Underwent Corneal Transplantation Research Articles

Predicted long‐term outcome of corneal transplantation

Abstract Purpose To analyze graft survival and the outcome of the corneal endothelium after corneal transplantation in a single model to predict the long‐term prognosis of these grafts. Methods Cohort study. Data were prospectively recorded and then analyzed retrospectively. Participants: One thousand one hundred and forty‐four consecutive eyes of 1,144 patients who underwent corneal transplantation between 1992 and 2006. Interventions: Penetrating keratoplasties and deep anterior lamellar keratoplasties. Main Outcome Measures: Slit lamp examination and wide‐field specular microscopy. A joint analysis of endothelial cell loss and time to graft failure was undertaken. From mid‐term simultaneous analysis of graft survival and endothelial cell loss, long‐term graft survival was predicted. Results The observed 5‐ and 10‐year graft survival estimates were, respectively, 74% and 64%. The average endothelial cell density (cell loss) was 2,270 cells/mm2 preoperatively, 1,058 cells/mm2 (‐53%) during the 6th post‐operative year, and 865 (‐61%) cells/mm2 during the 10th post‐operative year. Overall, the predicted graft survival estimate was 27% at 20 years and 2% at 30 years. Both observed and predicted graft survival were higher in patients with lamellar keratoplasty than in patients with penetrating keratoplasty and normal recipient endothelium and higher in patients with penetrating keratoplasty and normal recipient endothelium than in patients with penetrating keratoplasty and impaired recipient endothelium. Conclusion For corneal diseases involving the endothelium, penetrating keratoplasty appears to be a good therapeutic approach in elderly patients as the graft lifespan may be similar to the patient life expectancy. Conversely, for younger patients, penetrating keratoplasty is only a mid‐term therapeutic approach. For corneal diseases not involving the endothelium, deep anterior lamellar keratoplasty appears to be a promising therapeutic approach with higher long‐term expected survival.

The Boston keratoprosthesis in autoimmune disease

Abstract Purpose Patients with corneal blindness due to mucous membrane pemphigoid and Stevens Johnson syndrome who undergo corneal transplantation carry a poor prognosis for visual recovery. The Boston keratoprosthesis has been demonstrated to provide excellent retention rates and postoperative visual acuity in patients with corneal graft failure, however, poor visual outcomes still occur in patients with underlying autoimmune disease. Methods We reviewed the current literature to determine the results of keratoprosthesis in patients with blinding autoimmune diseases. Results Much of the published literature on keratoprosthesis fails to clearly differentiate outcomes on the basis of the underlying disorder. Based on available evidence, inflammation, retinal detachment, and glaucoma appear to be the most significant complications after keratoprosthesis in autoimmune patients, and a diagnosis of mucous membrane pemphigoid or Stevens Johnson Syndrome appears to be associated with a significantly higher complication rate than other preoperative conditions. Conclusion Patients with autoimmune diseases carry the worst prognosis for success with keratoprosthesis. Improvement in clinical outcomes might be achieved with changes in keratoprosthesis design and material, perioperative therapy, and/or surgical technique. Possible approaches to complications after Boston keratoprosthesis in patients with underlying autoimmune diseases will be discussed.

Recipient Risk Factors for Graft Failure in the Cornea Donor Study

To identify recipient factors that may be related to risk of corneal graft failure. Multicenter, prospective, double-masked, controlled clinical trial. One thousand ninety subjects undergoing corneal transplantation for a moderate-risk condition (principally Fuchs' dystrophy or pseudophakic corneal edema). Donor corneas were assigned using a random approach without respect to recipient factors, and surgeons were masked to information about the donor cornea, including donor age. Surgery and postoperative care were performed according to the surgeons' usual routines, and subjects were followed up for 5 years. Baseline factors were evaluated for their association with graft failure. Graft failure, defined as a regraft or a cloudy cornea that was sufficiently opaque to compromise vision for a minimum of 3 consecutive months. Preoperative diagnosis of pseudophakic or aphakic corneal edema increased graft failure risk approximately 4-fold compared with Fuchs' dystrophy (27% vs. 7%). Prior glaucoma surgery with preoperative glaucoma medication use substantially increased the graft failure rate. Factors not strongly associated with graft failure included age, gender, diabetes, smoking, and graft size. The risk of graft failure is significantly increased in eyes with pseudophakic or aphakic corneal edema compared with Fuchs' dystrophy, independent of lens status, and in eyes with a history of glaucoma. Proprietary or commercial disclosure may be found after the references.

