Risk Of Corneal Graft Rejection Research Articles

Nanoparticle-hydrogel composite as dual-drug delivery system for the potential application of corneal graft rejection

Immune rejection remains the major cause of corneal graft failure. Immunosuppressants (such as rapamycin; RAPA) adjunctive to antibiotics (such as levofloxacin hydrochloride; Lev) are a clinical mainstay after corneal grafts but suffer from poor ocular bioavailability associated with severe side effects. In this study, we fabricated a Lev@RAPA micelle loaded cationic peptide-based hydrogel (NapFFKK) as a dual-drug delivery system by integrating RAPA micelles with Lev into a cationic NapFFKK hydrogel to potentially reduced the risk of corneal graft rejection. The properties of the resulting hydrogels were characterized using transmission electronmicroscopy and rheometer. Lev@RAPA micelles loaded NapFFKK hydrogel provided sustained in vitro drug release without compromising their inherent pharmacological activities. Topical instillation of Lev@RAPA micelles loaded NapFFKK hydrogel resulted in the great ocular tolerance and extended precorneal retention over 60 min, thus significantly enhancing the ocular bioavailability of both Lev and RAPA. Overall, such dual-drug delivery system might be a promising formulation for the suppression of corneal graft failure.

Risk of Corneal Transplant Rejection Following COVID-19 Vaccination: A Systematic Review and Meta-analysis.

The COVID-19 pandemic has initiated an unparalleled global vaccination campaign, raising concerns about the vaccine's effects on various health conditions, including the risk of corneal transplant rejection. This systematic review aimed to identify the relationship between COVID-19 vaccination and rejection of corneal transplant, filling a significant gap in the existing medical literature. A literature search was performed across multiple databases up to February 12, 2024, to identify studies evaluating the risk of corneal transplant rejection post-COVID-19 vaccination. Eligible studies were original research that reported outcomes of corneal graft rejection following vaccination. Nested Knowledge web software facilitated screening and data extraction. The Newcastle-Ottawa Scale was employed for quality assessment. A meta-analysis was conducted to calculate the aggregated relative risk (RR) utilizing R software version 4.3. Six studies were included in the qualitative synthesis, with four meeting the criteria for meta-analysis. These studies varied in geographic location, surgical techniques, and types of vaccines used. The pooled RR for corneal transplant rejection following COVID-19 vaccination was 0.816 (95% CI 0.178-1.453), indicating no significant risk of rejection. No statistical heterogeneity was observed among the studies (I2 = 0%). This review and meta-analysis found no significant evidence that COVID-19 vaccination increases the risk of corneal graft rejection. However, the current evidence is insufficient to conclusively determine the vaccine's safety for corneal transplant recipients. These findings underscore the need for additional research to confirm these preliminary results and investigate the long-term effects of COVID-19 vaccination on corneal transplants, aiming to provide evidence-based guidance to healthcare providers and patients.

Risk of Corneal Graft Rejection and Vaccination: A Matched Case-Control Study From a United States Integrated Health Care System

Data on vaccine-associated corneal transplant rejections are limited. We examined the association between graft rejection and vaccination. Matched case-control METHODS: We used electronic health records to identify corneal transplant recipients between January 2008 and August 2022 at Kaiser Permanente Southern California. Cases were transplant recipients who experienced a graft rejection (outcome) during the study period. Randomly selected controls who did not experience a corneal graft rejection at their matched cases' index date (rejection date) were matched in a 3:1 ratio to cases. For controls, index date was determined by adding the number of days between transplant and graft rejection of their matched case to the control's transplant date. The study included 601 cases and 1803 matched controls (mean age 66 years [s.d. 17.0], 52% female, 47% non-Hispanic white). Twenty-three% of cases and 22% of controls received ≥1 vaccinations within 12 weeks prior to the index date. The adjusted odds ratio (aOR) for vaccination in the 12 weeks prior to index date, comparing cases to controls was 1.17 (95% CI: 0.91, 1.50]). The aOR was 1.09 (0.84, 1.43) for 1 vaccination, 1.53 (0.90, 2.61) for 2 vaccinations, and 1.79 (0.55, 5.57) for ≥3 vaccinations. The aOR was 1.60 (0.81, 3.14) for mRNA vaccines, and 1.19 (0.80, 1.78) for adjuvanted/high dose vaccines. We found no evidence to suggest an association between vaccination and graft rejection. Our findings provide support for the completion of recommended vaccinations for corneal transplant recipients, without significantly increasing the risk of graft rejection.

