Hossein Ameri

PMN-PT single crystal, high-frequency ultrasonic needle transducers for pulsed-wave Doppler application

High-frequency needle ultrasound transducers with an aperture size of 0.4 mm were fabricated using lead magnesium niobate-lead titanate (PMN-33%PT) as the active piezoelectric material. The active element was bonded to a conductive silver particle matching layer and a conductive epoxy backing through direct contact curing. An outer matching layer of parylene was formed by vapor deposition. The active element was housed within a polyimide tube and a 20-gauge needle housing. The magnitude and phase of the electrical impedance of the transducer were 47 Omega and -38deg, respectively. The measured center frequency and -6 dB fractional bandwidth of the PMN-PT needle transducer were 44 MHz and 45%, respectively. The two-way insertion loss was approximately 15 dB. In vivo high-frequency, pulsed-wave Doppler patterns of blood flow in the posterior portion and in vitro ultrasonic backscatter microscope (UBM) images of the rabbit eye were obtained with the 44-MHz needle transducer

Optical Coherence Tomography Angiography of Diabetic Retinopathy in Human Subjects

BACKGROUND AND OBJECTIVE Optical coherence tomography angiography (OCTA) is a novel, non-invasive OCT technique capable of imaging the retinal vasculature. This study aims to evaluate the retinal microvasculature in diabetic human subjects with OCTA and assess potential clinical applications. PATIENTS AND METHODS Cross-sectional study of 33 subjects with diabetic retinopathy. OCTA was performed on 3 mm × 3 mm sections using a swept-source OCTA prototype and a phase- and intensity-based contrasting algorithm. OCT angiograms were studied with corresponding clinical examination and fluorescein angiograms, when available, to assess accuracy and clinical utility. RESULTS OCTA was able to demonstrate most clinically relevant vascular changes in subjects with diabetic retinopathy, including microaneurysms, impaired vascular perfusion, some forms of intraretinal fluid, vascular loops, intraretinal microvascular abnormalities, neovascularization, and cotton-wool spots that were largely consistent with fluorescein angiography. CONCLUSION OCTA generates high-resolution angiograms that illustrate many of the clinically relevant findings in diabetic retinopathy and offers a novel complement or alternative to fluorescein angiography. Although currently an investigational technique, OCTA in combination with standard OCT imaging is at least as good as fluorescein angiography in the evaluation of the macular complications of diabetic retinopathy.

Type 3 neovascularization: evolution, association with pigment epithelial detachment, and treatment response as revealed by spectral domain optical coherence tomography.

Purpose: To demonstrate the evolution and treatment response of Type 3 neovascularization using spectral domain optical coherence tomography. Methods: We retrospectively analyzed 40 eyes treated with intravitreal anti-vascular endothelial growth factor therapy for Type 3 neovascularization over a variable follow-up period. Results: In 17 eyes, spectral domain optical coherence tomography captured the development of Type 3 neovascularization from punctate hyperreflective foci that preceded any outer retinal defect. The more mature Type 3 lesions were associated with outer retinal disruption and adjacent cystoid macular edema. In addition, 37 of 40 Type 3 lesions (93%) were associated with an underlying pigment epithelial detachment, of which 26 (70%) were drusenoid, 6 (16%) serous, and 5 (14%) mixed. Type 3 vessels appeared to leak fluid into the pigment epithelial detachment cavity, creating serous pigment epithelial detachments as large as 925 &mgr;m in maximal height. Treatment with anti-vascular endothelial growth factor agents led to prompt involution of the lesion and resorption of the intraretinal and subretinal pigment epithelium fluid after one or two injections (median = 1). Conclusion: In some eyes with age-related macular degeneration, the earliest sign of Type 3 neovascularization is punctate hyperreflective foci above the external limiting membrane. The mature Type 3 lesions and associated serous pigment epithelial detachments are highly responsive to anti-vascular endothelial growth factor therapy.

High-Density Flexible Parylene-Based Multielectrode Arrays for Retinal and Spinal Cord Stimulation

Novel flexible parylene-based high-density electrode arrays have been developed for functional electrical stimulation in retinal and spinal cord applications. These electrode arrays are microfabricated according to single-metal-layer and, most recently, dual-metal-layer processes. A new heat-molding process has been implemented to conform electrode arrays to approximate the curvature of canine retinas, and chronic implantation studies have been undertaken to study the mechanical effects of parylene-based prostheses on the retina, with excellent results to date. Electrode arrays have also been implanted and tested on the spinal cords of murine models, with the ultimate goal of facilitation of locomotion after spinal cord injury; these arrays provide a higher density and better spatial control of stimulation and recording than is typically possible using traditional fine-wire electrodes. Spinal cord stimulation typically elicited three muscle responses, an early (direct), a middle (monosynaptic), and a late (polysynaptic) response, classified based on latency after stimulation. Stimulation at different rostrocaudal levels of the cord yielded markedly different muscle responses, highlighting the need for such high-density arrays.

