Bio

Academic Appointments


Administrative Appointments


  • Director of Research, Department of Ophthalmology (2003 - Present)
  • Faculty Member, Hansen Experimental Physics Laboratory (2000 - Present)

Honors & Awards


  • R&D 100 award for the OCT-Guided Femtosecond Laser for Cataract Surgery, with OptiMedica Corp., R&D 100 (2012)
  • Medical Design Excellence Award for development of the Pulsed Electron Avalanche Knife (PEAK), Medical Design Excellence Awards; Canon Communications (February 2009)
  • R&D 100 Award for the Pattern Scanning Laser Photocoagulator (PASCAL). with OptiMedica Inc., R&D Journal (July 1, 2007)
  • Pascal Rol award for the best paper on Ophthalmic Technologies Conference (SPIE, Photonics West), SPIE (January, 2004)
  • Winner of the Collegiate Inventors Competition, US National Inventors Hall of Fame (2001)
  • First Place in Instrumentation and Devices: Plasma-based Cutting Instrument for Vitreoret. Surgery, US Vitreous Society (2000)
  • Dr. Shlomiuk award for outstanding Ph.D. Research., The Hebrew University of Jerusalem, Israel (1995)
  • Wolf Foundation scholarship for outstanding doctoral students., The Wolf Foundation (1992)
  • Prof. Rabau award for application of the ArF excimer laser to In Vitro Fertilization., Israel Society for Fertility Research (1991)

Professional Education


  • Postdoctoral, Stanford University, Free Electron Laser Center (Multiphoton Imaging with Ultrafast Lasers) (1997)
  • PhD, Hebrew University of Jerusalem, Israel, Applied Physics (1995)
  • MSc, Yerevan State University, USSR, Physics (1984)

Research & Scholarship

Current Research and Scholarly Interests


Mechanisms of interaction of electric field and light with biological cells and tissues and their applications to diagnostics, therapeutics and prosthetics.

Specific fields of interest include:
Minimally-invasive optical and electrical therapeutic technologies;
Interface of electronics with neural cells and tissues;
Microsurgical and cell-surgical technologies;
Optical imaging and spectroscopy;
Electronic control of cells and tissues.

Current research projects include:

1) Laser-Tissue Interactions: Non-damaging pulsed hyperthermia of cells and tissues; Selective and image-guided ocular laser therapies; Multiphoton interactions and their applications to laser surgery.

2) Electronic Retinal Prosthesis:
Photovoltaic system for restoration of sight to patients blinded by retinal degenerative diseases.

3) Electronic Control of Vasculature:
Reversible vasoconstriction induced by electrical stimulation: mechanisms and applications.

4) Retinal Plasticity:
Migration and rewiring of retinal neurons in response to selective ablation or separation of retinal layers: applications to models of retinal degeneration and therapy.

Teaching

2013-14 Courses


Postdoctoral Advisees


Publications

Journal Articles


  • Cortical responses elicited by photovoltaic subretinal prostheses exhibit similarities to visually evoked potentials. Nature communications Mandel, Y., Goetz, G., Lavinsky, D., Huie, P., Mathieson, K., Wang, L., Kamins, T., Galambos, L., Manivanh, R., Harris, J., Palanker, D. 2013; 4: 1980-?

    Abstract

    We have previously developed a wireless photovoltaic retinal prosthesis, in which camera-captured images are projected onto the retina using pulsed near-IR light. Each pixel in the subretinal implant directly converts pulsed light into local electric current to stimulate the nearby inner retinal neurons. Here we report that implants having pixel sizes of 280, 140 and 70??m implanted in the subretinal space in rats with normal and degenerate retina elicit robust cortical responses upon stimulation with pulsed near-IR light. Implant-induced eVEP has shorter latency than visible light-induced VEP, its amplitude increases with peak irradiance and pulse duration, and decreases with frequency in the range of 2-20?Hz, similar to the visible light response. Modular design of the arrays allows scalability to a large number of pixels, and combined with the ease of implantation, offers a promising approach to restoration of sight in patients blinded by retinal degenerative diseases.

    View details for DOI 10.1038/ncomms2980

    View details for PubMedID 23778557

  • Restoration of retinal morphology and residual scarring after photocoagulation. Acta ophthalmologica Lavinsky, D., Cardillo, J. A., Mandel, Y., Huie, P., Melo, L. A., Farah, M. E., Belfort, R., Palanker, D. 2013; 91 (4): e315-23

    Abstract

    Purpose:? To study healing of retinal laser lesions in patients undergoing PRP using SD-OCT. Methods:? Moderate, light and barely visible retinal burns were produced in patients with proliferative diabetic retinopathy scheduled for PRP using 100-, 20- and 10-ms pulses of 532-nm laser, with retinal spot sizes of 100, 200 and 400??m. Lesions were measured with OCT at 1?hr, 1?week, 1, 2, 4, 6, 9 and 12?months. OCT imaging was correlated with histology in a separate study in rabbits. Results:? Lesions produced by the standard 100-ms exposures exhibited steady scarring, with the damage zone stabilized after 2?months. For 400- and 200-?m spots and 100-ms pulses, the residual scar area at 12?months was approximately 50% of the initial lesion size for moderate, light and barely visible burns. In contrast, lesions produced by shorter exposures demonstrated enhanced restoration of the photoreceptor layer, especially in smaller burns. With 20-ms pulses, the damage zone decreased to 32%, 24% and 20% for moderate, light and barely visible burns of 400??m, respectively, and down to 12% for barely visible burns of 200??m. In the 100-?m spots, the residual scar area of the moderate 100-ms burns was 41% of the initial lesion, while barely visible 10-ms burns contracted to 6% of the initial size. Histological observations in rabbits were useful for proper interpretation of the damage zone boundaries in OCT. Conclusions:? Traditional photocoagulation parameters (400??m, 100?ms and moderate burn) result in a stable scar similar in size to the beam diameter. Restoration of the damaged photoreceptor layer in lighter lesions produced by shorter pulses should allow reducing the common side-effects of photocoagulation such as scotomata and scarring.

    View details for DOI 10.1111/aos.12045

    View details for PubMedID 23557390

  • Optical patient interface in femtosecond laser-assisted cataract surgery: Contact corneal applanation versus liquid immersion JOURNAL OF CATARACT AND REFRACTIVE SURGERY Talamo, J. H., Gooding, P., Angeley, D., Culbertson, W. W., Schuele, G., Andersen, D., Marcellino, G., Essock-Burns, E., Batlle, J., Feliz, R., Friedman, N. J., Palanker, D. 2013; 39 (4): 501-510

    Abstract

    To compare 2 optical patient interface designs used for femtosecond laser-assisted cataract surgery.Optimedica Corp., Santa Clara, California, USA, and Centro Laser, Santo Domingo, Dominican Republic.Experimental and clinical studies.Laser capsulotomy was performed during cataract surgery with a curved contact lens interface (CCL) or a liquid optical immersion interface (LOI). The presence of corneal folds, incomplete capsulotomy, subconjunctival hemorrhage, and eye movement during laser treatment were analyzed using video and optical coherence tomography. The induced rise of intraocular pressure (IOP) was measured in porcine and cadaver eyes.Corneal folds were identified in 70% of the CCL cohort; 63% of these had areas of incomplete capsulotomies beneath the corneal folds. No corneal folds or incomplete capsulotomies were identified in the LOI cohort. The mean eye movement during capsulotomy creation (1.5 sec) was 50 ?m with a CCL and 20 ?m with an LOI. The LOI cohort had 36% less subconjunctival hemorrhage than the CCL cohort. During suction, the mean IOP rise was 32.4 mm Hg ± 3.4 (SD) in the CCL group and 17.7 ± 2.1 mm Hg in the LOI group.Curved contact interfaces create corneal folds that can lead to incomplete capsulotomy during laser cataract surgery. A liquid interface eliminated corneal folds, improved globe stability, reduced subconjunctival hemorrhage, and lowered IOP rise.

    View details for DOI 10.1016/j.jcrs.2013.01.021

    View details for Web of Science ID 000317871900004

    View details for PubMedID 23434216

  • Modulation of Transgene Expression in Retinal Gene Therapy by Selective Laser Treatment INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Lavinsky, D., Chalberg, T. W., Mandel, Y., Huie, P., Dalal, R., Marmor, M., Palanker, D. 2013; 54 (3): 1873-1880

    Abstract

    To develop a method for modulation of transgene expression in retinal pigment epithelium (RPE) using scanning laser that spares neurosensory retina.Fifteen pigmented rabbits received subretinal injection of recombinant adeno-associated virus (rAAV-2) encoding green fluorescent protein (GFP). GFP expression was measured using confocal scanning laser ophthalmoscopy (cSLO) fluorescence imaging and immunohistochemistry. To reduce the total expression in RPE by half, 50% of the transfected RPE cells were selectively destroyed by microsecond exposures to scanning laser with 50% pattern density. The selectivity of RPE destruction and its migration and proliferation were monitored using fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and light, transmission, and scanning electron microscopy. 5-Bromo-2'-dioxyuridine (BrdU) assay was performed to evaluate proliferation of RPE cells.RPE cells were selectively destroyed by the line scanning laser with 15 ?s exposures, without damage to the photoreceptors or Bruch's membrane. RPE cells started migrating after the first day, and in 1 week there was complete restoration of RPE monolayer. Selective laser treatment decreased the GFP fluorescence by 54% as compared to control areas; this was further decreased by an additional 48% following a second treatment 1 month later. BrdU assay demonstrated proliferation in approximately half of the RPE cells in treatment areas.Microsecond exposures produced by scanning laser destroyed RPE cells selectively, without damage to neural retina. Continuity of RPE layer is restored within days by migration and proliferation, but transgene not integrated into the nucleus is not replicated. Therefore, gene expression can be modulated in a precise manner by controlling the laser pattern density and further adjusted using repeated applications.

    View details for DOI 10.1167/iovs.12-10933

    View details for Web of Science ID 000316942400040

    View details for PubMedID 23422827

  • EFFECT OF INTRAVITREAL TRIAMCINOLONE ACETONIDE ON HEALING OF RETINAL PHOTOCOAGULATION LESIONS RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Nomoto, H., Lavinsky, D., Paulus, Y. M., Leung, L., Dalal, R., Blumenkranz, M. S., Palanker, D. 2013; 33 (1): 63-70

    Abstract

    To evaluate the effect of intravitreal triamcinolone acetonide (TA) on healing of retinal photocoagulation lesions using drug and laser dosing typically employed in clinical practice.Laser burns with a 267-?m retinal beam size at 532-nm wavelength were applied to 40 eyes of Dutch belted rabbits. Barely visible to intense lesions were produced with pulses of 5, 10, 20, and 50 milliseconds and power of 175 mW. Eyes received intravitreal injections of either 2 mg TA/50 ?L or balanced salt solution administered either 1 week before or immediately after laser treatment. Lesion grades were assessed acutely ophthalmoscopically and by a masked observer histologically at 1, 3, 7, 30, and 60 days.Both TA groups demonstrated significant reduction in retinal thickness throughout follow-up compared with balanced salt solution groups (P < 0.001). The width of the lesions at 1 day after injection was not significantly different between groups. However, by 7 days, the lesions in balanced salt solution groups contracted much more than in the TA groups, especially the more intense burns, and this difference persisted to 2 months. The healing rate of the barely visible burns was not significantly affected by TA compared with the balanced salt solution control eyes.Triamcinolone acetonide injection previously or concurrently with photocoagulation significantly decreases laser-induced edema but interferes with lesions healing, thereby leaving wider residual scarring, especially persistent in more intense burns.

