[Corneal refractive surgery despite systemic diseases?] / Refraktive Hornhautchirurgie trotz systemischer Erkrankungen?

According to the literature there are a large number of potential systemic contraindications for corneal refractive surgery. In cases with relative contraindications, surgery should be performed only after weighing up the individual risks and under controlled disease conditions; however, the "evidence" for many of these contraindications is based only on case reports or series, expert opinions or known complications in non-laser-assisted eye surgery. Randomized clinical trials are therefore required.

Comparación de 5.468 retratamientos tras láser in situ queratomileusis levantando el lentículo o mediante queratectomía fotorrefractiva sobre el lentículo / Comparison of 5468 retreatments after laser in situ keratomileusis by lifting the flap or performing photorefractive keratectomy on the flap

Objetivo: Describir los resultados visuales del retratamiento tras láser in situ queratomileusis (LASIK) levantando el lentículo previamente o realizando queratectomía fotorrefractiva (PRK) sobre él, establecer si el riesgo de crecimiento epitelial de la interfase (CEI) es mayor cuanto más tiempo ha pasado entre el LASIK inicial y el retratamiento por levantamiento y determinar la incidencia de la opacidad corneal (haze) tras PRK. Métodos: Estudio retrospectivo de 4.077 pacientes (5.468 ojos) tratados mediante LASIK y retratamiento para estudiar los resultados visuales e identificar los casos de CEI y haze corneal. Resultados: Se estudiaron 5.196 ojos de 3.876 pacientes retratados de miopía levantando el lentículo y 272 ojos de 201 pacientes retratados mediante PRK en el lentículo. No se encontraron diferencias estadísticamente significativas entre los retratamientos en predictibilidad, eficacia y seguridad. Se encontró un total de 704 casos de CEI tras levantar el lentículo; se necesitó limpieza quirúrgica en 70. La limpieza quirúrgica disminuyó el índice de eficacia al compararlo con el de los pacientes con CEI que no precisaron limpieza (p = 0,01). Las diferencias en términos de seguridad y predictibilidad no fueron estadísticamente significativas. La incidencia de haze corneal tras la ablación de superficie sobre el lentículo previo fue del 14,34%, aunque ninguno de estos casos fue clínicamente relevante. Conclusiones: Los resultados visuales son similares entre los pacientes retratados mediante levantamiento del lentículo o mediante PRK. La incidencia de CEI levantando lentículo fue del 13,55%. La incidencia de CEI aumenta a medida que aumenta el tiempo entre el procedimiento primario y el retratamiento (AU)

Purpose: To assess visual outcomes of retreatment after laser in situ keratomileusis (LASIK) by lifting the flap or performing photorefractive keratectomy (PRK) on the flap, as well as to establish whether there was an increased risk of epithelial ingrowth (EIG) when LASIK and lifting of the flap are separated by a long time interval and to determine the incidence of corneal haze after PRK. Methods: Retrospective study of 4077 patients (5468 eyes) who underwent LASIK and subsequent retreatment were reviewed in order to study their visual results and identify cases of EIG and corneal haze. Results: Enhancements included 5196 eyes from 3876 patients that were retreated by lifting the flap, and 272 eyes from 201 patients that were retreated by PRK on the flap. No statistically significant differences were found between the retreatments in terms of predictability, efficacy, and safety. A total of 704 cases of EIG were found after lifting the flap, for which surgical cleansing was necessary in 70. Surgical cleansing decreased the efficacy index when compared with patients with EIG who did not need cleansing (P = .01). Differences in terms of safety and predictability were not statistically significant. The incidence of corneal haze after ablation of the surface of the previous flap was 14.34%, although none of these cases were clinically relevant. Conclusions: Visual outcomes were similar between patients who were retreated by lifting the flap and those who underwent PRK. The incidence of EIG when the flap was lifted was 13.55%. The incidence of EIG increases with the time elapsed between the primary procedure and retreatment (AU)

Comparison of 5468 retreatments after laser in situ keratomileusis by lifting the flap or performing photorefractive keratectomy on the flap. / Comparación de 5.468 retratamientos tras láser in situ queratomileusis levantando el lentículo o mediante queratectomía fotorrefractiva sobre el lentículo.

