1-month Postinjection Research Articles

Efficacy of Ranibizumab in the Treatment of Macular Edema Secondary to Retinal Vein Occlusion

Objective: Branch retinal vein occlusion (BRVO), a major cause of vision loss, is a significant ocular health concern. The frequency of macular edema due to BRVO is a critical area of study because of its profound impact on patient quality of life. This study investigated the effectiveness of ranibizumab, a monoclonal antibody fragment and VEGF inhibitor, in the treatment of macular edema in patients with BRVO. Material and Methods: Twelve patients (12 eyes) diagnosed with macular edema secondary to BRVO were included in this study. Patients were selected on the basis of specific visual acuity and macular thickness criteria, excluding those with other ocular conditions or systemic diseases. 0.05 milligrams of ranibizumab was administered intravitreally to each patient. Ophthalmological assessments were conducted both before and after the injection and at 1, 2, 3, and 6-month intervals following medication administration. Results: The average follow-up duration was 5.5±1.16 months (ranging from 2 to 6 months). The average central macular thickness before the injection was 542.66±191.44 µm, which decreased to 320.50±101.44 µm at 1-month post-injection, 283.66±125.01 µm at 2 months, 299.40±91.52 µm at 3 months, and 260.90±144.97 µm at 6 months. The reduction in central macular thickness at all time points was statistically significant (p<0.01). The mean Early Treatment Diabetic Retinopathy Study (ETDRS) letter score was 55.83±23.91 before the injection and improved to 71.25±17.07 at 1 month, 74.33±15.97 at 2 months, 66.7±21.60 at 3 months, and 71.2±17.38 at 6 months post-injection. The increase in visual acuity at 1, 2, 3, and 6 months after the injection was statistically significant compared to the pre-injection ETDRS letter scores (p<0.05). An improvement of two or more lines in visual acuity was observed in 58.3% of cases at 1 month, 58.3% at 2 months, 50% at 3 months, and 80% at 6 months (one line equivalent to five letters). Conclusion: Intravitreal Ranibizumab injections have been found to be effective and reliable in the early stages of treating macular edema due to branch retinal vein occlusion.

Formation of templated inclusions in a forebrain α-synuclein mouse model is independent of LRRK2

Leucine-rich repeat kinase 2 (LRRK2) and α-synuclein share enigmatic roles in the pathobiology of Parkinson's disease (PD). LRRK2 mutations are a common genetic cause of PD which, in addition to neurodegeneration, often present with abnormal deposits of α-synuclein in the form of Lewy-related pathology. As Lewy-related pathology is a prominent neuropathologic finding in sporadic PD, the relationship between LRRK2 and α-synuclein has garnered considerable interest. However, whether and how LRRK2 might influence the accumulation of Lewy-related pathology remains poorly understood. Through stereotactic injection of mouse α-synuclein pre-formed fibrils (PFF), we modeled the spread of Lewy-related pathology within forebrain regions where LRRK2 is most highly expressed. The impact of LRRK2 genotype on the formation of α-synuclein inclusions was evaluated at 1-month post-injection. Neither deletion of LRRK2 nor G2019S LRRK2 knockin appreciably altered the burden of α-synuclein pathology at this early timepoint. These observations fail to provide support for a robust pathophysiologic interaction between LRRK2 and α-synuclein in the forebrain in vivo. There was, however, a modest reduction in microglial activation induced by PFF delivery in the hippocampus of LRRK2 knockout mice, suggesting that LRRK2 may contribute to α-synuclein-induced neuroinflammation. Collectively, our data indicate that the pathological accumulation of α-synuclein in the mouse forebrain is largely independent of LRRK2.

Comparison of the Effectiveness of Intravitreal Bevacizumab Injections with and without Simultaneous Cataract Surgery in Diabetic Patients with Macular Edema.