    View details for DOI 10.1097/IAE.0b013e318261e34b

    View details for Web of Science ID 000313422500008

    View details for PubMedID 23026846

  • Femtosecond plasma mediated laser ablation has advantages over mechanical osteotomy of cranial bone LASERS IN SURGERY AND MEDICINE Lo, D. D., Mackanos, M. A., Chung, M. T., Hyun, J. S., Montoro, D. T., Grova, M., Liu, C., Wang, J., Palanker, D., Connolly, A. J., Longaker, M. T., Contag, C. H., Wan, D. C. 2012; 44 (10): 805-814

    Abstract

    Although mechanical osteotomies are frequently made on the craniofacial skeleton, collateral thermal, and mechanical trauma to adjacent bone tissue causes cell death and may delay healing. The present study evaluated the use of plasma-mediated laser ablation using a femtosecond laser to circumvent thermal damage and improve bone regeneration.Critical-size circular calvarial defects were created with a trephine drill bit or with a Ti:Sapphire femtosecond pulsed laser. Healing was followed using micro-CT scans for 8 weeks. Calvaria were also harvested at various time points for histological analysis. Finally, scanning electron microscopy was used to analyze the microstructure of bone tissue treated with the Ti:Sapphire laser, and compared to that treated with the trephine bur.Laser-created defects healed significantly faster than those created mechanically at 2, 4, and 6 weeks post-surgery. However, at 8 weeks post-surgery, there was no significant difference. In the drill osteotomy treatment group, empty osteocyte lacunae were seen to extend 699?±?27?µm away from the edge of the defect. In marked contrast, empty osteocyte lacunae were seen to extend only 182?±?22?µm away from the edge of the laser-created craters. Significantly less ossification and formation of irregular woven bone was noted on histological analysis for drill defects.We demonstrate accelerated bone healing after femtosecond laser ablation in a calvarial defect model compared to traditional mechanical drilling techniques. Improved rates of early regeneration make plasma-mediated ablation of the craniofacial skeleton advantageous for applications to osteotomy.

    View details for DOI 10.1002/lsm.22098

    View details for Web of Science ID 000312941600004

    View details for PubMedID 23184427

  • Retinal safety of near-infrared lasers in cataract surgery JOURNAL OF BIOMEDICAL OPTICS Wang, J., Sramek, C., Paulus, Y. M., Lavinsky, D., Schuele, G., Anderson, D., Dewey, D., Palanker, D. 2012; 17 (9)

    Abstract

    Femtosecond lasers have added unprecedented precision and reproducibility to cataract surgery. However, retinal safety limits for the near-infrared lasers employed in surgery are not well quantified. We determined retinal injury thresholds for scanning patterns while considering the effects of reduced blood perfusion from rising intraocular pressure and retinal protection from light scattering on bubbles and tissue fragments produced by laser cutting. We measured retinal damage thresholds of a stationary, 1030-nm, continuous-wave laser with 2.6-mm retinal spot size for 10- and 100-s exposures in rabbits to be 1.35 W (1.26 to 1.42) and 0.78 W (0.73 to 0.83), respectively, and 1.08 W (0.96 to 1.11) and 0.36 W (0.33 to 0.41) when retinal perfusion is blocked. These thresholds were input into a computational model of ocular heating to calculate damage threshold temperatures. By requiring the tissue temperature to remain below the damage threshold temperatures determined in stationary beam experiments, one can calculate conservative damage thresholds for cataract surgery patterns. Light scattering on microbubbles and tissue fragments decreased the transmitted power by 88% within a 12 deg angle, adding a significant margin for retinal safety. These results can be used for assessment of the maximum permissible exposure during laser cataract surgery under various assumptions of blood perfusion, treatment duration, and scanning patterns.

    View details for DOI 10.1117/1.JBO.17.9.095001

    View details for Web of Science ID 000309905700007

    View details for PubMedID 23085903

  • Photovoltaic retinal prosthesis: implant fabrication and performance JOURNAL OF NEURAL ENGINEERING Wang, L., Mathieson, K., Kamins, T. I., Loudin, J. D., Galambos, L., Goetz, G., Sher, A., Mandel, Y., Huie, P., Lavinsky, D., Harris, J. S., Palanker, D. V. 2012; 9 (4)

    Abstract

    The objective of this work is to develop and test a photovoltaic retinal prosthesis for restoring sight to patients blinded by degenerative retinal diseases. A silicon photodiode array for subretinal stimulation has been fabricated by a silicon-integrated-circuit/MEMS process. Each pixel in the two-dimensional array contains three series-connected photodiodes, which photovoltaically convert pulsed near-infrared light into bi-phasic current to stimulate nearby retinal neurons without wired power connections. The device thickness is chosen to be 30 µm to absorb a significant portion of light while still being thin enough for subretinal implantation. Active and return electrodes confine current near each pixel and are sputter coated with iridium oxide to enhance charge injection levels and provide a stable neural interface. Pixels are separated by 5 µm wide trenches to electrically isolate them and to allow nutrient diffusion through the device. Three sizes of pixels (280, 140 and 70 µm) with active electrodes of 80, 40 and 20 µm diameter were fabricated. The turn-on voltages of the one-diode, two-series-connected diode and three-series-connected diode structures are approximately 0.6, 1.2 and 1.8 V, respectively. The measured photo-responsivity per diode at 880 nm wavelength is ?0.36 A W(-1), at zero voltage bias and scales with the exposed silicon area. For all three pixel sizes, the reverse-bias dark current is sufficiently low (<100 pA) for our application. Pixels of all three sizes reliably elicit retinal responses at safe near-infrared light irradiances, with good acceptance of the photodiode array in the subretinal space. The fabricated device delivers efficient retinal stimulation at safe near-infrared light irradiances without any wired power connections, which greatly simplifies the implantation procedure. Presence of the return electrodes in each pixel helps to localize the current, and thereby improves resolution.

    View details for DOI 10.1088/1741-2560/9/4/046014

    View details for Web of Science ID 000306759600027

    View details for PubMedID 22791690

  • Panretinal Photocoagulation for Proliferative Diabetic Retinopathy AMERICAN JOURNAL OF OPHTHALMOLOGY Palanker, D., Blumenkranz, M. S. 2012; 153 (4): 780-781

    View details for Web of Science ID 000302387100035

    View details for PubMedID 22445637

  • LONG-TERM SAFETY, HIGH-RESOLUTION IMAGING, AND TISSUE TEMPERATURE MODELING OF SUBVISIBLE DIODE MICROPULSE PHOTOCOAGULATION FOR RETINOVASCULAR MACULAR EDEMA RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Luttrull, J. K., Sramek, C., Palanker, D., Spink, C. J., Musch, D. C. 2012; 32 (2): 375-386

    Abstract

    To determine the long-term safety of high-density subvisible diode micropulse photocoagulation (810 nm), compare the clinical findings with computational modeling of tissue hyperthermia and to report results for a subset of eyes treated for diabetic macular edema (ME) documented pre- and postoperatively by spectral-domain optical coherence tomography.All eyes treated for ME from diabetic retinopathy (diabetic ME) and branch retinal vein occlusion between April 2000 and January 2010 were reviewed for subvisible diode micropulse laser-induced retinal damage. Therapeutic outcomes were reviewed for a subgroup treated for diabetic ME with pre- and postoperative spectral-domain optical coherence tomography. Laser-induced retinal thermal effects were modeled computationally using Arrhenius formalism.A total of 252 eyes (212 diabetic ME, 40 branch retinal vein occlusion) of 181 patients qualified. None of the 168 eyes treated at irradiance <350 W/cm2 and 7 of 84 eyes at ? 590 W/cm2 had retinal damage (P = 0.0001) (follow-up 3-120 months, median, 47). Sixty-two eyes of 48 patients treated for diabetic ME with pre- and postoperative spectral-domain optical coherence tomography with median 12 months follow-up had no retinal injury by infrared, red-free, or fundus autofluorescence photos; fluorescein angiography or indocyanine green angiography; or spectral-domain optical coherence tomography. Central foveal thickness (P = 0.04) and maximum macular thickness decreased (P < 0.0001). Modeling of retinal hyperthermia demonstrates that the sublethal clinical regimen corresponds to Arrhenius integral >0.05, while damage is likely to occur if it exceeds 1.Subvisible diode micropulse can effectively treat retinovascular ME without laser-induced retinal damage, consistent with Arrhenius modeling of pulsed hyperthermia.

    View details for DOI 10.1097/IAE.0b013e3182206f6c

    View details for Web of Science ID 000300182700022

    View details for PubMedID 21971077

  • Photovoltaic Retinal Prosthesis with High Pixel Density. Nature photonics Mathieson, K., Loudin, J., Goetz, G., Huie, P., Wang, L., Kamins, T. I., Galambos, L., Smith, R., Harris, J. S., Sher, A., Palanker, D. 2012; 6 (6): 391-397

    Abstract

    Retinal degenerative diseases lead to blindness due to loss of the "image capturing" photoreceptors, while neurons in the "image processing" inner retinal layers are relatively well preserved. Electronic retinal prostheses seek to restore sight by electrically stimulating surviving neurons. Most implants are powered through inductive coils, requiring complex surgical methods to implant the coil-decoder-cable-array systems, which deliver energy to stimulating electrodes via intraocular cables. We present a photovoltaic subretinal prosthesis, in which silicon photodiodes in each pixel receive power and data directly through pulsed near-infrared illumination and electrically stimulate neurons. Stimulation was produced in normal and degenerate rat retinas, with pulse durations from 0.5 to 4 ms, and threshold peak irradiances from 0.2 to 10 mW/mm(2), two orders of magnitude below the ocular safety limit. Neural responses were elicited by illuminating a single 70 ?m bipolar pixel, demonstrating the possibility of a fully-integrated photovoltaic retinal prosthesis with high pixel density.

    View details for PubMedID 23049619

  • Fifty Years of Ophthalmic Laser Therapy ARCHIVES OF OPHTHALMOLOGY Palanker, D. V., Blumenkranz, M. S., Marmor, M. F. 2011; 129 (12): 1613-1619

    View details for Web of Science ID 000297995000016

    View details for PubMedID 22159684

  • THE IMPACT OF PULSE DURATION AND BURN GRADE ON SIZE OF RETINAL PHOTOCOAGULATION LESION Implications for Pattern Density RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Palanker, D., Lavinsky, D., Blumenkranz, M. S., Marcellino, G. 2011; 31 (8): 1664-1669

    Abstract

    Shorter pulses used in pattern scanning photocoagulation (10-20 milliseconds [ms]) tend to produce lighter and smaller lesions than the Early Treatment Diabetic Retinopathy Study standard 100-ms exposures. Smaller lesions result in fewer complications but may potentially reduce clinical efficacy. It is worthwhile to reevaluate existing standards for the number and size of lesions needed.The width of the coagulated zone in patients undergoing retinal photocoagulation was measured using optical coherence tomography. Lesions of "moderate," "light," and "barely visible" clinical grades were compared for 100, 200, and 400 ?m spot sizes and pulse durations of 20 ms and 100 ms.To maintain the same total area as in 1,000 standard burns (100 ms, moderate) with a 400-?m beam, a larger number of 20-ms lesions are required: 1,464, 1,979, and 3,520 for moderate, light, and barely visible grades, respectively. Because of stronger relative effect of heat diffusion with a smaller beam, with 200 ?m this ratio increases: 1,932, 2,783, and 5,017 lesions of 20 ms with moderate, light, and barely visible grades correspond to the area of 1,000 standard burns.A simple formula is derived for calculation of the required spot spacing in the laser pattern for panretinal photocoagulation with various laser parameters to maintain the same total coagulated area.

