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Thomas Kaercher,1 Elisabeth M Messmer,2,3 Thomas Berninger,4 Klaudia K Huber-van der Velden,5 Raphaela Geiger,6 Pauline Cipriano-Bonvin,7 Christina Jacobi8,9 1Augenarztpraxis, Heidelberg, Germany; 2Department of Ophthalmology, Ludwig-Maximilian-University, Munich, Germany; 3Praxis Professor Kampik & Kollegen, Munich, Germany; 4Augenzentrum, Olching, Germany; 5Augenheilkunde Lindenthal, Köln-Lindenthal, Germany; 6TRB Chemedica AG, Feldkirchen, Germany; 7TRB Chemedica International SA, Geneva, Switzerland; 8Augen & Haut Zentrum-Praxis Dr. Jacobi, Nuremberg, Germany; 9Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, GermanyCorrespondence: Thomas Kaercher, Augenarztpraxis, 48 Dossenheimer Landstr, Heidelberg, 69121, Germany, Tel +49 6221 400 888, Fax +49 6221 412 203, Email thomas.kaercher@meibomius.dePurpose: To investigate the efficacy, safety and tolerability of topical omega-3 polyunsaturated fatty acids (PUFA) as an innovative treatment of dry eye disease (DED).Patients and Methods: In a pilot, multicenter, masked-observer, randomized, active-controlled, non-inferiority study in Germany, patients self-treated their eyes with daily instillations of eye drops containing either omega-3 PUFA or povidone as major components for three months. At four and twelve weeks, efficacy was among others evaluated based on Ocular Surface Disease Index (OSDI), ocular surface symptoms intensity, general clinical impression, tear break-up time (TBUT), corneal fluorescein staining using the Oxford grading scale, tear volume, and matrix metalloproteinase-9 (MMP-9) concentration in the tear film. Safety evaluation included visual acuity, intraocular pressure, and the incidence of adverse events. Co-primary endpoints were the mean percent changes from baseline of TBUT and OSDI after four weeks.Results: In total 80 patients were included, of whom 37 in the PUFA group and 39 in the povidone group were evaluable for the co-primary endpoints. Patients had a mean age of 52 years and > 80% were women. Both co-primary endpoints (TBUT and OSDI) significantly improved from baseline in both treatment groups, at Week 4 and Week 12 and the statistical analysis demonstrated topical omega-3 PUFA to be non-inferior to 2% povidone for these two parameters. Both treatments resulted in a significant improvement of most secondary efficacy endpoints as well, often with a slight difference in favor of PUFA, not reaching statistical significance though. One non-severe, treatment-related local AE was reported in each group.Conclusion: Omega-3 PUFA-based eye drops proved to be non-inferior to povidone-containing eye drops in the treatment of signs and symptoms of dry eye. This treatment may thus be an additional tool for the management of DED.Keywords: polyunsaturated fatty acids, povidone, dry eye disease, artificial tears, omega-3 fatty acid

Early initiation of anti-inflammatory therapies is recommended for dry eye disease (DED) to break the vicious cycle of pathophysiology. However, there is limited guidance on how to implement topical ciclosporin (CsA) and corticosteroid treatment into clinical practice. This expert-led consensus provides practical guidance on the management of DED, including when and how to use topical CsA.A steering committee (SC) of seven European DED experts developed a questionnaire to gain information on the unmet needs and management of DED in clinical practice. Consensus statements on four key areas (disease severity and progression; patient management; efficacy, safety and tolerability of CsA; and patient education) were generated based on the responses. The SC and an expanded expert panel of 22 members used a nine-point scale (1 = strongly disagree; 9 = strongly agree) to rate statements; a consensus was reached if ≥75% of experts scored a statement ≥7.A stepwise approach to DED management is required in patients presenting with moderate corneal staining. Early topical CsA initiation, alone or with corticosteroids, should be considered in patients with clinical risk factors for severe DED. Patient education is required before and during treatment to manage expectations regarding efficacy and tolerability in order to optimise adherence. Follow-up visits are required, ideally at Month 1 and every 3 months thereafter. Topical CsA may be continued indefinitely, especially when surgery is required.This consensus fills some of the knowledge gaps in previous recommendations regarding the use of topical corticosteroids and CsA in patients with DED.

BACKGROUND Dry eye disease (DED) is a common disorder, accounting for up to 35% of the general population. Therefore, we hypothesized that laryngopharyngeal reflux (LPR), inducing refluxate rising into airways, may involve the ocular surface and may either induce or worsen DED. AIM To investigate the prevalence and relevance of suspected LPR in DED patients and subjects with refractive problems (RP) without DED, they were defined as non-dry eye group (NEG) in clinical practice. METHODS This retrospective study included consecutive patients evaluated because of dry eye-like symptoms at eight tertiary ophthalmological clinics. Parameters included reflux symptom index (RSI), ocular surface disease index (OSDI), symptom assessment in dry eye (SANDE) for frequency and severity, Schirmer test, tear break-up time (BUT), and Oxford grading. RESULTS The study included 245 subjects (72.5% females; mean age 56.3 years), 152 DED patients, and 93 sex- and age-matched NEG subjects. Pathological RSI (score>13) was detected in 80 subjects (32.6%); 68 (85%) with DED and 12 (15%) CG (OR = 8; p

Refractive surgery is one of the most common elective surgeries performed worldwide. The incidence of dry eye disease (DED) after corneal refractive surgery varies among different studies. Pre-existing untreated DED has been identified as a risk factor for postsurgical dry eye symptoms. On the basis of both evidence and clinical experience, some recommendations for ocular surface and DED management pre- and post-refractive surgery are described. In aqueous deficiency Dry Eye Disease, preservative-free lubricating drops should be preferred, in addition to ointment and gel forms. Topical anti-inflammatory agents (Cyclosporine 0.1%, hydrocortisone phosphate, fluorometholone) should be used for 3–6 months in cases of ocular surface damage. The therapy of evaporative DED includes lifestyle modifications, lid hygiene (either performed by the patient or offered as professional lid hygiene by the physician), use of lubricating eye drops with lipid components, topical and/or systemic antibiotic treatment with anti-inflammatory properties and Intense Pulsed Light (IPL-) Treatment for meibomian gland dysfunction.