Intravitreal bevacizumab (IVB), often injected during cataract surgery, is currently the main treatment for diabetic macular edema. This retrospective study aimed to compare the effectiveness of IVB injections alone and during cataract surgery in patients with diabetic macular edema. We examined 43 eyes in 40 patients who underwent cataract surgery with simultaneous IVB injections 3-12 months after IVB injections alone. Best-corrected visual acuity and central subfield macular thickness (CMT) were measured 1-month post-injection. The CMTs of the same eyes with IVB-only first and combined-treatment procedures later were 384 ± 149 vs. 315 ± 109 μm pretreatment (p = 0.0002), and after 1 month, they were 319 ± 102 vs. 419 ± 183 μm (p < 0.0001). In the IVB-only procedure, 56.1% of eyes had CMT < 300 μm 1 month after the injection compared to 32.5% after the combined treatment. Therefore, on average, when IVB was administered during cataract surgery, CMT increased, whereas after IVB injection alone, it effectively decreased. More prospective trials with large sample sizes are needed to evaluate the effectiveness of IVB injection performed simultaneously with cataract surgery.

One Year Outcomes and Longitudinal Changes in Voice Improvement With Single High Dose Intracordal Trafermin Injections for Age-Related Vocal Fold Atrophy

Although intracordal trafermin injection has been performed in the treatment of age-related vocal fold atrophy, the effects of single high dose trafermin injections are unknown. In this study, we examined the 1 year outcomes and longitudinal changes in voice improvement with single high dose intracordal trafermin injections. Retrospective study with approval by our Ethics Committee. The medical records of 34 patients who underwent single high dose (50ug per side) intracordal trafermin injections under local anesthesia for vocal fold atrophy were retrospectively reviewed at 1 month pre-injection and 1 month, 6 months and 1 year post injection. Maximum phonation time (MPT), pitch range (PR), Japanese version of voice handicap index (VHI), grade of GRBAS evaluation, and jitter% improved significantly at 1-year post-injection compared to 1-month pre-injection. MPT and PR improved as early as 1-month post-injection and continued to improve most at 1-year post-injection. VHI showed negative progression from 6-months to 1-year post-injection, during which time the speaking fundamental frequency (SFF) changed to the high pitch in men. Single high dose intracordal trafermin injections can be expected to improve voice in the early post-injection period and to maintain its effect for 1 year. SFF may play a role in worsening VHI in men. level 4.

Efficacy and safety assessment of glandular augmentation with hyaluronic acid for premature ejaculation.

Glandular augmentation (GA) with hyaluronic acid (HA) is a newly developed, minimally invasive therapy for patients with premature ejaculation (PE); however, evidence supporting its efficacy is scarce. To provide a comprehensive profile of GA with HA gel in managing PE, 184 patients with PE who received GA with HA gel therapy from October 2017 to November 2019 were included and followed up for 1 year. The Fan technique was applied. Intravaginal Ejaculation Latency Time (IELT), Chinese Index of Premature Ejaculation-5(CIPE-5) and Visualised Satisfaction Index (VSI) of sexual experience were assessed at initial and 1-, 3-, 6- and 12-month post injection. A total of 71 patients with primary PE (pPE, 38.6%) and 113 patients with acquired PE (aPE, 61.4%) were enrolled. The mean IELT increased to 100.7 ± 43.2s(p < .05) for pPE patients and 359.2 ± 87.1s (p < .05) for aPE patients 1-month post injection and remained significantly higher at the end point with acceptable attenuation. The mean CIPE-5 score increased to 17.6 ± 6.4 (p < .05) in the 1st month and remained steady. The VSI scores increased to 6.6 ± 1.0 (p < .05) for patients with pPE and 7.7 ± 1.2 (p < .01) for patients with aPE. Increments in VSI in patients with aPE were significantly higher than those in patients with pPE (p < .01). No severe complications were noted. GA with HA may be an effective and safe method to treat PE. Patients with acquired PE were also more satisfied post treatment.

