Does placental abruption cause neonatal anemia?

INTRODUCTION: Placental abruption can result in serious perinatal morbidity and mortality. However, it is not clear whether placental abruption could lead to neonatal anemia, as a direct relation has not been described yet. The objective of this study is to investigate whether there is a relation between occurrence of placental abruption and neonatal anemia. MATERIAL AND METHODS: All women with a clinical diagnoses of placental abruption between January 2016 and April 2021 in Amsterdam UMC, from both the VU University Medical Center and Amsterdam Medical Center, were included. Demographic data and delivery outcomes were collected retrospectively using the medical files. The primary outcome was neonatal anemia, defined as hemoglobin levels less than the fifth percentile for gestational age. RESULTS: A total of 65 mothers and 65 neonates were included in our study. Average gestational age was 30 + 5 weeks. Mean hemoglobin level of the neonates at birth was 16.5 g/dl (10.2 mmol/L) with hemoglobin levels comparable to the reference curve. Two neonates (3.6%) were diagnosed with anemia based on their hemoglobin level at birth, and six (9.2%) neonates received a blood transfusion within 24 h after birth. CONCLUSIONS: With this study, we found that the hemoglobin levels of the neonates born after placental abruption are comparable to the reference curve and do not show more neonates than expected below the fifth percentile for gestational age. It remains unclear whether there is fetal blood loss during a placental abruption but our results suggest that at least a big amount of fetal blood is not lost, since we did not found a large number of anemic neonates. Severe neonatal anemia in the case of placental abruption does not need to be expected.

Histopathology of Failed Descemet Membrane Endothelial Transfer.

OBJECTIVES: To describe the postmortem histologic features after an unsuccessful Descemet membrane endothelial transfer (DMET) and assess any potential clinical implications. METHODS: Postmortem, an eye from a patient who previously underwent unsuccessful DMET for pseudophakic bullous keratopathy (PPBK) was harvested and processed for morphologic evaluation. RESULTS: Clinically and histologically, the host cornea showed evidence of diffuse stromal edema. Although the edges of the surgical descemetorhexis were well visualized, there was no evidence of endothelial migration or repopulation of the posterior stroma from any direction. A multilayered, retrocorneal membrane was present that appeared to originate from the trabecular meshwork. CONCLUSIONS: Descemet membrane endothelial transfer and "descemetorhexis alone" may be insufficient treatment for eyes operated on for PPBK, that is, eyes with a significantly depleted or dysfunctional endothelium.

Histopathologic Features of Descemet Membrane Endothelial Keratoplasty Graft Remnants, Folds, and Detachments.

PURPOSE: To describe the histologic features of postmortem eyes after Descemet membrane endothelial keratoplasty (DMEK) and their potential clinical implications. DESIGN: Histopathologic study. PARTICIPANTS: Eleven postmortem DMEK corneas of 8 patients who underwent surgery for Fuchs endothelial dystrophy, with an average postoperative time of 4±1.9 years (range, 7 months-6.5 years). METHODS: Eleven corneas transplanted with a DMEK graft were procured after death and processed for light microscopy evaluation. MAIN OUTCOME MEASURES: Histologic findings at the donor-host interface and at the host edge. RESULTS: Of the 11 corneas available for analysis, 9 showed normal anatomic features in the corneal center; that is, the donor-host interface resembled that of a virgin eye. One eye also had an anatomically normal periphery, but the remaining 10 eyes showed specific abnormalities in the periphery. Nine demonstrated overlapping of the DMEK graft onto the host edge of the descemetorhexis (and in 6 of these, the overlapping tissue showed a contracted inward fold at its peripheral edge with scar tissue); 1 eye showed a dense, acellular scar overlying a portion of the DMEK graft that clinically had shown a detachment followed by spontaneous adherence; 3 eyes showed subtle graft folds with scar tissue anteriorly; in 2 eyes (of the same patient), the anterior banded layer of the host Descemet membrane (DM) was still in situ across the cornea (both of these eyes had required rebubbling); and 2 eyes showed host DM remnants within the corneolimbal tunnel incision that may have interfered with incisional wound healing. CONCLUSION: Incomplete host DM removal may relate to postoperative DMEK graft detachment and wound instability. Graft detachments may reattach with interface scarring. Rebubbling procedures may be performed within 4 to 6 weeks, before portions of the detached graft scar. Subtle DMEK graft folds may explain subjective reports of monocular diplopia.