    View details for Web of Science ID 000294456100027

    View details for PubMedID 21642898

  • Femtosecond laser capsulotomy JOURNAL OF CATARACT AND REFRACTIVE SURGERY Friedman, N. J., Palanker, D. V., Schuele, G., Andersen, D., Marcellino, G., Seibel, B. S., Battle, J., Feliz, R., Talamo, J. H., Blumenkranz, M. S., Culbertson, W. W. 2011; 37 (7): 1189-1198

    Abstract

    To evaluate a femtosecond laser system to create the capsulotomy.Porcine and cadaver eye studies were performed at OptiMedica Corp., Santa Clara, California, USA; the human trial was performed at the Centro Laser, Santo Domingo, Dominican Republic.Experimental and clinical study.Capsulotomies performed by an optical coherence tomography-guided femtosecond laser were evaluated in porcine and human cadaver eyes. Subsequently, the procedure was performed in 39 patients as part of a prospective randomized study of femtosecond laser-assisted cataract surgery. The accuracy of the capsulotomy size, shape, and centration were quantified and capsulotomy strength was assessed in the porcine eyes.Laser-created capsulotomies were significantly more precise in size and shape than manually created capsulorhexes. In the patient eyes, the deviation from the intended diameter of the resected capsule disk was 29 ?m ± 26 (SD) for the laser technique and 337 ± 258 ?m for the manual technique. The mean deviation from circularity was 6% and 20%, respectively. The center of the laser capsulotomies was within 77 ± 47 ?m of the intended position. All capsulotomies were complete, with no radial nicks or tears. The strength of laser capsulotomies (porcine subgroup) decreased with increasing pulse energy: 152 ± 21 mN for 3 ?J, 121 ± 16 mN for 6 ?J, and 113 ± 23 mN for 10 ?J. The strength of the manual capsulorhexes was 65 ± 21 mN.The femtosecond laser produced capsulotomies that were more precise, accurate, reproducible, and stronger than those created with the conventional manual technique.

    View details for DOI 10.1016/j.jcrs.2011.04.022

    View details for Web of Science ID 000292783100004

    View details for PubMedID 21700099

  • Non-damaging Retinal Phototherapy: Dynamic Range of Heat Shock Protein Expression INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Sramek, C., Mackanos, M., Spitler, R., Leung, L., Nomoto, H., Contag, C. H., Palanker, D. 2011; 52 (3): 1780-1787

    Abstract

    Subthreshold retinal phototherapy demonstrated clinical efficacy for the treatment of diabetic macular edema without visible signs of retinal damage. To assess the range of cellular responses to sublethal hyperthermia, expression of the gene encoding a 70 kDa heat shock protein (HSP70) was evaluated after laser irradiation using a transgenic reporter mouse.One hundred millisecond, 532 nm laser exposures with 400 ?m beam diameter were applied to the retina surrounding the optic nerve in 32 mice. Transcription from the HSP70 promoter was assessed relative to the control eye using a bioluminescence assay at 7 hours after laser application. The retinal pigmented epithelium (RPE) viability threshold was determined with a fluorescence assay. A computational model was developed to estimate temperature and the extent of cell damage.A significant increase in HSP70 transcription was found at exposures over 20 mW, half the threshold power for RPE cell death. Computational modeling estimated peak temperature T = 49°C at HSP70 expression threshold. At RPE viability threshold, T = 57°C. Similar temperatures and damage indices were calculated for clinical subvisible retinal treatment parameters.Beneficial effects of laser therapy have been previously shown to extend beyond those resulting from destruction of tissue. One hundred millisecond laser exposures at approximately half the threshold power of RPE damage induced transcription of HSP70, an indication of cellular response to sublethal thermal stress. A computational model of retinal hyperthermia can guide further optimization of laser parameters for nondamaging phototherapy.

    View details for DOI 10.1167/iovs.10-5917

    View details for Web of Science ID 000288965300070

    View details for PubMedID 21087969

  • SELECTIVE RETINAL THERAPY WITH MICROSECOND EXPOSURES USING A CONTINUOUS LINE SCANNING LASER RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Paulus, Y. M., Jain, A., Nomoto, H., Sramek, C., Gariano, R. F., Andersen, D., Schuele, G., Leung, L., Leng, T., Palanker, D. 2011; 31 (2): 380-388

    Abstract

    To evaluate the safety, selectivity, and healing of retinal lesions created using a continuous line scanning laser.A 532-nm Nd:YAG laser (PASCAL) with retinal beam diameters of 40 ?m and 66 ?m was applied to 60 eyes of 30 Dutch-belted rabbits. Retinal exposure duration varied from 15 ?s to 60 ?s. Lesions were acutely assessed by ophthalmoscopy and fluorescein angiography. Retinal pigment epithelial (RPE) flatmounts were evaluated with live-dead fluorescent assay. Histological analysis was performed at 7 time points from 1 hour to 2 months.The ratios of the threshold of rupture and of ophthalmoscopic visibility to fluorescein angiography visibility (measures of safety and selectivity) increased with decreasing duration and beam diameter. Fluorescein angiography and live-dead fluorescent assay yielded similar thresholds of RPE damage. Above the ophthalmoscopic visibility threshold, histology showed focal RPE damage and photoreceptor loss at 1 day, without inner retinal effects. By 1 week, photoreceptor and RPE continuity was restored. By 1 month, photoreceptors appeared normal.: Retinal therapy with a fast scanning continuous laser achieves selective targeting of the RPE and, at higher power, of the photoreceptors without permanent scarring or inner retinal damage. Continuous scanning laser can treat large retinal areas within standard eye fixation time.

    View details for DOI 10.1097/IAE.0b013e3181e76da6

    View details for Web of Science ID 000286586500024

    View details for PubMedID 20930656

  • Improving the therapeutic window of retinal photocoagulation by spatial and temporal modulation of the laser beam JOURNAL OF BIOMEDICAL OPTICS Sramek, C., Leung, L., Leng, T., Brown, J., Paulus, Y. M., Schuele, G., Palanker, D. 2011; 16 (2)

    Abstract

    Decreasing the pulse duration helps confine damage, shorten treatment time, and minimize pain during retinal photocoagulation. However, the safe therapeutic window (TW), the ratio of threshold powers for thermomechanical rupture of Bruch's membrane and mild coagulation, also decreases with shorter exposures. Two potential approaches toward increasing TW are investigated: (a) decreasing the central irradiance of the laser beam and (b) temporally modulating the pulse. An annular beam with adjustable central irradiance was created by coupling a 532-nm laser into a 200-?m core multimode optical fiber at a 4-7 deg angle to normal incidence. Pulse shapes were optimized using a computational model, and a waveform generator was used to drive a PASCAL photocoagulator (532 nm), producing modulated laser pulses. Acute thresholds for mild coagulation and rupture were measured in Dutch-Belted rabbit in vivo with an annular beam (154-163 ?m retinal diameter) and modulated pulse (132 ?m, uniform irradiance "flat-top" beam) with 2-50 ms pulse durations. Thresholds with conventional constant-power pulse and a flat-top beam were also determined. Both annular beam and modulated pulse provided a 28% increase in TW at 10-ms duration, affording the same TW as 20-ms pulses with conventional parameters.

    View details for DOI 10.1117/1.3542045

    View details for Web of Science ID 000288939200056

    View details for PubMedID 21361711

  • New Horizons in Retinal Laser Treatment: Sublethal Laser Therapy. Retinal Physician Y. M. Paulus, C. Sramek, M.S. Blumenkranz, D. Palanker 2011
  • Impact of Pulse Duration and Burn Grade on Size of Retinal Photocoagulation Lesion: Implications for Pattern Density. RETINA D. Palanker, D. Lavinsky, M.S. Blumenkranz, G. Marcellino. 2011
  • Optical breakdown in transparent media with adjustable axial length and location OPTICS EXPRESS Toytman, I., Simanovski, D., Palanker, D. 2010; 18 (24): 24688-24698

    Abstract

    We demonstrate a highly elongated (aspect ratio over 500:1) optical breakdown in water produced by a single pulse of a picosecond laser focused with a combination of an axicon and a lens. Locations of the proximal and distal ends of the breakdown region can be adjusted by modifying radial intensity distribution of the incident beam with an amplitude mask. Using Fresnel diffraction theory we derive a transmission profile of the amplitude mask to create a uniform axial intensity distribution in the breakdown zone. Experimentally observed dynamics of the bubbles obtained with the designed mask is in agreement with the theoretical model. A system producing an adjustable cylindrical breakdown can be applied to fast linear or planar dissection of transparent materials. It might be useful for ophthalmic surgical applications including cataract surgery and crystalline lens softening.

    View details for Web of Science ID 000285586800048

    View details for PubMedID 21164815

  • Femtosecond Laser-Assisted Cataract Surgery with Integrated Optical Coherence Tomography SCIENCE TRANSLATIONAL MEDICINE Palanker, D. V., Blumenkranz, M. S., Andersen, D., Wiltberger, M., Marcellino, G., Gooding, P., Angeley, D., Schuele, G., Woodley, B., Simoneau, M., Friedman, N. J., Seibel, B., Batlle, J., Feliz, R., Talamo, J., Culbertson, W. 2010; 2 (58)

    Abstract

    About one-third of people in the developed world will undergo cataract surgery in their lifetime. Although marked improvements in surgical technique have occurred since the development of the current approach to lens replacement in the late 1960s and early 1970s, some critical steps of the procedure can still only be executed with limited precision. Current practice requires manual formation of an opening in the anterior lens capsule, fragmentation and evacuation of the lens tissue with an ultrasound probe, and implantation of a plastic intraocular lens into the remaining capsular bag. The size, shape, and position of the anterior capsular opening (one of the most critical steps in the procedure) are controlled by freehand pulling and tearing of the capsular tissue. Here, we report a technique that improves the precision and reproducibility of cataract surgery by performing anterior capsulotomy, lens segmentation, and corneal incisions with a femtosecond laser. The placement of the cuts was determined by imaging the anterior segment of the eye with integrated optical coherence tomography. Femtosecond laser produced continuous anterior capsular incisions, which were twice as strong and more than five times as precise in size and shape than manual capsulorhexis. Lens segmentation and softening simplified its emulsification and removal, decreasing the perceived cataract hardness by two grades. Three-dimensional cutting of the cornea guided by diagnostic imaging creates multiplanar self-sealing incisions and allows exact placement of the limbal relaxing incisions, potentially increasing the safety and performance of cataract surgery.

    View details for DOI 10.1126/scitranslmed.3001305

    View details for Web of Science ID 000288441800003

    View details for PubMedID 21084720

  • Multifocal laser surgery: Cutting enhancement by hydrodynamic interactions between cavitation bubbles PHYSICAL REVIEW E Toytman, I., Silbergleit, A., Simanovski, D., Palanker, D. 2010; 82 (4)

    Abstract

    Transparent biological tissues can be precisely dissected with ultrafast lasers using optical breakdown in the tight focal zone. Typically, tissues are cut by sequential application of pulses, each of which produces a single cavitation bubble. We investigate the hydrodynamic interactions between simultaneous cavitation bubbles originating from multiple laser foci. Simultaneous expansion and collapse of cavitation bubbles can enhance the cutting efficiency, by increasing the resulting deformations in tissue, and the associated rupture zone. An analytical model of the flow induced by the bubbles is presented and experimentally verified. The threshold strain of the material rupture is measured in a model tissue. Using the computational model and the experimental value of the threshold strain one can compute the shape of the rupture zone in tissue resulting from application of multiple bubbles. With the threshold strain of 0.7 two simultaneous bubbles produce a continuous cut when applied at the distance 1.35 times greater than that required in sequential approach. Simultaneous focusing of the laser in multiple spots along the line of intended cut can extend this ratio to 1.7. Counterpropagating jets forming during collapse of two bubbles in materials with low viscosity can further extend the cutting zone-up to approximately a factor of 1.5.