Biological substrate modification suppresses ventricular arrhythmias in a porcine model of chronic ischaemic cardiomyopathy.

Cardiomyopathy patients are prone to ventricular arrhythmias (VA) and sudden cardiac death. Current therapies to prevent VA include radiofrequency ablation to destroy slowly conducting pathways of viable myocardium which support re-entry. Here, we tested the reverse concept, namely that boosting local tissue viability in zones of slow conduction might eliminate slow conduction and suppress VA in ischaemic cardiomyopathy. Exosomes are extracellular vesicles laden with bioactive cargo. Exosomes secreted by cardiosphere-derived cells (CDCEXO) reduce scar and improve heart function after intramyocardial delivery. In a VA-prone porcine model of ischaemic cardiomyopathy, we injected CDCEXO or vehicle into zones of delayed conduction defined by electroanatomic mapping. Up to 1-month post-injection, CDCEXO, but not the vehicle, decreased myocardial scar, suppressed slowly conducting electrical pathways, and inhibited VA induction by programmed electrical stimulation. In silico reconstruction of electrical activity based on magnetic resonance images accurately reproduced the suppression of VA inducibility by CDCEXO. Strong anti-fibrotic effects of CDCEXO, evident histologically and by proteomic analysis from pig hearts, were confirmed in a co-culture assay of cardiomyocytes and fibroblasts. Biological substrate modification by exosome injection may be worth developing as a non-destructive alternative to conventional ablation for the prevention of recurrent ventricular tachyarrhythmias.

Rapid Induction of Dopaminergic Neuron Loss Accompanied by Lewy Body-Like Inclusions in A53T BAC-SNCA Transgenic Mice

Parkinson's disease (PD), the most common neurodegenerative movement disorder, is characterized by dopaminergic neuron loss in the substantia nigra pars compacta (SNpc) and intraneuronal α-synuclein (α-syn) inclusions. It is highly needed to establish a rodent model that recapitulates the clinicopathological features of PD within a short period to efficiently investigate the pathological mechanisms and test disease-modifying therapies. To this end, we analyzed three mouse lines, i.e., wild-type mice, wild-type human α-syn bacterial artificial chromosome (BAC) transgenic (BAC-SNCA Tg) mice, and A53T human α-syn BAC transgenic (A53T BAC-SNCA Tg) mice, receiving dorsal striatum injections of human and mouse α-syn preformed fibrils (hPFFs and mPFFs, respectively). mPFF injections induced more severe α-syn pathology in most brain regions, including the ipsilateral SNpc, than hPFF injections in all genotypes at 1-month post-injection. Although these Tg mouse lines expressed a comparable amount of α-syn in the brains, the mPFF-injected A53T BAC-SNCA Tg mice exhibited the most severe α-syn pathology as early as 0.5-month post-injection. The mPFF-injected A53T BAC-SNCA Tg mice showed a 38% reduction in tyrosine hydroxylase (TH)-positive neurons in the ipsilateral SNpc, apomorphine-induced rotational behavior, and motor dysfunction at 2 months post-injection. These data indicate that the extent of α-syn pathology induced by α-syn PFF injection depends on the types of α-syn PFFs and exogenously expressed α-syn in Tg mice. The mPFF-injected A53T BAC-SNCA Tg mice recapitulate the key features of PD more rapidly than previously reported mouse models, suggesting their usefulness for testing disease-modifying therapies as well as analyzing the pathological mechanisms.

