Jutta Horwath-Winter

This study investigated the distribution of IgA-expressing cells in human ocular tissues and IgA subclass profiles in Schirmer strip extracts from patients with dry eye disease (DED) and primary Sjögren’s syndrome (pSS). Immunofluorescence staining was performed on paraffin-embedded lacrimal gland, conjunctival, and corneal tissues from body donors. Independently, Schirmer strip extracts from healthy controls (n = 18), patients with DED (n = 75), and patients with pSS (n = 10) were analyzed. Total protein concentrations were determined using a bicinchoninic acid assay, while total IgA, IgA1, and IgA2 were quantified by ELISA and normalized to total protein. CD38⁺ and CD38⁻ IgA-expressing cells were detected in the lacrimal gland and conjunctival stroma, with IgA1-expressing cells predominating over IgA2-expressing cells. No IgA-positive cells were detected in the examined corneal sections. Total protein concentrations were lower in pSS than in DED. Normalized IgA2 abundance was reduced in both DED and pSS compared with controls, while normalized total IgA was additionally reduced in pSS. Unnormalized extract concentrations showed broadly similar patterns. These independent findings demonstrate differences in recovered IgA subclass profiles, although differences in collection materials and patient characteristics preclude attributing these alterations exclusively to the underlying diseases.

To characterize the distribution of IgA-producing plasma cells across the human ocular surface and to assess alterations in tear IgA subclass profiles in Schirmer strip extracts from patients with dry eye disease (DED) and primary Sjögren’s syndrome (pSS). Immunofluorescence staining was performed on paraffin-embedded lacrimal gland, conjunctival, and corneal tissues to identify IgA- and subclass-producing B/plasma cells. Samples were collected from controls (n = 18), patients with DED (n = 75), and patients with pSS (n = 10). Total protein concentrations in Schirmer strip extracts were deter-mined using a bicinchoninic acid assay. Total IgA, IgA1 and IgA2 were quantified by ELISA and normalized to total protein. IgA-producing plasma cells were abundant in the lacrimal gland and conjunctival stroma but absent from the corneal sections. In both tissues, IgA1-producing cells predominated over IgA2-producing cells. Total protein concentrations in Schirmer strip extracts were significantly lower in pSS than in DED. The most consistent change was reduced normalized IgA2 abundance in Schirmer strip extracts, whereas changes in IgA1 were less consistent across the analyzed disease groups. IgA-producing plasma cells are prominent in the lacrimal gland and conjunctiva. DED and pSS are associated with reduced normalized IgA2 abundance and altered IgA sub-class profiles.

Purpose: Lubricant eye drops are the main therapeutic resource for dry eye disease (DED), with each drop representing the equivalent of ocular surface disease treatment. Thus, any reduction in the frequency of eye drop application reflects a degree of therapeutic success. Considering also the socioeconomic burden of DED, we investigated eye drop application frequency (DF) as a parameter to potentially track the success of therapy in severe DED. Hyaluronan (HA)‐containing eye drops have become the first choice for tear substitution in many countries, and recent data indicate that the average molecular weight (Mw) of HA determines the therapeutic efficacy of such eye drops. This post‐hoc subgroup analysis of a previously published multicentre prospective randomized open‐label study, HYLAN M, is set out to compare the effects of very high Mw HA (hylan A) eye drops to comparator eye drops, containing lower Mw HA (control).Methods: Patients with severe DED (n = 47), recruited as part of the larger HYLAN M prospective, multicentre, open‐label study, were randomized into two groups: hylan A and control group. In the hylan A group, 24 patients replaced their HA‐containing eye drops with eye drops containing 0.15% hylan A, whereas the 23 control patients continued to use comparator HA eye drops. The DF was recorded daily by all participants over 8 weeks, and other subjective and objective parameters of DED were assessed at the time of inclusion (baseline), as well as at week 4 and 8.Results: There was a significant decrease in DF in the hylan A users between the baseline and week 4 (p = 0.004), remaining stable until week 8. Indeed, in contrast to the baseline, the hylan A group had a significantly lower DF than the control group at weeks 4 (p = 0.018) and 8 (p = 0.008). Likewise, the ocular surface disease index (OSDI) improved significantly between the time of inclusion and week 4 (p < 0.001) in hylan A users, remaining stable until week 8. The OSDI was similar in both groups at the baseline but it was significantly lower in the hylan A group than in the control group at week 4 (p = 0.002), remaining lower at week 8. Such a decrease in the DF and OSDI was not witnessed in the control group at any time point. The objective parameters assessed did not differ significantly within or between the two groups.Conclusion: When treating severe DED, the DF can be significantly reduced by using very high Mw HA (3 MDa) lubricant eye drops, which better alleviate DED symptoms and decrease the OSDI scores. These drops not only provide an attractive and comfortable alternative for patients with severe DED but also offer the possibility of reducing the disease's socioeconomic burden, both for affected individuals and society as a whole.

The purpose of this study was to investigate the effect of high molecular weight hyaluronan (HMWHA) eye drops on subbasal corneal nerves in patients suffering from severe dry eye disease (DED) and to evaluate the damage of subbasal corneal nerves associated with severe DED. Designed as an international, multicenter study, 16 patients with symptoms of at least an Ocular Surface Disease Index (OSDI) score of 33, and corneal fluorescein staining (CFS) of at least Oxford grade 3, were included and randomized into two study arms. The control group continued to use their individual optimum artificial tears over the study period of eight weeks; in the verum group, the artificial tears were substituted by eye drops containing 0.15% HMWHA. At the baseline visit, and after eight weeks, the subbasal nerve plexus of 16 patients were assessed by confocal laser scanning microscopy (CSLM). The images were submitted to a masked reading center for evaluation. Results showed a significant increase of total nerve fiber lengths (CNFL) in the HMWHA group (p = 0.030) when compared to the control group, where the total subbasal CNFL did not significantly change from baseline to week 8. We concluded that in severe DED patients, HMWHA from topically applied eye drops could cross the epithelial barrier and reach the subbasal nerve plexus, where it exercised a trophic effect.

The aim of the HYLAN M study was to investigate if symptoms and/or signs of patients suffering from severe dry eye disease (DED) can be improved by substituting individually optimized artificial tear therapy by high molecular weight hyaluronan (HMWHA) eye drops. In this international, multicenter study, patients with symptoms of at least ocular surface disease index (OSDI) 33 and corneal fluorescein staining (CFS) of at least Oxford grade 3 were included. A total of 84 per-protocol patients were randomized in two study arms. The control group continued to use their individual optimum artificial tears over the study period of eight weeks; in the verum group, the artificial tears were substituted by eye drops containing 0.15% HMWHA. At the week 8 visit, the average OSDI of the verum group had improved by 13.5 as compared to the control group (p = 0.001). The best corrected visual acuity (BCVA) had improved by 0.04 logMAR (p = 0.033). CFS, tear film break-up time (TBUT), Schirmer I, lid wiper epitheliopathy (LWE), mucocutaneous junction (Yamaguchi score), and tear osmolarity were not significantly different between the verum and control groups (p > 0.050). We conclude that for most patients with severe DED, 0.15% HMWHA eye drops provide excellent improvement of symptoms without impairment of dry eye signs.