Stromal fibroblast-bone marrow-derived cell interactions: implications for myofibroblast development in the cornea.

The purpose of this study was to test the hypothesis that mouse corneal stromal fibroblast and bone marrow-derived cell interactions augment corneal myofibroblast generation and, if so, to study whether such interactions are mediated by paracrine or juxtacrine mechanisms. Mouse bone marrow-derived cells and mouse corneal stromal fibroblasts were obtained from both mice with green fluorescent protein (GFP) expressed in all cells and normal GFP- BL6 control mice. To study the interactions of the different cell types, GFP+ cells of one type were co-cultured with GFP- cells of the other type in Primaria plates (to monitor juxtacrine signaling) or Transwell System plates (to monitor paracrine effects mediated by soluble mediators). Both cell types were cultured at a cell density of 1 × 10(5) cells per ml. The percentage of alpha smooth muscle actin+ myofibroblasts was significantly higher (ANOVA, p<0.001) when bone marrow-derived cells and mouse corneal stromal fibroblasts were co-cultured compared to when bone marrow-derived cells and mouse corneal stromal fibroblasts were cultured alone (control). The in vitro studies using GFP+ corneal fibroblasts or GFP+ bone marrow-derived cells demonstrated conclusively that both cells types could transform into myofibroblasts. However, the percentage of alpha smooth muscle actinassds+ myofibroblasts generated from either cell type precursor was higher when both cells were co-cultured together (juxtacrine) as compared to when bone marrow-derived cells and mouse corneal stromal fibroblasts were co-culture in different compartments of Transwell System (paracrine). Thus, more alpha smooth muscle actin+ GFP+ myofibroblasts were generated from GFP+ corneal stromal fibroblasts when GFP- bone marrow-derived cells were present and more alpha smooth muscle actin+ GFP+ myofibroblasts were generated from GFP+ bone marrow-derived cells when GFP- corneal stromal fibroblasts were present. Polyclonal anti-human latency associated peptide (LAP) (transforming growth factor-ß1) neutralizing antibody (a-LAP) and/or transforming growth factor-ß type I receptor kinase inhibitor (LY-364947) inhibited the generation of alpha smooth muscle actin+ myofibroblasts from either precursor cell in Transwell System co-culture experiments. These data suggest that TGFß is a paracrine modulator that regulates the generation of myofibroblasts from either corneal fibroblasts or bone marrow-derived cell precursors.

Interleukin-1 receptor role in the viability of corneal myofibroblasts.

The purpose of this study was to investigate the role of interleukin-1 (IL-1) in modulating myofibroblast viability in mouse corneas with stromal opacity. Twenty-four female B6; 129S1-Il1r1tm1Roml/J homozygous IL-1RI knockout mice and 24 control B6129SF2/J mice were included in this study. Each mouse had opacity-generating irregular phototherapeutic keratectomy (PTK) performed with an excimer laser in one eye. Groups of 8 mice from each group were euthanized at one month, three months and six months after surgery and the eyes cryo-preserved. The contralateral eye served as unwounded control. Immunohistochemistry was performed for α-smooth muscle actin (SMA) in central sections of all corneas. The TUNEL assay for apoptosis was performed on 8 sections of four eyes from each group. No SMA+ cells were detected in the stroma of unwounded control or knockout corneas. SMA+ myofibroblast density was significantly higher (p < 0.001) in the IL-1RI knockout group than in the control group at one month, three and six months after irregular PTK. Mean TUNEL+ stromal cells in the anterior 50 µm of stroma was significantly lower in the IL-1RI knockout group compared to the control group at six months after irregular PTK (p = 0.04). These results corroborate the findings of recent in vitro work that demonstrated an antagonistic effect of TGFß and IL-1 on myofibroblast viability, and found that IL-1-triggered myofibroblast apoptosis was suppressed by TGFß. Thus, IL-1 is an important modulator of myofibroblast viability during corneal wound healing.

Effect of TGFß and PDGF-B blockade on corneal myofibroblast development in mice.

