Fixed bimonthly aflibercept in naïve and switched neovascular age-related macular degeneration patients: one year outcomes

AIM: To determine real life clinical outcomes in poorly responsive and treatment-naïve neovascular age related macular degeneration (nvAMD) patients using bimonthly fixed dosing aflibercept regimen. METHODS: This was a retrospective study of 165 eyes with nvAMD started on aflibercept at Southampton Eye Unit between June 2013 and June 2014. Patients were either switched from pro re nata (PRN) ranibizumab/bevacizumab due to poor response (107 eyes), or treatment-naïve (58 eyes). Patients initially received 3-monthly intravitreal aflibercept injections followed by 2-monthly fixed doses. Clinic visits were scheduled at month 0, 4, 10 and 12. Mean change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline were assessed using the Wilcoxon signed-rank test. The proportion of patients maintaining BCVA (<15 letters loss) at 12mo was also evaluated. RESULTS: Mean BCVA change at month 12 was +3.29 and +4.67 letters in the switched and naïve aflibercept groups respectively (P<0.01). BCVA was maintained in 95.3% of switched and 96.6% of naïve patients. CRT at month 12 showed a decrease of -6.16 µm in the switched group and -35.36 µm in the naïve group (P<0.01). Patients previously treated with ranibizumab/bevacizumab had on average received 7.4 ranibizumab/bevacizumab injections over 12.6mo, attending 10 clinic visits. The fixed dosing aflibercept regimen required an average of 7.1 injections (naïve group), 7.5 injections (switched group) and 4 clinic visits per year. CONCLUSION: Fixed bimonthly aflibercept is effective in both treatment-naïve and poorly responsive nvAMD patients. Adopting a fixed dosing regimen can reduce patient burden without compromising on outcomes.     

Subacute sclerosing panencephalitis resembling Rasmussen’s encephalitis on magnetic resonance imaging

Subacute sclerosing panencephalitis (SSPE) is a rare, slowly progressing but invariably fatal disease that is related to a prior measles virus infection and most commonly affects paediatric patients. Magnetic resonance (MR) imaging is the modality of choice for determining such changes in white matter. SSPE typically demonstrates bilateral but asymmetric periventricular and subcortical white matter involvement. We herein report a rare case of unilateral white matter involvement in a 13-year-old boy with SSPE that closely simulated Rasmussen’s encephalitis. To the best of our knowledge, this is the first report of an atypical presentation on MR imaging in which SSPE was a rare cause of unilateral brain parenchymal involvement in a patient with intractable seizures.     

Self-Mutilation in Neurodegeneration with Brain Iron Accumulation

Neurodegeneration with brain iron accumulation (NBIA) is the term applied to a heterogeneous group of disorders resulting in iron deposition in the basal ganglia. Well-known phenotypic features are progressive regression with extra pyramidal involvement and a variable course. A 10-year-old child born to consanguineous parents presented with progressive generalized opisthotonic dystonia, retrocollis, oromandibular dyskinesias, apraxia for swallowing, optic atrophy and severe self-mutilation of lips. MR imaging showed brain iron accumulation. Other causes of self-mutilation were excluded. Early infantile onset, ophisthotonic dystonia with oromandibular dyskinesias and characteristic MR images are suggestive of NBIA. There is only one case reported in the literature of self-mutilation in this condition.     

