Evaluation of the efficiency of an ultrasound-supported infiltration technique in patients with tennis elbow applying the ITEC medical device: a multicenter study.

Background: The treatment of lateral epicondylitis remains unsatisfactory in certain cases. The aim of this study is to investigate the efficiency of an ultrasound-guided infiltration combined with fenestration of the extensor tendon postulating a 50% reduction in pain on exertion within 6 months. Methods: In a prospective, nonrandomized, multicenter study design, 68 patients with chronic lateral epicondylitis and symptoms lasted for at least 6 weeks were included. Each hospital has been assigned for Traumeel (A), autologous whole blood (B), or dextrose (C) in advance. Preinterventional, 6 weeks, 12 weeks, 6 and 12 months after infiltration, patient-related outcome parameter, and dorsal wrist extension strength were documented. Preinterventional (obligate) and after 6 months (optional) radiological evaluation (magnetic resonance imaging) was performed. Results: The Visual Analog Scale showed a significant reduction after 6 months in all groups (A. 4.8-2.5, B. 6.2-2.3, C. 5.8-2.4). Similar results could be observed with Subjective elbow value, Disabilities of Arm, Shoulder, and Hand Score, Mayo Elbow Performance Score, and Patient Rated Tennis Elbow Evaluation. The loss of strength could be completely compensated after about 6 months. Magnetic resonance imaging did not fully reflect clinical convalescence. Re-infiltrations were sometimes necessary for final reduction of symptoms (A = 11, B = 8, C = 4). Switching to surgical intervention was most frequently observed in group C (A = 2, B = 1, C = 5). In 14.5% of the cases, no improvement of the symptoms could be achieved with this method. Conclusion: The primary hypothesis of a significant long-term pain reduction of at least 50% could be achieved regardless of the medication chosen.

[Infiltration therapies for lateral epicondylopathy]. / Infiltrationstherapien am Ellenbogengelenk bei Epicondylopathia humeri radialis.

The therapy of the lateral epicondylopathy (tennis elbow) includes drug injection into the extensor tendon insertion in chronic cases. The choice of medication and the type of injection is decisive for the success of therapy. Furthermore, accurate application is indispensable for therapy success (e.g. peppering injection technique, ultrasound-supported injection technique). Corticosteroid injection is often associated with short-term success, so that other options have found their way into everyday practice. Objectification of treatment success is usually defined by Patient-Reported Outcome Measurements (PROM). With the introduction of Minimal Clinically Important Differences (MCID), statistically significant results are put into perspective in terms of clinical significance. Therapy for lateral epicondylopathy was considered effective if the mean difference in score results between baseline and follow-up exceeded 1.5 points for the Visual Analogue Scale (VAS), 16 points for Disabilities of Arm, Shoulder and Hand Score (DASH), 11 points for Patient-Rated Tennis Elbow Evaluation (PRTEE), and 15 points for Mayo Elbow Performance Score (MEPS). However, the effectiveness must still be critically questioned according to meta-analytical evaluations, in which healing within 12 months was found in 90% of the cases of untreated chronic tennis elbow in the placebo groups. The use of substances, such as Traumeel (Biologische Heilmittel Heel GmbH, Baden-Baden, Germany), hyaluronic acid, botulinum toxin, platelet rich plasma (PRP), autologous blood or polidocanol, are based on various mechanisms. In particular, the use of PRP or autologous blood for the treatment of musculotendinous and degenerative articular pathologies has become popular, although the studies regarding effectiveness are inconsistent. PRP can be divided into leukocyte-rich (LR-PRP) and leukocyte-poor plasma (LP-PRP) according to its preparation. In contrast to LP-PRP, LR-PRP incorporates the middle and intermediate layers, but there is no standardized preparation described in the literature. Conclusive data regarding effective efficacy are still pending.

[Surgical treatment of distal triceps tendon ruptures]. / Operative Therapie der distalen Trizepssehnenruptur.

