The effect of topical corticosteroids on refractive outcome and corneal haze after photorefractive keratectomy

BACKGROUND: The effect of topical corticosteroids after excimer laser photorefractive keratectomy (PRK) remains a matter of some controversy. Refractive effects may be different according to the amount of myopia and timing of instillation. METHODS: Two groups of patients were studied: Study A consisted of 215 eyes (128 patients) with PRK (mean baseline myopia, -6.53 +/- 2.22 D) that received no corticosteroids (No Corticosteroid Group) unless significant regression or corneal haze appeared (Delayed Corticosteroid Group), and in Study B, we randomly assigned eyes to the Initial Corticosteroid Group (mean baseline myopia, -6.39 +/- 1.84 D) or the No/delayed Corticosteroid Group (mean baseline myopia -5.78 +/- 2.02 D). Clinical results after PRK for low-to-moderate and high myopia were compared. RESULTS: In the first group, 70.9% (73 eyes) of moderately myopic eyes (mean, -4.56 +/- 1.10 D) belonged to the No Corticosteroid Group that had a mean refraction of -5.39 +/- 1.77 D. Delayed Corticosteroid Group eyes were more myopic (mean, -7.52 +/- 2.10 D), and showed more severe haze than those in the No Corticosteroid Group. In study B, only in high myopes with more than -6.00 D (mean, -7.76 +/- 1.15 D) did refraction and corneal haze outcomes show significant difference between the Initial Corticosteroid Group and the No/delayed Corticosteroid Group. CONCLUSIONS: The effects of topical corticosteroids after PRK were less in moderate myopes compared to high myopes. Delayed instillation of corticosteroids did not reverse the regression or haze whereas initial instillation showed a beneficial effect on high myopes but not on moderate myopes.     

Short-term effects of flurbiprofen and diclofenac on refractive outcome and corneal haze after photorefractive keratectomy

PURPOSE: To evaluate the short-term effects of topical nonsteroidal anti-inflammatory drugs (NSAIDs) on refractive outcome and corneal haze after excimer laser photorefractive keratectomy (PRK) according to the degree of myopia and to compare the results with those of topical steroids. SETTING: Seoul National University Hospital, Seoul, Korea. METHODS: Patients were divided into two groups: low to moderate myopia (-6.00 diopters [D] or less) and high myopia (greater than 6.00 D). Then, each patient was randomly assigned to one of three drug subgroups for initial management (4 months post-PRK): corticosteroids (fluorometholone 0.1%); flurbiprofen sodium 0.03% (Ocufen); diclofenac sodium 0.1% (Decrol). Follow-up was 6 months. RESULTS: In eyes with low to moderate myopia, the steroid and diclofenac subgroups had significantly different refractions 2 and 4 months postoperatively but no difference at 6 months; subjective haze grading was consistently lower in the steroid subgroup than in the NSAID subgroups (flurbiprofen, diclofenac) after 2 months. In eyes with high myopia, the steroid subgroup had significantly less myopic regression after 3 weeks and lower subjective haze after 2 months than the NSAID subgroups. The steroid subgroup had severe myopic regression or corneal haze less frequently than the NSAID subgroups. CONCLUSION: Topical NSAIDs were less effective than topical steroids in reducing myopic regression and haze after PRK, especially in highly myopic eyes.     

Quantification of stromal thinning, epithelial thickness, and corneal haze after photorefractive keratectomy using in vivo confocal microscopy

