Comparative Outcomes and Immune Mechanisms in Murine Endothelial Versus Penetrating Keratoplasty.

To calculate the number of corneal endothelial cells (CEC) on the posterior surface of the normal human cornea by measuring specific surface areas through anterior segment optical coherence tomography. The effects of age, sex, and variations between the right and left eyes were also investigated. This study involved 60 eyes of 30 normal subjects with no history of corneal disease. Subjects were divided into the following groups according to age: group A (20-39 years old), group B (40-59 years old), and group C (60-79 years old). Set areas of the corneal posterior surface were imaged and analyzed using anterior segment optical coherence tomography, and the number of CECs was calculated based on the area measured and a CEC density. The posterior corneal surface area measured within the central circular diameters of 10.2, 8.5, and 7.5 mm was 86.8, 63.8, and 48.4 mm in group A, 86.0, 63.8, and 48.4 mm in group B, and 87.0, 64.2, and 48.6 mm in group C, respectively. The total number of CECs on the posterior surface in the diameters of 10.2, 8.5, and 7.5 mm was 2.3 × 10, 1.7 × 10, and 1.3 × 10, respectively. No clinically relevant differences in the posterior surface were found in relation to age, sex, or variation between right and left eyes. Calculation of the CEC number on the corneal posterior surface is essential for determining the number of cells applied during penetrating keratoplasty, endothelial keratoplasty, or cultivated CEC injection therapy when available.

Corneal transplantation can restore visual function when visual impairment is caused by a corneal disease. However, this treatment is associated with the scarcity of cornea donors. The suitability of corneal donation from patients with glaucoma using ocular hypotensive agents (OHAs) is controversial. This study aimed to elucidate changes in corneal thickness, corneal endothelial cell density, and corneal endothelial cell hexagonality after OHA use in patients with primary open‐angle glaucoma. We retrospectively reviewed the data of 53 glaucoma suspect eyes without OHA use and 106 primary open‐angle glaucoma eyes under OHA use. All participants underwent corneal parameter assessment using SP‐3000P (Topcon Corp., Tokyo, Japan) at the time of diagnosis and the final visit. The OHA dose and timing of use were recorded. The ocular hypotensive agents score (OHAS) was determined based on the number, formula, frequency, and duration of OHA use. Baseline data showed no significant differences between the two groups with and without OHA use. At the final visit, the OHA‐treated group showed significantly lower corneal thickness and corneal endothelial cell density than those of the control group. A weak positive correlation between the OHAS and changes in corneal endothelial cell hexagonality was noted. However, no correlation was observed between the OHAS and changes in corneal thickness or endothelial cell density. In conclusion, patients with glaucoma and using OHAs should undergo the corneal structural properties examinations before donation to ensure the quality of donor cornea.

Some patients show poor visual outcomes after Descemet stripping automated endothelial keratoplasty. In such cases, secondary Descemet membrane endothelial keratoplasty can be performed to achieve complete visual recovery. Anterior segment optical coherence tomography (AS-OCT) is a valuable tool for the follow-up of posterior lamellar keratoplasty outcomes and complications. This study aimed to report the clinical outcome of secondary Descemet membrane endothelial keratoplasty for managing poor visual results in a patient with graft failure after a previous Descemet stripping automated endothelial keratoplasty, highlighting the importance of AS-OCT in the follow-up of endothelial keratoplasty. A 38-year-old woman with high myopia underwent Descemet stripping automated endothelial keratoplasty for bullous keratopathy after explantation of an angle-supported phakic intraocular lens. Two years after keratoplasty, the patient experienced poor visual acuity (counting fingers), and significant corneal edema was observed on clinical examination hindering visualization of the anterior chamber structures. Anterior segment optical coherence tomography showed a failed and thickened graft adhering well to the recipient cornea in an anterior chamber without other comorbidities. Therefore, the graft was removed and replaced with a Descemet membrane endothelial keratoplasty graft without any complications. One year later, the clinical outcome was evaluated by comparing the pre-operative and post-operative best-corrected visual acuity, biomicroscopy findings, endothelial cell density, and corneal central thickness. Anterior segment optical coherence tomography is an important tool when deciding on the surgical technique to be applied and for the post-surgical monitoring of endothelial corneal grafts. This case demonstrates the successful management of Descemet stripping automated endothelial keratoplasty graft failure with Descemet membrane endothelial keratoplasty graft, highlighting the importance of AS-OCT in detecting complications such as graft dislocation and primary graft failure. In addition, corneal thickness measured using AS-OCT serves as a critical predictor of graft failure, as observed in this case.