Suppression of Neovascularization by Topical and Subconjunctival Bevacizumab After High-Risk Corneal Transplantation

To assess the effectiveness of topical and subconjunctival bevacizumab in suppressing vascularization in graft and host bed after high-risk corneal transplantation. Secondary analysis of prospective, randomized, double-blind, placebo-controlled multicentric clinical trial. The study includes patients aged > 18 years who underwent high-risk penetrating keratoplasty, which was defined as corneal vascularization in ≥ 1 quadrants of the corneal graft and host bed, excluding the limbus. Patients were randomized to treatment and control groups. The patients in the treatment group received subconjunctival injection of bevacizumab (2.5 mg/0.1 ml) on the day of the procedure, followed by topical bevacizumab (10 mg/ml) 4 times per day for 4 weeks. The patients in control group received injection of vehicle (0.9% sodium chloride) on the day of procedure, followed by topical vehicle (carboxymethylcellulose sodium 1%) 4 times a day for 4 weeks. Vessel and invasion area of vessels in the corneal graft and host beds. This study included 56 eyes of 56 patients who underwent high-risk corneal transplantation, with equal numbers in the bevacizumab and vehicle (control) treatment groups. The mean age of patients who received bevacizumab was 61.2 ± 15.9 years, and the mean age of those treated with vehicle was 60.0 ± 16.1 years. The vessel area at baseline was comparable in the bevacizumab (16.72% ± 3.19%) and control groups (15.48% ± 3.12%; P= 0.72). Similarly, the invasion areas were also similar in the treatment (35.60% ± 2.47%) and control (34.23% ± 2.64%; P= 0.9) groups at baseline. The reduction in vessel area was significantly higher in the bevacizumab-treated group (83.7%) over a period of 52 weeks compared with the control group (61.5%; P < 0.0001). In the bevacizumab-treated group, invasion area was reduced by 75.8% as compared with 46.5% in the control group. The vessel area was similar at 52 weeks postprocedure in cases of first (3.54% ± 1.21%) and repeat (3.80% ± 0.40%) corneal transplantation in patients who received bevacizumab treatment. In the vehicle-treated patients, the vessel area was significantly higher in repeat (9.76% ± 0.32%) compared with first (8.06% ± 1.02%; P < 0.0001) penetrating keratoplasty. In the bevacizumab treatment group, invasion areas at week 52 were comparable in first (11.70% ± 3.38%) and repeat (11.64% ± 1.74%) procedures, whereas invasion area was significantly higher in repeat (27.87% ± 2.57%) as compared with first (24.11% ± 2.17%) penetrating keratoplasty in vehicle-treated patients. In patients undergoing vascularized high-risk corneal transplantation, bevacizumab is efficacious in reducing vascularization of corneal graft and host bed, thereby reducing the risk of corneal graft rejection in vascularized host beds. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Examining the Influence of COVID-19 Infection and Pandemic Restrictions on the Risk of Corneal Transplant Rejection or Failure: A Multicenter Study

ABSTRACT Purpose The purpose of this study was to evaluate two aims. The first was whether patients with a history of keratoplasty who developed COVID-19 were at a higher risk of corneal graft rejection or failure. The second was examining whether patients who underwent a new keratoplasty during the first 2 years of the pandemic from 2020–2022 were at a higher risk of the same outcomes compared to those undergoing keratoplasty from 2017–2019 before the pandemic. Methods A multicenter research network, TriNetX, was used to query for keratoplasty patients with or without a COVID-19 between January 2020 and July 2022. Additionally, the database was also queried to identify new keratoplasties performed from January 2020-July 2022 and compare it to keratoplasties performed during a similar pre-pandemic interval between 2017–2019. 1:1 Propensity Score Matching was utilized to adjust for confounders. Graft complication of either a rejection or failure was assessed within 120 day follow-up using the Cox proportional hazard model and survival analysis. Results A total of 21,991 patients with any keratoplasty history were identified from January 2020-July 2022, of which 8.8% were diagnosed with COVID-19. Matching revealed two balanced cohorts of 1,927 patients where no significant difference in risk of corneal graft rejection or failure among groups ((aHR [95% CI] = 0.76 [0.43,1.34]; p = .244)). Comparing first-time keratoplasties performed in a pandemic period of January 2020-July 2022 to a corresponding pre-pandemic interval from 2017–2019 also similarly revealed no differences in graft rejection or failure in matched analysis (aHR = 0.937[0.75, 1.17], p = .339). Conclusions This study found no significant increase in the risk of graft rejection or failure in patients with a prior keratoplasty history following COVID-19 diagnosis nor in any patients who had a new keratoplasty done during 2020–2022 when compared to a similar pre-pandemic interval.