OBJECTIVE: Restoration of the anatomy and the original length of the muscle-tendon unit in triceps tendon ruptures. INDICATIONS: Acute and chronic triceps tendon ruptures with persisting symptoms and significant strength deficits. CONTRAINDICATIONS: Infections and tumors in the surgical area. SURGICAL TECHNIQUE: Prone position. Skin incision over the distal triceps in a lateral direction around the olecranon. Mobilization of the tendon and débridement of the olecranon. Drilling of 2â€¯× 2.9 mm suture anchor holes medial and lateral into the footprint of the olecranon. In addition, drilling through the olecranon 12 mm distal to the tip of the olecranon and transosseous introduction of 4 sutures. Then the suture anchors (all-suture or titanium anchors) are inserted into the drill holes. Refix the deep and superficial tendons with the anchor threads. Refix the upper tendon portions with the transosseous sutures. In the case of chronic lesions, a graft interposition is necessary. POSTOPERATIVE MANAGEMENT: Dorsal 10 ° splint, then change to an orthosis fixed in 20 ° extension and passive mobility 0-30 ° flexion for 6 weeks. From the 7th week onwards, load-free, physiotherapeutically controlled increasing mobilization. Starting weight-loading from the 13th week on. Full load after 6 months. RESULTS: In all, 34 male strength athletes with acute triceps tendon rupture underwent surgery using the hybrid technique described and were prospectively recorded. The MEPS­G score averaged 94.7 points, there were no permanent limitations in mobility, and the postoperative strength ability averaged 94% of the original strength performance ability. The return to sport achieved 100%. The complication rate was 20.6%. Reconstruction of the distal triceps tendon using hybrid technology leads to very good functional results. Half of all patients complained of symptoms even before the rupture, which suggests previous damage to the distal triceps tendon caused by degeneration.

Autologous triceps tendon graft for LUCL reconstruction of the elbow: clinical outcome after 7.5 years.

PURPOSE: The objective of this study was to assess mid- to long-term functional outcomes in patients treated for symptomatic posterolateral instability of the elbow (PLRI) using an autologous ipsilateral triceps tendon as graft. METHODS: A total of 196 patients were treated with autologous triceps tendon graft for symptomatic PLRI at single orthopedic institution from 2006 to 2013. The surgical treatment contained arthroscopic instability testing, reconstruction of the lateral ulnar collateral ligament (LUCL) and harvesting autologous ipsilateral triceps tendon as graft. The follow-up outcomes included range of motion (ROM), pain measured on a visual analogue scale (VAS), Mayo Elbow Performance Score (MEPS), Oxford Elbow Score (OES) and ultrasound to evaluate the integrity of the refixation of the common extensor. RESULTS: A total of 178 patients (female: 73; male: 105) were available for follow-up at a mean of 91 months (range 48-144). No patient reported pain at rest; VAS during activity was 1.8 (range 0-5). The ROM decreased slightly compared to preoperative measurements. Flexion decreased significantly from 135.4 to 131.1, though still within the functional arc of motion. All but 13 patients (8.5%) were clinically stable. However, only two patients received a revision of the LUCL reconstruction due to subjective instability. The mean MEPS in the final follow-up was 91.3 (range 73-100). The mean OES was 46.5 (range 39-48). Three patients reported a pain-free clicking of the elbow. No patient complained about donor site morbidity of the ipsilateral triceps tendon. Ultrasound evaluation showed integrity of the common extensors in all patients. CONCLUSIONS: LUCL reconstruction using the ipsilateral triceps tendon as graft shows good to excellent mid- to long-term results in the treatment of symptomatic posterolateral elbow joint instability with a low re-instability and complication rate.

Clinical and radiological outcomes of a stemless reverse shoulder implant: a two-year follow-up in 56 patients.

