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Eye pathology and intraocular pressure in workers of modern petrochemical industry of Azerbaijan
Aghayeva F. A.1*, Ibrahimova S. N.1, Kasimov E. M.1
1National Centre of Ophthalmology named after academician Zarifa Aliyeva, Baku, Azerbaijan
Introduction: Th e petrochemical industry occupies a leading position among the sectors of the Azerbaijan economy. Th us, health care of the oil industry employees that are exposed to the complex of chemical, physical and psychoemotional harmful factors is becoming more socially signifi -cant. In the 1980s academician Zarifa Aliyeva conducted research on oc-cupational eye diseases in workers of petrochemical industry. Taking into account the use of new modern industry technologies continuation of such type of studies are of great interest.
The aim: of this study was to study the prevalence of eye pathology and intraocular pressure (IOP) in workers of modern petrochemical industry of Azerbaijan.
Methods: Analysis of eye condition and IOP was performed in 367 work-ers (734 eyes) of the oil refi nery factory named aft er Heydar Aliyev. All
Results: Two patients were operated for the new device. Th e fi rst patient was a 58 year old with multiple surgeries, including cataract and vitreoreti-nal surgery with following corneal decompensation and status aft er DMEK and multiple re-bubbeling procedures and still had bullous keratopathy.
Preoperative corneal thickness was 780 μm, surgery was uneventful. At the fi rst day already cornea thickness reduced to 593 μm, aft er two weeks cornea thickness was 495 μm and the cornea was clear. Aft er two months the cornea thickness stabilized between 450 and 500 μm.
Patient 2 was an 82 year old with Fuchs’ cornea dystrophy. Aft er phaco and IOL he had cornea decompensation. Aft er DMEK including multiple re-bubbelings the cornea presents still bullous keratopathy. Th e surgery was performed without any problems. Preoperative cornea thickness was be-tween 600 and 650 μm. One day postoperative it was reduced to 497 μm.
Implant detached aft er 25 days was repositioned, since than implant is in place. Aft er 3 months cornea thickness is around 500 μm. Again cornea completely cleared in the center, visual acuity improved by 2 lines.
Conclusion: Implantation of an artifi cial endothelial layer made from hy-drophilic acrylic material resulted in fi rst clearance of corneal pacity and normalization of corneal thickness. Adhesiveness and long term results still need to be evaluated in multi center trials. But fi rst experience are very promising.
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Ten-year graft survival and clinical outcomes after descemet membrane endothelial keratoplasty
Baydoun L.1*, Vasiliauskaitė I.2,3, Oellerich S.2, Ham L.2,3,4, Dapena I.2,3, van Dijk K.2,3, Melles G. R. J.2,3,4,5
1Universitätsaugenklinik Münster, Münster, Germany; 2Netherlands Institute for Innovative Ocular Surgery (NIIOS), Rotterdam, Netherlands; 3Melles Cornea Clinic Rotterdam, Rotterdam, Netherlands; 4Amnitrans EyeBank Rotterdam, Rotterdam, Netherlands; 5NIOS-USA, San Diego, United States Purpose: To assess the 10-year graft survival and clinical outcomes aft er Descemet membrane endothelial keratoplasty (DMEK).
Methods: Aft er excluding the very fi rst 25 DMEK eyes that constitute the technique learning curve, the following 100 consecutive primary DMEK eyes (88 patients) were included in this retrospective analysis. Graft sur-vival, best-corrected visual acuity (BCVA), central endothelial cell densi-ty (ECD), central corneal thickness (CCT) were evaluated up to 10-years postoperatively and postoperative complications were documented.
Results: At 5 and 10 years aft er DMEK, respectively 68 and 57 out of 100 eyes were still available for analysis. Of those eyes, 82 and 89 % reached a BCVA of ≥20/25 (0.8) at 5- and 10 years postoperatively, respectively. Pre-operative donor ECD decreased by 59 % at 5 years and 68 % at 10 years postoperatively. Within 10 years, 4 % of eyes developed allograft rejection, and 6 % of the eyes developed secondary graft failure. Primary graft failures were not observed. Graft survival probability was 0.83 [95 % Confi dence Interval (CI), 0.75–0.92] and 0.79 [95 % CI, 0.70–0.88] at 5- and 10-years postoperatively, respectively.