    View details for DOI 10.1103/PhysRevE.82.046313

    View details for Web of Science ID 000283540900002

    View details for PubMedID 21230396

  • Strength-Duration Relationship for Extracellular Neural Stimulation: Numerical and Analytical Models JOURNAL OF NEUROPHYSIOLOGY Boinagrov, D., Loudin, J., Palanker, D. 2010; 104 (4): 2236-2248

    Abstract

    The strength-duration relationship for extracellular stimulation is often assumed to be similar to the classical intracellular stimulation model, with a slope asymptotically approaching 1/? at pulse durations shorter than chronaxy. We modeled extracellular neural stimulation numerically and analytically for several cell shapes and types of active membrane properties. The strength-duration relationship was found to differ significantly from classical intracellular models. At pulse durations between 4 ?s and 5 ms stimulation is dominated by sodium channels, with a slope of -0.72 in log-log coordinates for the Hodgkin-Huxley ion channel model. At shorter durations potassium channels dominate and slope decreases to -0.13. Therefore the charge per phase is decreasing with decreasing stimulus duration. With pulses shorter than cell polarization time (?0.1-1 ?s), stimulation is dominated by polarization dynamics with a classical -1 slope and the charge per phase becomes constant. It is demonstrated that extracellular stimulation can have not only lower but also upper thresholds and may be impossible below certain pulse durations. In some regimes the extracellular current can hyperpolarize cells, suppressing rather than stimulating spiking behavior. Thresholds for burst stimuli can be either higher or lower than that of a single pulse, depending on pulse duration. The modeled thresholds were found to be comparable to published experimental data. Electroporation thresholds, which limit the range of safe stimulation, were found to exceed stimulation thresholds by about two orders of magnitude. These results provide a biophysical basis for understanding stimulation dynamics and guidance for optimizing the neural stimulation efficacy and safety.

    View details for DOI 10.1152/jn.00343.2010

    View details for Web of Science ID 000282649900039

    View details for PubMedID 20702740

  • Anterior capsulotomy with a pulsed-electron avalanche knife JOURNAL OF CATARACT AND REFRACTIVE SURGERY Palanker, D., Nomoto, H., Huie, P., Vankov, A., Chang, D. F. 2010; 36 (1): 127-132

    Abstract

    To evaluate a new pulsed-electron avalanche knife design for creating a continuous curvilinear capsulotomy (CCC) and compare the CCC with a mechanical capsulorhexis.Department of Ophthalmology, Stanford University, Stanford, California, USA.In this study, CCCs were created in freshly enucleated bovine eyes and in rabbit eyes in vivo. The cutting velocity was adjusted by controlling the burst repetition rate, voltage amplitude, and burst duration. Tissue samples were fixed and processed for histology and scanning electron microscopy (SEM) immediately after surgery.The study included 50 bovine eyes and 10 rabbit eyes. By adjusting the electrosurgical waveforms, gas-bubble formation was minimized to permit good surgical visualization. The optimum voltage level was determined to be +/-410 V with a burst duration of 20 mus. Burst repetition rate, continuously adjustable from 20 to 200 Hz with footpedal control, allowed the surgeon to vary linear cutting velocity up to 2.0 mm/s. Histology and SEM showed that the pulsed-electron avalanche knife produced sharp-edged capsule cutting without radial nicks or tears.The probe of the pulsed-electron avalanche knife duplicated the surgical feel of a 25-gauge cystotome and created a histologically smooth capsule cut. It may improve precision and reproducibility of creating a CCC, as well as improve its proper sizing and centration, especially in the face of surgical risk factors, such as weak zonules or poor visibility. FINANCIAL DISCLOSURES: Drs. Palanker and Vankov hold patents to the pulsed electron avalanche knife technology, which are licensed to PEAK Surgical by Stanford University. Drs. Palanker and Chang are consultants to PEAK Surgical. Dr. Vankov is an employee of PEAK Surgical. Neither of the other authors has a financial or proprietary interest in any material or method mentioned.

    View details for DOI 10.1016/j.jcrs.2009.07.046

    View details for Web of Science ID 000277410700021

    View details for PubMedID 20117716

  • Patterned Laser Trabeculoplasty. Ophthalmic Surgery Lasers and Imaging M. Turati, F. Gil-Carrasco, A. Morales, H. Quiroz-Mercado, D. Andersen, G. Marcellino, G. Schuele, D. Palanker. 2010; 41: 538-545
  • Short-pulse Laser Treatment: Redefining Retinal Therapy. Retinal Physician Y. Paulus, D. Palanker, M.S. Blumenkranz. 2010; 7 (1): 54-59
  • Comparative Healing of Surgical Incisions Created by the PEAK PlasmaBlade, Conventional Electrosurgery, and a Scalpel PLASTIC AND RECONSTRUCTIVE SURGERY Loh, S. A., Carlson, G. A., Chang, E. I., Huang, E., Palanker, D., Gurtner, G. C. 2009; 124 (6): 1849-1859

    Abstract

    The PEAK PlasmaBlade is a new electrosurgical device that uses pulsed radiofrequency to generate a plasma-mediated discharge along the exposed rim of an insulated blade, creating an effective cutting edge while the blade stays near body temperature.Full-thickness incisions were made on the dorsums of pigs with the PlasmaBlade, a conventional electrosurgical device, and a scalpel, and blood loss was quantified. Wounds were harvested at designated time points, tested for wound tensile strength, and examined histologically for scar formation and tissue damage.Bleeding was reduced significantly (59 percent) in PlasmaBlade incisions compared with scalpel incisions, and acute thermal damage from the PlasmaBlade (66 +/- 5 microm) was significantly less than both cut and coagulation mode electrosurgical incisions (456 +/- 35 microm and 615 +/- 22 microm, respectively). Histologic scoring for injury and wound strength was equivalent between the PlasmaBlade and scalpel incisions. By 6 weeks, the healed PlasmaBlade and scalpel incisions were approximately three times stronger, and scar cosmetic appearance was significantly better compared with electrosurgical incisions.The PlasmaBlade is a promising new surgical instrument that provides atraumatic, scalpel-like cutting precision and electrosurgical-like hemostasis, resulting in minimal bleeding, tissue injury, and scar formation.

    View details for DOI 10.1097/PRS.0b013e3181bcee87

    View details for Web of Science ID 000272615600015

    View details for PubMedID 19952641

  • Dynamics of retinal photocoagulation and rupture JOURNAL OF BIOMEDICAL OPTICS Sramek, C., Paulus, Y., Nomoto, H., Huie, P., Brown, J., Palanker, D. 2009; 14 (3)

    Abstract

    In laser retinal photocoagulation, short (<20 ms) pulses have been found to reduce thermal damage to the inner retina, decrease treatment time, and minimize pain. However, the safe therapeutic window (defined as the ratio of power for producing a rupture to that of mild coagulation) decreases with shorter exposures. To quantify the extent of retinal heating and maximize the therapeutic window, a computational model of millisecond retinal photocoagulation and rupture was developed. Optical attenuation of 532-nm laser light in ocular tissues was measured, including retinal pigment epithelial (RPE) pigmentation and cell-size variability. Threshold powers for vaporization and RPE damage were measured with pulse durations ranging from 1 to 200 ms. A finite element model of retinal heating inferred that vaporization (rupture) takes place at 180-190 degrees C. RPE damage was accurately described by the Arrhenius model with activation energy of 340 kJ/mol. Computed photocoagulation lesion width increased logarithmically with pulse duration, in agreement with histological findings. The model will allow for the optimization of beam parameters to increase the width of the therapeutic window for short exposures.

    View details for DOI 10.1117/1.3130282

    View details for Web of Science ID 000268536300016

    View details for PubMedID 19566300

  • On illumination schemes for wide-field CARS microscopy OPTICS EXPRESS Toytman, I., Simanovskii, D., Palanker, D. 2009; 17 (9): 7339-7347

    Abstract

    New system for a wide-field CARS microscopy is demonstrated, including two schemes of non-phase-matching illumination. Several advantages including high Stokes pulse energy, pulse-to-pulse stability and inherent synchronization between pump and Stokes pulses were brought by use of methane-filled Raman converter. Spatial resolution of the system with axially symmetric illumination, 0.5 microm, was found to correspond to diffraction limit of the imaging objective. Selective sensitivity to lipid-rich myelin sheaths in the nerve tissue has been demonstrated and confirmed by comparison with histological samples stained with myelin-specific dye. Single-shot imaging capability of the system has been demonstrated with a speckling-free illumination on a monolayer of 3 microm polystyrene beads.

    View details for Web of Science ID 000266381700049

    View details for PubMedID 19399112

  • Effect of shape and coating of a subretinal prosthesis on its integration with the retina EXPERIMENTAL EYE RESEARCH Butterwick, A., Huie, P., Jones, B. W., Marc, R. E., Marmor, M., Palanker, D. 2009; 88 (1): 22-29

    Abstract

    Retinal stimulation with high spatial resolution requires close proximity of electrodes to target cells. This study examines the effects of material coatings and 3-dimensional geometries of subretinal prostheses on their integration with the retina. A trans-scleral implantation technique was developed to place microfabricated structures in the subretinal space of RCS rats. The effect of three coatings (silicon oxide, iridium oxide and parylene) and three geometries (flat, pillars and chambers) on the retinal integration was compared using passive implants. Retinal morphology was evaluated histologically 6 weeks after implantation. For 3-dimensional implants the retinal cell phenotype was also evaluated using Computational Molecular Phenotyping. Flat implants coated with parylene and iridium oxide were generally well tolerated in the subretinal space, inducing only a mild gliotic response. However, silicon-oxide coatings induced the formation of a significant fibrotic seal around the implants. Glial proliferation was observed at the base of the pillar electrode arrays and inside the chambers. The non-traumatic penetration of pillar tips into the retina provided uniform and stable proximity to the inner nuclear layer. Retinal cells migrated into chambers with apertures larger than 10 mum. Both pillars and chambers achieved better proximity to the inner retinal cells than flat implants. However, isolation of retinal cells inside the chamber arrays is likely to affect their long-term viability. Pillars demonstrated minimal alteration of the inner retinal architecture, and thus appear to be the most promising approach for maintaining close proximity between the retinal prosthetic electrodes and target neurons.

    View details for DOI 10.1016/j.exer.2008.09.018

    View details for Web of Science ID 000262395800004

    View details for PubMedID 18955050

  • Healing of Retinal Photocoagulation Lesions INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Paulus, Y. M., Jain, A., Gariano, R. F., Stanzel, B. V., Marmor, M., Blumenkranz, M. S., Palanker, D. 2008; 49 (12): 5540-5545

    Abstract

    To systematically assess the changes in retinal morphology during the healing of retinal photocoagulation lesions of various clinical grades.Rabbits were irradiated with a 532-nm Nd:YAG laser with a beam diameter of 330 microm at the retinal surface, a power of 175 mW, and pulse durations between 5 and 100 ms. Retinal lesions were clinically graded 1 minute after placement as invisible, barely visible, light, moderate, intense, very intense, and rupture and were assessed histologically at six time points from 1 hour to 4 months.At all pulse durations, the width of the retinal lesions decreased over time. At clinical grades of light and more severe (pulse durations, 10-100 ms), retinal scarring stabilized at 1 month at approximately 35% of the initial lesion diameter. Lesions clinically categorized as barely visible and invisible (pulse durations of 7 and 5 ms) exhibited coagulation of the photoreceptor layer but did not result in permanent scarring. In these lesions, photoreceptors completely filled in the damaged areas by 4 months.The decreasing width of the retinal damage zone suggests that photoreceptors migrating from unaffected areas fill in the gap in the photoreceptor layer. Laser photocoagulation parameters can be specified to avoid not only the inner retinal damage, but also permanent disorganization and scarring in the photoreceptor layer. These data may facilitate studies to determine those aspects of laser treatment necessary for beneficial clinical response and those that result in extraneous retinal damage.

