Patients Undergoing Corneal Transplantation Research Articles

Higher Order Aberrations After Keratoplasty for Keratoconus

To compare higher order aberrations (HOAs) caused by the anterior and posterior corneal surfaces after conventional penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), and automated lamellar therapeutic keratoplasty (ALTK) in patients undergoing corneal transplantation for keratoconus (KC). This retrospective, observational, cross-sectional study included one eye of the following subjects: 40 patients with KC, 23 KC patients after PK, 17 KC patients after DALK, 18 KC patients after ALTK, and 38 healthy controls. All underwent imaging with a rotating Scheimpflug camera (at least 6 months after complete suture removal in grafted subjects) to assess the HOAs from the anterior and posterior corneal surfaces within the central 4-mm and 6-mm zones. The conversion of the corneal elevation profile into corneal wavefront data was performed using Zernike polynomials. Total and third- and fourth-order HOAs were considered. The root mean square of the Zernike vector magnitude, expressed in micrometers, was used. Differences among groups were assessed using the Kruskal-Wallis and Duncan multiple range tests. Statistical significance was defined as p < 0.05. In both 4-mm and 6-mm central zones, the total HOAs from the anterior corneal surfaces were significantly lower in DALK than in ALTK and PK groups (p < 0.05). The total HOAs from the posterior corneal surface were comparable amongst postoperative groups (p > 0.05). The aberration components that were significantly greater included coma in the KC and ALTK eyes, trefoil and coma in the DALK eyes, and trefoil in the PK eyes. The corneal anterior surface optical quality appeared significantly better after DALK than after ALTK and PK.

The relationship between corneal lymphangiogenesis and inflammation index after corneal alkali injury

To discuss the relationship between corneal lymphangiogenesis and inflammation index (IF) in alkali burned corneas. Experimental research. Rat corneal hemangiogenesis and lymphangiogenesis were examined by 5'-nase-alkaline phosphatase (5'-NA-ALP) double enzyme-histochemistry and whole mount immunofluorescence at 1 day, 3 days, and 1, 2, 3, 4, 5, 6, 7, 8 weeks after alkaline burns, and the blood vessel counting (BVC) and the lymphatic vessel counting (LVC) were recorded. The state of corneal inflammation was observed under the slit lamp and evaluated by inflammation index (IF) grading at the same time. Then, the association of LVC with IF was examined. In addition, eleven human alkali burned corneas were obtained from 11 patients undergoing corneal transplantation in Zhongshan Ophthalmic Center from January 2005 to June 2008. Corneal lymphangiogenesis was examined by lymphatic vessel endothelial receptor (LYVE-1) immunohistochemistry. The significance of the differences in IF, inflammatory cells counting, burn history, and age between two groups was analyzed by using paired student's t-test. New lymphatic vessels were present in rat alkali burned corneas. Corneal lymphangiogenesis developed 3 days after alkaline burns, reached the top 2 weeks after the injury, then decreased gradually, and disappeared at the end of the 5th week. Corneal lymphatics occurred behind corneal inflammation, but disappeared before corneal inflammation and hemangiogenesis. LVC was strongly and positively correlated with IF (r = 0.572, P < 0.01) after corneal alkaline burns. Among eleven human alkali burned corneas, corneal lymphatic vessels were present in 3 corneas. Compared with the other 8 cases without corneal lymphangiogenesis, the scores of IF was significantly higher (t = 3.28, P < 0.05), the inflammatory cells counting dramatically increased (t = 2.42, P < 0.05), but the age decreased significantly (t = 2.62, P < 0.05). However, the difference in burn history between two groups was not significant (t = 1.28, P > 0.05). Corneal lymphangiogenesis develops after alkaline-burns and correlates closely with inflammation index.

Factor XIII subunits in human tears; their highly elevated levels following penetrating keratoplasty

Background As blood coagulation factor XIII (FXIII) is of high importance in wound healing, we determined the concentrations of FXIII A and B subunits (FXIII-A and FXIII-B) and their complex (FXIII-A 2B 2) in normal tears and in tears from patients undergoing penetrating keratoplasty (PKP). Methods FXIII complex and subunit concentrations were measured by highly sensitive chemiluminescent ELISAs in tears from 60 healthy volunteers and from 31 patients undergoing corneal transplantation. Results In non-stimulated tears from healthy volunteers, low but consistent amounts of FXIII-A and FXIII-B (medians: 2.13 μg/L and 7.22 μg/L, respectively) were measured, mostly in non-complexed form. Following stimulation of tear secretion FXIII levels moderately decreased, but if normalized to protein concentration they did not change. One day after PKP FXIII levels became highly elevated, then gradually decreased, but even on day 7 significantly exceeded pre-surgery values. The elevation of tear FXIII levels was significantly higher in PKP patients who later developed neovascularization of donor cornea. Conclusions FXIII subunits are low concentration components of normal tear. The striking elevation of FXIII subunit and FXIII-A 2B 2 concentrations after PKP suggests the involvement of FXIII in corneal wound healing. Perioperatively measured high FXIII levels in tears seem to represent a risk of neovascularization.