Conclusions: Most eyes operated in the pioneering phase of DMEK show excellent and stable clinical outcomes with low postoperative complication rates and promising graft longevity over the fi rst decade aft er surgery. Th is suggests that DMEK may be a safe long-term treatment option for eyes with corneal endothelial diseases.
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Eff ect of surgical indication and preoperative lens status on Descemet membrane endothelial keratoplasty outcomes Baydoun L.1*, Birbal R. S.2,3,4, Ham L.2,3,4, van Dijk K.2,3, Jager M. J.5, Oellerich S.2, Melles G. R. J.2,3,4,6
1Universitätsaugenklinik Münster, Münster, Germany; 2Netherlands Institute for Innovative Ocular Surgery (NIIOS), Rotterdam, Netherlands; 3Melles Cornea Clinic Rotterdam, Rotterdam, Netherlands; 4Amnitrans EyeBank Rotterdam, Rotterdam, Netherlands; 5Leiden University Medical Center, Leiden, Netherlands; 6NIOS-USA, San Diego, United States
Conclusions: In these 2 cases, we demonstrated the feasibility of BL trans-plantation during pterygium surgery. Further study on this approach is required.
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First results of a prospective multicentre Phase I/IIa clinical trial on application of purifi ed allogenic ABCB5+ limbal stem cells for treatment of severe limbal stem cell defi ciency
Auff arth G.1*, Meller D.2, Cursiefen C.3, Wasielica-Poslednik J.4, Chodosh J.5
1Universitäts-Augenklinik Heidelberg, Heidelberg, Germany; 2 Universitäts-Augenklinik Jena, Jena, Germany; 3Universitäts-Augenklinik Köln, Cologne, Germany; 4Universitäts-Augenklinik Mainz, Mainz, Germany; 5Department of Ophthalmology, Harvard University, Boston, United States
Background: Limbal stem cell defi ciency (LSCD) is characterized by a loss or defi ciency of limbal stem cells (LSCs), which causes a loss of the regen-eration potential of the cornea, a loss of the barrier function between con-junctiva and cornea and severely impaired vision up to blindness.
Methods: In this study purifi ed LSCs from cadaveric donors were prepared by using the LSC marker ABCB5. Th e aim of this study is to test this LSC-based ATMP in a fi rst-in-human multicenter phase I/IIa clinical trial to evaluate the safety and effi cacy of ascending doses of allogeneic ABCB5+ LSCs for the treatment of LSCD. Th e LSCs are expected to permanently engraft in the limbal stem cell niche, so that the limbal barrier is restored and a transparent cornea is regenerated.
Results: Th e study is planned with 16 LSCD patients in 4 ascending dose groups of 4 patients each. Th e inclusion criteria involve patients with sec-ondary LSCD with vessel penetration of at least 2 quadrants with cen-tral cornea involvement. Cells are topically applied on the entire corneal and limbal area following surgical dissection of conjunctival pannus tis-sue from the corneal surface. To date, 2 patients have been recently treat-ed with the IMP, but as the primary effi cacy endpoint is measured aft er 1 year it is not yet possible to present the primary effi cacy endpoints. In preclinical studies, transplantation of ABCB5+ LSCs in mice with induced LSCD led to normal and transparent human corneas without corneal neo-vascularization.
Th e inclusion criteria involve patients with secondary LSCD with vessel penetration of at least 2 quadrants with central cornea involvement. Cells are topically applied on the entire corneal and limbal area following surgi-cal dissection of conjunctival pannus tissue. To date, 2 patients have been recently treated with the IMP, but as the primary effi cacy endpoint is meas-ured aft er 1 year it is not yet possible to present the primary effi cacy end-points. In preclinical studies, transplantation of ABCB5+ LSCs in mice with induced LSCD led to normal and transparent human corneas with-out corneal neovascularization.
Discussion: ABCB5+ LSCs are a promising new treatment method that could possibly be a permanent cure to patients with LSCD, but before any statistically signifi cant statement about effi cacy is possible, more patients need to be treated and the already treated patients need to be observed for a longer period.