The ocular manifestations of novel coronavirus: A literature review

Apart from the systemic cardinal symptoms such as fever, cough, fatigue, headache, and diarrhea, ocular symptoms have gained much importance during the peak hours of the COVID pandemic. Since an exposed ocular surface can act as a gateway for various respiratory viruses, there is an increased interest in exploring the ocular route of transmission and viral RNA detection in ocular fluids. Moreover, the ocular surface can also share some common viral binding receptors. A large number of case reports and observational studies have been published so far reporting anterior, posterior, orbital, and neurological complications of the eye and orbit. Ocular complications can range from mild self-limiting pathologies such as conjunctivitis, episcleritis, and retinal cotton wool spots to severe blinding pathologies such as mucormycosis, retinal vessel occlusions, candida retinitis, and optic neuritis. There is an increased risk of corneal graft rejection and reactivation of certain microorganisms post severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) vaccination. The present narrative review provides a brief overview of the current literature and an in-depth understanding of the ocular implications of SARS-CoV-2.

Five Cases of Corneal Graft Rejection After Recent COVID-19 Vaccinations and a Review of the Literature.

The purpose of this study was to report 5 cases of acute corneal graft rejection after COVID-19 vaccination and perform a review of the literature. This was a case series and review of literature dated on the October 10, 2021. We describe 5 cases-2 patients with Descemet stripping automated endothelial keratoplasty (for Fuchs endothelial dystrophy) who presented with acute corneal graft rejection after their first dose of mRNA (BNT162) vaccine. The other 3 patients who had penetrating keratoplasty performed more than 10 years ago for keratoconus presented with acute graft rejection-2 patients after their second dose of adenovirus vector (AZD1222) vaccine and 1 patient after first dose of mRNA (BNT162) vaccine. Three patients were not using any topical steroid treatment at the time of diagnosis of graft rejection. The mean duration between vaccination and onset of symptoms was 16.86 ± 6.96 days for the mRNA vaccine and 17 ± 11.89 days for the adenovirus vector vaccine. Corneal graft rejection has recently been reported after COVID-19 vaccination. Patients with keratoplasty need to be advised regarding the risk of corneal graft rejection and warning symptoms of rejection after COVID-19 vaccination. Seeking early referral to the emergency department and increasing topical steroids pre-COVID-19 and post-COVID-19 vaccination may reduce the risk of rejection.

Prediction of corneal graft rejection using central endothelium/Descemet\u2019s membrane complex thickness in high-risk corneal transplants

To determine whether measurements of Endothelium/Descemet complex thickness (En/DMT) are of predictive value for corneal graft rejection after high-risk corneal transplantation, we conducted this prospective, single-center, observational case series including sixty eyes (60 patients) at high risk for corneal graft rejection (GR) because of previous immunologic graft failure or having at least two quadrants of stromal vascularization. Patients underwent corneal transplant. At 1st, 3rd, 6th, 9th, and 12th postoperative month, HD-OCT imaging of the cornea was performed, and the corneal status was determined clinically at each visit by a masked cornea specialist. Custom-built segmentation tomography algorithm was used to measure the central En/DMT. Relationships between baseline factors and En/DMT were explored. Time dependent covariate Cox survival regression was used to assess the effect of post-operative En/DMT changes during follow up. A longitudinal repeated measures model was used to assess the relationship between En/DMT and graft status. Outcome measures included graft rejection, central Endothelium/Descemet’s complex thickness, and central corneal thickness (CCT). In patients with GR (35%), the central En/DMT increased significantly 5.3 months (95% CI: 2, 11) prior to the clinical diagnosis of GR, while it remained stable in patients without GR. During the 1-year follow up, the rejected grafts have higher mean pre-rejection En/DMTs (p = 0.01), compared to CCTs (p = 0.7). For En/DMT ≥ 18 µm cut-off (at any pre-rejection visit), the Cox proportional hazard ratio was 6.89 (95% CI: 2.03, 23.4; p = 0.002), and it increased to 9.91 (95% CI: 3.32, 29.6; p < 0.001) with a ≥ 19 µm cut-off. In high-risk corneal transplants, the increase in En/DMT allowed predicting rejection prior to the clinical diagnosis.

