Chronic Endothelial Cell Loss Research Articles

Changes in visual outcomes and ocular morphometrics after foldable myopic and toric intraocular lens implantation: 5-year results.

To evaluate the refractive, visual, and morphometric changes after implantation with a foldable iris-fixated phakic intraocular lens (pIOL) to correct myopia or astigmatism. University Eye Clinic Maastricht, the Netherlands. Prospective case series. We evaluated patients implanted with the Artiflex Myopia Toric (Ophtec B.V.) iris-fixated pIOL as of January 2004. Measurements were performed annually and reported after 1 and 5 years. The study included 481 eyes (277 patients; age 39.8 ± 10.9 years [SD]). 5 years postoperatively, 91% of eyes were within ±1.0 diopter (D) of target, and the mean myopization over a 5-year period was 0.22 D (P < .001). The logMAR corrected distance visual acuity (CDVA) increased by a mean 0.015 (P = .015) over 5 years; 88% of eyes had a CDVA of 20/20 or better, and 5.5% lost 2 or more lines of CDVA. Mean uncorrected distance visual acuity (UDVA) increased by 0.045 logMAR over 5 years (P < .001); 96% reached an UDVA of 20/40 or more. Anterior chamber depth (ACD) decreased by 0.04 mm (P < .001), and axial length (AL) increased by 0.23 mm (P < .001) over 5 years. Chronic endothelial cell loss showed a 5-year decline of 320 cells/mm2 in the myopic and 310 cells/mm2 in the toric subgroups (P < .001). Cataract resulted in pIOL explantation in 4.0% of eyes (mean survival 59.0 ± 40.0 months); higher preoperative age (hazard ratio [HR], 1.13; P < .001) and smaller ACD (HR, 6.80; P = .035) were risk factors for shorter survival due to cataract formation. Over 5 years, logMAR CDVA and UDVA decreased significantly due to myopization caused by lenticular changes and AL elongation.

Comparison of Endothelial Cell Loss following the Big Bubble versus the Microbubble Incision Technique during Deep Anterior Lamellar Keratoplasty in Eyes with Keratoconus

Introduction. Deep anterior lamellar keratoplasty (DALK) is now becoming an increasingly popular surgical technique in treating corneal stromal pathologies with healthy endothelium. Several advantages of DALK over penetrating keratoplasty (PKP) have been described such as maintenance of globe integrity, absence of endothelial rejection, and a low rate of chronic endothelial cell loss (ECL). ECL following PKP results in 50% cell loss after 2 years from the estimated graft endothelial cell density (ECD). Although there are several reports confirming that ECL following DALK is similar to the physiologic cell loss 2 years after surgery, few reports discussed the surgically induced ECL due to difficulty in preoperative imaging of ECD. Materials and Methods. This prospective, interventional study included 20 eyes of 20 patients, who underwent DALK surgery. 11 eyes underwent DALK using the big bubble technique, while 9 eyes underwent the microbubble technique. Postoperative evaluation was done 3 months after surgery and included best spectacle corrected visual acuity (BSCVA), keratometric readings, and refraction measured using an autokeratorefractometer (Topcon KR800, Japan) and endothelial cell density (ECD) using noncontact specular microscopy (Nidek CEM-530, Japan). Results. Regarding postoperative parameters such as postoperative logMAR visual acuity, postoperative mean K, and postoperative K max, there was no statistical difference found between both groups ( P = 0.754 , P = 0.119 , and P = 0.970 , respectively). Regarding change in specular endothelial cell density and percent change in the specular endothelial cell density, again there was no statistical difference between both groups with P = 0.057 and P = 0.126 , respectively (significance defined as P &lt; 0.05 ). Conclusion. ECD is not affected by failure of the big bubble to form and continuing DALK via the microbubble technique.

Explantation of phakic intraocular lenses: causes and outcomes.