64
CSI Heidelberg: DMEK with artifi cial implant instead of human tissue – Videobeitrag
Auff arth G.1*, Daphna O.1, Koch M.1, Weindler J.1
1Universitäts-Augenklinik Heidelberg, Heidelberg, Germany
Purpose: Descemet membrane endothelial keratoplasty (DMEK) has be-come the most frequent procedure in corneal surgery. Unfortunately avail-ability of human tissue is still a problem. Th erefore artifi cial DMEK lamella would be an interesting alternative.
Methods: We present two patients with a new hydrophilic acrylic artifi cial lamella (EndoArt®, EyeYon Medical, Israel). Th e implant has a diameter of 6 mm, it is implanted and applied with an air gas mixture and similar to a normal DEMK surgical approach.
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Expressionsveränderungen infl ammatorischer Marker (NFkB, iNOS und IL-6) in kornealen Keratokonus-Fibroblasten nach Ribofl avin-UV-A-Bestrahlung
Berger T.1*, Szentmáry N.1,2, Latta L.1, Seitz B.1, Stachon T.1
1Klinik für Augenheilkunde, Universitätsklinikum des Saarlandes UKS, Homburg/Saar, Deutschland; 2Klinik für Augenheilkunde, Semmelweis Universität, Budapest, Ungarn
Einleitung: Das Crosslinking (CXL) stellt eine Th erapiemöglichkeit dar, um die Progression des Keratokonus (KC) zu verlangsamen. Bei CXL ent-steht oxidativer Stress, der möglicherweise zu einer Erhöhung infl amm-atorischer Marker führen kann. Ziel dieser Studie war es, die Expressi-on der infl ammatorischen Marker Nukleärer TranskriptiExpressi-onsfaktor kappa B (NFkB), induzierbare NO-Synthase (iNOS) und Interleukin-6 (IL-6) bei humanen kornealen Fibroblasten (HCF) und Keratokonus-HCF (KC-HCF) nach Ribofl avin-UV-A-Bestrahlung zu bestimmen.
Methoden: Keratozyten wurden aus gesunden und KC-Hornhäuten (je-weils n = 3) isoliert und in Basalmedium mit 5 % fetalem Kälberserum kul-tiviert, was eine Transformation in Fibroblasten bewirkte. Die Zellkultu-ren wurden mit 0,1 % Ribofl avin inkubiert und mit UV-A-Licht für 250 s bestrahlt. Das Expressionsprofi l von NFkB, iNOS und IL-6 wurde mittels qPCR und Western Blot untersucht. Die IL-6-Konzentration im Zellkul-turüberstand und im Zelllysat wurde mit einem ELISA gemessen.
Ergebnisse: Die unbehandelten KC-HCF zeigten im Vergleich zu unbe-handelten HCF eine erhöhte NFkB-mRNA-Expression (p = 0,002). Eine Ribofl avin-UV-A-Bestrahlung führte in der HCF-Gruppe zum Anstieg der NFkB-mRNA-Expression (p = 0,001). Auf Proteinebene wurden keine Unterschiede gemessen. Im Vergleich zu den unbehandelten HCF bestand in den unbehandelten KC-HCF eine 7-fach-erhöhte iNOS-mRNA-Expres-sion (p = 0,140). Nach einer Ribofl avin-UV-A-Bestrahlung konnten in der HCF- und KC-HCF-Gruppe keine Veränderungen der iNOS-mRNA- und Proteinexpression beschrieben werden. Die IL-6-mRNA-Expression war in unbehandelten KC-HCF im Vergleich zu unbehandelten HCF ernied-rigt (p = 0,002). In der HCF-Gruppe wurde die IL-6-mRNA-Expression nach einer Ribofl avin-UV-A-Bestrahlung um das 3,5-fache erhöht, zusätz-lich mit einer Erhöhung der IL-6-Konzentration im Zellkulturüberstand (p = 0,024). Diese Erhöhung trat im Zellkulturüberstand bei KC-HCF nicht auf (p = 0,094). Die IL-6-Konzentration im Zelllysat zeigte sowohl bei HCF (p = 0,115) als auch bei KC-HCF (p = 0,079) keine Unterschiede.
