Corneal flattening by shallow circular trephination in human eye bank eyes

Recent reports documenting central keratometric changes after removal of failed epikeratoplasty lenticules, compared to preoperative keratometry measurements, suggest that the annular corneal wound alters corneal curvature. Central corneal steepening has also been reported following circular and hexagonal keratotomy. We performed standard epikeratoplasty trephination with a Hessburg-Barron suction trephine followed by a peripheral lamellar spreading keratotomy on seven human eye bank eyes to determine the effect of these incisions on corneal topography. In seven human eye bank eyes, the mean acute central keratometric flattening from the shallow trephine incision was 2.81 D (SD 2.28, P = .017), with no significant change in keratometry due to peripheral lamellar spreading (P = .916). Computerized numeric and three-dimensional graphic analysis of the keratographs demonstrated this central topographic flattening. Further studies are needed to investigate the reversibility of host corneal changes induced by epikeratoplasty procedures.     

Tyrosine phosphorylation following lectin meiated endothelial cell stimulation

Abstract: Terminal alpha (1,3) galactosyl galactoside epitopes (α-gal) on membrane glycoproteins expressed by vascular endothelial cells represent the major xenoreactive antigens in pig to primate xenotransplantation. In other discordant xenotransplantation combinations, such as from guinea pig to rat, carbohydrate epitopes other than α-gal may be targeted by xenoreactive antibodies (XNA). We have shown that agonist binding to α-gal epitopes induces proinflammatory activation of porcine aortic endothelial cells (PAEC). Binding of α-gal epitopes by Bandeiraea simplicifolia isolectin B₄ results in both type I and type II PAEC activation. This includes the phosphorylation of tyrosine residue(s) of a protein with an apparent molecular weight of 130 kDa (p130). In order to investigate whether binding of other carbohydrate epitopes could induce a similar phosphorylation event, several lectins with different carbohydrate specificities were used to stimulate PAEC and human umbilical endothelial cells (HUVEC). In addition to BS-IB₄ binding to α-gal, lectins binding to sialic acid isolated from Sambucus nigra (SNA), Maackia amurensis (MAA), Wheat germ agglutinin (WGA), and lectin from jack bean (Concanavalin A, ConA), that binds to mannose residues within the core structure of N-glycosylated proteins all induced the phosphorylation of the p130 protein(s). Lectins with affinity to alpha bound N-acetylgalactosamine, Dolichos biflorus (DOB), and Sophora japonoca (SOJ) did not induce this phosphorylation event. A similar negative result was obtained with Ulex europaeus lectin I, which binds to fucose residues. Conclusively, endothelial cell activation can be observed upon binding of various lectins to the glycosylated moiety of surface glycoproteins. These carbohydrate epitopes against which XNA may exist in certain models might represent minor xenoantigens from porcine to primates or may comprise the major xenoepitopes in other discordant xenograft models. Binding of XNA and subsequently the elicited xenoreactive antibodies to carbohydrate epitopes may therefore contribute to xenograft rejection even in the absence of complement inactivation.     

Phenoxybenzamine treatment can lead to loss of endothelial cell viability

Phenoxybenzamine, an irreversible alpha-adrenoceptor antagonist, is used as a topical treatment against catecholamine-induced contraction in radial artery bypass grafts. Published data suggest that a wide range of phenoxybenzamine doses may be equally effective. This study aimed to investigate whether lower doses of phenoxybenzamine would benefit grafts by better preserving endothelium. To this end human vascular endothelial cells were isolated from sections of radial artery or saphenous vein, and treated with phenoxybenzamine for 30 min. Cells were then washed free of drug and viability assayed using a resazurin-based toxicology assay or returned to culture for assay at 24 h. Phenoxybenzamine treatment showed a dose-dependent effect on cell viability over several clinically employed concentrations. Concentrations above 0.1 mM led to a loss of viability, which became more pronounced with time. The loss of viability was shown to be independent of the carrier used, as results were identical when phenoxybenzamine was dissolved in dimethylsulphoxide, which alone did not affect viability. Changes in pH alone were also not sufficient to affect viability. In conclusion, phenoxybenzamine treatment is likely to cause damage to graft endothelium if employed at concentrations above 0.1 mM (0.03 mg/ml). Phenoxybenzamine may be safely used at lower doses with no potential loss of endothelial cell viability.     

Pulmonary endothelial cell ATP depletion following intestinal ischemia.