To describe reasons for explantation of anterior and posterior chamber phakic intraocular lenses (pIOLs), as well as outcomes of the surgery. The medical files of patients who underwent pIOL explantation due to complications were reviewed. All patients were divided into three groups based on the type of explanted pIOL: anterior chamber angle-supported (AS pIOL), anterior chamber iris-fixated (IF pIOL), and posterior chamber (PC pIOL). Sixty-two eyes of 41 patients were evaluated. There were 26 (41.9%), 16 (25.8%), and 20 (32.2%) eyes in the AS pIOL, IF pIOL, and PC pIOL groups, respectively. The mean interval between the implantation and removal of the pIOL (i.e., survival time) was 13.6 ± 8.1years (range 0.01-21.22years). The mean follow-up after the explantation was 22.5 ± 4.0months (range 11.3-28.7months). The main causes of explantation were cataract in the PC pIOL group (60%) and chronic endothelial cell loss in the AS pIOL group (53.8%) and IF pIOL group (56.2%). Overall, the procedure most often combined with pIOL explantation was phacoemulsification and implantation of a posterior chamber IOL (40.3%), followed by keratoplasty (9.6%). Intraoperative complications were significantly more common in the AS pIOL group than the other groups (p < 0.001). Explantation of anterior chamber pIOLs due to severe endothelial cell loss and the proportion of keratoplasty was more common in patients with a relatively long survival time. Therefore, patients with pIOL implantation should be monitored regularly after surgery.

Five-Year Endothelial Cell Loss After Implantation With Artiflex Myopia and Artiflex Toric Phakic Intraocular Lenses

To evaluate the long-term changes in endothelial cell density (ECD) after the implantation of 2 types of foldable iris-fixated phakic intraocular lenses (pIOLs) for the treatment of myopia and astigmatism. Prospective clinical cohort study. Two-hundred and ninety-three and 188 eyes implanted with, respectively, the Artiflex Myopia and Artiflex Toric (Ophtec B.V., Groningen, The Netherlands) iris-fixated pIOL for the treatment of myopia or astigmatism at the University Eye Clinic Maastricht as of January 2004. One-hundred and forty-six eyes from the myopic and 64 eyes from the toric groups completed a 5-year follow-up. Main outcome measures were chronic endothelial cell (EC) loss, percentage of eyes with a ≥25% decrease in ECD, and the percentage of eyes with an ECD < 1500 cells/mm2. Chronic EC loss showed an annual decline of 64 cells/mm2 in the myopic (P < .001, standard error 3.58) and 62 cells/mm2 in the toric (P < .001, standard error 3.77) groups. Total chronic EC loss from 6months to 5 years postoperatively was 10.5% in the myopic and 10.2% in the toric groups. After 5 years, an ECD decrease of ≥25% occurred in 4.4% and 4.3% of eyes, and an ECD < 1500 cells/mm2 was reported in 3.0% and 0.0% of eyes, respectively. Explantation of a pIOL owing to EC loss was required in 3.1% and 0% of eyes. Chronic EC loss was around 10% over a 5-year period in eyes implanted with the foldable myopic (toric) pIOL. In up to 3.1% of eyes significant EC loss resulted in subsequent pIOL explantation.

Progressive idiopathic unilateral corneal endothelial failure of unknown aetiology in phakic eyes

AimTo describe a cohort of patients with irreversible unilateral bullous keratopathy (BK) of undetermined aetiology.MethodRetrospective, single-centre case series in a tertiary corneal referral centre.ResultsEleven consecutive patients (nine females; mean age...

Association between corneal endothelial cell densities and elevated cytokine levels in the aqueous humor