Risk of Corneal Graft Rejection After High-risk Keratoplasty Following Fine-needle Vessel Coagulation of Corneal Neovascularization Combined With Bevacizumab: A Pilot Study

Background.Corneal neovascularization is considered an important risk factor for allograft rejection after corneal transplantation (keratoplasty). Therefore, the aim of this study was to determine whether preoperative reduction of corneal neovascularization by fine-needle thermal cauterization combined with bevacizumab reduces the incidence of allograft rejection after subsequent high-risk keratoplasty.Methods.In this interventional uncontrolled clinical pilot study, 31 eyes of 31 patients with corneal neovascularization in at least one corneal quadrant were included. All eyes were treated by fine-needle thermal cauterization of corneal vessels and subconjunctival injection of bevacizumab. Both treatments were repeated in the cases of visible reperfusion of occluded vessels. Afterward, penetrating keratoplasty was performed. When corneal neovascularization was present on the day of keratoplasty, additional vessel cauterization and injection of bevacizumab was performed. Patients were then followed to determine the incidence of allograft rejection.Results.In 18 eyes, vessel cauterization with bevacizumab injection was performed once before keratoplasty, whereas 13 eyes required retreatment before keratoplasty. No complications were observed. In 23 eyes, corneal neovascularization was present on the day of keratoplasty due to reperfusion of previously occluded vessels and simultaneous vessel cauterization with bevacizumab injection was performed. During follow-up (mean: 560 days; range: 59–1095 days), 4 graft rejection episodes in 4 eyes were observed. Estimated probabilities of corneal graft survival were 92.9% after 1 year (number at risk: 23), 78.4% after 2 years (number at risk: 9), and 78.4% after 3 years (number at risk: 3).Conclusions.Our initial results indicate that angioregressive treatment of pathological corneal vessels by fine-needle thermal cauterization combined with subconjunctival injection of bevacizumab before high-risk keratoplasty seems to result in graft survival rates comparable to survival rates seen in normal-risk keratoplasty. The findings of our pilot study warrant further controlled clinical trials with longer follow-up in a larger patient cohort.

Functional Tumor Necrosis Factor Alpha Polymorphisms and Haplotype Analysis in High-Risk Corneal Transplantation

BackgroundTumor necrosis factor alpha (TNF-α) plays a critical role in diverse cellular processes including ocular immune tolerance, inflammation, and allograft rejection. The ubiquitous transcription factor nuclear factor kappa B (NF-κB) regulates expression of numerous genes. Induction of the TNF-α pathway is involved in the inflammatory response and loss of transplant tolerance. ObjectivesWe investigated functional single nucleotide polymorphisms (SNPs) in the promoter region of TNF-α and an insertion/deletion (indel) polymorphism of NF-κB1 in corneal transplant recipients considered to be at increased risk of immunological rejection (ie, high-risk corneal transplantations) and looked for any associations with corneal transplantation outcome. Patients and MethodsThree hundred eighty-four full thickness corneal transplant recipients were followed for 3 years and episodes of reversible and irreversible allograft rejection were recorded. Using DNA obtained from these patients, 5 SNPs located in the promoter region −1031 T/C rs1799964, −863 C/A (rs1800630), −857 C/T (rs1799724), −308 G/A (rs1800629), and −238 G/A (rs361525), and one SNP upstream from the transcription start site (+489) rs1800610 of TNF-α were analyzed using induced heteroduplex generation. A functional NF-κB1 indel (−94) was also investigated. Haplotypes were inferred by PHASE and associations with rejection were determined by chi-square analysis. ResultsThe TNF-α haplotype TCTGGA was significantly associated with reduced risk of corneal graft rejection (Pc < .005) and TCTAGA was associated with increased risk of rejection (Pc < .005) in high-risk corneal transplants. There was no association with the NF-κB1 indel (Pc > .05). ConclusionAccording to haplotype frequencies, our results suggest that the TCTGGA haplotype may confer additional protection against risk of immunological rejection whereas TCTAGA may increase risk of corneal allograft rejection in the high-risk setting. However, both haplotypes were relatively rare and thus would not warrant genotyping for individual patient selection for anti-TNF therapy.

