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Copyright of Die Ophthalmologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Die Ophthalmologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose : To evaluate the outcome of phacoemulsification in patients with chronic ocular Graft-versus-host disease (oGVHD) after allogeneic hematopoietic stem cell transplantation (aHSCT). Methods: Retrospective, observational multicenter study from 1507 oGVHD patients. From the patient files, data were collected including best-corrected visual acuity (BCVA), intraocular pressure (IOP), Schirmer's test I, tear film break-up time (TFBUT), corneal fluorescein staining score, postoperative complications, and pre- and post-operative topical therapy. Results: Seventy-three patients underwent cataract surgery in 104 eyes. In n = 84 eyes, the oGVHD NIH grade was documented; 12% (n = 12) of analyzed eyes were staged oGVHD NIH grade 1, 31% (n = 32) NIH 2 and 39% (n = 41) NIH 3. The mean BCVA improved in 82% of the eyes (n = 86 eyes). BCVA significantly increased from 0.7 ± 0.5 to 0.4 ± 0.4 LogMAR after surgery independent from oGVHD severity. The mean IOP decreased from 14 ± 4 to 13 ± 4 mmHg after surgery. Visual acuity was moderately correlated to the pre-operative degree of corneal staining (Pearson p = 0.26, p = 0.002, Cohen's effect size f = 0.29). The visual acuity decreased by 0.078 LogMar units (95% CI = 0.027–0.141) with each increase of corneal staining by one grade (p = 0.05). After surgery, corneal epitheliopathy increased significantly in 42% (n = 44) of the eyes. Postoperative complications included corneal perforation (n = 6, 6%), cystoid macular edema (n = 4, 4%), and endophthalmitis (n = 1, 1%). Conclusion: Phacoemulsification in patients with chronic oGVHD significantly improves visual acuity, but is associated with an increased risk of complications in particular corneal epitheliopathy and corneal perforations. [ABSTRACT FROM AUTHOR]

Meibomian glands (MG) are large sebaceous glands located below the tarsal conjunctiva and the abnormalities of these glands cause Meibomian gland dysfunction (MGD) which is responsible for evaporative dry eye disease (DED). Accurate MG segmentation is a key prerequisite for automated imaging based MGD related DED diagnosis. However, Automatic MG segmentation in infrared meibography is a challenging task due to image artifacts. A deep learning-based MG segmentation has been proposed which directly learns MG features from the training image dataset without any image pre-processing. The model is trained and evaluated using 728 anonymized clinical meibography images. Additionally, automatic MG morphometric parameters, gland number, length, width, and tortuosity assessment were proposed. The average precision, recall, and F1 score were achieved 83%, 81%, and 84% respectively on the testing dataset with AUC value of 0.96 based on ROC curve and dice coefficient of 84%. Single image segmentation and morphometric parameter evaluation took on average 1.33 s. To the best of our knowledge, this is the first time that a validated deep learning-based approach is applied in MG segmentation and evaluation for both upper and lower eyelids. [ABSTRACT FROM AUTHOR]

Purpose: Chronic graft versus host disease is a major consequence after allogeneic stem cell transplantation (allo-SCT) and has great impact on patients' morbidity and mortality. Besides the skin, liver, and intestines, the eyes are most commonly affected, manifesting as severe ocular surface disease. Treatment protocols include topical steroids, cyclosporine, tacrolimus, and ASED. Since these patients often receive systemic immunosuppressant therapy from their oncologists, a topical re-administration of these drugs via ASED with potentially beneficial or harmful effects is possible. The purpose of the study was to determine whether and to which extent systemic immunosuppressants are detectable in ASED. Methods: A total of 34 samples of ASED from 16 patients with hemato-oncological malignancies after allo-SCT were collected during the manufacturing process and screened for levels of cyclosporine, mycophenolic acid, everolimus, and tacrolimus via liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The study followed the tenets of the Declaration of Helsinki and informed consent was obtained from the subjects after explanation of the nature and possible consequences of the study. Results: Cyclosporine was found in 18 ASED samples in concentrations ranging from 6.5–105.0 ng/ml (32.0 ± 22.8 ng/ml, mean ± SD). The concentration range of mycophenolic acid in 19 samples was 0.04–25.0 mg/l (4.0 ± 5.4 mg/l, mean ± SD). Everolimus and tacrolimus concentrations were well below the respective limits of quantification (< 0.6 and < 0.5 ng/ml) of the established LC-MS/MS method in all samples. Conclusions: Our study suggests that orally administered cyclosporine and mycophenolic acid for the treatment of systemic GvHD, but not everolimus and tacrolimus, are distinctly detectable in ASED in relevant concentrations. It is highly likely that these agents affect topical therapy of ocular GvHD. However, the extent of this effect needs to be evaluated in further studies. [ABSTRACT FROM AUTHOR]