Multiple organ failure (MOF) is known to follow systemic inflammatory mediator activation associated with intestinal ischemia-reperfusion injury. In particular, the pulmonary microvasculature appears to be susceptible to MOF-related injury. This study was designed to evaluate the hypothesis that non-cellular plasma factors associated with intestinal ischemia without reperfusion also mediate pulmonary endothelial cell injury. Male Sprague-Dawley rats had intestinal ischemia induced by microvascular clip occlusion of the superior mesenteric artery for 30, 60, 90, or 120 min. Following each period of ischemia, plasma samples were obtained from the protal vein. Time-matched sham-operated animals served as controls. Monolayers of cultured rat pulmonary artery endothelial cells were then incubated with the plasma samples and ATP levels determined using a luciferin-luciferase assay. A 51Cr-release assay using labeled endothelial cells was performed under identical conditions to assess cytotoxicity. Endothelial cell ATP levels were 1.99 +/- 0.23 x 10(-11) mole/micrograms DNA in sham preparations. After a 4-hr incubation in plasma from the 90 and 120 min ischemia groups, cellular ATP levels fell significantly to 1.07 +/- 0.23 x 10(-11) mole/micrograms DNA, respectively (P less than 0.005). No significant cytotoxic injury resulted from incubation with plasma from the 120 min group (1.0 +/- 0.4% versus 0.8 +/- 0.4% in sham group, P = NS). All animals survived 24 hr in the sham, 30, and 60 min groups. However, survival was 40 and 0% in the 90 and 120 min groups, respectively (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Endothelial cell loss following phacoemulsification in the pupillary plane

Endothelial cell loss following posterior chamber phacoemulsification with and without posterior chamber lens implantation was studied. Postoperative cell counts were taken four months after surgery. Three surgeons participated in this study. Posterior chamber phacoemulsification alone (30 patients) resulted in a mean cell loss of 9%, with a maximum cell loss of 22% in one patient. Posterior chamber phacoemulsification with posterior chamber lens implantation (30 patients) resulted in a mean cell loss of 8% with a maximum cell loss of 26% in one patient. Statistical analysis shows no difference in postoperative cell loss between these two groups.     

Corneal decompensation following acute angle-closure glaucoma

Ten eyes of nine patients with endothelial dystrophy requiring iridectomy for acute angle-closure glaucoma developed corneal edema sufficient to require penetrating keratoplasty. Because of the proximity of iris to cornea, simultaneous lens extraction was carried out to prevent malignant glaucoma. Penetrating keratoplasty using techniques presented here provided improved visual acuity and control of glaucoma in all cases.     

Correlation of full-thickness corneal wound length with endothelial cell loss.

We studied 12 patients who had sustained penetrating corneal lacerations with corneal wound lengths ranging from 1 to 9 mm to determine whether wound size was directly proportional to endothelial cell loss 3 or more months after injury. Endothelial cell counts in the uninjured eye averaged 2973 +/- 330 cells/mm2 (range, 2500 to 3700). In the injured eye, near the wound (less than 2 mm from the wound), the cell counts averaged 1260 +/- 590 cells/mm2 (range, 575 to 2500); away from the wound, where cells appeared healthiest, counts averaged 1619 +/- 544 cells/mm2 (range, 850 to 2750). The average total cell loss near the wound was 1713 +/- 622 cells/mm2 (range, 500 to 2575), vs 1354 +/- 582 cells/mm2 (range, 250 to 2150) away from the wound, compared with the uninjured eye. Cell loss near the wound was not significantly different from that away from the wound. There was a positive correlation between wound length and total cell loss measured both near the wound (r = 0.830) and away from the wound (r = 0.755). Pars plana lensectomy was not associated with detectable additional cell loss. Our results suggest that patients with corneal lacerations sustain significant endothelial cell loss, which correlates closely with wound length, and that patients with larger wounds may be at greater risk for developing corneal decompensation with additional procedures or trauma.     

Corneal lathing using the excimer laser and a computer-controlled positioning system: Part II--Variable trephination of corneal buttons

A new system is presented that allows a variable trephination of donor corneas for the preparation of corneal buttons used in penetrating keratoplasty. With the help of a computer-controlled positioning system that uses high-precision micropositioning elements (both translation and rotational stages) the donor cornea is removed, epithelial side up, in a fixation device in front of a focused excimer laser beam (ArF, lambda = 193 nm). User friendly computer software allows the surgeon to select a variety of parameters (diameter, shape, angle of trephination) of the corneal graft. Histological and electron microscopical data of human corneas trephined with this "Excimer Laser Corneal Shaping System" are presented.     

Vascular endothelial growth factor expression and glomerular endothelial cell loss in the remnant kidney model.

