Advanced Anterior Eye Segment Imaging for Ichthyosis

Abstract

The purpose of this study was to describe ocular surface and anterior eye segment findings in various types of ichthyoses.

Methods: This was a single-center prospective observational study. The study group consisted of five patients (P1-P5) aged 13-66 years. Multimodal imaging was performed, including slit-lamp examinations, swept-source optical coherence tomography (SS-OCT), and in vivo confocal microscopy (IVCM).

Results: All patients were diagnosed with moderate-to-severe dry eye disease (DED). The corneas showed a significant pattern of irregularity, with a significant difference between the corneal thickness at the apex (CAT) and the corneal thinnest thickness (CTT), exceeding 375 µm. Three patients were diagnosed with ectasia patterns based on SS-OCT. All patients showed abnormalities in at least one Fourier index parameter for at least one eye at 3 or 6 mm in the keratometric, anterior, or posterior analyses. IVCM examinations revealed changes in all corneal layers.

Conclusions: By combining the results of multimodal imaging, we were able to detect preclinical abnormalities, distinguish characteristic changes common to ichthyosis, and reveal the depth and characteristics of corneal abnormalities. Therefore, patients with ichthyosis should be examined for DED and ectatic disorders early in clinical practice.

Keywords: confocal microscopy; cornea; dystrophy; ichthyosis; ocular surface; optical coherence tomography.

Figure 1

Representative slit-lamp eye photographs of the study group. The quality of the photos is compromised due to the increased light sensitivity among ichthyosis patients. (A) (mag. 10×, after the installation of fluorescein) P1. RE. (LI) Excessive scaling with hyperkeratinization of the lid margin and crust and scales at the base of the eyelashes. Severe exposure keratopathy with significant irregular fluorescein staining located in the lower half of the cornea. (B) (mag. 10×) P2. RE. (LI) Cicatricial ectropion of the upper and lower eyelids with eyelid margin deformation and hyperkeratinization (X), arcus lipoides, peripheral vascularization on two thirds of the lower cornea (arrowheads), corneal scarring with irregularity of the epithelium due to exposure keratopathy (arrow). (C) (mag. 10×) P2. LE. (LI) Cicatricial ectropion of the upper and lower eyelids with eyelid margin hyperkeratinization and crust at the base of the eyelashes (X); arcus lipoides with mild corneal peripheral vascularization, diffuse, dense, central, and paracentral corneal scars with temporal focal pigmentation subsequent to corneal perforation (arrowhead). (D) (mag. 16×) P3. RE. (IV) Localized, central irregular scar involving the lower peripheral cornea. Invading vessels from the lower periphery (arrow). (E) (mag. 10×) P3. LE. (IV) Hiperkeratinisation of the lower lid exceeding the lid margin, central, diffuse corneal scar with vessel ingrowth from the lower cornea (arrow). (F) (mag. 10×) P4. LE. (HI) Upper eyelid deformation. Paracentral area of reticular vascularization, lipid keratopathy, and calcification.

Figure 2

Representative results of swept-source OCT (SS-OCT); the Ectasia Screening Index (ESI) report of the affected eyes from the study group (a, anterior; p, posterior). The report includes the following data: APK (axial power keratometric); APP (axial power posterior); Sph.6: spherical component of FI at a 6 mm diameter (D), Reg.6: regular astigmatism component at a 6 mm diameter (D), Asy.6: asymmetric component at a 6 mm diameter (D), and Hio.6: higher-order irregular astigmatism component at a 6 mm diameter (D); P (pachymetry), the corneal thickness (μm) of the thinnest part and the location relative to the corneal apex (coordinates: X, Y) (mm); IPP (instantaneous power posterior), Steepest@6 (mm): the value of the steepest instantaneous posterior power and its location relative to the corneal apex (coordinates: X, Y) (mm). ASM (anterior eye segment morphology) line scan. (A) P2, RE (LI). Note the high degree of irregularity on the anterior corneal surface (arrow). The 6 mm k Asymmetry FI is 10.39 D, which reflects the significant difference between the upper and lower anterior corneal surfaces. The summarized similarity of the ectasia corneal pattern is 95% (aESI 95%; pESI 66%). (B) P3, RE (IV). Note the high degree of irregularity on the posterior corneal surface (arrow); the CTT decreased to 356 µm, and Sph@6 increased to 53.55 D. The summarized similarity of the ectasia corneal pattern is 95% (aESI 95%; pESI 95%).

