SD-OCT-histopathologic correlation in Schnabel's cavernous optic nerve atrophy

Abstract

Background: Until now, Schnabel's cavernous optic nerve atrophy (SCONA) has solely been a histopathological diagnosis exhibiting variable degrees of optic nerve (ON) atrophy with characteristic cavernous spaces filled with acid mucopolysaccharides. We report the first correlation of histopathologic findings with spectral domain-optical coherence tomography (SD-OCT) imaging in SCONA.

Methods: We examined the eye of an index patient with histopathologically identified SCONA who had undergone multimodal imaging before enucleation for iris ring melanoma. The extent of SCONA in the index patient and three other enucleated eyes with SCONA were determined histopathologically. The histopathological findings of our index patient were correlated with in vivo SD-OCT images before enucleation and compared to representative images from eyes with a normal versus glaucomatous optic disc.

Results: Histopathologic examination of our index patient showed a pre- and intralaminar extension of SCONA. Atrophy of the inner retinal layers was observed corresponding to the extent of SCONA. Correlation with SD-OCT showed small intralaminar hyporeflective pseudocysts which were detected in multiple scans corresponding to the histologically affected areas. These changes were neither visible in scans of patients with glaucomatous atrophy nor those with a normal ON.

Conclusions: We present the first correlation of clinical and pathological findings in SCONA and were able to identify distinct SD-OCT characteristics for this condition. These findings may help to detect SCONA in vivo and to study this rare entity clinically with regard to its clinical course, risk factors, and pathogenesis. However, more cases of SCONA are needed to confirm our findings.

Fig. 1. Index patient.

A clinical picture OD showing a blue iris with many dark spots; B fundus image with optic nerve atrophy; C macroscopic image of the enucleated globe illustrating the posterior pole; D macroscopic image highlighting the iris ring melanoma (arrow) and the ciliary body lesion (arrow head); E corresponding histopathologic image [hematoxylin eosin (HE) stain, magnification 20×] with the iris ring melanoma (arrow) and the ciliary body lesion (arrow head); F higher magnification of the iris ring melanoma with infiltration of the inferior chamber angle, iris spots and vitreous seeds [HE stain, 100×]; G iris ring melanoma composed of pigmented and non-pigmented epithelioid cells [HE stain, 400×]; H histopathologic section showing the excavated optic nerve head (arrow) with Schnabel’s optic nerve atrophy (SCONA) [HE stain, 20×]; I optic nerve exhibiting SCONA (asterisk) and focal areas of normal optic nerve (arrow head) close to the central retinal vessels [HE stain, 40×]; J higher magnification of SCONA [HE stain, 400×]; K Alcian blue stain highlighting the acid mucopolysaccharides [Alcian blue, 400×].

Fig. 2. Correlation of SCONA.

A Spectral domain-optic coherence tomography (SD-OCT) section through the optic nerve (ON). The left part (superotemporal, marked with parenthesis) of the ON shows septae of low reflectivity and cystoid spaces in a matrix of intermediate reflectivity. The right part of the optic nerve (inferonasal) shows a different morphology with hyperreflective septae. B Schematic picture of SCONA in our index patient based on the histological serial sections (blue: SCONA; green: area without SCONA). The lamina cribrosa is not affected in this section. This section does not correspond with the SD-OCT section. C Vertical histological section of the nasal part of the optic nerve head. SCONA is present in the superonasal (SN) part of the ON but mostly absent in the inferonasal (IN) part (asterisk; H&E stain, 40×). D Higher magnification of SCONA with amorphous material replacing the ON fibers (H&E stain, 100×). E Alcian blue stain highlighting mucopolysaccharides (100×).

Fig. 3. Measurements of histology and OCT.

A Thickness measurements of the optic nerve head and adjacent retina in an H&E stained section of the index patient (central vertical section). The lamina cribrosa shows an extension of 542 µm. Optic nerve sheaths are marked by asterisk. B Thickness measurements of the optic nerve head and the adjacent retina in the corresponding vertical SD-OCT section (ONH mode, 1:1 pixel). It has to be acknowledged that histological tissues often undergo shrinkage during processing which may affect e.g., the retinal thickness in a way that the measurements in the histological sample can be slightly differ from in vivo OCT measurements.

Fig. 4. Bruch’s membrane opening minimum rim width with ONH radial and circular scans (BMO-MRW: ONH-RC).

Imaging of our index patient with SCONA (Case 1) that had received both histological and OCT imaging showed cystoid spaces with minimal reflectivity (arrowheads) located within areas of medium reflectivity which represent areas of former nerve fibers as well as septae of predominantly low reflectivity (arrows). Exemplary cases of BMO-MRW with ONH-RC scan of patients with glaucomatous atrophy and regular ON are shown for comparison. No cystoid hyporeflective spaces were seen and the septae of glaucomatous eyes (arrows) were mainly hyperreflective. The scans of regular ON also displayed hyperreflective areas in the intralaminar region, but these changes did not have such a clear septate appearance (arrows). We further observed that the morphology of the optic nerve in regular ON was not as clearly visible as in glaucomatous ON.