Purpose: Cyclosporine A (Cs) has been used as effective topical therapy for inflammatory dry eye disease since more than a decade. However, due to its lipophilic character, Cs is formulated as emulsions or oily solutions for topical application. This experimental study aimed to test if the use of semifluorinated alkanes (SFAs) as a preservative-free, well-tolerated non-stinging or burning vehicle maintains or even improves the benefits of Cs in the topical therapy of dry-eye disease. Methods: Desiccating stress was applied to C57BL/6 mice for 14 consecutive days to induce experimental dry-eye. Cs dissolved in SFA (perfluorobutylpentane = F4H5with 0.5% Ethanol), F4H5 with 0.5% ethanol only, 0.05% Cs (Restasis®), and dexamethasone (Monodex®) were applied three times daily beginning either at day 4 or day 11 of desiccating stress for up to 3 weeks after end of dry-eye induction. Results: In comparison to other groups, Cs/F4H5 demonstrated high efficacy and earlier reduction of corneal staining. In this study, Cs/F4H5 had the ability to maintain conjunctival goblet cell density once applied on day 4. Flow cytometry analysis from cervical lymphnodes demonstrated a significantly lower CD4+ and CD8+ T-cells in the Cs/F4H5 group following 3 weeks of therapy than at baseline, but no difference in regulatory T cells from regional lymphnodes were seen. Conclusions: Overall, compared to a commercially available Cs formulation (Restasis®) and dexamethasone, Cs/F4H5 was shown to be equally effective but with a significantly faster therapeutic response in reducing signs of dry-eye disease in an experimental mouse model. [ABSTRACT FROM AUTHOR]

Purpose: Correct early graft attachment is believed to be crucial for final visual outcome after Descemet membrane endothelial keratoplasty (DMEK). Nonetheless, it is not yet known which imaging technique gives superior results for examining early postoperative graft adherence status. We compared imaging data taken with two different OCT devices to examine the development of graft adherence immediately after DMEK and to determine the superior device in terms of visualization of graft adherence. Methods: Ten consecutive patients (1 man/9 women) were examined three times postoperatively within the first 7 h after DMEK surgery using spectral domain OCT (SD-OCT) and time domain OCT (TD-OCT), as prospective case series and retrospective image data analyses. The parameters analyzed were localization and number, visibility and size of graft detachments. Results: TD-OCT was able to detect a greater number of graft detachments after DMEK; however, SD-OCT provided better resolution of minor detachments. Graft detachments varied in position and degree at different time points immediately after surgery. All patients had some graft detachment within the first 7 h after DMEK surgery. Conclusions: TD-OCT enabled better overall analysis of graft detachments, even in the periphery, whereas SD-OCT allowed for the detection of even minor detachments, which suggests that a combination of the two techniques is optimal. Our results indicate that dynamic processes affecting the DMEK graft immediately after transplantation are responsible for changes in the attachment of donor tissue at an early postoperative stage. Modulation of early graft attachment may improve the final graft attachment. [ABSTRACT FROM AUTHOR]