BACKGROUND: Since the introduction of stemless anatomic shoulder arthroplasty, many studies have been published on anatomic implants. For reverse stemless implants, however, there are only a few clinical follow-up studies available. The current clinical case series aims to present clinical and radiological outcomes of a new stemless reverse prosthesis system (Lima Shoulder Modular Replacement stemless). METHODS: We prospectively evaluated the outcome of 56 stemless total shoulder arthroplasties in 56 patients with a mean age of 61.2 years (46-76 years) at the time of implantation at a minimum follow-up of 24 months (range 24-41 months). All patients were physically and radiologically examined. Clinical outcomes were evaluated by using the Constant-Murley Score and the Subjective Shoulder Value. RESULTS: The mean Subjective Shoulder Value was 84.27% at the latest follow-up. Significant improvements from preoperative to latest follow-up were documented for Constant-Murley Score (34.9 pts to 74.43 pts, P < .001) and active range of motion (abduction 72° to 130°, flexion 36° to 138°, and external rotation 16°to 28°). There was one complete loosening of the humeral component without reoperation. Radiolucency lines were observed in anteroposterior or axial radiographs at the humeral component in 23% of the cases, most of them in anteroposterior view at the calcar region. Radiolucency line findings did not affect clinical outcomes. Major complications or revisions did not occur so far. CONCLUSION: At short-term follow-up, stemless reverse shoulder systems show comparable clinical and radiological outcomes compared to stemmed reverse implants in the literature.

Clinical and radiologic results after anatomic stemless shoulder prosthesis: a minimum 4-year follow-up.

BACKGROUND: Since the introduction of stemless anatomic shoulder arthroplasty, few midterm functional and radiographic results have been published. This article presents results of the Arthrex Eclipse prosthesis with a mean follow-up of 70 months. METHODS: We prospectively evaluated the outcome of 53 arthroplasties in 51 patients with a mean age of 65 years at the time of implantation with a minimum follow-up of 48 months. All patients were physically and radiologically examined, and the results documented by Constant-Murley and Disabilities of the Arm, Shoulder, and Hand (DASH) scores. RESULTS: Significant improvements from preoperative to last follow-up were documented in the Constant-Murley score (53.8%-83.5%, P < .001) and active range of motion (abduction 84°-108°, flexion 98°-125°, and external rotation 19°-41°). There was no significant difference between total and hemiarthroplasty. The mean DASH score was 28.3 points (95% confidence interval 20.1-35.2). Lowering of bone mineral density was observed in anteroposterior radiographs at the humeral component in 24.5% and at the glenoid component in 33.3%. The rate of complications was 15.7%. CONCLUSION: This study finds improvements in functional, radiographic, and subjective midterm results comparable to other accessible data for stemless and stemmed arthroplasty.

Revision of a Stemless Anatomic Implant into a Stemless Reverse Implant.

INTRODUCTION: Stemless anatomic implants are the growing standard for solving osteoarthritis of the shoulder. If there are secondary rotator cuff insufficiency and the need to revise the implant into a reverse total shoulder, there is usually the option to revise it into a stemmed implant with losing the benefits of stemless implants. There are only a few stemless reverse implants available on the market. Usually, they are recommended as primary implants, but not for revision surgery. Case Report. A 61-year-old male with an indwelling anatomic stemless TESS (Total Evolutive Shoulder System, Zimmer Biomet, Warsaw, USA) implant presented in our clinic with growing pain and loss of range of motion. The TESS was implanted in 2007 as a hemishoulder arthroplasty. The X-ray was showing a stable implanted corolla with clearly growing protrusion of the glenoid. Because of the clinical presentation and the ultrasound investigation that showed only remnants of the supraspinatus and infraspinatus left, we decided that it is necessary to revise the stable implant in a reverse total shoulder arthroplasty. As the TESS was not designed to be convertible, it was clear that it has to be explanted. Due to the young age of the patient, we proposed an "off-label" change to a stemless reverse implant, e.g., the LIMA SMR stemless reverse prosthesis. A revision was possible without much bone loss, so the stemless reverse implant could be used. The clinical and radiological 2-year follow-up showed a good result. CONCLUSION: Stemless implants are well known for anatomic implants, rarely for reverse implants, and seldom used for revision into reverse stemless. This case report shows that it is possible to revise a stemless anatomic implant with a stemless reverse, as long as the rules for implantation are applicable.