Purpose: Endothelial keratoplasty (EKP) has become increasingly popular in the treatment of corneal disease. However, the global shortage of human donor corneas limits clinical corneal transplantation. Genetically engineered (GE) pigs may provide an alternative source of corneas for EKP. The aim of this study was to evaluate corneal endothelial cells (CECs) from wild-type (WT) and GE pigs. Methods: Density, size of CECs, and the percentage of hexagonal cells (as a measure of heterogeneity) were measured by ex vivo confocal microscopy in corneas from WT and GE pigs of different ages – neonatal (4–5 days), young (5–15 weeks), adult (5–15 months), and old (20–42 months). α1,3-galactosyltransferase gene-knockout (GTKO) pigs transgenic for the human complement-regulatory protein(s), CD46 (GTKO/CD46) +/− CD55 (GTKO/CD46/CD55) were used as sources of GE corneas. Results: Mean CEC densities (cells/mm2) were neonatal (5968), young (3789), adult (2589), and old (2070). As with human corneas, there was an age-dependent decrease in pig CEC density and increase in pig CEC size. However, unlike human corneas, there was no correlation between the percentage of hexagonal cells (approximately 50% in all pig corneas) and age, suggesting that heterogeneity is intrinsic for pig corneas. Genetic modification did not affect CEC density, size, or morphology compared to WT pigs. Conclusion: Because of the availability of young pigs and their greater CEC density (and the protection afforded against the human immune response), GE pigs could provide an unlimited source of corneas for clinical EKP.

To describe histopathologic characteristics of an endothelial keratoplasty (EK) that was performed to treat a previously failed penetrating keratoplasty (PK) and in which the cornea failed to clear after partial detachment of Descemet membrane from the EK donor button. The Descemet membrane and endothelium from the PK were intentionally retained during the EK procedure. After EK, the cornea failed to fully clear in 5 months, and a PK was performed. The removed corneal button was grossly described and routinely processed for hematoxylin-eosin (H&E) and periodic acid-Schiff (PAS) staining, with photographs taken of any pertinent findings. Grossly on the endothelial side, there was some adherent iris pigment delineating an off-center fold in the EK Descemet membrane, consistent with intraoperative observation of a fold across the width of the donor button and postoperative slit-lamp images showing partial detachment of Descemet membrane. Microscopic examination revealed a recipient corneal button from a prior PK centrally and EK donor button attached posteriorly. Descemet membrane was not stripped from the prior PK during EK and was intact. No endothelial cells were detected on the PK Descemet membrane. The anterior stromal surface of the EK was well apposed to the prior PK Descemet membrane, with no pseudoanterior chamber or cleft of any type noted between them. The EK Descemet membrane had a central fold, and the endothelium was markedly attenuated. The EK graft was well apposed with apparent good adherence to the recipient's prior failed PK, and early endothelial failure was attributable to partial Descemet membrane detachment.

Changing Practice Patterns and Long-term Outcomes of Endothelial Versus Penetrating Keratoplasty: A Prospective Dutch Registry Study

Regulatory T cells promote corneal endothelial cell survival following transplantation via interleukin-10.

Fibrillar Layer as a Marker for Areas of Pronounced Corneal Endothelial Cell Loss in Advanced Fuchs Endothelial Corneal Dystrophy

The aim of this study was to evaluate the effect of trabeculotomy (TLO) on glaucoma and endothelial cell loss after penetrating keratoplasty (PK). A retrospective study was conducted on consecutive patients who underwent PK and in whom more than 24 months of follow-up was available. Patients were categorized into the PK+TLO group [ie, TLO for post-PK glaucoma (n = 10)] and the PK group [PK alone (n = 73)]. Intraocular pressure (IOP) was evaluated during each follow-up examination. Central corneal endothelium images were obtained and analyzed to determine corneal endothelial cell (CEC) density. The mean duration period from original PK to TLO for secondary glaucoma was 25.5 ± 34.9 months in the PK+TLO group. Mean preoperative IOP in the PK+TLO group was 35.8 mm Hg, and decreased to 17.5 mm Hg at 24 months postoperative (P < 0.01). CEC density decreased in the same manner in both groups. In the PK+TLO group, mean CEC density was 1838 cells per square millimeter before TLO and decreased to 1195 cells per square millimeter at 24 months after TLO. In the PK group, mean CEC density decreased from 1870 to 1209 cells per square millimeter at each corresponding time point. TLO for post-PK glaucoma appeared to safely lower IOP, although repeated surgeries were required in some patients, and did not accelerate CEC loss.

Lamellar Keratoplasty

Graft survival and endothelial outcomes in the new era of endothelial keratoplasty