PURPOSE: To assess visual outcomes of retreatment after laser in situ keratomileusis (LASIK) by lifting the flap or performing photorefractive keratectomy (PRK) on the flap, as well as to establish whether there was an increased risk of epithelial ingrowth (EIG) when LASIK and lifting of the flap are separated by a long time interval and to determine the incidence of corneal haze after PRK. METHODS: Retrospective study of 4077 patients (5468 eyes) who underwent LASIK and subsequent retreatment were reviewed in order to study their visual results and identify cases of EIG and corneal haze. RESULTS: Enhancements included 5196 eyes from 3876 patients that were retreated by lifting the flap, and 272 eyes from 201 patients that were retreated by PRK on the flap. No statistically significant differences were found between the retreatments in terms of predictability, efficacy, and safety. A total of 704 cases of EIG were found after lifting the flap, for which surgical cleansing was necessary in 70. Surgical cleansing decreased the efficacy index when compared with patients with EIG who did not need cleansing (P=.01). Differences in terms of safety and predictability were not statistically significant. The incidence of corneal haze after ablation of the surface of the previous flap was 14.34%, although none of these cases were clinically relevant. CONCLUSIONS: Visual outcomes were similar between patients who were retreated by lifting the flap and those who underwent PRK. The incidence of EIG when the flap was lifted was 13.55%. The incidence of EIG increases with the time elapsed between the primary procedure and retreatment.

[Multifocal intraocular lens (MIOL) surgery in young non-presbyopic ametropes : Reasonable and safe?] / Multifokale Intraokularlinsen (MIOL) bei jungen, nicht-presbyopen Patienten : Sinnvoll und sicher?

BACKGROUND: Refractive lens exchange and implantation of a multifocal intraocular lens (MIOL) is mainly advised for ametropes with presbyopia. Non-presbyopic young ametropes who wish spectacle-independence are usually treated with corneal refractive surgery or phakic lenses. OBJECTIVES: This retrospective case series aimed to analyse the refractive and subjective satisfaction outcome after MIOL surgery in both eyes of non-presbyopic ametropes where other treatment options were not possible. MATERIALS AND METHODS: This retrospective case series comprised consecutively treated 32 eyes of 16 patients (5 myopic, 11 hyperopic patients; mean age 31 ± 6 years) who wished spectacle-independence and thus received an aspheric bifocal biconvex refractive-diffractive single-piece MIOL (Acri.Lisa 366/809, Carl Zeiss Meditec AG). Refractive data prior to and after surgery as well as subjective satisfaction at the 1­year follow-up examination were assessed. RESULTS: Related to distance corrected near visual acuity myopic eyes had a median efficacy index (EI) of 0.92 (±0.20) and hyperopes of 0.91 (±0.12) (P = 0.415). For intermediate vision, in both groups a lower EI (<0.5; P = 0.188) resulted in lower subjective satisfaction, which was higher for near and distance vision. Some of hyperopic patients reported limitations in near and distance vision, only one hyperopic patient would not have chosen this surgery again. None had a related complication during the follow-up. CONCLUSIONS: When neither laser refractive surgery nor implantation of a phakic lens is possible, young non-presbyopic ametropes do profit from MIOL surgery with an aspheric bifocal biconvex refractive-diffractive MIOL.

Recurrence rate and subjective symptoms after standardized (Hamburg protocol) phototherapeutic keratectomy on recurrent corneal erosions.

PURPOSE: To evaluate the objective and subjective outcome after phototherapeutic keratectomy (PTK) on recurrent corneal erosions (Hamburg protocol). METHODS: For the standardized PTK according to Hamburg protocol a manual abrasio corneae performed with 20 % alcohol is followed by an excimer ablation depth of ≥15 µm (group1 15 µm; group 2 > 15 µm ablation depth) and 7 mm optical zone. All patients (N = 48) were invited for follow-up examinations and the evaluation of changes concerning subjective symptoms. RESULTS: A significantly reduced subjective impairment of night vision, significantly less pain and less foreign body sensations (for all p < 0.05) were noted in 48 patients that met the inclusion criteria (26 women, 22 men). In the follow-up period an improvement of corrected distance visual acuities (cdva) from 0.80 to 1.08 (group 1) and from 0.58 to 0.99 (group 2) was demonstrated. CONCLUSION: PTK (Hamburg Schema) is a safe and effective procedure to reduce subjective symptoms and improve discomfort in recurrent corneal erosion.

PO-45 - The role of microvesicles in multiple myeloma progression.