Flexible Parylene-based Microelectrode Technology for Intraocular Retinal Prostheses

We present the first single metal layer flexible microelectrode arrays designed for intraocular implantation that utilize parylene C as their primary structural and insulating material. These electrodes are fabricated as a key component of an intraocular retinal prosthesis comprising a radio-frequency coil for power and data transfer, a packaged high lead-count telemetry-recovery and driving application-specific integrated circuit (ASIC), and a high-density epiretinal stimulating microelectrode array for the treatment of retinal degenerative blindness in humans. Electrochemical tests have demonstrated that these thin-film platinum electrodes perform as necessary for neuronal stimulation. A novel bioconformal MEMS geometry for a complete intraocular system with capsular retaining-wings that enables all the components of the system to be implanted and retained within the lens capsule and vitreous cavity of the eye is also presented. The efficacy of this geometry when compared with a previous model without capsular retaining-wings has been verified by surgical implantation in animal models.

Toward a wide-field retinal prosthesis.

The purpose of this paper is to present a wide field electrode array that may increase the field of vision in patients implanted with a retinal prosthesis. Mobility is often impaired in patients with low vision, particularly in those with peripheral visual loss. Studies on low vision patients as well as simulation studies on normally sighted individuals have indicated a strong correlation between the visual field and mobility. In addition, it has been shown that an increased visual field is associated with a significant improvement in visual acuity and object discrimination. Current electrode arrays implanted in animals or human vary in size; however, the retinal area covered by the electrodes has a maximum projected visual field of about 10 degrees. We have designed wide field electrode arrays that could potentially provide a visual field of 34 degrees, which may significantly improve the mobility. Tests performed on a mechanical eye model showed that it was possible to fix 10 mm wide flexible polyimide dummy electrode arrays onto the retina using a single retinal tack. They also showed that the arrays could conform to the inner curvature of the eye. Surgeries on an enucleated porcine eye model demonstrated feasibility of implantation of 10 mm wide arrays through a 5 mm eye wall incision.

Natural course of experimental retinal vein occlusion in rabbit; arterial occlusion following venous photothrombosis.

BackgroundRetinal vein occlusion (RVO) is the second leading cause of vascular eye disease. Currently there is no definite treatment for this condition. Animal models could be potentially helpful in developing new treatments; however, it is essential to understand the differences these models may have with human RVO. The aim of our study was to examine the course of experimentally created retinal vein occlusion (RVO) in rabbits.MethodsTwenty-nine pigmented rabbits were included in the study. RVO was created in all using an argon green laser following intravenous injection of Rose Bengal. A laser was applied to all major veins at the optic disc margin to mimic central retinal vein occlusion. Animals were followed-up for a maximum of 2 months.ResultsImmediately following laser application, blood flow ceased or the flow was extremely slow in the retinal veins in all cases. At day 2 post laser, 86% showed significant retinal hemorrhages. On FA, no retinal blood flow was observed in the eye (neither arteries nor veins) in the majority of rabbits. Between weeks 1 and 3, laser sites reopened and partial or complete revascularization of both retinal arteries and veins occurred; however, the vascular pattern was abnormal.ConclusionsRVO in rabbits has a different course than in human and it can be classified into three stages. At stage 1 (the first few days after laser photothrombosis), there is a retrograde propagation of the blood clot in the retinal veins that extends to the retinal arteries and choriocapillaries. As a result, there is no retinal blood flow at this stage in most cases. At stage 2 (between weeks 1 and 3), partial or complete revascularization occurs but the vessels have an abnormal pattern. At stage 3 (after week 3) no significant change takes place.