Dehydration of corneal anterior donor tissue with polyethylene glycol (PEG)-enriched media.

Anterior donor grafts (including scleral rim, without Descemet membrane) increase in thickness and become hazy upon storage in organ culture (OC) medium. Transfer of these grafts to standard dehydration media just before transplantation does not reduce their thickness to normal. Therefore, we assessed the efficacy of different media enriched with polyethylene glycol (PEG) as dehydrating agents for organ-cultured anterior donor grafts. Grafts were harvested and stored in the commercial OC medium 'Max' (without dextran) for 1 week, and subsequently dehydrated in the standard commercial dehydration medium 'Jet' (with dextran) supplemented with 4-20% PEG3350, or 'Max' supplemented with 20% PEG6000 and PEG20.000, or 5-20% PEG35.000. Central corneal thickness (CCT), as assessed by anterior segment-optical coherence tomography, and transparency were evaluated before, and at 1, 4 and 7 days of dehydration. Transfer of grafts after 1 week of OC (average 1,200 µm) to 'Jet' supplemented with PEG3350 revealed a concentration-dependent effect of dehydration; CCT was restored to normal (500-600 µm) when 10% PEG3350 was added. However, transparency was only temporarily restored; after 1 day, the grafts turned hazy. In contrast, grafts transferred to 'Max' supplemented with 20% PEG35.000 were transparent throughout the evaluation period, but were dehydrated to beyond normal levels (average 300 µm). 'Max' supplemented with 5% PEG35.000 dehydrated grafts to normal values and restored transparency throughout. Thus, dehydration of anterior donor grafts prior to surgery in dextran-free OC medium supplemented with 5% PEG35.000 reduces graft thickness to normal and may facilitate anterior keratoplasty procedures.

Descemet membrane endothelial transfer.

PURPOSE OF REVIEW: To elaborate on the recent concept of Descemet membrane endothelial transfer (DMET) and to explore the concepts that underpin its success through reviewing the key articles that have challenged our current understanding of corneal endothelial cell behavior. RECENT FINDINGS: DMET challenges the paradigm that complete graft-host apposition is required for successful corneal clearance in endothelial keratoplasty. It offers the promise of a simpler procedure to restore corneal clarity. Its success may lie in the ability of endothelial cells to migrate and proliferate. Endothelial host cells have been found in isolation and at disparate locations among donor cells within the corneal buttons of patients who have had a penetrating keratoplasty. New evidence for the continued slow proliferation of endothelial cells from the corneal periphery throughout life comes from the microanatomy of the peripheral cornea, and the demonstration of stem cell markers and markers of DNA synthesis in this area. SUMMARY: DMET offers us a tantalizing taste of a simpler way of treating corneal endothelial disease by harnessing the ability of corneal endothelial cells to migrate and proliferate. An understanding of these processes will be the key stepping stone to developing future treatments for corneal endothelial disease.

Dyes for Eyes™: hydrodynamics, biocompatibility and efficacy of 'heavy' (dual) dyes for chromovitrectomy.

As epiretinal membranes (ERMs), the internal limiting membrane (ILM) and the vitreous cortex are essentially transparent tissues, or translucent structures, nontraumatic removal may be challenging in various types of macular surgery. Vital dyes stain these thin tissues, thus allowing for better visualization of these structures during vitrectomy and selective 'membrane peeling' from the underlying retina. To avoid swirling of the dye within the fluid-filled vitreous cavity, and to better target the dye onto the macula, a fluid-air exchange is commonly performed. However, this may jeopardize visualization of the macula during peeling due to clouding of the posterior lens capsule, and may lead to postoperative visual field defects. Recently, a new dye solution for staining the ERM and ILM simultaneously has been developed that circumvents the need for fluid-air exchange, i.e. MembraneBlue-Dual™. This paper will focus on the hydrodynamics and biocompatibility of this 'heavy' dual dye and its efficacy for staining of the ILM and/or ERMs during posterior segment surgery in a multicenter clinical setting.

