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Purpose: To compare posterior capsule opacification (PCO) by observing lens epithelial cell growth in the human capsular bag in vitro between conventional lens surgery using phacoemulsification (Phaco) technique and femtosecond laser-assisted lens surgery (FLACS)., Methods: For the in vitro human capsular bag model, 18 cadaver eyes from nine human donors underwent three types of lens surgery. Three groups consisting of six capsular bags were established, that is FLACS, Phaco and extracapsular lens extraction (ECCE). The capsular bag was transferred into equal cell culture conditions after using one of the defined surgical approaches. Cellular growth of lens epithelial cells was observed and photo-documented. The time until full cell-coverage of the capsular bag was measured., Results: The human capsular bag model can be successfully prepared using FLACS. There was no statistically significant difference in time until cell-coverage of the human donor capsular bag in vitro in all three surgical settings (ECCE versus Phaco p = 0.6; ECCE versus FLACS p = 1.0; Phaco versus FLACS p = 1.0)., Conclusions: In our in vitro human capsular bag model, we could not observe a statistically significant difference in PCO formation using different surgical approaches of lens extraction. Therefore, PCO formation might not be attributed to the type of surgery. Furthermore, this study shows that FLACS can be used for the human capsular bag model preparation and validates the human capsular bag model for future research., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Objetivo: Evaluar la rigidez de la membrana limitante interna (MLI) humana y evaluar los posibles cambios de las propiedades mecánicas tras administrar una inyección intravítrea de ocriplasmina para tratar la tracción vitreomacular. Métodos: Este estudio se compone de una serie de casos intervencionales y comparativos de 12 muestras de MLI extraídas mediante cirugía y obtenidas de forma consecutiva de 9 ojos de 9 pacientes después de someterse sin éxito a vitreólisis farmacológica con ocriplasmina. Durante el mismo periodo de tiempo, 16 muestras de otros 13 ojos sin tratamiento con ocriplasmina se obtuvieron mediante vitrectomía y sirvieron como controles. Todos los pacientes presentaron agujeros maculares o tracción vitreomacular y se sometieron a vitrectomía con disección de la MLI tanto con tinción con azul brillante (AB) como sin ella. Todas las muestras se analizaron con un microscopio de fuerza atómica con imágenes de las regiones de 25 × 25 μm. En todas las muestras, se analizaron tanto la parte de la retina como la del vítreo de la MLI. Resultados: La microscopia de fuerza atómica no reveló diferencias significativas en cuanto a elasticidad de las muestras de MLI extraídas de ojos con o sin tratamiento con ocriplasmina. Las áreas onduladas de la parte de la retina presentaron una mayor rigidez que la parte del vítreo de la MLI. La cartografía topográfica tanto de la parte del vítreo como de la retina de la MLI no mostró ninguna alteración aparente de la morfología en ojos tratados con ocriplasmina en comparación con los ojos no tratados. La tinción con azul brillante conllevó un aumento de la rigidez tisular. Conclusiones: Las inyecciones intravítreas de ocriplasmina no varían las propiedades biomecánicas de la MLI humana. No existen pruebas de un posible efecto enzimático que interfiera con la rigidez de esta membrana basal., (© 2017 S. Karger AG, Basel.)

The gold standard for the assessment of the vitreoretinal interface (VRI) is high resolution OCT. It is therefore essential to select the appropriate scan modalities to detect all morphological changes in different diseases, not only at the VRI, but also in all layers of the retina and in the foveal and parafoveal areas. These can be raster scans, radial scans or "en face" scans. Morphological changes at the VRI and especially in the outer retinal layers are good prognostic factors in high resolution OCT for the success of surgery for vitreomacular interface disorders. The following article gives an overview of current OCT procedures as well as correlations between morphological and functional findings., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To evaluate the effects of current hygiene standards for the enucleation of postmortem eyes by investigating the number of microorganisms during subsequent steps of decontamination and tissue processing., Materials and Methods: This prospective, non-randomized cohort study includes 184 postmortem eyes of 92 human donors. Enucleation was performed, according to an ophthalmic surgical procedure. Two groups were generated as follows: right eyes were allocated to group A, left eyes were allocated to group B. In group A, a mucosal disinfectant was used accessorily. Conjunctival smears were taken to examine germ load in both groups before any intervention, in group A after mucosal disinfection, in both groups after transportation of the whole globes in transport fluid, and in both groups after a bath in 0.75% povidone iodine solution for at least 3 minutes just before preparation of the corneoscleral disc. Smears were sent to the local microbiologic laboratory in an aseptic package for testing., Results: All smears showed multiple contaminations (n = 184/184 eyes) before treatment with povidone iodine solution. Contamination was in both groups significantly prevented using the treatment strategy of an at least 3-minute bath in 0.75% povidone iodine solution (n = 1/184 eyes; p < 0.01) As a side effect, almost every eye of group A and none of group B showed brown iodine staining corresponding to corneal epithelial erosion., Conclusions: An aseptic setting for donor enucleation similar to a surgical procedure seems not to influence the outcome of germ colonization. The most effective step to decontaminate donor eyes is to use 0.75% povidone iodine solution for at least 3 minutes.

Background: To evaluate a recently established grading protocol for diabetic macular edema (DME) over the course of intravitreal anti-VEGF treatment with ranibizumab., Methods: Fluorescein angiography images and optical coherence tomography scans before treatment and after 3 monthly applied intravitreal ranibizumab injections were retrospectively graded for each included study eye according to the recently introduced "SAVE" grading protocol ("S"= subretinal fluid; "A"= "area of retinal thickening"; "V"="vitreo-retinal abnormalities"; "E"="etiology of leakage focal versus non-focal") and correlated with best-corrected visual acuity (BCVA) in letters (lett)., Results: Five of the 39 included study eyes had subretinal fluid ("S") before treatment which resolved during treatment. BCVA of study eyes with an initial retinal thickening smaller than one disc diameter ("A") was non-significantly higher compared to patients with a retinal thickening greater than one disc diameter (34.0 ± 17.9 lett versus 25.3 ± 13.3 lett, p=0.236) but became significant during treatment (40.5 ± 10.0 lett versus 28.3 ± 13.1 lett, p=0.004). No difference in BCVA was observed between patients with or without vitreo-retinal abnormalities ("V") before and during therapy. BCVA in patients with focal leakage ("E") was significantly higher than in patients with non-focal leakage before (33.1 ± 12.3 lett versus 23.3 ± 13.3 lett, p=0.017) and during (38.9 ± 10.9 lett versus 26.3 ± 12.6 lett, p=0.002) therapy., Conclusions: Applying the grading protocol "SAVE", focal leakage ("E") was the only retrospectively observed parameter which significantly correlated with a better BCVA before therapy and over the course of treatment in patients with fovea-involving DME.