The Maintenance of Lymphatic Vessels in the Cornea Is Dependent on the Presence of Macrophages

It has been shown previously that the presence in the cornea of antigen-presenting cells (APC), such as macrophages (MPS) and lymphangiogenesis, is a risk for corneal transplantation. We sought to determine whether the existence of lymphatic vessels in the non-inflamed cornea is associated with the presence of MPS. Flat mounts were prepared from corneas of untreated C57BL/6, CD11b(-/-), F4/80(-/-), and BALB/c mice, and after suture placement or corneal transplantation, observed by immunofluorescence for the presence of lymphatic vessels using LYVE-1 as a marker of lymphatic endothelium. Innate immune cells were detected in normal mouse corneas using CD11b, F4/80, CD40, as well as MHC-class II. Digital images of the flat mounts were taken using a spot image analysis system, and the area covered by lymphatic vessels was measured using NIH Image software. The number of spontaneous lymphatic vessels in C57BL/6 corneas was significantly greater than in BALB/c corneas (P = 0.03). There were more CD11b(+) (P < 0.01) and CD40(+), MHC-class II (+) cells in the C57BL/6 corneas than in BALB/c mouse corneas. MPS depletion via clodronate liposome in C57BL/6 mice led to fewer spontaneous lymphatic vessels and reduced inflammation-induced lymphangiogenesis relative to control mice. Mice deficient in CD11b or F4/80 had fewer spontaneous lymphatic vessels and less lymphangiogenesis than control C57BL/6 mice. C57BL/6 mouse corneas have more endogenous CD11b(+) cells and lymphatic vessels. The endogenous lymphatic vessels, along with pro-inflammatory MPS, account for the high risk of corneal graft rejection in C57BL/6 mice. CD11b(+) and F4/80(+) MPS appear to have an important role in of the formation of new lymphatic vessels.

Incidence of Rigid Gas-Permeable Contact Lens Wear After Keratoplasty for Keratoconus

To review retrospectively the charts of all 190 patients who underwent penetrating keratoplasty for keratoconus in one hospital during a 5-year period (1995-2000), with special attention paid to contact lens fitting. The frequency of postoperative contact lens use, the time to fit lenses after grafting, tolerance and visual acuity, and postoperative risks for the graft were studied. The authors successfully fitted large-diameter (12 mm) tricurve rigid gas-permeable contact lenses for 90 (47%) of 190 penetrating keratoplasty patients with good tolerance. There were nine dropouts, and 91 eyes were corrected in another way. Fitting contact lenses after grafting usually started after 8.5 months (range, 1-60 months). The average tolerance was 9.2 hours a day (range, 2-12 hours), and best-corrected visual acuity was 20/25 (range, 20/16-20/200). The average follow-up was at least half a year. The average age of the patient at the first lens fitting was 36.2 years (range, 14-75 years). There was no increased risk in graft rejection. Twelve-millimeter rigid gas-permeable contact lens wear was successful in 47% of patients who underwent penetrating keratoplasty for keratoconus. It does not interfere with the use of chronic postoperative topical medication, nor does it increase the risk of corneal graft rejection. It is necessary to recommend likely use of contact lenses to patients who have undergone grafting surgery.

Management of corneal ectasia and cataract following photorefractive keratectomy

A 42-year-old man was referred to our clinic 18 months after bilateral photorefractive keratectomy (PRK). He had been on topical prednisolone acetate for 12 months because of post-PRK grade 4 haze. On his first visit, visual acuity was limited to light perception in both eyes because of moderate haze, significant corneal ectasia, and a white cataract. A 2-step surgical approach was elected in both eyes. First, a deep anterior lamellar keratoplasty was performed. Six weeks later, phacoemulsification with intraocular lens implantation was performed. Compared with a triple procedure combining penetrating keratoplasty and cataract surgery in 1 stage, the 2-step approach may lower the risk for corneal graft rejection and reduce ametropia.