Hidden instability in posttraumatic stiff elbows.

BACKGROUND: Hidden instability could be one of the reasons for reoccurring stiffness after arthrolysis in posttraumatic elbows. Associated instability in stiff posttraumatic elbows is clinically hard to detect. Surgical treatment for instability and stiffness in the same surgical setting is challenging and has not been evaluated as of yet. HYPOTHESIS: The primary hypothesis assumes (1) the existence of a posttraumatic "stiff and unstable elbow" and (2) that coexisting instability can be detected by arthroscopic instability testing. The secondary objective was to report the midterm results after arthrolysis and ligament stabilization in the stiff and unstable elbow. METHODS: From 2005 to 2015, 55 patients received arthroscopic arthrolysis of the elbow due to posttraumatic elbow stiffness at our institution. The arthroscopic instability was categorized into three grades with a switching stick: grade I (= stable), grade II (mild instability) and grade III (grossly instable). In cases of persisting instability (grade II-III), a ligament stabilization procedure was performed and all patients were followed up clinically at a minimum of 12 months. Besides ROM and clinical joint stability, PROs (patient reported outcomes) were assessed with the PREE-score (patient-rated elbow evaluation) and the Oxford-Elbow-score (OES). Furthermore, the MEPS (Mayo-elbow-performance-score) was assessed. RESULTS: Out of 55 cases presenting for arthrolysis, coexisting elbow instability was detected during arthroscopic instability testing in 22 cases (40%). All 22 patients received additional ligament stabilization. At final follow-up 62.7 ± 35.7 months postoperatively, 20 patients (12 men; 8 women) with a mean age of 42 ± 16.8 were available. PREE, OES and MEPS were 19.8 ± 25.3, 37.5 ± 9.8 and 80 ± 14.5, respectively. ROM improved significantly from 95° ± 29° to 110° ± 24° postoperatively (p = 0.045). Five patients required revision arthrolysis within the follow-up period (20%). One patient demonstrated persisting instability (5%). CONCLUSION: Intraoperative instability diagnostics during arthroscopic arthrolysis helps detect persisting posttraumatic instability and may provide a solid indication for a concurrent ligament stabilization procedure. This study is the first to present the postoperative results after arthrolysis with stabilization of the posttraumatic, stiff and unstable elbow. However, the results are heterogenic with 25% requiring revision arthrolysis. Therefore, the stiff but unstable elbow remains a complex clinical presentation in need of further investigations. LEVEL OF EVIDENCE: IV.

Short-term safety, function, and quality of life in patients treated with Univers Revers prosthesis: a multicenter 2-year follow-up case series.

BACKGROUND: The use of reverse total shoulder arthroplasty (RTSA) has dramatically increased in recent years with the advent of new prosthesis designs regularly entering the market. We define the rate of local complications during the first 2 years after RTSA with the Univers Revers prosthesis and describe the changes in radiologic outcomes, as well as function, pain, satisfaction, and quality of life. METHODS: This multicenter, prospective case series included rotator cuff tear arthropathy patients who underwent RTSA with the Univers Revers. Incidence percentages of complications and pathologic radiographic changes were documented. Mixed-model linear regression was used to examine changes in range of motion, shoulder function (Constant score, Shoulder Pain and Disability Index, Subjective Shoulder Value), and quality of life (EQ-5D-5L [European Quality of Life 5 Dimensions 5 Level] and EQ-VAS [EuroQol Visual Analog Scale]). RESULTS: Of 187 patients, 59.4% were women, and the mean age was 75.3 years (range, 56-91 years). Twenty-five percent of patients had a postoperative complication; 5 complications were severe (2.7%, 5 of 187), whereby 2 were implant related (1.1%; 95% confidence interval [CI], 0.1%-3.8%). The incidence of scapular notching was 10.6% (95% CI, 6.5%-16%). After 2 years, abduction, flexion, and abduction strength improved by 54° (95% CI, 50°-58°), 57° (95% CI, 53°-60°), and 5 kg (95% CI, 4-5 kg), respectively (P < .001), whereas external rotation at 0° (1°; 95% CI, -1° to 3°) did not improve (P = .4). The Constant score improved by 39 (95% CI, 38-41); Shoulder Pain and Disability Index, by 50 (95% CI, 47-52); and Subjective Shoulder Value, by 43 (95% CI, 41-45) (P < .001). Furthermore, the EQ-5D-5L index value improved by 0.31 (95% CI, 0.30-0.33), and the EQ-VAS score improved by 16 (95% CI, 14-18) (P < .001). CONCLUSION: Our case series showed a low complication rate with a consistent clinically relevant and statistically significant improvement across most clinical and patient-reported outcomes for the Univers Revers. Long-term safety requires further investigation.