ZusammenfassungDas Trockene Auge führt häufig zu Sehstörungen trotz guter Sehleistung in der Standardvisusprüfung. Die Beschwerden treten meist beim Lesen, Arbeiten am Computer und/oder beim Autofahren auf. Grund ist die schlechte optische Qualität der Augenoberfläche beim Trockenen Auge mit Zunahme von topometrischer Irregularität und Asymmetrie, Anstieg des irregulären Astigmatismus, Zunahme der kornealen und okulären Aberrationen höherer Ordnung, Abnahme der Kontrastsensitivität und Zunahme der Lichtstreuung. Die funktionelle Sehschärfe repräsentiert die Visusfunktion im Zeitverlauf und reflektiert die Visusleistung eines Individuums bei täglichen Aktivitäten. Sie ist beim Trockenen Auge signifikant reduziert im Vergleich zu Normalprobanden. Eine Vielzahl von Testmethoden zur Evaluierung der funktionellen Sehschärfe wurde beschrieben. Kein Verfahren hat sich bisher in der täglichen Praxis durchgesetzt.

To evaluate the effect of IPL (intense pulsed light) treatment in patients with meibomian gland dysfunction (MGD).Clinical data of 25 patients with MGD who underwent IPL treatment at the department of ophthalmology of Ludwig-Maximilians-University between 2016 and 2018 were analyzed. Demographics, clinical history, examination findings (eyelid vascularization, meibomian gland findings, conjunctival redness, tear film break-up time [TFBUT], corneal staining (Oxford grading scale [OGS]), and subjective patients' findings (including ocular surface disease index [OSDI]) were collected from each visit (D1, D15, D45, D75).All included patients underwent three sessions of IPL treatment in both eyes (D1, D15, D45). There was a significant improvement after IPL treatment (D75) in TFBUT (p 0.001), corneal staining (OGS) (p 0.001), conjunctival redness (p 0.001), lid margin edema (p 0.001) and redness (p 0.001), meibum quality (p 0.001), lid margin telangiectasia (p = 0.005), meibomian gland obstruction (p = 0.001), and OSDI score (p = 0.004). Even after the first IPL session, significant improvements in TFBUT (p 0.001), corneal staining (OGS p 0.001), conjunctival redness (p 0.022), lid margin edema (p 0.001) and redness (p 0.016), meibum quality (p = 0.014), and OSDI score (p 0.013) were noted. There were no relevant negative side effects. Subgroup analysis for age, sex, duration or severity of disease, and associated diagnosis of rosacea showed no significant difference in effectiveness.IPL is an effective and safe treatment for patients with MGD, which can be used as a supportive therapeutic option.ZIEL: Beurteilung der Wirkung der IPL-Therapie (IPL: Intensive pulsed Light) bei Patienten mit Meibomdrüsendysfunktion (MDD).Analysiert wurden die Daten von 25 Patienten mit MDD, die zwischen 2016 und 2018 in der Abteilung für Augenheilkunde der LMU mittels IPL behandelt wurden. Demografische Daten, klinische Anamnese sowie Untersuchungsbefunde (Lidrandvaskularisation, Meibomdrüsenbefunde, Bindehautrötung, Tränenfilmaufrisszeit (TFBUT), Hornhautoberflächenfärbung (Oxford Grading Scale [OGS]) und subjektive Symptome (einschließlich des Ocular Surface Disease Index [OSDI]) wurden bei jedem Besuch erhoben (D1, D15, D45, D75).Alle Patienten erhielten eine IPL-Behandlung in 3 Sitzungen an beiden Augen (D1, D15, D45). Am Ende der IPL-Behandlung (D75) zeigte sich eine signifikante Verbesserung von TFBUT (p 0,001), Hornhautoberflächenfärbung (OGS) (p 0,001), Bindehautrötung (p 0,001), Lidrandödem (p 0,001) und Lidrandrötung (p 0,001), Meibumqualität (p 0,001), Lidrandteleangiektasien (p = 0,005), Meibomdrüsenobstruktion (p = 0,001) und OSDI-Score (p = 0,004). Bereits nach der 1. IPL-Sitzung konnte eine signifikante Verbesserung von TFBUT (p = 0,001), Hornhautoberflächenfärbung (OGS p 0,001), Bindehautrötung (p = 0,022), Lidrandödem (p = 0,001) und -rötung (p = 0,016), Meibumqualität (p = 0,014) und OSDI-Score (p = 0,013) festgestellt werden. Es gab keine relevanten negativen Nebenwirkungen. Eine Subgruppenanalyse hinsichtlich Alter, Geschlecht, Dauer oder Schwere der Erkrankung sowie der assoziierten Diagnose der Rosazea zeigte keinen signifikanten Unterschied in der Wirksamkeit.IPL ist eine wirksame und sichere Behandlung für Patienten mit MGD, die als unterstützende therapeutische Option eingesetzt werden kann.