Multifocal Electroretinogram, Central Macula Thickness and Visual Acuity in Diabetic Macular Edema Following Intravitreal Injection of anti-VEGF

Introduction : Diabetic Retinopathy (DR) is one of the major cause of visual acuity deterioration in diabetic patients. The loss of central visual acuity in diabetic patients are mainly due to macula edema, which is found in 29% diabetic patients with the over 20 years duration of disease. The aim of this study is to evaluate and investigate the possible correlation among changes of visual acuity (VA), central macular thickness (CMT) using Spectral Domain Optical Coherence Tomography (SD-OCT). Electrophysiological responses using multifocal electroretinography (MfERG) in diabetic macular edema (DME) following intravitreal injection of bevacizumab.&#x0D; Methods: Single arm clinical trial. Thirty-three eyes of 33 DME patients (16 non-proliferative diabetic retinopathy and 17 non-high-risk proliferative diabetic retinopathy), receives intravitreal bevacizumab 1,25mg. All patients underwent complete ophthalmic examination including ETDRS VA testing, Sixty-one scaled hexagon MfERG and SD-OCT scan at baseline, 1-week and 1-month post-injection. Components of the first order kernel (N1, N2 and P1) in central 2o were measured.&#x0D; Result : MfERG showed reduced P1 amplitude (P&lt;0.05) at 1-week after injection followed by increased P1 amplitude (P&gt;0.05) at 1-month after treatment as compared to the baseline in all subjects. There was 19% improvement CMT and 0.2Logmar VA improvement in 1-month post-injection compared to the baseline (P&lt;005). This study showed no serious ocular adverse effects. There was no significant correlation between changes in visual acuity with changes in CMT or other MfERG parameters.&#x0D; Conclusion: Intravitreal injection bevacizumab resulting in improved VA, reduction in CMT and mild improvement in the MfERG responses. Although VA changes did not correlate with reduced CMT nor with improved responses of MfERG, the combined use of SD-OCT and MfERG may be used to evaluate macular function in DME patient with worsened visual acuity post anti-VEGF injection.

Inflammation during Lung Cancer Progression and Ethyl Pyruvate Treatment Observed by Pulmonary Functional Hyperpolarized 129Xe MRI in Mice.

This study aimed to assess the suitability of hyperpolarized 129Xe (HPXe) MRI for noninvasive longitudinal evaluation of pulmonary function in preclinical lung cancer models. A mouse model of lung cancer (LC) was induced in 5 mice by intraperitoneal injection of urethane, while a negative-control (NC) mice (N = 5) was prepared by injection of saline solution. Longitudinal HPXe MRI was performed over a 5-month period to monitor lung ventilation and gas exchange. The treatment efficacy of ethyl pyruvate (EP), an anti-inflammatory drug, to the mouse LC model was monitored using HPXe MRI by commencing administration of EP pre (early-phase) and 1-month post (late-phase) injection of urethane (N = 5 mice for each group). Gas-exchange function in LC mice was significantly reduced at 1-month after urethane injection compared with NC mice administered with saline (P < 0.01). Thereafter, it remained consistently lower than that of the NC group for the full 5-month measurement period. In contrast, the ventilation function of the LC model mice was not significantly different to that of the NC mice. Histological analysis revealed alveolar epithelial hyperplasia in LC mice alveoli at 1 month after urethane injection, and adenoma was confirmed 3 months after the injection. The early- and late-phase EP interventions were found to improve HPXe MRI metrics (reduced at 1 month postinjection of urethane) and significantly inhibit tumor growth. These results suggest that HPXe MRI gas-exchange metrics can be used to quantitatively assess changes in the precancerous lesion microenvironment and to evaluate therapeutic efficacy in cancer. Thus, HPXe MRI can be utilized to noninvasively monitor pulmonary pathology during LC progression and can visualize functional changes during therapy.

Exudative retinal detachment in treatment naïve aggressive posterior retinopathy of prematurity

We report the first case of bilateral exudative retinal detachment in treatment naïve zone one aggressive posterior retinopathy of prematurity. Exudative detachments in retinopathy of prematurity have been reported in literature following laser photocoagulation or cryotherapy. But exudative detachment as an initial presentation in APROP is rather rare. The abnormality in our case was noticed at the second visit. A 20-day-old infant (born at 32 weeks of gestation) was diagnosed to have APROP. He was advised intravitreal bevacizumab injection (0.625 mg) in both eyes. Two days later when the infant was brought in for injection, he was found to have bilateral exudative retinal detachments almost reaching the posterior pole. We administered the intravitreal injections of bevacizumab in both eyes and the baby was followed up at regular intervals. Review at 1-month post-injection revealed resolution of detachments.

