Superficial corneal effects of experimental nonmechanical penetrating keratoplasty using a Q-switched Er:YAG laser

PURPOSE: To assess thermal effects of Q-switched Er:YAG laser trephination to corneal epithelium and superficial stroma using different mask types and materials for experimental penetrating keratoplasty. METHODS: Laser trephination was performed in 20 freshly-enucleated porcine eyes (repetition rate 5 Hz, pulse energy 65 mJ, spot size 0.7 mm). We used flat, open-metal and ceramic masks for donor and recipient trephination placed directly onto the corneal surface. Main outcome measures as assessed by light microscopy after PAS staining of 8-microm paraffin sections included: extension of tissue thermal damage at the cut edge in the superficial and basal epithelial layers, the basement membrane and subepithelial stroma, and depth and width of epithelial/stromal involvement in the area of the donor mask contact. RESULTS: The thermal damage in the superficial epithelium was more pronounced in donor (mean extension 61.6 +/- 15.6 microm) than in recipient (29.4 +/- 24.9 microm, p= 0.05) trephination. In donor trephination, thermal damage zone of the superficial epithelial layer was significantly smaller with ceramic than with metal masks (21.0 +/- 23.0 versus 61.6 +/- 15.6 microm, p= 0.014). In contrast, differences at basal epithelial layer (p= 0.44), basement membrane (p= 0.79), and subepithelial stroma (p= 0.2) were not statistically significant. Superficial donor involvement of the cornea adjacent to the paracentral donor mask contact zone was seen neither with ceramic nor with metal masks. CONCLUSION: Superficial corneal alterations adjacent to the mask-cornea contact zone may be minimized by using the Er:YAG laser in a Q-switched mode. Ceramic masks, in contrast to metal masks, further reduce superficial thermal alterations at the cut edge.     

Risk factors for corneal allograft rejection: intermediate results of a prospective normal-risk keratoplasty study

PURPOSE: To analyze the incidence of and possible risk factors for endothelial corneal allograft rejection in a well-defined population following penetrating normal-risk keratoplasty. METHODS: Since 1996 a longitudinal prospective study has been conducted to analyze the results of normal-risk penetrating keratoplasty. All patients underwent a standardized protocol of follow-up treatment and examinations in our institution. Diagnosis of corneal endothelial rejection was based on slit-lamp biomicroscopy and laser flare photometry. Data were analyzed using a proportional hazard model for censored data (Cox model), and Kaplan-Meier survival curves. The following parameters were analyzed: age, gender, atopic dermatitis, dry eye symptoms of the recipient; surgeon, graft diameter, post-mortem time, storage time and graft preservation method; and duration of postoperative epithelial defects. RESULTS: Between 1996 and May 2001, 397 patients were recruited and followed with a median follow-up of 18 months. Episodes of endothelial graft rejection were observed in 22 patients (5.5%; 18 eyes with acute diffuse episodes and 4 eyes with chronic focal rejection episodes). In addition, 12 eyes (3%) showed isolated small keratic precipitates ("graft rejection suspects"). All but one graft regained clarity after topical and systemic steroid treatment. Most episodes occurred 11-18 months postoperatively. The percentage of grafts without any episode of endothelial allograft rejection was 95% after 12 months, 89% after 18 months, and 86.5% after 24 months. The following factors were associated with graft rejection: atopic dermatitis (P=0.021), clinically manifest tear insufficiency (P=0.007), and short duration of graft storage (P=0.008). No significant correlation was detected for the remainder of the analyzed factors (P>0.05). CONCLUSION: The incidence of episodes of corneal endothelial allograft rejection following normal-risk keratoplasty was 13.5% within the first two postoperative years. However, the frequency of irreversible immunologic graft failure (3 per thousand) was lower than reported in the literature. Patients should be regularly followed up for at least 18 months postoperatively. Patients with underlying atopic dermatitis or dry eyes should receive special ophthalmological care.     