ObjectiveDry eye disease (DED) is a multifactorial disease involving the tears and ocular surface. It impacts a patient’s quality of life (QoL) and ability to perform daily activities. This study assessed the burden of self-reported DED among adults in eight European countries.DesignOnline cross-sectional survey.SettingGeneral population in France, Italy, Germany, Greece, the Netherlands, Portugal, Spain and Sweden.ParticipantsAdults aged ≥18 years with (n=6084) and without (n=6161) self-reported DED were recruited via emails and screened.Main outcome measuresAll participants completed National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) and EuroQol-5 Dimension-5 Level Questionnaire (EQ-5D-5L). All DED participants completed the Eye Dryness Score (EDS) Visual Analogue Scale, and Ocular Comfort Index and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem questionnaires. In addition, half of the respondents with DED completed Survey A (Impact of Dry Eye on Everyday Life) and the other half completed Survey B (Standard Patient Evaluation of Eye Dryness Questionnaire) and Dry Eye Questionnaire-5.ResultsParticipants with self-reported DED had lower functional vision and lower overall health status than participants without self-reported DED as measured by the NEI-VFQ and EQ-5D-5L, respectively.Increasing self-reported DED severity as measured by the EDS was shown to correspond with worse symptom severity/frequency, lower functional vision, higher impact on work productivity, daily activities and QoL.ConclusionThis study showed that patients’ reported burden of self-reported DED was similar across the eight European countries. Those with self-reported DED reported lower health status and functional vision compared to those without self-reported DED and these parameters worsen with increasing disease severity.

Hornhautveranderungen bei Liderkrankungen sind haufig und konnen den Krankheitsverlauf erheblich komplizieren. Sie konnen sich als Refraktionsanomalien, Hornhautdegenerationen, Erkrankungen der Augenoberflache, Hornhautinfiltrate, Hornhautvaskularisationen und Hornhautulzerationen bis hin zur Hornhautperforation manifestieren. Pathophysiologisch sind Druckkrafte, Exposition, Trichiasis und Distichiasis, Augenreiben, Entzundung und Infektion bedeutsam. Eine Vielzahl von Liderkrankungen geht mit Erkrankungen der Hornhaut einher wie Lidfehlstellungen, Lidtumoren, Lidinfektionen, die allergische Liddermatitis und Blepharitis, Meibomitis oder Meibom-Drusen-Dysfunktion.

Die Kenntnis der Wundheilungsvorgange nach Amnion‑, Limbus- und Hornhauttransplantation ermoglicht eine Einordnung klinischer Befunde sowie eine zielgerichtete Therapie. Amnion dient als Basalmembransubstrat oder vorubergehendes Transplantat zur kornealen epithelialen Wundheilung. Es wirkt antientzundlich, unterstutzt die korneale Wundheilung und wirkt der Narbenbildung entgegen. Die Amnionmembran wird im Verlauf intraepithelial, subepithelial oder intrastromal integriert. Limbusepithelzellen exprimieren multiple Gene der kornealen Wundheilung. Der ROCK-Inhibitor Y‑27632 kann die Proliferation von Limbusepithelzellen verbessern und stellt somit einen neuen Therapieansatz fur die Therapie der Limbusstammzellinsuffizienz dar. An der Wundheilung nach Keratoplastik sind Fibroblasten, Typ-III- und -IV-Kollagen, Proteoglykane und Chondroitin-6-Sulfat beteiligt. Eine gewisse Entzundungsreaktion scheint fur den Wundverschluss notwendig.

ZusammenfassungDas Trockene Auge stellt eine heterogene Erkrankung der Augenoberfläche dar. Das Krankheitsbild hat multifaktorielle Ursachen und geht normalerweise mit einer Erhöhung der Osmolarität des Tränenfilms und mit Entzündungsprozessen der Gewebe der Augenoberfläche einher. Die Bedeutung der Entzündung beim Trockenen Auge geht nicht zuletzt auch aus der aktuellen Definition des Dry Eye Workshops (DEWS) hervor. Das Verständnis der Pathomechanismen und therapeutischen Möglichkeiten für diese Entzündungsprozesse ist daher für das Management des Trockenen Auges von zentraler Bedeutung. Der Beitrag fasst den aktuellen Kenntnisstand zum Thema „Entzündung und Trockenes Auge“ zusammen und versucht, praktische Empfehlungen für die Diagnostik, Verlaufskontrolle und die Anwendung der aktuell verfügbaren Therapieoptionen für die dem Trockenen Auge zugrunde liegenden Entzündungsprozesse zu geben.

Zusammenfassung Hintergrund Die Hyperosmolarität des Tränenfilms gilt als bedeutendes klinisches Zeichen des trockenen Auges und als wichtigster singulärer diagnostischer Parameter. Neben dem seit einigen Jahren verfügbaren Ocusense TearLab-Osmometer (TearLab Corp, San Diego, CA) ist seit Kurzem auch das I-Pen-Osmometer (I-MED Pharma Inc., Dollard-des-Ormeaux, Quebec, Kanada) verfügbar. Das Ziel unserer Studie war die Vergleichbarkeit der mittels TearLab- und I-Pen-Osmometer erhobenen Tränenfilmosmolarität bei gesunden Probanden zu untersuchen. Material und Methoden 51 gesunde Probanden (mittleres Alter 40,6 Jahre, Altersspanne 17 – 63 Jahre, 66,7% weiblich) ohne Beschwerden und Zeichen eines trockenen Auges (Ocular Surface Disease Index 7 s, unauffälliger Schirmer-Test > 10 mm/5 min) wurden eingeschlossen. Die Tränenfilmosmolarität wurde im Tränenfilmmeniskus (TearLab) und an der subtarsalen Bindehaut (I-Pen) mit einem Zeitintervall von 30 min erhoben. Die Reihenfolge der beiden Osmolaritätsuntersuchungen erfolgte im alternierenden Wechsel. Die statistische Analyse erfolgte mittels Wilcoxon- und Spearman-Tests. Ergebnisse Die mittlere TearLab-Osmolarität war 295,1 mosmol/l (rechtes Auge), 294,0 mosmol/l (linkes Auge) sowie 294,6 mosmol/l (bilateral) mit einer Variationsbreite von 268 – 394 mosmol/l. Mittels I-Pen-Osmometer erhobene mittlere Osmolaritätswerte lagen bei 301,6 mosmol/l (rechtes Auge), 302,5 mosmol/l (linkes Auge) und 302,1 mosmol/l bilateral mit einer Variationsbreite von 276 – 394 mosmol/l. Es zeigte sich ein signifikanter Unterschied in den erhobenen Tränenfilmosmolaritäten mit den beiden Techniken für beide Augen einzeln (p Schlussfolgerung Die mittels I-Pen gemessenen Osmolaritätswerte zeigten sich signifikant höher im Vergleich zu den mit TearLab erhobenen Messwerten. Für diesen Unterschied verantwortlich könnte u. a. die Lokalisation der Messung an der subtarsalen Konjunktiva mit dem I-Pen im Vergleich zur Messung im Tränenfilmmeniskus mit dem TearLab sein. Es könnte daher notwendig sein, den Grenzwert zur Unterscheidung pathologischer Werte von physiologischen Werten bei Messungen der Tränenfilmosmolarität mit dem I-Pen-Osmometer zu ändern. Weiterführende Untersuchungen an einer größeren Kohorte von Normalprobanden sowie bei Patienten mit trockenem Auge sind hierfür notwendig.