Annual reduction rate of corneal endothelial cell density (ECD) varies among etiologies, however, the cause of chronic endothelial cell loss is still unknown. We recently reported the elevation of inflammatory cytokines in the aqueous humor (AqH) in eyes with bullous keratopathy and low ECD. To evaluate the association between ECD and aqueous cytokine levels, we collected a total of 157 AqH samples prospectively. The AqH levels of cytokines were measured and multivariate analyses were conducted to find the correlation between ECD, aqueous cytokine levels and clinical factors, such as number of previous intraocular surgeries and protein concentration in AqH. As a result, ECD was negatively correlated with specific cytokine levels, including IL-1α, IL-4, IL-13, MIP-1β, TNF-α and E-selectin (all P < 0.05). The aqueous cytokine levels showed different correlations with these clinical factors; the number of previous intraocular surgeries was associated with all cytokines except MIP-1α. The AqH protein concentration and the status of intraocular lens showed similar patterns of elevation of IL-1α, IL-4, IL-6, IL-8, IL-10, IL-13, IL-17A, MIP-1β, MCP-1, E-selectin, P-selectin and sICAM-1. In conclusion, elevation of AqH cytokine levels was associated with reduced ECDs. AqH cytokine levels showed significant correlations with clinical factors associated with low ECDs.

Long-Term Endothelial Cell Loss in Patients with Artisan Myopia and Artisan Toric Phakic Intraocular Lenses: 5- and 10-Year Results

To evaluate the long-term change in endothelial cell density (ECD) after the implantation of 2 types of rigid iris-fixated phakic intraocular lenses (pIOLs) for the treatment of myopia and astigmatism. Prospective, clinical cohort study. A total of 507 eyes of 289 patients receiving the Artisan Myopia or Artisan Toric (Ophtec B.V., Groningen, The Netherlands) iris-fixated pIOL for the treatment of myopia or astigmatism at the University Eye Clinic Maastricht as of January1998. A total of 381 myopic and 126 toric pIOLs were implanted. Five- and 10-year follow-ups were completed by 193 and 127 eyes implanted with the myopic pIOL and by 40 and 20 eyes implanted with the toric pIOL, respectively. Chronic endothelial cell (EC) loss, percentage of eyes with a decrease of ≥25% in ECD, and percentage of eyes with an ECD <1500 cells/mm2. Chronic EC loss was calculated from 6 months postoperatively to the end of follow-up and showed an annual ECD decline of 48 cells/mm2 (standard error, 3.14) and 61 cells/mm2 (standard error, 6.30) in the myopic (P < 0.001) and toric (P < 0.001) groups, respectively, resulting in a total EC loss of 16.6% and 21.5% from 6 months to 10 years postoperatively, respectively. Ten years after implantation, ECD had decreased by ≥25% in 7.9% and 6.3%, whereas ECD was <1500 cells/mm2 in 3.9% and 4.0% in the myopic and toric groups, respectively. Explantation of the pIOL occurred in 6.0% in the myopic group and 4.8% in the toric group. Risk factors for increased EC loss were a shallow anterior chamber depth (ACD) (P ≤ 0.005) and a smaller distance between the central and peripheral pIOL edge to the endothelium (P ≤ 0.005). A significant linear chronic EC loss was reported after implantation with myopic or toric iris-fixated pIOLs. A smaller ACD and smaller distance between pIOL edge and endothelium were risk factors for EC loss. Modification of preoperative age-related ECD thresholds is indicated to maintain an ECD that warrants safe future combined pIOL explantation and cataract surgery.

Prolonged organ culture reduces the incidence of endothelial immune reactions.

PURPOSE The number of antigen-presenting cells decreases during organ culture of corneoscleral discs. This might result in a decrease of immune reactions with increasing duration of organ culture. To investigate this hypothesis, we performed a retrospective analysis of all penetrating keratoplasties that were consecutively performed over the last 5 years.PATIENTS AND METHODS All cases of penetrating keratoplasties (n=1006) were divided into two groups, with the division made at the median of the storage time (21 days). These two groups were compared by a Cox proportional hazards survival model regarding the incidence of endothelial immune reactions, clear graft survival, and chronic endothelial cell loss following penetrating keratoplasty considering patient's age, donor's age, and risk situation as co-variates.RESULTS We observed statistically significantly fewer endothelial immune reactions (20.1% (95% confidence interval 15.5-24.5%) after 2 years) in the group with a storage time of more than 21 days compared with the group with a storage time of <21 days (26.5% (95% confidence interval 21.6-31.2%) after 2 years). However, the duration of organ culture did not have a statistically significant effect on clear graft survival or chronic endothelial cell loss.CONCLUSION Our results demonstrate that an increased duration of organ culture leads to a lower incidence of endothelial immune reactions following penetrating keratoplasty. However, we do not recommend increased storage times in general as overall graft survival did not improve. The reason for this apparent paradox may be that the endothelial cell count decreases during storage time.