Corneal oedema after cataract surgery: predisposing factors and corneal graft outcome

Pseudophakic bullous keratopathy (PBK) is one of the main indications for corneal transplantation. Graft survival and visual outcome in this group are often poorer than for other indications. The aim of this study was to find risk factors for developing corneal oedema after cataract surgery and factors that influence the subsequent survival of the graft and the visual outcome. We carried out an observational, retrospective cohort study using data from the Swedish Cornea Transplant Register and patient medical records. A total of 273 patients whose indication for corneal transplantation was corneal oedema after cataract surgery were included in the study. Multiple logistic regression analysis and, where appropriate, univariate analyses were applied. A total of 43% of the patients developed persistent corneal oedema immediately after cataract surgery, the main risk factors for which were phacoemulsification and pre-existing endothelial disease. Almost a third (32%) of the transplants for PBK failed within 2 years, for which rejection and other postoperative complications increased the risk. Half (50%) the patients had visual acuity < or = 0.1 at 2 years after keratoplasty. Comorbidity, increasing duration of the bullous keratopathy and increasing age affected the visual outcome negatively. Phacoemulsification was a risk factor for immediate persistent corneal oedema after cataract surgery, although it did not increase the overall risk of developing PBK. However, transplants for immediate PBK had a better survival rate than those for later onset PBK. Shorter duration of PBK and intraocular lens exchange at the time of penetrating keratoplasty increased the likelihood of good visual acuity.

The Effect of ABO Blood Incompatibility on Corneal Transplant Failure in Conditions with Low-risk of Graft Rejection

To determine whether corneal graft survival over a 5-year follow-up period was affected by ABO blood type compatibility in participants in the Cornea Donor Study undergoing corneal transplantation principally for Fuchs dystrophy or pseudophakic corneal edema, conditions at low-risk for graft rejection. Multi-center prospective, double-masked, clinical trial. ABO blood group compatibility was determined for 1,002 donors and recipients. During a 5-year follow-up period, episodes of graft rejection were documented, and graft failures were classified as to whether or not they were attributable to immunologic rejection. Endothelial cell density was determined by a central reading center for a subset of subjects. ABO donor-recipient incompatibility was not associated with graft failure attributable to any cause including graft failure because of rejection, or with the occurrence of a rejection episode. The 5-year cumulative incidence of graft failure attributable to rejection was 32 (6%) for recipients with ABO recipient-donor compatibility and 12 (4%) for those with ABO incompatibility (hazard ratio, 0.65; 95% confidence interval, 0.33 to 1.25; P = .20). The 5-year incidence for a definite rejection episode, irrespective of whether graft failure ultimately occurred, was 64 (12%) for ABO compatible compared with 25 (8%) for ABO incompatible cases (P = .09). Among clear grafts at 5 years, percent loss of endothelial cells was similar in ABO compatible and incompatible cases. In patients undergoing penetrating keratoplasty for Fuchs dystrophy or pseudophakic corneal edema, ABO matching is not indicated since ABO incompatibility does not increase the risk of transplant failure attributable to graft rejection.

Increased Rac2 mRNA expression in peripheral blood during human corneal graft rejection