INTRODUCTION: Multiple myeloma (MM) is an incurable, genetically heterogeneous malignancy of plasma cells that secrete non-functioning immunoglobulins and present high proteasome activity. MM is characterized by bone marrow infiltration leading to multiple lytic bone lesions, cytopenia and increased rate of thrombotic events. Microvesicles (MVs) include exosomes (30-100 nm) and microparticles (0.1-1 micron) shed from various cells and expressing antigens reflecting their cellular origin. MVs are involved in thrombosis, inflammation and cancer.However, the effect of MM-MVs on disease progression and their mechanism of action are unclear. We assume that MVs play a role in the interaction between malignant plasma cells and mesenchymal and endothelial cells (EC). AIM: To characterize MM-MVs and investigate their effects on microenvironment cells. MATERIALS AND METHODS: MVs were isolated from MM cell line RPMI 8226 untreated or treated with bortezomib and from peripheral blood (PB) and bone marrow (BM) of MM patients (n=13) and healthy controls (n=14). MM-MV size, concentration and cell origin were measured by Nanosite and FACS. Protein content was evaluated by protein arrays and ELISA. Coagulation and proteasome activity were assessed using chromogenic assays. Migratory capacity (migration assay), proliferative rate (XTT assay) and cell-signaling effects (Western blot analysis) of MVs on BM-mesenchymal and ECs were analyzed. RESULTS: MM cells exhibited high MV shedding rate, which further increased with the exposure to bortezomib. Significant elevation in MV production was found in MM patients compared to controls. MM-MVs expressed membrane MM markers (syndecan-1/ CD138, CD38), coagulation factor (TF, TFPI, EPCR, TM) and angiogenic factors (VEGFR1, VEGFR2, and CD31). MM-MVs contained high levels of growth factors (Angiogenin, PDGF-BB and VEGF) and displayed procoagulant and proteasome activity. MM-MVs penetrated cells and affected their function. MVs of untreated cells and patient MVs increased EC and mesenchymal cell migration and EC proliferation, while MVs obtained from bortezomib-treated cells decreased these effects. MVs of untreated cells increased ERK1/2 and c-Jun phosphorylation in ECs (by 6.15 and 1.84 fold) but did not affect MAPKAPK-2. MVs of bortezomib-treated cells reduced c-Jun phosphorylation in ECs. CONCLUSIONS: MM cells are characterized by high shedding rate of MVs. They are pro-coagulants and increase EC thrombogenicity, suggesting their involvement in MM-related thrombosis. MVs contain high levels of angiogenic factors that affect mesenchymal and EC, induce cell migration and proliferation via specific signal transductions. MVs exposed to bortezomib display lower levels of angiogenic factors, which limits proliferation and migration of MVs, reflecting the efficacy of therapy and MM dynamics.

[Corneal biomechanics: Corvis® ST parameters after LASIK]. / Korneale Biomechanik : Corvis® ST-Parameter nach Laser-in-situ-Keratomileusis.

BACKGROUND: Corneal refractive surgery alters the biomechanical properties of the cornea. OBJECTIVES: This study was initiated to evaluate corneal biomechanical parameters after LASIK using a Corvis® ST tonometer (CST). METHODS: This retrospective study included 51 eyes of 32 myopic patients. All CST measurements were performed 1 day before surgery and at the 1-month follow-up examination. The LASIK procedure included mechanical flap preparation using a Moria SBK microkeratome and an Allegretto excimer laser platform. RESULTS: Statistically significant differences were observed for mean second applanation length, mean first and second deflection lengths, mean first and second deflection amplitudes, peak distance and radius of curvature. Statistically significant positive correlations were found between the change (Δ) in radius of curvature and Δ in manifest refraction spherical equivalent (MRSE), between the ablation depth and the Δ in intraocular pressure. Applying multiple regression models also revealed statistically significant differences in parameters obtained by CST measurements. CONCLUSION: Several CST parameters were statistically significantly altered by LASIK thereby indicating that flap creation, ablation or both, significantly change the ability of the cornea to absorb or dissipate energy.

[Pachymetry and intraocular pressure measurement by corneal visualization Scheimpflug technology (Corvis ST): A clinical comparison to the gold standard]. / Pachymetrie und Augeninnendruckmessung mittels Corneal-Visualization-Scheimpflug-Technologie (Corvis ST) : Ein klinischer Vergleich zum Goldstandard.