Purpose: To analyze potential alterations in corneal nerve morphology and function in different stages of Fuchs' endothelial corneal dystrophy (FECD). Methods: Thirty eyes with FECD underwent in vivo confocal microscopy using the Heidelberg Retina Tomograph II (HRT II; Heidelberg Engineering, Heidelberg, Germany) and the Rostock Cornea Module (RCM) to quantify the morphology of the central subbasal corneal nerve plexus (total nerve length, total nerve number, number of main nerve trunks, number of nerve branches) as well as esthesiometry (using the Cochet-Bonnet esthesiometer) of the central cornea to determine central corneal sensation as a measure of nerve function. Findings were correlated with an age-matched control group of 30 healthy individuals. Comparisons to biomicroscopical stage of FECD, visual acuity and central corneal thickness were performed using Spearman correlation. Results: Depending on slit-lamp examination, all 30 eyes were classified into FECD stage 1-4 (stage 1: six eyes; stage 2: 15 eyes; stage 3: six eyes; stage 4: three eyes). Total nerve length ( ρ = −0.8, p < 0.001), total nerve number ( ρ = −0.7, p < 0.001), number of main nerve trunks ( ρ = −0.6, p < 0.001), and number of nerve branches ( ρ = −0.7, p < 0.001) decreased significantly with increasing FECD stages. Comparing to the visual acuity, significant positive correlations were found for total nerve length ( ρ = 0.5, p = 0.012), total nerve number ( ρ = 0.5, p = 0.005), number of main nerve trunks ( ρ = 0.4, p = 0.017), and number of nerve branches ( ρ = 0.5, p = 0.009). With central corneal thickness, there were significant inverse correlations for total nerve length ( ρ = −0.6, p = 0.001), total nerve number ( ρ = −0.5, p = 0.012), number of main nerve trunks ( ρ = −0.4, p = 0.015), and number of nerve branches ( ρ = −0.4, p = 0.017). Central corneal sensation was full in all FECD stage 1, stage 2 and stage 3 eyes, but mildly reduced in FECD stage 4 eyes. Conclusions: Increasing severity of Fuchs' endothelial corneal dystrophy (FECD) is concurrent with marked attenuation of the density, as well as mild diminishment of the function, of the subbasal corneal nerve plexus in late stage of the disease. [ABSTRACT FROM AUTHOR]

Background: Early and correct diagnosis of delayed or absent corneal epithelial wound healing is a key factor in the prevention of infection and consecutive destruction of the corneal stroma with impending irreversible visual loss. Two-photon microscopy (TPM) is a novel technology that has potential to depict epithelial cells and to evaluate cellular function by measuring autofluorescence properties such as fluorescence intensity and fluorescence lifetimes of metabolic co-factors such as NAD(P)H. Methods: Using non-invasive TPM in a tissue-culture scratch model and an organ-culture erosion model, fluorescence intensity and fluorescence lifetimes of NAD(P)H were measured before and during closure of the epithelial wounds. Influence of temperature and selective inhibition of metabolism on intensity and lifetimes were tested additionally. Results: Decrease of temperature resulted in significant increase of fluorescence lifetimes and decrease of the relative amount of free NAD(P)H due to decreased global metabolism. Increase in temperature and upregulation of glycolysis through blocking the mitochondrial electron transport chain by rotenone resulted in increased intensity, decreased lifetimes and increase in the relative amount of free NAD(P)H. Changes of lifetimes and free:protein-bound NAD(P)H ratios were similar to changes measured during wound healing in both scratch and erosion models. Conclusions: Fluorescence lifetime measurements (FLIM) detected enhancement of cellular metabolism following epithelial damage in both models. The prospective detection of cellular autofluorescence in vivo, in particular FLIM of metabolic cofactor NAD(P)H, has the potential to become an indispensible tool in clinical use to differentiate healing from non-healing epithelial cells and to evaluate effects of newly developed substances on cellular metabolism in preclinical and clinical trials. [ABSTRACT FROM AUTHOR]