Allograft rejection is the main cause of graft failure in human corneal transplantation, for which underlying pathomechanism is not yet clear. We compared gene expression in the peripheral blood of patients who after undergoing corneal transplantation experienced graft rejection with those patients who accepted grafts. Sixty-six patients who underwent corneal transplantation were studied including 18 patients who suffered subsequent graft rejection. cDNA array technology was used to survey and quantify transcript expression. A semiquantitative reverse transcriptase-PCR (RT-PCR) was used to confirm the gene expression pattern measured by a cDNA array of selected genes. Among 265 genes present on the array, eight genes were found to be differentially expressed. Four genes (Rac 2, RhoA, paxillin, and CD18) were further analysed by semiquantitative RT-PCR, and significant differences in mRNA expression levels in the rejection group were confirmed. Our study demonstrated that the expression of Rac2 mRNA was upregulated in the peripheral blood of patients experiencing corneal transplantation rejection compared to those patients who had no rejection episodes. In addition, three genes, RhoA, paxillin, and CD18, showed decreased expression in rejecting patients. cDNA array technology provides a potentially useful approach to identify novel genes that might participate in pathogenic pathways during corneal graft rejection.

Assessment of visual outcomes of deep anterior lamellar keratoplasty (DALK)

Abstract Purpose To evaluate visual outcomes following Anwar's 'Big Bubble' technique for deep anterior lamellar keratoplasty (DALK) Methods Retrospective Case note review of all patients who were treated with DALK in a single university teaching hospital in the UK between January 2004 and December 2007. The main outcome measures were intra operative and postoperative complications, graft clarity and best corrected visual acuity. Results The study group consisted of 37 eyes of 36 patients (21 male, 15 female). Average age of the cohort was 34.5 years (range: 16 ‐‐ 65), with a mean follow‐up of 20.4 months (range: 6 ‐‐ 46) Keratoconus was the most common indication for attempted DALK (65%). Big bubble was achieved in 62% of cases with microperforations in 14%. A further 14% needed to have manual dissection. Clear Graft Host interface was achieved in 87% of cases where the big bubble was achieved and 76% gained best corrected visual acuity (BCVA) of &gt;6/12. Conclusion DALK offers visual outcomes similar to that of a penetrating keratoplasty and should be offered to all patients with a healthy endothelium undergoing corneal transplantation.

Comparison of Three Different Techniques of Corneal Transplantation for Keratoconus

To compare the visual outcomes following deep anterior lamellar keratoplasty (DALK), penetrating keratoplasty (PK), and manual top-hat PK (TH-PK) in subjects undergoing corneal transplantation for keratoconus (KC). A retrospective comparative case series. settings: Cornea clinic at the Toronto Western Hospital. study population: Fifty patients who underwent corneal transplantation for KC: 17 eyes underwent DALK, 20 eyes underwent traditional PK, and 13 had TH-PK. main outcome measures: Preoperative and postoperative uncorrected and best spectacle-corrected visual acuity (UCVA, BSCVA), high-order aberrations (HOA), complication rate, and endothelial cell counts. The median BSCVA at 12 months follow-up was 20/40 in the DALK eyes and 20/30 in the traditional PK and TH-PK eyes. The mean final spherical equivalent power in the three groups was less than -1 diopter (D). The median astigmatism was less than 3.5 D in the three groups. Complication rates were similar for three groups, although the DALK group tended toward more complications. Although DALK and TH-PK procedure results in significantly shorter time to suture removal (P < .01), they caused increased levels of HOAs (P = .02). Endothelial cell counts at 12 months were significantly higher in DALK and TH-PK eyes when compared to the traditional PK eyes (P < .001). DALK, PK, and TH-PK provide comparable visual outcomes in keratoconus patients. Although DALK and TH-PK induce more HOA, they speed up the time to suture removal and provide higher endothelial cell density at one year of follow-up.

Corneal Ectasia After Excimer Laser Keratorefractive Surgery: Histopathology, Ultrastructure, and Pathophysiology