Zusammenfassung: In KC-HCF konnten durch eine Ribofl avin-UV-A-Bestrahlung keine Expressionsveränderungen bei NFkB, iNOS und IL-6 gemessen werden. Veränderungen nach Ribofl avin-UV-A-Bestrahlung wurden lediglich in HCF nachgewiesen. Somit zeigen KC-HCF im Ver-gleich zu HCF eine veränderte Reaktion auf die Ribofl avin-UV-A-Bestrah-lung, was möglicherweise durch vorbestehende pathologische metaboli-sche Funktionen zu erklären ist.
69
Multicolor confocal laser scanning microscopy of the cornea Bohn S.1*,2,3, Sperlich K.1,3, Schünemann M.1,3, Stolz H.2, Guthoff R. F.1,3, Stachs O.1,3
1Augenklinik der Universitätsmedizin Rostock, Rostock, Germany; 2Institut für Physik der Universität Rostock, Rostock, Germany; 3Department Life, Light & Matter, Universität Rostock, Rostock, Germany
Purpose: Although the absorption characteristics of the total cornea are well investigated, the spectrally dependent refl ectance of diff erent cellular structures is yet unknown. Refl ectance images captured at diff erent wave-lengths may potentially reveal diff erent cellular structures. Th erefore, the aim of this work is to investigate the infl uence of diff erent wavelengths on corneal imaging.
Methods: To acquire multicolor images of the cornea, a commercial scan-ning laser ophthalmoscope (SLO) with three distinct laser wavelengths (blue–488 nm, green–518 nm, near-infrared–815 nm) was used. A cus-tom-built objective module was adapted to the SLO to shift the focal plane Purpose: To analyze 6-month results of 1000 consecutive cases that
re-ceived Descemet membrane endothelial keratoplasty (DMEK), and to evaluate if outcomes are infl uenced by surgical indication and preopera-tive lens status.
Methods: A series of 1000 eyes (738 patients) underwent DMEK for Fuchs endothelial corneal dystrophy (FECD; 85.3 %), bullous keratopathy (BK;
10.5 %), failed previous transplant (3.7 %) or other indications (0.5 %).
Main outcome measures were best-corrected visual acuity (BCVA), en-dothelial cell density (ECD), postoperative complications and re-trans-plantations.
Results: At 6 months postoperatively, BCVA outcome did not diff er be-tween FECD and BK eyes (P = 0.170), or bebe-tween phakic and pseudopha-kic FECD eyes (P = 0.066). Donor ECD decrease at 6 months postopera-tively was higher for BK eyes than FECD eyes (46 % versus 39 %, P = 0.001), but similar for phakic and pseudophakic FECD eyes (39 %; P = 0.852). Pri-mary and secondary graft failure occurred in 3 (0.3 %) and 2 eyes (0.2 %), respectively, and 7 eyes developed allograft rejection (0.7 %). Eighty-two eyes (8.2 %) received re-bubbling for graft detachment and re-transplan-tation was performed in 20 eyes (2.0 %). Re-bubbling rates were higher in BK than in FECD eyes (P = 0.022).
Conclusions: DMEK consistently provides excellent short-term results, with similar high visual acuity levels for both FECD and BK eyes. As pre-operative lens status did not infl uence DMEK outcomes, for phakic FECD eyes with a still relatively clear crystalline lens, it may be preferable to pre-serve the lens in a selected group of younger patients, who may still benefi t from their residual accommodative capacity.
67
High endothelial cell density decrease after Descemet membrane endothelial keratoplasty: possible risk factors
Baydoun L.1*, Oellerich S.2, Ham L.2,3,4, Bourgonje V.2,3,4, van Dijk K.2,3, Melles G. R. J.2,3,4,5
1Universitätsaugenklinik Münster, Münster, Germany; 2Netherlands Institute for Innovative Ocular Surgery (NIIOS), Rotterdam, Netherlands; 3Melles Cornea Clinic Rotterdam, Rotterdam, Netherlands; 4Amnitrans EyeBank Rotterdam, Rotterdam, Netherlands; 5NIOS-USA, San Diego, United States Purpose: To assess possible parameters that may aff ect endothelial cell den-sity (ECD) decrease aft er Descemet membrane endothelial keratoplasty (DMEK) by comparing eyes in the low versus high quartile of ECD de-crease over a follow-up period of four years.