Die Meibom-Drusen-Dysfunktion (MDD) ist eine haufige Ursache fur die Entstehung des trockenen Auges. Die IPL(„intense pulsed light“)-Therapie stellt eine neue, zugelassene Behandlungsmethode dar. Der Behandlungszyklus sieht 2 bis 4 Sitzungen vor, bei denen Lichtimpulse im Bereich des Unterlids und des temporalen Lidwinkels appliziert werden. Bei der Therapie handelt es sich um eine sichere Behandlungsform bei Befolgung der vorgeschriebenen Sicherheitsvorkehrungen. In aktuellen Studien wird sowohl von einer Besserung der subjektiven Beschwerden als auch der objektiv messbaren klinischen Parameter berichtet.

Mucins are key actors in tear film quality and tear film stability. Alteration of membrane-bound mucin expression on corneal and conjunctival epithelial cells and/or gel-forming mucin secretion by goblet cells (GCs) promotes in ocular surface diseases and dry eye disease (DED). Changes in the mucin layer may lead to enhanced tear evaporation eventually contributing to tear hyperosmolarity which has been associated with ocular surface inflammation. Inflammatory mediators in turn may have a negative impact on GCs differentiation, proliferation, and mucin secretion. This sheds new light on the position of GCs in the vicious circle of DED. As contributor to ocular surface immune homeostasis, GC loss may contribute to impaired ocular surface immune tolerance observed in DED. In spite of this, there are no tools in routine clinical practice for exploring ocular surface mucin deficiency/dysregulation. Therefore, when selecting the most appropriate treatment options, there is a clear unmet need for a better understanding of the importance of mucins and options for their replacement. Here, we comprehensively revisited the current knowledge on ocular surface mucin biology, including functions, synthesis, and secretion as well as the available diagnostic tools and treatment options to improve mucin-associated homeostasis. In particular, we detailed the potential link between mucin dysfunction and inflammation as part of the uncontrolled chronic inflammation which perpetuates the vicious circle in DED.

Die neurotrophe Keratopathie ist gekennzeichnet durch Hornhautoberflachenveranderungen, persistierende Epitheldefekte und/oder Hornhautulzerationen im Rahmen einer Hornhautsensibilitatsstorung. Aufgrund des variablen Erscheinungsbildes wird die neurotrophe Keratopathie oft ubersehen oder zu spat im Krankheitsverlauf diagnostiziert. Ziele sind eine Darstellung der Klinik sowie Empfehlungen zur korrekten Diagnose. Es erfolgen eine Analyse der vorhandenen Literatur und eine Diskussion von aktuellen Grundlagenarbeiten zum Thema. Die neurotrophe Keratopathie geht definitionsgemas mit Veranderungen der Hornhautnerven einher, die zur Beeintrachtigung von sensorischen und trophischen Funktionen mit konsekutivem Zusammenbruch des Hornhautepithels und Storungen in Tranenfilm, Hornhautepithel und -stroma fuhren. Sie kann im Rahmen von Infektionen, Autoimmunerkrankungen, nach Trauma und okularer Chirurgie, bei intrakraniellen Neoplasien, bei Systemerkrankungen und genetischen Syndromen auftreten. Sie wird in 3 Stadien eingeteilt: mild (Epithelveranderungen ohne Epitheldefekt), moderat (Epitheldefekt) und schwer (Stromabeteiligung). Wichtigstes klinisches Zeichen ist die reduzierte oder fehlende Hornhautsensibilitat. Daher ist die Testung der Hornhautsensibilitat neben Anamnese, klinischer Untersuchung und Zusatzuntersuchungen wie Vitalfarbung und, wenn moglich, konfokaler In-vivo-Mikroskopie unerlasslich zur Diagnose der Erkrankung. Die korrekte Diagnose und Klassifikation der neurotrophen Keratopathie ermoglichen eine stadiengerechte Stufentherapie der Erkrankung sowie die Reduktion von Progression und Komplikationen.

International audience; The pathophysiology of glaucoma is complex, multifactorial and not completely understood. Elevated intraocular pressure (IOP) and/or impaired retinal blood flow may cause initial optic nerve damage. In addition, age-related oxidative stress in the retina concurrently with chronic mechanical and vascular stress is crucial for the initiation of retinal neurodegeneration. Oxidative stress is closely related to cell senescence, mitochondrial dysfunction, excitotoxicity, and neuroinflammation, which are involved in glaucoma progression. Accumulating evidence from animal glaucoma models and from human ocular samples suggests a dysfunction of the para-inflammation in the retinal ganglion cell layer and the optic nerve head. Moreover, quite similar mechanisms in the anterior chamber could explain the trabecular meshwork dysfunction and the elevated IOP in primary open-angle glaucoma. On the other hand, ocular surface disease due to topical interventions is the most prominent and visible consequence of inflammation in glaucoma, with a negative impact on filtering surgery failure, topical treatment efficacy, and possibly on inflammation in the anterior segment. Consequently, glaucoma appears as an outstanding eye disease where inflammatory changes may be present to various extents and consequences along the eye structure, from the ocular surface to the posterior segment, and the visual pathway. Here we reviewed the inflammatory processes in all ocular structures in glaucoma from the back to the front of the eye and beyond. Our approach was to explain how para-inflammation is necessary to maintain homoeostasis, and to describe abnormal inflammatory findings observed in glaucomatous patients or in animal glaucoma models, supporting the hypothesis of a dysregulation of the inflammatory balance toward a pro-inflammatory phenotype. Possible anti-inflammatory therapeutic approaches in glaucoma are also discussed.