Phakic intraocular lens: Two-year results and comparison of endothelial cell loss with iris-fixated intraocular lenses

To evaluate the efficacy, safety, and stability of a foldable angle-supported Acrysof Cachet phakic intraocular lens (pIOL) to correct moderate to high myopia and compare endothelial cell loss after iris-fixated Artisan and Artiflex pIOL implantation. University Eye Clinic Maastricht, the Netherlands. Retrospective observational study. Foldable angle-supported pIOL implantation for myopia ranging from -6.0 to -16.5 diopters (D) was done. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, spherical equivalent (SE), and adverse events were documented preoperatively and 6 months and 1 and 2 years postoperatively. Endothelial cell loss after implantation of the foldable angle-supported pIOL and iris-fixated pIOLs was compared 6 months and 1 and 2 years postoperatively. There were 158 eyes. The UDVA was equal to or more than 20/25 in 95% of eyes at 1 and 2 years postoperatively. The mean SE was -0.17 D ± 0.43 (SD) 2 years postoperatively. One patient developed pupil ovalization, resulting in explantation of the pIOL from both eyes. Acute endothelial cell loss in the foldable angle-supported pIOL group was -3.2% ± 0.7%, significantly higher than after iris-fixated pIOL implantation. Chronic endothelial cell loss from 6 to 24 months after surgery was -3.8% ± 0.7%. At the 2-year follow-up, the chronic endothelial cell loss in the foldable angle-supported pIOL group was not different than with iris-fixated pIOLs (P > .05). The foldable angle-supported pIOL effectively corrected moderate to high myopia. However, acute surgical endothelial cell loss was significantly higher than with iris-fixated pIOLs. Dr. Nuijts is a consultant to Alcon Laboratories, Inc., Théa Pharma GmbH, and ASICO LLC; he has received study grants from Acufocus, Inc., Alcon Laboratories, Inc., Carl Zeiss Meditec AG, Ophtec BV, and Physiol S.A. No other author has a financial or proprietary interest in any material or method mentioned.

Hornhautendothelzelldichte in Abhängigkeit vom Schweregrad der Pseudoexfoliation

Pseudoexfoliation (PEX) syndrome is a common, age-related disease which is associated with the multifocal deposition of fibrillar PEX material in intra- and extraocular tissues. Subsequently among others second chronic open-angle glaucoma and corneal endothelial cell loss occurs. The present study analysed whether there is a correlation between the stage of the PEX process and corneal endothelial cell density (cECD), regardless of the non-existence or proof of secondary glaucoma. One eye of 109 Caucasian subjects (mean age 71.7 years) was examined by slit-lamp microscopy and classified based on visible PEX deposits on the lens (mild and severe) and presence of glaucoma in 4 study groups. The control groups were healthy subjects and patients with primary open angle glaucoma (POAG). The cECD was measured with the endothelial cell mirror microscope (SeaEagle). All study groups and the POAG group showed a significant cECD reduction compared to the healthy control group: POAG: 6.0 %; PEX syndrome: mild 5.5 % and severe 11.0 %, PEX glaucoma: mild 7.7 % and severe 12.3 %. Further the cECD was significantly lower compared to the POAG group in severe PEX syndrome by 5.4 % and in severe PEX glaucoma by 6.8 %. cECD significantly decreased with increasing PEX stage independently of the presence of glaucoma. These differences remained statistically significant after Bonferroni-Holm correction. The analysis of the entire group of test subjects showed only a weak correlation between mean intraocular pressure and mean cECD. The results of this study showed a decreasing cECD with increasing PEX stage, regardless of whether glaucoma is present or not. The influence of the PEX process appears to be more pronounced than the influence of intraocular pressure.