Methods: For 351 eyes (275 patients) who underwent DMEK for Fuchs endothelial corneal dystrophy (FECD), donor ECD decrease as compared to preoperative donor ECD was evaluated up to four years aft er surgery.
Eyes with a postoperative ECD decrease in the lower quartile at all avail-able follow-up moments were assigned to Group 1 (n = 51), and those in the upper quartile to Group 2 (n = 42). Multinominal regression was used to assess which covariates were related to the diff erent patterns of ECD de-crease (i. e. high versus low ECD dede-crease).
Results: Within the entire study group, mean ECD decrease was 33(±16)%, 36(±17)%, and 52(±18)% at 1, 6 and 48 months postoperatively, while at those time-points ECD decrease of Group 1 was 12(±7)%, 13(±6)%, and 26(±8)% and of Group 2 was 59(±10)%, 64(±9)%, and 75(±5)%. Partial graft detachment (Odds ratio (OR) 15.41, 95 % confi dence interval (CI) [15.22,15.61], P < 0.01, postoperative complications other than graft de-tachment (OR 1.78, CI [1.69,1.87], P < 0.01) and severity of preoperative FECD (OR 1.77, CI [1.42, 2.13], P < 0.01) showed the strongest relation with diff erent patterns of ECD decrease.
Conclusions: Post DMEK eyes with completely attached graft s and that have been operated in an early stage of FECD may show the lowest ECD decrease aft er surgery.
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Einfl uss der Komplement-Anaphylatoxine auf die corneale Wundheilung und Fibrogenese
Brockmann T.1*,2, Bertelmann E.2, Pleyer U.2
1Klinik und Poliklinik für Augenheilkunde der Universitätsmedizin Rostock, Rostock, Deutschland; 2Klinik und Poliklinik für Augenheilkunde der Charité – Universitätsmedizin Berlin, Berlin, Deutschland
Fragestellung: Degenerative Hornhauterkrankungen, die mit einem mas-siven Verlust der Sehschärfe einhergehen, sind meist das Ergebnis fehlge-leiteter Wundheilung bzw. Fibrogenese und entstehen häufi g als Reaktion ischämischer oder entzündlicher Prozesse. Bis heute gibt es keine kausa-len therapeutischen Ansätze zur Behandlung von fi brotischen Augener-krankungen. Ziel dieses Projekts war es daher, den Einfl uss des Komple-mentsystems, und insbesondere der Komplement-Anaphylatoxine, auf die Wundheilung und Fibrogenese der Hornhaut zu untersuchen.
Methodik: Molekulare Mechanismen der Wundheilung wurden auf geno-mischer und proteogeno-mischer Ebene an humanen erkrankten Hornhäuten, sowie in Zellkultur- und Tierversuchen analysiert, um beteiligte Schlüs-selprozesse zu identifi zieren.
Ergebnisse: An humanen Hornhäuten konnte eine beträchtliche Kom-plementaktivierung sowohl bei infektiösen als auch bei sterilen Kerato-pathien festgestellt werden. Während bei infektiösen KeratoKerato-pathien die klassische Komplementaktivierung vorherrschte, zeigte sich bei sterilen Keratopathien eine alternative Komplementaktivierung. Basierend auf Da-ten aus Zellkultur- und Tierversuchen zeigte sich die zentrale Bedeutung der Komplementfaktoren C5 und C3 mit ihren Spaltprodukten, im Spezi-ellen der Komplement-Anaphylatoxine C3a, C4a und C5a, während der Wundheilung und Fibrogenese. In einem ersten therapeutischen Ansatz konnten wir die anti-infl ammatorische und anti-fi brotische Wirkungen Komplement-Anaphylatoxin-bindender Peptide, welche an C3a, C4a und C5a binden, im Mausmodell der cornealen Laugenverätzung nachweisen.
Dies zeigte sich klinisch durch eine reduzierte Ausprägung der Hornhaut-narbe unter Verwendung des Cowell-Scores als auch in genomischen und proteomischen Expressionsprofi len.
Schlussfolgerungen: Diese Ergebnisse führten zu neuen Erkenntnissen und einem besseren Verständnis grundlegender Pathomechanismen im Rahmen der Wundheilung und Fibrogenese an der Hornhaut, die sich auch auf neue therapeutische Konzepte translatieren lassen. Somit könn-ten Komplement-Anaphylatoxin (C3a/C4a/C5a)-bindende Peptide den Weg für neuartige, wirksame Th erapeutika zur Behandlung fi bro-in-fl ammatorischer Augenerkrankungen ebnen.