Oral Contraceptives Moderately Effect Bone Resorption Markers and Serum-Soluble Interleukin-6 Receptor Concentrations

This study investigated the effect of ethinylestradiol(EE2)-containing oral contraceptives on mineral and bone metabolism and on serum soluble-interleukin-6-receptor (sIL-6R) during the menstrual cycle. Twelve women, aged 24.3 +/- 2.9 years, were examined. Blood and 24-hour and fasting urine samples were obtained during one menstrual cycle between cycle day 3-5 (t(1)), cycle day 10-12 (t(2)), cycle day 24-26 (t(3)), and again on day 3-5 of the next cycle (t(4)). EE2 intake was 0 mg at t(1), 30 mg at t(2), 30 mg at t(3) and 0 mg at t(4). Fasting renal phosphorus and calcium excretions were slightly reduced at t(2) and t(3) compared with t(1) and t(4) (P < 0.05-0.001). Moreover, renal excretion of the bone resorption marker C-Teleopeptide was at t(3) reduced by 26% compared with t(1)(P < 0.01) and by 13% compared with t(4)(P > 0.05). Fasting sIL-6R levels were 16.5% lower at t(2) and 12% lower at t(3) than at t(4) (P < 0.01 and P < 0.05). sIL-6R was correlated with total deoxypyridinoline excretion (r = +0.35; P < 0.05) and with fasting renal excretions of calcium (r = +0.36; P < 0.05) and phosphorus (r = +0.29; P < 0.05). In summary, our data suggest that in young women, cyclic monthly oral contraceptive intake is associated with small, but significant variations in bone resorption processes and in serum sIL-6R levels. Results are a further indication that monthly fluctuations of bone resorption in young women are mediated by sex hormones and that osteoclastic activity is stimulated by cytokines in vivo.     

5,10-Methylenetetrahydrofolate reductase genotype determines the plasma homocysteine-lowering effect of supplementation with 5-methyltetrahydrofolate or folic acid in healthy young women

BACKGROUND: Elevated plasma total homocysteine (tHcy) is a risk factor for vascular disease and neural tube defects. The polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (FADH(2)) (MTHFR) influences the tHcy concentration and the response to tHcy-lowering therapy. Supplementation with folic acid (FA) decreases plasma tHcy, but limited data are available on the effect of 5-methyltetrahydrofolate (MTHF). OBJECTIVE: We evaluated the tHcy-lowering potential of low-dose FA and of MTHF with respect to the MTHFR genotype. DESIGN: In this randomized, placebo-controlled, double-blind study, 160 women received 400 microg FA, the equimolar amount of MTHF (480 microg, racemic mixture), or a placebo daily during an 8-wk treatment period. Blood samples were collected at baseline and at 4 and 8 wk. RESULTS: Changes in plasma tHcy concentration depended on the supplemented folate derivative and the MTHFR genotype. Supplementation with FA significantly decreased tHcy concentrations by > or = 13% in women of all 3 genotypes after both 4 and 8 wk. The greatest decrease was 20% (P < 0.05) in the women with the TT genotype after 4 wk. MTHF supplementation also decreased tHcy, but only the women with the CT genotype had a significant decrease after 4 wk (7%; P < 0.05). The largest nonsignificant reduction (15%) occurred in the women with the TT genotype after 4 wk of MTHF supplementation. CONCLUSIONS: The response to tHcy-lowering therapy is influenced by MTHFR genotype. Women with the TT genotype seem to benefit the most from supplementation with either FA or MTHF. In women with the CT or CC genotype, FA is more effective than MTHF in lowering plasma tHcy.     

Association of factor V Leiden mutation with delayed graft function, acute rejection episodes and long-term graft dysfunction in kidney transplant recipients

We analysed whether the factor V Leiden mutation--the most common hereditary predisposing factor for venous thrombosis--is associated with early and long-term graft dysfunction after kidney transplantation in 394 Caucasian kidney transplant recipients. The presence of factor V Leiden mutation was identified by allele specific PCR. The prevalence of the factor V Leiden mutation was compared to 32216 unselected neonates. The prevalence of the factor V Leiden mutation (GA genotype) was similar in 394 kidney transplant recipients and 32216 neonates. The frequency of known factors predicting long-term graft function were similar in patients with the GA genotype and with the normal factor V gene (GG genotype). The GA genotype was associated with the occurrence of no primary graft function (risk: 2.87: 95% confidence interval: 1.01-8.26; p < 0.05), the number of dialysis after transplantation in patients with no primary graft function until graft function (7.5 +/- 2.06 dialysis in GA patients; 4.2 +/- 0.36 dialyses in GG patients; p < 0.05), and the risk for at least one acute rejection episode (risk: 3.83; 95% confidence interval: 1.38-10.59; p < 0.02). The slope of l/creatinine per year was significantly lower in patients with the GA genotype (GA patients: -0.0204 +/- 0.008 dl/mg per year; GG patients: 0.0104 +/- 0.004 dl/mg per year; p < 0.02). The annual enhancement of the daily protein excretion rate was elevated in patients with the GA genotype (GA patients: 38.5 +/- 16.6 mg/24 h per year; GG patients: 4.9 +/- 4.4 mg/24 h per year; p < 0.02). Our study showed that the factor V Leiden mutation is associated with the occurrence of delayed graft function, acute rejection episodes and chronic graft dysfunction after kidney transplantation.     

