Dry eye disease (DED) is a multifactorial disorder with recognized pathology, but not entirely known pathomechanism. It is suggested to represent a continuum with neuropathic corneal pain with the paradox that DED is a pain-free disease in most cases, although it is regarded as a pain condition. The current paper puts into perspective that one gateway from physiology to pathophysiology could be a Piezo2 channelopathy, opening the pathway to a potentially quad-phasic non-contact injury mechanism on a multifactorial basis and with a heterogeneous clinical picture. The primary non-contact injury phase could be the pain-free microinjury of the Piezo2 ion channel at the corneal somatosensory nerve terminal. The secondary non-contact injury phase involves harsher corneal tissue damage with C-fiber contribution due to the lost or inadequate intimate cross-talk between somatosensory Piezo2 and peripheral Piezo1. The third injury phase of this non-contact injury is the neuronal sensitization process with underlying repeated re-injury of the Piezo2, leading to the proposed chronic channelopathy. Notably, sensitization may evolve in certain cases in the absence of the second injury phase. Finally, the quadric injury phase is the lingering low-grade neuroinflammation associated with aging, called inflammaging. This quadric phase could clinically initiate or augment DED, explaining why increasing age is a risk factor. We highlight the potential role of the NGF-TrkA axis as a signaling mechanism that could further promote the microinjury of the corneal Piezo2 in a stress-derived hyperexcited state. The NGF-TrkA-Piezo2 axis might explain why female sex represents a risk factor for DED.

Purpose. Investigation of dry eye and corneal Langerhans cells (LCs) in systemic lupus erythematosus (SLE). Methods. Prospective consecutive case series of 27 SLE patients and 27 control subjects. Dry eye was evaluated by lid-parallel conjunctival folds (LIPCOF), Schirmer test, tear break-up time (TBUT), and ocular surface disease index (OSDI) questionnaire. In vivo investigation of corneal LCs density and morphology (LCM) was performed with confocal corneal microscopy (Heidelberg Retina Tomograph with Rostock Cornea Module). Results. Tear production and stability were pathological in SLE subjects compared to control (Schirmer: 8.45 ± 9.82 mm/5 min versus 11.67 ± 3.21 mm/5 min; TBUT: 6.86 ± 3.53 s versus 11.09 ± 3.37 s). OSDI was significantly greater in SLE patients (25.95 ± 17.92) than in controls (11.06 ± 7.18). Central LC density was greater in SLE patients (43.08 ± 48.67 cell/mm2) than in controls (20.57 ± 21.04 cell/mm2). There was no difference in the peripheral LC density (124.78 ± 165.39 versus 78.00 ± 39.51 cell/mm2). LCM was higher in SLE patients in the centre (1.43 ± 0.79) and in the periphery (2.89 ± 0.42) compared to controls (centre: 1.00 ± 0.69, periphery: 2.35 ± 0.54). Conclusions. Significant changes in dry eye parameters and marked increase of central LCs could be demonstrated in SLE patients. SLE alters not only the LC density but also the morphology, modifies corneal homeostasis, and might contribute to the development of dry eye.

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BackgroundMacular edema is a common cause of visual loss at uveitic patients. The aim of our study was to investigate retinal and choroidal thickness at the macula in anterior (AU) and intermediate (IMU) uveitis and in healthy individuals using spectral domain optical coherence tomography (SD-OCT).MethodsCase-control study of 21 patients with AU and 23 patients with IMU and 34 age-matched healthy controls was performed with Spectralis SD-OCT (Heidelberg Engineering, Germany). High resolution SD-OCT scans and macular mapping were applied for automated measurement of retinal thickness. Standardized, masked manual measurement of the choroidal thickness was performed in the center of the ETDRS fields on enhanced depth imaging (EDI) scans. Evaluation of central retinal subfield thickness, 3 mm and 6 mm perifoveal rings was performed in the corresponding ETDRS zones in patient groups.ResultsThe mean central retinal subfield thickness was significantly higher in IMU (368.65 ± 115.88 μm, p = 0.0003), but not significantly different in AU (290.42 ± 26.37 μm p = 0.6617) compared to that of in controls (278.55 ± 18.31 μm). In both uveitis groups retina was significantly thicker in the 3 and 6 mm perifoveal rings than that of in controls (359 ± 15.24 μm in AU and 390.55 ± 70.90 μm in IMU vs 345,41 ± 15.28 μm in the control group, p = 0.0388 and p < 0.0001) in the 3 mm and (313.83 ± 16.63 μm in AU and 343.33 ± 57.29 μm in IMU vs 299 ± 13.82 μm in the control group, p = 0.0171 and p < 0.0001) in the 6 mm ring. Central choroidal thickness was 311.94 ± 60.48 μm in the control eyes, showed no significant difference in AU (312.61 ± 90.35 μm) and IMU (303.17 ± 93.66 μm) eyes, and was also similar at the perifoveal rings.ConclusionSignificant topographical changes could be detected in the macula of AU and IMU patients. Retinal thickness in the perifoveal rings was increased both in AU and IMU, but in the center only in IMU. Choroidal thickness seems to be unaffected by uveitis, even in the presence of macular edema, at least in the early stage of the inflammatory disease process.

