Martin Alexander Leitritz

Reliability of differentiating human coronary plaque morphology using contrast-enhanced multislice spiral computed tomography : A comparison with histology

Background: Initial clinical results indicate that multislice spiral computed tomography (MDCT) might be useful for the noninvasive characterization of human coronary plaque morphology by determining tissue density within the lesions. This seems to be of clinical relevance, because coronary artery disease might be detected at an early stage before calcifications occur and noncalcified plaques that may be more likely to rupture could also be visualized noninvasively. The aim of the present study was to evaluate the reliability of contrast-enhanced MDCT in differentiating human atherosclerotic coronary plaque morphology by comparing it with the histopathologic gold standard. Methods and Results: Twelve human hearts were scanned postmortem using an MDCT (Somatom Volume Zoom; Siemens, Forchheim, Germany) high-resolution computed tomography scanner to detect atherosclerotic coronary plaques. Density measurements were performed within detected plaque areas. The exact location of each plaque was marked at the surface of the heart to assure accurate histopathologic sectioning of these lesions. The plaques were classified according to a modified Stary classification. Seventeen plaques were identified by MDCT. Six plaques were histopathologically classified as lipid rich (Stary III/IV), 6 plaques as intermediate (Stary V), and 5 plaques as calcific (Stary VII). Lipid-rich plaques had a mean density on MDCT of 42 ± 22 Hounsfield units (HU), intermediate plaques had a mean density of 70 ± 21 HU, and calcific plaques had a mean density of 715 ± 328 HU. ANOVA analysis revealed a significant difference in plaque density between the 3 groups (P < 0.0001). Conclusions: The comparison with histopathology confirms that tissue density as determined by contrast-enhanced MDCT might be used to differentiate atherosclerotic plaque morphology.

The retinal tolerance to bevacizumab in co‐application with a recombinant tissue plasminogen activator

Aim: To investigate the retinal toxicity of bevacizumab in co-application with a commercially available recombinant tissue plasminogen activator (rt-PA), and to facilitate a new therapeutic concept in the treatment of massive subretinal haemorrhage caused by neovascular age-related macular degeneration (AMD). Methods: Isolated bovine retinas were perfused with an oxygen-preincubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using Ag/AgCl electrodes. Bevacizumab (0.25 mg/ml) and rt-PA (20 μg/ml) were added to the nutrient solution for 45 min. Thereafter, the retina was reperfused for 60 min with normal nutrient solution. Similarly, the effects of rt-PA (20 μg/ml, 60 μg/ml and 200 μg/ml) on the a- and b-wave amplitudes were investigated. The percentages of a- and b-wave reduction during application and at washout were calculated. Results: During application of bevacizumab (0.25 mg/ml) in co-application with 20 μg/ml (rt-PA), the ERG amplitudes remained stable. The concentrations of rt-PA alone (20 μg/ml and 60 μg/ml) did not induce significant reduction of the b-wave amplitude. In addition, 20 μg/ml rt-PA did not alter the a-wave amplitude. However, 60 μg/ml rt-PA caused a slight but significant reduction of the a-wave amplitude. A full recovery was detected for both concentrations during the washout. At the highest tested concentration of 200 μg/ml rt-PA, a significant reduction of the a- and b-wave amplitudes was provoked during the exposure. The reduction of ERG amplitudes remained irreversible during the washout. Conclusion: The present study suggests that a subretinal injection of 20 µg/ml rt-PA in co-application with bevacizumab (0.25 mg/ml) for the treatment of massive subretinal haemorrhage seems possible. This is a safety study. Therefore, we did not test the clinical effectiveness of this combined treatment.