To evaluate the histopathology and ultrastructure of corneas developing ectasia after LASIK or photorefractive keratectomy (PRK). Retrospective case series. Thirteen specimens from 12 patients undergoing corneal transplantation for progressive ectasia after LASIK (12 specimens) or PRK (1 specimen) were obtained for histopathologic and ultrastructural evaluation. All 13 ectatic corneas were submitted in formalin for light microscopy. Nine specimens were bisected, and the second half was placed in 2.5% glutaraldehyde for transmission electron microscopy (TEM). Corneal histopathology, ultrastructure, and pathophysiology. Light microscopy of the post-LASIK specimens showed corneal epithelial hypoplasia and occasional foci of epithelial hyperplasia, Bowman's layer breaks, a normal stromal thickness of the LASIK flap, a normal thickness of the hypocellular primitive stromal scar, a thinned residual stromal bed (RSB), and larger than normal artifacteous interlamellar clefts in the RSB of the ectatic region. The post-PRK specimen showed similar findings with the addition of a thinned hypercellular fibrotic stromal scar. TEM showed thinning of the collagen lamellae and loss of lamellar number in the RSB of post-LASIK ectasia corneas or throughout the entire corneal stromal bed in the post-PRK ectasia cornea, with the posterior aspect of the corneal stroma being most affected. Histopathologic and ultrastructural studies suggest that interlamellar and interfibrillar biomechanical slippage occurs when the cornea becomes ectatic after LASIK or PRK in the postoperative stress-bearing regions of the corneal stroma. This 2-phase chronic biomechanical failure process is similar to that seen in keratoconus. Composite sciences classify this chronic biomechanical failure process as interfiber fracture. The authors have no proprietary or commercial interest in any materials discussed in this article.

Comparison of oral antiviral therapy with valacyclovir or acyclovir after penetrating keratoplasty for herpetic keratitis

Aims:To compare the outcome of prophylactic oral valacyclovir (VAL) or oral acyclovir treatment (ACV) in patients having undergone penetrating keratoplasty for herpetic keratitis (HK).Methods:All patients having received a penetrating keratoplasty...

Amantadine-Associated Corneal Edema: Potentially Irreversible Even after Cessation of the Medication

To describe the clinical features of 3 patients with amantadine-associated corneal edema, including the histopathologic findings from 1 patient who underwent corneal transplantation for irreversible corneal edema. Interventional case series. Three patients who sought treatment at the authors' institution with abrupt-onset, bilateral, diffuse corneal edema associated with systemic amantadine use. Retrospective chart review. Visual acuity, corneal thickness, slit-lamp observations, and histopathologic findings. The duration of use of amantadine ranged from 2 months to 6 years before onset of corneal edema. Discontinuation of amantadine resulted in resolution of corneal edema in both eyes of 2 patients. A third patient underwent a full-thickness corneal transplantation, and subsequently, edema developed in the grafted cornea. Cessation of amantadine therapy in this patient resulted in resolution of corneal edema in both eyes, but the ungrafted corneal eventually decompensated and became edematous, requiring corneal transplantation. Histopathologic analysis of the cornea buttons showed significant loss of endothelial cells. Amantadine can cause corneal edema that begins a few months to several years after institution of therapy, and the edema can occur even in a corneal graft. Prolonged corneal edema in the setting of amantadine use can be irreversible. In cases of corneal edema without an obvious causative disease, the systemic medication list of the patient must be reviewed, and amantadine must be considered as a possible cause.

The Effect of Donor Age on Corneal Transplantation Outcome: Results of the Cornea Donor Study

To determine whether graft survival over a 5-year follow-up period using corneal tissue from donors older than 65 is similar to graft survival using corneas from younger donors. Multicenter prospective, double-masked, controlled clinical trial. One thousand ninety subjects undergoing corneal transplantation for a moderate-risk condition (principally Fuchs' dystrophy or pseudophakic corneal edema); 11 subjects with ineligible diagnoses were not included. Forty-three participating eye banks provided corneas from donors in the age range of 12 to 75 with endothelial cell densities of 2300 to 3300 cells/mm(2), using a random approach without respect to recipient factors. The 105 participating surgeons at 80 sites were masked to information about the donor cornea including donor age. Surgery and postoperative care were performed according to the surgeons' usual routines. Subjects were observed for 5 years. Graft failure, defined as a regraft or a cloudy cornea that was sufficiently opaque as to compromise vision for a minimum of 3 consecutive months. The 5-year cumulative probability of graft survival was 86% in both the <66.0 donor age group and the >/=66.0 donor age group (difference = 0%, upper limit of 1-sided 95% confidence interval = 4%). In a statistical model with donor age as a continuous variable, there was no significant relationship between donor age and outcome (P = 0.11). Three graft failures were due to primary donor failure, 8 to uncorrectable refractive error, 48 to graft rejection, 46 to endothelial decompensation (23 of which had a prior, resolved episode of probable or definite graft rejection), and 30 to other causes. Distributions of the causes of graft failure did not differ between donor age groups. Five-year graft survivals for cornea transplants at moderate risk for failure are similar using corneas from donors >/= 66.0 years and donors < 66.0. Surgeons and patients now have evidence that corneas comparable in quality to those used in this study from donors through age 75 are suitable for transplantation.

