In this study, we primarily applied advanced imaging techniques including Scheimpflug imaging and AS-OCT in dark iris Chinese patients with unilateral FUS to analyze the anterior segment morphology changes. These data can help to elucidate anterior segment characteristics of unilateral FUS in this population.
Previous studies described changes in CCT in FUS eyes and drew different conclusions. Szepessy et al.[12] found significantly thinner CCT in FUS eyes using Scheimpflug imaging with a 20-µm difference between affected and unaffected eyes. Conversely, using the same imaging technology, Simsek et al.[14] reported that CCT was comparable between both eyes of unilateral FUS cases. The studies of Basarir et al.[13] (measured with ultrasonographic pachimetry) and Goker et al. [20] (device not known) also detected similar results. Consistently, there was no statistically significant difference in CCT between FUS eyes and unaffected eyes in our study. However, these studies did not compare corneal volume. Corneal volume may be a more meaningful measure than CCT to detect change in corneal thickness and to monitor corneal swelling [21–24]. What’s more, according to Takács, Suzuki and co-investigators, change in corneal volume due to swelling after phacoemulsification persisted longer than that of CCT [21, 22]. In our research we found that corneal volume, centered on the vertex with a diameter of 10 mm, was significantly larger in FUS eyes. This result indicates that there was invisible corneal swelling in affected eyes even though the cornea was "all clear" by slit-lamp examination. Given that a large proportion of our subjects had secondary glaucoma, we speculate that micro edema of the cornea might be due to repeatedly elevated IOP.
The corneal densitometry obtained through light backscattering measurements provide precise information about corneal transparency [25]. The density is expressed in gray scale unit (GSU) ranged from 0 to 100. Zero means no opacification of cornea (maximum transparency) and 100 means completely opaque cornea (no transparency). In our study, significantly increased corneal densitometry was observed in FUS eyes in midstromal zones (0–2, 2–6, or 10–12 mm), posterior zones (0–2, 2–6, 10–12, or 0–12 mm) and total thickness zones (0–2 or 2–6 mm) compared to unaffected eyes. Coincidently, Simsek and colleagues [14] reported a significant elevation in densitometry values of midstromal zones (2–6 or 6–10 mm), posterior zones (all), and total thickness zones (2–6 or 6–10 mm) in eyes with FUS compared to unaffected eyes. This indicated that even though the cornea observed by slit-lamp is “clear” in FUS, actually the clarity of cornea is decreased. It is known that corneal clarity is maintained depending on intact corneal structure, a framework of collagen fibrils arranged in a special manner and a functional corneal endothelium [26]. Among them, the corneal endothelium plays an essential role in preserving stromal dehydration, thereby maximizing the fidelity of light passing through the cornea [26] However, endothelial cell loss in FUS eyes have been widely reported [12, 14, 16, 18] Our study also showed that ECD was significantly lower in affected eyes. CV and ACA, respectively, were significantly higher in FUS eyes compared to unaffected eyes. In addition, the densitometry values of center, posterior, and total layers with various diameters were confirmed as strongly related to ECD, CV, and ACA. Simsek and colleagues [14] reported similar results. Therefore, we hypothesize that chronic inflammation in the anterior segment and ocular hypertension in subjects with secondary glaucoma resulted in numerical loss and redistribution of endothelial cells, impairing the barrier function of the endothelial layer and contributing to a net influx of aqueous fluid into the cornea presenting as greater corneal densitometry in the stromal and posterior layers. Furthermore, Labbe´ et al.[17] reported large hyperreflective deposits corresponding to KPs on the endothelium of all FUS patients. Hashida et al. [27] also reported low/moderate reflectivity of KPs in FUS. In our study, all affected eyes presented with dispersive KPs to varying degrees (Fig. 2), which may lead to increased densitometry of posterior zones as well. Therefore, the “clear” cornea we observed in slit-lamp may be not truly transparent in FUS eyes which might affect the visual quality rather than visual acuity. Especially, in secondary glaucoma, the disorder of corneal clarity and endothelium needs more attention. Additionally, since cataract is an important complication of FUS, when consider the premium intraocular lens implantation, the possible impact of reduced corneal transparency on postoperative visual quality should also be considered.