Long-Term Effects With Potential Clinical Importance of Botulinum Toxin Type-A on Mechanics of Muscles Exposed.

Botulinum toxin type-A (BTX-A) is widely used for spasticity management and mechanically aims at reducing passive resistance at the joint and widening joint range of movement. However, recent experiments on acute BTX-A effects showed that the injected rat tibialis anterior (TA) muscle’s passive forces increased, and the length range of active force exertion (lrange) did not change. Additionally, BTX-A was shown to spread into non-injected muscles in the compartment and affect their mechanics. Whether those effects persist in the long term is highly important, but unknown. The aim was to test the following hypotheses with experiments conducted in the anterior crural compartment of the rat: In the long term, BTX-A (1) maintains lrange, (2) increases passive forces of the injected TA muscle, and (3) spreads into non-injected extensor digitorum longus (EDL) and the extensor hallucis longus (EHL) muscles, also affecting their active and passive forces. Male Wistar rats were divided into two groups: BTX-A and Control (0.1 units of BTX-A or only saline was injected into the TA). Isometric forces of the muscles were measured simultaneously 1-month post-injection. The targeted TA was lengthened, whereas the non-targeted EDL and EHL were kept at constant length. Hydroxyproline analysis was done to quantify changes in the collagen content of studied muscles. Two-way ANOVA test (for muscle forces, factors: TA length and animal group) and unpaired t or Mann-Whitney U test (for lrange and collagen content, where appropriate) were used for statistical analyses (P < 0.05). BTX-A caused significant effects. TA: active forces decreased (maximally by 75.2% at short and minimally by 48.3%, at long muscle lengths), lrange decreased (by 22.9%), passive forces increased (by 12.3%), and collagen content increased (approximately threefold). EDL and EHL: active forces decreased (up to 66.8%), passive force increased (minimally by 62.5%), and collagen content increased (approximately twofold). Therefore, hypothesis 1 was rejected and 2 and 3 were confirmed indicating that previously reported acute BTX-A effects persist and advance in the long term. A narrower lrange and an elevated passive resistance of the targeted muscle are unintended mechanical effects, whereas spread of BTX-A into other compartmental muscles indicates the presence of uncontrolled mechanical effects.

Vocal Fold Insufficiency: How Effective is Injection Laryngoplasty? Short Term Clinical Outcomes.

Office based Injection Laryngoplasty has become a common and feasible method of addressing vocal fold insufficiency (VFI) resulting from a plethora of aetiologies. Contemporary to various injectates, Calcium Hydroxylapatite has met with great success across usage with various techniques. But, irrespective of the technique and injectate material, the burning question in mind of "realistic" clientele remains, "How soon will I have by voice back?". Aim of this study is to evaluate the short term (3months postoperative) effects of Injection Laryngoplasty in cases of VFI using Calcium Hydroxylapatite via trans cricothyroid route, in terms of both objective and subjective parameters. 12 patients with mean age of 35.67years underwent vocal fold injections (via transnasal flexible fibreoptic laryngoscopic guided trans-cricothyroid membrane approach using CaHA) for VFI. The pre injection and 1, 2- and 3-months post injection scores' changes in outcome measures in form of videostroboscopic parameters, Voice Handicap Index scores and acoustic analysis were compiled and analysed. 91.6% of patients showed statistically significant benefit after 3months post injection. 0.1% patients showed loss of benefit of the CaHA material even 3months post injection. Average length of benefit was 1-month post injection. No significant complication was observed in any patient. We conclude that the objective evidence of structural and functional improvement may be seen immediately post injection laryngoplasty, minimum of 3months is required for evident improvement in patient's perception of his own voice in terms of Quality of Life parameters.

