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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., (© 2022. The Author(s).)

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.

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.

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.

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.