Die perforierende Keratoplastik im Kindesalter - das ewige Dilemma

Penetrating keratoplasty (PKP) in children is associated with specific age-related problems. In contrast to adults, children can be examined less easily and they are not readily complaining about symptoms. Thus, the rate of intra- and postoperative complications is higher than in adults. In addition, amblyopia is a major issue before the age of seven years potentially resulting in irreversible reduction of visual acuity. Potential indications for surgery are classified as follows: (i) congenital cloudiness (e.g., congenital hereditary endothelial dystrophy--CHED), (ii) acquired traumatic scars, (iii) acquired non-traumatic scars (e.g., infections, keratoconus) and (iv) irreversible graft failure. Our experience concerning 126 paediatric PKPs between 1980 and 2002 in children under age 16 is reported. Five case reports of PKPs performed in Homburg/Saar from 2006 are added. To minimise the risk of immunological graft rejection and chronic endothelial cell loss, we prefer PTK, lamellar keratoplasty or ipsilateral autologous rotational keratoplasty whenever possible. In cases of sclerocornea we feel that PKP should be avoided in view of the histopathology, in cases of Peters' anomaly an optical sector iridectomy may be considered as a valid alternative to high-risk PKP. In cases of buphthalmos the IOP must be controlled before PKP (e.g., previous trabeculotomy). In cases of central penetrating cornea and lens injuries we advocate simultaneous PKP and IOL implantation in the quiet interval after primary wound closure to achieve quick optical rehabilitation. We prefer smaller grafts and interrupted sutures in children. In addition, early suture removal is attempted, especially in cases of progressive corneal neovascularisation threatening the graft. If in doubt, examinations are performed in general anaesthesia readily. Corneal grafting in children should be performed as soon as necessary (less amblyopia!), but as late as possible (better cooperation!). In children, critical indication, repeated in-depth counselling of the parents, good cooperation with the anaesthetist and excellent cooperation with the paediatric ophthalmologist are indispensable in order to achieve good morphological and functional results after PKP.

Long-Term Graft Survival in Penetrating Keratoplasty: The Biexponential Model of Chronic Endothelial Cell Loss Revisited

To present a novel interpretation of the biexponential nature of chronic endothelial cell loss after penetrating keratoplasty (PK). We hypothesize that the fast component of endothelial cell loss reflects the endothelial cells of graft origin. The slow component might just reflect cell loss of the recipient endothelium. We investigate herein whether this hypothesis is in line with long-term survival in bullous keratopathy (BK: almost no endothelium in the recipient bed) and keratoconus (KK: recipient bed with plenty of endothelium). We reviewed endothelial graft failures in PK for BK (n = 88) and KK (n = 87). Patients with immune reactions or a history of glaucoma were excluded. We built a statistical model to predict graft failures from biexponential endothelial cell loss and compared this data to the actual outcomes. After 15 years, the incidence of late endothelial failures was 8% in KK and 33% in BK. The 95% confidence intervals of the simulated outcomes corresponded completely to the actual outcomes during follow-up. Our novel interpretation of the biexponential model is in line with long-term data of PK for BK and KK. Our findings highlight the importance of the recipient bed endothelial reservoir on the long-term prognosis in PK.

Corneal Endothelial Cell Loss after Penetrating Keratoplasty in Relation to Preoperative Recipient Endothelial Cell Density

Aim: Our purpose was to assess recipient endothelial cell density and trephination diameter as predictive factors for corneal endothelial cell density after penetrating keratoplasty (PKP). Methods: Forty-eight eyes showing keratoconus (group I, with sufficient recipient endothelial cell density) and 42 eyes demonstrating bullous keratopathy or Fuchs’ dystrophy (group II, with insufficient recipient endothelial cell density) were included in this retrospective study. The endothelial cell density after PKP was assessed over 2 years. Results: Chronic endothelial cell loss was significantly higher in group II than in group I patients at all follow-up times >3 months (p < 0.05). In group II patients, an inverse correlation between endothelial cell loss and trephine diameter was observed. Conclusion: This study shows that recipient endothelial cell density is a risk factor for increased endothelial cell loss following PKP. In patients with insufficient endothelial cell density, a large trephine size could reduce chronic endothelial cell loss.