Rehabilitation following rotator cuff repair: A work of the Commission Rehabilitation of the German Society of Shoulder and Elbow Surgery e. V. (DVSE) in collaboration with the German Association for Physiotherapy (ZVK) e. V., the Association Physical Therapy, Association for Physical Professions (VPT) e. V. and the Section Rehabilitation-Physical Therapy of the German Society for Orthopaedics and Trauma e. V. (DGOU).

BACKGROUND: Tears and lesions of the rotator cuff are a frequent cause of shoulder pain and disability. Surgical repair of the rotator cuff is a valuable procedure to improve shoulder function and decrease pain. However, there is no consensus concerning the rehabilitation protocol following surgery. OBJECTIVES: To review and evaluate current rehabilitation contents and protocols after rotator cuff repair by reviewing the existing scientific literature and providing an overview of the clinical practice of selected German Society of Shoulder and Elbow Surgery e. V. (DVSE) shoulder experts. MATERIALS AND METHODS: A literature search for the years 2004-2014 was conducted in relevant databases and bibliographies including the Guidelines International Network, National Guidelines, PubMed, Cochrane CentralRegister of Controlled Trials, Cochrane Database of Systematic Reviews, and the Physiotherapy Evidence Database. In addition, 63 DVSE experts were contacted via online questionnaire. RESULTS: A total of 17 studies, four reviews and one guideline fulfilled the inclusion criteria. Based on these results and the obtained expert opinions, a four-phase rehabilitation protocol could be developed.

Suprapectoral biceps tenodesis using a suture plate: clinical results after 2 years.

PURPOSE: Several techniques for performing a tenodesis of the long head of biceps (LHB) are described. Only few outcome studies are published. This note describes a unicortical fixation via a suture plate-comparable to a distal biceps refixation-performed arthroscopically or mini-open via standard suprapectoral approach. The aim of this study is to show the clinical outcome after 6, 12, and 24 months. MATERIALS AND METHODS: A consecutive series of 50 (35 male, 15 female) patients at the mean age of 49 years (range 23-75) who underwent tenodesis of the LHB were followed for 2 years. All patients were operated by a single surgeon (CS). The clinical evaluation included Constant score, Scheibel LHB score and VAS. Structural integrity of the tenodesis was checked by ultrasound control. Integrity of the tenodesis was evaluated indirectly by detecting the LHB-tendon up to the ultrasound-reflex of the button. No tendon at the button-reflex was considered as failure of the tenodesis. An independent examiner who was not the operating surgeon performed all evaluations. (MG evaluated the patients operated by CS). RESULTS: Mean follow-up was 29.5 (range 22-32) months. The mean pre-operative Constant Murley score (CMS) was 67.4 points (range 45-78) and increased to 84.7 points (range 51-99) after 2 years. LHB Score was 90.8 after 24 months. We identified 2 failed biceps fixations (4%). Pain relief was achieved in most patients within the first 12 weeks. After 2 years, the mean biceps flexion strength averaged 84% of the healthy arm. CONCLUSIONS: Tenodesis of the LHB with a unicortical suture plate is a safe fixation technique with good-to-excellent clinical results after a minimum follow-up of 2 years. Long-term follow-up is needed.