Langzeitergebnisse mit FK 506-Augentropfen nach Hornhaut-Transplantation

Immunological graft rejection is the main reason for graft failure following corneal transplantation despite the use of topical and systemic steroids. As steroids are associated with side effects, alternative therapeutic strategies are needed. In this clinical trial patients undergoing corneal transplantation have been prospectively randomised to receive either prednisolone acetate 1 % eye drops 5 x /day, tapering off by one drop every month (n = 20), or to receive FK 506 eye drops 3 x /day for six months (n = 20). Patients in both groups received additionally systemic steroids for three weeks (fluocortolon 1 mg/kg body weight). Primary endpoints were the number of immune reactions and the clear graft survival, the secondary endpoint was the number of side effects. Three immune reactions in the steroid group and one immune reaction in the FK 506 group were seen within the follow-up time of three years. No irreversible graft rejections occurred in either group. Eight patients in the FK 506 group concluded the study early due to local side effects. In this long-term follow-up the use of FK 506 eye drops following corneal transplantation resulted in a lower number of immune reactions when compared to topical steroids. With a change in the galenic formulation FK 506 might be a powerful therapeutic option for preventing immunological graft rejection.

Indications of paediatric keratoplasty in north China

To analyse indications of paediatric keratoplasty in north China and provide information for the prevention of corneal blindness. A retrospective study was carried out in 371 children (410 eyes) aged 14 years or younger who underwent corneal transplantation at Shandong Eye Institute between 1994 and 2005. Data of preoperative diagnoses, aetiological factors and rural or urban backgrounds were evaluated. The study included 259 boys and 112 girls, with a mean age of 7.8 +/- 4.3 years (range 2.5 months to 14 years). Of the 410 eyes, 99 eyes (24.2%) had mechanical trauma, and 93 (22.7%) had infectious keratitis. Congenital corneal opacity developed in 53 eyes (12.9%), chemical or thermal burn in 42 eyes (10.2%) and keratoconus in 37 eyes (9.0%). There were twice as many children from a rural background as those from urban background, and an even higher proportion in the category of infectious keratitis (4.8:1). Regraft was performed in 42 eyes, of which 17 had an original diagnosis of chemical or thermal burn. Mechanical trauma and infectious keratitis are the most common indications of paediatric keratoplasty, as well as childhood corneal blindness, in north China. Regraft occurs more often in children with ocular burns.

Ocular Changes in Patients With Mucopolysaccharidosis I Receiving Enzyme Replacement Therapy

To describe the progression of ocular changes in patients with mucopolysaccharidosis I receiving enzyme replacement therapy. Three male and five female patients with mucopolysaccharidosis I were followed up for 4 years while undergoing enzyme replacement therapy with alpha-l-iduronidase (Aldurazyme). Visual acuity, corneal clouding, intraocular pressure, ophthalmoscopy, and optic disc measurements were performed yearly. Vision remained stable in 5 patients and deteriorated by at least 2 Snellen lines in 3 patients. Deterioration in 2 of these patients was related to progressive corneal clouding. Visual acuities improved in 1 patient after bilateral penetrating keratoplasties. In the third patient, deterioration was related to increasing papilloedema. All patients had typical corneal stromal opacities, however, to a variable extent. Two patients had already undergone corneal transplantation before recruitment in the study. Their grafts remained clear throughout follow-up. Of 2 patients with an elevated intraocular pressure, 1 developed intraocular pressure-related optic nerve damage. Vision remained stable in a patient with bilateral optic atrophy. Ocular findings remain stable in most patients with mucopolysaccharidosis I receiving enzyme replacement therapy. However, enzyme replacement therapy does not seem to prevent progression of corneal or optic disc changes and, thus, the related worsening of visual function.