The purpose of this study was to investigate the role of transforming growth factor beta (TGFß) and/or platelet-derived growth factor-B (PDGF-B) blockade on the differentiation of vimentin and alpha-smooth muscle actin (αSMA)-expressing myofibroblasts associated with haze in mice. Mouse corneas had haze-generating irregular PTK (phototherapeutic keratectomy) and topical treatment with the vectors. Six study groups of PTK treated corneas, with four corneas per group in each experiment, were Group 1) treated with TGFß-KDEL vector interfering with TGFß signaling through anomalous sorting of cytokine bound to the expressed altered receptor; Group 2) treated with PDGF-B-KDEL vector interfering with PDGF signaling through anomalous sorting of cytokine bound to the expressed altered receptor; Group 3) treated with both TGFß-KDEL vector and PDGF-B-KDEL vector to interfere with signaling of both cytokines; Group 4) empty pGFPC1 vector; Group 5) empty pCMV vector; and Group 6) no vector treatment control. At one month after surgery, the corneas were analyzed by immunocytochemistry (IHC) for central stromal cells expressing myofibroblast markers vimentin and αSMA. The stroma of corneas treated with the TGFß-KDEL vector alone (p < 0.05) or both the TGFß-KDEL and PDGF-B-KDEL vectors (P < 0.05) had significantly lower density of vimentin-positive cells compared to the corresponding control group. The central stroma of corneas treated with the TGFß-KDEL vector (p < 0.05) or the PDGF-B-KDEL vector (p < 0.05) had lower density of αSMA-positive cells compared to the corresponding control group. The density of αSMA-positive stromal cells was also significantly lower (p < 0.05) when both the TGFß-KDEL and PDGF-B-KDEL and vectors were applied together compared to the corresponding control groups. This study provides in situ evidence that TGFß and PDGF-B have important roles in modulating myofibroblast generation in the mouse cornea after haze-associated injury.

Monocyte development inhibitor PRM-151 decreases corneal myofibroblast generation in rabbits.

This study investigated whether PRM-151 (Promedior, Inc., Malvern, PA), a recombinant form of human pentraxin-2 (PTX-2, also referred to as serum amyloid P, hSAP), that inhibits differentiation of circulating monocytes into fibrocytes and profibrotic macrophages, could modulate generation of myofibroblasts after opacity-producing corneal injury in rabbits, and, therefore, have potential to reduce or prevent haze after PRK. Nine diopter PRK for myopia was performed with the VISX S4 IR laser. Four groups of 6 animals were treated in masked fashion: Group 1: 30 µl of topical PRM-151 (20 mg/ml) 6 times a day for 5 days; Group 2: 30 µl topical vehicle 6 times a day for 5 days; Group 3: 200 µl sub-conjunctival PRM-151 (total injection of 4 mg) immediately after surgery and every other day until day 8; Group 4: 200 µl sub-conjunctival injections of vehicle according to the same schedule as group 3. At one month after PRK, the animals were euthanized and immunohistochemistry was performed for the myofibroblast marker α-smooth muscle actin (SMA). The density of SMA+ cells/400× field in the central stroma was determined in each cornea. Myofibroblast density at one month after surgery was significantly lower (p = 0.006) after sub-conjunctival PRM-151 treatment (5.8 ± 2.8 cells/400× stromal field) compared to sub-conjunctival vehicle treatment (15.3 ± 2.9 cells/400× stromal field). There was no significant (p = 0.27) decrease in stromal myofibroblasts triggered by topical PRM-151 treatment (11.8 ± 6.6 cells/400× stromal field) compared to the topical vehicle treatment (14.2.8 ± 6.2 cells/400× stromal field). PRM-151 inhibits myofibroblast generation when administered by sub-conjunctival injection, but not when administered topically, after opacity-producing corneal injury. This study provides additional confirmation that bone marrow-derived cells contribute to corneal myofibroblast generation.

Stromal interleukin-1 expression in the cornea after haze-associated injury.