Effects of local all-trans-retinoic acid delivery on experimental atherosclerosis in the rabbit carotid artery

BACKGROUND Retinoids regulate a variety of biological processes and play an important role in cell differentiation and proliferation. All-trans retinoid acid (atRA) is known to inhibit smooth muscle cell growth and thus is supposed to have favorable effects on the incidence of restenosis after percutaneous coronary interventions. The broad biological spectrum, however, leads to numerous severe side effects which limit the clinical use of a systemic application of atRA. In order to avoid systemic side effects, local delivery of atRA is preferable. The aim of this study was to evaluate the effects of atRA on the response to injury in a second-injury model of experimental balloon angioplasty. METHODS After induction of a fibromuscular plaque in the right carotid artery of 40 New Zealand rabbits, 35 animals underwent balloon angioplasty of the preformed plaque formation. Subsequent local atRA delivery (10 ml, 10 microM) with the double-balloon catheter was performed in 15 animals. Five animals received vehicle only as sham controls, and five animals were solely electrostimulated, 15 animals served as control group with balloon angioplasty only. Vessels were excised 7 days (n=15) and 28 days (n=30) after intervention. Immunocytochemistry with antibodies against smooth muscle alpha-actin and myosin, bromodeoxyuridine, macrophages, collagen I and III and von Willebrand factor was performed. Quantitative analysis was done by computerized morphometry. RESULTS After local atRA delivery in vivo, the extent of stenosis was markedly reduced with 21.7+/-8.3% (mean+/-S.D.) 4 weeks after intervention compared to 31.8+/-13.4% in balloon-dilated animals (P=0.0937). Both a reduced early neointimal proliferation (P=0.0002) and an increase in overall vessel diameter (4 weeks after intervention, P=0.0264) contributed to a limitation of restenosis in atRA-treated animals. Immunocytochemistry revealed a more intense alpha-actin staining pattern after local atRA therapy indicating redifferentiating effects of atRA on vascular smooth muscle cells. CONCLUSIONS Local delivery of atRA led to limitation of restenosis formation in this animal model. The concept of a local atRA therapy might be a promising way to exploit the potential of atRA for vascular indications while minimizing the severe side effects of systemic retinoid therapy.

A New Technique for Treating Posttraumatic Aniridia With Aphakia: First Results of Haptic Fixation of a Foldable Intraocular Lens on a Foldable and Custom-Tailored Iris Prosthesis

We describe a new surgical technique for treating traumatic aniridia with aphakia and its results in a small consecutive case series. We attached a 3-piece acrylic intraocular lens through the haptics to a customized silicone iris prosthesis. The combined implant was inserted through a 5-mm incision and fixated with a transscleral suture in the ciliary sulcus using a knotless technique (Z suture). In all patients, the combined implant stayed firmly fixed within the sulcus and showed a stable and centered position without any tilt or torque during follow-up. Thus, managing posttraumatic aniridia with aphakia by means of haptic fixation of a foldable intraocular lens on a custom-tailored iris prosthesis is a promising approach for visual rehabilitation and cosmetic improvement.

Does intravitreal injection of bevacizumab have an effect on the blood‐aqueus barrier function?

Bevacizumab (Avastin), a humanised monoclonal anti-VEGF antibody originally developed for intravenous therapy of metastatic cancer, is now being used as off-label therapy in age related macular degeneration.1 The cost effective drug promises not only anti-angiogenic capabilities in neovascular eye disease, but has also anti-exudative effects by lowering transendothelial permeability of blood vessels.2 Blood-aqueous barrier (BAB) breakdown has been reported after intraocular application of lyophilised rhuFab formulations.3 Anterior chamber inflammation is one of the most frequently reported adverse events (19%) after pegaptanib injections.4 We wanted to post these safety issues for bevacizumab by objective detection of aqueous protein concentration. The anterior chamber reaction was analysed in 60 patients receiving 1.25 mg of bevacizumab for age …

Grid laser photocoagulation for macular oedema due to branch retinal vein occlusion in the age of bevacizumab? Results of a prospective study with crossover design