Combined chlorhexidine and PVP-I decontamination of human donor eyes prior to corneal preservation.

The aim of this study was to report the efficacy of adding chlorhexidine to the protocol for decontamination of human donor globes prior to excision of corneo-scleral rims for future keratoplasty procedures. In 2005, chlorhexidine was introduced by our eye bank as an additional step in the protocol for decontaminating human donor globes. After 5 years, we prospectively evaluated the number of contaminations. Out of 2,891 globes included in our study, 2,663 globes were processed, of which 36 (1.4%) were considered contaminated. Seventeen contaminations (0.6%) were detected by culturing limbal swabs, directly after decontamination, eight (0.3%) by visible discoloration of the culture medium carrying a corneo-scleral rim, and eleven (0.4%) after inoculation of the culture medium on blood agar plates. Importantly, after 4 weeks of incubation, none of the aerobic and anaerobic cultures taken from the secondary 'transport medium' (dextran containing medium used to transport corneal tissue to the transplantation centre) showed microbiological growth. In conclusion, the combined use of 0.02% chlorhexidine and 0.5% povidone-iodine may allow decontamination of donor globes to a level at which the risk of tissue contamination at the time of transplantation is minimized, while corneal viability is preserved.

Keratinocyte growth factor improves allogeneic bone marrow engraftment through a CD4+Foxp3+ regulatory T cell-dependent mechanism.

Keratinocyte growth factor (KGF) protects mice from acute graft-vs-host disease and graft rejection by cytoprotective and yet incompletely understood immunological mechanisms. Recently, we showed that administration of KGF induces selective peripheral expansion of CD4(+)Foxp3(+) regulatory T cells (Treg). In this study, we set out to assess whether the peripheral expansion of Treg accounts for the immunomodulatory effects of KGF after bone marrow (BM) transplantation. To exclude potentially confounding cytoprotective and thymopoietic effects of KGF, we applied KGF to congenic wild-type mice that served as T cell provider mice for T and B cell-deficient RAG-1(-/-) mice that were subsequently transplanted with allogeneic BM. Treatment of congenic T cell provider mice with KGF significantly improved engraftment and reduced graft rejection in BMT recipients. CD4(+)Foxp3(+) Treg remained increased for 4 wk, while expansion of congenic CD3(+) T cells was inhibited. To assess a causal relationship between expansion of Treg and improved BM engraftment, congenic Scurfy mice, which lack Foxp3(+) Treg, served as T cell provider mice and were treated with KGF. KGF-treatment of Scurfy mice did not affect engraftment nor did it inhibit the expansion of congenic T cells. These data demonstrate that administration of KGF to the T cell provider mice improves engraftment of allogeneic BM through a CD4(+)Foxp3(+) Treg-dependent mechanism.

New developments in corneal endothelial cell replacement.

Corneal transplantation is currently the most effective treatment to restore corneal clarity in patients with endothelial disorders. Endothelial transplantation, either by Descemet membrane endothelial keratoplasty (DMEK) or by Descemet stripping (automated) endothelial keratoplasty (DS(A)EK), is a surgical approach that replaces diseased Descemet membrane and endothelium with tissue from a healthy donor eye. Its application, however, is limited by the availability of healthy donor tissue. To increase the pool of endothelial grafts, research has focused on developing new treatment options as alternatives to conventional corneal transplantation. These treatment options can be considered as either 'surgery-based', that is tissue-efficient modifications of the current techniques (e.g. Descemet stripping only (DSO)/Descemetorhexis without endothelial keratoplasty (DWEK) and Quarter-DMEK), or 'cell-based' approaches, which rely on in vitro expansion of human corneal endothelial cells (hCEC) (i.e. cultured corneal endothelial cell sheet transplantation and cell injection). In this review, we will focus on the most recent developments in the field of the 'cell-based' approaches. Starting with the description of aspects involved in the isolation of hCEC from donor tissue, we then describe the different natural and bioengineered carriers currently used in endothelial cell sheet transplantation, and finally, we discuss the current 'state of the art' in novel therapeutic approaches such as endothelial cell injection.

Combined specular microscopy and Scheimpflug imaging to improve detection of an upcoming allograft rejection after DMEK.