Secreted frizzled‐related protein 1 (SFRP1) is highly upregulated in keratoconus epithelium: a novel finding highlighting a new potential focus for keratoconus research and treatment

To investigate the expression of Wnt signalling pathway genes in keratoconic (KC) epithelium. RNA was extracted from the epithelium of four KC patients undergoing corneal transplantation and five age-matched controls. The expression of 84 genes known to be involved in the Wnt signalling pathway was tested by reverse transcription-polymerase chain reaction (RT-PCR) with a pathway-targeted array (Human Wnt RT(2) Profiler PCR Array, Superarray). Using RT-PCR arrays, LEF1, PITX2 and secreted frizzled-related protein 1 (SFRP1) were upregulated more than twofold in KC compared with control epithelium. Only SFRP1 was significantly upregulated, approximately 25-fold compared with pooled controls (range 9.12-fold to 98.6-fold; P = 0.019). SFRP1 expression was associated with patient age and possibly the rate of progression of the keratoconus. Immunohistochemistry was used to assess SFRP1 protein distribution and confirm the SFRP1 microarray result (n = 3 KC and n = 2 control corneas). SFRP1 immunolablelling was seen in all KC corneas, mostly in the basal epithelium; however, control corneas showed minimal SFRP1 immunoreactivity. SFRP1 is highly upregulated in the epithelium of these KC patients, suggesting a role in the pathogenesis and progression of keratoconus. Future investigations are required to establish if SFRP1 may be a potential marker of KC progression or if manipulation of its expression can be used to therapeutic effect in this disease.

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.

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.

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.

Corneoscleral rim cultures: lack of utility and implications for clinical decision-making and infection prevention in the care of patients undergoing corneal transplantation.

To assess the utility of donor corneoscleral rim cultures. A retrospective review of the culture results of 774 corneoscleral rims that remained after trephination of corneas for transplantation into patients at our academic medical center between January 1992 and November 1997. Forty-one (5.3%) corneoscleral rim cultures yielded microorganisms, mostly coagulase-negative staphylococci. Two patients developed endophthalmitis (one with Staphylococcus aureus and one with Pseudomonas aeruginosa) within 3 months after transplantation; each had a negative corneoscleral rim culture and neither patient's infection was temporally related to the transplant procedure. Preoperative donor corneoscleral rim cultures are unreliable predictors of endophthalmitis complicating corneal transplantation and, therefore, are not useful in the clinical management of patients having corneal transplants. Moreover, the discrepancy between the results of corneoscleral rim cultures and subsequent endophthalmitis renders them invalid as a quality assurance procedure. Instead, for patients with suspected endophthalmitis after corneal transplantation, we recommend that corneal surgeons select antimicrobial therapy based on current guidelines and the results of directed sampling. Furthermore, eye banks should prospectively track recipients who develop clinical endophthalmitis, immediately notify the corneal surgeon who transplanted the matched cornea of that used for the index case, and, in selected situations, attempt to identify a possible source of contamination.

Corneal Graft Outcome Study

To determine overall 2- and 5-year corneal graft survival rates and to identify risk factors for corneal graft failure in our patient population. A retrospective chart review of 696 patients undergoing corneal transplantation performed by a single surgeon at The Toronto Western Hospital over a 7.5-year period. A total of 468 eyes met the inclusion criteria for this study. Overall, the 2- and 5-year graft survival rates were 78.8% and 64.5%, respectively. In a univariate analysis, patient age, gender, history of glaucoma, preoperative diagnosis, type of operative procedure, and postoperative factors all were shown to be significantly associated with graft survival. In a multivariate analysis, six independent predictors of graft failure were identified: preoperative diagnosis, neovascularization of the graft, the presence of peripheral anterior synechiae, gender, occurrence of one or more rejection episodes, and age of the recipient at the time of corneal transplantation. Risk of graft failure can vary substantially within a population of patients receiving a corneal transplant. The outcomes of this study concur with the risk factors for corneal graft failure in the literature and can be used as prognostic guidelines for both surgeons and patients.

Detection of herpes simplex virus DNA sequences in corneal transplant recipients by polymerase chain reaction assays.

Polymerase chain reaction (PCR) assays were used to amplify herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) sequences in DNA extracted from formalin-fixed, paraffin embedded corneas of patients undergoing corneal transplantation. PCR reamplification with an internal (nested) set of primers was required for detection in 10 of the 12 positive corneas indicating very low abundance of viral sequences. Three of the positive corneal samples were from failed corneal grafts. Overall, TK sequences were detected in 8 of 11 corneas from subjects with a past history of herpes keratitis and in 4 of 11 corneas from subjects with no past history of herpetic eye disease.

Endothelial Cell Density Determined by Specular Microscopy and Scanning Electron Microscopy

Human eyes were photographed with a specular microscope and later examined wit a scanning electron microscope. Corneas from patients undergoing corneal transplantation in whom we were able to obtain preoperative specular micrographs were similarly analyzed. An attempt was made to correlate the counts obtained with both microscopic techniques by determining the amount of shrinkage the cornea undergoes while being processed for SEM. All specimens were counted with a planimeter. We found that the specular microscope adequately analyzes the endothelial cell density in the central and paracentral cornea of a normal eye, but because of its small sampling area specular microscopic counts are subject to significant error when dealing with nonhomogeneous populations such as postoperative cases. We found the peripheral corneal endothelial density to be less than the central endothelial density. Furthermore, we found that we could maximize the accuracy of counting by using a variable frame in a nonhomogeneous population, counting a minimum of four photographs per specimen, analyzing different areas, and analyzing larger areas.