High-resolution manometry and swallow outcomes after vocal fold injection medialization for unilateral vocal fold paralysis/paresis.

Injection medialization is performed to improve glottic closure, thereby airway protection. Overall objective to determine if unilateral injection medialization changes glottal area with concomitant adjustments in penetration/aspiration scale (PAS) scores and pharyngeal high-resolution manometry (HRM) parameters. Enrolled 17 adults with unilateral vocal fold paralysis/paresis and aspiration/penetration. Fiberoptic endoscopic evaluation of swallowing and pharyngeal HRM completed at (1) baseline (within 1 week before injection), (2) postinjection (within 1 week post injection), and (3) 1-month postinjection. Comparisons between time points for PAS scores, glottal area, pharyngeal pressure, and timing. No significant differences in normalized glottal area. No significant differences in PAS scores, for any consistency. Significantly increased rate of mesopharynx pressure rise and maximum pressure at 1 month postinjection (P = .01 and .02, respectively) compared to baseline. Significant decrease in mesopharynx integral from baseline to 1 week postoperative (P = .03). Findings suggest unilateral vocal fold injection medialization had limited effect on swallow function.

The effect of vocal fold augmentation on cough symptoms in the presence of glottic insufficiency.

To determine the effect of injection augmentation of the vocal folds on chronic cough symptoms in patients with glottic insufficiency. Medical records from 146 consecutive patients who underwent vocal fold injection augmentation by a fellowship-trained laryngologist between 2013 and 2015 were reviewed. Twenty-three patients (12 male) met inclusion criteria of a vocal fold augmentation injection, cough symptoms lasting more than 8 weeks, and glottic insufficiency as determined by shortened closed phase on stroboscopy. Exclusion criteria included lack of cough complaints, diagnosis of vocal fold immobility, previous history of vocal fold augmentation, and incomplete data sets. Data collected included age, gender, pre- and 1-month postinjection Cough Severity Index (CSI) scores, location of injection (unilateral or bilateral), and patient statement of percent change in symptoms that was recorded at 1-month postinjection visit. Paired t test indicated a significant decrease in CSI scores from pre- (m = 18.5) to 1-month postinjection (m = 12.1) (P = 0.004). Eighteen patients (78.2%) reported a 50% or greater improvement in cough symptoms at the 1-month postinjection visit. Injection augmentation of the vocal folds in the presence of glottic insufficiency appears to improve cough symptoms, as was reported by CSI in patients who are refractory to other medical and behavioral treatments. 4. Laryngoscope, 128:1316-1319, 2018.

Long Term Outcomes from CT-guided Indirect Cervical Nerve Root Blocks and their relationship to the MRI findings--A prospective Study.

To investigate long-term pain reduction and 'improvement' in patients with indirect cervical nerve-root-blocks in comparison to MRI findings. One hundred and twelve patients with MRI confirmed cervical radiculopathy and an indirect cervical nerve-root-block were included. Two radiologists independently evaluated the MRI examinations. 12 different MRI abnormalities at the level and side of infiltration were compared to pain relief and 'improvement' at 1-month, 3-months and 1-year post injection. The proportion of patients reporting clinically relevant 'improvement' was 36.7% at 1-month, 53.9% at 3-months and 68.1% at 1-year. At 1-month post injection, a statistically significantly lower percentage of patients eventually requiring surgery reported improvement and lower NRS change scores compared to those who did not undergo surgery (p = 0.001). Patients with extrusion of the disc were around 4-times more likely to have surgery. At 1-year post-injection the presence of nerve-root compromise was significantly linked to treatment outcome (p = 0.011). Patients with nerve root compression were more likely to report improvement at 1 year. Patients with disc extrusions have less pain relief and are 4 times more likely to go to surgery than patients with disc protrusions. • Good long term outcomes after indirect nerve root infiltrations with non-particulate steroids. • The presence of nerve root compression was a predictive finding of 'improvement'. • Significantly less patients subsequently having surgery had lower NRS scores 1-month post injection. • There is less pain relief in patients with disc extrusions. • There are less improvement in patients with modic type I changes.

