Nayagam David A X, Williams Richard A, Allen Penelope J, Shivdasani Mohit N, Luu Chi D, Salinas-LaRosa Cesar M, Finch Sue, Ayton Lauren N, Saunders Alexia L, McPhedran Michelle, McGowan Ceara, Villalobos Joel, Fallon James B, Wise Andrew K, Yeoh Jonathan, Xu Jin, Feng Helen, Millard Rodney, McWade Melanie, Thien Patrick C, Williams Chris E, Shepherd Robert K
Bionics Institute, East Melbourne, Victoria, Australia; Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
Department of Pathology, University of Melbourne, Parkville, Victoria, Australia; Department of Anatomical Pathology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.
PLoS One. 2014 May 22;9(5):e97182. doi: 10.1371/journal.pone.0097182. eCollection 2014.
To assess the safety and efficacy of chronic electrical stimulation of the retina with a suprachoroidal visual prosthesis.
Seven normally-sighted feline subjects were implanted for 96-143 days with a suprachoroidal electrode array and six were chronically stimulated for 70-105 days at levels that activated the visual cortex. Charge balanced, biphasic, current pulses were delivered to platinum electrodes in a monopolar stimulation mode. Retinal integrity/function and the mechanical stability of the implant were assessed monthly using electroretinography (ERG), optical coherence tomography (OCT) and fundus photography. Electrode impedances were measured weekly and electrically-evoked visual cortex potentials (eEVCPs) were measured monthly to verify that chronic stimuli were suprathreshold. At the end of the chronic stimulation period, thresholds were confirmed with multi-unit recordings from the visual cortex. Randomized, blinded histological assessments were performed by two pathologists to compare the stimulated and non-stimulated retina and adjacent tissue.
All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. After an initial post-operative settling period, electrode arrays were mechanically stable. Mean electrode impedances were stable between 11-15 kΩ during the implantation period. Visually-evoked ERGs & OCT were normal, and mean eEVCP thresholds did not substantially differ over time. In 81 of 84 electrode-adjacent tissue samples examined, there were no discernible histopathological differences between stimulated and unstimulated tissue. In the remaining three tissue samples there were minor focal fibroblastic and acute inflammatory responses.
Chronic suprathreshold electrical stimulation of the retina using a suprachoroidal electrode array evoked a minimal tissue response and no adverse clinical or histological findings. Moreover, thresholds and electrode impedance remained stable for stimulation durations of up to 15 weeks. This study has demonstrated the safety and efficacy of suprachoroidal stimulation with charge balanced stimulus currents.
评估脉络膜上视觉假体对视网膜进行慢性电刺激的安全性和有效性。
七只视力正常的猫科动物受试者植入脉络膜上电极阵列96 - 143天，其中六只在能激活视觉皮层的水平上进行了70 - 105天的慢性刺激。以单极刺激模式将电荷平衡的双相电流脉冲输送到铂电极。每月使用视网膜电图（ERG）、光学相干断层扫描（OCT）和眼底摄影评估视网膜完整性/功能以及植入物的机械稳定性。每周测量电极阻抗，每月测量电诱发视觉皮层电位（eEVCPs）以验证慢性刺激是否高于阈值。在慢性刺激期结束时，通过视觉皮层的多单元记录确认阈值。由两名病理学家进行随机、盲法组织学评估，以比较受刺激和未受刺激的视网膜及相邻组织。
所有受试者均耐受手术和刺激过程，没有不适或意外不良后果的迹象。经过术后初始的稳定期后，电极阵列机械稳定。植入期间平均电极阻抗在11 - 15 kΩ之间保持稳定。视觉诱发的ERG和OCT正常，平均eEVCP阈值随时间没有显著差异。在检查的84个电极相邻组织样本中的81个中，受刺激和未受刺激组织之间没有明显的组织病理学差异。在其余三个组织样本中，有轻微的局灶性成纤维细胞和急性炎症反应。
使用脉络膜上电极阵列对视网膜进行慢性阈上电刺激引起的组织反应最小，没有不良临床或组织学发现。此外，在长达15周的刺激持续时间内，阈值和电极阻抗保持稳定。本研究证明了电荷平衡刺激电流进行脉络膜上刺激的安全性和有效性。