72
Lebensqualität von Keratokonus-Patienten im frühen Stadium der Erkrankung
Bußmann N.-H.1*, Linke S. J.1, Vasyl D.1, Katz T.2, Frings A.1, Steinberg J.3
1Univ.-Augenklinik Hamburg, Hamburg, Deutschland; 2Care Vision Germany GmbH, Hamburg, Deutschland; 3zentrumsehstärke, Hamburg, Deutschland Fragestellung: Erfassen der Lebensqualität (VrQol) von Keratokonuspa-tienten im frühen Stadium.
Methodik: Das „frühe Stadium“ des Keratokonus wurde funktionell de-fi niert, es wurde eine bestkorrigierte Sehschärfe (DCVA) von >0,7 Dezi-mal gefordert.
Es wurden Keratokonus-Patienten eingeschlossen, bei denen ein topogra-phisch und funktionell stabiler Befund vorliegt, sowie Patienten, bei de-nen eine Progression verifi ziert und die Indikation zur Quervernetzung der Hornhaut (CXL) gestellt wurde.
In einem weiteren Schritt wurde bei jenen Patienten, die ein CXL erhalten haben 3 Monate nach erfolgtem CXL eine erneute Befunderhebung durch-geführt. Hierbei soll herausgearbeitet werden, inwiefern die therapeutische Intervention Auswirkungen auf die VrQol (zumindest im beobachteten Zeitraum von 3 Monaten) hat. Ein Vergleich mit emmetroper und myoper Kontrollgruppe wurde gemacht.
from the retina to the cornea and to increase the in-plane resolution. Fur-thermore, a piezo actuator is implemented to control the focal plane within the cornea. Measurements on various corneal layers were performed ex vivo on pig and lamb eyes as well as in vivo on human eyes.
Results: In general, imaging could be performed at all investigated wave-lengths and species. Exemplifying the found imaging patterns, the cell bor-ders and nuclei of the human superfi cial epithelium are shown, which have a stronger refl ectance using the blue or green compared to near-infrared light. At deeper layers, almost all cellular structures (nerves, keratocyte nu-clei) are comparable, but the image quality decreases with shorter wave-lengths due to scattering (not shown here). Interestingly, although the en-dothelium is the deepest layer, the cellular structure could only be resolved by the blue or green light and not by the near-infrared light.
Conclusions: Most diff erences in image quality can be attributed to depth- and wavelength-dependent scattering. However, there are also layers that vary in spectral refl ectance of certain cellular structures (e. g. endotheli-um). Th is demonstrates the importance of choosing the right wavelength for certain target structures. In order to answer the question of the optimal wavelength, various aspects have to be considered: (1) corneal target struc-tures (being a compromise between low scatting and high resolution), (2) light hazard and (3) glaring the patient. Th e optimal solution would be a multimodal instrument using diff erent wavelengths.
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Fallbericht: Interstitielle Keratitis im Rahmen einer Symptomtrias Borgardts K.1*, Menzel-Severing J.1, Roth M.1, Guthoff R.1, Geerling G.1, Spaniol K.1
1Universitätsaugenklinik Düsseldorf, Düsseldorf, Deutschland
Einleitung: Das „Cogan-Syndrom“ mit einer okulären, nicht infektiösen Entzündung, Innenohrschwerhörigkeit und vestibulären Einschränkun-gen ist sehr selten. Okuläre Entzündungsreaktionen können sich verschie-denartig äußern. Die interdisziplinäre Zusammenarbeit zwischen Oph-thalmologen, HNO-Ärzten, Internisten und Neurologen ist wichtig für
Einleitung: Das „Cogan-Syndrom“ mit einer okulären, nicht infektiösen Entzündung, Innenohrschwerhörigkeit und vestibulären Einschränkun-gen ist sehr selten. Okuläre Entzündungsreaktionen können sich verschie-denartig äußern. Die interdisziplinäre Zusammenarbeit zwischen Oph-thalmologen, HNO-Ärzten, Internisten und Neurologen ist wichtig für