Sustained improvement of reading symptoms following botulinum toxin A injection for convergence insufficiency

Introduction: We evaluated the use of botulinum toxin A in adults with convergence insufficiency in whom prior treatment had failed.Methods: We studied 8 patients (median age 36 years, range 17 to 77 years) with reading symptoms due to convergence insufficiency defined as an exodeviation greater at near, not exceeding 10 PD in the distance measured by prism and alternate cover test, and either convergence near point >6 cm or reduced fusional amplitudes. All patients were still symptomatic after prior treatment by convergence exercises (n = 8), base-in prism glasses (n = 5) or strabismus surgery (n = 2). Five patients received injection of 5 IU botulinum toxin in 0.1 ml saline to one lateral rectus muscle, two received 2.5 IU, and one received 2.5 IU to both lateral rectus muscles.Results: At 1 month post injection, all patients had an initial reduction of exodeviation from baseline (median 9 PD, p = 0.008) at near, although 2 patients had a temporary intermittent esotropia in the distance with diplopia associated with difficulty driving. At 6 months, when the pharmacological effect of botulinum toxin had completely worn off, patients still maintained a small reduction of exodeviation (median 4 PD, p = 0.3) at near. Reading symptoms improved in 7 of 8 patients at 1-month post injection, and in all patients at 6 months. Two patients had health-related quality of life assessed with the Adult Strabismus 20 Questionnaire, showing improved Reading Function scores at 6 months. Interestingly, 3 patients reported improved reading despite returning to the baseline angle at 6 months, and 2 of 4 with 12-month follow-up still reported improvement.Conclusions: In adult convergence insufficiency, botulinum toxin injection to a lateral rectus muscle improves reading symptoms beyond the duration of the pure pharmacological effect. Botulinum toxin injection may be useful in management of adult convergence insufficiency, although repeat injections may be needed.

Incidence and Risk Factors for Macular Hemorrhage Following Intravitreal Ranibizumab Injection for Neovascular Age-Related Macular Degeneration

To analyze the incidence of and risk factors for newly developed or increased macular hemorrhage after intravitreal ranibizumab injection (IVR) for neovascular age-related macular degeneration (AMD). We performed a retrospective chart review of 220 subjects (220 eyes) from 5 hospitals who received IVRs for neovascular AMD between 1 June 2009 and 30 June 2010. Systemic conditions (age, sex, presence of diabetes, hypertension, cardiovascular disease, smoking, and use of anticoagulation agent) and presence of hemorrhage at the initial exam were evaluated. The primary study outcome was the incidence of newly developed or increased macular hemorrhage during the 1-month postinjection period. The incidence of newly developed or increased macular hemorrhage including vitreous hemorrhage was 8% (18/220). Presence of diabetes was found to be a risk factor for macular hemorrhage [odds ratios (OR): 2.16, 95% confidence intervals (CI): 1.07-8.13]. When subjects had both diabetes and hypertension, the risk of macular hemorrhage after injection increased 4.8-fold (OR: 4.84, CI: 1.24-18.85). The systemic condition of subjects was found to be an important risk factor for newly developed or increased macular hemorrhage after IVR for neovascular AMD. More consideration should be given to the status of diabetes and hypertension in subjects who receive ranibizumab for neovascular AMD.