Infectious keratitis after lamellar keratoplasty

The aim of this study was to investigate the immune cells on corneal endothelium of the graft in patients who underwent penetrating keratoplasty (PK), Descemet-stripping endothelial keratoplasty (DSEK), and Descemet membrane endothelial keratoplasty (DMEK). A total of 43 eyes of 43 patients who underwent PK (17 eyes), DSEK (13 eyes), and DMEK (13 eyes) and who did not show any sign of graft rejection were recruited for the study. Patients who underwent cataract surgery (26 eyes) served as controls. Immune cells on the corneal endothelium were examined with laser in vivo confocal microscopy. The associations between the corneal endothelial cell density, type of keratoplasty, aqueous flare, repeated keratoplasty, and time after surgery versus the density of immune cells were investigated. In vivo confocal microscopy visualized similar numbers of immune cells on the corneal endothelium in the PK, DSEK, and DMEK groups, whereas no immune cells were observed in any of the control patients. The numbers of immune cells tended to be higher in regraft eyes in the PK group (P = 0.00221) and in the DSEK group (P = 0.168) than those in the primary graft eyes. No significant association was found between the density of immune cells and corneal endothelial cell density in the PK, DSEK, and DMEK groups. Immune cells were observed to a similar extent in the eyes of PK, DSEK, and DMEK subjects even in the absence of any clinical sign of immune rejection. A further prospective longitudinal study will evaluate the effect of immune cells on long-term graft survival and the risk for graft rejection.

We appreciate the invitation to respond to Lee's correspondence titled “Management of iridocorneal endothelial syndrome from a cornea and glaucoma perspective.”1 We would like to thank the author for the positive comments regarding our original article “A comparison of penetrating and endothelial keratoplasty in patients with iridocorneal endothelial syndrome: a registry study.”2 Iridocorneal endothelial (ICE) syndrome is a particularly challenging pathology with serious complications, most notably secondary glaucoma and corneal oedema. We agree that, if possible, close follow-up and continuous care including surgical intervention should best be performed by a specialist experienced in both cornea and glaucoma. Our study focused on graft survival and showed poor long-term corneal graft survival in patients with ICE syndrome compared to corneal grafts for other indications, consistent with previous reports. Surprisingly, we observed higher median graft survival of penetrating keratoplasty (PK) compared to Descemet stripping (automated) endothelial keratoplasty (DS(A)EK) in our patient cohort, which may seem counterintuitive at first glance. Our original article lists a few possible factors that could have contributed to this outcome such as the crowded anterior chamber often found in ICE syndrome and, hence, less space to perform endothelial keratoplasty (EK), a higher rate of endothelial cell loss in the first postoperative year after DS(A)EK compared to PK or corneal changes other than endothelial transformation, which remain to be further elucidated. Interestingly, better graft survival after PK compared to EK has also been observed for indications such as Fuchs' dystrophy or pseudophakic bullous keratopathy in previous large registry studies.3, 4 We do agree upon the many advantages of EK over PK in terms of refractive outcome, visual recovery, tectonic stability and difficulty of repeated grafting if necessary.5 The high risk of secondary glaucoma after PK also should be mentioned as a disadvantage compared to EK. Hence, despite longer graft survival after PK, the choice of EK over PK as the first intervention for corneal decompensation in ICE syndrome may be preferable in many cases. We appreciate Lee's insights and suggestions, particularly regarding the placement of a glaucoma drainage tube in the sulcus rather than the anterior chamber angle as well as the preference of a hydrophobic intraocular lens over a hydrophilic model due to their propensity to calcify after exposure to air or gas. These valuable suggestions highlight the fact that treating patients with ICE syndrome requires careful consideration of possible further surgical interventions in the trajectory of the disease as well as complex strategies to achieve the best outcome for the patient. Despite longer graft survival of PK in our patient cohort, we do highlight in our original article that this is not the only factor in deciding on the choice of graft type. This decision requires synthesis of other factors including the individual patient's situation and anterior segment anatomy as well as their surgeon's preference. Hence, we do not wish to give general advice for treating ophthalmic surgeons in their preference of one method over the other. The operations of the Australian Corneal Graft Registry are funded by the Australian Organ and Tissue Authority (DonateLife). The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.

This study investigates the possible role of the filtration bleb in the continuous decrease in corneal endothelial cell (CEC) density observed following trabeculectomy. This study involved 51 eyes of 37 glaucoma patients who underwent trabeculectomy. TheCEC density was determined by contact specular microscopy in three areas: (1) the cornea center, (2) near the trabeculectomy filtration bleb, and (3) the opposite side of the bleb. The eyes were grouped according to post-surgical follow-up years: 0-1 (Group 1), 1-2 (Group 2), 2-3 (Group 3), 3-4, (Group 4), and 4+ years (Group 5). The mean CEC densities at the opposite side of the bleb, in the cornea center, and near the bleb were 2210 ± 487, 1930 ± 528, and 1519 ± 507 cells/mm2, respectively, in all eyes. The CEC density was significantly lower near the bleb than at the other two sites. The coefficient of variation was significantly higher near the bleb than at the other two sites. The CEC densities at the cornea center and at the opposite side of the bleb showed no significant differences. However, the CEC densities near the bleb showed time-dependent decreases to 1790, 1601, 1407, 1339, and 1224 cells/mm2 for Groups 1, 2, 3, 4, and 5, respectively. CEC density following trabeculectomy decreased near the bleb, but not at the cornea center, suggesting that the involvement of the filtration bleb in CEC density loss should be further examined to elucidate the pathology of CEC loss following trabeculectomy.