LETTERS
Dry Eye in Rheumatoid Arthritis: Tear Film Osmolarity and Inflammation To the Editor: We read with great interest the article titled “Correlation Between Tear Film Osmolarity, Dry Eye Disease, and Rheumatoid Arthritis” by Schargus et al.1 The authors of this cross-sectional cohort study concluded that tear film osmolarity correlates positively with rheumatoid arthritis (RA) activity and that patients with RA with high disease activity are at an increased risk of developing dry eye disease (DED) with high tear osmolarity values. Contrary to Fujita et al,2 the authors found similar correlations between DED and RA activity in both patients with and without secondary Sjogren syndrome (SSII), and they attributed these findings to the use of osmolarity as a diagnostic tool. In recent years, our group published 2 articles on DED in RA,3,4 focusing on inflammation. We reported data on in vivo confocal microscopy inflammatory and neuroinflammatory parameters, correlating with RA activity in both patients with and without secondary SSII.3 Moreover, in RA with SSII subjects, corneal subbasal dendritic cell density and tear fluid concentrations of IL-1a and IL-6 significantly decreased after remission of the RA activity (defined as disease activity score 28 , 2.6), obtained by systemic therapy without topical interventions.4 We believe that our findings are complementary to the interesting data reported by Schargus et al,1 providing not yet fully understood insights into the pathogenesis of DED in RA and into the relationship between ocular surface osmolarity and inflammation. Financial disclosures/conflicts of interest: None reported. Edoardo Villani, MD Paolo Nucci, MD Department of Clinical Sciences and Community Health, University of Milan, Eye Clinic San Giuseppe Hospital, Milan, Italy
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| www.corneajrnl.com
TO THE
EDITOR
REFERENCES 1. Schargus M, Wolf F, Tony HP, et al. Correlation between tear film osmolarity, dry eye disease, and rheumatoid arthritis. Cornea. 2014;33:1257–1261. 2. Fujita M, Igarashi T, Kurai T, et al. Correlation between dry eye and rheumatoid arthritis activity. Am J Ophthalmol. 2005;140:808–813. 3. Villani E, Galimberti D, Viola F, et al. Corneal involvement in rheumatoid arthritis: an in vivo confocal study. Invest Ophthalmol Vis Sci. 2008;49:560–564. 4. Villani E, Galimberti D, Del Papa N, et al. Inflammation in dry eye associated with rheumatoid arthritis: cytokine and in vivo confocal microscopy study. Innate Immun. 2013;19:420–427.
Reply: We thank Villani et al for their valuable comments on our article, “Correlation Between Tear Film Osmolarity, Dry Eye Disease, and Rheumatoid Arthritis”.1 We had already read carefully with great interest the published articles of Villani et al when preparing our manuscript.2,3 Unfortunately, because we examined our patients in the rheumatology unit and not in the ophthalmological department, we did not have the opportunity to perform corneal confocal microscopy and collect the tear fluid for cytokine analysis. It is an important, although not surprising, observation that cytokines are elevated in active rheumatoid arthritis (RA). One could hypothesize that there may be 2 mechanisms that lead to elevated cytokines and tear film osmolarity in patients with RA: (1) lower tear production leading to higher concentration of cytokines and higher solute concentration; (2) the inflammatory process involving the ocular surface itself resulting in higher instability of the tear film and a subsequent rise of the solute concentration, and therefore higher osmolarity values. Unfortunately, in our RA group, we could not find a correlation between Schirmer test, tear break-up time, and RA activity. However, the mean Schirmer test score in our group was much higher (11.3 mm) than that of the study by Villani et al (mean in all groups between 3.2 and 5.4 mm), which selectively analyzed patients with manifest dry eye or Sjögren syndrome (SS). Further studies in patients with SS are required to establish whether correlations between inflammatory tear film
markers, osmolarity, classical tear film evaluation tests (Schirmer test, break-up time, corneal and conjunctival staining, ocular surface disease index) exist with inflammatory serological parameters and clinical RA activity scores. A fast noninvasive evaluation of disease activity, trend, and treatment success in patients with RA and SS as well as other systemic inflammatory conditions from tear samples could potentially be of great clinical benefit. This would be even easily accessible for the nonophthalmic community than confocal microscopy. Financial disclosures/conflicts of interest: None reported. Marc Schargus, MD Gerd Geerling, MD University Eye Hospital, Wuerzburg, Germany
REFERENCES 1. Schargus M, Wolf F, Tony HP, et al. Correlation between tear film osmolarity, dry eye disease, and rheumatoid arthritis. Cornea. 2014;33:1257–1261. 2. Villani E, Galimberti D, Viola F, et al. Corneal involvement in rheumatoid arthritis: an in vivo confocal study. Invest Ophthalmol Vis Sci. 2008;49:560–564. 3. Villani E, Galimberti D, Del Papa N, et al. Inflammation in dry eye associated with rheumatoid arthritis: cytokine and in vivo confocal microscopy study. Innate Immun. 2013;19:420–427.