Purpose To examine the density and the distribution of corneal Langerhans cells (LCs) and to compare the results with dry‐eye related parameters in rheumatoid arthritis (RA). Methods 52 RA patients (mean age: 58 [49‐66]) with various degree of disease activity and 24 healthy subjects (mean age: 61 [52.5‐67]) were enrolled. Central and peripheral LC number and morphology were assessed with in vivo confocal laser corneal microscopy. In addition, lid parallel conjunctival folds (LIPCOF), tear break up time (TBUT), Schirmer’s‐test (ST), and ocular surface disease index (OSDI) were also evaluated. . Results The prevalence of central and peripheral LCs and the central LC morphology values (LCM) were higher in RA compared to controls (median [interquartile range]: 42.50 [22.95‐93.50] vs 10.00 [0.00‐42.33] cell/mm2, 98.00 [62.00‐154.5] vs 59.50 [45.25‐94.75] cell/mm2, and 2.00 [1.00‐2.00] vs 1.00 [0.25‐1.00], respectively, p<0.05 for all). Within the RA group, LC prevalence and morphology were not affected by disease activity. However, patients on anti‐TNF or corticosteroid therapy exhibited LCM and central and peripheral LC density comparable to controls. TBUT values were lower and OSDI scores were higher in RA than in controls (9.00 [7.00‐12.00] vs 12.00[9.00‐14.00] seconds and 20.00 [10.93‐38.21] vs 9.75 [4.93‐16.28], respectively, p<0.05 for all). ST results were comparable in RA and controls. Conclusion Dendritic cell accumulation and maturation in the corneal center suggest the involvement of the cornea in RA, even in patients in inactive stage and without ocular symptoms.

APCs of the ocular surface, including corneal Langerhans cells (LCs), offer the opportunity to gain insight into the activity of innate immunity. We examined corneal LCs and dry eye parameters in ankylosing spondylitis (AS). Twenty-four AS patients with varying degrees of disease activity and 24 healthy participants were enrolled. Central and peripheral LC numbers, and Langerhans cell morphology (LCM) were assessed with in vivo laser confocal microscopy. In addition, ocular surface disease index, lid parallel conjunctival folds, tear break up time, and Schirmer test were evaluated. LC densities and central LCM were greater in AS patients than in the controls. Moreover, LCM was significantly greater in patients with higher systemic inflammation according to elevated C-reactive protein (CRP). Also, tear production was greatly suppressed in patients with more severe onset of the systemic inflammation according to the Bath Ankylosing Spondylitis Disease Activity Index and elevated CRP. Greater corneal LC density and LCM in AS may reflect an increased activation state of the innate immune system of the cornea in AS, which correlates with the systemic activity of AS even without ocular symptoms. Nonetheless, higher systemic inflammation might impair tear production, and it might partly explain the dry eye mechanism.

Corneal Langerhans cells (LCs) offer the opportunity to gain insight into the activity of the innate immunity. We examined the density and the distribution of LCs and compared the results with dry-eye parameters in rheumatoid arthritis (RA). Fifty-two RA patients with various degrees of disease activity and 24 healthy subjects were enrolled. Peripheral and central LC number and morphology were assessed with in vivo laser confocal microscopy. In addition, ocular surface disease index (OSDI), lid parallel conjunctival folds, Schirmer test, and tear break-up time (TBUT) were evaluated. The prevalence of central and peripheral LC, and the central LC morphology values (LCM) were higher than normal in RA. Within the RA group, LC prevalence and morphology were not affected by disease activity. However, patients on anti-TNF or glucocorticosteroid (GCS) therapy exhibited normal LCM, and normal central and peripheral LC density. OSDI was higher and TBUT was lower than normal in RA. The alteration of LC in RA suggests an active inflammatory process in the cornea, which may reflect an increased activation state of the innate immune system-even in inactive stages of RA and without ocular symptoms. The results also indicate ocular effects of GCS therapy in RA.

Patients with chronic central serous chorioretinopathy can safely be treated with eplerenone as it can reverse choroidal vasodilation with an accompanying resolution of the SRF and improvement in visual acuity. These beneficial therapeutic effects are more pronounced in the exudative eyes.