Detection of systemic immunosuppressants in autologous serum eye drops (ASED) in patients with severe chronic ocular graft versus host disease.

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.

Retinal Detachment Rates After Uncomplicated DMEK Versus Cataract Surgery Combined (Triple-)DMEK.

PURPOSE: To evaluate the rate of and risk factors for rhegmatogenous retinal detachment (RRD) after Descemet membrane endothelial keratoplasty (DMEK) either alone or in combination with cataract surgery. DESIGN: Retrospective analysis of prospective database. METHODS: Consecutive eyes with Fuchs endothelial corneal dystrophy (FECD) that received DMEK surgery with a minimum follow-up of 1 year between July 2011 and January 2021 at the Department of Ophthalmology at the University of Cologne were analyzed. Exclusion criteria were complicated history including repeat DMEK within 1-year, previous retinal or glaucoma surgery, complicated phacoemulsification, congenital cataract, history of trauma. RESULTS: From 3858 consecutive DMEKs, 1961 patients were identified suitable for analysis. 846 (43.1%) were pseudophakic DMEK, 91 (4.6%) phakic DMEK and 1,024 (52.2%) combined with cataract surgery. RRD occurred in 13 eyes (12 patients). Within two years after DMEK RRD occurred in 0.49% and 0.47% after DMEK and DMEK with cataract surgery, respectively. Mean age of 59.24 ± 8.42 years with subsequent RRD was significantly lower than overall 68.81 ± 9.89 years (t-test two-tailed; p < 0.001). The spherical equivalent was -4.69 ± 3.98 D (range -9.00 to 0.5) in RRD after pseudophakic DMEK compared to -2.79 ± 3.54 D (range -7.5 to 0.75) in combined procedures. Re-bubbling had no influence on RRD rate. CONCLUSIONS: DMEK alone or in combination with cataract surgery showed similar postoperative RRD rates in the first two years, generally in the range of pseudophakic RRDs. Risk factors such as myopia and younger age could be identified. Re-bubbling has no influence on RRD rates.

Allogeneic limbo-deep anterior lamellar keratoplasty (Limbo-DALK)-A novel surgical technique in corneal stromal disease and limbal stem cell deficiency.

PURPOSE: To describe a novel corneal surgical technique combining Deep Anterior Lamellar Keratoplasty (DALK) with grafting of allogeneic limbus (Limbo-DALK) for the treatment of eyes with corneal stromal pathology and limbal stem cell deficiency (LSCD). METHODS: Clinical records of six Limbo-DALKs performed in five patients diagnosed with LSCD and corneal stromal pathology requiring keratoplasty were retrospectively reviewed. All patients were diagnosed with LSCD due to various pathologies including thermal and chemical burns, congenital aniridia or chronic inflammatory ocular surface disease. Parameters analysed included demographics, diagnoses, clinical history, thickness measurements using anterior segment OCT, visual acuity, and epithelial status. Regular follow-up visits were scheduled at 6 weeks as well as 3, 6, 9, and 12 and 18 months postoperatively. Main outcome measures were time to graft epithelialisation and the occurrence of corneal endothelial decompensation. RESULTS: Two grafts showed complete epithelial closure at 2 days, two at 14 days. In one eye, complete epithelial closure was not achieved after the first Limbo-DALK, but was achieved one month after the second Limbo-DALK. No endothelial decompensation occurred except in one patient with silicone oil associated keratopathy. Endothelial graft rejection was not observed in any of the grafts. CONCLUSION: Based on the data from this pilot series, limbo-DALK appears to be a viable surgical approach for eyes with severe LSCD and corneal stromal pathology, suitable for emergency situations (e.g. corneal ulceration with impending corneal perforation), while minimising the risk of corneal endothelial decompensation.

P49-A103†Allogeneic limbo-DALK: a novel surgical technique for patients with corneal stromal disease and limbal stem cell deficiency.

PURPOSE: To describe a novel corneal surgical technique combining Deep Anterior Lamellar Keratoplasty (DALK) with grafting of allogeneic limbal stem cells (limbo-DALK) as treatment for eyes with corneal stromal pathology and limbal stem cell deficiency (LSCD). METHODS: This is a series of six Limbo-DALKs in five eyes of five patients. One patient received a second limbo-DALK after graft failure following the first procedure. Two of the donor corneae were HLA matched. Clinical records of included patients were reviewed retrospectively. All patients had been diagnosed with LSCD due to various pathologies. Analysed data included demographic data, diagnoses and clinical history, graft visualization and thickness measurements by anterior segment OCT, visual acuity and epithelial status. Follow-up visits were 6 weeks and 3, 6, 9, 12 and 18 months postoperatively with final suture removal at 18 months and further follow-up examinations twice yearly thereafter. RESULTS: Two grafts showed total epithelial closure after 2 days, two after 14 days. In one eye, full closure of corneal epithelium did not occur after the first limbo-DALK, but could be achieved one month after second limbo-DALK. No endothelial graft rejection was seen. CONCLUSION: Based on data from this pilot series, limbo-DALK seems to be a novel viable surgical approach for eyes with severe LSCD and stromal corneal pathology.