Purpose: To evaluate theoretical biomechanical advantages of human corneas treated with small incision lenticule extraction (SMILE) compared with femtosecond laser-assisted LASIK (FS-LASIK) Patients and methods: In a prospective, comparative, non-randomized, consecutive case series patients with moderate to high myopia and/or astigmatism underwent corneal refractive surgery. Patients either received standard FS-LASIK or SMILE. Preoperatively and up to 3 months postoperatively data were analyzed including tomography with Pentacam HR, Goldmann tonometry, non-contact tonometry, and deformability of the cornea using an ultra-high-speed camera (Corvis ST). Data were analyzed and p < 0.05 was considered as statistically significant (t-test)., Results: Seventy-three patients (128 eyes) were treated. Forty-eight eyes of 29 patients underwent FS-LASIK and 80 eyes of 44 patients underwent SMILE. Preoperative spherical equivalent (SE) was -3.23 ± 1.64 D (FS-LASIK group) and -4.83 ± 1.63 D (SMILE group) (p < 0.0001). Almost all parameters obtained by Corvis ST between preoperative and postoperative measurements showed significant changes after refractive surgery. Significant changes were seen between both groups postoperatively. However, matched pair subgroup analysis (n = 69; 26 eyes FS-LASIK; 43 eyes SMILE) of eyes with initially equal pachymetry, intraocular pressure, SE, and difference of pre- to postoperative pachymetry (p>0.05), showed no significant changes in parameters measured with Corvis ST (p>0.05)., Conclusions: Corneal biomechanical parameters measured preoperatively with Corvis ST showed significant differences postoperatively in total and in both groups. In subgroup analysis with homogenous groups, FS-LASIK showed no significant changes in biomechanical data measured with Corvis ST compared with SMILE.

Purpose: To assess the stiffness of the human internal limiting membrane (ILM) and evaluate potential changes of mechanical properties following intravitreal ocriplasmin injection for vitreomacular traction., Methods: This is an interventional comparative case series of 12 surgically excised ILM specimens consecutively obtained from 9 eyes of 9 patients after unsuccessful pharmacologic vitreolysis with ocriplasmin. During the same time period, 16 specimens from 13 other eyes without ocriplasmin treatment were harvested during vitrectomy and served as controls. All patients presented with macular holes or vitreomacular traction and underwent vitrectomy with ILM peeling either with or without brilliant blue (BB) staining. All specimens were analyzed using atomic force microscopy with scan regions of 25 × 25 μm. In all specimens, both the retinal side and vitreal side of the ILM were analyzed., Results: Atomic force microscopy revealed no significant differences in elasticity of ILM specimens removed from eyes with or without ocriplasmin treatment. Undulated areas of the retinal side presented stiffer than the vitreal side of the ILM. Topographical mapping of both the vitreal and retinal side of the ILM showed no apparent alteration of the morphology in ocriplasmin-treated eyes compared to untreated eyes. Staining with BB resulted in an increase of tissue stiffness., Conclusions: Intravitreal injection of ocriplasmin does not change biomechanical properties of the human ILM. There is no evidence of a potential enzymatic effect of ocriplasmin interfering with the stiffness of this basement membrane., (© 2016 S. Karger AG, Basel.)

Purpose: The present study investigated the treatment effect of dexamethasone implant (Ozurdex®, group 1) and anti-VEGF injection (Lucentis®, group 2) in course of macular oedema due to retinal vein occlusion in a retrospective, non-randomised case series., Material and Methods: Group 1 comprised 60 patients (31 with CRVO and 29 with BRVO) and group 2 included 52 patients, 27 with CRVO and 25 with BRVO) and both groups were further treated in case of recurrence. Preoperative and in monthly intervals best corrected visual acuity (BCVA), central retinal thickness using SD-OCT (Spectralis, Heidelberg Engineering), intraocular pressure, biomicroscopy status and a fundus photo documentation (Optomap) were evaluated. The primary clinical endpoint was visual acuity 12 months after the first intravitreal therapy, while secondary endpoints included the central retinal thickness change and safety of therapy., Results: In group 1, an increase of BCVA (± standard deviation) of 8.4 (± 1.9) letters was observed in CRVO patients and a gain of 10.7 (± 3.8) letters in BRVO patients after 12 months, while in group 2, an increase of BCVA of 6.9 (± 1.9) letters (CRVO) compared to 12.5 (± 3.7) letters (BRVO) was observed after the same time span. In both groups a significant reduction in retinal thickness was achieved. An increase of intraocular pressure above 5 mmHg was observed in nearly half of the cases In group 1, but was well controlled by conservative antiglaucomatous therapy. We observed a progression of lens opacity in approximately 50 % of the cases in group 1., Conclusion: The treatment with Ozurdex compared to Lucentis appears to provide a trend towards a better although not significant visual acuity increase after 12 months in CRVO patients. A similar trend favouring anti-VEGF treatment with Lucentis was seen in patients with BRVO. However, the lens status and age of the patient should be taken into account when considering a treatment with Ozurdex., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To describe ultrastructure and immunocytochemistry of internal limiting membrane peelings after unsuccessful treatment with ocriplasmin, to compare with untreated eyes, and to correlate with clinical imaging data., Design: Interventional comparative case series., Methods: Internal limiting membrane specimens were removed from 10 eyes with small macular holes and vitreomacular traction during vitrectomy after intravitreal ocriplasmin injection without release of traction or closure of macular holes during follow-up. Based on optical coherence tomography analysis, specimens from 10 other eyes without ocriplasmin treatment served as controls. All specimens were processed as flat mounts for phase-contrast microscopy followed by immunolabeling for fluorescence microscopy and embedding in epoxy resin with serial sectioning for transmission electron microscopy., Results: Despite the absence of contractive epiretinal membranes on optical coherence tomography, we found epiretinal cells and vitreous collagen fibrils on the internal limiting membrane in specimens removed from eyes with and without previous pharmacologic vitreolysis. Immunolabeling revealed glial cells and hyalocytes in macular holes, whereas myofibroblasts were predominant in vitreomacular traction. There was no apparent damage of the vitreoretinal interface after unsuccessful pharmacologic vitreolysis compared to untreated controls., Conclusions: Epiretinal cell proliferation and vitreous collagen fibrils with close adhesions to the internal limiting membrane are not always detectable by optical coherence tomography or may not have been recognized. Since they are associated with unsuccessful ocriplasmin treatment, presence and topography of epiretinal cells and vitreous collagen remnants on the internal limiting membrane should be further elucidated in order to refine criteria and indications for case selection in pharmacologic vitreolysis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the prevalence of dual platelet inhibition in cases of severe retrobulbar hemorrhage following retrobulbar and peribulbar anesthesia., Setting: Department of Ophthalmology, Ludwig-Maximilans Universität, München, Germany., Design: Retrospective study., Methods: Two groups of patients were screened retrospectively over a 5-year period for the inclusion criterion of severe retrobulbar hematoma after retrobulbar or parabulbar injection. The first group consisted of emergency cases referred to the clinic. A second group of patients had received retrobulbar block at the hospital. All cases were collected and screened for the presence of antiplatelet therapy., Results: Among roughly 160 000 patient records screened, 3 patients with grade IV retrobulbar hematoma were identified. Two of these patients were taking dual antiplatelet medications and 2 were on anticoagulation therapy during the time of retrobulbar or peribulbar anesthesia. None of the cases showed single medication platelet inhibition. The visual acuity of all patients stayed low at the 6-month follow-up (1.2 logMAR in 1 patient and no light perception in 2 patients)., Conclusions: Retrobulbar hematoma is a rare but severe complication of retrobulbar anesthesia. With the high prevalence of dual platelet inhibition found in these cases, a prospective controlled trial seems unethical. In these high-risk patients, surgery should be performed under topical anesthesia if possible or general anesthesia if necessary., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2015. Published by Elsevier Inc.)

