Purpose: To evaluate the clinical outcome and complications of Descemet membrane endothelial keratoplasty (DMEK), using Descemet-stripping endothelial keratoplasty (DSEK) as a back-up procedure, in the management of Fuchs endothelial dystrophy. Design: Non-randomised prospective clinical study. Methods: The first fifty consecutive eyes that underwent DMEK, that is, transplantation of an isolated donor Descemet membrane carrying its endothelium, for Fuchs endothelial dystrophy were evaluated. In all eyes, the best-corrected visual acuity (BCVA) as well as the endothelial cell density (ECD) was measured before and at 6 months after surgery, as clinical outcome parameters. Results: Ten patients required a secondary DSEK for failed DMEK. In the remaining 40 DMEK eyes, 95% had a BCVA of X20/40 (X0.5) and 75% X20/25 (X0.8) at 6 months after surgery. ECD averaged 2618 ( ± 201) cells/mm 2 before, and 1876 ( ± 522) cells/mm 2 at 6 months after surgery (n ¼ 35). When the outcomes of DMEK and secondary DSEK procedures were combined, 94% reached a BCVA of X20/40 (X0.5) and 66% X20/25 (X0.8) (n ¼ 47), and ECD averaged 2623 ( ± 193) cells/mm 2 before, and 1815 ( ± 578) cells/mm 2 at 6 months after surgery (n ¼ 43). Conclusion: With DSEK as a back-up procedure, DMEK may provide relatively quick and complete visual rehabilitation in a majority of patients operated on for Fuchs endothelial dystrophy. Endothelial cell survival may be similar to earlier types of (lamellar) keratoplasty. Early graft detachment was the main complication in this first series of DMEK surgeries for Fuchs endothelial dystrophy.
Biomarkers in tear fluid of dupilumab-treated moderate-to-severe atopic dermatitis patients To the Editor, Atopic dermatitis (AD) patients treated with dupilumab, a biologic therapy targeting the shared receptor component for interleukin (IL)-4 and IL-13, frequently reported dupilumab-associated ocular surface disease (DAOSD) as a side effect. 1 Additionally, the majority of AD patients have ocular surface disease (OSD) before starting dupilumab, suggesting that AD patients may be predisposed to develop DAOSD. 2 The exact pathomechanism of DAOSD remains unclear, and little information is available regarding conjunctival inflammation. Therefore, our aim was to characterize conjunctival inflammation by measuring tear fluid biomarker levels and relate this to OSD severity before and during dupilumab treatment in AD patients. This prospective study included moderate-to-severe AD adult patients between February 2020 and March 2021 from the University Medical Center Utrecht, the Netherlands. Dupilumab was dosed according to the label (300 mg every 2 weeks). Examination was performed by a dermatologist and an ophthalmologist at the start of dupilumab (baseline) and after 4 and 28 weeks of dupilumab treatment. An additional ophthalmological examination was performed in patients who developed DAOSD. During dupilumab treatment, the ophthalmologist could start OSD treatment and selected therapy depended on OSD severity. Written informed consent was provided, and the study was approved by the Institutional Review Board.
Background:The patho-mechanism of ocular surface disease (OSD) in dupilumabtreated atopic dermatitis (AD) patients remains unclear. The aim of this study is to measure dupilumab levels in tear fluid and serum, and relate these findings to the severity of OSD during dupilumab treatment in AD patients.Methods: This prospective study included dupilumab-treated moderate-to-severe AD patients who were seen by a dermatologist and an ophthalmologist before the start of dupilumab (baseline), and after 4 and 28 weeks of dupilumab treatment.Dupilumab levels in tear fluid and serum were measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Additionally, a pilot study was conducted to measure dupilumab on conjunctival epithelial cells using flow cytometry and LC-MS/MS.Results: At baseline, 89.6% (n = 43/48) of the patients had OSD, with 50.0% having moderate-to-severe OSD. After 28 weeks of dupilumab treatment, the median dupilumab tear fluid levels were 0.55 mg/L (IQR 0.35-1.31) and 0.29 mg/L (IQR 0.16-0.60) in patients with moderate-to-severe OSD and patients with no or mild OSD, respectively (p = 0.02). Dupilumab levels could be detected on conjunctival epithelial cells of 5 AD patients treated with dupilumab for 4 weeks.
Conclusion:Patients with moderate-to-severe OSD had higher dupilumab tear fluid levels compared to patients with no or mild OSD, indicating that dupilumab reaches the ocular surface. Dupilumab was also detected in conjunctival cell suspensions and was found to directly bind CD45-conjunctival epithelial cells. This suggests that ADinduced changes of the conjunctival epithelium may play a role in the development of OSD as well as increased local drug availability.
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