PURPOSE: The authors establish, for the first time, observer-independent quantification of stromal thinning, epithelial thickness, and corneal haze after excimer laser photorefractive keratectomy (PRK) using a unique, new form of in vivo confocal microscopy. METHODS: Rapid, continuous z-scans of high-resolution confocal images, termed confocal microscopy through focusing (CMTF), were performed in the central corneal area of 17 patients before and 1 month after PRK for low- to moderate-grade myopia (-2.88-9.13 diopters [D]). Corneal, epithelial, and stromal thickness measurements and an objective haze estimate were obtained from each CMTF scan by digital image analysis. RESULTS: Epithelial thickness averaged 51 +/- 4 microns before and 45 +/- 10 microns 1 month post-PRK (P < 0.005), whereas stromal thinning ranged from 20 to 154 microns, representing a direct estimate of the actual photoablation depth. Corneal thickness averaged 560 +/- 36 microns before PRK and 462 +/- 52 microns at 1 month. The change in corneal thickness correlated closely with the change in spherical equivalent refraction (r = 0.94, P < 0.0001); linear regression analysis revealed a value of 14.3 microns corneal thinning per diopter of correction. A significant correlation was found between the objective CMTF haze estimate and a clinical haze grading obtained by slit-lamp examination (r = 0.73, P < 0.001). CONCLUSIONS: Confocal microscopy through focusing is a new, powerful in vivo tool that enables quantitative, unbiased evaluation of PRK procedures over time by providing epithelial and stromal thickness analysis, photoablation depth assessment, and unbiased haze measurement. The method is uniquely valuable in the pre- and postoperative assessment of PRK patients and for determining the optimal treatment strategy, especially in assessing refractive and visual outcomes in individual cases.     

Topical interferon alpha 2b for corneal haze after excimer laser photorefractive keratectomy. The Melbourne Excimer Laser Group

PURPOSE: To determine whether topical interferon alpha 2b (IFN-alpha) prevents corneal haze after excimer laser photorefractive keratectomy (PRK). SETTING: Tertiary referral ophthalmic hospital. METHOD: A prospective, double-blind, placebo-controlled, randomized study of 31 patients was undertaken. After surgery in a single institution, patients received a drop of either a placebo or IFN-alpha (5 x 10(6) IU/ml) four times daily for 4 weeks. The main outcome measures were corneal haze, refraction, and visual acuity. RESULTS: The major side effect of interferon alpha treatment was a significant delay in epithelial healing by a mean of 2 days. The means of the average post-treatment clinical scores for haze in all patients up to 12 months after surgery were 0.46 +/- 0.25 for the IFN-alpha group and 0.64 +/- 0.43 for the placebo group (P = .20). Of patients with a correction of greater than 5.00 diopters (D), the IFN-alpha group had significantly less haze over the course of the study (0.39 +/- 0.23 versus 0.98 +/- 0.50; P = .03). After 12 months, the mean absolute spherical equivalent in the two groups was not significantly different (1.02 +/- 1.13 D versus 1.44 +/- 2.64 D). There was a tendency toward better uncorrected visual acuity in the INF-alpha group (P < .10, Kolmogorov-Smirnov). CONCLUSION: Topical IFN-alpha may merit further investigation as a treatment to reduce corneal haze after excimer laser PRK for corrections greater than 5.00 D.     

The shape of the corneal apical zone after excimer photorefractive keratectomy

Applying an experimental photo-keratoscope, which assesses the shape of cornea within the pupillary region, to a group of subjects who have undergone excimer laser photorefractive keratectomy over a central 4 mm chord diameter of the cornea, we report the shape of the typical cornea within the ablated zone conforms to a steepening ellipse (average shape factor, 1.25). A statistically significant difference in the mean shape factor (asphericity) between the photoablated and the normal cornea (average shape factor 0.89) was not confirmed. However, there is more variability in the shape factors found in the photorefractive keratectomy group compared with normals, within the same distance from the corneal apex. Using the criterion of overlap within two standard deviations, averaging the vertical horizontal meridians, 75% of photorefractive keratectomy eyes fall within the shape factor limits of the normal eye group. In all cases the post-ablated corneal surface was found to be regular in terms of surface quality alone. The excimer photorefractive keratectomy technique is therefore a clinically acceptable method of refractive surgery.     