The purpose of this study was to determine whether myofibroblasts or other cells in the stroma in the cornea produce interleukin (IL)-1alpha or IL-1beta that could modulate myofibroblast viability in corneas with haze after photorefractive keratectomy (PRK). Twenty-four female rabbits had haze-generating PRK for 9 diopters of myopia and were sacrificed at 1 week, 2 weeks, 3 weeks or 4 weeks after surgery. Corneal rims were removed, frozen in OCT at -80 degrees C, and analyzed by immunocytochemistry using primary antibodies to IL-1alpha, IL-1beta and alpha smooth muscle actin (SMA). Double immunostaining was performed for the co-localization of SMA with IL-1alpha or IL-1beta. Central dense haze and peripheral slight haze regions of each cornea were analyzed. SMA+ cells that expressed IL-1alpha protein were detected in both regions of the corneas at most time points following PRK. However, in the haze region at the 1, 3 and 4 week time points, significantly more (p<0.01) SMA+ cells did not express IL-1alpha. Also, in the haze region at all three time points, significantly more (p<0.01) SMA- cells than SMA+ cells expressed interleukin-1alpha protein. IL-1beta expression patterns in SMA+ and SMA- stromal cells was similar to that of IL-1alpha after PRK. Previous studies have demonstrated that IL-1alpha or IL-1beta triggers myofibroblast apoptosis in vitro, depending on the available concentration of apoptosis-suppressive TGFbeta. This study demonstrates that SMA- cells such as corneal fibroblasts, keratocytes, or inflammatory cells may produce IL-1alpha and/or IL-1beta that could act in paracrine fashion to regulate myofibroblast apoptosis--especially in the region where there is haze in the cornea after PRK was performed and SMA+ myofibroblasts are present at higher density. However, some SMA+ myofibroblasts themselves produce IL-1alpha and/or IL-1beta, suggesting that myofibroblast viability could also be regulated via autocrine mechanisms.

Laparoscopic esophagectomy.

Minimally invasive esophagectomy is emerging as an alternative option to open esophagectomy for benign and malignant esophageal diseases. This article provides a detailed review of the history of minimally invasive esophagectomy and an update on the currently accepted techniques for minimally invasive esophagectomy and its outcomes.

Characterization of human and mouse angiopoietin-like factor CDT6 promoters.

PURPOSE: Angiogenesis refers to the latter stage of vascular development. It has been reported that angiopoietin-like factor cornea-derived transcript 6 (CDT6) encodes a protein homologous to angiopoietins that could play a critical role in blocking a receptor of angiopoietin (Tie2) and therefore contribute to the avascularity and transparency of the cornea in the developing embryo and the adult. This study was focused on isolation and characterization of the CDT6 promoter. METHODS: Rapid amplification of cDNA ends (5'-RACE) was used to isolate the CDT6 promoter from an adaptor-ligated genomic DNA fragment library and to identify the transcription initiation site of the CDT6 gene. The RNase protection assay was performed to confirm the initiation site. The sequence similarity, binding sites for putative transcription factors, and transcriptional activity of human and mouse CDT6 promoters were compared. Corneal and noncorneal cells from humans and other animals were transiently transfected with CDT6 promoter-chloramphenicol acetyltransferase (CAT) reporter constructs to analyze the transcriptional activity of the promoter. RESULTS: A 2956-bp human CDT6 promoter fragment and a 3142-bp mouse CDT6 promoter fragment were isolated. The major transcription initiation sites of the human and mouse CDT6 genes were located at 224 and 168 bp, respectively, upstream of the translation initiation site. Human and mouse CDT6 promoter sequences were very similar. Both promoters were minus TATA and CAAT boxes close to the transcription initiation site. Transfection into human corneal and noncorneal cells and into nonhuman cells revealed that the human CDT6 promoter probably contains positive and negative cis-regulatory elements that modulate cell, tissue, and species specificity. The human CDT6 promoter contains four interferon (IFN)-stimulated response elements (ISREs). No ISREs could be identified in the mouse promoter. IFN-alpha stimulated transcriptional activity of the human promoter. CONCLUSIONS: The human and mouse CDT6 promoters have similar sequences and share many cis-regulatory elements. IFN-alpha appears to have an important role in regulating transcription of the human, but not the mouse, CDT6 promoter.

Proinflammatory chemokine induction in keratocytes and inflammatory cell infiltration into the cornea.