BACKGROUND: Vascular endothelial growth factor (VEGF) is constitutively expressed in the glomerulus where it may have a role in the maintenance of capillary endothelial cell integrity. The present study sought to examine changes in VEGF expression in a model of progressive renal disease and to assess the effects of angiotensin converting enzyme (ACE) inhibition. METHODS: Subtotal nephrectomized (STNx) rats were randomly assigned to receive vehicle (n=10) or the ACE inhibitor perindopril (8 mg/l drinking water) for 12 weeks duration (n=10). Sham-operated rats were used as controls (n=10). Glomerular capillary endothelial cell density was evaluated by immunostaining for the pan-endothelial cell marker RECA-1 and VEGF expression was assessed by quantitative in situ hybridization. RESULTS: In STNx rats glomerular capillary endothelial cell density was reduced to 19% that of sham rats (P<0.01) with a concomitant reduction in glomerular VEGF expression, also to 19% of sham rats (P<0.01). Perindopril treatment was associated with normalization of both capillary endothelial cell density and glomerular VEGF mRNA. CONCLUSIONS: Reduction in glomerular VEGF expression is a feature of the renal pathology that follows subtotal nephrectomy. In the context of the known functions of this growth factor, these findings suggest that diminution in VEGF may contribute to the demonstrated loss of glomerular endothelium that develops in this model of progressive renal disease.     

Corneal edema following argon laser iridotomy.

Laser iridotomy is generally a safe and effective procedure for narrow-angle glaucoma. However, since surgical success with the argon laser depends on a focal thermal effect, a corneal burn is a possible complication. I describe five patients with occludable anterior chamber angles and bilateral corneal guttata who developed uniocular progressive corneal edema with visual loss following argon laser iridotomy. These five patients underwent iridotomy with a total laser energy of 63, 48.5, 7, 25, and 25 J, respectively, and began to lose vision due to corneal edema immediately, and 5, 2, 4, and 2 years later, respectively. Following penetrating keratoplasty with cataract surgery, histopathology of the corneal buttons showed generalized endothelial cell loss in all five. Microstructural findings of guttata and thickened Descemet's membrane implied that prior endothelial dystrophy had predisposed these patients to laser-induced damage. Risk factors for immediate or delayed-onset bullous keratopathy after argon laser iridotomy include prior angle closure, preexisting endothelial guttata, and high laser energy with multiple applications. Recognizing the potential of this complication offers opportunities for preventive strategies.     

Serial corneal endothelial cell loss with lathe-cut and injection-molded posterior chamber intraocular lenses

We compared endothelial cell loss of patients implanted with lathe-cut posterior chamber lenses and those implanted with injection-molded lenses over a three-year postoperative period. Results were based on more than 2,500 measurements of corneal endothelial density. Although the technique of cataract extraction (anterior chamber phacoemulsification, posterior chamber phacoemulsification, or planned extracapsular extraction) significantly affected cell loss (P < .01), the type of implant (lathe-cut or injection-molded) did not. Significant continuing endothelial cell loss did not occur during the first three postoperative years with injection-molded lenses. There was, however, a statistically significant 7% to 15% additional cell loss after surgery over the first two to three postoperative years with lathe-cut implants. There have been no cases of corneal endothelial decompensation developing after implantation of injection-molded or lathe-cut lenses. Because a standard field clinical specular microscope was used in this study, cell counting errors cannot be ruled out as a cause of these findings.     

Initial results of endothelial cell seeding following argon laser carotid endarterectomy.

This study evaluates the initial results of endothelial cell (EC) seeding following argon laser carotid endarterectomy. Venous endothelial cells were harvested from 12 dogs and cultured. A laser endarterectomy was performed on both carotids of each dog. One side was seeded with endothelial cells. Six dogs had both carotids harvested 1 hour after restoring blood flow. The others were harvested in 24 hours. The percentage of lumen covered with EC was evaluated by scanning electron microscopy. At 1 hour, the seeded arteries demonstrated 35 +/- 3 percent EC coverage, whereas the unseeded arteries had no EC coverage (P = 0.0002). At 24 hours, the seeded arteries had 58 +/- 15 percent EC coverage, whereas the unseeded arteries had no coverage (P = 0.01). Significant gross thrombus developed only in unseeded arteries (P = 0.047), two of which were occluded at 24 hours. EC seeding is beneficial following argon laser carotid endarterectomy resulting in improved patency and less surface thrombogenicity.     

Corneal wedge resection for high astigmatism following penetrating keratoplasty

Fourteen corneal wedge resections performed between April 1980 and January 1986 at the Wills Eye Hospital were retrospectively reviewed. Mean pre-operative refractive (subjective) astigmatism was 8.13 diopters (D), with a range of 3.75 to 15.0 D. Following wedge resection, the mean residual astigmatism was 3.04 D, with a range of 0 to 5.0 D. Although the mean keratometric astigmatism measurements were generally similar to the astigmatism measured during refraction, there was little correlation between them on a case-by-case basis. Corneal wedge resection appears to remain an effective and moderately predictable technique for managing high astigmatism following penetrating keratoplasty.     

Mechanisms of bone loss following allogeneic and autologous hemopoietic stem cell transplantation.