Factors determining the refractive effects of intrastromal photorefractive keratectomy with the picosecond laser

PURPOSE: To determine the relationship between laser parameters and tissue removal with picosecond laser intrastromal photorefractive keratectomy (ISPRK) and to assess the effect of the parameters on the healing process and the long-term refractive changes. SETTING: Medical Laser Center Lübeck, Germany. METHODS: A modified Intelligent Surgical Lasers (ISL) 2001 system with a cone angle of 30 degrees was used for in vitro investigations of the laser effects in water and on the porcine cornea. Photographic methods were used to determine the plasma volume and to investigate the thickness of the intrastromal bubble layer as a function of the laser pulse energy, the number of layers in which the pulses were applied, and the layer separation. The data were used to calculate the amount of tissue removal. Histologic evaluation was done by polarization microscopy after Sirius-red staining. RESULTS: The laser pulses produced a sponge-like appearance of the stroma in a layer extending through about one third the corneal thickness, accompanied by mechanical distortions of the stromal lamellae. Thermal changes were weak. Tissue removal was impaired by the cavitation bubbles from preceding laser pulses. The amount of evaporated tissue depended only weakly on laser pulse energy and number of layers in which the pulses were applied. The maximum amount of tissue that could be evaporated without damaging the outer corneal layers was a 10.0 microm thick layer. With a 6.0 mm optical zone, the tissue removal produced an immediate refractive effect of only 0.85 diopter. CONCLUSIONS: Intrastromal PRK does not work as originally envisioned because the amount of evaporated tissue is very small. The greater long-term refractive changes observed in animal experiments and clinical studies must therefore be due to the healing response of the cornea. Because the refractive effects are strongly influenced by the healing response of the cornea, they are poorly predictable.     

Effect of beam variables on corneal sensitivity after excimer laser photorefractive keratectomy

AIM: To investigate changes in corneal touch sensitivity following excimer laser photorefractive keratectomy (PRK) using different beam configurations. METHODS: 20 subjects were given a unilateral -3.00 D correction with either a 5 mm (26 micrograms, n = 10) or 6 mm (42 micrograms, n = 10) beam diameter. Thirty subjects underwent a unilateral -6.00 D correction with 5 mm (62 micrograms, n = 10), 6 mm (78 micrograms, n = 10), or multizone (62 micrograms, n = 10) treatments. The multizone treatment was 6 mm in diameter with the depth of the 5 mm treatment. Corneal sensitivity was measured using a slit-lamp mounted Cochet-Bonnet aesthesiometer before and at 1, 3, 6, and 12 months after PRK. Stimulus locations included points lying within the ablated zone (central) and outside (peripheral). These were compared with the equivalent locations in control (untreated) eyes. RESULTS: There was a significant reduction in corneal sensitivity within the central (ablated) zone in all treatment groups after PRK. In most groups a return to full sensitivity was achieved by 6 months with the exception of the multizone treatment group which showed significant corneal hypoaesthesia at 12 months. Peripheral corneal sensitivity was also reduced in this group up to 3 months after the procedure. A comparison between the -3.00 D and -6.00 D treatment groups showed no significant difference. However, combining data from all treatment groups, a significant correlation was found between the interocular difference in central corneal sensitivity and postoperative haze at 3 and 6 months. CONCLUSIONS: For corrections up to -6.00 D ablation depth and treatment zone diameter do not appear to be clinically important determinants of corneal hypoaesthesia. In contrast, postoperative corneal haze appears to correlate with sensitivity loss.     

Real-time confocal microscopic observations on human corneal nerves and wound healing after excimer laser photorefractive keratectomy