Die Prognose der Rekeratoplastik: Indikationsbezogene Analysen in einer großen monozentrischen Kohorte

Data from national graft registries suggests a limited prognosis in the group of all repeat keratoplasties. This group might rather consist mostly of cases already classified as high risk in the first place, however. Thus, repeat keratoplasties in normal risk indications might have a substantially better prognosis. In particular, any specific increase of immune reactions following repeat keratoplasty as compared to first keratoplasties is unknown at present. Furthermore, the contribution of chronic endothelial cell loss to graft failure following repeat keratoplasty has not yet been investigated. The aim of this analysis on a large retrospective cohort is to estimate the incidence of graft rejections and failures als well as chronic endothelial cell loss following repeat keratoplasty. All keratoplasties that had been performed from 1986 to 2006 at the University Eye Hospital Düsseldorf were selected for the 4 most relevant indications. A total of 2073 first keratoplasties and 236 repeat keratoplasties for keratoconus, Fuchs endothelial dystrophy, bullous keratopathy and herpetic corneal scars were included in the analysis. For each indication, the incidence of graft rejections and failures was compared between first and repeat keratoplasty using the Kaplan-Meier method and log-rank test. Endothelial cell loss was quantified by means of exponential regression analysis in the cases without immune reactions. Data of 65 repeat keratoplasties and 532 initial keratoplasties were available for analysis in a generalised linear model. After five years, the risk of graft rejections was not increased in repeat keratoplasties for keratoconus as compared to initial keratoplasties. In Fuchs endothelial dystrophy (p = 0.03) and herpetic corneal scars (n. s.) an increase of 11 % was observed. In bullous keratopathy the increase was as high as 24 % (p < or = 0.01). Irreversible graft failure increased by 4 % in keratoconus, 11 % in Fuchs endothelial dystrophy, 7 % in herpetic eye disease and by 31 % in bullous keratopathy. Only the latter difference reached statistical significance (p < or = 0.01), however. In this group, chronic endothelial cell loss was accelerated to a great extent as well: annual cell loss averaged 43 % in repeat keratoplasties whereas this rate was as low as 20 % for the initial surgery (p = 0.01). In the other indications, acceleration of cell loss in repeat keratoplasties as compared to the first transplantation did not exceed 12 % (p = 0.03). The prognosis of repeat keratoplasties for keratoconus does not seem to fall short of that of initial keratoplasty. A slight deterioration can be assumed in Fuchs endothelial and herpetic eye disease dystrophy. Repeat keratoplasties in initial bullous keratopathy, however, seem to have a substantially poorer prognosis with respect to immune reactions, graft survival and chronic endothelial cell loss.

Impact of short‐term versus longterm topical steroid treatment on ‘idiopathic’ endothelial cell loss after normal‐risk penetrating keratoplasty

Chronic endothelial cell loss after penetrating keratoplasty (PK) is suspected to result from a subclinical immune reaction. The aim of this study was to investigate whether the prolonged use of a topical steroid after normal-risk PK has a favourable impact on chronic endothelial cell loss. The study included 305 eyes from the prospective Erlangen Normal-risk Keratoplasty Study, with a mean follow-up of 3.1 +/- 0.9 years. Postoperative treatment was initiated with prednisolone acetate 1% eyedrops five times a day and was tapered slowly over the first 6 months. Patients were then randomized into two treatment groups: a short-term group (n = 161), which stopped topical steroid treatment, and a longterm group (n = 144), which continued topical treatment with prednisolone acetate 1% eyedrops once a day until 12 months postoperatively. Endothelial cell counts were determined at each follow-up examination (after 6 weeks, then every 3 months until 2 years, then once a year). Endothelial cell density in the short-term and longterm groups decreased significantly from 1941 +/- 550 cells/mm(2) and 1957 +/- 568 cells/mm(2) to 1535 +/- 535 cells/mm(2) and 1472 +/- 549 cells/mm(2), respectively, from 6 weeks to 2 years postoperatively (p < 0.001). In a linear regression model, cell count in the short-term group decreased by 216 +/- 93 cells/mm(2) and in the longterm group by 206 +/- 111 cells/mm(2) per year. There was no significant difference in endothelial cell loss between the short-term and longterm groups (p = 0.5). Longterm, low-dose, topical steroid treatment does not seem to prohibit chronic endothelial cell loss after normal-risk penetrating keratoplasty, in contrast to its favourable effect on immunological graft reactions. Our results may indicate that the aetiology of chronic endothelial cell loss is not of inflammatory origin. Further studies are needed to investigate this phenomenon.