PURPOSE: To assess whether combined analysis of specular microscopy and Scheimpflug imaging improves detection of an upcoming allograft rejection following Descemet membrane endothelial keratoplasty (DMEK). METHODS: Retrospective analysis of 22 eyes that had developed a clinical proven allograft rejection 28 (±22) months (range: 4-84 months) after DMEK. Specular microscopy and Scheimpflug images routinely made after DMEK were retrospectively analysed for changes in endothelial cell morphology (e.g. nuclear activation), cell density (>10%) and pachymetry (>7%), and/or the presence of subclinical keratic precipitates. The same parameters were evaluated for 22 control eyes matched for age, gender and surgery indication. RESULTS: A total of 20/22 eyes (91%) showed detectable changes 0.25-75 months before allograft rejection became clinically manifest: 13/22 (59%) showed both specular microscopy and Scheimpflug imaging changes; 5/22 (23%) only had changes on Scheimpflug imaging; and 2/22 (9%) only had specular microscopy changes. In 18/22 (82%) and 14/22 (64%) eyes, subclinical keratic precipitates and endothelial cell morphology changes could be detected, respectively. A total of 11/22 (50%) eyes concurrently showed a >10% drop in endothelial cell density and 4/22 (18%) a >7% pachymetry increase. Of the control eyes, 7/22 (32%) showed changes with specular microscopy but not with Scheimpflug imaging. CONCLUSIONS: Combined analysis of specular microscopy and Scheimpflug imaging may allow recognizing an upcoming allograft rejection in over 90% of eyes and up to 6 years before rejection becomes clinically manifest. Early recognition of eyes at risk may allow for targeted intensified steroid treatment to prevent endothelial cell damage associated with rejection.

Evaluation of the Suitability of Biocompatible Carriers as Artificial Transplants Using Cultured Porcine Corneal Endothelial Cells.

Purpose/Aim: Evaluating the suitability of bioengineered collagen sheets and human anterior lens capsules (HALCs) as carriers for cultivated porcine corneal endothelial cells (pCECs) and in vitro assessment of the cell-carrier sheets as tissue-engineered grafts for Descemet membrane endothelial keratoplasty (DMEK). MATERIALS AND METHODS: pCECs were isolated, cultured up to P2 and seeded onto LinkCell™ bioengineered matrices of 20 µm (LK20) or 100 µm (LK100) thickness, and on HALC. During expansion, pCEC viability and morphology were assessed by light microscopy. ZO-1 and Na+/K+-ATPase expression was investigated by immunohistochemistry. Biomechanical properties of pCEC-carrier constructs were evaluated by simulating DMEK surgery in vitro using an artificial anterior chamber (AC) and a human donor cornea without Descemet membrane (DM). RESULTS: During in vitro expansion, cultured pCECs retained their proliferative capacity, as shown by the positive staining for proliferative marker Ki67, and a high cell viability rate (96 ± 5%). pCECs seeded on all carriers formed a monolayer of hexagonal, tightly packed cells that expressed ZO-1 and Na+/K+-ATPase. During in vitro surgery, pCEC-LK20 and pCEC-LK100 constructs were handled like Descemet stripping endothelial keratoplasty (DSEK) grafts, i.e. folded like a "taco" for insertion because of challenges related to rolling and sticking of the grafts in the injector. pCEC-HALC constructs behaved similar to the DMEK reference model during implantation and unfolding in the artificial AC, showing good adhesion to the bare stroma. CONCLUSIONS: In vitro DMEK surgery showed HALC as the most suitable carrier for cultivated pCECs with good intraoperative graft handling. LK20 carrier showed good biocompatibility, but required a DSEK-adapted surgical protocol. Both carriers might be notional candidates for potential future clinical applications.