Purpose: To investigate the effectiveness and safety of a dexamethasone implant (Ozurdex) to treat pseudophakic macular edema (Irvine-Gass syndrome)., Setting: Department of Ophthalmology, Ludwig-Maximilians-University Munich, Munich, Germany., Design: Prospective nonrandomized study., Methods: Preoperatively and in 12 monthly postoperative intervals, a complete ophthalmic examination was performed in study patients, including measurement of corrected distance visual acuity (CDVA) using the standard Early Treatment Diabetic Retinopathy Study chart, intraocular pressure, foveal thickness using spectral-domain optical coherence tomography (SD-OCT), and retinal sensitivity (mean defect depth) using microperimetry. Morphological aspects of the inner segment-outer segment junction and visual function were correlated., Results: Twenty-three eyes (23 patients) with pseudophakic macular edema after uneventful cataract surgery were included. The mean duration of macular edema before treatment with a dexamethasone implant was 5.4 months (range 2 to 8 months). The CDVA increased in all patients from 30.2 letters ± 4.3 (SD) at baseline to 50.4 ± 4.9 letters at 12 months (P = .0016), regardless of the time of macular edema duration. Foveal thickness decreased from 520.8 ± 71.4 μm to 232.7 ± 26.6 μm (P < .002). Retinal sensitivity (mean defect depth) increased significantly over a 12-month follow-up, correlating positively with a restored inner segment-outer segment junction on SD-OCT analyses. No relevant adverse events were reported, and 9 recurrences occurred with a peak after 3 months and required a second dexamethasone implant injection., Conclusion: The dexamethasone implant was safe and effective in treating pseudophakic macular edema regardless of the duration of the edema., Financial Disclosure: Drs. Mayer and Haritoglou are consultants to Allergan, Inc. No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare immunocytochemical and ultrastructural characteristics of "lamellar hole-associated epiretinal proliferation" in lamellar macular holes with "conventional epiretinal membrane" in macular pseudoholes., Design: A consecutive observational case series, laboratory investigation., Methods: We analyzed surgically excised flat-mounted internal limiting membrane specimens and epiretinal membrane specimens removed from 25 eyes of 25 patients with lamellar macular holes (11 eyes) and macular pseudoholes (14 eyes) using interference and phase-contrast microscopy, immunocytochemistry, and transmission electron microscopy. By spectral-domain optical coherence tomography, epiretinal material of homogenous reflectivity without contractive properties was categorized as lamellar hole-associated epiretinal proliferation, whereas tractional epiretinal membranes presenting contractive properties were termed conventional epiretinal membrane., Results: Lamellar hole-associated epiretinal proliferation was seen in 73% of eyes with lamellar macular hole. Eyes with macular pseudohole presented with conventional epiretinal membrane. In lamellar hole-associated epiretinal proliferation, positive immunoreactivity for anti-glial fibrillary acidic protein, hyalocyte markers, and anti-collagen type I and III was seen. In contrast, specimens of macular pseudoholes were positive for α-smooth muscle actin and anti-glial fibrillary acidic protein, predominantly. Cellular ultrastructure showed that lamellar hole-associated epiretinal proliferation of lamellar macular holes mainly consisted of fibroblasts and hyalocytes, whereas myofibroblasts dominated in conventional epiretinal membranes of macular pseudoholes., Conclusions: Cells within lamellar hole-associated epiretinal proliferation appear to originate from vitreous and possess less contractive properties than cells of conventional epiretinal membranes. Our findings point to differences in pathogenesis in a subgroup of lamellar macular holes presenting lamellar hole-associated epiretinal proliferation on the retinal surface., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To determine whether erufosine alone or erufosine-loaded intraocular lenses (IOLs) can inhibit growth of human lens epithelial cells after a single administration in the human capsular bag model., Setting: Laboratory for Cell Biology, Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany., Design: Experimental study., Methods: Sixteen human cadaver eyes had sham cataract surgery. The capsular bag was transferred into cell culture. The tissue was exposed to the half maximum inhibitory concentrations of erufosine alone for 72 hours; solvent-only tissue served as a control. Erufosine is a potent inhibitor of phosphoinositide-3-kinase, a downstream kinase with major implications in posterior capsule opacification (PCO) pathogenesis. The IOLs were soaked with erufosine and implanted in the capsular bags; unsoaked IOLs served as controls. For both settings, the time until confluence of the capsular bag was measured. Cell growth was observed and photodocumented., Results: Erufosine as a single therapeutic agent increased the time until confluence of the capsular bag, but not significantly compared with the control. When IOLs were soaked with erufosine, a long-term prophylactic effect was observed in this organ model for PCO, which is known to closely reflect the clinical situation., Conclusion: Erufosine-soaked IOLs effectively inhibited PCO formation as seen in long-term organ culture and might become of clinical relevance., Financial Disclosures: Drs. Kampik and Eibl-Lindner are inventors of IOLs treated with alkylphosphocholines for pharmacological after-cataract prophylaxis, patent international application PCT/EP2010/051490. No other author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To report on epiretinal membrane (ERM) characteristics and photoreceptor layer integrity of lamellar macular holes (LMHs) and macular pseudoholes (MPHs), and to compare with clinical course in operated and untreated eyes., Methods: We consecutively reviewed the charts of patients with LMH and MPH between 2003 and 2013. For clinical analysis, we included 87 eyes (48 with LMH, 39 with MPH) with a minimum follow-up of 6 months. Of these, we included 64 eyes (37 with LMH, 27 with MPH) for high-resolution spectral domain optical coherence tomography analysis with examinations fulfilling the required resolution and quality of optical coherence tomography images. Epiretinal membranes were termed "typical tractional ERM" if presenting with contractive properties, or "atypical epiretinal tissue" if presenting as epiretinal material of homogeneous medium reflectivity without contractive properties. Integrity or discontinuity of the inner and outer segment (IS/OS) and the external limiting membrane (ELM) was evaluated by differentiating between "defect present" and "defect absent.", Results: In eyes with LMH, atypical epiretinal tissue presented in 29%, typical tractional ERMs were seen in 57%, and a combination of both in 14%. In contrast, eyes with MPH rarely presented atypical epiretinal tissue, and typical tractional ERMs were found in 89%. Comparing cases with LMH, eyes with atypical epiretinal tissue showed significantly more defects of the IS/OS and the ELM than eyes with typical tractional ERM. Both IS/OS and ELM defects correlated with a significant lower best-corrected visual acuity. Defects of the IS/OS were seen in 41% of LMH and 11% of MPH. Defects of the ELM revealed in 27% of LMH and in 11% of MPH. Operated eyes with disrupted IS/OS but intact ELM had significant better best-corrected visual acuity than eyes with defects in both layers., Conclusion: Atypical epiretinal tissue is related to the presence of photoreceptor layer defects and to poor visual acuity. It seems that integrity of the ELM is most important for functional recovery after surgery in both LMH and MPH. The presence of atypical epiretinal tissue in eyes with LMH may represent differences in the pathogenesis compared with MPH, and might have therapeutic implications for the proceeding with macular surgery in selected cases.