AB0-Blutgruppenexpression in Hornhäuten mit Transplantatversagen

ABO blood group antigens are only expressed by the epithelial cells of normal human corneas. Since AB0 blood group antigens are also known to be expressed on stromal and endothelial cells of inflamed corneas, this study aimed to investigate the extend of ABO blood group antigen expression in corneal allograft failures. Twenty-two failed corneal allografts of 22 patients were examined. In 12 cases the patients had clinically proven corneal allograft rejection. In 10 cases there was no evident history of allograft rejection and the diagnosis graft failure due to chronic endothelial cell loss was made. Immunohistochemical staining of paraffin embedded sections was performed with monoclonal mouse antibodies to human blood group antigen A or B using the streptavidin-biotin-peroxidase complex technique. Blood group antigens A or B were expressed by stromal keratocytes in 5 out of 12 and by endothelial cells in 7 out of 12 corneas with clinically proven immunologic graft rejection. Corneal transplants with chronic endothelial cell loss expressed blood group antigens A and/or B on the endothelial cells in three out of ten cases. The results of this study show that ABO blood group antigens can be up-regulated in cases of corneal allograft failure, especially in cases of immune mediated graft rejection. This phenomenon might play a role in corneal allograft rejection.

Outcome of Rotational Keratoplasty

The nature of chronic endothelial cell loss in homologous corneal grafts is still unclear. Possible causes are cell migration to the recipient bed and chronic subclinical immune reaction. To compare endothelial cell loss after autologous rotational keratoplasty and homologous keratoplasty and present the clinical outcome of patients after rotational keratoplasty. In this open prospective study, we included 7 consecutive patients who underwent rotational keratoplasty between 1998 and 2000 in our hospital. Patients were examined clinically every 3 months, and visual acuity, astigmatism, and endothelial cell density were evaluated. Endothelial cell densities were compared with endothelial cell counts of 293 homologous keratoplasties. Mean follow-up for autologous grafts was 39 months. Mean increase in visual acuity was 3.5 lines. Mean astigmatism was 4.75 diopters in the autologous graft group. Mean preoperative endothelial cell density was 2058 (637 cells/mm(2)). Mean endothelial cell density after 1 year was 1865 (639 cells/mm(2)), which represents a mean +/- SD cell loss of 15% +/- 7.19%. At the end of follow-up, endothelial cell number after autologous grafting was 1630 +/- 622 cells/mm(2). Endothelial cell loss after 1 year in homologous grafts was 40% +/- 21.34%. There was 1 decompensation of autologous graft in the follow-up period. Main Outcome Measure Comparison of endothelial cell count at different postoperative time points using nonpaired t test. Endothelial cell loss in autologous grafts is significantly lower than in homologous grafts, which supports the hypothesis that chronic endothelial cell loss is due to chronic subclinical immune reactions in homologous grafts. Autologous keratoplasties can lead to good functional results and can be superior to homologous corneal grafting in suitable situations.