    View details for DOI 10.1167/iovs.08-1928

    View details for Web of Science ID 000261193900049

    View details for PubMedID 18757510

  • Pulsed electrical stimulation for control of vasculature: Temporary vasoconstriction and permanent thrombosis BIOELECTROMAGNETICS Palanker, D., Vankov, A., Freyvert, Y., Huie, P. 2008; 29 (2): 100-107

    Abstract

    A variety of medical procedures is aimed to selectively compromise or destroy vascular function. Such procedures include cancer therapies, treatments of cutaneous vascular disorders, and temporary hemostasis during surgery. Currently, technologies such as lasers, cryosurgery and radio frequency coagulation, produce significant collateral damage due to the thermal nature of these interactions and corresponding heat exchange with surrounding tissues. We describe a non-thermal method of inducing temporary vasoconstriction and permanent thrombosis using short pulse (microseconds) electrical stimulation. The current density required for vasoconstriction increases with decreasing pulse duration approximately as t(-0.25). The threshold of electroporation has a steeper dependence on pulse duration-exceeding t(-0.5). At pulse durations shorter than 5 micros, damage threshold exceeds the vasoconstriction threshold, thus allowing for temporary hemostasis without direct damage to surrounding tissue. With a pulse repetition rate of 0.1 Hz, vasoconstriction is achieved approximately 1 min after the beginning of treatment in both arteries and veins. Thrombosis occurs at higher electric fields, and its threshold increases with vessel diameter. Histology demonstrated a lack of tissue damage during vasoconstriction, but vascular endothelium was damaged during thrombosis. The temperature increase does not exceed 0.1 degrees C during these treatments.

    View details for DOI 10.1002/bem.20368

    View details for Web of Science ID 000253250000003

    View details for PubMedID 17918191

  • Electrosurgery with cellular precision IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Palanker, D. V., Vankov, A., Huie, P. 2008; 55 (2): 838-841

    Abstract

    Electrosurgery, one of the most-often used surgical tools, is a robust but somewhat crude technology that has changed surprisingly little since its invention almost a century ago. Continuous radiofrequency is still used for tissue cutting, with thermal damage extending to hundreds of micrometers. In contrast, lasers developed 70 years later, have been constantly perfected, and the laser-tissue interactions explored in great detail, which has allowed tissue ablation with cellular precision in many laser applications. We discuss mechanisms of tissue damage by electric field, and demonstrate that electrosurgery with properly optimized waveforms and microelectrodes can rival many advanced lasers. Pulsed electric waveforms with burst durations ranging from 10 to 100 micros applied via insulated planar electrodes with 12 microm wide exposed edges produced plasma-mediated dissection of tissues with the collateral damage zone ranging from 2 to 10 microm. Length of the electrodes can vary from micrometers to centimeters and all types of soft tissues-from membranes to cartilage and skin could be dissected in liquid medium and in a dry field. This technology may allow for major improvements in outcomes of the current surgical procedures and development of much more refined surgical techniques.

    View details for DOI 10.1109/TBME.2007.914539

    View details for Web of Science ID 000252622500006

    View details for PubMedID 18270030

  • Effect of pulse duration on size and character of the lesion in retinal photocoagulation ARCHIVES OF OPHTHALMOLOGY Jain, A., Blumenkranz, M. S., Paulus, Y., Wiltberger, M. W., Andersen, D. E., Huie, P., Palanker, D. 2008; 126 (1): 78-85

    Abstract

    To systematically evaluate the effects of laser beam size, power, and pulse duration of 1 to 100 milliseconds on the characteristics of ophthalmoscopically visible retinal coagulation lesions.A 532-nm Nd:YAG laser was used to irradiate 36 retinas in Dutch Belt rabbits with retinal beam sizes of 66, 132, and 330 mum. Lesions were clinically graded 1 minute after placement, their size measured by digital imaging, and their depth assessed histologically at different time points.Retinal lesion size increased linearly with laser power and logarithmically with pulse duration. The width of the therapeutic window, defined by the ratio of the threshold power for producing a rupture to that of a mild coagulation, decreased with decreasing pulse durations. For 132- and 330-mum retinal beam sizes, the therapeutic window declined from 3.9 to 3.0 and 5.4 to 3.7, respectively, as pulse duration decreased from 100 to 20 ms. At pulse durations of 1 millisecond, the therapeutic window decreased to unity, at which point rupture and a mild lesion were equally likely to occur.At shorter pulse durations, the width and axial extent of the retinal lesions are smaller and less dependent on variations in laser power than at longer durations. The width of the therapeutic window, a measure of relative safety, increases with the beam size.Pulse durations of approximately 20 milliseconds represent an optimal compromise between the favorable impact of speed, higher spatial localization, and reduced collateral damage on one hand, and sufficient width of the therapeutic window (> 3) on the other.

    View details for Web of Science ID 000252312800011

    View details for PubMedID 18195222

  • On Mechanisms of Interaction in Electrosurgery New Journal of Physics D. Palanker, A. Vankov, P. Jayaraman 2008; 10: 123022
  • Tissue damage by pulsed electrical stimulation IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Butterwick, A., Vankov, A., Huie, P., Freyvert, Y., Palanker, D. 2007; 54 (12): 2261-2267

    Abstract

    Repeated pulsed electrical stimulation is used in a multitude of neural interfaces; damage resulting from such stimulation was studied as a function of pulse duration, electrode size, and number of pulses using a fluorescent assay on chick chorioallontoic membrane (CAM) in vivo and chick retina in vitro. Data from the chick model were verified by repeating some measurements on porcine retina in-vitro. The electrode size varied from 100 microm to 1 mm, pulse duration from 6 micros to 6 ms, and the number of pulses from 1 to 7500. The threshold current density for damage was independent of electrode size for diameters greater than 300 microm, and scaled as 1/r2 for electrodes smaller than 200 microm. Damage threshold decreased with the number of pulses, dropping by a factor of 14 on the CAM and 7 on the retina as the number of pulses increased from 1 to 50, and remained constant for a higher numbers of pulses. The damage threshold current density on large electrodes scaled with pulse duration as approximately 1/t0.5, characteristic of electroporation. The threshold current density for repeated exposure on the retina varied between 0.061 A/cm2 at 6 ms to 1.3 A/cm2 at 6 micros. The highest ratio of the damage threshold to the stimulation threshold in retinal ganglion cells occurred at pulse durations near chronaxie-around 1.3 ms.

    View details for DOI 10.1109/TBME.2007.908310

    View details for Web of Science ID 000251226200016

    View details for PubMedID 18075042

  • Wide-field coherent anti-Stokes Raman scattering microscopy with non-phase-matching illumination OPTICS LETTERS Toytman, I., Cohn, K., Smith, T., Simanovskii, D., Palanker, D. 2007; 32 (13): 1941-1943

    Abstract

    We have developed and tested a wide-field coherent anti-Stokes Raman scattering (CARS) microscopy technique, which provides the simultaneous imaging of an extended illuminated area without scanning. This method is based on the non-phase-matching illumination of a sample and imaging of a CARS signal with a CCD camera using conventional microscope optics. We have identified a set of conditions on the illumination and imaging optics, as well as on sample preparation. Imaging of test objects proved high spatial resolution and chemical selectivity of this technique.

    View details for Web of Science ID 000248348300059

    View details for PubMedID 17603621

  • Optoelectronic retinal prosthesis: system design and performance JOURNAL OF NEURAL ENGINEERING Loudin, J. D., Simanovskii, D. M., VijayRaghavan, K., Sramek, C. K., Butterwick, A. F., Huie, P., McLean, G. Y., Palanker, D. V. 2007; 4 (1): S72-S84

    Abstract

    The design of high-resolution retinal prostheses presents many unique engineering and biological challenges. Ever smaller electrodes must inject enough charge to stimulate nerve cells, within electrochemically safe voltage limits. Stimulation sites should be placed within an electrode diameter from the target cells to prevent 'blurring' and minimize current. Signals must be delivered wirelessly from an external source to a large number of electrodes, and visual information should, ideally, maintain its natural link to eye movements. Finally, a good system must have a wide range of stimulation currents, external control of image processing and the option of either anodic-first or cathodic-first pulses. This paper discusses these challenges and presents solutions to them for a system based on a photodiode array implant. Video frames are processed and imaged onto the retinal implant by a head-mounted near-to-eye projection system operating at near-infrared wavelengths. Photodiodes convert light into pulsed electric current, with charge injection maximized by applying a common biphasic bias waveform. The resulting prosthesis will provide stimulation with a frame rate of up to 50 Hz in a central 10 degrees visual field, with a full 30 degrees field accessible via eye movements. Pixel sizes are scalable from 100 to 25 microm, corresponding to 640-10,000 pixels on an implant 3 mm in diameter.

    View details for DOI 10.1088/1741-2560/4/1/S09

    View details for Web of Science ID 000245612700010

    View details for PubMedID 17325419

  • Nanosecond plasma-mediated electrosurgery with elongated electrodes Journal of Applied Physics A. Vankov, D. Palanker 2007; 101: 124701
  • Pulsed Electron Avalanche Knife (PEAK-fc): New Technology for Cataract Surgery British Journal of Ophthalmology S.G. Priglinger, D. Palanker, C.S. Alge, T.C. Kreutzer, C. Haritoglou, M. Grueterich, A. Kampik 2007; 91: 949-954
  • Image processing for a high-resolution optoelectronic retinal prosthesis IEEE Transactions on Biomedical Engineering A Asher, WA Segal, SA Baccus, LP Yaroslavsky, DV Palanker 2007; 54 (6): 993-1004
  • Gene transfer to rabbit retina with electron avalanche transfection INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Chalberg, T. W., Vankov, A., Molnar, F. E., Butterwick, A. F., Huie, P., Calos, M. P., Palanker, D. V. 2006; 47 (9): 4083-4090

    Abstract

    Nonviral gene therapy represents a promising treatment for retinal diseases, given clinically acceptable methods for efficient gene transfer. Electroporation is widely used for transfection, but causes significant collateral damage and a high rate of cell death, especially in applications in situ. This study was conducted in the interest of developing efficient and less toxic forms of gene transfer for the eye.A novel method for nonviral DNA transfer, called electron avalanche transfection, was used that involves microsecond electric plasma-mediated discharges applied via microelectrode array. This transfection method, which produces synchronized pulses of mechanical stress and high electric field, was first applied to chorioallantoic membrane as a model system and then to rabbit RPE in vivo. Gene transfer was measured by using luciferase bioluminescence and in vivo fluorescent fundus photography. Safety was evaluated by performing electroretinograms and histology.In chorioallantoic membrane, electron avalanche transfection was approximately 10,000-fold more efficient and produced less tissue damage than conventional electroporation. Also demonstrated was efficient plasmid DNA transfer to the rabbit retina after subretinal DNA injection and transscleral electron avalanche transfection. Electroretinograms and histology showed no evidence of damage from the procedure.Electron avalanche transfection is a powerful new technology for safe DNA delivery that has great promise as a nonviral system of gene transfer.

    View details for DOI 10.1167/iovs.06-0092

    View details for Web of Science ID 000240050700055

    View details for PubMedID 16936128

  • Cellular tolerance to pulsed hyperthermia PHYSICAL REVIEW E Simanovskii, D. M., Mackanos, M. A., Irani, A. R., O'Connell-Rodwell, C. E., Contag, C. H., Schwettman, H. A., Palanker, D. V. 2006; 74 (1)

    Abstract

    Transient heating of tissues leading to cellular stress or death is very common in medicine and biology. In procedures involving a mild (below 70 degrees C) and prolonged (minutes) heating, such as hyperthermal tumor therapy, the cellular response to thermal stress is relatively well studied. However, there is practically no data on cell viability at higher temperatures and shorter exposures, while the demand for this knowledge is growing. Two main reasons motivate this research: (i) a growing number of laser therapies and surgical procedures involving pulsed heating, and (ii) cellular viability data at short exposures to high temperatures provide a unique insight into the understanding of processes leading to thermally induced cellular death. We designed a technique and performed a study of cell viability under pulses of heat from 0.3 to 100 ms in duration with peak temperatures as high as 130 degrees C. We found that the threshold of cellular death in this range can be accurately approximated by the Arrhenius law with the activation energy of 1 eV, a significantly lower value than was reported in studies based on multisecond exposures.