BACKGROUND: Analyses regarding accuracy and reproducibility of intraocular pressure (IOP) measurements and pachymetry with corneal visualization Scheimpflug technology (Corvis ST®, CST). MATERIAL UND METHODS: Retrospective analysis of 72 eyes with primary open angle glaucoma (POAG) and ocular hypertension (OHT) with no prior surgery or other pathology. The results of Goldmann applanation tonometry (GAT), non-contact tonometry (NCT) and ultrasound pachymetry (USP) were compared with repeat measurements with CST. For statistical analyses the t-test and Bland-Altman plots were applied. RESULTS: The mean IOP was 15.5 ± 4.4 mmHg (CST), 14.8 ± 4.4 mmHg (GAT) and 15.6 ± 4.8 mmHg (NCT). The results of GAT and CST as well as GAT and NCT demonstrated statistically significant differences (p < 0.001) whereas NCT and CST displayed no significant differences in IOP (p = 0.72). The mean differences between the repeat measurements were 0.35 ± 1.7 mmHg (CST) and 0.04 ± 0.85 mmHg (GAT). The mean CST pachymetry results showed 551.3 ± 46.5 µm and the USP 526.5 ± 46.4 µm (p < 0.001). The mean difference between the repeated CST measurements was 24.8 ± 21 µm. No repeat measurement data were available for USP. CONCLUSION: The CST is a new device for simultaneously measuring the IOP, pachymetry and biomechanical properties of the cornea. Whether the deviations in the IOP measured by CST and CST pachymetry from the manually performed gold standard has to be evaluated as deficient, tolerable or maybe as an improvement, has to be evaluated in further studies. Because of the automated and contact-free measurement method as well as the potential for simultaneously analyzing biomechanical properties of the cornea, the CST is a device that might help the quest for measuring the 'true' IOP.

[Perspectives of laser-assisted keratoplasty: current overview and first preliminary results with the picosecond infrared laser (λ = 3 µm)]. / Perspektiven der laserassistierten Keratoplastik: Eine aktuelle Übersicht und erste experimentelle Erfahrungen mit dem Pikosekundeninfrarotlaser (λ = 3 µm).

BACKGROUND: This article provides a review of the current state of laser-assisted keratoplasty and describes a first proof of concept study to test the feasibility of a new mid-infrared (MIR) picosecond laser to perform applanation-free corneal trephination. METHODS: The procedure is based on a specially adapted laser system (PIRL-HP2-1064 OPA-3000, Attodyne, Canada) which works with a wavelength of 3,000 ± 90 nm, a pulse duration of 300 ps and a repetition rate of 1 kHz. The picosecond infrared laser (PIRL) beam is delivered to the sample by a custom-made optics system with an implemented scanning mechanism. Corneal specimens were mounted on an artificial anterior chamber and subsequent trephination was performed with the PIRL under stable intraocular pressure conditions. RESULTS: A defined corneal ablation pattern, e.g. circular, linear, rectangular or disc-shaped, can be selected and its specific dimensions are defined by the user. Circular and linear ablation patterns were employed for the incisions in this study. Linear and circular penetrating PIRL incisions were examined by macroscopic inspection, histology, confocal microscopy and environmental scanning electron microscopy (ESEM) for characterization of the incisional quality. Using PIRL reproducible and stable incisions could be made in human and porcine corneal samples with minimal damage to the surrounding tissue. CONCLUSION: The PIRL laser radiation in the mid-infrared spectrum with a wavelength of 3 µm is exactly tuned to one of the dominant vibrational excitation bands of the water molecule, serves as an effective tool for applanation-free corneal incision and might broaden the armamentarium of corneal transplant surgery.

[Cross-linking and neurodermitis: prolonged re-epithelisation with severe corneal vascularisation after cross-linking in a patient with neurodermitis and keratoconus]. / Crosslinking bei Neurodermitis: schwerwiegende Wundheilungsstörung nach kornealem Crosslinking bei einem Patienten mit Keratokonus und Neurodermitis.

This case report describes a patient with keratoconus and neurodermitis suffering from a significantly prolonged postoperative time interval to re-epithelisation after corneal cross-linking. The development of corneal calcifications and vascularisations additionally inhibited proper re-epithelisation. Therefore the patient received four subsequent subconjunctival injections of Bevacizumab and an additional keratectomy to remove the calcifications. This therapeutic scheme led to a significant reduction of corneal vascularisation and finally a full rehabilitation of the epithelium.