Pharmacologic strategies in the prevention and treatment of corneal transplant rejection

Corneal transplantation remains one of the most successful organ transplantation procedures in humans. The unique structure of the cornea, with its absence of blood vessels and corneal lymphatic, allows the survival of corneal allograft. Recent advances in sutures, storage media, microsurgical instrumentation, and new pharmacological strategies have greatly improved the success of corneal transplantation and the prevention of corneal allograft rejection. Our strategies in the management and prevention of corneal graft rejection can modify and improve the survival of corneal allografts. Preoperative evaluation, understanding the risk factors, and management of ocular surface disorders may greatly improve the survival of the corneal transplant. Early recognition of corneal allograft rejection and aggressive treatment may improve the survival of the corneal graft. Furthermore, patients who undergo corneal transplantation should be maintained under close ophthalmic surveillance and patients should be informed to report immediately whenever symptoms of corneal graft rejection occur. The mainstay of therapy is topical corticosteroids. In severe cases, periocular, intravenous, and oral corticosteroids therapy can be rendered. New therapeutic modalities such as cyclosporine, tacrolimus, daclizumab, mycophenolate mofetil, leflunomide, rapamycin, and others may prove to be of help in the prevention and treatment of corneal graft rejection. Early recognition of corneal graft rejection and prompt treatment are mandatory for the successful survival of the corneal allograft.

Long-term Visual Prognosis in Children after Corneal Transplant Surgery for Peters Anomaly Type I

To evaluate the long-term visual prognosis in children with corneal transplant surgery for Peters anomaly type I. Retrospective review of interventional case series. Twenty-four children treated in a university-based practice were divided into two groups for analysis: a younger preverbal group and an older group of children three years of age or older. Children underwent corneal transplantation surgery (penetrating keratoplasty [PKP]) for Peters anomaly type I as infants (age range, two to 18 months). Visual acuity using Snellen or Allen charts and glaucoma and other complications were tabulated. Twenty-four patients had Peters anomaly; 16 had unilateral disease, eight had bilateral disease. Thirty eyes underwent PKP. Average age at PKP was five months. The mean follow-up from PKP to the most recent visit was 78.9 months. Fifteen eyes (50%) were treated for glaucoma. Five transplants (17%) had graft rejection episodes; two of these failed and were regrafted. Six eyes (20%) required cataract surgery. One eye had a retinal detachment. Currently, 27 eyes (90%) have clear grafts. In the younger group of children, five of six grafts are clear (83%). In the older group of 24 eyes of verbal children, seven eyes (29%) have visual acuity ranging from 20/20 to 20/50, six (25%) have visual acuity ranging from 20/60 to 20/100, nine (38%) have visual acuity ranging from 20/200 to counting fingers, and two eyes (8%) have visual acuity of hand movements. In this group, nine of 12 eyes without glaucoma had visual acuity better than 20/100; only four of 11 eyes with glaucoma were better than 20/100. Many children with PKP for Peters anomaly type I can experience good or functional vision in their operated eye. Children with glaucoma have a poorer visual prognosis.

Clinical analysis of keratoplasty for 121 children in Shanghai

To determinate the clinical characteristics of children underwent corneal transplantation in Shanghai, including the indications, the age and gender distributions, etc.. Records of 122 keratoplasties in 122 eyes of 121 children below 17 years old, undertaken from January 1, 2003 to January 1, 2006, were gathered by four ophthalmic units in Shanghai as a multiple centre study and the data were analyzed by the statistic software SPSS 13.0 retrospectively, especially on the indication, the age and gender distributions. One hundred and twenty one patients were enrolled in this study. Traumatic corneal scar (22.3%) and scarring after keratitis (19.8%) were the leading indications for keratoplasty, followed by congenital corneal opacity (11.6%), keratoconus (10.7%), corneal ulceration (9.1%), graft rejection (5.0%), band keratopathy (5.0%), chemical injury (5.0%), thermal burns (4.1%), corneoconjunctival dermatosis (4.1%) and congenital hereditary corneal endothelial dysfunction (3.3%). The median age was 11.0 years with the interval quartile range at 8 - 14 years. The number of male patients (77) was approximately twice as many as the female patients (44). Ninety-five patients underwent penetrating keratoplasty (78.5%), 19 patients underwent lamellar keratoplasty (15.7%) and 7 patients underwent combined penetrating keratoplasty with other surgeries (5.8%). Traumatic corneal scar and scarring after keratitis were the leading indications. The age of operated cases mainly in the school age. Male is more frequent than the female.