Introduction Previous studies have examined the patient experience regarding the diagnosis and management of dry eye disease (DED). The current study explored the ways in which the DED diagnostic pathway differs for those living with and without Sjögren’s syndrome (SS), to identify aspects that influence the patient experience and associated quality of life (QoL). Methods An observational/descriptive, non-interventional, retrospective, self-reported online survey was conducted among adults living in France, Spain and Italy who were diagnosed with DED (with/without SS), were using topical DED treatments (≥ 6 months), and were not contact lens users. Recruitment was via an online database for non-SS participants and through local patient advocacy groups for SS respondents. Results The analysis included 827 respondents; 416 (50.3%) had SS and 82% were female. The mean age was 55 (SD 11; range 16–99) years. The mean age at diagnosis was 46 (SD 12; range 13–78) years and 50 (SD 10; range 21–73) years for SS and non-SS groups, respectively (p

The pathophysiology of Dry Eye Disease (DED) is complex, and therapy may be a challenge. Tear film instability, tear film hyperosmolarity, ocular surface damage and ocular surface inflammation are accepted key events in the pathogenesis of the disease. New anti-inflammatory targets have been identified and novel anti-inflammatory treatments may enrich our therapeutic armamentarium in the future. Neurosensory changes in DED secondary to neuroinflammation in the corneal nerves, the trigeminal ganglion, and the trigeminal brainstem sensitivity complex have recently been reported and may play an important role in the pathophysiology of DED. Receptor complexes on the axonal membranes of corneal nerves may be promising novel therapeutic targets. Recent studies have shown changes in the both the systemic and local (conjunctival) microbiomes with DED as well as an association of DED with laryngopharyngeal reflux. These new insights into DED suggest new treatment approaches. In hyperevaporative DED typically associated with meibomian gland dysfunction (MGD), hyperkeratinized and obstructed meibomian glands are important treatment targets, and novel techniques may be available soon to better manage patients with MGD. The observation of changes in brain function in patients with DED sheds a completely new light on the pathophysiology of the disease. Increased understanding of the pathogenetic events described above may define novel treatment targets, guide management and may allow customized treatment of DED in the future.

Corneal changes associated with eyelid disease are frequent and can considerably complicate the course of the disease. They can manifest as refraction anomalies, corneal degeneration, ocular surface disease, corneal infiltrates, corneal vascularization and corneal ulceration up to corneal perforation. Pathophysiologically relevant are compressive forces, exposure, trichiasis and distichiasis, eye rubbing, inflammation and infection. A multitude of eyelid diseases is associated with diseases of the cornea including eyelid malposition, eyelid tumors, eyelid infections, allergic eyelid dermatitis, blepharitis, meibomitis, and Meibomian gland disease.Hornhautveränderungen bei Liderkrankungen sind häufig und können den Krankheitsverlauf erheblich komplizieren. Sie können sich als Refraktionsanomalien, Hornhautdegenerationen, Erkrankungen der Augenoberfläche, Hornhautinfiltrate, Hornhautvaskularisationen und Hornhautulzerationen bis hin zur Hornhautperforation manifestieren. Pathophysiologisch sind Druckkräfte, Exposition, Trichiasis und Distichiasis, Augenreiben, Entzündung und Infektion bedeutsam. Eine Vielzahl von Liderkrankungen geht mit Erkrankungen der Hornhaut einher wie Lidfehlstellungen, Lidtumoren, Lidinfektionen, die allergische Liddermatitis und Blepharitis, Meibomitis oder Meibom-Drüsen-Dysfunktion.

The ocular surface flora perform an important role in the defense mechanisms of the ocular surface system. Its regulation of the immunological activity and the barrier effect against pathogen invasion are remarkable. Composition of the flora differs according to the methods of investigation, because the microbiome, composed of the genetic material of bacteria, fungi, viruses, protozoa, and eukaryotes on the ocular surface, differs from the microbiota, which are the community of microorganisms that colonize the ocular surface. The observed composition of the ocular surface flora depends on harvesting and examining methods, whether with traditional culture or with more refined genetic analysis based on rRNA and DNA sequencing. Environment, diet, sex, and age influence the microbial flora composition, thus complicating the analysis of the baseline status. Moreover, potentially pathogenic organisms can affect its composition, as do various disorders, including chronic inflammation, and therapies applied to the ocular surface. A better understanding of the composition and function of microbial communities at the ocular surface could bring new insights and clarify the epidemiology and pathology of ocular surface dynamics in health and disease. The purpose of this review is to provide an up-to-date overview of knowledge about this topic.