PURPOSE: Corneal wound healing after excimer laser photorefractive keratectomy (PRK) passes through a series of characteristic stages which have earlier been defined by means of histological, histochemical, and biochemical approaches. We investigated the potential of confocal microscopy to verify morphological changes in human corneas in vivo after PRK. METHODS: Ten corneas of eight patients that had earlier undergone PRK were examined at different postoperative time points (7 days-34 months). One of the PRK patients was examined sequentially three times. Three additional corneas, which had earlier undergone corneal grafting surgery and then were subjected to excimer laser photoastigmatic keratectomy (PARK), were studied as well. Seven healthy untreated corneas served as controls to define the normal morphology of human cornea. A tandem scanning confocal microscope (TSCM) was used to generate real-time images of the corneas on an S-VHS videotape. The images were either digitized and further processed or the individual video frames were produced with a video printer. RESULTS: Seven days post-PRK in vivo confocal microscopy revealed the presence of morphologically immature surface epithelial cells. Delicate nerves, activated keratocytes and deposition of extracellular light-reflecting scar tissue were perceived. The epithelium appeared normal one month post-PRK. Ongoing activation of the anterior stromal keratocytes along with extracellular scar tissue were detected. We also observed increasing numbers of regenerating subepithelial nerve leashes with somewhat twisted pattern. Highly reflective, presumably activated keratocytes were no longer detected 6-7 months post-PRK. Hypercellularity with scar tissue could still be found up to 30 months post-PRK. Only one cornea examined 34 months post-PRK showed normal keratocyte morphology and recovery of the anterior stroma. However, the morphology of subepithelial nerves was still somewhat abnormal. The two corneal grafts examined 11 or 32 months post-PARK exhibited a normal-appearing epithelium but considerable stromal hypercellularity and extracellular scar deposition. The subepithelial nerves were poorly regenerated in one eye and fairly well detectable in the other. The third graft examined 15 months post-PARK revealed the presence of enlarged surface epithelial cells and dense stromal scarring but no nerves. CONCLUSION: TSCM clinically confirms the earlier histological data on healing of excimer laser wounds. It offers a distinct improvement in the assessment of excimer laser-treated corneas, as it enables cellular details and nerves to be perceived in vivo. In addition the thickness of the stromal scar can be be measured for e.g. planning of phototherapeutic keratectomy.     

Effect of surface photorefractive keratectomy and laser in situ keratomileusis on the corneal endothelium

PURPOSE: To investigate endothelial cell loss in pairs of fresh human autopsy globes following high-diopter myopic photorefractive keratectomy (PRK) or laser in situ keratomileusis (LASIK). SETTING: Center for Research on Ocular Therapeutics and Biodevices and Magill Laser Center for Vision Correction, Storm Eye Institute, Charleston, South Carolina, USA. METHODS: In the first part of the study, 12 globes had either -10 diopters (D) multizone surface PRK or -10 D single-zone LASIK. In the second part, three groups of 5 globes each had -15 D, -20 D, or -25 D multizone-blend LASIK procedures. Fellow globes in both groups were used as untreated controls. Corneoscleral buttons were excised from all globes. Following 7 days in corneal organ culture, the endothelial surface was stained with two vital dyes: calcein-AM and ethidium homodimer. Fluorescence microscopy was used to obtain endothelial cell counts. RESULTS: The mean dead cells per square millimeter (cells/mm2) were 0.94 in the -10 D PRK treated corneas compared with 0.91 in the fellow untreated eyes (P = 0.06(. The mean dead cells/mm2 in the -10 D single-zone LASIK-treated corneas and in the fellow untreated eyes were 0.61 (P = 0.88). The mean dead cells/mm2 in the -15 D, -20 D, and -25 D multizone-blend LASIK-treated corneas were 3.08, 2.33, and 5.55, respectively, compared with 3.49, 1.92, and 5.01 in the fellow untreated eyes (P = 0.276, P = 0.339, and P = 0.427, respectively). Dead cell counts for treated and control paired corneas were highly correlated in all treatment groups. CONCLUSIONS: No significant endothelial cell loss occurred after -10 D PRK or LASIK corrections up to -25 D. Although this study has limitations that prevent direct extrapolation to the clinical situation, it does afford a comparable clinical correlate for endothelial cell toxicity following a typical excimer laser ablations.     

Mathematical simulation of retinal image contrast after photorefractive keratectomy with a diaphragm mask

BACKGROUND: Photorefractive keratectomy (PRK) using a dilating diaphragm mask engraves a delicate three-dimensional staircase pattern into a formerly smooth corneal surface. The created steps are later smoothed by tear film and wound healing processes. The present study investigates, in a mathematical simulation, the effects that such staircase patterns and their smoothing may have on retinal image contrast. METHODS: All simulations are based on the Gullstrand eye model and calculate retinal image contrast from point spread function (PSF) analysis of Gullstrand eyes treated by simulated PRK under various conditions. RESULTS: The simulations indicate that PRK can reduce retinal contrast markedly. The most critical factor for such a reduction is the step height of the ablation pattern. With step heights below 0.4 microns, loss of contrast due to the created staircase pattern is always moderate and should be restored during early wound healing. Complete wound healing may smooth out larger step heights. Micromovements during PRK also can lead to partial loss of retinal image contrast. CONCLUSIONS: Simulation of retinal contrast after PRK shows that step heights below 0.4 microns seem to be acceptable. A minimization of the micromovements during PRK can offset some of the reduction of retinal contrast.     