PURPOSE: To determine the effect of interleukin (IL)-1alpha and tumor necrosis factor (TNF)-alpha on cytokine, chemokine, and receptor expression in corneal stromal cells; the effect of corneal scrape injury on monocyte chemotactic and activating factor (MCAF) expression and monocyte-macrophage influx into the stroma; and the effect of MCAF and granulocyte colony-stimulating factor (G-CSF) microinjection on inflammatory cell infiltration into the stroma. METHODS: Gene array technology was used to evaluate changes in cytokine, chemokine, and receptor gene expression in stromal fibroblasts in response to IL-1alpha and TNFalpha. Expression of MCAF mRNA and protein was monitored with an RNase protection assay and Western blot analysis, respectively. Keratocyte MCAF protein expression in the rabbit cornea was detected with immunocytochemistry. After epithelial scrape injury, monocytes-macrophages were detected in rabbit corneas, by immunocytochemistry for monocyte-macrophage antigen. Inflammatory cell infiltration after MCAF and G-CSF microinjection into the stroma of mouse corneas was monitored with hematoxylin and eosin staining. RESULTS: IL-1alpha or TNFalpha upregulated the expression of several proinflammatory chemokines in stromal fibroblasts in culture. These included G-CSF, MCAF, neutrophil-activating peptide (ENA-78), and monocyte-derived neutrophil chemotactic factor (MDNCF). MCAF mRNA upregulation was confirmed by RNase protection assay, and MCAF protein was detected by Western blot analysis. MCAF protein was detected in keratocytes at 4 hours and 24 hours after epithelial injury, but not in keratocytes in the unwounded cornea. Corneal epithelial injury triggered the influx of monocytes-macrophages into the corneal stroma in the rabbit. Microinjection of MCAF and G-CSF into mouse cornea resulted in the influx of monocytes-macrophages and granulocytes, respectively, into the stroma. CONCLUSIONS: Proinflammatory chemokine induction in keratocytes is mediated by IL-1alpha and TNFalpha. The proinflammatory chemokines produced by the keratocytes probably trigger the influx of inflammatory cells into the stroma after epithelial injury associated with corneal surgery, contact lenses, or trauma.

Laser in situ keratomileusis-induced neurotrophic epitheliopathy.

PURPOSE: To report two cases of laser in situ keratomileusis-induced neurotrophic epitheliopathy with punctate epitheliopathy and rose bengal staining of the corneal flap. METHODS: Interventional case reports. RESULTS: A 42-year-old woman and a 37-year-old man with no preoperative symptoms or signs of dry eye developed dry eye symptoms and bilateral punctate epithelial erosions as well as rose bengal staining of the corneal flaps after laser in situ keratomileusis. Neither patient had less than 12 mm of wetting with the Schirmer test without anesthesia at any time point between development and resolution of the flap surface abnormalities. The flap surface abnormalities resolved approximately 6 months after laser in situ keratomileusis. CONCLUSIONS: Laser in situ keratomileusis-induced neurotrophic epitheliopathy may be attributable to loss of trophic influence from severed corneal nerve trunks. The condition typically resolves approximately 6 months after laser in situ keratomileusis or laser in situ keratomileusis retreatment.

Abdominal aortic aneurysm in women.

OBJECTIVE: The purpose of this study was to compare abdominal aortic aneurysm (AAA) associations in men and women. METHODS: Veterans aged 50 to 79 years without a previous history of AAA underwent ultrasound screening for AAA after completing a questionnaire on demographic information and potential risk factors. RESULTS: A total of 122,272 men and 3450 women were successfully screened. An AAA of 3.0 cm or greater in diameter was found in 4.3% of men and 1.0% of women (P <.001). Contrary to a previous report, we did not find suprarenal aortic enlargement accompanying AAA to be more common in women. The principal associations that we have previously reported for AAA in this cohort (age, smoking, family history of AAA, and a negative association with diabetes) were all similar in women compared with men. In age- and smoking-adjusted models, the interaction terms indicated that black race and cancer were more strongly associated with AAA in women than men (P <.05). Height and cerebral vascular disease were also more strongly associated with AAA in women than in men, but these interaction terms did not reach statistical significance (P <.10). Although the other differences were unexpected and require confirmation, the trend toward a stronger association of cerebral vascular disease with AAA in women is consistent with two previous reports. CONCLUSIONS: Despite the much lower prevalence of AAA in women, the most important associations with AAA are similar to those seen in men. Our data provide some support for a previous finding that cerebrovascular disease may be more closely associated with AAA in women than in men.