A significant proportion of patients will be long-term survivors of bone marrow transplantation (BMT) and little is known about their risk of late bony complications. We therefore evaluated bone mineral density (BMD) prior to BMT, post-transplantation changes in BMD, and mechanisms of bone loss in long-term survivors. We performed two analyses. The first was a cross-sectional study of 83 consecutive BMT patients (38 F, 45 M), examining the relationship between BMD and bone turnover, measured immediately prior to transplantation, and a number of disease and patient variables. The second was a prospective study of 39 patients (19F, 20 M) followed for a median of 30 months (range 5-64 months) following either allogeneic (allo, n = 29) or autologous (auto, n = 10) BMT to determine if bone loss was related to treatment of graft versus host disease (GVHD) with glucocorticoids and cyclosporine A, high bone turnover rates, or hypogonadism. Auto BMT recipients acted as a control group for effects of GVHD therapy on BMD. Prior to BMT, spinal and femoral neck (FN) BMDs were 8.6% and 14% lower in female auto BMT recipients than in female allo BMT recipients, respectively (p = 0.12 and p = 0. 003). Urinary bone resorption markers were higher than in normal gender- and age-matched control subjects. Patients treated previously with glucocorticoids also had 8% lower FN BMD. Glucocorticoid-pretreated women with amenorrhoea had lower lumbar spine (LS) and FN BMDs than eumenorrheic women and women receiving HRT. Post-allo BMT, patients lost 11.7% of FN BMD compared with a nonsignificant decrease of 1.1% post-auto BMT (p < 0.001). Spinal BMD and total body bone mineral content (TBBMC) decreased by 3.9% and 3.5%, respectively, post-allo, compared with an increase (1.5%, p = 0.03) or nonsignificant decrease (-3.7%, p = NS), respectively, post-auto BMT. Post-allo BMT bone loss correlated best with the cumulative prednisolone dose at the LS and FN, and with average daily prednisolone dose for TBBMC. At the spine, the rate of bone loss was 4%/10 g of prednisolone, while the rate of bone loss at the FN was greater (9%/10 g of prednisolone). Bone loss was also negatively related to the duration of cyclosporine therapy for GVHD and baseline deoxypyridinoline concentrations. Avascular necrosis of the femoral head occurred in four, and vertebral and rib fractures occurred in one of the allo BMT patients, but in no auto BMT patients. In conclusion, BMT recipients are at risk of osteoporosis secondary to bone loss associated with their underlying illness and/or chemotherapy, particularly in female autograft recipients, and in allograft recipients secondary to GVHD and its treatment.     

Endothelial cell loss following "modern" phacoemulsification by a senior resident.

Historically, extracapsular cataract extraction (ECCE) has been shown to cause less endothelial cell loss than phacoemulsification. To further evaluate endothelial cell loss following phacoemulsification, we prospectively studied 60 patients who underwent cataract extraction with "in situ" phacoemulsification within the capsular bag following a continuous-tear circular capsulotomy, with placement of a posterior chamber intraocular lens (PC-IOL) in the capsular bag. All procedures were performed by a single senior ophthalmology resident. The average preoperative endothelial count was 2318 +/- 36 cells/mm2; the average postoperative count (at 8.5 weeks) was 2167 +/- 41 cells/mm2. The average endothelial cell loss, then, was 6.4 +/- 1.2%. This level of cell loss with a capsular-bag-fixed PC-IOL is comparable to that reported for ECCE.     

环锯切除骨原位直立移植在颈椎前路减压融合术中的应用

目的 探讨环锯减压切除骨可否替代髂骨进行颈椎前路单一节段减压融合术中的自体骨移植融合操作。方法 回顾性分析了 30例单一节段受累的脊髓型颈椎病病例,采用经颈椎前路环锯减压、骨原位直立移植融合术,治疗脊髓型颈椎病并观察其临床效果。平均随访 4.75年,按 JOA评分及 Hirabayashi等恢复率评定手术效果,颈椎正、侧位及屈、伸侧位 X线检查判定融合效果。结果 随访时,手术效果优 15例 (50％ )、良 11例 (36.7％ )、可 3例 (10％ )、差 1例 (3.3％ ),优良率达 86.7％。经 X线检查证实融合率为 100％,植骨块无移位、脱落,颈椎曲度仅有部分丧失。结论 颈椎前路环锯减压切除骨可替代其他方式的自体骨进行移植融合术。此术式操作简便,融合率高,术后颈椎曲度虽有部分丧失,但不影响手术效果,随访时手术效果无减退。     

Vacuum trephination of the hypotonous eye

Removal of the recipient cornea in therapeutic keratoplasties is made more difficult by the hypotonous eye. A deep and symmetrical cut can be obtained by use of the vacuum trephine without unduly endangering the iris or lens. This technique may be preferred to other more time-consuming methods of pre-pressurizing the eye, and allows a better removal of the recipient cornea than with scissors removal following an epithelial mark.