Purpose: Posterior capsule opacification (PCO) occurs as a common complication after cataract surgery. Gefitinib is a selective inhibitor of the epidermal growth factor receptor (EGFR) which represents a potential pharmacological target for PCO prevention. In this in vitro study, we assessed the effect and biocompatibility of Gefitinib in PCO prophylaxis., Methods: The effect of Gefitinib on the key pathological features of PCO was assessed in vitro. We determined growth in the human capsular bag model, prepared from sixteen cadaver eyes that underwent sham cataract surgery. Furthermore, two lens epithelial cell lines, HLE-B3 and FHL-124, were used to determine concentration-based effects on cell proliferation. In addition, cell-migration, matrix-contraction, and cell spreading were investigated. To exclude toxic concentrations, Gefitinib was assessed for its biocompatibility on six different human ocular cell types from the anterior and posterior segment of the eye., Results: Gefitinib significantly increased the time until confluence of the capsular bag compared to controls (p < 0.001)). In both human lens epithelial cell lines (HLE-B3 and FHL-124), proliferation decreased significantly and as equally strong after incubation with Gefitinib (p < 0.001), as did chemotactic migration (p = 0.004), matrix contraction (p = 0.001), and cell-spreading (p = 0.001). At the IC50 concentration, Gefitinib was well tolerated by six different human ocular cell types of the anterior and posterior segment., Conclusion: The specific EGFR inhibitor Gefitinib might become of clinical relevance in PCO prophylaxis as it attenuated cellular growth and other pathological PCO factors in the ex vivo human capsular bag model and in two human lens epithelial cell lines, while showing good biocompatibility in vitro.

Purpose. To describe morphology of lamellar hole-associated epiretinal proliferation (LHEP) removed from eyes with lamellar macular holes (LMH). Methods. Based on optical coherence tomography data, 10 specimens of LHEP were removed from 10 eyes with LMH during standard vitrectomy. Specimens were prepared for correlative light and electron microscopy (CLEM) using an immunonanogold particle of 1.4 nm diameter that was combined with a fluorescein moiety, both having been attached to a single antibody fragment. As primary antibodies, we used antiglial fibrillary acidic protein (GFAP), anti-CD45, anti-CD64, anti-α-smooth muscle actin (α-SMA), and anticollagen type I and type II. Results. In LHEP, GFAP-positive cells possess ultrastructural characteristics of fibroblasts and hyalocytes. They represent the major cell types and were densely packed in cell agglomerations on vitreous collagen strands. Epiretinal cells of LHEP rarely demonstrated contractive properties as α-SMA-positive myofibroblasts were an infrequent finding. Conclusion. CLEM indicates that epiretinal cells in LHEP might originate from the vitreous and that remodelling processes of vitreous collagen may play an important role in pathogenesis of eyes with LMH.

Purpose. To assess functional and morphological alterations following video-documented surgery for epiretinal membranes. Methods. Forty-two patients underwent video-documented 23-gauge vitrectomy with peeling of epiretinal (ERM) and inner limiting membrane (ILM). Patient assessment was performed before and 3 and 6 months including best corrected visual acuity (BCVA), slit lamp biomicroscopy, SD-OCT, and central 2° and 18° microperimetry. In addition, all video-documented areas of peeling on the retinal surface were evaluated postoperatively using an additional focal 2° microperimetry. Retinal sensitivity and BCVA were correlated with morphological changes (EZ and ELM) in the foveal region and in regions of membrane peeling. Results. Overall, BCVA increased from 0.6 (±0.2) to 0.2 (±0.2) logMAR after 6 months with an increase in retinal sensitivity (17.9 ± 2.7 dB to 26.8 ± 3.1 dB, p < 0.01). We observed a significant correlation between the integrity of the EZ but not of the ELM and the retinal sensitivity, overall and in peeling areas (p < 0.05). However, no significant correlation between alterations in the area of peeling and overall retinal sensitivity regarding visual acuity gain could be observed after 6 months (p > 0.05). In contrast, overall postoperative retinal sensitivity was significantly decreased in patients with a visual acuity gain lower than 2 lines (p < 0.05) correlating with EZ defects seen in OCT. Conclusions. Mechanical trauma of epiretinal membrane and ILM peeling due to the use of intraocular forceps may affect the outer retinal structure. Nevertheless, these changes seem to have no significant impact on postoperative functional outcome.

Optical coherence tomography (OCT) is the standard examination for assessment of the vitreoretinal interface (VRI); therefore, it is essential to select the appropriate scan modalities to detect the total amount of morphological changes, not only at the VRI but also in all layers of the retina and in both the foveal and parafoveal areas. For the success of a surgical intervention in the treatment of vitreomacular interface disorders, morphological changes, especially in the outer retinal layers, have been determined to be of prognostic interest in high-resolution OCT. This article gives an overview of current OCT examination procedures as well as correlative aspects of morphological and functional findings.

Purpose: To retrospectively evaluate the re-injection interval, efficacy and safety of dexamethasone (DEX) intravitreal implant 0.7 mg in the treatment of macular oedema (ME) due to retinal vein occlusion (RVO) in Germany in 2009-2012., Methods: Retrospective, multicentre, anonymised observational study of data collected from the first DEX implant 0.7 mg injection through 3-6 months following the last injection. Data were included if the patient was >18 years old, had a diagnosis of ME secondary to branch or central RVO, and received at least 2 DEX implant 0.7 mg injections during routine practice., Results: Data from 87 patients were analysed. Mean time to re-injection between first and second treatments was 5.03 months in the total RVO population, and 5.46 and 4.52 months for the branch and central RVO subpopulations, respectively. An intraocular pressure increase of >25 mm Hg was recorded in 20% of patients, and 34% of patients began treatment with anti-glaucoma medication, but surgery was not needed for this condition., Conclusions: DEX implant 0.7 mg was found to be well tolerated and effective with repeat treatments in clinical practice., (© 2014 S. Karger AG, Basel.)

Background: The pathogenesis of central serous chorioretinopathy (CSC) is still poorly understood. An animal model of CSC proved that the mineralocorticoid receptor [1] of the choroid also plays a role in CSC. Since there is still no evidence-based therapy for non-self-limiting CSC, this case series evaluates the effect of oral spironolactone in CSC patients., Methods: In this interventional, uncontrolled, prospective case series, we present 18 consecutive CSC patients. Patients were treated with spironolactone 25 mg twice daily (Spironolacton AL® 50 mg, ALIUD PHARMA) for up to 12 weeks. Follow-up examinations with BCVA, OCT, and EDI-OCT were performed at 1, 2, and 3 months after starting the treatment. Main outcome measure was a change of subretinal fluid (SRF) (in micrometers) measured by optical coherence tomography. Secondary outcome was a change in central retinal thickness (CRT) (in micrometers) measured by OCT and a change in BCVA., Results: The subretinal fluid (SRF; mean) decreased from 219 μm (baseline) to 100 μm (visit 3) (difference 119 μm). Total central retinal thickness (CRT; mean) decreased from 405 μm before treatment (baseline) to 287 μm after treatment (difference 118 μm). The BCVA (in logMAR; mean) increased from 0.32 at baseline to 0.20 at visit 3., Conclusion: Our case series could confirm a positive influence of spironolactone on the course CSC. Longer follow-up with a larger number of cases could provide more data about the long-term efficiency, recurrences, and safety of this well-tolerated and non-invasive treatment option of CSC.