Computerized corneal topography and its importance to wavefront technology.

PURPOSE: To review the development and application of corneal topography in refractive surgery. METHODS: Review of the literature and discussion of recent developments in corneal topography and wavefront technology. RESULTS: Analysis of corneal topography provides critical information for the preoperative examination of patients before refractive surgery and for the evaluation and treatment of patients with complications after surgery. CONCLUSIONS: Corneal topography will continue to be a critical diagnostic modality for refractive surgery. Even with the advent of wavefront analysis designed to detect refractive error and aberrations of the eye, it will be necessary to have detailed corneal topographic information to understand the contribution the cornea makes to vision so that custom alteration of that surface can be used to optimize vision. This will be true of the normal eye, but it will be of special importance in eyes with abnormalities that were induced by corneal surgery.

Complications of laser in situ keratomileusis: etiology, prevention, and treatment.

PURPOSE: To review the etiology, prevention, and management of laser in situ keratomileusis (LASIK) complications. METHODS: Review of literature and the experience of the authors. RESULTS: Careful preoperative screening is critical to prevention of many potential complications of LASIK. Flap complications that occur during surgery are typically managed by replacement of the flap and repeating the surgery or applying special methods such as transepithelial photorefractive keratectomy weeks to months following the initial procedure. A common source of serious complications is the use of a microkeratome that functions after improper assembly. Timely treatment of postoperative complications such as diffuse lamellar keratitis, flap striae, and infection is critical to an optimal outcome. CONCLUSION: Most complications of LASIK can be treated effectively and have minimal effect on the final outcome after surgery, if appropriate methods are used for management.

The wound healing response after laser in situ keratomileusis and photorefractive keratectomy: elusive control of biological variability and effect on custom laser vision correction.

Biological diversity in the wound healing response is thought to be a major factor limiting the predictability of the outcome of refractive surgical procedures such as laser in situ keratomileusis and photorefractive keratectomy. Corneal wound healing is critical to the success of topography-linked or wave front-linked excimer laser ablation to optimize visual performance. This is because of the importance of retaining subtle features of custom ablation and the tendency of epithelial hyperplasia and stromal remodeling to obscure these features following either procedure. The corneal wound healing response is exceedingly complex. Keratocyte apoptosis, which occurs in response to epithelial injury, is the earliest observable event in the wound healing cascades and is therefore an excellent target for pharmacological intervention. Alterations of surgical technique can be designed to limit keratocyte apoptosis and the subsequent events in corneal wound healing. Abnormalities of the cascades could contribute to the pathogenesis of corneal diseases. For example, recent data have suggested that perturbation of the keratocyte apoptosis/mitosis balance could underlie the development of keratoconus in a proportion of patients.

Endovascular photodynamic therapy using mono-L-aspartyl-chlorin e6 to inhibit Intimal hyperplasia in balloon-injured rabbit arteries.

BACKGROUND AND OBJECTIVE: Intimal hyperplasia (IH) leading to restenosis is a major complication of arterial revascularization. The purpose of this study was to investigate the effect of photodynamic therapy (PDT) using mono-L-aspartyl chlorin e6 (NPe6) as a photosensitizer and intraluminal radial irradiation for inhibition of IH experimentally. STUDY DESIGN/MATERIALS AND METHODS: Study of laser transmission through the blood indicated that exclusion of blood is a prerequisite for intraluminal PDT. For homogeneous radial laser irradiation to the vessel wall, we used a newly developed cylindrical diffusing balloon laser fiber. Injuries were induced by pulling a balloon catheter through the right iliac artery of rabbits. One and 6 hours after the NPe6 injection (5mg/kg i.v.), drug distribution was examined by fluorescence microscopy. Nineteen rabbits received NPe6 at the time of injuries and PDT was performed with 664-nm laser at 30 and 10 J/cm(2) (20, 30, 40 mW/cm(2)) 1 hour after the injuries. The arteries were harvested at 2 days. In a second group of rabbits, PDT was given at 30 mW/cm(2) (30 J/cm(2)). Two weeks after treatment, the arteries were removed and examined histologically. RESULTS: NPe6 was found to be distributed selectively in the injured media. Endovascular NPe6-PDT showed complete depletion of smooth muscle cells even with 10 J/cm(2) at 2 days. IH was significantly inhibited at 14 days after PDT. CONCLUSIONS: Endovascular PDT of injured artery using NPe6 can prevent IH in this model of arterial wall injury and may become clinically useful for the prophylaxis of IH.