Evaluation of a Novel Non-Diffractive Extended Depth of Focus Intraocular Lens - First Results from a Prospective Study.

PURPOSE: To evaluate a novel hydrophobic, non-diffractive, extended depth of focus (EDOF) intraocular lens (IOL) design in comparison to two monofocal aspheric lenses. METHODS: Inclusion criteria for this prospective, monocentric cohort study were opacification of the crystalline lens and patients' wishes for surgery. In the case of the EDOF IOL, patients asked for a presbyopia correction. All patients received surgery on both eyes. Corrected and uncorrected distance visual acuity (CDVA, UCDVA), uncorrected and distance corrected intermediate visual acuity (UIVA, DCIVA) and defocus curves (all monocular and binocular) were compared three months postoperatively. RESULTS: Fifty-six eyes were implanted with an EDOF IOL (LuxSmartTM, Bausch & Lomb GmbH, Berlin, Germany), 50 eyes with a monofocal aspheric IOL: 32 eyes with a clear IOL (Polylens® AS 61, Polytech Domilens, Roßdorf, Germany), 16 eyes with a yellow IOL (iSert® 251, Hoya Surgical Optics GmbH, Frankfurt, Germany). Three months postoperatively, UCDVA was comparable with the EDOF IOL, versus the monofocal IOL (P > 0.9). Binocular DCIVA in the EDOF IOL was significantly higher than in the monofocal IOL (P = 0.001). Monocular DCIVA better than 20/23 Snellen was achieved in 10% with the monofocal IOL and in 68% (P < 0.0001) with the EDOF IOL. Defocus curves showed a depth of focus at 20/23 Snellen of 1.6 vs. 0.83 diopters (D) in the EDOF IOL, vs. the monofocal IOL. No patient reported halos or starbursts in non-standardized questioning. CONCLUSION: This non-diffractive EDOF IOL provided comparably high UCDVA and significantly higher DCIVA than the mono-focal lenses, causing only mild optical phenomena.

Desiccating Stress Significantly Increases the Risk for Chronic Ocular Graft-versus-Host-Disease.

Desiccating stress (DS) is known to induce dry eye disease but has not been studied in the context of ocular graft-versus-host disease (oGVHD). Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are exposed to DS on transplantation wards, which are highly climate-regulated for hygienic purposes. Because oGVHD demonstrates features of dry eye disease, this retrospective study aimed to analyze DS as a risk factor for chronic oGVHD. A total of 444 patients undergoing allo-HSCT were investigated with a maximum follow-up of 5.8 years post-transplantation. Relative humidity (%rH) on the transplantation ward was monitored, and data were correlated with the occurrence, severity, and onset of chronic oGVHD, as well as the occurrence of acute skin GVHD. A logistic regression model was used to predict the development of oGVHD. One hundred three of 213 surviving patients developed oGVHD. oGVHD was significantly correlated with a lower %rH (r = .2; P = .03), and more patients (73%) developed oGVHD after transplantation under DS compared with patients after transplantation under high-humidity conditions (30%; P = .02). Reduced humidity increased the relative risk for oGVHD by 4% for each %rH, but it did not affect the severity or time of first diagnosis of oGVHD. In this study, we demonstrate that DS is an independent risk factor for oGVHD. Adjusting air humidity during allo-HSCT has the potential to serve as a preventive measure with clinical relevance.

Treatment of severe chronic ocular graft-versus-host disease using 100% autologous serum eye drops from a sealed manufacturing system: a retrospective cohort study.

BACKGROUND/AIMS: To analyse patients with chronic ocular graft-versus-host disease (GvHD) under treatment with 100% autologous serum eye drops from a sealed manufacturing system. METHODS: 17 patients with chronic ocular GvHD received 100% autologous serum eye drops from single use vials manufactured in a sealed system. Retrospective analysis included visual acuity, corneal staining, frequency of artificial tears, ocular symptoms by means of a questionnaire and information on subjective side effects and cost compensation. RESULTS: Data of prior to autologous serum eye drops therapy and at a 6-month follow-up were obtained. They demonstrated a significant increase in visual acuity (logMAR oculus dexter/right eye (OD) 0.5±0.32 to 0.4±0.3; oculus sinister/left eye (OS) 0.6±0.35 to 0.3±0.35; p=0.177/0.003) and significant improvement in corneal staining (Oxford grading scheme: OD from 3±1.03 to 2±1.43, OS from 4±1.0 to 2±1.09, p=0.004/0.001) and ocular symptoms (ocular surface disease index: 88±20.59 to 63±22.77; p=0.02). Frequency of artificial tears was reduced and no side effects were reported. Patient satisfaction was 100%, and cost compensation by health insurance reached 80%. CONCLUSIONS: 100% autologous serum eye drops using a sealed manufacturing system were efficient in improving the ocular surface, patient symptoms and visual acuity without side effects. It seems to be safe to use 100% autologous serum despite earlier suspicions regarding immune complex accumulations and exacerbation of ocular surface inflammation. The potential effects of serum levels of systemic immunosuppressives through readministration onto the ocular surface need to be elucidated.