Rheological study of chitosan/polyol-phosphate systems: influence of the polyol part on the thermo-induced gelation mechanism.

Thermo-sensitive gelling systems, like chitosan/polyol-phosphate, are candidates with a high potential for the design of biodegradable drug delivery systems, notably for in situ forming depots. They consist of stable and low viscosity aqueous solutions, liquid at room temperature, which turn into a gel state upon an increase of temperature (e.g., after subcutaneous administration). This technology enables a sustained release of potentially encapsulated active substances. Despite these thermo-gelling solutions being widely studied for the development of parenteral drug delivery systems, most commonly using ß-glycerophosphate (ß-GP) as gelling agent, the mechanism inducing the gelation and the role of the polyol part in this mechanism has not been clearly elucidated. To investigate the mechanism of the gelation process, comprehensive rheological studies were performed, comparing different chitosan/polyol-phosphate systems varying in the chemical structure of the polyol parts of the gelling agents. As reference, ß-GP was compared to glucose-1-phosphate (G1-P) and glucose-6-phosphate (G6-P) and to a polyol-free phosphate salt, Na2HPO4, as well. Frequency sweep experiments at different temperatures or different gelling agent concentrations, temperature, and time sweep tests were performed as complementary experimental approaches. The results disclosed significant trends with widespread implications, establishing a relationship between the chemical structure of the polyol part and the macroscopic gelling behavior of the solutions, that is, transition temperature, gelation time, and gel strength. The new results presented in this study show that increasing the size of the polyol part prevents the interactions between the chitosan chains, strongly influencing the gelling process.

Total hemoglobin mass--a new parameter to detect blood doping?

PURPOSE: All kinds of blood manipulations aim to increase the total hemoglobin mass (tHb-mass). To establish tHb-mass as an effective screening parameter for detecting blood doping, the knowledge of its normal variation over time is necessary. The aim of the present study, therefore, was to determine the intraindividual variance of tHb-mass in elite athletes during a training year emphasizing off, training, and race seasons at sea level. METHODS: tHb-mass and hemoglobin concentration ([Hb]) were determined in 24 endurance athletes five times during a year and were compared with a control group (n = 6). An analysis of covariance was used to test the effects of training phases, age, gender, competition level, body mass, and training volume. Three error models, based on 1) a total percentage error of measurement, 2) the combination of a typical percentage error (TE) of analytical origin with an absolute SD of biological origin, and 3) between-subject and within-subject variance components as obtained by an analysis of variance, were tested. RESULTS: In addition to the expected influence of performance status, the main results were that the effects of training volume (P = 0.20) and training phases (P = 0.81) on tHb-mass were not significant. We found that within-subject variations mainly have an analytical origin (TE approximately 1.4%) and a very small SD (7.5 g) of biological origin. CONCLUSION: tHb-mass shows very low individual oscillations during a training year (<6%), and these oscillations are below the expected changes in tHb-mass due to Herythropoetin (EPO) application or blood infusion (approximately 10%). The high stability of tHb-mass over a period of 1 year suggests that it should be included in an athlete's biological passport and analyzed by recently developed probabilistic inference techniques that define subject-based reference ranges.

Effect of ketotifen fumarate, olopatadine, and levocabastine on ocular active anaphylaxis in the guinea pig and ocular immediate hypersensitivity in the albino rat.

PURPOSE: To study the effects of ketotifen fumarate, olopatadine, and levocabastine on ocular active anaphylaxis in guinea pigs and on ocular immediate hypersensitivity in albino rats. METHODS: Clinical grading scores and Evans blue dye leakage to eyelids and to eyeballs were assessed in five treatment groups (n = 10): ketotifen fumarate 0.025%, olopatadine 0.1%, levocabastine 0.05%, negative control, and positive control. RESULTS: At 20 minutes after challenge, edema scores for ketotifen-treated guinea pigs were statistically significantly lower than those for levocabastine or olopatadine. Active treatment significantly reduced vascular leakage in both models. Ketotifen significantly reduced vascular leakage in eyelids compared with the other drugs. In guinea pigs, vascular leakage in eyeballs was significantly reduced with ketotifen fumarate compared with olopatadine and levocabastine. CONCLUSIONS: In the guinea pig model, ketotifen was more effective than olopatadine and levocabastine at reducing conjunctival edema and vascular permeability in eyelids and eyeballs. In the rat model, ketotifen was more effective at reducing vascular permeability in eyelids than olopatadine and levocabastine.

