Disrupted Neural Regeneration in Dry Eye Secondary to Ankylosing Spondylitis - With a Theoretical Link between Piezo2 Channelopathy and Gateway Reflex, WDR Neurons, and Flare-Ups

This study aimed at analyzing the corneal neural regeneration in ankylosing spondylitis patients using in vivo corneal confocal microscopy in correlation with Langerhans cell density, morphology, and dry eye parameters. Approximately 24 ankylosing spondylitis subjects and 35 age- and gender-matched control subjects were enrolled. Data analysis showed that all corneal nerve-fiber descriptives were lower in the ankylosing spondylitis group, implicating disrupted neural regeneration. Peripheral Langerhans cell density showed a negative correlation with nerve fiber descriptions. A negative correlation between tear film break-up time and corneal nerve fiber total branch density was detected. The potential role of somatosensory terminal Piezo2 channelopathy in the pathogenesis of dry eye disease and ankylosing spondylitis is highlighted in our study, exposing the neuroimmunological link between these diseases. We hypothesized earlier that spinal neuroimmune-induced sensitization due to this somatosensory terminal primary damage could lead to Langerhans cell activation in the cornea, in association with downregulated Piezo1 channels on these cells. This activation could lead to a Th17/Treg imbalance in dry eye secondary to ankylosing spondylitis. Hence, the corneal Piezo2 channelopathy-induced impaired Piezo2-Piezo1 crosstalk could explain the disrupted neural regeneration. Moreover, the translation of our findings highlights the link between Piezo2 channelopathy-induced gateway to pathophysiology and the gateway reflex, not to mention the potential role of spinal wide dynamic range neurons in the evolution of neuropathic pain and the flare-ups in ankylosing spondylitis and dry eye disease

A hályogoperálás története Magyarországon [History of cataract operations in Hungary]

A szürkehályog eltávolításának története több ezer éves múltra tekint vissza. A kezdeti, sokszor durva, gyakran a hályogos szem elvesztésével járó műtétekből kifinomult műtéti eljárás fejlődött ki. A hályogoperálás szorosan összefüggött az anatómiai-patológiai ismeretek elmélyülésével és a rendelkezésre álló műszerek tökéletesedésével. Habár Daviel 1747-ben elvégezte az első tudatos hályogkivonást, majd száz évet kellett várni, hogy az ősi, a hályogos lencse üvegtesti térbe történő diszlokációját végleg felváltsa a hályog nyitott tokos eltávolítása (extracapsularis cataracta-extractio). A XX. század közepére a műtéti technika és műszerezettség tökéletesedése mellett a kevesebb komplikációt ígérő zárt tokos hályogkivonás (intracapsularis cataracta-extractio) különböző formái váltak uralkodóvá. A XX. század második felében a műlencse megjelenése és elterjedése a nyitott tokos hályogkivonás újbóli felfedezését jelentette a műtéti eljárás további tökéletesedése mellett. A sebméret zsugorodása, a hályog szemen belüli feldarabolásának (phacoemulsificatio) lehetősége, valamint az összehajlítható műlencsék használata mellett végzett műtétek ma a szürkehályog eltávolításának gold standardját jelentik. A dolgozat a különböző hályogoperálási technikák ismertetésén túl a különböző korszakok nehézségeit és úttörő munkáit is hivatott bemutatni, és ezzel összefoglalót adni a szemészetben leggyakrabban végzett műtéti beavatkozásról. Orv. Hetil., 2013, 154(45), 1802–1805. | The history of the cataract operations dates back to thousands of years ago. Initially, surgery was carried out using rudimentary operating techniques resulting in the loss of many eyes. Cataract surgery has evolved immersely and now it is a highly refined surgical practice. Evolution of the cataract surgery was closely linked to broadening of anatomical-pathological knowledge and to the development of the instruments applied. Although Daviel performed the first intentional cataract removal in 1747, almost one hundred years passed before the extracapsular cataract extraction method finally replaced the old couching technique. By the middle of the 20th century, with the progression of the operation techniques and instruments, different forms of intracapsular cataract extraction methods became prevalent. Introduction and widespread use of the artificial intraocular lenses from the second half of the 20th century led to the rediscovery and further perfection of the extracapsular cataract extraction technique. Today, phacoemulsification through small incision, along with the foldable intraocular lenses is the gold standard of cataract surgery. The aim of this study is to present the different cataract surgery methods applied throughout the centuries, as well as the difficulties encountered. It discusses pioneering steps of each era, in order to give a closer look at the most frequently performed surgical intervention in ophthalmology. Orv. Hetil., 154(45), 1802–1805

Dry eye and corneal langerhans cells in systemic lupus erythematosus.

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/mm(2)) than in controls (20.57 +/- 21.04 cell/mm(2)). There was no difference in the peripheral LC density (124.78 +/- 165.39 versus 78.00 +/- 39.51 cell/mm(2)). 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

In vivo confocal microscopic evaluation of corneal Langerhans cell density, and distribution and evaluation of dry eye in rheumatoid arthritis

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

Corneal Langerhans cell and dry eye examinations in ankylosing spondylitis

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

Evidence of Disruption in Neural Regeneration in Dry Eye Secondary to Rheumatoid Arthritis

The purpose of our study was to analyze abnormal neural regeneration activity in the cornea through means of confocal microscopy in rheumatoid arthritis patients with concomitant dry eye disease. We examined 40 rheumatoid arthritis patients with variable severity and 44 volunteer age- and gender-matched healthy control subjects. We found that all examined parameters were significantly lower (p 2P-TASK1 signaling axis. This could accelerate neuroimmune-induced sensitization on the spinal level in this autoimmune disease, with Langerhans-cell activation in the cornea and theorized downregulated Piezo1 channels in these cells. Even more importantly, suggested principal primary-damage-associated corneal keratocyte activation could be accompanied by upregulation of Piezo1. Both activation processes on the periphery would skew the plasticity of the Th17/Treg ratio, resulting in Th17/Treg imbalance in dry eye, secondary to rheumatoid arthritis. Hence, chronic somatosensory-terminal Piezo2 channelopathy-induced impaired Piezo2–Piezo1 crosstalk could result in a mixed picture of disrupted functional regeneration but upregulated morphological regeneration activity of these somatosensory axons in the cornea, providing the demonstrated abnormal neural corneal morphology