with corneal opacification due to corneal edema. The grading scale is not linear and is only semiquantitative. The SUN group acknowledged the nonlinear nature of their ordinal grading system where there is a hierarchy of increasing magnitude which does “not have a numerical relationship to the amount of inflammation.” A method to quantify the amount of cells more precisely and objectively is needed to evaluate and manage many conditions characterized by intraocular inflammation.

Li et al. [12] employed two concentric circular scans with diameters of 2 and 4 mm of time domain OCT to grade AC cells in uveitis patients. In Yan et al.’s study [12], the average OCT cell count per grade in nongranulomatous eyes was almost doubled that in granulomatous eyes (3.7 cells/grade vs. 2.0 cells/grade). One explanation could be that the visibility of the AC cells under the slit-lamp microscope may depend on both the cell size and the cell type. Different types of cells, such as inflammatory cells, macrophages, and pigment granules, may be present in aqueous humor with intraocular inflammation. The average size of the lymphocytes, neutrophils, and monocytes ranges from 10 to 20 μm, and the axial resolution of their OCT device was 17 μm with a transverse resolution of 45.

A single-line OCT scan centered on the pupil with an axial resolution of 18 μm and transverse resolution of 60 μm was employed by Agarwal et al. [13], who identified the inflammatory cells as hyperreflective spots. However, even with OCT, it is difficult to determine whether the hyperreflective spots seen on the scans represent inflammatory cells versus pigment or cellular clumps of immune cells. Agarwal et al. hypothesized that hyperreflective spots that are picked up in the AC might be attributable to cellular clumps whose size are large enough to be picked up by the OCT [13]. This possibly occurs because of cell to cell adhesion, either between inflammatory cells or between inflammatory cells and pigment cells released from the iris. Secondary to the increased protein and fibrin content of aqueous in inflamed eyes, cells adhere to each other, forming clumps, thereby increasing the size of the particle. Agarwal et al. concluded that there was no significant difference seen in mean values between the manual and automated method except in grade 4 [13]. It seems likely that the automated method works better than the manual method in detecting cells that can be missed at higher grades of uveitis.

The uneven distribution of cells in the anterior chamber is thought to be caused by the thermally driven aqueous humor circulation. The aqueous humor is cooler near the cornea and warmer near the iris due to heat conduction. The cooler aqueous will flow downward, and the warmer aqueous will flow upward to form a circulation inside the anterior chamber. However, this gentle aqueous current may not be strong enough to circulate the large and relatively heavy cells; therefore, the large and heavier cells can become trapped in the inferior part of the anterior chamber. Thus, they are likely to be missed by the slit-lamp biomicroscopy. OCT imaging may identify these cells better than clinical exam, but only if imaging of the inferior anterior chamber is performed. However, to obtain a more complete measure of total cells, a three-dimensional volume-based measure is needed (Fig. 7.2).