Ciglitazone inhibits plasmin-induced proinflammatory monocyte activation via modulation of p38 MAP kinase activity

Plasmin triggers chemotaxis and NF-kappa B- and AP-1-mediated proinflammatory gene expression in human peripheral monocytes (PM). Compared with macrophages and dendritic cells, PM express mainly the peroxisome proliferator-activated receptor (PPAR) gamma and traces of PPAR alpha as detected by semiquantitative RT-PCR and immunoblotting. The PPAR gamma agonist ciglitazone, but not the PPAR alpha agonist clofibric acid, concentration-dependently inhibited the plasmin-, but not the FMLP-induced PM chemotaxis. Similarly, release of interleukin (IL)-1 alpha, IL-1 beta and tumor necrosis factor (TNF)-alpha from plasmin-stimulated PM was concentration-dependently inhibited by ciglitazone, but not by clofibric acid, while the LPS-induced TNF-alpha release remained unaffected by any of both PPAR agonists. Ciglitazone activates PPAR gamma as shown by a novel surface plasmon resonance analysis and inhibits the plasmin-induced activation of NF-kappa B and AP-1. It also inhibits p38 MAPK phosphorylation essential for the plasmin-induced PM chemotaxis and gene activation. Thus, activation of PPAR gamma by ciglitazone may allow controLling of the plasmin-mediated recruitment and activation of PM at sites of inflammation.     

Long-term refractive and visual outcome after penetrating keratoplasty only versus the triple procedure in Fuchs' dystrophy

Background Long-term refractive and visual outcome after penetrating keratoplasty (PK) only and the triple procedure in eyes with Fuchs' endothelial dystrophy were assessed and compared.Design Retrospective, non-randomized, cross-sectional, clinical, single-centre study.Methods Ninety-two eyes of 87 patients were divided into two groups. Group 1 consisted of 28 eyes (mean age 62±13 years) that had undergone PK only and group 2 consisted of 64 eyes (mean age 69±10 years) that had undergone the triple procedure. Inclusion criteria were: (1) Fuchs' dystrophy, (2) central nonmechanical trephination, (3) double-running suturing technique and (4) availability of ‘two-sutures-out’ findings.In all eyes, a central trephination was performed (donor trephination from the epithelial side) using the 193-nm excimer laser along metal masks with eight ‘orientation teeth/notches’. A double-running 10–0 nylon suture was applied in all eyes. Subjective refractometry (trial glasses), standard keratometry (Zeiss) and corneal topography analysis (TMS-1, Tomey) were performed in all eyes with ‘two-sutures-in’, ‘one-suture-out’, and ‘two-sutures-out’. Main outcome measures included refractive cylinder, keratometric and topographic net astigmatism, keratometric and topographic central power, best-corrected visual acuity (BCVA), spherical equivalent (SE) of manifest refraction, surface regularity index (SRI), surface asymmetry index (SAI), and regularity of keratometry mires.Results The results were compared between the two groups (i.e. group 1 vs group 2) at various stages (i.e. ‘two-sutures-in’, ‘one-suture-out’, ‘two-sutures-out’). Refractive cylinder in dioptres [D] was 2.5/2.0/2.5 vs 2.0/1.5/3.0, keratometric astigmatism [D] was 3.5/2.6/3.0 vs 3.5/3.1/3.5 and topographic astigmatism [D] was 3.9/4.1/4.9 vs 4.2/5.0/5.1. Keratometric central power [D] was 41.7/42.4/43.8 vs 41.5/41.9/43.3 and topographic central power [D] was 42.3/43.6/43.7 vs 42.6/41.8/44.3. BCVA was 0.5/0.6/0.6 vs 0.5/0.5/0.5. SE [D] was 0.0 /0.0/–0.5 vs –0.5/–0.5/–1.1. SRI was 1.5/1.1/1.0 vs 1.4/1.4/1.2 and SAI was 1.0/0.8/1.0 vs 1.3/1.2/1.0. The proportion of ‘regular’ and ‘mildly irregular’ keratometry mires was 44% / 69% / 68% vs 29% / 46% / 66%. The differences between the two groups did not reach statistical significance at any of the stages.Conclusions Refractive and visual outcome after the triple procedure did not differ significantly from that after PK only. Therefore, we recommend the triple procedure in elderly patients with Fuchs’ dystrophy and cataract to avoid delayed visual rehabilitation and a second surgical procedure.     

Neuroblastom

Monatsschrift Kinderheilkunde -