TWEAK/Fn14 Pathway Is a Novel Mediator of Retinal Neovascularization

PURPOSE Retinal neovascularization (NV) is a major cause of vision loss in ischemia-induced retinopathy. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor inducible-14 (Fn14), have been implicated in angiogenesis, but their role in retinal diseases is unknown. The goal of this study was to investigate the role of TWEAK/Fn14 pathway in retinal NV. METHODS Studies were performed in a mouse model of oxygen-induced retinopathy (OIR) and in primary human retinal microvascular endothelial cells (HRMECs). Hyperoxia treatment was initiated on postnatal day (P)14. Immunohistochemistry and quantitative PCR (qPCR) were used to assess retinal vascular changes in relation to expression of Fn14 and TWEAK. RESULTS Fibroblast growth factor-inducible 14 mRNA was prominently increased from P13 to P17 in OIR retinas, whereas TWEAK level was slightly decreased. These alterations were normalized by hyperoxia treatment and were more striking in isolated retinal vessels. There was a discernible shift in the immunoreactivity of Fn14 and TWEAK from the neuronal layers in the healthy retina to the neovascular tufts in that of OIR. Blockade of TWEAK/Fn14 significantly prevented retinal NV while slightly accelerated revascularization. In contrast, activation of Fn14 positively regulated survival pathways in the B-cell lymphoma-2 (Bcl2) family and robustly enhanced HRMEC survival. Furthermore, gene analysis revealed the regulatory region of Fn14 gene contains several conserved hypoxia inducible factor (HIF)-1α binding sites. Overexpression of HIF-1α prominently induced Fn14 expression in HRMECs. CONCLUSIONS We found that the TNF-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor inducible-14 (Fn14) pathway is involved in the development of pathologic retinal neovascularization. Hypoxia inducible factor-1α is likely implicated in the upregulation of Fn14.

Vitreal oxygenation in retinal ischemia reperfusion.

PURPOSE To study the feasibility of anterior vitreal oxygenation for the treatment of acute retinal ischemia. METHODS Twenty rabbits were randomized into an oxygenation group, a sham treatment group, and a no treatment group. Baseline electroretinography (ERG) and preretinal oxygen (Po(2)) measurements were obtained 3 to 5 days before surgery. Intraocular pressure was raised to 100 mm Hg for 90 minutes and then normalized. The oxygenation group underwent vitreal oxygenation for 30 minutes using intravitreal electrodes. The sham treatment group received inactive electrodes for 30 minutes while there was no intervention for the no treatment group. Preretinal Po(2) in the posterior vitreous was measured 30 minutes after intervention or 30 minutes after reperfusion (no treatment group) and on postoperative days (d) 3, 6, 9, and 12. On d14, rabbits underwent ERG and were euthanatized. RESULTS Mean final (d12) Po(2) was 10.64 ± 0.77 mm Hg for the oxygenation group, 2.14 ± 0.61 mm Hg for the sham group, and 1.98 ± 0.63 mm Hg for the no treatment group. On ERG, scotopic b-wave amplitude was significantly preserved in the oxygenation group compared with the other two groups. Superoxide dismutase assay showed higher activity in the operated eyes than in the nonoperated control eyes in the sham treatment group and no treatment group only. Histopathology showed preservation of retinal architecture and choroidal vasculature in the oxygenation group, whereas the sham-treated and nontreated groups showed retinal thinning and choroidal atrophy. CONCLUSIONS In severe total ocular ischemia, anterior vitreal oxygenation supplies enough oxygen to penetrate the retinal thickness, resulting in rescue of the RPE/choriocapillaris that continues to perfuse, hence sparing the retinal tissue from damage.

Intravitreal and subretinal injection of tissue plasminogen activator (tPA) in the treatment of experimentally created retinal vein occlusion in rabbits.

Purpose: To evaluate the effectiveness of intravitreal or subretinal injection of tPA in the treatment of experimentally created retinal vein occlusion (RVO) in rabbits. Methods: Fifteen rabbits were included in this study. RVO was created in all using an argon green laser following intravenous injection of rose Bengal. Follow-up examinations included color fundus photography, fundus fluorescein angiography, and optical coherence tomography. Following examinations at day 2, animals were divided into three groups: six rabbits were kept as control, four rabbits received subretinal injection of tPA, and five rabbits received intravitreal tPA. Results: Of 14 eyes that had capillary drop out at day 2 following creation of RVO, 12 remained the same at week 3. Only one eye in the control group and one eye in the subretinal group developed complete reperfusion of capillaries. Although there was more revascularization in all groups at week 3, there was not a significant difference in the amount of revascularization between the control group and those animals receiving subretinal or intravitreal tPA. Conclusion: Intravitreal or subretinal injection of tPA 2 days following vein occlusion did not improve reperfusion of retinal vessels in experimentally created RVO in rabbits when compared to control group.