The hyperosmolarity of the tear film is an important clinical sign of dry eye disease. It is the most important diagnostic parameter. In addition to the TearLab osmometer (TearLab Corp, San Diego, CA), which has been available for several years, the I-Pen osmometer (I-MED Pharma Inc, Dollard-des-Ormeaux, Quebec, Canada) has been recently marketed. The intention of our study was to compare tear film osmolarities in normal individuals as measured by TearLab and I-Pen.51 healthy subjects (mean age 40.6 years, range 17 - 63 years, 66.7% females) without dry eye disease (ocular surface disease index 13, tear film break-up time 7 s, normal Schirmer test 10 mm/5 min) were included in this study. Tear film osmolarity was measured in the tear meniscus (TearLab) and the palpebral conjunctiva (I-Pen) with a 30 min interval. The osmolarity testing techniques were alternated. Statistical analysis was performed using Wilcoxon tests and Spearman correlations.Mean TearLab osmolarities were 295.1 mosmol/l (right eye), 294.0 mosmol/l (left eye), and 294.6 mosmol/l (mean of both eyes) with a range of 268 to 394 mosmol/l. I-Pen measured mean osmolarites of 301.6 mosmol/l (right eye), 302.5 mosmol/l (left eye), and 302.1 mosmol/l (mean of both eyes) with a range of 276 to 394 mosmol/l. There was a significant difference in tear film osmolarities for the two techniques for both single eyes (p 0.02) and the mean value of both eyes (p 0.001). TearLab and I-Pen measurements did not correlate significantly in any eye (r = 0.27 and r = 0.08 for right and left eye, respectively). With a cut-off value of 308 mosmol/l (as suggested for TearLab), 98.0% of TearLab values and 68.6% of I-Pen values were in the normal range.I-Pen measured significantly higher tear film osmolarities than TearLab. The location of the measurement site in the palpebral conjunctiva could be responsible for this difference. Our results indicate that cut-off values should be changed when using I-Pen for evaluation of tear film osmolarity. Further examinations and studies with greater cohorts of healthy subjects and patients suffering from dry eye disease are necessary.Die Hyperosmolarität des Tränenfilms gilt als bedeutendes klinisches Zeichen des trockenen Auges und als wichtigster singulärer diagnostischer Parameter. Neben dem seit einigen Jahren verfügbaren Ocusense TearLab-Osmometer (TearLab Corp, San Diego, CA) ist seit Kurzem auch das I-Pen-Osmometer (I-MED Pharma Inc., Dollard-des-Ormeaux, Quebec, Kanada) verfügbar. Das Ziel unserer Studie war die Vergleichbarkeit der mittels TearLab- und I-Pen-Osmometer erhobenen Tränenfilmosmolarität bei gesunden Probanden zu untersuchen.51 gesunde Probanden (mittleres Alter 40,6 Jahre, Altersspanne 17 – 63 Jahre, 66,7% weiblich) ohne Beschwerden und Zeichen eines trockenen Auges (Ocular Surface Disease Index 13, Tränenfilmaufrisszeit 7 s, unauffälliger Schirmer-Test 10 mm/5 min) wurden eingeschlossen. Die Tränenfilmosmolarität wurde im Tränenfilmmeniskus (TearLab) und an der subtarsalen Bindehaut (I-Pen) mit einem Zeitintervall von 30 min erhoben. Die Reihenfolge der beiden Osmolaritätsuntersuchungen erfolgte im alternierenden Wechsel. Die statistische Analyse erfolgte mittels Wilcoxon- und Spearman-Tests.Die mittlere TearLab-Osmolarität war 295,1 mosmol/l (rechtes Auge), 294,0 mosmol/l (linkes Auge) sowie 294,6 mosmol/l (bilateral) mit einer Variationsbreite von 268 – 394 mosmol/l. Mittels I-Pen-Osmometer erhobene mittlere Osmolaritätswerte lagen bei 301,6 mosmol/l (rechtes Auge), 302,5 mosmol/l (linkes Auge) und 302,1 mosmol/l bilateral mit einer Variationsbreite von 276 – 394 mosmol/l. Es zeigte sich ein signifikanter Unterschied in den erhobenen Tränenfilmosmolaritäten mit den beiden Techniken für beide Augen einzeln (p 0,02) und beim Mittelwert beider Augen (p 0,001). Die Messungen mit beiden Geräten korrelierten nicht signifikant (r = 0,27 rechts und r = 0,08 links). Bei einem – wie von TearLab vorgeschlagenen – Grenzwert von 308 mosmol/l lagen 98,0% der TearLab-Werte, aber nur 68,6% der I-Pen-Werte im Normbereich.Die mittels I-Pen gemessenen Osmolaritätswerte zeigten sich signifikant höher im Vergleich zu den mit TearLab erhobenen Messwerten. Für diesen Unterschied verantwortlich könnte u. a. die Lokalisation der Messung an der subtarsalen Konjunktiva mit dem I-Pen im Vergleich zur Messung im Tränenfilmmeniskus mit dem TearLab sein. Es könnte daher notwendig sein, den Grenzwert zur Unterscheidung pathologischer Werte von physiologischen Werten bei Messungen der Tränenfilmosmolarität mit dem I-Pen-Osmometer zu ändern. Weiterführende Untersuchungen an einer größeren Kohorte von Normalprobanden sowie bei Patienten mit trockenem Auge sind hierfür notwendig.

Corneal nerves are key components of the physiological system that controls ocular surface homeostasis. The cornea is primarily innervated by the ophthalmic branch of the trigeminal nerves (cranial nerve V), which distend bilaterally from the pons. The nasociliary branch (afferent) of the ophthalmic nerve is sensory for cornea, eyelid and conjunctiva. These nerve fibres play a role in sensing temperature, chemical and mechanical stimuli, and pain, whereas, branches of the facial nerve (cranial nerve VII) contain motor nerves that control blinking and autonomic (sympathetic and a paucity of parasympathetic) fibres that stimulate tear production and secretion via feedback loops between the ocular surface, lacrimal glands and brain. Disruption of these nerves with interruption of neural feedback loops between the ocular surface and lacrimal glands can lead to corneal diseases such as dry eye disease (DED) and neurotrophic keratopathy (NK). Inversely, hypersensitivity of the nerve fibres and/or dysregulation of pain-controlling nervous centres may lead to neuropathic pain. Recently, medications that specifically target regeneration of corneal nerves have started to become available - and considering the high prevalence of diseases associated with corneal nerve dysfunction, these agents promise to fulfil a hitherto important unmet need. In this review, we explore the physiology of corneal nerves, the pathology of corneal nerve diseases and how these relate to neuropathic pain, NK and DED. We also discuss what novel treatments may be useful against diseases involving corneal nerves.