Background: This study was designed to evaluate the effectiveness and safety of femtosecond laser-assisted lens surgery depending on interface design and laser pulse energy settings., Methods: In this non-randomized, consecutive case series200 eyes underwent femtosecond laser-assisted (LenSx, Alcon) lens surgery between November 2012 and June 2013. Group 1 consisted of 85 eyes with 60 cataracts and 25 refractive lens exchanges (RLE) which were treated with a curved direct contact interface, and group 2 consisting of 115 eyes with 72 cataracts and 43 RLEs treated with a modified interface using an additional soft contact lens (SoftFit™, Alcon) between the corneal surface and the interface. The degree of opacity of the lens in cataract eyes was measured with a Scheimpflug camera. Afterwards, phacoemulsification was performed with intraocular lens (IOL) implantation in all eyes. Primary endpoints were the effective phacoemulsification time (EPT), the average laser treatment time and the occurrence of intraoperative complications., Results: The mean EPT in group 1 was 1.62 ± 1.12 s (cataract 1.94 ± 1.31 s, RLE 1.29 ± 1.01 s) and in group 2 the mean EPT was 1.66 ± 0.92 s (cataract 1.98 ± 1.28 s, RLE 1.33 ± 1.22 s, p = 0.32 between groups). The laser treatment lasted on average 48.90 ± 2.45 s (group 1) and 49.70 ± 2.87 s (group 2) with an average lens fragmentation thickness of 3401.48 ± 401.12 µm (all groups). In four cases of group 1, a second applanation of the interface was necessary. Furthermore, one anterior capsule tear, 39 cases of intraoperative wrinkling of the corneal surface and 21 cases in which the corneal incision had to be opened manually were documented in group 1. In group 2 no second applanation of the interface, no anterior capsule tears and no corneal wrinkling but 9 cases with a manual opening of corneal incisions were documented (p < 0.01 between groups)., Conclusion: The minor intraoperative complications of the femtosecond laser technique investigated could be significantly reduced using an optimized interface and reduced laser pulse energy.

Background: To evaluate the fulfillment of retreatment criteria in recurrent neovascular age-related macular degeneration (nAMD) for a pro-re-nata treatment regime with ranibizumab in routine clinical care., Methods: Data from patients with treatment-naive nAMD were analysed retrospectively. As an 'upload', all patients had received three-monthly intravitreal ranibizumab injections in a university eye hospital and were then seen by ophthalmologists in private practice who referred them back in case of recurrence. Recurrence was defined as a decrease of visual acuity (VA) of one line or more (functional retreatment criteria), a central retinal thickness (CRT) increase of at least 100 µm upon Optical Coherence Tomography (OCT) examination (morphological retreatment criteria) or a new macular haemorrhage (clinical retreatment criteria)., Results: We included 92 patients (36 men and 56 women). The mean VA before retreatment of a recurrence was -0.63 ± 0.33 logMAR and improved significantly (p<0.001) by 0.10 ± 0.16 logMAR to -0.53 ± 0.28 logMAR thereafter. Mean CRT before retreatment was 278.07 ± 87.56 µm and decreased significantly (p<0.001) by 71.22 ± 106.93 to 206.85 ± 60.30 µm. Evaluation of the fulfillment of retreatment criteria revealed functional retreatment criteria in 82.6% of patients. However, upon re-evaluation of VA using Early Treatment Diabetic Retinopathy Study (ETDRS) charts in the treatment centre, mean decrease of VA was 10 letters as compared with the end of upload therapy. All patients presented an increased CRT when treated for recurrence of nAMD (mean increase 69.47 µm), but the morphological retreatment criteria (CRT increase of 100 µm or more) were fulfilled in only 44.4% of patients upon Spectral Domain OCT (SD-OCT) evaluation in the treatment centre., Conclusions: In a routine clinical care, evaluation of VA using ETDRS charts seems to be more sensitive than Snellen VA testing. Quantitative OCT-based retreatment criteria (eg, increase of CRT of 100 µm or more) appear to be not sensitive enough in a clinical setting with referring ophthalmologists., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: To compare inflammatory cell response and morphological aspects of femtosecond laser-created corneal incisions., Setting: Department of Ophthalmology, Goethe-University, Frankfurt am Main, Germany., Design: Experimental study., Methods: In 16 of 22 human corneoscleral buttons, clear corneal tunnel incisions were created using a femtosecond laser (Lensx) with 7 μJ laser pulse energy on the outer periphery and manually using a phaco knife on the respective opposite side (180 degrees). In 6 corneas, no treatment was performed (controls). Corneas were then kept in organ culture for 12 or 48 hours, and the inflammatory reaction was evaluated using standard immunofluorescence analyses for monocytes (CD11b) and for dendritic cells (HLA-DR). For morphological analyses and apoptosis, van Gieson staining and terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling was performed., Results: There were no statistically significant differences in inflammatory cell response between femtosecond laser corneal incisions and manually performed incisions. Apoptosis was significantly more pronounced in the femtosecond incisions. The ratio of dendritic cells between femtosecond incisions and manual incisions was 1:2 (12 hours and 48 hours; P=.07), the ratio of monocytes was 1:2 (12 hours and 48 hours; P=.08), and the ratio of apoptotic cells was 1:5 (12 hours) and 1:6 (48 hours) (P=.02). Femtosecond laser incisions showed a more sawtooth-like cutting edge than manual incisions., Conclusions: Femtosecond laser-created corneal incisions in human corneas showed no differences in inflammatory cell response but a significantly higher cell death rate than manually performed incisions, indicating an upregulated postoperative wound-healing response., Financial Disclosure(s): Proprietary or commercial disclosures are listed after the references., (Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate cell death and ultrastructural effects on capsulotomy specimens derived from femtosecond laser-assisted cataract surgery., Methods: In 26 eyes, an anterior capsulotomy was performed using a femtosecond laser. In 10 eyes (group 1), the laser-pulse energy was set to 15 μJ using a rigid curved interface and in another 10 eyes (group 2) to 5 μJ using a curved interface combined with a soft contact lens. The control group (6 eyes, group 3) underwent manual anterior capsulorhexis using forceps. All extracted capsule specimens underwent cell death analysis using the TUNEL kit, ultrastructural analyses using atomic force microscopy (AFM), and scanning electron microscopy (SEM). Counterstaining was performed with 4',6-diamidino-2-phenylindol (DAPI) and hematoxylin-eosin (HE)., Results: Cell death was found in all capsule specimens along the cutting edge but was significantly more pronounced in group 1. DAPI and HE staining showed regular epithelial cell distribution with a demarcation line along the cutting edge of both laser groups, which was more pronounced in group 1. In AFM analysis, laser spot size in the femtosecond laser groups were in accordance with the preoperative planned size (P < 0.01). Cutting edges in SEM observations were smoother and more roundly shaped using 5 μJ (group 2)., Conclusions: Cutting edges of femtosecond laser-performed capsulotomies are precise and laser spot lesions are within planned size. Cell death reaction depends on the laser pulse energy settings and can be reduced to the level observed in a manual capsulorhexis.

Background: To ascertain the morphological changes in the edge structure of femtosecond laser-derived capsulotomy specimens using varying patient interfaces and different laser pulse energies., Methods: In this experimental clinical study femtosecond laser-assisted capsulotomies were performed in 30 eyes using the LenSx femtosecond laser (LenSx, Alcon, Fort Worth, TX, USA). Surgery was performed using either a rigid curved contact interface (group 1, 15 eyes) or a curved interface with a soft contact lens between cornea and interface (group 2, 15 eyes). The laser pulse-energy was set to 15 μJ in group 1 and to 5 μJ in group 2. After the removal of the anterior capsule, half of the specimens from each group underwent either further staining for light microscopy (LM) or scanning electron microscopy (SEM). Cell configuration, capsule shape, and edge abnormalities were analysed on a morphological basis., Results: LM showed continuous anterior capsular incisions with a prominent demarcation line along the cutting edge, as well as tags and bridges, which were more pronounced in group 1. SEM revealed further smaller microgrooves and sawtooth patterns in both groups, and a more regular demarcation line configuration in group 2., Conclusion: A soft contact lens interface with a subsequent laser pulse energy of 5 μJ resulted in fewer tags and bridges, smoother edges, and a more regular and thinner demarcation line on specimens edges of femtosecond laser-performed capsulotomies compared to a rigid curved 15 μJ interface application.