Endothelial cell loss after autologous rotational keratoplasty

To investigate whether it may be possible to ascertain the influence of immunological factors on chronic endothelial cell loss by comparing chronic endothelial cell loss after autologous rotational penetrating keratoplasty and after homologous penetrating keratoplasty. For six patients who had undergone autologous rotational penetrating keratoplasty the relative annual loss of endothelial cells was calculated by means of an exponential regression analysis. The findings were compared with those in a homogeneous historical control group (53 patients undergoing homologous penetrating keratoplasty for keratoconus). After autologous rotational keratoplasty relative annual loss of endothelial cells was 1.1%+/-2.6% (mean +/- standard deviation). Relative annual loss of endothelial cells in the control-group was 16.7%+/-20.8%. The results of the study lead to the assumption that immunological influences might be the main cause for chronic endothelial cell loss after homologous penetrating keratoplasty.

Endotoxin in storage medium of human corneal grafts and clinical course after penetrating normal-risk keratoplasty.

It is well known that endotoxins in storage medium may stimulate cytokine production and expression of adhesion molecules as well as endothelial damage in human corneal grafts. It has been supposed that endotoxin exposure of corneal grafts may, therefore, cause immune reactions and lead to reduced endothelial cell count after penetrating keratoplasty. It was the purpose of this prospective study to evaluate if this hypothesis is true. A consecutive series of 274 samples of sterile organ culture storage medium from 274 human corneal grafts was collected between August 1998 and February 1999 and tested for endotoxin using Limulus amebocyte-lysate assay (LAL) after 7 days of organ culture. Threshold endotoxin level was set at 1.0 U/ml. A total of 161 grafts were transplanted and 113 were discarded. Within the 161 corneas transplanted, 62 were grafted to normal-risk patients and 99 to high-risk patients. Only normal-risk keratoplasty patients were included in the study and followed for at least 10 months. Immune reactions, graft failures, and postoperative endothelial cell counts were recorded. The mean endotoxin level in organ culture medium of all transplanted grafts was 1.07+/-2.96. Mean endotoxin level in organ culture medium of discarded grafts was 1.68+/-5.76, with 71 samples being below and 42 above the threshold of 1.0 U/ml called endotoxin-negative and endotoxin-positive, respectively. In all 36 culture medium samples from the 62 grafts transplanted to the group of normal-risk keratoplasty patients were endotoxin-negative and 26 endotoxin-positive. An influence of endotoxin levels on incidence of immune reactions, graft failure, and postoperative endothelial cell counts could not be revealed in patients with normal-risk keratoplasty. Low endotoxin levels in storage medium neither seem to promote immune reactions nor to contribute to postoperative chronic endothelial cell loss in normal-risk keratoplasty patients.

HLA class I/II matching and chronic endothelial cell loss in penetrating normal risk keratoplasty.

Chronic endothelial cell loss of the graft is very common after penetrating keratoplasty. The aetiology of this is unknown. Clinically, non-identifiable immune reactions have been suspected. Recently, we were able to demonstrate that proper human leucocyte antigen (HLA) matching is a suitable means to reduce classical immune reactions in normal risk keratoplasty patients. In this study, we therefore investigated whether HLA-matched grafts also experience less chronic endothelial cell loss. A homogenous group of 223 normal risk keratoplasty patients was divided into six groups with different degrees of HLA matching (group 1 with unknown HLA data, group 2 with up to two mismatches, group 3 with three mismatches, group 4 with four mismatches, group 5 with five mismatches and group 6 with six mismatches on the HLA A, B, DR loci). All serological HLA A, B, C and all moleculargenetic HLA DRB, DRQB typings of donors and recipients were performed in a single laboratory accredited by the American Society for Histocompatibility and Immunogenetics. Only patients with at least three postoperative endothelial cell density values were included in the study. The slopes of the regression lines for each individual scatterplot of endothelial cell density values plotted against postoperative time (linear regression, lost cells/mm2/day), and after logarithmic transformation (exponential regression, annual relative loss of cells) were evaluated, respectively. There were no statistically significant differences between the six groups. Whereas proper HLA matching at present standards is already a suitable means to reduce identifiable immune reactions and to prolong graft survival even in normal risk keratoplasty patients, the same HLA matching procedures are not effective in reducing the extent of chronic endothelial cell loss. For several reasons this does not yet exclude, however, the possibility that the underlying cause of chronic endothelial cell loss is immunological.