Changes in the micromorphology of the corneal subbasal nerve plexus in patients after plaque brachytherapy

Abstract

Background: To quantify the development of radiation neuropathy in corneal subbasal nerve plexus (SNP) after plaque brachytherapy, and the subsequent regeneration of SNP micromorphology and corneal sensation.

Methods: Nine eyes of 9 melanoma patients (ciliary body: 3, iris: 2, conjunctiva: 4) underwent brachytherapy (ruthenium-106 plaque, dose to tumour base: 523 ± 231 Gy). SNP micromorphology was assessed by in-vivo confocal microscopy. Using software developed in-house, pre-irradiation findings were compared with those obtained after 3 days, 1, 4 and 7 months, and related to radiation dose and corneal sensation.

Results: After 3 days nerve fibres were absent from the applicator zone and central cornea, and corneal sensation was abolished. The earliest regenerating fibres were seen at the one-month follow-up. By 4 months SNP structures had increased to one-third of pre-treatment status (based on nerve fibre density and nerve fibre count), and corneal sensation had returned to approximately two-thirds of pre-irradiation values. Regeneration of SNP and corneal sensation was nearly complete 7 months after plaque brachytherapy.

Conclusions: The evaluation of SNP micromorphology and corneal sensation is a reliable and clinically useful method for assessing neuropathy after plaque brachytherapy. Radiation-induced neuropathy of corneal nerves develops quickly and is partly reversible within 7 months. The clinical impact of radiation-induced SNP damage is moderate.

Figure 1

Clinical situation and isodose distribution by Ru-106 brachytherapy. (a) Schematic diagram of the corneal zones: applicator zone (A), central zone (B) and distal zone (C), each representing approximately one-third of the corneal vertical diameter. Note that vertical diameter of the cornea is approx. 10.5 mm, and the horizontal diameter 11.5 mm. (b) Photograph of a patient’s eye during brachytherapy: the Ru-106 plaque is located in the upper third of the cornea. (c) Diagram of isodose distribution: Simulation of CCB plaque with a dose of 522 Gy to the tumour base. The directly adjacent cornea receives 2.29 Gy (0.44% isodose), the central zone 0.63 Gy (0.12%) and the distal zone 0.08 Gy (0.015%) over the entire time course of plaque brachytherapy.

Figure 2

Imaging and automated quantification of SNP. (a) Representative in-vivo confocal image of the corneal SNP (distal zone, 4 months after plaque brachytherapy). (b) Results of automated image segmentation and analysis: total fibre length 1578 μm, nerve fibre density 9.863 mm/mm², and single nerve fibre count (n) 19. Image size: 400 x 400 μm.

Figure 3

Representative in-vivo confocal images of the corneal SNP of patients over time. Image size: 400 × 400 μm. Each image also shows data on corneal sensation (in mm).

Figure 4

Automated quantification of SNP structures and corneal sensation over time (percentage changes compared with pre-irradiation level): (a) Automated quantification of nerve fibre density. (b) Automated quantification of single nerve fibres. (c) Corneal sensation.