Purpose: To compare effective phacoemulsification time in cataract surgery performed by manual phacoemulsification vs femtosecond laser-assisted lens fragmentation., Design: Retrospective, consecutive, nonrandomized, comparative case series., Methods: The setting was the Department of Ophthalmology, Goethe-University, Frankfurt, Germany. The study population included 150 eyes of 86 patients with senile cataract. In the intervention, 88 eyes (group 1) underwent femtosecond laser-assisted surgery (corneal incisions, capsulotomy, lens fragmentation) using the LenSx platform (Alcon) and residual lens work-up with pulsed ultrasound energy (Infiniti Vision System; Alcon). In 62 eyes (group 2), complete cataract removal was performed with phacoemulsification only, using pulsed ultrasound energy with the same device (Infiniti). Nucleus staging (Pentacam nucleus staging; PNS) was evaluated using Pentacam HR (Oculus); endothelial cell density was measured using specular microscopy (NonCon Robo). The main outcome measures were as follows. Mean preoperative PNS staging was assessed using an automatic ordinal scaling (PNS-O, grades 0-5) and a manually defined density grid derived from Scheimpflug imaging (PNS-P [%]). Effective phacoemulsification time and endothelial cell loss were evaluated in both groups., Results: Preoperative PNS-O and PNS-P showed no significant difference between groups (P = 0.267). Overall mean effective phacoemulsification time was significantly lower in group 1 (1.58 ± 1.02 seconds) compared to 4.17 ± 2.06 seconds in group 2 (P = 0.001). Effective phacoemulsification time was significantly lower in group 1 for all PNS-O stages (P < 0.001). With increasing preoperative PNS-P, effective phacoemulsification time increased in both groups; however, this gain was noticeably, but not significantly, lower in group 2. Endothelial cell loss was significantly lower in group 1 (P = 0.02)., Conclusions: Femtosecond laser-assisted cataract surgery allows a significant reduction in effective phacoemulsification time, which correlates positively with the preoperative lens opacity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The femtosecond laser technology continues its progress in ophthalmology and now also plays an increasingly important role in lens surgery. Using this technology it is possible to create corneal sections and to perform capsulorhexis and lens fragmentation. There are currently four instruments on the market with more to follow. The individual benefits and also critical issues are presented and the results of current studies are discussed.

Background: The purpose of this study is to establish the correlation between functional and morphological aspects before and 12 months after macular hole surgery., Methods: In this prospective, interventional, consecutive study 16 eyes of 16 patients were included. All eyes received a successful transconjunctival 23-gauge vitrectomy with ILM peeling after initial diagnosis and maximum duration of symptoms of two months. Preoperatively and 3, 6 and 12 months postoperatively determinations of best-corrected visual acuity (logMAR), a 10° microperimetry (MP-1) and a spectral-domain based optical coherence tomography (SD-OCT) examination were performed. The photoreceptor layer (inner and outer segment, IS/OS) was evaluated based on SD-OCT images and correlated with data assessed by microperimetry analysis in the foveal and parafoveal region., Results: After three months a stabilisation of BCVA with regeneration of the IS/OS line, an improvement of the fixation behaviour and the macular sensitivity could be observed. A significant restitution of the IS/OS line was observed after 12 months. Best corrected visual acuity, mean overall macular sensitivity and fixation improved significantly within the twelve month observation period (p < 0.05). Comparison of patients with at least two lines of visual acuity gain with patients having less than two lines of visual acuity gain 12 months after surgery showed no statistically significant difference in regeneration of the IS/OS integrity in the fovea (p = 0.433), but a difference was seen in the parafoveal region. A postoperative visual acuity gain of at least two lines was significantly more often seen in eyes with postoperative continuous IS/OS line in the parafoveal sectors compared to eyes with persistent IS/OS defects (p < 0.02)., Conclusion: Correlations of morphological and functional improvements can be observed after successful micro-invasive macular hole surgery. The extent of the preoperative IS/OS defect, particularly in the parafoveal region, is a good predictive parameter for the postoperatively obtained macular sensitivity. The prediction of the postoperative visual acuity should not be made on the basis of a single clinical, anatomic finding., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To study the microanatomic edge structures of anterior lens capsule specimens derived from manual and femtosecond laser-assisted capsulotomies., Setting: Department of Ophthalmology, Goethe-University, Frankfurt, Germany., Design: Experimental study., Methods: Of 60 eyes with lens removal and intraocular lens implantation, 30 received a manual capsulotomy and 30 received a femtosecond laser-assisted capsulotomy (Lensx, rigid curved interface, pulse energy 15 μJ, spot separation 4 μm, layer separation 3 μm). After anterior capsule removal, tissues were immediately fixed in 4.5% formalin. Approximately 30 minutes after fixation, the tissues were removed from the fixation containers and air dried for at least 2 hours. Fifteen capsules in each group had further staining for light microscopy (LM). The surface of the capsulotomy edge was the primary focus of LM and scanning electron microscopy (SEM). Cell configuration, capsule shape, and abnormalities were evaluated., Results: Subjective LM and SEM analysis showed smooth edges at all magnifications, no cell destruction, and cells up to the cutting edge in the manual capsulotomy group. Light microscopy demonstrated almost continuous anterior capsule incisions of the femtosecond laser-assisted capsulotomy, a prominent demarcation line along the cutting edge, and several tags and bridges. Scanning electron microscopy showed microgrooves and valley- and mountain-like structures as signs of the photodisruption process., Conclusion: Compared with manual procedures, curved, rigid interface femtosecond laser-assisted capsulotomy specimens using 15 μJ pulse energy showed tags, bridges, rougher edges, and demarcation lines on the capsulotomy edges on SEM but subjectively estimated a more round shape on LM., Financial Disclosures: Mr. Klaproth received travel reimbursements and/or lecture fees from Alcon Laboratories, Inc., Rayner Intraocular Lenses Ltd., and Oculus GmbH. Dr. Kohnen received travel reimbursements, grant support, and/or lecture fees from Alcon Laboratories, Inc., Abbott Medical Optics, Inc., Bausch & Lomb, Carl Zeiss Meditec AG, Neoptics AG, Rayner Intraocular Lenses Ltd., and Schwind eye-tech-solutions GmbH and Co. KG; he is a consultant to Alcon Laboratories, Inc., Carl Zeiss Meditec AG, Rayner Intraocular Lenses Ltd., and Schwind eye-tech-solutions GmbH and Co. KG. No other author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy and safety of a dexamethasone implant (Ozurdex) alone or in combination with bevacizumab., Methods: Sixty-four eyes were prospectively investigated. Group 1 (22 central retinal vein occlusion (CRVO) and 16 branch retinal vein occlusion (BRVO)) was treated with Ozurdex alone, and group 2 (14 CRVO and 12 BRVO) was treated with three consecutive bevacizumab injections followed by Ozurdex. Recurrences were treated with Ozurdex only. Patients were seen preoperatively and thereafter in monthly intervals. The primary end point was best-corrected visual acuity (BCVA) at 12 months., Results: In group 1, BCVA improved by 6.6 (±1.7) letters in CRVO and 7.8 (±2.9) in BRVO patients, and in group 2 by 9.8 (±1.0) vs 9.4 (±2.1) letters. A significant difference was only seen between CRVO patients in group 1 and 2 at 12 months (P<0.05). Recurrence after the first Ozurdex injection occurred after 3.8 (CRVO) and 3.5 months (BRVO) in group 1, vs 3.2 and 3.7 months in group 2. Elevated intraocular pressure (>5 mm Hg) was measured in approximately 40% cataract progression requiring surgery in about 50% of eyes after three Ozurdex injections., Conclusion: Combined treatment showed slightly better functional outcome for CRVO patients. Increased intraocular pressure and cataract progression was frequent and should be considered when an individual treatment is planned.