The effect of tranilast on subepithelial corneal opacity after excimer laser keratectomy

Recent studies have reported that tranilast inhibited in vitro the proliferation of keratocytes from corneal subepithelial opacities (haze) and collagen synthesis in cultured corneas after excimer laser photorefractive keratectomy (PRK). In this study 0.5% tranilast eye drops, 0.1% betametazone phosphate eyedrops, and a 0.5% tranilast base solution (control) were administered four times daily to rabbits which had undergone PRK. Weekly evaluation of the inhibitory effect of these drugs on haze began two weeks after surgery according to Fantes' classification. 0.5% tranilast suppressed haze from six weeks to thirteen weeks after PRK (p < 0.05). 0.1% betametazone phosphate showed no effect. These results suggested that 0.5% tranilast had a satisfactory therapeutic effect on haze after PRK.     

Effects of corticosteroid and nonsteroid antiinflammatory drugs on corneal transparency after photorefraction keratectomy

The paper reports 20-year follow-up results (from 1976-1977 to 1996-1997) of 175 patients with drug addiction that began at the young age. The patients with opiate addiction prevailed. Structural-dynamic alterations of the main clinic symptom complexes, the validity of the factors that are essential for the reduction of pathological drive are analyzed. There was a tendency to progressive decrease of narcotics administration as the severity of somatic pathology increased. Episodes of narcotics administration were permanent by the end of the second decade of the disease in less than 20% of the patients from the primary cohort; alcohol and psychotropic drug (hypnotics, tranquilizers) dependence has developed in about 1/3 of the patients. The most influence on the regress of pathologic drive had the factors related with both the duration of the isolation from narcotics and the development of schizophrenic process; therapeutic regress was observed much rarer. High lethality of the patients with drug addiction was found: more than 46% during 20 years of the disease.     

Corneal reinnervation after photorefractive keratectomy and laser in situ keratomileusis: an in vivo study with a confocal videomicroscope

The purpose of this study was to compare the regeneration of corneal nerves after photorefractive keratectomy (PRK) versus laser in situ keratomileusis (LASIK) in vivo with a confocal videomicroscope. In all, 15 eyes that had undergone PRK and 15 eyes that had been subjected to LASIK were compared with a confocal in vivo slit-scanning video-microscope. The subepithelial nerves were observed preoperatively and at 3, 6, and 12 months postoperatively. In all eyes, good microscope images of the subepithelial nerve plexus could be obtained preoperatively. Because of postoperative light reflection and scattering in the treated area, subepithelial nerve-fiber regeneration could be followed satisfactorily only in seven eyes after PRK and in five eyes following LASIK. In the eyes treated with PRK, recovery of subepithelial reinnervation started from the margin of the ablation zone, being directed toward the center of the cornea. At 8 weeks postoperatively, rarefied subepithelial nerve fibers were visible at the edges, and after 3 months, single nonbranched nerve fibers could be visualized in the center of the ablation zone. At 6-8 months following PRK, subepithelial nerve regeneration seemed to be completed; however, abnormal branching and accessory thin nerve fibers were present without exception. After LASIK, corneal nerve-fiber regeneration followed the same course described for PRK except that regenerated subepithelial nerve fibers were barely visible in the center after 6 months. Further changes in nerve structure were visible for up to 12 months postoperatively. Recovery of corneal sensitivity in humans has been reported to start at 4-6 weeks after PRK and is said to be completed within 6-12 months of surgery. Slit-scanning videomicroscope findings were in accordance with these observations.     