Incidence of non-candidal fungal infections in severe burn injury: an Australian perspective.

INTRODUCTION: Infection remains the primary cause of morbidity and mortality in the burns patient population. While candidal infection in burns patients is well described, there is dearth of information regarding non-candidal fungal infections in this setting. METHOD: All adult burns patients who developed non-candidal fungal infections over a period of 10 years (between January 2001 and June 2011) were included. Retrospective data analyzed included patient demographics, organisms cultured, antibiotic susceptibility patterns, treatment, length of stay and overall mortality. RESULTS: The incidence of non-candidal fungal infections at our centre over the time period studied was 0.04%. A total of 12 patients had a fungus other than Candida isolated. Of these 12 patients, seven were thought to have clinically significant fungal infections and were treated with targeted anti-fungal therapy. Between them, seven species of fungus were isolated: Aspergillus fumigatus (n=7), Scedosporium prolificans (n=2), Fusarium solani (n=2), Mucor spp. (n=2), Absydia corymbifera (n=1), Penicillium (n=1) and Alternaria spp. (n=1). Of those definitively treated, two died, although fungal infection was not believed to be a contributing factor to these deaths. CONCLUSION: We demonstrate a low incidence and attributable mortality of non-candidal fungal infections in the setting of early antifungal therapy and extensive surgical debridement at our state-wide Burns Service.

[Difference and distance between the central and thinnest points of the cornea: impact of refractive state, age and ocular side]. / Differenz und Entfernung zwischen zentraler und dünnster Stelle der Hornhaut: Einfluss von Refraktion, Alter und Augenseite.

BACKGROUND: The aim of the study was to quantify the difference in corneal thickness between the central and thinnest points (∆PachyZ-PachyD), the distance between the center of the cornea and its thinnest point (vector length PachyD) and to explore the impact of refractive state, age and ocular side. PATIENTS AND METHODS: This was a multicenter, retrospective, cross-sectional study and medical records of 16,872 eyes were reviewed. The Orbscan® (Bausch and Lomb) procedure was used for pachymetry and keratometry. RESULTS: The results showed that ∆PachyZ-PachyD and vector length PachyD were higher in hyperopic eyes (∆PachyZ-PachyD: 11.99 ± 12.08 µm, vector length PachyD: 0.85 ± 0.44 mm) compared to myopic eyes (∆PachyZ-PachyD: 9.2 ± 7.86 µm, vector length PachyD: 0.7 ± 0.37 mm; p < 0.001). Refractive state, age and ocular side demonstrated an independent, statistically significant impact on ∆PachyZ-PachyD and vector length PachyD. CONCLUSIONS: As a result of the significant impact of refractive state, age and ocular side on ∆PachyZ-PachyD and vector length PachyD, these variables should be considered in a normative data collection.

[Therapeutic excimer laser treatment of the cornea]. / Therapeutische Excimerlaserchirurgie der Hornhaut.

Concomitant with new innovations in the field of refractive surgery, therapeutic excimer laser applications like phototherapeutic keratectomy (PTK) and topography-guided customised ablation treatment are gaining high importance and undergoing rapid evolution. Nowadays, PTK is an effective treatment modality for superficial corneal pathologies. Primary indications are decreased epithelial adherence, superficial opacifications and an irregular corneal surface. For the right indication and successful treatment of corneal pathologies with PTK, a knowledge of the size, depth and nature of the pathology, as well as the refractive status of both eyes is important. Next to slit-lamp examination, objective measuring systems like the topography, confocal microscopy and the anterior segment OCT facilitate presurgical planning. Regarding the treatment procedure the surgeon can choose between a variety of methods. PTK can be combined with manual epithelial debridement or done by only using the excimer laser. In the case of an irregular corneal surface, depending on the pathology, masking fluids or topography-guided custom ablation protocols can increase the visual outcome. To avoid recurrence of the underlying pathology (e.g., corneal dystrophy, haze), the topical application of 0.02% mitomycin C for 20-60 seconds has proved to be a safe and effective procedure. If the surgeon considers all the patient-related factors carefully and manages to combine the available treatment options correctly, PTK embodies an effective and minimally invasive alternative to lamellar or penetrating keratoplasty.