    View details for DOI 10.1103/PhysRevE.74.011915

    View details for Web of Science ID 000239425600098

    View details for PubMedID 16907135

  • Pulsed electron avalanche knife for capsulotomy in congenital and mature cataract JOURNAL OF CATARACT AND REFRACTIVE SURGERY Priglinger, S. G., Haritoglou, C., Palanker, D., Kook, D., Grueterich, M., Mueller, A., Alge, C. S., Kampik, A. 2006; 32 (7): 1085-1088

    Abstract

    The pulsed electron avalanche knife (PEAK-fc, Carl Zeiss Meditec) is an electrosurgical cutting device that allows precise "cold" and traction-free tissue dissection. We describe its applicability and safety for anterior capsulotomy in a child with congenital cataract and an adult patient with mature cataract. The PEAK-fc was set at a voltage of 600 V and a pulse repetition rate of 80 Hz. Anterior capsulotomies were successfully and safely performed in both cases, with the edges of capsulotomies appearing sharp and showing only limited collateral damage. The PEAK-fc appears to be a helpful cutting device for complicated cases of cataract surgery, especially for mature and congenital cataracts.

    View details for DOI 10.1016/j.jcrs.2006.03.020

    View details for Web of Science ID 000239334000010

    View details for PubMedID 16857491

  • Semiautomated patterned scanning laser for retinal photocoagulation RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Blumenkranz, M. S., Yellachich, D., Andersen, D. E., Wiltberger, M. W., Mordaunt, D., Marcellino, G. R., Palanker, D. 2006; 26 (3): 370-376

    View details for Web of Science ID 000241684700024

    View details for PubMedID 16508446

  • Pulsed electron avalanche knife (PEAK-fc) for dissection of retinal tissue ARCHIVES OF OPHTHALMOLOGY Priglinger, S. G., Haritoglou, C., Palanker, D. V., Alge, C. S., Gandorfer, A., Kampik, A. 2005; 123 (10): 1412-1418

    Abstract

    To evaluate the effectiveness and precision of tractionless retinal tissue dissection by the advanced version of the pulsed electron avalanche knife for fine cutting (PEAK-fc; Carl Zeiss Meditec, Jena, Germany).Porcine retina (in vivo) and human retina (in vitro) were incised with the PEAK-fc using various pulse parameters. The globes were then processed for light microscopy. Evaluation of all specimens focused on depth of the retinal cuts and on the degree of collateral damage.Retinal cuts performed both in vivo on porcine eyes and on human donor eyes showed very sharp edges with only little collateral damage. With probes of 600 mum in length, the optimal pulse parameters for precise and reproducible cutting of the retina were an amplitude of 350 to 380 V, a repetition rate of 300 Hz, and 30 "minipulses" per pulse of 100-microsecond duration. With increasing voltage, cuts also affected the retinal pigment epithelium and the choroid, followed by intravitreal bleeding during in vivo application.We demonstrated that PEAK-fc is capable of precisely cutting retinal tissue in vivo and in vitro using optimal pulse parameters. Further in vivo studies will be necessary to determine the efficacy of this new tractionless cutting device in vitreoretinal surgery.

    View details for Web of Science ID 000232502700014

    View details for PubMedID 16219733

  • Pulsed electron avalanche knife in vitreoretinal surgery RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Priglinger, S. G., Haritoglou, C., Mueller, A., Grueterich, M., Strauss, R. W., Alge, C. S., Gandorfer, A., Palanker, D., Kampik, A. 2005; 25 (7): 889-896

    Abstract

    To evaluate the advantages, disadvantages, safety, and surgical applicability of the pulsed electron avalanche knife (PEAK-fc), a new electrosurgical knife for "cold" and tractionless cutting, in vitreoretinal surgery. PEAK-fc is equipped with an integrated fiberoptic that makes bimanual procedures in intraocular surgery possible.A prospective consecutive trial of 18 eyes in 18 patients who underwent vitreoretinal surgery for proliferative diabetic retinopathy, proliferative vitreoretinopathy, subretinal macular hemorrhage, or macular pucker was performed. The following specific maneuvers were performed with PEAK-fc: transection of epiretinal membranes, retinotomies, retinal vessel coagulation, and posterior membranectomy.Detached and attached retina could be dissected successfully in eight cases. Intraoperatively, incision edges were sharply demarcated, showing no visible collateral damage. Deeper layers than the neurosensory retina were not affected. With the bimanual approach, epiretinal avascular and vascular membranes could be removed in 10 cases. Hemorrhages occurring during transection of vascularized membranes could be stopped immediately using the coagulation mode of PEAK-fc. Posterior capsule fibrosis was successfully excised in one patient. No complications were observed.PEAK-fc offers precise and tractionless tissue cutting during ocular surgery. Using different waveform parameters, the same device performs cold cutting and/or "hot" coagulation, thus improving the precision, safety, and ergonomics of vitreoretinal surgery.

    View details for Web of Science ID 000235012900012

    View details for PubMedID 16205569

  • Optical spectroscopy noninvasively monitors response of organelles to cellular stress JOURNAL OF BIOMEDICAL OPTICS Schuele, G., Vitkin, E., Huie, P., O'Connell-Rodwell, C., Palanker, D., Perelman, L. T. 2005; 10 (5)

    Abstract

    Fast and noninvasive detection of cellular stress is extremely useful for fundamental research and practical applications in medicine and biology. We discovered that light scattering spectroscopy enables us to monitor the transformations in cellular organelles under thermal stress. At the temperatures triggering expression of heat shock proteins, the refractive index of mitochondria increase within 1 min after the onset of heating, indicating enhanced metabolic activity. At higher temperatures and longer exposures, the organelles increase in size. This technique provides an insight into metabolic processes within organelles larger than 50 nm without exogenous staining and opens doors for noninvasive real-time assessment of cellular stress.

    View details for DOI 10.1117/1.2075207

    View details for Web of Science ID 000233711300006

    View details for PubMedID 16292941

  • Design of a high-resolution optoelectronic retinal prosthesis. Journal of neural engineering Palanker, D., Vankov, A., Huie, P., Baccus, S. 2005; 2 (1): S105-20

    Abstract

    It has been demonstrated that electrical stimulation of the retina can produce visual percepts in blind patients suffering from macular degeneration and retinitis pigmentosa. However, current retinal implants provide very low resolution (just a few electrodes), whereas at least several thousand pixels would be required for functional restoration of sight. This paper presents the design of an optoelectronic retinal prosthetic system with a stimulating pixel density of up to 2500 pix mm(-2) (corresponding geometrically to a maximum visual acuity of 20/80). Requirements on proximity of neural cells to the stimulation electrodes are described as a function of the desired resolution. Two basic geometries of sub-retinal implants providing required proximity are presented: perforated membranes and protruding electrode arrays. To provide for natural eye scanning of the scene, rather than scanning with a head-mounted camera, the system operates similar to 'virtual reality' devices. An image from a video camera is projected by a goggle-mounted collimated infrared LED-LCD display onto the retina, activating an array of powered photodiodes in the retinal implant. The goggles are transparent to visible light, thus allowing for the simultaneous use of remaining natural vision along with prosthetic stimulation. Optical delivery of visual information to the implant allows for real-time image processing adjustable to retinal architecture, as well as flexible control of image processing algorithms and stimulation parameters.

    View details for PubMedID 15876646

  • Migration of retinal cells through a perforated membrane: Implications for a high-resolution prosthesis INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Palanker, D., Huie, P., Vankov, A., Aramant, R., Seiler, M., Fishman, H., Marmor, M., Blumenkranz, M. 2004; 45 (9): 3266-3270

    Abstract

    One of the critical difficulties in design of a high-resolution retinal implant is the proximity of stimulating electrodes to the target cells. This is a report of a phenomenon of retinal cellular migration into a perforated membrane that may help to address this problem.Mylar membranes with an array of perforations (3-40 microm in diameter) were used as a substrate for in vitro retinal culture (chicken, rats) and were also transplanted into the subretinal space of adult RCS rats. A membrane was also constructed with a seal on one side to restrict the migration.Retinal tissue in vitro grew within 3 days through perforations of greater than 5 microm in diameter when the membranes were positioned on the photoreceptor side, but no migration occurred if the implant was placed on the inner retinal surface. Histology with light microscopy and transmission electron microscopy (TEM) demonstrated that migrating cells retain neuronal structures for signal transduction. Similar growth of RCS rat retinal cells occurred in vivo within 5 days of implantation. A basal seal kept the migrating tissue within a small membrane compartment.Retinal neurons migrate within a few days into perforations (> 5 microm in diameter) of a membrane placed into the subretinal space. This may provide a means of gaining close proximity between electrodes in a retinal prosthetic chip and target cells, and thus allow a greater density of stimulating elements to subserve higher resolution. Further studies are needed to explore the long-term stability of the retinal migration.

    View details for DOI 10.1167/iovs.03-1327

    View details for Web of Science ID 000223500900055

    View details for PubMedID 15326150

  • The chick chorioallantoic membrane as a model tissue for surgical retinal research and simulation RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Leng, T., MILLER, J. M., Bilbao, K. V., Palanker, D. V., Huie, P., Blumenkranz, M. S. 2004; 24 (3): 427-434

    Abstract

    We describe the use of chick chorioallantoic membrane (CAM) as a model system for the study of the precision and safety of vitreoretinal microsurgical instruments and techniques.The CAM was prepared for experimentation with and without its inner shell membrane (ISM) attached for in vivo and in vitro experiments that simulated medical and surgical interventions on the retina.The CAM's ease of use, low cost, and anatomic structure make it a convenient model for surgical retinal and retinal vascular modeling.While CAM has been used extensively in the past for ocular angiogenesis studies, we describe the tissue as a useful tool for a variety of other applications, including (1) testing of novel surgical tools and techniques for cutting and coagulating retina and its vasculature, (2) testing vessel cannulation and injection techniques, (3) angiographic studies, and (4) endoscopic surgery.

    View details for Web of Science ID 000222156800014

    View details for PubMedID 15187666

  • A genetic reporter of thermal stress defines physiologic zones over a defined temperature range FASEB JOURNAL O'Connell-Rodwell, C. E., Shriver, D., Simanovskii, D. M., Mcclure, C., Cao, Y. A., Zhang, W. S., Bachmann, M. H., Beckham, J. T., Jansen, E. D., Palanker, D., Schwettman, H. A., Contag, C. H. 2004; 18 (2): 264-271

    Abstract

    We define five unique cellular responses to thermal stress using a reporter construct generated using the stress-inducible promoter from the gene encoding a murine 70 kDa heat shock protein (Hsp70A.1) to express luciferase (luc). Thermal stress was delivered over a range of temperatures (42-68 degrees C) for 5 s to 20 min and luciferase activity was measured in live cells using a cooled CCD camera as a measure of reporter gene transcription. Reporter gene expression was assessed every 2 h for 10 h, and at 24 h post-stress. Expression patterns were validated for selected temperatures. A transition zone where cells lose the ability to produce light and beyond which >50% of cells die was observed to occur within a narrow (2.5 degrees C) temperature window. Although luc and hsp70 mRNA levels in this transition zone were high, there were reduced levels of Luc and Hsp70 protein and ATP levels. Cells treated at these temperatures recovered the ability to produce light in response to a secondary stress at 30 h. This Hsp70-luc reporter gene construct may be useful for defining zones of physiologic responses and assessing collateral thermal damage generated during treatment of biological tissue with lasers and other sources of heat.