Neurotrophic Keratopathy (NK) refers to a condition where corneal epitheliopathy leading to frank epithelial defect with or without stromal ulceration (melting) is associated with reduced or absent corneal sensations. Sensory nerves serve nociceptor and trophic functions, which can be affected independently or simultaneously. Loss of trophic function and consequent epithelial breakdown exposes the stroma making it susceptible to enzymatic degradation. Nerve pathology can range from attrition to aberrant re-generation with corresponding symptoms from anaesthesia to hyperaesthesia/allodynia. Many systemic and ocular conditions, including surgery and preserved medications can lead to NK. NK can be mild (epithelium and tear film changes), moderate (non-healing epithelial defect) or severe (stromal melting and perforation). Moderate and severe NK can profoundly affect vision and adversely impact on the quality of life. Medical management with lubricating agents from artificial tears to serum/plasma drops, anti-inflammatory agents, antibiotics and anti-proteases all provide non-specific relief, which may be temporary. Contact lenses, punctal plugs, lid closure with botulinum toxin and surgical interventions like tarsorrhaphy, conjunctival flaps and amniotic membrane provide greater success but often at the cost of obscuring sight. Corneal surgery in a dry ocular surface with reduced sensation is at high risk of failure. The recent advent of biologicals such as biopolymers mimicking heparan sulfate; coenzyme Q10 and antisense oligonucleotide that suppress connexin 43 expression, all offer promise. Recombinant nerve growth factor (cenegermin), recently approved for human use targets the nerve pathology and has the potential of addressing the underlying deficit and becoming a specific therapy for NK.

A cystic lesion of the lid margin was excised suspecting basal cell carcinoma. On histology, black-turquoise pigment was seen in the dermis adjacent to the basal cell carcinoma. It was pronounced perivascular, intracellular in macrophages and fibroblasts, but also extracellular as free pigment in the tissue, compatible with an eyelid line tattoo. Typical tissue reactions to tattoo ink, meibomian gland dysfunction after lid margin tattoo, as well as inflammatory reactions in the retina and choroid associated with tattoos distant from the eye are discussed. The correlation of lid tumors and lid margin tattoos seems coincidental.

Das trockene Auge wurde im Mai 2017 vom „Dry Eye Workshop – DEWSII“ neu definiert. Dementsprechend handelt es sich um eine „multifaktorielle Erkrankung der Augenoberflache, gekennzeichnet durch einen Verlust der Homoostase des Tranenfilms und verbunden mit okularen Symptomen“. Die aktuelle Definition umfasst atiologische Faktoren wie eine Instabilitat und Hyperosmolaritat des Tranenfilms, Entzundung und Schadigung der Augenoberflache sowie – als neuen Aspekt im Vergleich zur alten Definition – neuronale Storungen. Aktuelle und zukunftige Therapieoptionen zielen auf die Behandlung der oben beschriebenen pathogenetischen Ereignisse ab. Neue Tranenersatzprodukte, Medikamente und Instrumente zur Tranenfilmstimulation, innovative antientzundliche Therapien, Medikamente zur Beeinflussung der kornealen Innervation und neue Methoden zur Behandlung der meibom-Drusen-Dysfunktion stehen bereits jetzt oder in der nahen Zukunft zur Verfugung.

Purpose: Meibomian gland disease is generally accepted as the leading cause for evaporative dry eye disease (DED). In a previous study, perfluorohexyloctane, a semifluorinated alkane, has been demonstrated to significantly increase tear film breakup time and to reduce corneal fluorescein staining in patients with evaporative DED, thereby vastly reducing dry eye-related symptoms. This study was set up to evaluate perfluorohexyloctane in a larger population of patients with Meibomian gland dysfunction. Methods: Seventy-two patients with Meibomian gland disease and associated dry eye received 1 drop of perfluorohexyloctane 4 times daily during an observational, prospective, multicenter, 6–8-week study. Clinical assessment included best-corrected visual acuity, intraocular pressure, Schirmer test I, tear film breakup time, anterior and posterior blepharitis assessment, number of expressible Meibomian glands, meibum quality and quantity, ocular surface fluorescein staining, lid margin and symptom assessment, and Ocular Surface Disease Index (OSDI©). Results: From the 72 patients recruited, 61 completed the trial per protocol. Nine patients did not apply the medication as recommended and 2 patients were lost to follow-up. Tear film breakup time, corneal and conjunctival fluorescein staining, number of expressible Meibomian glands, and severity of anterior and posterior blepharitis significantly improved after 6–8 weeks of perfluorohexyloctane application. In addition, symptoms improved as demonstrated by a significant decrease of OSDI-values from 37 (±13) to 26 (±16). Conclusions: In concordance with previous findings, 6–8 weeks of topical application of perfluorohexyloctane significantly improves clinical signs of Meibomian gland disease and associated mild to moderate DED.

Dry eye is a prevalent condition and one of the main reasons for patients to seek ophthalmic medical care. A low systemic level of omega fatty acids is a risk factor for dry eye disease (DED). There are two groups of essential fatty acids (EFAs): the omega-6 (n-6) family and the omega-3 (n-3) family. Humans evolved on a diet in which the n-6:n-3 ratio was approximately 1:1, however the current Western diet tends to be deficient in n-3 EFAs and this ratio is typically much higher (approaching 17:1). The metabolism of EFAs generates four new families of local acting mediators: lipoxins, resolvins, protectins, and maresins. These molecules have anti-inflammatory and pro-resolution properties. We present a critical overview of animal model studies and human clinical trials that have shown that dietary modification and oral supplementation could be complementary therapeutic strategies for the treatment of dry eye. Furthermore, we discuss preliminary results of the topical application of n-3 and n-6 EFAs because these molecules may act as natural anti-inflammatory agents with positive changes of the entire ocular surface system.