Deletion of the Chemokine Receptor CCR1 Prolongs Corneal Allograft Survival

Many corneal grafts undergo immune rejection, and current therapies are associated with many side effects. The purpose of this study was to identify critical chemokine pathways involved in generating the alloimmune response to corneal transplants. Orthotopic corneal transplantation was performed in fully mismatched strains. Cytokine and chemokine receptor gene expression was determined by the RNase protection assay. Knockout (KO) strains for chemokine-chemokine receptors that are upregulated after transplantation underwent corneal transplantation. Results derived from KO murine hosts were compared with cyclosporine (Cy) therapy. In addition to graft survival, graft infiltration, allospecific delayed-type hypersensitivity (DTH), and cytokine expression were compared among the recipient groups. Initial experiments revealed gene upregulation of the chemokine receptors CCR1, -2, and -5 after corneal allorejection. Although CCR1 KO hosts showed a significant increase in graft survival compared with wild-type (WT) hosts, allografts in CCR5, CCR2/CCL3(MIP-1alpha), CXCR3, CXCL10/IP-10, and CCL3/MIP-1alpha KO mice did not show a significant improvement in graft survival. Further, CCR1 KO hosts showed a significantly higher survival rate than with systemic Cy therapy in WT hosts. Moreover, graft infiltration by leukocytes and gene expression of proinflammatory cytokines were reduced in CCR1 KO mice compared with both Cy treated and untreated WT mice, as was the induction of allospecific DTH. These studies provide, for the first time, evidence that targeting of specific chemokine pathways can significantly promote survival of corneal transplants, and suggest that select deletion or suppression of CCR1 can be a useful therapeutic target in corneal transplant immunity.

The ocular penetration of levofloxacin 1.5% and gatifloxacin 0.3% ophthalmic solutions in subjects undergoing corneal transplant surgery

ABSTRACTObjective: To compare corneal tissue and aqueous humor concentrations of levofloxacin 1.5% and gatifloxacin 0.3% ophthalmic solutions after topical dosing.Research design and methods: This was a randomized, observer-masked, parallel-group, multicenter study. Fifty-nine subjects undergoing planned penetrating keratoplasty were randomly assigned to receive either levofloxacin 1.5% or gatifloxacin 0.3% as follows: one drop 15 min prior to surgery and a second drop 10 min before surgery. Corneal button and aqueous humor samples were collected during surgery and immediately stored at –70 °C. Levofloxacin and gatifloxacin concentrations were determined by high-pressure liquid chromatography and mass spectrometry.Main outcome measures: Corneal tissue and aqueous humor concentrations of levofloxacin and gatifloxacin.Results: Levofloxacin achieved statistically significantly higher concentrations in both corneal tissue and aqueous humor compared to gatifloxacin in patients undergoing penetrating keratoplasty. In corneal tissue the mean concentration of levofloxacin was 64.8 ± 123.4 µg/g vs. 7.0 ± 9.3 µg/g for gatifloxacin (p < 0.0001). Mean aqueous humor concentration of levofloxacin was 0.976 ± 2.215 µg/mL vs. 0.0523 ± 0.143 µg/mL for gatifloxacin (p = 0.0002).Conclusions: The high concentrations of levofloxacin achievable in corneal tissue with topical dosing suggest that levofloxacin 1.5% should be a useful agent in the treatment of ocular bacterial infections. However, the corneal concentrations achieved in this study may not be representative of concentrations in patients using less frequent dosing.