Modulation of Corneal Vascularization

Avascularity of normal cornea is a result of homeo-stasis between anti-angiogenic and pro-angiogenic stimuli. Disruption of this delicate balance during corneal wound healing can lead to pathological corneal vascularization. Several unique characteristics in the ocular surface epithelia modulate corneal avascularity. Normal cornea contains heparan sulfate to prevent the release of potent angiogenic cytokines, such as basic fibroblast growth factor (bFGF) from the Bowman's layer. Potent angiostatic factors, such as endostatin and angiostatin, can be produced from degradation of corneal extracelluar matrix. In contrast, conjunctiva contains angiogenic cytokines, such as bFGF and vascular endothelial growth factor. In addition to regulating release of angiogenic and angiostatic cytokines, matrix metalloproteinases (MMPs) and other proteolytic enzymes can modulate corneal vascularization via matrix degradation to allow endothelial migration and tissue remodeling. When the cornea becomes vascularized, inflammatory cells and mediators gain uninhibited access to the cornea, thus rendering immune sensitization and increased risk of corneal graft rejection. Novel therapies targeting angiogenic cytokines or MMPs have been shown to suppress corneal vascularization effectively in animal models, and may have therapeutic potential for clinical use.

Opinions on Risk Factors and Management of Corneal Graft Rejection in the United Kingdom

To determine the opinions regarding risk factors and practice preferences for corneal graft rejection by members of the Bowman Club (UK) and to compare them with those of members of the Castroviejo Society (USA). A questionnaire was sent in 1999 to members of the Bowman Club (UK), who were responsible for two thirds of all corneal grafts undertaken annually. The survey included 8 questions identical to those given to members of the Castroviejo Society (USA) in a survey carried out in 1989. Thirty-six out of 40 surgeons replied. Factors considered by respondents to be high risk for corneal graft rejection were previous corneal graft rejection in the operated eye (97%), significant corneal vessels (97%), and previous herpetic eye disease (94%). The preferred routine preoperative treatment in "high-risk" patients included no treatment (47%), topical corticosteroids (33%), and oral prednisolone (22%). In postoperative "high-risk" patients, 100% of surgeons used topical and 42% used oral corticosteroids. Immune suppression agents were used by 44% of respondents, the majority (92%) using cyclosporine A. In previous herpes simplex patients, 47% of surgeons used oral and 14% used topical antivirals preoperatively, whereas 75% used oral and 47% used topical postoperatively. This study documents the perceived risk factors and management of corneal graft rejection by corneal surgeons in the UK. It showed wide variation in practice preferences, allowing individual surgeons a comparison with peer practice. It highlights the need for greater use of postoperative antiviral prophylaxis in the presence of previous herpetic corneal pathology.

Fate of MHC-matched corneal allografts in Th1-deficient hosts.

To determine whether the Th1 cytokine, interferon (IFN)-gamma, is necessary for corneal graft rejection. Full-thickness penetrating keratoplasties were performed in normal mice and in IFN-gamma knockout (KO) mice. Sixty-four percent of the MHC-mismatched corneal allografts were rejected in IFN-gamma KO mice. By contrast, MHC-matched corneal allografts were rejected in 50% to 77% of the wild-type hosts, but were not rejected in any of the IFN-gamma KO mice or the wild-type mice treated with anti-IFN-gamma monoclonal antibody. Corneal graft rejection in IFN-gamma-deficient hosts was characterized by an eosinophilic infiltrate compared with a mononuclear inflammatory infiltrate in normal mice. IFN-gamma is not necessary for the rejection of MHC-mismatched corneal grafts. However, IFN-gamma and Th1 immune mechanisms are necessary for the rejection of MHC-matched corneal allografts that confront the host with foreign minor histocompatibility antigens. The immune response in atopic patients, as in IFN-gamma KO mice, is characterized by cross-regulation of Th1 cytokines, such as IFN-gamma. The present results indicate that MHC matching dramatically reduces the risk of corneal graft rejection when IFN-gamma is depressed or absent. Thus, MHC matching may reduce the risk of corneal graft rejection in patients with atopic keratoconus.