Alterations of corneal extracellular matrix after multiple refractive procedures: a clinical and immunohistochemical study

PURPOSE: To describe the clinical course and alterations of the corneal extracellular matrix (ECM) and basement membrane (BM) in a cornea after hexagonal keratotomy, transverse keratotomies, and keratomileusis. METHODS: Frozen sections of this cornea and of 12 normal corneas were studied by immunofluorescence with specific antibodies. The patient history was analyzed to allow a clinical correlation. RESULTS: In the treated cornea, keratotomy scars and subepithelial fibrosis with neovascularization were seen. Around and beneath the epithelial plugs and along the keratotomy scars, deposits of types III, VI, VIII, and XIV collagen; fibrillin-1; fibronectin; and tenascin-C were found, together with short streaks of types IV (alpha 1-alpha 2) and VII collagen, laminin-1 and -5, entactin, and perlecan. alpha 3-alpha 4 Type IV collagen chains were abnormally absent from the BM around the epithelial plugs. At the edges of the keratomileusis flap, subepithelial fibrosis areas were found, with abnormal deposits of eight different collagen types, perlecan, fibronectin, fibrillin-1, and tenascin-C. The major part of the flap interface did not show ECM abnormalities. ECM alterations outside the scarred areas included the appearance of tenascin-C in the stroma and of alpha 1-alpha 2 type IV collagen in the epithelial BM, and the disappearance of fibronectin from Descemet's membrane. CONCLUSION: Five years after surgery, the treated cornea still presented BM abnormalities at sites of keratotomy scars and epithelial plugs. Several ECM components were abnormally expressed outside the scarred areas, consistent with an ongoing fibrosis in the treated cornea.     

A prospective clinical study of correction of myopic astigmatism by combined treatment with PRK and T-incision and photoastigmatic refractive keratectomy. The results after one year

BACKGROUND: In contrast to the correction of simple myopia there is no widely accepted technique for the correction of myopic astigmatism. Currently two techniques are available: the photoastigmatic refractive keratectomy (PARK) and the combination of arcuate keratotomies with standard PRK (PRK-T). METHODS: In two groups, 67 patients underwent a correction of myopic astigmatism in a total of 87 eyes (19 by PRK-T and 68 by PARK), and were followed for 1 year. The spherical equivalent was -6.7 D in both groups and the refractive astigmatism ranged from -1.0 to -6.5 D. The PARK procedure was performed by means of an elliptic ablation (Kertom I, Schwind) with a 5.8 x 8.1 mm zone. The PRK-T technique consisted of two arcuate keratotomies with a free optical zone of 7 mm and a standard myopic PRK at least 6 weeks later. RESULTS: The 1 year follow-up was completed in 57 out of 87 eyes included in the study. At 1 year post-operation, 83% of the PRK-T group and 80% of the PARK group had an uncorrected visual acuity of 20/40 or better. The refractive astigmatism was reduced by 76% in the PRK-T group and by 67% in the PARK group. The spherical equivalent was -0.59 +/- 1.1 D at 1 year after PRK-T and -0.28 +/- 1.04 D after PARK. In three eyes of the PARK group (6.7%) a visual loss of more than one Snellen line occurred. Two of these eyes had a preoperative myopia of more than -6 diopters. CONCLUSION: Both techniques have the potential to reduce myopic astigmatism, however, the success rate is not as high compared to spherical PRK. Also, the complication rate of 2.5% in corrections to -6 D is significantly higher than that with spherical myopic PRK.     

Effects of transforming growth factor beta on corneal epithelial and stromal cell function in a rat wound healing model after excimer laser keratectomy

BACKGROUND: Transforming growth factor beta (TGF-beta) regulates extracellular matrix deposition, cell proliferation, and migration, and is expressed in cornea. TGF-beta is thought to be involved in the corneal wound healing process. METHODS: The central corneal area (3 mm in diameter) of Lewis rats was ablated using PTK mode excimer laser and the wound healing process was observed at 12 and 24 h and 2, 5, 10, and 30 days after treatment. The expression of TGF-beta 1, -beta 2 and -beta 3, TGF-beta type I and type II receptors, alpha 3, alpha 5, beta 4 integrin subunits, laminin and fibronectin was studied immunohistochemically. Antibody neutralizing TGF-beta 1, -beta 2 and -beta 3 was administered intraperitoneally, 50 micrograms daily, for 5 days after the laser treatment to investigate the effects of TGF-beta function blockade. RESULTS: At the leading edge of the regenerating epithelium, no TGF-beta type I and type II receptors and beta 4 integrin subunits were expressed after 24 h. Regenerating epithelium covered the ablated area after 2 days. An abnormal fibrotic layer was formed in the subepithelial area. This layer contained round-shaped cells in the stroma in the early stage (2-5 days after laser ablation) and spindle-shaped fibroblast-like keratocytes after 10 days. Laminin and fibronectin expression increased in the fibrotic layer. The increased stromal cells expressed TGF-beta isoforms and TGF-beta receptors. Neutralizing TGF-beta inhibited the stromal cell increase in the laser ablated area after 5 days. CONCLUSION: TGF-beta may be involved in epithelial cell migration and stromal cell reaction during the corneal wound healing process after excimer laser ablation in rat models.     