Human β-defensins are cationic peptides produced by epithelial cells that have been proposed to be an important component of immune function at mucosal surfaces. In this study, the expression and inducibility of β-defensins at the ocular surface were investigated in vitro and in vivo. Expression of human β-defensins (hBD) was determined by RT-PCR and immunohistochemistry in tissues of the ocular surface and lacrimal apparatus. Cultured corneal and conjunctival epithelial cells were stimulated with proinflammatory cytokines and supernatants of different ocular pathogens. Real-time PCR and ELISA experiments were performed to study the effect on the inducibility of hBD2 and 3. Expression and inducibility of mouse β-defensins-2, -3 and -4 (mBD2–4) were tested in a mouse ocular surface scratch model with and without treatment of supernatants of a clinical Staphylococcus aureus (SA) isolate by means of immunohistochemistry. Here we show that hBD1, -2, -3 and -4 are constitutively expressed in conjunctival epithelial cells and also partly in cornea. Healthy tissues of the ocular surface, lacrimal apparatus and human tears contain measurable amounts of hBD2 and -3, with highest concentrations in cornea and much lower concentrations in all other tissues, especially tears, suggesting intraepithelial storage of β-defensins. Exposure of cultured human corneal and conjunctival epithelial cells to proinflammatory cytokines and supernatants of various bacteria revealed that IL-1β is a very strong inductor of hBD2 and Staphylococcus aureus increases both hBD2 and hBD3 production in corneal and conjunctival epithelial cells. A murine corneal scratch model demonstrated that β-defensins are only induced if microbial products within the tear film come into contact with a defective epithelium. Our finding suggests that the tear film per se contains so much antimicrobial substances that epithelial induction of β-defensins occurs only as a result of ocular surface damage. These findings widen our knowledge of the distribution, amount and inducibility of β-defensins at the ocular surface and lacrimal apparatus and show how β-defensins are regulated specifically. [ABSTRACT FROM AUTHOR]

The occurrence of primary extranodal marginal-zone B-cell lymphoma [of the mucosa-associated lymphoid tissue (MALT) type] has only been described in the supraglottic region, implying that preexistent organized lymphoid tissue is present at that site only. To date, studies have not established clearly whether organized MALT shows a site-related distribution in the larynx. The supraglottic region of the false vocal folds and the subglottis from 87 unselected cadavers with no known history of nasal, oral, pharyngeal, laryngeal, tracheal, or esophageal disease were examined for the presence of organized MALT. Organized lymphoid tissue was found with the cytomorphological and immunophenotypic features of MALT in 100% of false vocal folds of children and in more than 90% of adolescents, decreasing to 7.1% in persons in their sixth decade, whereas MALT was completely absent in the subglottis in all age groups. The results explain why primary extranodal marginal-zone B-cell lymphoma has only been described in the supraglottic region but is absent in the subglottis. Moreover, the results suggest a region-specific immunological response of the different laryngeal areas as reflected in clinical observations and animal studies. However, the impact on presence or absence of laryngeal MALT awaits clarification. [ABSTRACT FROM AUTHOR]

Inflammatory processes often lead to pathologic changes in the area of the larynx. A moistening function of the false vocal folds has been described frequently. Up to now we have little knowledge of the role of the false vocal folds in protection against pathogenic agents. The present study analyzes the structures of the false vocal folds in their relations to antimicrobial defense mechanisms. Investigations were performed on false vocal folds of larynges from 34 cadavers using histologic, histochemical and immunohistochemical methods. Seromucous glands, together with epithelial and goblet cells of the folds, synthesize a complex mucus layer. In all of the investigated samples this layer contains carbohydrates including N-acetyl-glucosamine, N-acetyl-galactosamine, galactose, mannose, fucose, and sialic acids. Furthermore, antimicrobial peptides like lactoferrin, lysozyme, alpha and beta defensins are also found in these structures. IgA, produced by plasma cells in the false vocal folds, is frequently integrated in the secretory product. Synthesized mucins, antimicrobial peptides and immunoglobulins form a specialized protective substance that is secreted mainly at the true vocal folds. Here the layer functions to lubricate the true vocal folds, resulting in positive functional consequences during vocal production. Moreover, together with immunocompetent cells, the protective layer seems to play a major role in antigen defense and prevents invasion of pathogenic agents. [ABSTRACT FROM AUTHOR]