    View details for DOI 10.1096/fj.03-0585com

    View details for Web of Science ID 000220425000006

    View details for PubMedID 14769820

  • Precision and safety of the pulsed electron avalanche knife in vitreoretinal surgery ARCHIVES OF OPHTHALMOLOGY MILLER, J. M., Palanker, D. V., Vankov, A., Marmor, M. F., Blumenkranz, M. S. 2003; 121 (6): 871-877

    Abstract

    We have developed a new surgical instrument, called the pulsed electron avalanche knife (PEAK; Carl Zeiss Meditec, Jena, Germany), for precise, "cold," and tractionless dissection of tissue in liquid media.To evaluate the 3-dimensional damage zone induced by the PEAK compared with 2 other standard intraocular surgical instruments, diathermy and retinal scissors.Damage zone and minimum safe distance were measured in vitro on chick chorioallantoic membrane and in vivo on rabbit retina with the use of propidium iodide staining.The PEAK produced a paracentral zone of cellular structure disruption surrounding a crater and a peripheral zone of structurally intact but abnormally permeable cells. The instrument induced a damage radius that varied from 55 to 300 micro m for the range of voltages and pulses typically used during surgery. For comparison, damage radius for microsurgical scissors was 50 micro m, and for diathermy, 400 to 850 micro m. The PEAK also damaged tissue up to 1.4 mm away by the creation of water flow that formed at the tip of convex probes during collapse of a cavitation bubble. Concave probes, which prevent formation of the water jet, eliminated this effect.The PEAK operated well within accept-able safety limits and may greatly facilitate both posterior segment surgeries (eg, membrane dissection and sheathotomy) and anterior segment procedures (eg, capsulotomy, nonpenetrating trabeculectomy, and iridectomy).

    View details for Web of Science ID 000183408600017

    View details for PubMedID 12796261

  • Transient optical elements: application to near-field microscopy JOURNAL OF MICROSCOPY-OXFORD Simanovskii, D., Palanker, D., Cohn, K., Smith, T. 2003; 210: 307-310

    Abstract

    We report methods of near-field infrared microscopy with transient optically induced probes. The first technique - a transient aperture (TA) - uses photoinduced reflectivity in semiconductors to generate a relatively large transient mirror (TM) with a small aperture at its centre. We report the optical properties of the TM and TA and experiments performed on near-field imaging with the TA. The second technique is based on solid immersion microscopy, in which high resolution is achieved when light is focused inside a solid with a high refractive index. By creating a transient Fresnel lens on the surface of a semiconductor wafer via photoinduction, we were able to form a solid immersion lens (SIL) for use as a near-field probe. The use of transient probes eliminates the need for mechanical scanning of the lens or sample, and thus provides a much faster scanning rate and the possibility to work with soft and liquid objects.

    View details for Web of Science ID 000183307500022

    View details for PubMedID 12787104

  • Prevention of tissue damage by water jet during cavitation Journal of Applied Physics D. Palanker, A.Vankov, J. Miller, M. Friedman, M. Strauss 2003; 94 (4): 2654-2661
  • Intravascular drug delivery with a pulsed liquid microjet ARCHIVES OF OPHTHALMOLOGY Fletcher, D. A., Palanker, D. V., Huie, P., Miller, J., Marmor, M. F., Blumenkranz, M. S. 2002; 120 (9): 1206-1208

    Abstract

    Occlusions of the retinal veins and arteries, associated with diseases such as hypertension and arteriosclerosis, are a major cause of severe and irreversible loss of vision. Treatments for retinal vascular diseases have been unsatisfactory owing in part to the difficulty of delivering drugs to the site of disease within the eye. In this article, we demonstrate that a new device, the vapor bubble-driven pulsed liquid microjet, can deliver drugs into the lumen of small vessels such as those found in the retina. A 15- micro m-diameter liquid jet traveling at more than 60 m/s was shown to penetrate and deliver fluid through the wall of a blood vessel that was 60 micro m in diameter. Perforation of the wall of the blood vessel did not extend beyond the jet diameter.

    View details for Web of Science ID 000178022300013

    View details for PubMedID 12215096

  • Effects of the pulsed electron avalanche knife on retinal tissue ARCHIVES OF OPHTHALMOLOGY Palanker, D. V., Marmor, M. F., Branco, A., Huie, P., MILLER, J. M., Sanislo, S. R., Vankov, A., Blumenkranz, M. S. 2002; 120 (5): 636-640

    Abstract

    To evaluate the precision of retinal tissue dissection by the pulsed electron avalanche knife (PEAK) and to assess possible toxic effects from this device.To demonstrate precision of cutting, bovine retina (in vitro) and rabbit retina (in vivo) were incised with the PEAK. Samples were examined by scanning electron microscopy and histologic examination (light microscopy). To evaluate possible toxic effects in rabbit eyes, 30 000 pulses were delivered into the vitreous 1 cm above the retina. Histologic examinations and electroretinography were performed at intervals up to 1 month after exposure.Cuts in postmortem bovine retina showed extremely sharp edges with no signs of thermal damage. Full-thickness cuts in living attached rabbit retina were similarly sharp and were typically less than 100 microm wide. No signs of retinal toxic effects were detected by histologic examination or electroretinography.The PEAK is capable of precise cutting through retinal tissue, and there are no demonstrable retinal toxic effects from its use. The precision and tractionless nature of PEAK cutting offers advantages over mechanical tools and laser-based instrumentation. We believe this new device will prove useful in a variety of vitreoretinal surgical applications.

    View details for Web of Science ID 000175503400015

    View details for PubMedID 12003616

  • Transient photoinduced diffractive solid immersion lens for infrared microscopy Applied Physics Letters K. Cohn, D. Simanovskii, T. Smith, D. Palanker 2002; 81 (19): 3678-3680
  • Pulsed Electron Avalanche Knife (PEAK) for intraocular surgery INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Palanker, D. V., MILLER, J. M., Marmor, M. F., Sanislo, S. R., Huie, P., Blumenkranz, M. S. 2001; 42 (11): 2673-2678

    Abstract

    To develop a better and more economical instrument for precise, tractionless, "cold" cutting during intraocular surgery. The use of highly localized electric fields rather than laser light as the means of tissue dissection was investigated.A high electric field at the tip of a fine wire can, like lasers, initiate plasma formation. Micrometer-length plasma streamers are generated when an insulated 25 micron (microm) wire, exposed to physiological medium at one end, is subjected to nanosecond electrical pulses between 1 and 8 kV in magnitude. The explosive evaporation of water in the vicinity of these streamers cuts soft tissue without heat deposition into surrounding material (cold cutting). Streamers of plasma and the dynamics of water evaporation were imaged using an inverted microscope and fast flash photography. Cutting effectiveness was evaluated on both polyacrylamide gels, on different tissues from excised bovine eyes, and in vivo on rabbit retina. Standard histology techniques were used to examine the tissue.Electric pulses with energies between 150 and 670 microJ produced plasma streamers in saline between 10 and 200 microm in length. Application of electric discharges to dense (10%) polyacrylamide gels resulted in fracturing of the gel without ejection of bulk material. In both dense and softer (6%) gels, layer by layer shaving was possible with pulse energy rather than number of pulses as the determinant of ultimate cutting depth. The instrument made precise partial or full-thickness cuts of retina, iris, lens, and lens capsule without any evidence of thermal damage. Because different tissues require distinct energies for dissection, tissue-selective cutting on complex structures can be performed if the appropriate pulse energies are used; for example, retina can be dissected without damage to the major retinal vessels.This instrument, called the Pulsed Electron Avalanche Knife (PEAK), can quickly and precisely cut intraocular tissues without traction. The small delivery probe and modest cost make it promising for many ophthalmic applications, including retinal, cataract, and glaucoma surgery. In addition, the instrument may be useful in nonophthalmic procedures such as intravascular surgery and neurosurgery.

    View details for Web of Science ID 000171433300037

    View details for PubMedID 11581215

  • Refraction Contrast Imaging With A Scanning Microlens. Applied Physics Letters D.A. Fletcher, K.B. Crozier, C.F. Quate, G.S. Kino, K.E. Goodson, D. Simanovskii, D.V. Palanker 2001; 78 (23): 3589-3591
  • Near-Field Infrared Microscopy With A Transient Photo-Induced Aperture. Applied Physics Letters D. Simanovski, D. Palanker, K. Cohn, T. Smith 2001; 79 (8): 1214-1216
  • Pulsed Liquid Microjet For Microsurgery. Applied Physics Letters D. A. Fletcher, D. V. Palanker 2001; 78 (13): 1933-35
  • Near-field infrared imaging with a microfabricated solid immersion lens. Applied Physics Letters D.A. Fletcher,, K.B. Crozier, C.F. Quate, G.S. Kino, K.E. Goodson, D. Simanovskii, D.V. Palanker 2000; 77 (14): 2109-2111
  • On Contrast Parameters and Topographic Artifacts in Near-Field Infrared Microscopy. Journal of Applied Physics D.V. Palanker, D.M. Simanovskii, P. Huie, T.I. Smith, H.A. Schwettman 2000; 88 (11): 6808-6814
  • Near-field scanning optical microscopy in cell biology TRENDS IN CELL BIOLOGY Lewis, A., Radko, A., Ben Ami, N., Palanker, D., Lieberman, K. 1999; 9 (2): 70-73

    Abstract

    Near-field optics has produced the highest optical resolution that has ever been achieved. The methods involved lie at the interface of far-field optical microscopy and scanned probe microscopy. This article describes the principles behind near-field scanning optical microscopy (NSOM) and highlights its potential in cell biology.

    View details for Web of Science ID 000079416700008

    View details for PubMedID 10087622

  • Early nonsurgical removal of chemically injured tissue enhances wound healing in partial thickness burns BURNS Eldad, A., Weinberg, A., Breiterman, S., Chaouat, M., Palanker, D., Ben-Bassat, H. 1998; 24 (2): 166-172

    Abstract

    Chemical burns are slow healing injuries and their depth is difficult to assess. Tissue destruction continues as long as active material is present in the wound site. The routine therapy for treatment of full thickness chemical burns is early excision; it shortens hospitalization and reduces morbidity. However, presently there is no specific treatment for chemical burns of partial thickness. This study examined several treatment modalities for partial thickness chemical burns: surgical excision; laser ablation and chemical debridement with Debridase or trypsin-linked to gauze. Chemical burns were inflicted with nitrogen mustard (NM -- a nitrogen analog to sulfur mustard -- mustard gas) in an experimental guinea pig model. Debridase was most effective and reduced significantly lesion area of burns after 'humid' exposure to 2 mg NM. The healing action of Debridase was also evident in the significantly higher histopathological score of biopsies from local tissue obtained on day 5. Laser ablation was most effective and accelerated healing of burn lesions after 'dry' exposure to 5 mg NM. The histopathology score of the laser treated burns was higher on day 4 compared to untreated controls. It is concluded that for partial thickness chemical burns early nonsurgical removal of the damaged tissues accelerates wound healing.