[Infectious keratitis after LASIK--update and survey of the literature]. / Infektiöse Keratitis nach LASIK--aktueller Stand und Literaturübersicht.

LASIK has become the preferred surgical procedure for the correction of refractive errors. Microbial keratitis is a rare but severe complication. The incidence of post-LASIK keratitis, (uni- and bilateral) is difficult to estimate. The risk of bilateral infection could until now only be approximated by calculating it from the risk of unilateral infection. Due to the fortunately low incidence of post-LASIK keratitis, large-scale studies are necessary to obtain valid statistical data. The American Society of Cataract and Refractive surgery (ASCRS) developed a post-LASIK infectious keratitis survey in 2001. 116 post-LASIK infections were reported by the members of the society. The calculated incidence was 0.035 % or 1 infection in every 2919 procedures. Llovet et al. found 9 patients (18 eyes) with bilateral post-LASIK keratitis out of 204 586 procedures (incidence 0.0084 %). Gram-positive bacteria and atypical mycobacteria are the most common causes for microbial post-LASIK keratitis. There is an increasing literature of post-LASIK case reports caused by rare or atypical species. Severe cases of keratitis are more often correlated with a prolonged onset of infection and caused by atypical species. An overview of the current literature and our own data regarding post-LASIK keratitis (uni-, and bilateral) are presented.

[Postkeratoplasty astigmatism: comparison of three suturing techniques]. / Astigmatismus nach perforierender Keratoplastik: Vergleich verschiedener Nahttechniken.

PURPOSE: The aim of this study was a retrospective analysis of postkeratoplasty astigmatism and best corrected visual acuity (BCVA) in patients following penetrating keratoplasty (PK) and a comparison of three suturing techniques. PATIENTS AND METHODS: In this retrospective analysis penetrating keratoplasty (PK) was carried out on 150 eyes with 3 suturing techniques: single running (SR), double running (DR counterclockwise) and interrupted (IR) sutures. Of the eyes 37 (24.7%) underwent PK with SR sutures, 81 eyes (54%) with DR sutures and 32 eyes (21.3%) had IR. PK for Fuchs' dystrophy was used on 46 eyes (30.7%), on 33 eyes (22%) for keratoconus, on 12 eyes (8%) for herpetic keratitis and on 7 eyes (4.6%) for pseudophakic bullous keratopathy. For trephination a guided trephine system (GTS) was used in 44%, rotortrepan in 46.6% and best trepan in 5.3%. Postkeratoplasty astigmatism and best corrected visual acuity (BCVA) were evaluated 1, 4, 12 and 24 months after surgery (all sutures removed). Subjective and objective refractions and corneal topography were performed to assess astigmatism. The Kolmogorov-Smirnov test (95% significance) was used to evaluate statistical significance. RESULTS: Mean topographic astigmatism 4 months (12 months/2 years) after keratoplasty was 4.9 dpt (5.3/4.1, n=4) for SR, 4.2 dpt (4.0/5.3) for DR and 9.7 dpt (n=7) (4.9, n=8/6.8, n=2) for IR suturing techniques. Mean objective astigmatism 4 months (12 months/2 years) after PK was 5.9 dpt (4.1, n=7/5.0, n=3) for SR, 3.4 dpt (4.5/4.98) for DR and 8.0 dpt (n=3) (6.9, n=4/7.4, n=2) for IR sutures. Mean refractive cylinder 4 months (12 months/2 years) after keratoplasty was 4.5 dpt (3.9/4.9) for SR, 3.2 dpt (3.3/3.6) for DR and 6.2 dpt (3.7/4.7) for IR suturing. Mean BCVA 4 months (12 months/2 years) was 0.3 (0.3/0.4) for SR, 0.3 (0.4/0.5) for DR and 0.3 (0.4/0.4) for IR sutures. BCVA 4 months (12 months/2 years) after PK (GTS only) reached 0.3 (0.3/0.5) for SR and 0.3 (0.4/0.6) for DR suturing. DISCUSSION: Topographic and objective astigmatisms were highest for the IR suturing technique. Topographic astigmatism and refractive cylinder were less in the DR (compared to SR) group 4 and 12 months after surgery (statistically significant). After suture removal (2 years after PK) refractive cylinder was still lower for DR compared to SR but there was no statistical difference between DR and SR regarding topographic and objective cylinders. For the interpretation of these data it should be emphasized that due to the retrospective character of this analysis the number of patients in the subgroups is decreasing with time and as a consequence single (strongly deviating) measurements can have a more powerful impact on the outcome in the individual subgroups.