Current Approaches to Combat the Shortage of Corneal Tissues: Split-DMEK and Double-Split Keratoplasty To the Editor: In the last few years, Descemet membrane endothelial keratoplasty (DMEK) has become the therapy of choice for many corneal endothelial diseases such as Fuchs endothelial dystrophy, bullous keratopathy, or secondary endothelial dystrophies.1,2 A shortage of
Cornea Volume 34, Number 3, March 2015
Copyright ª 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Dry Eye in Rheumatoid Arthritis: Tear Film Osmolarity and Inflammation To the Editor: We read with great interest the article titled “Correlation Between Tear Film Osmolarity, Dry Eye Disease, and Rheumatoid Arthritis” by Schargus et al.1 The authors of this cross-sectional cohort study concluded that tear film osmolarity correlates positively with rheumatoid arthritis (RA) activity and that patients with RA with high disease activity are at an increased risk of developing dry eye disease (DED) with high tear osmolarity values. Contrary to Fujita et al,2 the authors found similar correlations between DED and RA activity in both patients with and without secondary Sjogren syndrome (SSII), and they attributed these findings to the use of osmolarity as a diagnostic tool. In recent years, our group published 2 articles on DED in RA,3,4 focusing on inflammation. We reported data on in vivo confocal microscopy inflammatory and neuroinflammatory parameters, correlating with RA activity in both patients with and without secondary SSII.3 Moreover, in RA with SSII subjects, corneal subbasal dendritic cell density and tear fluid concentrations of IL-1a and IL-6 significantly decreased after remission of the RA activity (defined as disease activity score 28 , 2.6), obtained by systemic therapy without topical interventions.4 We believe that our findings are complementary to the interesting data reported by Schargus et al,1 providing not yet fully understood insights into the pathogenesis of DED in RA and into the relationship between ocular surface osmolarity and inflammation. Financial disclosures/conflicts of interest: None reported. Edoardo Villani, MD Paolo Nucci, MD Department of Clinical Sciences and Community Health, University of Milan, Eye Clinic San Giuseppe Hospital, Milan, Italy
e6
| www.corneajrnl.com
TO THE
EDITOR
REFERENCES 1. Schargus M, Wolf F, Tony HP, et al. Correlation between tear film osmolarity, dry eye disease, and rheumatoid arthritis. Cornea. 2014;33:1257–1261. 2. Fujita M, Igarashi T, Kurai T, et al. Correlation between dry eye and rheumatoid arthritis activity. Am J Ophthalmol. 2005;140:808–813. 3. Villani E, Galimberti D, Viola F, et al. Corneal involvement in rheumatoid arthritis: an in vivo confocal study. Invest Ophthalmol Vis Sci. 2008;49:560–564. 4. Villani E, Galimberti D, Del Papa N, et al. Inflammation in dry eye associated with rheumatoid arthritis: cytokine and in vivo confocal microscopy study. Innate Immun. 2013;19:420–427.
Reply: We thank Villani et al for their valuable comments on our article, “Correlation Between Tear Film Osmolarity, Dry Eye Disease, and Rheumatoid Arthritis”.1 We had already read carefully with great interest the published articles of Villani et al when preparing our manuscript.2,3 Unfortunately, because we examined our patients in the rheumatology unit and not in the ophthalmological department, we did not have the opportunity to perform corneal confocal microscopy and collect the tear fluid for cytokine analysis. It is an important, although not surprising, observation that cytokines are elevated in active rheumatoid arthritis (RA). One could hypothesize that there may be 2 mechanisms that lead to elevated cytokines and tear film osmolarity in patients with RA: (1) lower tear production leading to higher concentration of cytokines and higher solute concentration; (2) the inflammatory process involving the ocular surface itself resulting in higher instability of the tear film and a subsequent rise of the solute concentration, and therefore higher osmolarity values. Unfortunately, in our RA group, we could not find a correlation between Schirmer test, tear break-up time, and RA activity. However, the mean Schirmer test score in our group was much higher (11.3 mm) than that of the study by Villani et al (mean in all groups between 3.2 and 5.4 mm), which selectively analyzed patients with manifest dry eye or Sjögren syndrome (SS). Further studies in patients with SS are required to establish whether correlations between inflammatory tear film
markers, osmolarity, classical tear film evaluation tests (Schirmer test, break-up time, corneal and conjunctival staining, ocular surface disease index) exist with inflammatory serological parameters and clinical RA activity scores. A fast noninvasive evaluation of disease activity, trend, and treatment success in patients with RA and SS as well as other systemic inflammatory conditions from tear samples could potentially be of great clinical benefit. This would be even easily accessible for the nonophthalmic community than confocal microscopy. Financial disclosures/conflicts of interest: None reported. Marc Schargus, MD Gerd Geerling, MD University Eye Hospital, Wuerzburg, Germany
REFERENCES 1. Schargus M, Wolf F, Tony HP, et al. Correlation between tear film osmolarity, dry eye disease, and rheumatoid arthritis. Cornea. 2014;33:1257–1261. 2. Villani E, Galimberti D, Viola F, et al. Corneal involvement in rheumatoid arthritis: an in vivo confocal study. Invest Ophthalmol Vis Sci. 2008;49:560–564. 3. Villani E, Galimberti D, Del Papa N, et al. Inflammation in dry eye associated with rheumatoid arthritis: cytokine and in vivo confocal microscopy study. Innate Immun. 2013;19:420–427.
Current Approaches to Combat the Shortage of Corneal Tissues: Split-DMEK and Double-Split Keratoplasty To the Editor: In the last few years, Descemet membrane endothelial keratoplasty (DMEK) has become the therapy of choice for many corneal endothelial diseases such as Fuchs endothelial dystrophy, bullous keratopathy, or secondary endothelial dystrophies.1,2 A shortage of
Cornea Volume 34, Number 3, March 2015
Copyright ª 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
