SCLERAL PITS IN CHOROIDEREMIA: Implications for Retinal Gene Therapy

Abstract

Purpose: We report a novel finding on spectral domain optical coherence tomography in patients with choroideremia, which we describe as scleral pits (SCPs).

Methods: Cross-sectional observational case series of 36 patients with choroideremia, who underwent ophthalmic examination and multimodal imaging, including optical coherence tomography of the macula. Optical coherence tomography images were reviewed for SCP, which were defined as discrete tracts of hyporeflectivity that traverse the sclera with or without the involvement of Bruch membrane, retinal pigment epithelium, and retina. Unpaired two-tailed t-test with Welch correction was used for statistical analysis.

Results: Of the 36 patients, 19 had SCP in at least one eye. Scleral pits were confined to areas of advanced chorioretinal degeneration and never involved the foveola. Type 1 SCP affected only the sclera, whereas Type 2 SCP also involved the Bruch membrane and the retinal pigment epithelium. Type 3 SCP additionally had a full-thickness retinal defect. Patients with SCP were significantly older (51 ± 2 vs. 33 ± 4 years; P < 0.05) and had lower best-corrected visual acuity (20/160 vs. 20/30 or 0.9 ± 0.2 vs. 0.2 ± 0.07 logarithm of the minimum angle of resolution; P < 0.05) than patients without SCP. Patients with SCP had a greater myopic refractive error compared with patients without SCP (-2.6 ± 0.5 vs. -0.3 ± 0.5D; P < 0.05), but there was no significant correlation between the number of SCPs with refraction. Short posterior ciliary arteries were observed to enter the eye through one Type 3 SCP.

Conclusion: Scleral pits are, to the best of our knowledge, a novel optical coherence tomography finding in advanced choroideremia that likely represents the abnormal juxtaposition of penetrating short posterior ciliary arteries with the retina.

Figure 1

Three types of Scleral pits (SCP). Upper row, A–D: Type 1 SCP, patient #P3 right eye. A) OCT reveals subtle focal posterior bowing of the retina, retinal pigment epithelium (RPE), and choroid above an area of scleral cavitation and oblique tract. This type 1 SCP is visible as a hyporeflective spot on infrared (B, arrow) and a subtle grey lesion on color fundus photography (C, arrow), but is not visible on fundus autofluorescence (FAF; D, arrow). Middle row, E–H: Type 2 SCP, patient #P3, left eye. E) OCT shows prominent posterior bowing of the retina with no discernible retinal laminations, RPE, or choroidal layers, culminating in a sclera cavitation and tract at a right angle to the retinal surface. Type 2 SCP are easily visible as a prominent hyporeflective spot on infrared (F, arrow), a dark spot on color (G, arrow), and hypoautofluorescent spot on FAF (H, arrow). Lower row, I–L: Type 3, patient #P10, right eye. I) OCT reveals a full-thickness focal defect of the retina, RPE, and choroid with no visible membrane separating the equally hyporeflective space of the vitreous and scleral tract. Type 3 SCP are similar in appearance to Type 2 SCP on infrared, color, and FAF (J–L, arrows).

Figure 2

Angiogram of a Type 3 scleral pit. Magnified color photograph of a type 3 scleral pit (A, blue arrowhead) from figure 1–K (patient #P10, right eye) showing apparent interruption of a segment of a large retinal vein. Fluorescein angiogram reveals that the retinal vein is patent with decreased flow in semi-circinate path (B, blue arrowhead). Short posterior ciliary arteries appear to enter the globe through this pit (A, black arrowheads; B, white arrowheads).

Figure 3

Patients with scleral pits were significantly older (A), and had worse best-corrected visual acuity (B) than patients without scleral pits. SCP, scleral pits; BCVA, best-corrected vision; asterick, p <0.05.