The feasibility of a randomised, placebo-controlled clinical trial of homeopathic treatment of depression in general practice.

UNLABELLED: Depression is common in general practice and lack of concordance is an important problem in its treatment. Homeopathy has few side effects and is generally associated with good compliance. We report a study investigating the feasibility of a trial to compare the effectiveness of homeopathy with a conventional antidepressant and placebo. OBJECTIVES: To assess the feasibility of a general practice-based clinical trial comparing the effectiveness of individualised homeopathic treatment vs Fluoxetine (Prozac) vs placebo in the treatment of major depressive episodes of moderate severity. DESIGN: Randomised, double-dummy, double-blind parallel group clinical trial. SETTING: Lower Clapton Group Practice, East London. METHOD: Patients were recruited through their general practitioners as they presented during a 9 month period. Recruitment target was 30 patients. Eligibility was confirmed by a consultant psychiatrist using standard criteria (DSM-IV) and instruments Hamilton Depression Scale (HAMD). Suicidal and psychotic patients were excluded, additional precautions against suicide were incorporated. There was a 1 week run-in period and patients showing spontaneous improvement were excluded. Homeopathic treatment was prescribed by a GP qualified in homeopathy, from a 'limited list' of 30 homeopathic medicines, with the help of decision support software. Patients were randomised to receive verum Fluoxetine and placebo homeopathy, or verum homeopathy and placebo Fluoxetine, or placebo homeopathy and placebo Fluoxetine. Treatment duration was 12 weeks. The outcomes were: adverse drug reactions, clinical global impression (CGI); HAMD; mini international psychiatric Interview; Pittsburgh sleep quality index; Side-effects checklist; Short Form 12; treatment credibility questionnaire; work and social disability scale. The primary outcome measures were HAMD and CGI. RESULTS: A recruitment calculation indicated that over 230 suitable patients would be expected to attend the practice during the recruitment phase. Thirty one patients were referred for possible inclusion in the trial by their GPs. Twenty three met the entry criteria, 11 were randomised and 6 completed the study. Of the completers, one received homeopathy, 2 placebo and 3 Fluoxetine. CONCLUSIONS: A trial of this design in general practice is not feasible, because of recruitment difficulties, many of them linked to patient preference. Different approaches are required to recruit adequate patient numbers to trials of this sort.

Clinical efficacy of flunixin, carprofen and ketoprofen as adjuncts to the antibacterial treatment of bovine respiratory disease.

Three non-steroidal anti-inflammatory drugs (NSAIDs), flunixin, ketoprofen and carprofen, were used in conjunction with ceftiofur, in the treatment of naturally occurring bovine respiratory disease. Sixty-six mixed-breed beef cattle weighing on average 197 kg met the inclusion criteria of pyrexia of at least 40 degrees C, an illness score indicating at least moderate illness and at least moderate dyspnoea. They were allocated randomly to four treatment groups. All the groups received ceftiofur for three days at a dose rate of 1.1 mg/kg by intramuscular injection, and three groups received, in addition, a single dose of either flunixin (2.2 mg/kg by intravenous injection) or ketoprofen (3 mg/kg by intravenous injection) or carprofen (1.4 mg/kg by subcutaneous injection). During the first 24 hours of the study, the pyrexia of the three groups treated with a NSAID was reduced significantly more than the pyrexia of the group treated with ceftiofur alone, and two and four hours after treatment the reduction in pyrexia was significantly greater in the groups treated with flunixin and ketoprofen than in the group treated with carprofen. There were no statistically significant differences between the four groups with respect to depression, illness scores, dyspnoea or coughing. There was less lung consolidation in the three groups treated with a NSAID than in the animals treated with ceftiofur alone, but the difference was significant only in the group treated with flunixin.

A 12-month, multicenter, prospective, open-label trial of radiographic analysis of disease progression in osteoarthritis of the knee or hip in patients receiving celecoxib.