Dry eye can be caused by a variety of iatrogenic interventions. The increasing number of patients looking for eye care or cosmetic procedures involving the eyes, together with a better understanding of the pathophysiological mechanisms of dry eye disease (DED), have led to the need for a specific report about iatrogenic dry eye within the TFOS DEWS II. Topical medications can cause DED due to their allergic, toxic and immuno-inflammatory effects on the ocular surface. Preservatives, such as benzalkonium chloride, may further aggravate DED. A variety of systemic drugs can also induce DED secondary to multiple mechanisms. Moreover, the use of contact lens induces or is associated with DED. However, one of the most emblematic situations is DED caused by surgical procedures such as corneal refractive surgery as in laser-assisted in situ keratomileusis (LASIK) and keratoplasty due to mechanisms intrinsic to the procedure (i.e. corneal nerve cutting) or even by the use of postoperative topical drugs. Cataract surgery, lid surgeries, botulinum toxin application and cosmetic procedures are also considered risk factors to iatrogenic DED, which can cause patient dissatisfaction, visual disturbance and poor surgical outcomes. This report also presents future directions to address iatrogenic DED, including the need for more in-depth epidemiological studies about the risk factors, development of less toxic medications and preservatives, as well as new techniques for less invasive eye surgeries. Novel research into detection of early dry eye prior to surgeries, efforts to establish appropriate therapeutics and a greater attempt to regulate and oversee medications, preservatives and procedures should be considered.

Purpose The SICCANOVE study aimed to compare the efficacy and safety of 0.1% cyclosporine A cationic emulsion (CsA CE) versus vehicle in patients with moderate to severe dry eye disease (DED). Methods In this multicenter, double-masked, parallel-group, controlled study, patients were randomized (1:1) to receive CsA CE (Ikervis®) or vehicle for 6 months. The co-primary efficacy endpoints at month 6 were mean change from baseline in corneal fluorescein staining (CFS; modified Oxford scale) and in global ocular discomfort (visual analogue scale [VAS]). Results The mean change in CFS from baseline to month 6 (CsA CE: n = 241; vehicle: n = 248) was significantly greater with CsA CE than with vehicle (-1.05 ± 0.98 and -0.82 ± 0.94, respectively; p = 0.009). Ocular discomfort improved similarly in both groups; however, the percentage of patients with ≥25% improvement in VAS was significantly higher with CsA CE (50.2%) than with vehicle (41.9%; p = 0.048). In a post hoc analysis of patients with severe ocular surface damage (CFS score 4) at baseline (CsA CE: n = 43; vehicle: n = 42), the percentage of patients with improvements of ≥2 grades in CFS score and ≥30% in Ocular Surface Disease Index score was significantly greater with CsA CE (p = 0.003). Treatment compliance and ocular tolerability were satisfactory and as expected for CsA use. Conclusion Cyclosporine A CE was well-tolerated and effectively improved signs and symptoms in patients with moderate to severe DED over 6 months, especially in patients with severe disease, who are at risk of irreversible corneal damage.

Purpose To investigate histopathologic, immunohistochemical, and electron microscopic findings in 8 keratoplasty specimens with a history of corneal collagen crosslinking (CXL) for keratoconus. Five new (hitherto unreported) and 3 previously published specimens were analyzed. Methods Corneal buttons of 8 keratoconus corneas (5-114 months after CXL) were compared with 5 keratoconus specimens without CXL and 5 normal corneas for morphological alterations. Corneal buttons were evaluated by light microscopy and immunohistochemistry using antibodies against CD34, PGP 9.5, nestin, telomerase reverse transcriptase, and Ki67 as well as by transmission electron microscopy. Results Keratoconus corneas after CXL showed a significant keratocyte loss (except 1 specimen with an increased keratocyte number), whereas keratoconus corneas without CXL revealed a higher keratocyte density compared with healthy controls. Keratocyte loss could be clinically correlated with corneal opacification and corneal perforation. In corneas after CXL, the remaining keratocytes appeared more polymorphic and revealed a different expression of surface markers similar to keratocytes in corneal scars. The presence of proteoglycans, nerves, and endothelial cells was unaffected by CXL. Conclusions CXL may cause permanent keratocyte loss or repopulation of altered keratocytes, resulting in clinical complications such as corneal opacification or perforation. Despite its good safety profile and high effectiveness in progressive keratoconus, CXL should be performed in accordance with current guidelines strictly adhering to protocol and safety standards.

Background/aimTo assess the treatment effect of 0.1% ciclosporin A cationic emulsion (CsA CE) versus vehicle on signs/symptoms of dry eye disease (DED) in various subgroups (moderate-to-severe DED/severe DED/Sjögren’s syndrome (SS)/SS with severe DED).MethodsPooled data were analysed from two similar phase III studies: SICCANOVE (moderate-to-severe DED) and SANSIKA (severe DED with severe keratitis). In both studies, patients aged ≥18 years received CsA CE 0.1% (n=395) or vehicle (n=339) once daily for 6 months. A composite responder efficacy endpoint (corneal fluorescein staining–Ocular Surface Disease Index (CFS–OSDI) at month 6) was used to evaluate the efficacy of CsA CE in alleviating signs/symptoms of DED (response defined as improvement of ≥2 grades in CFS and ≥30% in OSDI (baseline to month 6)). Human leucocyte antigen-DR (HLA-DR) conjunctival expression was used as a biomarker of ocular surface inflammation.ResultsCsA CE–treated patients were significantly more likely to be CFS–OSDI responders than vehicle-treated patients in the overall (OR 1.66, 95% CI 1.11 to 2.50; P=0.015), severe DED (1.80, 1.04 to 3.19; P=0.038) and SS with severe DED (3.37, 1.20 to 11.19; P=0.030) populations. The difference was not significant for CsA CE versus vehicle for the overall Sjögren’s population (OR 1.77, CI 0.89 to 3.66; P=0.109). CsA CE also significantly reduced median HLA-DR expression versus vehicle at 6 months (P=0.002).ConclusionPooled phase III data indicate CsA CE produced significant improvement in signs/symptoms versus vehicle in patients with moderate-to-severe DED (especially in those with severe keratitis), including patients with SS with severe DED.