The effects of autologous serum tears on the cornea and ocular surface of patients with severe dry eye disease: a prospective, double-blind, randomized, controlled, contralateral eye study

Abstract

Purpose: To investigate how treatment with Autologous Serum (AS) tears 50% affects the ocular surface of patients with refractory Dry Eye Disease (DED) due to Sjogren’s Syndrome. To evaluate the safety of autologous serum tears 50% by reporting adverse effects from AS tears and by microbiological analysis of the remaining AS tears 50% after the use.

Study Design: Prospective, double-blind, randomized, controlled, contralateral eye study. Methods: Twenty (20) eyes of ten adult patients with severe DED due to Sjogren’s syndrome, either primary or secondary to rheumatoid arthritis, were contralaterally randomized into either the intervention (AS tears 50%) or the control group (artificial tears). Study visits were conducted at 1, 2 and 3 months. The degree of improvement between groups was assessed via objective assessment tests (corneal and conjunctival staining, tear break up time and Schirmer’s test). Best-Corrected Visual Acuity (BCVA) was also evaluated. High-resolution images of the corneal sub-basal nerves were acquired with the use of In Vivo Confocal Microscopy, IVCM (Heidelberg Retina Tomograph III, Heidelberg Engineering, Germany). Quantitative analysis of the corneal nerves was performed using the Automated Corneal Confocal Metrics software (ACCMetrics, M.A. Dabbah, Imaging Science and Biomedical Engineering, University of Manchester, UK). The intervention-related alterations in the status of the central corneal nerve plexus were evaluated after the quantification by frame of distinct parameters, such as Corneal Nerve Fiber Density (CNFD), Corneal Nerve Branch Density (CNBD) and Corneal Nerve Fiber Length (CNFL). The microbiological integrity of AS tears 50% after the use was investigated using Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry (MALDI-TOF MS). Results: Significant increase in the mean TBUT (p=0.004) and Schirmer’s test values (p=0.005) and decrease in the corneal staining (p=0.005) and conjunctival staining scores (p=0.011) in the AS group compared to the randomization visit. Improvement in DED objective measurements also at the 2-month (p=0.005, p=0.007, p=0.005 and p=0.005, respectively) and at the 3-month time points (p=0.005, p=0.005, p=0.005 and p=0.005, respectively) compared to baseline. No significant changes in the control group scores as compared to randomization at 1 month (TBUT, p=0.317; Schirmer’s test, p=0.518; corneal staining, p=1.000 and conjunctival staining, p=0.317), at 2 months (p=0.180, p=0.202, p=0.212 and p=1.000, respectively) and at 3 months (p=0.783, p=0.176, p=0.608 and p=0.527, respectively). Statistically significant improvement in BCVA at 2 months in the intervention group (p = 0.014) and at 3 months (p = 0.015) compared to the randomization visit. No corresponding changes in the control group, compared to baseline, at the first (p = 0.395), the second (p = 0.317) and the third time point (p = 0.317) of the study. Significant quantitative increase of all the IVCM parameters in the AS 50% group compared to baseline at 1 month (CNFD: p = 0.038; CNBD: p = 0.015 and CNFL: p = 0.047) at 2 months (CNFD: p = 0.005, CNBD: p = 0.007, CNFL: p = 0.005) and at 3 months (CNFD: p = 0.005, CNBD: p = 0.005, CNFL: p = 0.005). No corresponding alterations in the artificial tears group compared to randomization at the 1-month (CNFD: p = 0.767, CNBD: p = 0.859, CNFL: p = 0.359), 2-month (CNFD: p = 0.919, CNBD: p = 0.507, CNFL: p = 0.721) and 3-month follow-up (CNFD: p = 0.767, CNBD: p = 0.969, CNFL: p = 0.799). Positive correlation between the CNFD, CNBD and CNFL confocal parameters and the mean break up time (Spearman’s rank correlation coefficient r s = 0.46, p= 0.037; r s = 0.51, p=0.022 and r s = 0.59, p = 0.006, respectively) and Schirmer’s tear test scores at 3 months (r s = 0.50, p= 0.022; r s = 0.51, p=0.020 and r s = 0.64, p = 0.002, respectively). Negative correlation between CNFD, CNBD and CNFL and mean corneal (r s = -0.61, p= 0.004; r s = -0.52, p=0.018 and r s = -0.70, p < 0.001, respectively) and conjunctival staining at 3 months (r s = -0.57, p= 0.008; r s = -0.47, p=0.036 and r s = -0.60, p= 0.004, respectively). Microbiological analysis revealed the presence of Gram-negative bacteria in the remaining AS tears 50%. Conclusions: The use of AS tears 50% improves, the objective indicators of ocular surface dryness, visual acuity and confocal microscopy findings compared to the use of artificial tears at 3 months. The neurotrophic support provided by the implementation of AS tears 50% results in regeneration of the central corneal nerve plexus. Ocular surface healing after the implementation of autologous serum 50% occurs alongside corneal nerve regeneration. The post-treatment corneal nerve regeneration is proportional to tear stability and inversely proportional to the vital staining of the ocular surface. Autologous serum tears in higher concentrations show higher risk of contamination, prompting additional considerations for proper use to ensure safety.