Association between HLA-DPB1 matching and 1-year rejection-free graft survival in high-risk corneal transplantation.

We analyzed the effect of matching for HLA class II alleles on corneal graft outcome in a single-center, retrospective study from January 1991 through April 1996. The study involved 81 transplant recipients at high and low risk of corneal graft rejection, who were typed by the polymerase chain reaction-restriction fragment length polymorphism method and who completed at least 1-year of follow-up. The DRB1, DQB1, and DPB1 alleles were analyzed together and transplant recipients were subdivided into groups with matching (one to four alleles matched in the high risk or one to five alleles matched in the low risk) and without matching (no allele matched) for HLA class II. A significantly higher rate of 1-year rejection-free graft survival was revealed in high-risk transplant recipients with matching, compared with those without matching (P=0.0238). We have shown that matching for at least one HLA class II allele was actually beneficial in high-risk transplants. An analysis of matching for each allele separately, detected that only HLA-DPB1 matching was significantly associated with a higher rate of 1-year rejection-free graft survival in high-risk transplant recipients with matching (one or two alleles matched) compared with those without matching (no allele matched) (P=0.0139). In particular, matching for one DPB1 allele was significantly beneficial compared with no matching (P=0.0140). There was no significant effect of HLA-DRB1 and -DQB1 matching (P=0.3177 and P=0.2878, respectively). Furthermore, a strong association between DPB1 matching and 1-year rejection-free graft survival was observed in DRB1-incompatible high-risk transplant recipients (P=0.0308). Nevertheless, no significant effect of DPB1 matching was detected in DQB1-incompatible transplant recipients. Our findings indicate that HLA class II DNA typing is clinically relevant for corneal transplant recipients and that especially HLA-DPB1 matching has a beneficial effect in high-risk corneal transplantation.

Effect of neodymium:YAG laser posterior capsulotomy on corneal grafts

Patients undergoing neodymium: yttrium-aluminum-garnet (Nd: YAG) laser posterior capsulotomy for posterior capsular opacification after penetrating keratoplasty were reviewed retrospectively for incidence of graft rejection. All patients underwent extracapsular cataract extraction with posterior chamber intraocular lens implantation (PC-IOL) performed as a separate or combined procedure. Only one of 20 eyes (4.7%) of 20 patients developed corneal graft rejection over a follow-up period of 6 months to 6 years after capsulotomy. Nd: YAG laser capsulotomy does not appear to increase the risk of corneal graft rejection.

Visual Correction Following Penetrating Keratoplasty

Postoperative visual correction following penetrating keratoplasty usually includes spectacles, but for some patients optimal vision may be obtained using contact lenses. We studied 126 eyes of 101 patients undergoing penetrating keratoplasty to determine the frequency of postoperative contact-lens use, its clinical associations, its effect on the risk of corneal graft rejection, and its potential effects on topical medications. A total of 20 patients (16%) wore contact lenses postoperatively for maximal optical correction. Among eyes with good macular potential, 17 of 63 (27%) wore contact lenses. Contact-lens wear did not preclude the use of chronic postoperative topical medications, nor did it increase the risk of corneal graft rejection. We conclude that contact lenses may be useful for optimizing vision after penetrating keratoplasty, especially when macular potential is good.

Reducing the risk of corneal graft rejection. A comparison of different methods.

Corneal graft rejection represents the leading cause of failure in corneal transplantation. Two of the major risk factors for graft rejection are previous sensitization, usually in the form of a previous rejected corneal graft and corneal vascularization. The major histocompatibility MHC antigens (HLA, A, B and DR) are the target of the corneal graft rejection process. Because HLA, A, B, and DR antigens have been found in the corneal epithelium, the corneal stroma, and the corneal endothelium, matching patients and donors would seem to reduce the incidence of rejection. The results of studies on HLA, A, B, and DR matching are discussed. Cyclosporin, a fungal by-product, prevents the proliferation of sensitized cytotoxic T cells. Its use topically in corneal transplant patients in a controlled series has also reduced the incidence of rejection. Its use systemically has also been tried in an effort to prevent corneal graft rejection.