Confocal Microscopy Is Useful for Detection of Bortezomib Related Neuropathy (BOR-PN) in Multiple Myeloma (MM) Patients (PTS)
Authors: Cocito Federica , Mangiacavalli Silvia , Ricciardelli Gabriella , Ferretti Virginia , Ceccuzzi Roberto , Cazzola Mario , Bianchi paolo Emilio , Corso Alessandro 
Published: October 2019

Abstract
Background: Bortezomib-related painful sensory peripheral neuropathy (Bor-PN) represents the main dose-limiting toxicity of Bor. Cornea is the most innervated tissue in human body, with the highest density of small sensitive fibers, which are the main target of Bor-PN. Corneal confocal microscopy is a rapid, noninvasive, clinical examination technique that quantifies small nerve fiber damage and is already used for early identification of neural damage in course of diabetic sensory PN.
Aims: To evaluate the possible role of confocal microscopy for identification and monitoring of corneal sub-basal neural plexus damage in Multiple Myeloma (MM) patients (pts) treated with Bor and to correlate confocal microscopy findings with Bor-PN.
Patients and Methods: Patients underwent corneal examination with corneal confocal microscope (Confoscan 4). Corneal sub-basal fibers were evaluated in terms of the following morphometric measurements used as sign of neural damage: nerve fiber length, nerve fiber number, beadings number, tortuosity (according to Oliveira scale and Nidek index). The study was approved by local ethic committee, all patients signed informed consent before confocal microscopy evaluation. Twenty-six MM pts treated with Bor entered the study and were compared with 20 healthy controls. Control group morphometric findings were similar to data on healthy population reported in the literature. At time of confocal assessment among MM group there were 20 MM pts (77%) under active bor treatment, 6 pts were off bor-therapy (23%), clinically evident PN (NCI grade ≤2) was reported in 10 pts (38.5%).
Results: MM pts and healthy controls were well matched as far as median age and sex. Compared to healthy controls, MM pts showed: I) a significant reduction in terms of length and number of corneal fibers (median length 552 μm in MM vs 1223.5 μm in control p<0.001; median number 4/field vs 7/field p<0.001) II) a higher grade of fiber tortuosity with both methods (1.8 vs 0.5 according to Oliveira scale, p<0.001; 4 vs 2 according to Nidek index p<0.001) III) a significant reduced number of beadings (40.8/mm vs 68/mm, p<0.001). Finally, we found a trend for sign of increased neural damage in terms of length reduction and tortuosity of corneal fibers in MM pts with clinically evident Bor-PN when compared with pts asymptomatic for Bor-PN, these differences were not statistically significant maybe due to the limited number of pts evaluable (median fiber length 524.7 vs 557.5, p<0.416; grade of fiber tortuosity 2 vs 1.5 according to Oliveira scale, p<0.493; 4.3 vs 3.9 according to Nidek index, p<0.247 respectively in MM pts with vs without bor-PN)
Conclusions: Confocal microscopy can be a useful tool for detection of Bortezomib induced neural damage in MM patients. Prospective studies are needed to evaluate if it could help physicians in detecting neural damage in advance with respect to the emergence of clinically evident Bor-PN.

Disclosures
No relevant conflicts of interest to declare.