In Vivo Endothelial Cell Density Decline in the Early Postoperative Phase After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To evaluate endothelial cell density (ECD) in the first 6 months after Descemet membrane endothelial keratoplasty (DMEK) by eliminating method error as a confounding variable. METHODS: From 24 DMEK eyes operated for Fuchs endothelial corneal dystrophy, from which specular microscopy images could be taken at 1 day and 6 months postoperatively, ECD values were compared between these 2 time points. RESULTS: Using the 1-day ECD measurement as baseline, mean ECD decreased from 1913 (±326) cells/mm to 1524 (±393) cells/mm at 6 months, a decline of -18 (±19)%. With the 1-week ECD as baseline [1658 (±395) cells/mm], the decline at 6 months was -6 (±19)% and when using preoperative ECD as baseline [2521 (±122) cells/mm], the decline was -39 (±16)% at 6 months. CONCLUSIONS: After DMEK, ECD shows an in vivo decline of 18% from 1 day to 6 months postoperatively, with a sharp 13% drop in the first week, and a slower decrease thereafter. The remaining difference of 20% from preoperative ECD values may be attributed to a measurement error in the eye bank with an overestimation of the graft's viable endothelial cell population and/or intraoperative trauma to the graft.

Asymmetrical endothelial cell migration from in vitro Quarter-Descemet membrane endothelial keratoplasty grafts.

PURPOSE: To investigate in vitro central and peripheral corneal endothelial cell (EC) migration from Quarter-Descemet membrane endothelial keratoplasty (Quarter-DMEK) grafts. METHODS: Quarter-DMEK grafts were obtained from 10 corneas ineligible for transplantation but with intact and viable ECs. Ten Quarter-DMEK grafts were 'sandwiched' between two glass slides and cultured over 1 week in a humidified atmosphere at 37 °C and 5% CO2 . Cell migration was evaluated by light microscopy at standardized time intervals. In addition, immunohistochemistry analyses were performed to assess the detailed structural organization of ECs in the corneal centre and far periphery. RESULTS: Endothelial cell (EC) migration occurred from the radial cut graft edges, but not from the far peripheral area. Cell migration followed three different migration patterns: (1) individual cell migration, (2) uncoordinated cell migration of cell clusters and (3) collective migration in which ECs moved as a sheet. Immunostaining showed the presence of ECs up to the far periphery but with different expression patterns of phenotypical markers ZO-1, Na+ /K+ -ATPase and vimentin compared to central ECs. CONCLUSION: In vitro EC migration from Quarter-DMEK grafts occurs along the radial cut edges with a decrease in migration activity towards the corneal far periphery. No migration occurred along the outer peripheral corneal edge possibly due to a different anatomical matrix in the far periphery. Hence, ECs from the far periphery may not contribute to corneal clearance of the adjacent bare area after Quarter-DMEK surgery, but these cells may constitute a valuable cellular reserve on the graft.

IL-7-mediated protection against minor-antigen-mismatched allograft rejection is associated with enhanced recovery of regulatory T cells.

BACKGROUND AND OBJECTIVES: Interleukin-7 (IL-7) has been studied for its possible immunorestorative capacities following stem cell transplantation and has been shown to enhance post-transplant immune recovery predominantly by peripheral T-cell expansion. A major concern of IL-7 is its possible aggravating effect on graft-versus-host and host-versus-graft reactivity. DESIGN AND METHODS: To study the effect of IL-7 on host-versus-graft reactivity, we applied IL-7 in an experimental transplantation model using RAG-1-/- mice supplied with B6 CD45.1 congenic T cells as recipients of T-cell depleted allogeneic bone marrow grafts. RESULTS: Rejection of minor antigen-mismatched bone marrow was significantly reduced in IL-7 treated recipients compared with PBS treated control mice. Rejection was observed in 2 out of 18 IL-7 treated mice compared with 9 out of 17 PBS treated mice (11% vs. 53%; p=0.012). IL-7 administration resulted in enhanced recovery of peripheral blood CD4+CD25+ regulatory T cells (Treg) with a concomitant increase in peripheral blood Foxp3 mRNA expression. IL-7Ra (CD127) was expressed by the vast majority of CD4+Foxp3+ T cells. The incidence of graft rejection following fully MHC mismatched bone marrow transplantation was not reduced nor enhanced by IL-7 administration. INTERPRETATION AND CONCLUSIONS: Post-transplant IL-7 administration protects against minor antigen-mismatched bone marrow rejection, which may be due to enhanced Treg recovery.