Purpose: To compare the inflammatory cell response within the corneal flap interface created by a mechanical microkeratome and a femtosecond laser., Setting: Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany., Design: Experimental in vitro study., Methods: Corneoscleral buttons of 12 enucleated human eyes not suitable for transplantation were put into organ culture. Corneal flaps were created using a 200 kHz femtosecond laser (Visumax) (femtosecond group) or a mechanical microkeratome (Amadeus) (microkeratome group). Flaps were not lifted after treatment. In 2 corneas, no treatment was performed (control group). Corneas were kept in organ culture for 12 hours thereafter. To evaluate cell-mediated immune reaction, immunofluorescent staining for leucocytes (cluster of differentiation 45) and specifically for dendritic cells (human leukocyte antigen-DR) was performed in every group. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to determine apoptosis reaction., Results: The ratio of dendritic cells in the femtosecond group compared with the microkeratome group was 1.2 (P=.02), the ratio of leucocytes was 1.4 (P=.06), and the ratio of apoptotic cells was 1.0 (P=.59). There was no marked significant difference in the distribution of inflammatory cell reaction. The control group showed neither specific inflammatory reaction nor apoptosis., Conclusion: This in vitro series of human corneas showed similar inflammatory tissue reaction after femtosecond laser-assisted and microkeratome-assisted flap creation (P<.05)., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To report the 12 months efficacy of initial intravitreal bevacizumab or intravitreal recombinant tissue plasminogen activator (rtPA) combined with expansile gas in patients with subretinal haemorrhage caused by neovascular age-related macular degeneration (AMD)., Methods: Forty-five eyes of 45 patients with subretinal haemorrhage (1-5 disc diameters) involving the fovea secondary to neovascular AMD were evaluated retrospectively consecutively. Thirty-two eyes underwent treatment with rtPA (50 μg/0.05 ml) combined with intravitreal sulphur hexafluoride (SF6). The other 13 eyes were treated with bevacizumab (1.25 mg/0.05 ml) and SF6. Thereafter, all patients received Vascular Endothelial Growth Factor (anti-VEGF) treatment according to modified PrONTO criteria. Main outcome was change of best-corrected visual acuity (VA) at 12 months as determined by Early Treatment Diabetic Retinopathy (ETDRS)., Results: There was more improvement in patients initially treated with rtPA and gas (14 letters; bevacizumab and gas eight letters) and not suffering from adverse events. The incidence of vitreous haemorrhages was significantly higher in the rtPA group (nine of 32 versus one of 13, p < 0.01). In both groups, an average of 3.5 anti-VEGF injections were performed per patient during 12 months (no difference between both groups)., Conclusion: Both initial treatment regimen lead to improved functional results after 1 year. However, patients, not suffering from adverse events, who underwent initial treatment with rtPA and gas showed better results. To maintain VA, controlling neovascular AMD by anti-VEGF treatment regime after initial treatment with rtPA+gas is important for all cases., (© 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.)

Purpose: Corneal ulceration may be treated with human amniotic membrane (HAM) while neovascularization remains a common complication of corneal ulceration. As several factors contained within HAM may contribute to reduced corneal scarring, we investigated if HAM may be additionally loaded with bevacizumab and potentially serve as a carrier for anti-vascular endothelial growth factor (VEGF) drugs to provide constant VEGF blockade., Materials and Methods: Cryo-preserved HAM were incubated with different bevacizumab concentrations in organ culture medium for 2-5 d. Controls were incubated without bevacizumab. Then, all samples were placed into an organ culture medium without bevacizumab for 48 h, 72 h or for 5 d at 37 °C with the medium being changed at all time points. After that, VEGF165 was added to the supernatants for 24 h and free VEGF 165 was measured by ELISA., Results: Free VEGF was significantly blocked at 48 and 72 h (p < 0.01). VEGF blockade was less pronounced after 1 week. However, as compared to control, VEGF was significantly blocked at all times (p < 0.05)., Conclusion: In this in-vitro setting, we could demonstrate effective VEGF-blockade for up to 1 week by incubating HAM with bevacizumab. HAMs might be potentially used as a carrier for drugs delivered to the cornea.

Purpose: To analyze the correlation between morphological and functional results 12 months after epiretinal membrane (ERM) surgery., Methods: 31 eyes from 31 consecutive patients with metamorphopsia and best corrected visual acuity (BCVA) below 20/32 underwent a transconjunctival 23- gauge vitrectomy with ERM and internal limiting membrane peeling. Preoperatively and 3, 6 and 12 months postoperatively, we assessed BCVA, microperimetry (MP-1) and spectral domain optical coherence tomography (SD-OCT). Photoreceptor inner and outer segment (IS/OS) was graded on SD-OCT images and correlated with microperimetry measurements in the fovea and parafoveal region., Results: The postoperative BCVA was significantly better in eyes with an intact IS/OS junction (p < 0.01). In addition, the mean defect depth was postoperatively decreased in the foveal and parafoveal area in eyes with an intact IS/OS junction. A correlation of SD-OCT IS/OS images and microperimetry in eyes with improvement in BCVA of at least 2 lines revealed a statistically significant result for the parafoveal quadrants (p < 0.011 for SD-OCT and p < 0.005 for microperimetry) but not for the foveal area alone., Conclusions: The IS/OS regeneration in the parafoveal quadrants contributes significantly to the recovery of BCVA following ERM surgery. Consequently, functional and morphological tests of the macular area should not be limited to the fovea but should be extended to the parafoveal region., (Copyright © 2013 S. Karger AG, Basel.)

Purpose: The purpose of this study was to determine the quantity and distribution of antigen presenting cells (APC) in various inflammatory and non-inflammatory corneal diseases, comparing in vivo confocal microscopy (IVCM) and immunohistochemistry., Material and Methods: Corneae of 41 eyes, composed of group 1 (status post herpes-keratitis), group 2 (keratoconus) and group 3 (graft rejection after keratoplasty) were investigated. IVCM was used preoperatively to assess the distribution and density of dendritic cells in the corneal center versus the paracentral area. Afterwards, all patients underwent penetrating keratoplasty. The host corneas were analyzed by immunohistochemistry for antigen presenting cell distribution, density and characterization by using specific markers for CD207/Langerin, CD209/DC-SIGN and HLA-DR. The IVCM findings were compared with immunohistochemistry results in the corneal epithelium., Results: Cells with branching dendritic morphology were visualized by IVCM mainly in the basal epithelial layer and subepithelial nerve plexus of the central and paracentral cornea. The density of APC in IVCM decreased in all groups towards the central part of the cornea. The highest gradient was observed in group 2, followed by groups 1 and 3. The corneal paracenter showed similiar distribution of APC in group 1 and 2 (76.7 cells/mm(2) and 74.4 cells/mm(2)). The highest density of central APC was observed in group 1 (53.76 cells/mm(2)), followed by group 3 (27.0 cells/mm(2)) and group 2 (24.2 cells/mm(2)). In immunohistochemistry positive stained, APC were distributed similarly to IVCM but with a higher density (p < 0.05)., Conclusion: Distribution, density and stage of maturation of corneal epithelial APCs can be evaluated on morphological basis by IVCM. However, the corneal APCs density was about three-fold lower compared to immunohistochemistry findings.