The effects of preoperative therapy with angiotensin-converting enzyme inhibitors on clinical outcome after cardiovascular surgery

PURPOSE: Quality of life of breast cancer survivors 8 years after diagnosis was compared with that among similarly aged women who had never confronted cancer (controls). METHODS: Survivors of a consecutive series of 227 breast cancer patients first treated in 1984 were approached for this study. Random-digit dialing was used to identify controls with the same age and residential distribution as the survivors. Quality of life was assessed in terms of physical health, functional status, psychologic distress, and social functioning. RESULTS: Participation was obtained from 96% (n = 124) of 129 eligible survivors and 61% (n = 262) of 427 potentially eligible controls. Consistently smaller proportions of survivors reported positive quality-of-life outcomes compared with controls, but these differences were generally small and nonsignificant statistically. When limited to women who remained free of disease over the entire follow-up period (n = 98), survivors' quality of life was similar to that among controls, with the exception of arm problems and sexual satisfaction for those women who lived with a partner. In contrast, survivors who developed recurrence or new primary breast cancer (n = 26) experienced a worse quality of life in all domains except social functioning. CONCLUSION: In most domains and for women without further disease events after diagnosis, quality of life does not seem to be permanently and globally impaired by breast cancer. Consequently, breast cancer survivors who remain free of disease probably do not need organized late psychosocial follow-up to improve quality of life. However, arm problems and sexuality are two areas in which additional effort may be still needed to improve quality of life of long-term survivors.     

Effect of topical steroids on nasal nitric oxide production in children with perennial allergic rhinitis: a pilot study

It has been hypothesized that concentrations of exhaled nitric oxide (NO) may be related to the extent of cytokine-mediated airway inflammation. Recent findings indicate the nasal airways as an important site of NO production. Our objective was to evaluate whether children with allergic rhinitis show different nasal NO levels when compared with normal healthy subjects and the effect of topical steroids and anti-histamine therapy. We have measured the concentration of NO drawn from the nose of 21 children (5-17 years old) affected by perennial allergic rhinitis (house dust mite) out of therapy for at least 3 weeks. Thirteen children were then treated with nasal beclomethasone dipropionate (BDP) (400 micrograms daily) and eight subjects with nasal anti-histamine levocabastine (200 micrograms daily). Measurements were performed before and after 10 days of treatment. As a control group we evaluated 21 healthy children aged 5-15 years. To measure NO we used a chemiluminescence analyser. Before treatment the whole group of children with allergic rhinitis showed a mean (+/- SEM) nasal NO concentration of 267 +/- 18 ppb, significantly higher (P < 0.01) than the control group (186 +/- 15 ppb). The group of children treated with BDP showed, after 10 days of therapy, a significant (P < 0.05) decrease of nasal NO concentration (271 +/- 21 ppb vs. 212 +/- 20 ppb). Indeed, in the group treated with levocabastine, nasal NO concentrations did not present a significant difference (P not significant) compared with baseline (261 +/- 33 ppb and 252 +/- 31 ppb, respectively). These data suggest that (1) children with allergic rhinitis have higher levels of nasal NO than non-atopic controls and (2) intranasal steroid therapy significantly reduces nasal NO production in children with allergic rhinitis. We speculate that the allergic inflammatory response may influence the nasal NO levels and that NO measurements may be a useful marker of nasal inflammation.