使用棱镜重新定位双侧中心暗点患者视网膜物像的预试验

目的 本研究使用激光扫描检眼镜(SLO)评价双侧中央暗点患者使用棱镜后的眼球运动反应.方法 本预试验共招募6例有双侧中央暗点的年龄相关性黄斑变性(AMD)患者以及6例正常视力的志愿者.首先用Nidek MP-1微视野仪确认患者的中央暗点和优选视网膜注视点(PRL),然后用Rodenstock SLO,在将视标投射在优选视网膜注视点时拍下实时视网膜像,接着在受检者眼前加入6～8 PD的棱镜,要求受检者保持注视视标,这时通过视网膜标记来测量视网膜像的移位量,以及随后发生的优选视网膜注视点的再次注视.过程中平均移位量和再次注视时间通过图像软件(ImageJ software)来计算.结果 实验组再次注视时的移位量在3个像素点或11.66个弧分之内(x轴:2.90±3.92,y轴:2.53±4.18).对照组再次注视时的移位会准确些(x轴:0.33±1.15,y轴:0.89±2.50),但与实验组差异无统计学意义(tx=1.32,Px＞0.05;ty=0.80,Py＞0.05).对照组再次注视时间(0.98±0.19)s较实验组(2.83±1.63)s要短,差距有统计学意义(t=5.03,P＜0.01).其中有1例实验组受检者没有发生再次注视,其结果被排除并单独分析.结论 研究发现,双眼中央暗点患者对棱镜物像转移后的再注视反应与正常人接近,但实验组再注视明显较对照组慢,并有1例受检者没有发生再注视.该数据说明双侧中央暗点患者无论眼前有没有棱镜,都会利用相同的视网膜位置视物,因此,通过棱镜物像再定位的意义不大.     

A modality-specific somatosensory evoked potential test protocol for clinical evaluation: A feasibility study

ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system.MethodsIn order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference.ResultsWe found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings.ConclusionIn this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application.SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials.     

电针联合右美托咪定对骨科老年患者术中应激的影响研究

目的：探讨电针联合右美托咪定对老年骨科患者术中应激的影响。方法：选取拟行手术治疗的老年下肢骨折患者56例为研究对象，采用随机数字表法分为单纯全麻组、电针复合全麻组（简称复合电针组）、右美托咪定复合全麻组（简称复合右美组）及电针联合右美托咪定复合全麻组（简称针药复合组），各14例。记录各组各时间点血压、心率、血氧饱和度等各项监护指标，术前、术后神经心理学指标（简易智力检查评分和疼痛视觉模拟评分）及各时间点血糖水平，术中心血管活性药物使用情况及患者住院天数。结果：术后各时间点针药复合组简易智力检查评分高于单纯全麻组（P＜0.05）；术后72 h内，针药复合组疼痛评分低于其他三组（P＜0.05）；针药复合组术中循环系统指标及血糖水平更稳定；针药复合组术后意识恢复时间最短（P＜0.05）；四组术后呼吸恢复时间与住院天数比较，差异无统计学意义（P＞0.05）；四组心血管活性药物使用率比较，差异无统计学意义（P＞0.05）。结论：老年骨科患者手术中采用电针联合右美托咪定治疗，能够稳定围术期血糖、术中循环系统指标水平，减少术后认知功能障碍发生率，显著降低术中应激水平。     

Advances in understanding the mechanisms of retinal degenerations

Photoreceptor death is an important contributor to irreversible vision loss worldwide. In this review, I outline our work examining the role that purines, such as adenosine triphosphate (ATP), have in normal retinal function and in retinal disease. Our work shows that the actions of ATP, mediated by P2X receptors, are expressed in various retinal layers including photoreceptor terminals, and when stimulated by excessive levels of ATP is associated with rapid death of neurons. Treatment with a compound that blocks the action of P2X and some P2Y receptors reduces photoreceptor death in a mouse model of retinal degeneration. Our observations not only provide a means for developing a potential treatment for reducing photoreceptor death, but also provides a novel way of studying the neural plasticity effects that develop in the inner retina following photoreceptor death. There are a range of inner retinal changes that could influence the effectiveness of retinal prostheses. Indeed, using an ATP-induced degeneration model, we established that the amount of electrical stimulation required to elicit a response in the visual cortex was affected by the level of glial scarring. However, changes in P2X7 receptor expression by OFF ganglion cells during retinal degeneration can also be exploited by photoswitches to restore light sensitivity to degenerated retinae. Finally, our work has also considered how P2X7 expression by innate immune cells, and its role as a scavenger receptor, contributes to age-related macular degeneration (AMD). Our results show that loss of P2X7 function is associated with thickening of Bruch's membrane as well as increased risk of advanced disease in people with AMD. Overall, our work over the last 20 years highlights the importance of purinergic signalling in normal retinal function and retinal disease and suggest that developing therapies that target P2X7 function could be of benefit for these diseases.