Background and aim To investigate the long term effectiveness of grid laser photocoagulation (GLP) versus intravitreal bevacizumab (BEV) in macular oedema (MO) secondary to branch retinal vein occlusion (BRVO), and to evaluate the treatment courses after treatments were switched. Methods In this prospective interventional consecutive case series, previously untreated eyes with perfused MO were enclosed over a period of 16 months for BEV and for 29 months for GLP. The follow-up period was 1 year. Patients with persistent MO after 12 months of BEV were offered GLP and vice versa, and were followed-up for another 12 months. Results Both BEV (23 eyes) and GLP (21 eyes) caused a significant (p<0.05) reduction in central retinal thickness (CRT) at 12 months although this was delayed with GLP. However, BEV revealed a significantly better best corrected visual acuity (BCVA) compared with GLP (0.2 vs 0.5 logMAR; p<0.04). Switching therapy for non-responders revealed a reduced CRT at another 12 months, although this was not significant. Conclusions Functionally and anatomically, BEV appears to be more effective than GLP for the therapy of MO due to BRVO. BCVA is significantly better after 1 year and the anatomical response of the MO is faster. Furthermore, non-responders with persistent MO despite BEV or GLP treatment might benefit from switching therapy.

CRITICAL EVALUATION OF THE USABILITY OF AUGMENTED REALITY OPHTHALMOSCOPY FOR THE TRAINING OF INEXPERIENCED EXAMINERS

Purpose: To measure the value of augmented reality technology usage to teach the medical students performing binocular indirect ophthalmoscopy. Methods: Thirty-seven medical students were randomly assigned to the training of binocular indirect ophthalmoscopy either in the conventional way or with augmented reality ophthalmoscopy (ARO). For testing students skills, they had to examine a real person using a conventional ophthalmoscopy system and draw the optic disk. They also had to fill out a questionnaire. Subjective and objective evaluations were performed. Results: Thirty-seven students were randomly assigned to two groups. Eighteen students were trained with conventional ophthalmoscopy and 19 students with ARO. The questionnaires showed no differences. Performing an objective analysis, the median ophthalmoscopy training score for the conventional ophthalmoscopy group was 1.2 (range, 0.67–2) and showed a significant difference (P < 0.0033) to the ARO group (median 2; range, 0.67–2). Conclusion: The study provides evidence that a single ARO training is efficient to improve ophthalmoscopy skills. As the objective analysis showed, the ARO group had a significantly superior performance. Our study also indicates that subjective evaluation of the fundus drawings without systematic analysis is prone to errors.

Switching intravitreal anti-VEGF treatment in neovascular age-related macular degeneration

Purpose To compare the outcomes after switching between bevacizumab and ranibizumab therapy due to poor treatment effect in neovascular age-related macular degeneration (AMD). Methods This is a retrospective review of patients with neovascular AMD with first treatment using intravitreal bevacizumab (group 1) or ranibizumab (group 2) who switched to the other drug due to poor treatment effect. Primary outcome measures were change in mean best-corrected visual acuity (BCVA) and mean central retinal thickness (CRT) at 1 year and last visit. Results Eighty-seven eyes met the inclusion criteria. In group 1 (43 eyes), the mean BCVA decreased from 20/94 to 20/100 at 1 year after being switched (p = 0.573) and to 20/150 (p = 0.015) at final visit (mean 29.2 months, range 12-53). In group 2 (44 eyes), mean BCVA decreased from 20/72 to 20/90 (p = 0.401) and 20/100 (p = 0.081) at 1 year after switch and at final visit (mean 20.1 months, range 10-40), respectively. The mean CRT at switch, 1 year after switch, and at final visit were 344.4 ± 140 µm (mean ± SD), 286.26 ± 155 µm (p = 0.019), and 290.58 ± 196 µm (p = 0.009) in group 1 and 329.36 ± 144 µm, 302.0 ± 179 µm (p = 0.215), and 309.5 ± 220 µm (p = 0.154) in group 2, respectively. Conclusions The mean BCVA decreased over time in both groups; however, nearly 30% of the eyes in each group showed vision improvement after switching. Mean CRT decreased in both groups, which was more pronounced after being switched from bevacizumab to ranibizumab. In neovascular AMD, a switch between ranibizumab and bevacizumab can be considered as a further therapy option if poor treatment effect is seen with the initial therapy.