The alteration of iris is a characteristic sign of FUS. Other than conventional slit-lamp biomicroscope, researchers also applied some more delicate and advanced approaches to observe and evaluate the iris change in FUS. In 1978, Melamed et al.[28] investigated the irises of two FUS patients by electron microscopy and described abnormal melanocytes with relatively few, small, and at times immature, melanin granules. However, this method is invasive and difficult to perform in vivo. Afterwards, using Scheimpflug imaging, Szepessy et al.[12] noninvasively observed that the iris shape had significantly decreased its convexity in all FUS eyes, but iris cannot be quantitively assessed. With the advent of AS-OCT, investigators who attempted to quantitatively document iris atrophic changes in vivo drew conflicting conclusions by measuring iris thickness [13, 18, 19]. Therefore, in these years, Zarei et al. [9] proposed using iris SI to quantitatively document diffuse smoothness of iris anterior surface. They pointed out that prior to the advent of OCT, when using the term “atrophy” to describe iris findings in FUS, ophthalmologists often referred to a decrease in surface features largely based on observations with slit lamp exam. They also considered SI was more precise and objective than iris heterochromia and iris thickness, which may potentially help in correctly diagnosing dubious cases. In our study, we analyzed overall SI, temporal SI, and nasal SI in affected and unaffected eyes using AS-OCT. The results demonstrated that the SI in temporal, nasal and overall iris was significantly greater in affected eyes, which was consistent with the result of Zarei et al. Comparing the outcomes of both studies, we found that temporal, nasal and overall SI measured by us was numerically greater than that of Zarei et al. either in affected eyes or unaffected eyes. We speculated that the difference of ethnicity could have a possible effect on the results. It’s noteworthy that the enrolled patients in their study were all Iranian while in our study were all Chinese. In addition, both investigations didn’t belong to large sample research, a larger sample size is needed to confirm this conjecture.
Using Visante OCT (anterior segment TD-OCT), Basarir et al.[13] found wider nasal, temporal iridocorneal angle and thinner iris in FUS eyes. They concluded that atrophy of iris and the trabecular meshwork plays a major role in widening of the angle. AS-OCT has the advantage of observing the precise structure of iris, however, neither Visante OCT nor Cirrus HD-OCT (anterior segment SD-OCT) used in our study can rapidly acquire the iridocorneal angle information in all directions due to inherent limitation. Therefore, Pentacam was simultaneously used in our study to estimate iridocorneal angle in 0- to 360-degree meridian through 3-dimantional anterior segment reconstruction. The result demonstrated that the average iridocorneal angle in affected eyes (38.10 ± 5.41°) was larger than unaffected eyes (36.01 ± 4.77°). Szepessy et al.[12] reported similar results when comparing binocular iridocorneal angle in the unilateral FUS patient by Pentacam. Because Pentacam cannot quantitively measure the parameters of iris (e.g., iris thickness or SI), they only subjectively compared the shape of iris and supposed that the decreased convexity of iris caused widening of iridocorneal angle. In the current study, we not only used Pentacam to evaluate average iridocorneal angle, but used AS-OCT to precisely assess the change of iris by SI. Therefore, we had vigorous evidence to confirm that iris atrophy attribute to widening of iridocorneal angle.
The first limitation of our study is the small sample size; a larger future study of patients with unilateral FUS would substantiate validity. Second, we compared subjects' affected eyes with contralateral healthy eyes; the addition of a normal healthy control group would strengthen the study design.
In conclusion, we used contemporary technology including Scheimpflug imaging camera, noncontact specular microscopy, and AS-OCT to elucidate the anterior segment disorders in Chinese patients suffering from unilateral FUS. It appears that corneal volume is a more meaningful approach to characterize true corneal thickness changes, especially in the setting of transparent cornea by slit-lamp examination after repeatedly elevated IOP. Densitometry values could provide additional evidence for corneal micro-swelling in these “clear” corneas and yield valuable information regarding corneal endothelial function along with ECD, AVA, polymegathism, and pleomorphism. In eyes without obvious heterochromia, SI and iridocorneal angle may provide additional insight for diagnosis, especially in dark or brown-colored eyes. Our findings supplement previous data of Chinese patients with unilateral FUS.