Purpose: To compare the efficacy and safety of three intravitreal bevacizumab upload injections followed by a dexamethasone implant versus dexamethasone implant monotherapy in eyes with macular edema due to retinal vein occlusion., Methods: Sixty-four eyes of 64 patients were included in this prospective, consecutive, nonrandomized case series: group 1 consisted of 38 patients (22 with central retinal vein occlusion, CRVO, 16 with branch retinal vein occlusion, BRVO) treated using a dexamethasone implant (Ozurdex) alone; group 2 consisted of 26 patients (14 CRVO, 12 BRVO) treated with three consecutive intravitreal bevacizumab injections at monthly intervals followed by a dexamethasone implant. In case of recurrence, both cohorts received further dexamethasone implants. Preoperatively and monthly best corrected visual acuity (BCVA, ETDRS), central retinal thickness (Spectralis-OCT), intraocular pressure, and wide-angle fundus photodocumentation (Optomap) were performed. The primary clinical endpoint was BCVA at 6 months after initiation of therapy. Secondary endpoints were central retinal thickness and safety of the therapy applied., Results: In group 1, an increase in BCVA of 2.5 (±1.6) letters in the CRVO and of 13.0 (±3.2) letters in BRVO patients was seen after 6 months, in group 2 of 5.9 (±0.4) letters (CRVO) and 3.8 (±2.4) letters (BRVO), which was not statistically significant. When comparing the two treatment groups with respect to the type of vein occlusion, there was a significant advantage for BRVO patients for the dexamethasone implant monotherapy (BRVO patients in group 1, p = 0.005). Central retinal thickness showed a significant reduction after 6 months only in patients of group 1, both for CRVO (p = 0.01) and BRVO (p = 0.003). First recurrence after the first dexamethasone implant injection occurred after 3.8 months (mean) in CRVO and 3.5 months in BRVO patients (group 1), versus 3.2 and 3.7 months, respectively, in group 2. In group 1, 63.6% with CRVO and 50% with BRVO showed an increased intraocular pressure after treatment; in group 2, 57.1% with CRVO and 50.0% with BRVO, respectively., Conclusion: In CRVO, there was no difference between the two treatment strategies investigated. However, in BRVO, dexamethasone implant monotherapy was associated with better functional outcome., (Copyright © 2012 S. Karger AG, Basel.)

A 43-year-old woman presented with a 2-month history of contact lens-associated keratitis and corneal ulceration on the left eye. Without having isolated the pathogenic agent, a calculated anti-infective and anti-inflammatory therapy had already been administered with no signs of improvement. Filamentous fungi (Acremonium sp) were found in the scraping material and the contact lens solution. A keratoplasty à chaud was necessary despite immediate initiation of pathogen-specific therapy. Early identification of the pathogen via corneal debridement and culturing are standard procedures in order to initiate a specific therapy and prevent ulceration which can threaten the visual outcome.

Kearns-Sayre syndrome is a rare mitochondrial disease which usually occurs sporadically with the presence of ptosis and the clinical triad of chronic progressive external ophthalmoplegia, atypical retinitis pigmentosa and cardiac conduction disorders. We show on the example of a young patient with unexplained atypical acquired ptosis and eye movement disorders, the correct interpretation of the diagnostic findings. Of importance is the early detection of potentially life-threatening complications which can lead to sudden cardiac death.

Background: For the fate of a graft the antigen presenting cells play an important role. Chemokines can lead to enhanced migration of these cells. We therefore investigated if fresh human corneas bear the chemokine receptor 7 (CCR7) and if its ligands can force the emigration of dendritic cells in an in vitro model., Methods: We used human corneas excluded for transplantation and performed migration tests using chemokine ligands 19 (CCL19) and 21 (CCL21) or the complement factor 5a (C5a). Emigrated cells were collected up to 35 days and stained by immunofluorescent double labeling in triple layer technique with Langerin/CD207, DC-SIGN/CD209, CD14, and HLA-DR. In parallel, fresh and cultured human corneas were stained for CCR7., Results: We found in fresh human corneas, as well as in long-term cultured ones, a low CCR7 expression that nearly diminished after 28 days. In vitro Langerhans cell emigration could be enhanced only by CCL19, whereas dendritic cells were strongly influenced by CCL19, CCL21, and C5a. HLA-DR(+) cells showed numerically the highest in vitro emigration rate. Macrophages/monocytes were not influenced by the used chemokines., Conclusions: Although human corneas reduce their antigen presenting cells numbers during long-term culture, this effect could be significantly enhanced by using chemokines.

Purpose: Adult healthy human corneas bear a distinctive number of antigen-presenting cells (APCs) important for the fate of a graft. The purpose of this study was to differentiate between Langerhans cells (LCs) and other dendritic cells (DCs) and between mature and immature APCs in fresh and cultured human corneas using specific markers., Methods: Immunofluorescence double staining was performed for Langerin/CD207, CD1a, DC-SIGN/CD209, DC-LAMP/CD208, CD45, CD11c, CD11b and HLA-DR., Results: Langerin(+)/CD1a(+)/HLA-DR(+) LCs (approximately 100 cells/mm(2) in fresh corneas) were found in the limbal and peripheral regions of corneal epithelium and the anterior stroma up to 83 days of culture. All these cells coexpressed CD45 and CD11c. DC-SIGN(+)/CD45(+) DCs (approximately 150 cells/mm(2) in fresh corneas) were detected mainly peripherally and in the anterior stroma, even in long-term cultured corneas. Most of these cells were HLA-DR(-). Few mature DCs (DC-LAMP(+)/HLA-DR(+)) were found in fresh and cultured corneas. Macrophages (CD11c(-)/CD11b(+)) were seen in the peripheral, paracentral, and even central regions of the posterior stroma., Conclusions: This is the first demonstration that human corneas harbor populations of Langerin(+)/CD1a(+)/HLA-DR(+) LCs and DC-SIGN(+) DCs in a distribution pattern similar to that in the skin. Few APCs are in a mature state (DC-LAMP(+)). Given the reduced but not complete depletion of APCs during organ culture, these grafts still bear a potential risk for rejection.

Theophylline and its derivatives are determined by high-performance liquid chromatographic separation on a C8 reversed-phase column with electrochemical detection. The analyte is oxidized at 1.24 V (vs. the standard calomel electrode) on a wax-impregnated graphite electrode using classical d.c. and current sampled d.c. modes, and the results obtained compared with those of a 254 nm ultraviolet (UV) detector. Polarographic detection offers greater sensitivity for theophylline than UV detection; further, interferences which hamper UV detection may be selectively eliminated with polarographic detection.

The relation between race, type of initial treatment, and survival with breast cancer were investigated using 36,905 cases reported to nine registries in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute in the years 1978-82 and followed for survival through 1984. Using the crude treatment categories of surgical/nonsurgical/untreated, Blacks were found to have received less aggressive therapy. They were more likely than Whites to be treated nonsurgically (OR = 1.4; 95% CI = 1.2-1.7) or have no cancer-directed therapy (OR = 1.7; 95% CI = 1.3-2.3), even after adjusting by logistic regression for differences in age, stage, and histology. These treatment variables strongly affected five-year survival, after adjusting for age, stage, race, and histology. This finding of racial differences in survival-associated treatment patterns demonstrates the need to consider treatment variables in studies of race and cancer survival.