Minimizing Graft Preparation Failure in Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To report the failure rate of 2 graft preparation techniques for Descemet membrane endothelial keratoplasty (DMEK) and to evaluate how to minimize graft preparation failure. METHODS: Retrospective, nonrandomized study at an eye bank specialized in graft preparation for lamellar keratoplasty. For 1416 donor corneas, the DMEK graft preparation failure rate was evaluated for 2 different techniques, technique I: "Standardized traditional technique" (n = 341) and technique II: "Standardized no-touch technique" (n = 933), and for grafts that were converted from technique II to technique I during preparation (n = 142). RESULTS: The overall failure rate averaged 3.9% (55/1416): 7.0% (24/341) for technique I and 2.9% (31/1075) for technique II (P < 0.05). Tissue preparations which were converted from technique II to technique I failed in 13.4% (19/142), whereas for grafts that were entirely prepared by technique II, the failure rate was only 1.3% (12/933). The endothelial cell density decrease (before compared with after preparation) did not differ for both techniques (1.1% vs. 0.2%, P > 0.05). CONCLUSIONS: Various DMEK graft preparation techniques may provide failure rates of <4%. A "no-touch preparation" approach (technique II) may combine good graft quality (completely intact endothelial cell layer, ie, negligible preparation-induced endothelial cell density decrease) with low risk of dissection failure, leaving the possibility of conversion to "traditional preparation" (technique I) as a backup method.

Sex Chromosome Analysis of Postmortem Corneal Endothelium After Sex-Mismatch Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To identify the origin of corneal endothelial cells (host or donor) present on grafts at various time points after Descemet membrane endothelial keratoplasty (DMEK), using fluorescence in situ hybridization (FISH) of sex chromosomes on post mortem corneas with sex mismatch between the donor and host. METHODS: Corneoscleral buttons of 6 post mortem DMEK eyes of 4 patients, operated for Fuchs endothelial dystrophy, with an average postoperative time of 2.6 (±1.8) years (range, 7 months-4.5 years), of 2.5 (±1.7) years (range, 7 months-4 years), were processed for FISH detection of XX (female) or XY (male)-labeling signals in corneal endothelial cells in the central area of the DMEK graft. Two male patients underwent bilateral DMEK with grafts from female donors, and 2 female patients underwent unilateral DMEK and received a graft from a male donor. RESULTS: FISH consistently showed the presence of donor endothelial cells across the graft area, with signaling of sex chromosomes opposite to the sex of the host. CONCLUSIONS: Donor endothelial cells may survive up to 4.5 years after DMEK. If so, the lower incidence of allograft rejection in DMEK may not be explained by early host cell replacement. Potential host cell migration may be limited by donor/recipient cell-cell contact inhibition.

Outcome and Histopathology of Secondary Penetrating Keratoplasty Graft Failure Managed by Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To describe the clinical outcome and histopathology of Descemet membrane endothelial keratoplasty (DMEK) performed for secondary graft failure after penetrating keratoplasty (PK). METHODS: A total of 11 eyes from 10 patients who underwent DMEK for secondary PK graft failure at a tertiary referral center were included in this retrospective study. Best-corrected visual acuity, endothelial cell density, and central pachymetry were evaluated before and at regular time intervals up to 36 months after DMEK and complications were recorded; 1 post mortem cornea was available for light microscopy. RESULTS: At their last follow-up visit (on average, 16 months after DMEK), 7 of 11 transplanted corneas were clear. In the 7 eyes with clear grafts, 5 had a best-corrected visual acuity of ≥20/25 (≥0.8), central pachymetry averaged 535 (±70) µm, and endothelial cell density averaged 1045 (±500) cells/mm. Of the 11 eyes, 4 required rebubbling in the early postoperative phase; 1 eye was left with a small (<1/3) detachment. Light microscopy of the pathology specimen showed complete attachment of the DMEK graft onto the preexisting PK posterior stroma, with interface scarring over DMEK graft folds and underneath the graft area that had initially been detached. CONCLUSIONS: DMEK may be a viable option to manage secondary PK graft failure with acceptable outcomes in many cases. Rebubbling for graft detachment may be anticipated, especially because of preexisting glaucoma conditions (severe decompensation, hypotony, and tubes from glaucoma-draining devices). Graft reattachment may occur through interface scarring.