Laser in situ keratomileusis versus photorefractive keratectomy in the correction of myopic astigmatism.

PURPOSE: To evaluate retrospectively the effectiveness of astigmatism correction in eyes treated with laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). METHODS: Patients with low to moderate myopia with astigmatism ranging from +0.25 to +4.50 diopters were included in the study. PRK was performed on 62 eyes and LASIK on 70 eyes. Six-month data were analyzed with regard to astigmatism power, astigmatism axis, spherical equivalent, uncorrected visual acuity, vector astigmatism change, and topographic corneal regularity. RESULTS: Mean astigmatism magnitude change was 0.54 +/- 0.76 in PRK-treated eyes and 0.60 +/- 0.67 in LASIK-treated eyes (61% versus 64% change, respectively, p = 0.61) at 6 months after surgery. Mean spherical correction change was -2.79 +/- 1.51 for PRK and -2.90 +/- 1.03 for LASIK (p = 0.63). Mean spherical equivalent change was -2.5 +/- 1.57 for PRK and -2.6 +/- 1.23 for LASIK (p = 0.73). Mean change in astigmatism axis was 20.8 +/- 73.1 for PRK and 33.8 +/- 81.7 for LASIK (p = 0.34). Mean change in uncorrected visual acuity (LogMar) was 0.84 +/- 0.26 for PRK and 0.89 +/- 0.23 for LASIK (p = 0.21). Mean vector-corrected astigmatism change was 0.88 +/- 0.66 for PRK and 0.95 +/- 0.59 for LASIK (p = 0.51). Mean vector-corrected astigmatism axis for PRK was 86.9 +/- 59 degrees and for LASIK 83.8 +/- -47.6 degrees (p = 0.75). CONCLUSION: There was no significant difference in astigmatism correction between PRK and LASIK at 6 months after surgery.

Hyperopic laser in situ keratomileusis: primary and secondary treatments are safe and effective.

PURPOSE: To retrospectively analyze the safety and efficacy of hyperopic laser in situ keratomileusis (LASIK) treatment of eyes with primary hyperopia and consecutive hyperopia after initial myopic treatment. METHODS: Thirty-two eyes of 19 patients with primary hyperopia (group 1) and 37 eyes of 26 patients with consecutive hyperopia after initial myopic LASIK overcorrection (group 2) that had LASIK for hyperopia with the Hansatome microkeratome and VISX S2 Smoothscan excimer laser with 6 months' follow-up after surgery were analyzed. Uncorrected visual acuity, best spectacle-corrected visual acuity, fogged manifest refraction, and corneal topography with corneal irregularity measurement (CIM) were evaluated 1 month, 3 months, and 6 months after surgery. RESULTS: In group 1, the mean preoperative cycloplegic spherical equivalent was +4.0 +/- 4.5 diopters (D) (range, +1.5 to + 8.75 D) and the 6-month postoperative cycloplegic spherical equivalent was +0.26 +/- 1.74 D (range, -3.00 to +2.75 D). Fifty-three percent of eyes (n= 17) in group 1 were within 1 D of emmetropia. Sixty-six percent of eyes (n= 21) had uncorrected visual acuity of at least 20/40. Three eyes (9%) lost two lines of best spectacle-corrected visual acuity. Changes in uncorrected visual acuity, best spectacle-corrected visual acuity, spherical equivalent, and the CIM topographic index 6 months after surgery were statistically significant compared with the preoperative values. In group 2, the mean preoperative cycloplegic spherical equivalent was +1.58 +/- 0.35 D (range, +0.125 to +2.75 D), and the mean postoperative cycloplegic spherical equivalent was -0.48 +/- 0.46 (range, -2.75 to +0.38 D). Eighty-six percent of eyes (n= 32) were within 1 D of emmetropia. Eighty-four percent of eyes (n= 31) in group 2 had uncorrected visual acuity of at least 20/40. One eye (2.7%) lost two lines of best spectacle-corrected visual acuity. Complications included an epithelial nest that resolved 3 months after surgery in one eye in group 2. CONCLUSIONS: LASIK is a relatively safe treatment of primary hyperopia and hyperopia resulting from overcorrection after initial LASIK treatment of myopia (consecutive hyperopia). Patients with high hyperopia (>5 D) are at risk for loss of two lines of best spectacle-corrected visual acuity. A reduction in the level of attempted correction appears to be necessary in the treatment of consecutive hyperopia.