BACKGROUND: Studies have suggested that nonspecific nonsteroidal anti-inflammatory drugs may inhibit matrix biosynthesis by articular cartilage, thereby accelerating the progression of osteoarthritis (OA). OBJECTIVE: The objective of this analysis was to determine whether 1-year treatment with the cyclooxygenase-2-specific inhibitor celecoxib at up to twice the recommended and maximally effective dose for OA had any deleterious effects on OA progression by assessing radiographic changes in knee or hip joint morphology in patients with OA. METHODS: In a 12-month, multicenter, prospective, open-label trial, patients with OA of the knee or hip or rheumatoid arthritis received celecoxib at doses ranging from that recommended for the treatment of OA (200 mg/d) to twice the recommended daily dosage (400 mg/d). Available radiographs showing baseline and end-of-treatment status were analyzed using semiquantitative measures of index joint morphology in patients with mild to moderate OA. The morphologic scores were then subjected to mean change and shift-table analysis to determine the extent and rate of disease progression. RESULTS: A total of 2,327 patients (796 with OA of the knee, 1,531 with OA of the hip) were included. A subset of 344 patients (160 with OA of the knee, 184 with OA of the hip) had radiographs from both before and after 12 months' celecoxib treatment. One hundred forty-seven and 158 pairs of knee and hip radiographs, respectively, were available for analysis. These revealed that, with the exception of significant hip joint-space narrowing (P = 0.029), no evidence of disease progression with long-term celecoxib treatment could be detected. The observed increase in hip joint-space narrowing was small (0.14 units/y) (95% CI, 0.08-0.20), was observed prior to celecoxib exposure (by mean change or shift-table analysis), and was not dose related. CONCLUSION: These results are consistent with the hypothesis that long-term therapy with celecoxib does not accelerate progression of OA of the knee or hip.

Synthesis and properties of an aggregating heterocyclic helicene.

Heterohelicene 10 is synthesized in six steps from 3,3'-bithienyl. Because the number of steps is small, because the yield is 95% in the last (the reaction of a bis-enol ether with 1,4-benzoquinone-a six-step one pot procedure that constructs the helicene skeleton), and because chromatography is not required to purify any of the products in the synthesis, significant amounts are easily prepared. To convert 10 into enantiopure 3, a helicenebisquinone surrounded by four dodecyloxy groups, requires only a precedented three-step sequence. Enantiopure helicene 3, either without solvent or in dodecane (but not in chloroform) aggregates into columnar structures whose optical properties differ markedly from those of the monomer but resemble those shown previously only by aggregates of 1. Evidence of aggregation in the pure material includes optical microscopic observation of long fibrous structures and X-ray diffraction and combined transmission electron microscopic and electron diffraction analyses showing the molecules within the fibers to be organized in columnar arrays. The circular dichroism spectra, specific rotations, and fluorescent emission spectra of the aggregated structures are all distinctive, and, as reported elsewhere, the second harmonic response is very large. The linear polarizations of the monomers' and aggregates' fluorescent emissions differ greatly. The circular polarization of the aggregates' fluorescent emission, after excitation by unpolarized light, is large.

Cells from chronic myelogenous leukaemia patients at presentation exhibit multidrug resistance not mediated by either MDR1 or MRP1.

Tetramethylrosamine (TMR) is excluded from P-glycoprotein (MDR1)-enriched cell lines, but it stains efficiently MDR1-poor parent lines. Application of the TMR resistance assay to cells obtained from chronic myelogenous leukaemia (CML) patients revealed, in all individuals, a significant resistance compared with healthy donors (P < 0.001). Cells from the same patients at later phases exhibited a further increase in TMR resistance. Doxorubicin was excluded from all cell samples obtained from CML patients at presentation. The resistance to TMR and doxorubicin was energy-dependent, and was not modulated by inhibitors of MDR1 and multidrug-resistance protein-1 (MRP1). Transcription of mRNAs suspected as relevant to multidrug resistance was assessed using comparative reverse transcription polymerase chain reaction. All cells from the CML patients transcribed high levels of MRP3, MRP4 and MRP5 compared with healthy donors. Low levels of MDR1, MRP1, MRP2, MRP6, lung resistance-related protein and anthracycline resistance-associated protein were equally transcribed in cells from healthy donors and CML patients. These results indicated that neither MDR1 nor MRP1 mediate the resistance in these cells. Our results shed light on a resistance mechanism operative in CML patients, which, together with the resistance to apoptosis, is responsible for the lack of response of CML patients to induction-type protocols used to treat acute myeloid leukaemia patients.