360-Degree Scheimpflug Imaging to Predict Allograft Rejection After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To describe the use of 360-degree Scheimpflug imaging as a diagnostic tool for detection and documentation of subtle corneal changes preceding upcoming allograft rejection after Descemet membrane endothelial keratoplasty (DMEK). METHODS: A total of 17 eyes (16 patients) were diagnosed with clinically manifest allograft rejection 2 to 42 months after DMEK. 360-degree Scheimpflug images of consecutive follow-up examinations (from 3-60 mo) of "asymptomatic" eyes before, during, and after rejection were retrospectively analyzed, to determine which abnormalities could be detected before allograft rejection became clinically manifest. The images were compared with DMEK control eyes (without rejection episode). RESULTS: Scheimpflug images at the time of rejection showed keratic precipitates as distinct retrocorneal nodular elevations and/or a significant increase in pachymetry of ≥7%. More subtle changes could be identified retrospectively in 9/17 eyes (53%) on an average at 8 (±5) months before rejection became clinically manifest; in all eyes, these subtle changes were not recognized at routine slit-lamp examinations by various ophthalmologists as inflammatory changes heralding allograft rejection. Secondary graft failure occurred in 4/17 eyes (24%). None of the control eyes showed relevant abnormalities with Scheimpflug imaging. CONCLUSIONS: By screening the posterior corneal surface with 360-degree Scheimpflug imaging, subtle inflammatory retrocorneal deposits can be detected and recorded during consecutive follow-up visits. Hence, Scheimpflug imaging may have the potential to become a diagnostic tool for early detection of upcoming allograft rejection in asymptomatic DMEK eyes, that is, before the immune response becomes clinically manifest and before substantial endothelial cell damage occurs.

"Salt and Pepper Endothelium" Recurring After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To describe the presence of "salt and pepper endothelium", that is, typical cellular inclusion bodies in a patient with Fuchs endothelial corneal dystrophy (FECD), that recurred in the donor corneal endothelial cells after Descemet membrane endothelial keratoplasty (DMEK). METHODS: A 76-year-old man underwent DMEK for FECD in his left eye. Routine specular microscopy imaging, best-corrected visual acuity measurements, and pachymetry measurements were performed before and after surgery. RESULTS: Besides large guttae indicating FECD, preoperative specular microscopy images showed variable-sized dark cellular inclusion bodies in the endothelial cells. One month after DMEK, donor endothelial cells appeared normal; however, at 3 months, the typical inclusion bodies reappeared and progressed slowly within a 4-year follow-up period. Both best-corrected visual acuity and pachymetry were stable throughout the study period. CONCLUSIONS: "Salt and pepper endothelium" recurred after the host tissue was exchanged by donor Descemet membrane, that is, a DMEK graft. These changes may indicate that either the donor corneal endothelial cell morphology is modified by adjacent tissue structures or that it is completely replaced by recipient endothelium within the first months after surgery.

Association Between Graft Storage Time and Donor Age With Endothelial Cell Density and Graft Adherence After Descemet Membrane Endothelial Keratoplasty.

IMPORTANCE: After retrospectively evaluating the clinical outcome of 500 consecutive cases after Descemet membrane endothelial keratoplasty (DMEK), we extended the analysis in this study by assessing the effect of donor-related parameters on endothelial cell density (ECD) decline and detachment rate in this group. OBSERVATIONS: This retrospective case series included 500 cases who had undergone DMEK from October 2007 to September 2012 at the Netherlands Institute for Innovative Ocular Surgery (NIIOS), Rotterdam, the Netherlands. Logistic regression analysis (n = 332 eyes) showed that donor age might be associated with a 3% increase in the risk for a detachment (odds ratio, 0.97; 95% CI, 0.94-1.00; P = .049) (ie, higher donor age seems to be associated with lower chances of a detachment). In addition, linear regression analysis indicated that graft storage time in medium was associated with ECD decrease (ie, the longer the storage time, the larger the decrease at 6 months after DMEK) (P = .01). CONCLUSIONS AND RELEVANCE: We showed an association between graft storage time and ECD decline after DMEK and possibly between donor age and graft detachment. Therefore, donor storage times should be kept as short as possible to improve short-term ECDs. More research is needed to draw definite conclusions on the possible effect of donor age on the chance of a detachment after DMEK.