Laser in situ keratomileusis-induced (presumed) neurotrophic epitheliopathy.

OBJECTIVE: To evaluate tear production, corneal topography, accuracy of refractive correction, and best spectacle-corrected visual acuity in eyes that had moderate to severe rose bengal staining develop on the flap compared with eyes with little or no staining on the flap, the first few months after laser in situ keratomileusis (LASIK). None of the eyes in this study had significant preoperative dry eye disease. DESIGN: Retrospective case control study. PARTICIPANTS: Individual eyes of 19 consecutive patients with moderate to severe punctate epithelial erosions and rose bengal staining on the flap 1 to 3 months after LASIK were compared with eyes of 19 concurrent patients who did not have punctate epithelial erosions or more than trace staining on the flap develop. METHODS: Nonparametric statistical analyses were used to compare tear secretion, corneal topographic irregularity, spherical equivalent, and visual acuity 3 and 6 months after surgery. Some eyes in both groups also had analysis of tear secretion 1 month after surgery. MAIN OUTCOME MEASURES: Schirmer's test without anesthesia, the topographic corneal irregularity measurement (CIM), the difference between attempted and achieved spherical equivalent, and the loss of best spectacle-corrected visual acuity. RESULTS: There was no difference in tear production 1, 3, or 6 months after LASIK in patients who had punctate epithelial erosions and rose bengal staining on the flap develop and those who did not. There was no significant difference in the CIM or mean accuracy of the refractive correction in the two groups, but some patients had a transient decrease in best spectacle-corrected visual acuity. Flap rose bengal staining resolved by 6 months after LASIK in most affected patients. CONCLUSIONS: LASIK-induced rose bengal staining in patients without preexisting dry eye is likely neurotrophic epitheliopathy, because there is no difference in mean tear production between patients who have significant punctate epithelial erosions and rose bengal staining develop on the flap and those who do not. The signs and symptoms of LASIK-induced (presumed) neurotrophic epitheliopathy tend to resolve approximately 6 months after surgery. This disorder tends to be more common and severe in patients with pre-existing dry eye disease.

Recovery of uncorrected visual acuity after laser in situ keratomileusis or photorefractive keratectomy for low myopia.

PURPOSE: To compare uncorrected visual acuity and refractive error in patients undergoing photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) between 1 week and 6 months after surgery. METHODS: All eyes underwent PRK or LASIK with the VisX StarS2 excimer laser. We retrospectively analyzed data from 77 random eyes of 77 patients in the PRK group and 76 eyes of 76 patients in the LASIK group. All eyes had a low myopic refractive error (spherical equivalent range, -0.88 diopters (D) to -5.13 D; mean PRK. -2.8 +/- 0.20 D: LASIK, -2.5 +/- 0.22 D). Uncorrected visual acuity and manifest refractive error were evaluated 1 week, 1 month, and 6 months after surgery. RESULTS: Each eye undergoing PRK was paired with an eye undergoing LASIK for a similar level of spherical equivalent. Mean uncorrected visual acuity after 1 week was 0.85 +/- 0.06 (20/25, logMAR 0.12 +/- 0.04) for the PRK group and 1.01 +/- 0.06 (20/20, logMAR 0.01 +/- 0.03) for the LASIK group (p < 0.001). Mean spherical equivalent after 1 week was 0.23 +/- 0.12 D for the PRK group and -0.02 +/- 0.07 D for the LASIK group (p = 0.02). Mean uncorrected visual acuity after 1 month was 1.03 +/- 0.05 (20/20, logMAR 0.02 +/- 0.03) for the PRK group and 1.05 +/- 0.05 (20/20. -0.02 +/- 0.03) for the LASIK group (p = 0.16). Mean spherical equivalent after I month was 0.19 +/- 0.10 D for the PRK group and -0.02 +/- 0.09 D for the LASIK group. This difference was statistically significant (p = 0.02), but was unlikely to be clinically significant. Mean uncorrected visual acuity after 6 months was 1.05 +/- 0.06 (20/20, logMAR -0.01 +/- 0.03) for the PRK group and 1.06 +/- 0.05 (20/20, logMAR -0.14 +/- 0.03) for the LASIK group (p = 0.41). Mean spherical equivalent after 6 months was 0.02 +/- 0.08 D for the PRK group and 0.00 +/- 0.08 D for the LASIK group (p = 0.35). CONCLUSION: Uncorrected visual acuity 1 week after surgery is significantly better in eyes undergoing LASIK than in eyes undergoing PRK. Both procedures provide functional vision by 1 week after surgery. The difference does not relate to refractive error, which was similar between the two groups, but to differences in healing of the epithelium. By 1 month after surgery, there is no difference in mean uncorrected visual acuity between eyes that undergo PRK or LASIK for low myopia.