Outcomes of Ahmed Glaucoma Valve Implantation for Glaucoma Secondary to Fuchs Uveitis Syndrome

ABSTRACT Purpose: To present the outcomes of Ahmed glaucoma valve implantation (AGV) in glaucoma secondary to Fuchs uveitis syndrome (FUS). Methods: In this retrospective chart review, two definitions of success were used: 6 mmHg ≤intraocular pressure (IOP) ≤21 mmHg (success 1), and 6 mmHg ≤ IOP ≤21 mmHg and at least 25% reduction from baseline (success 2). Depending on the need of postoperative antiglaucoma medication, success was defined as either complete or qualified. Results: In total, 17 eyes of 17 patients were included. Complete success rates (both definitions) were 23.5% (n = 17) after 1 year and 23% (n = 13) after 3 years. Qualified success rates (both definitions) were 58.3% (n = 17) after 1 and 38.4% (n = 13) after 3 years. Encapsulated bleb formation was the most common complication (47% of eyes). Conclusions: AGV was moderately successful in the management of glaucoma secondary to FUS. Success rates are improved by medications, needling, and cycloablative procedures.

Treatment efficacy and safety of canaloplasty for open‐angle glaucoma after 5 years

(SD 0.9), and postoperative score was 0.7 (SD 0.5). Average change in corneal score was −1.1 (SD 0.9, P-value = 0.001). Five eyes experienced complete resolution of keratopathy, and 11 had mild epithelial keratopathy. Half of patients had concomitant procedures: lower lid tightening +/− mid-face lift (six eyelids), direct brow lift (three eyelids) and lateral tarsorrhaphy (two eyelids). The change in MRD1 was −1.3 mm (+/− 1.2) with weight only, and −1.1 mm (+/− 1.4) in weight plus another procedure (P-value = 0.77). The change in lagophthalmos was 2.6 mm (+/− 1.3) with weight only, and 4.5 mm (+/− 1.9) with weight plus another procedure (P-value = 0.03). Average preoperative lagophthalmos was 4 mm (+/− 2.4) in the weight only cohort, and 6 mm (+/− 2.9) in the weight plus another procedure group. None experienced infection, migration or extrusion. There were no complaints regarding cosmesis or ptosis. Our technique combines recession of the levator aponeurosis with supratarsal weight implantation. The implant becomes a ‘spacer’ between the recessed levator aponeurosis and tarsus. It addresses both lagophthalmos and eyelid retraction caused by weakened orbicularis tone. Additionally, it addresses the visible and palpable weight contour with pretarsal placement. This study is first to quantify preoperative and postoperative MRD1, lagophthalmos and corneal changes with upper eyelid loading. Other studies have reported extrusion and complication rates or corneal changes. No previous study separately analysed subjects undergoing other procedures in addition to weight placement. Tower and Dailey’s manuscript is the only study that quantified change in lagophthalmos. All patients experienced significant improvement in lagophthalmos and corneal status. Our average reduction of 3.5 mm lagophthalmos was similar to 3.2 mm reported by Tower and Dailey, although we used on average 1.5 gm, compared to their standardized 2.2 gm. We achieved upper lid recession of 1.2 mm, which was statistically significant. We believe this should be sufficient to address upper lid retraction from weakened orbicularis tone. Concomitant lower lid tightening +/− cheek lift had significantly more reduction of lagophthalmos than weight placement alone. This seems intuitive, as both lower lid retraction and upper lid closure contribute to lagophthalmos. Those with other procedures in addition to weight placement had more lagophthalmos preoperatively. No patients had implant migration or extrusion, with an average of 11.5 months follow-up. Posterior extrusion of the weight remains a concern, as only Müller’s and conjunctiva separate the weight from the surface of the globe, and late extrusion has previously been described. Our study is limited by small size, and retrospective review of a single surgeons cases. These do not negate the efficacy of our modification of a widely accepted procedure. This modification is simple, efficacious and cosmetically acceptable. It can be added to the surgical armamentarium for treating exposure keratopathy due to lagophthalmos. Ali Mokhtarzadeh MD, Edward W Lee MD, Behin I Barahimi MD, Michael S Lee MD and Andrew R Harrison MD Departments of Ophthalmology, Ophthalmology, Neurology and Neurosurgery and Ophthalmology and Otolaryngology, University of Minnesota, Minneapolis, Minnesota, USA Received 10 April 2015; accepted 12 April 2015.