Effect of pre-competition and altitude training on blood models used to detect erythropoietin abuse by athletes.

This study reports blood model scores used for detection of recombinant human erythropoietin (rHuEPO) abuse by athletes. Elite female rowers were monitored prior to their World Championships, including a period spent training at moderate altitude. In contrast to previous results, no substantial increase in model scores was found following altitude exposure.

Periocular injection of microspheres containing PKC412 inhibits choroidal neovascularization in a porcine model.

PURPOSE: Oral administration of PKC412, a kinase inhibitor that blocks several isoforms of protein kinase C (PKC) and receptors for vascular endothelial growth factor (VEGF), platelet-derived growth factor, and stem cell factor, inhibits ocular neovascularization in a murine model. The purpose of this study was to determine whether sustained local delivery of PKC412 in a human-sized eye inhibits choroidal neovascularization (CNV). METHODS: Laser photocoagulation was used to rupture Bruch's membrane in young domestic pigs, and then a periocular injection of control microspheres or microspheres containing 25% or 50% PKC412 was given. After 10 days the integrated area of CNV at Bruch's membrane rupture sites was measured by image analysis. The levels of PKC412 in choroid, retina, and vitreous were measured either 10 or 20 days after periocular injection of 50% PKC microspheres or at 20 days after injection of 25% PKC412 microspheres. RESULTS: The areas of CNV at Bruch's membrane rupture sites were significantly smaller in eyes that received a periocular injection of microspheres containing 25% (P=0.0042) or 50% (P=0.0012) PKC412 than those in eyes injected with control microspheres. Ten days after periocular injection of 50% PKC412 microspheres, PKC412 was detected in the choroid, but not in the retina or vitreous. Twenty days after periocular injection of 50% PKC412, high levels of PKC412 were measured in the choroid, vitreous, and retina. Levels were lower but still substantial in all three compartments 20 days after periocular injection of 25% microspheres. CONCLUSIONS: Sustained local delivery of PKC412 provides a promising approach for treatment of CNV.

Effects of ketotifen 0.025% and lodoxamide 0.1% on eosinophil infiltration into the guinea pig conjunctiva in a model of allergic conjunctivitis.

The effects of ketotifen and lodoxamide on eosinophil infiltration were assessed in a guinea pig model of allergic conjunctivitis. The two active treatments were coded in this masked study in which 30 male guinea pigs, sensitized to chicken egg albumin (ovalbumin), were randomly assigned to one of three groups: Group 1, instillation of 0.9% NaCl into the conjunctival sac of both eyes; Group 2, instillation of 0.025% ketotifen into the left eye and 0.9% NaCl into the right eye; Group 3, instillation of 0.1% lodoxamide into the left eye and 0.9% NaCl into the right eye. Ovalbumin was administered topically to each eye, except in Group 1 where it was only applied to the left eye. (111)In-oxine labeled eosinophils were injected into the jugular vein of each guinea pig; the animals were sacrificed 17 hours after ovalbumin had been applied. The level of radioactivity in the ketotifen- and lodoxamide-treated eyes was approximately 60% of that in the saline-treated eyes. Moreover, the mean level of radioactivity in the ketotifen- and lodoxamide-treated eyes was comparable with the mean level of radioactivity in the saline-treated eye of Group 1, which had not been exposed to allergen. These results indicate that the therapeutic effects of ketotifen and lodoxamide in allergic conjunctivitis may be partly mediated by an inhibitory effect on eosinophils.