Adeno‐associated virus‐mediated gene delivery of the human ND4 complex I subunit in rabbit eyes

To assess intravitreal injection dose and safety of recombinant adeno-associated virus-mediated gene delivery of human NADH dehydrogenase subunit 4 (ND4) in rabbit eyes. An open reading frame for human ND4 or adeno-associated virus-green fluorescent protein were fused to the mitochondrial targeting sequence and packed into separate adeno-associated virus capsids. Rabbits of three treatment groups were administered 0.1 mL adeno-associated virus-ND4, 0.1 mL adeno-associated virus-green fluorescent protein or 0.1 mL vehicle via intravitreal injection, respectively. The safety of recombinant adenoassociated virus-mediated gene delivery of human ND4 in rabbit eyes was assessed with a slit-lamp microscope and direct ophthalmoscope, measurements of intraocular pressure and flash visual evoked potential, and optical coherence tomography. The mRNA and protein expressions of human ND4 in the retina of rabbits were determined with real-time polymer chain reaction (PCR), immunofluorescence and Western blot. No complications occurred in any of the three treatment groups after the intravitreal injection. At 1-month post-injection, no significant difference in the mean thickness of retinal nerve fibre layer was found among the three groups. Results of the visual evoked potential test showed that there was no difference in the latency of the visual P100 wave among the three groups. Real-time PCR, immunofluorescence and Western blot analyses verified the expressions of ND4 and green fluorescent protein in the retinal nerve fibre layer. Intravitreal injection of adeno-associated virus-ND4 expression vectors was effectively and safely performed in our study. The data on the dose and method of intravitreal injection from our study will provide a valuable reference for clinical intravitreal injection of adeno-associated virus-ND4 for the treatment of Leber's hereditary optic neuropathy.

Differential effects of amyloid-β peptide aggregation status on in vivo retinal neurotoxicity.

The present study examined the relationship between amyloid beta (Aβ)-peptide aggregation state and neurotoxicity in vivo using the rat retinal-vitreal model. Following single unilateral intravitreal injection of either soluble Aβ1-42 or Aβ1-42 preaggregated for different periods, retinal pathology was evaluated at 24 hours, 48 hours, and 1-month postinjection. Injection of either soluble Aβ (sAβ) or preaggregated Aβ induced a rapid reduction in immunoreactivity (IR) for synaptophysin, suggesting that direct contact with neurons is not necessary to disrupt synapses. Acute neuronal ionic and metabolic dysfunction was demonstrated by widespread loss of IR to the calcium buffering protein parvalbumin (PV) and protein gene product 9.5, a component of the ubiquitin-proteosome system. Injection of sAβ appeared to have a more rapid impact on PV than the preaggregated treatments, producing a marked reduction in PV cell diameters at 48 hours, an effect that was only observed for preaggregated Aβ after 1-month survival. Extending the preaggregation period from 4 to 8 days to obtain highly fibrillar Aβ species significantly increased the loss of choline acteyltransferase IR, but had no effect on PV-IR. These findings prompt the conclusion that Aβ assembly state has a significant impact on in vivo neurotoxicity by triggering distinct molecular changes within the cell.

Prospective Study Examining Remote Effects of Botulinum Toxin A in Children With Cerebral Palsy

We examined the remote effects on muscle strength and functional decline of lower-extremity botulinum toxin A injections in children with cerebral palsy. This prospective study enrolled 34 children (19 boys, 15 girls; mean age, 7.7 years) diagnosed with spastic cerebral palsy. Patients were examined at baseline and 1 month to determine if they experienced a change in upper-extremity strength (handheld dynamometry) or function (Pediatric Outcomes Data Collection Instrument). Subjects were analyzed in aggregate and by dosing group (low dose, 0-10 U/kg body weight; high dose, 11-25 U/kg) to determine if injection dose was associated with a change in remote muscle strength or function. We measured baseline and 1-month postinjection strength in shoulder flexor, shoulder abductor, elbow flexor, elbow extensor, and finger flexor muscles. None of these remote muscle groups was significantly weaker at 1 month after injection. No correlation was evident between change in muscle strength and toxin dose. These findings indicate that doses of botulinum toxin A in the lower extremities, at up to 21 U/kg, do not affect upper-extremity strength. This information can help guide dosages of botulinum toxin A in the management of spasticity in children with cerebral palsy.