Figure 3

Representative high-definition morphology SS-OCT scans of the most severely affected patients. (A) P2. RE. (LI). Line 0–180°. Irregularity of the anterior corneal surface (arrow). Increased reflectivity of the corneal stroma corresponding with the area of the corneal scar (Figure 1B). (B) P2. LE. (LI). Line 0–180°. Generalized anterior iris synechiae (arrows). Significant irregularity on both corneal surfaces. Increased reflectivity of the stroma due to diffuse, dense corneal scar subsequent to exposure keratopathy (Figure 1C). Corneal edema with different local severity (X). The area of Descemet membrane detachment, shown paracentrally (arrowhead). Increased lens reflectivity due to cataract. (C) P3. RE. (IV). Line 80–260°. Irregular anterior and posterior corneal surface. Central hyperreflectivity corresponding to the central corneal scar visible in Figure 1D. Anterior iris synechiae (arrow). The localized Descemet membrane rupture (arrowhead) and local corneal edema (X). (D) P4. LE. (HI). Line 150–330°. Marked hyperreflectivity in the anterior and central corneal sections (arrows). Additionally, the diffuse region of hyperreflectivity extends to the paracentral part at the axis of 330° (arrowheads). This region of increased reflectivity corresponds to the central lipid keratopathy with a reticular pattern of vascularization (Figure 1F).

Figure 4

Representative IVCM images at different scanning depths. (A–D); P1. RE. (A) Confocal image at a depth of 21 µm. Corneal epithelium. The irregular shape of cells, and hyperreflectivity pattern of cells with hyperreflective patches (*), along with multiple highly reflective irregular deposits (arrow). (B) Confocal image at a depth of 55 µm. Irregularity of cells with hyperreflective patches (*), subepithelial fibrosis with an absent nerve plexus (arrow). (C) Confocal image at a depth of 330 µm. Stroma. Confluent group of abnormally hyperreflective keratocyte nuclei with visible cytoplasmic processes (arrow). (D) Confocal image at a depth of 530 µm. Endothelium. Hyperreflective, small precipitates (*), a few hyporeflective spots containing a central highlight (arrow). (E–H); P2. RE. (E) Confocal image at a depth of 48 µm. Corneal epithelium. Marked irregularity of cells. Notable hyperreflective patches (arrow). (F) Confocal image at a depth of 175 µm. Stromal haze and scaring. Numerous small hyperreflective dots (arrow). (G) Confocal image at a depth of 300 µm. Non-homogenous area of massive scarring and fibrosis. (H) Confocal image at a depth of 400 µm. Dark differently orientated striae (*). Stromal haze. Keratocyte nuclei are barely distinguishable. (I–L); P3. RE. (I) Confocal image at a depth of 15 µm. Epithelial squamous metaplasia. Enlarged, hyperreflective cells, irregularly arranged, and decreased cell density. (J) Confocal image at a depth of 54 µm. Loss of nerves increased tortuosity. Hyperreflective, non-homogenous patches (*). (K) Confocal image at a depth of 320 µm. Hyperreflective scarring with neovascularization (arrow). (L) Confocal image at a depth of 566 µm. Cell pleomorphism. Hyperreflective, small precipitates (arrow). (M–P) P4. LE. (M) Confocal image at a depth of 30 µm. Marked irregularity of cells. Hyperreflective areas covering epithelium (arrow). (N) Confocal image at a depth of 80 µm. Homogenous, hyperreflective, distinctive area of calcification (arrow). Stromal haze and keratocyte nuclei are barely distinguishable. Multiple, small microdots. (O) Confocal image at a depth of 310 µm. Multiple hyperreflective needle-like opacities, which are differently orientated. Crystalline lipid keratopathy (P) Confocal image at a depth of 520 µm. Scaring with vessels (arrow). Dark stromal striae (*). (R–U) P5. LE. (R) Confocal image at a depth of 20 µm. Corneal epithelium. (S) Confocal image at a depth of 60 µm. Nerve-plexus. (T) Confocal image at a depth of 340 µm. Multiple stromal microdots (arrow). (U) Confocal image at a depth of 550 µm. Posterior stroma and endothelium. Image quality is compromised due to the patient’s age and poor cooperation during the examination.