Threats to the surgical residency in the academic medical center.

Threats to the current form of surgical training in the academic medical center include financial pressures from the government and managed care organizations. A diminishing medical student interest in surgical careers has been noted. The constraints of managed care hold the potential to introduce weaknesses in surgical training in the academic medical center.

Three-year outcome of endovascular treatment of superficial femoral artery occlusion.

HYPOTHESIS: Patency after primary percutaneous transluminal angioplasty (PTA) and stenting of superficial femoral artery (SFA) occlusions is better than historical experience with PTA alone. DESIGN: Consecutive case series of primary PTA with stenting, and follow-up with duplex imaging every 6 months (mean +/- SD follow-up, 32 +/- 15 months). SETTING: Veterans Affairs medical center. PATIENTS AND METHODS: Patients were 57 previously untreated men with 71 limbs having chronic atherosclerotic SFA occlusion with suprageniculate reconstitution and patent tibial runoff. Critical ischemia (Society for Vascular Surgery [SVS] category, 4-6) was present in 7 (10%), the remainder had intermittent claudication only (SVS, 1-3). INTERVENTIONS: Guidewire recanalization followed by PTA, Wallstent deployment, and adjunctive thrombolysis as necessary; 19 limbs (27%) required thrombolysis to manage periprocedural thrombosis. MAIN OUTCOME MEASURES: Cumulative patency, limb salvage, and complications. RESULTS: Length (mean +/- SD) of occlusion was 14.4 +/- 9.9 cm. Length of stented artery was 24.3 +/- 11.1 cm. Ankle brachial index increased from 0.59 +/- 0.14 to 0.86 +/- 0.16 (P<.001) after stenting. One- and 3-year patencies were as follows: primary, 54.6% +/- 6.3% and 29.9% +/- 6.6%; assisted primary, 72.3% +/- 5.6% and 59.0% +/- 6.8%; and secondary, 81.6% +/- 4.8% and 68.3% +/- 6.5%. Three-year secondary patency when periprocedural thrombolysis was required was 35.7% +/- 12.5% compared with 70.6% +/- 7.4% for limbs not requiring periprocedural thrombolysis (P=.02); the differences in occlusion length and severity of ischemia were not significant between these 2 groups. Limbs undergoing adjunctive PTA during angiography 6 to 12 months after initial stenting had 63.0% +/- 13.3% patency at 3 years compared with 100% patency in limbs not requiring PTA at 6 to 12 months angiography (P=.046). Periprocedural mortality and morbidity were 2.8% and 15.5%, respectively. Three of the 7 limbs with critical ischemia underwent amputation during follow-up compared with 2 (3%) of 64 limbs with functional ischemia (chi(2) test, P<.006). A mean of 1.8 endovascular interventions per limb were performed. CONCLUSIONS: Percutaneous transluminal angioplasty and stenting yielded higher patency rates than historical controls undergoing PTA alone. When periprocedural thrombolysis is required, subsequent patency appears to be significantly worse. Poor results after PTA and stenting of limbs with critical ischemia and the need for additional endovascular therapy limit the technique's utility.