    View details for Web of Science ID 000073712900015

    View details for PubMedID 9625245

  • IR Microscopy with a Transient Photo-induced Near-field Probe (Tipless Near-field Microscopy). Optics Communications D. V. Palanker, G.M.H. Knippels, T.I. Smith, H.A. Schwettman 1998; 148 (4-6): 215-220
  • Pulse Shape Measurements Using Differential Optical Gating Of A Picosecond Free Electron Laser Source With An Unsynchronized Femtosecond Ti:Sapphire Gate. Optics Comm C.W. Rella, G.M.H. Knippels, D. Palanker, H.A. Schwettman 1998; 157 (1-6): 335-42
  • Fast IR Imaging with Sub-Wavelength Resolution using a Transient Near-field Probe. Nuclear Instruments and Methods in Physics, Section B: Beam Interactions with Materials and Atoms D. V. Palanker, G.M.H. Knippels, T.I. Smith, H.A. Schwettman 1998; 144: 240-245
  • Etched Chalcogenide Fibers for Near-Field IR Scanning Microscopy. Review of Scientific Instruments M.A. Unger, D.A. Kossakovski, R. Kongovi, J.L. Beauchamp, D.V. Palanker 1998; 69 (8): 2988-93
  • Vitreoretinal surgery assisted by the 193-nm excimer laser INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Hemo, I., Palanker, D., TUROVETS, I., Lewis, A., Zauberman, H. 1997; 38 (9): 1825-1829

    Abstract

    Ablating and cutting vitreoretinal membranes using a 193-nm excimer laser-based microsurgical system.A 193-nm microsurgical system enables delivery of the beam into a fluid medium to cut preretinal and subretinal membranes. Two patients with proliferative diabetic retinopathy and one patient with proliferative vitreoretinopathy were treated with this new device.Gentle ablation and cutting of the preretinal and subretinal membranes without exerting any traction on or apparent damage to the neighboring tissue was achieved.The technology is applicable to a variety of intraocular vitreoretinal surgical procedures.

    View details for Web of Science ID A1997XU43000020

    View details for PubMedID 9286272

  • Electrical Alternative to Pulsed Fiber-Delivered Lasers in Microsurgery. Appl. Phys. Palanker D., Turovets I., Lewis A., J. 1997; 81 (11): 7673-7680
  • Nanometer-Sized Electrochemical Sensors. Anal. Chem. Y. Shao, M. V. Mirkin, G. Fish, S. Kokotov, D. Palanker, A. Lewis 1997; 69: 1627-1634
  • Dynamics of ArF excimer laser-induced cavitation bubbles in gel surrounded by a liquid medium LASERS IN SURGERY AND MEDICINE Palanker, D., TUROVETS, I., Lewis, A. 1997; 21 (3): 294-300

    Abstract

    Cavitation bubbles have been shown to be the driving force of tissue cutting in 193 nm ArF excimer laser-based vitreoretinal microsurgery. In the present work we investigate the dynamics of cavitation bubbles inside a gelatin gel in a saline environment using fast flash microphotography.The screening influence of the saline medium was found to restrict the maximal distance between the tip and the tissue at which cavitation bubbles are created to < 100 microns at an energy fluence up to 0.3 J/cm2/pulse (the maximal energy fluence applied in vitreoretinal surgery).Single laser pulses did not cause disruption of gelatin at an energy fluence of up to 0.4 J/cm2/pulse. During the application of repetitive pulses small insoluble gas-containing bubbles were produced and often trapped between the tip and the tissue. They completely changed the shape of the subsequent cavitation bubbles and caused deep crater formation in the gel.

    View details for Web of Science ID A1997XV00300010

    View details for PubMedID 9291087

  • Dynamics of Cavitation Bubble Induced by 193 nm ArF Excimer Laser in Concentrated Sodium Chloride Solutions. Journal of Applied Physics Turovets I., Palanker D., Kokotov Yu, Hemo I., Lewis A 1996; 79 (5): 2689-2693
  • Ultrafast Response Micropipette-Based Submicron Thermocouple. Review of Scientific Instruments G. Fish, O. Bouevitch, S. Kokotov, K. Lieberman, D. Palanker, I. Turovets, A. Lewis 1995; 66 (5): 3300-3306
  • ARF EXCIMER LASER-INDUCED BUBBLE FORMATION DURING IRRADIATION OF NACL SOLUTIONS PHOTOCHEMISTRY AND PHOTOBIOLOGY TUROVETS, I., Palanker, D., Lewis, A. 1994; 60 (5): 412-414

    Abstract

    During application of the 193 nm excimer laser to vitreoretinal surgery, very deep cutting of the retina of about 100 microm/pulse was detected at the energy fluence in the range of 0.25-0.35 J/cm2/pulse. At the surface of the ablating tip insoluble bubbles were observed during the irradiation. In this paper we study production of these bubbles in aqueous solutions of sodium chloride. The yield of gaseous photoproducts was measured as a function of NaCl concentration and energy fluence. At concentrations of 100 g/L powerful water vapor bubbles and shock waves were observed. A mechanism of soft tissue cutting by the 193 nm laser in highly absorbing liquid media is suggested that explains the features of vitreoretinal ablation with this system: (1) the high cutting depth when the tip touches the tissue and (2) the absence of cutting when the tip is not in contact with tissue. The advantages of the ArF laser for microsurgery of internal organs are discussed.

    View details for Web of Science ID A1994PR25800003

    View details for PubMedID 7800714

  • VITREORETINAL ABLATION WITH THE 193-NM EXCIMER-LASER IN FLUID MEDIA INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Palanker, D., Hemo, I., TUROVETS, I., Zauberman, H., Fish, G., Lewis, A. 1994; 35 (11): 3835-3840

    Abstract

    To ablate retina and vitreous membranes using the 193-nm argon fluoride excimer laser in a fluid medium.A special delivery system for the 193-nm excimer laser was developed that enabled the delivery of the laser into high-absorption liquid environments. The system was tested on the retina in an in vitro cup preparation of cow's eyes, and also in vivo on retina and vitreous membranes of rabbit eyes. The depth of cut as a function of laser energy was determined for an ablating needle with a 0.25-mm exit diameter.Gentle cutting of retinal tissue and of vitreous membranes was obtained in an energy range of 0.075 to 0.25 mJ/pulse. At the energy level of 0.075 mJ/pulse, four pulses were required for full-depth cut formation in rabbit retina, whereas at energy levels greater than 0.17 mJ/pulse, one pulse was sufficient for full-depth cut formation. The maximal rate of cutting achieved for the bovine retina was 2 mm/sec at a 20-Hz repetition rate of the laser. Ablation occurred only when the tip was held in contact with the tissue.The technology described herein appears to be advantageous and applicable to a variety of vitreoretinal surgical procedures.

    View details for Web of Science ID A1994PM51000008

    View details for PubMedID 7928180

  • PERMEABILIZING MILLIONS OF CELLS WITH SINGLE PULSES OF AN EXCIMER-LASER BIOTECHNIQUES TUROVETS, I., Lewis, A., Palanker, D., GILO, H., VILENZ, A., BRODER, J. C., Lewis, S. 1993; 15 (6): 1022-?

    Abstract

    Poration of millions of cells with single laser pulses of an argon fluoride excimer laser is developed and demonstrated on plant cells. The essence of the technique is to use the large beam size (10 x 25 mm) of the excimer laser and to split it using an appropriate mask into millions of micron- or submicron-sized beams of 193-nm radiation with enough energy to perforate cell membranes and walls. The extremely small depth of penetration of the 193-nm radiation in biological tissue (< 1 microns) is used to great advantage in this technique to provide for a gentle method that does not lead to cell death. This is the first laser-based method that has enough throughput to make it viable for biotechnological applications. Of considerable significance is that the method is applicable not only in the case of the single cells in suspension, but also for cells growing on the leaves of living plants.

    View details for Web of Science ID A1993MK53300012

    View details for PubMedID 8292334

  • INTERACTION BETWEEN HUMAN SPERM CELLS AND HAMSTER OOCYTES AFTER ARGON FLUORIDE EXCIMER-LASER DRILLING OF THE ZONA-PELLUCIDA FERTILITY AND STERILITY Simon, A., Palanker, D., HARPAZEISENBERG, V., Lewis, A., Laufer, N. 1993; 60 (1): 159-164

    Abstract

    To provide conclusive evidence that sperm cells gain access to the perivitelline space exclusively through a laser-drilled opening. To assess the optimal size of the hole and to evaluate the efficacy of laser drilling in comparison with that of mechanical zona dissection.An interspecies model of human sperm cell that interacts with a laser-drilled or partially zona-dissected hamster oocytes.Penetration rate into the perivitelline space as related to the size of the opening (group A [5 microns], group B [10 microns], and group C [15 microns]) and to the sperm cell concentrations (1 x 10(6), 5 x 10(6), and 10 x 10(6) cells/mL) used for insemination.For each sperm cell concentration, the penetration rate into the perivitelline space was lowest for group A followed by group C and highest for group B. When penetration was compared for each hole size, it was found that sperm concentration had no effect on the rate of penetration in groups A and C but significantly affected this rate in group B. The highest penetration rate of 73% was observed with a concentration of 10 x 10(6) cell/mL and declined to 58% and 23% at 5 x 10(6) cell/mL and 1 x 10(6) cell/mL, respectively. Oocytes drilled by laser (10-microns hole) demonstrated a significantly higher penetration rate when compared with those treated by partial zona dissection (73% versus 20% and 58% versus 21% for sperm densities of 10 x 10(6) cells/mL and 5 x 10(6) cells/mL, respectively).Human sperm cells gain access into the perivitelline space of hamster oocytes exclusively through a hole drilled by an argon fluoride excimer laser. An opening of 10 microns was found to yield optimal results. Laser drilling of the zona pellucida seems to be superior to that of mechanical slitting in terms of sperm oolema interaction.

    View details for Web of Science ID A1993LK48000028

    View details for PubMedID 8513935

  • THE EFFICACY AND SAFETY OF ZONA-PELLUCIDA DRILLING BY A 193-NM EXCIMER LASER FERTILITY AND STERILITY Laufer, N., Palanker, D., Shufaro, Y., Safran, A., Simon, A., Lewis, A. 1993; 59 (4): 889-895

    Abstract

    To examine the efficiency of argon fluoride excimer laser drilling of the zona pellucida of mouse oocytes in improving in vitro fertilization (IVF) at low sperm concentrations and to assess its safety.Oocytes obtained from (Balb/c x C57BL6)CB6F1 female mice were drilled by laser and divided into two groups: group I (89 oocytes) were inseminated with 10(5) sperm cells/mL, and group II (94 oocytes) were inseminated with 10(6) sperm cells/mL. Both groups' fertilization rate and development in vitro was compared with control oocytes that underwent the same preparation steps but no drilling (94 and 88 oocytes for group I and group II, respectively).The fertilization rate and the development in vitro of the laser-drilled groups is compared with that of the control. In addition, in vivo development of embryos generated from laser-drilled oocytes after transfer to pseudopregnant recipients is assessed.For both sperm concentrations, laser drilling significantly enhanced fertilization over control (67% versus 31% at 10(5) sperm cells/mL and 90% versus 54% at 10(6) sperm cells/mL). The development into the blastocyst stage after 96 hours of incubation was similar for both the laser-drilled and control groups at any sperm cell concentration. However, complete hatching at this point was significantly enhanced by the drilling procedure. Normal litters were obtained from the transfer of embryos developed from zona-drilled oocytes into pseudopregnant recipients.Excimer laser drilling enhanced IVF at low sperm cell concentration. The procedure is safe and did not interfere with embryo development in vitro or in vivo.

    View details for Web of Science ID A1993KV24900030

    View details for PubMedID 8458512

  • MICROSURGERY OF THE RETINA WITH A NEEDLE-GUIDED 193-NM EXCIMER LASER INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Lewis, A., Palanker, D., Hemo, I., Peer, J., Zauberman, H. 1992; 33 (8): 2377-2381

    Abstract

    This article presents a method used to guide the beam from an argon fluoride excimer laser to make it suitable for microsurgical purposes and confine it to areas that can be varied in dimension from 1 micron to tens or hundreds of microns. This approach guides the excimer laser beam with an articulated mechanical arm and confines it with variable-diameter tapered tubes, possibly allowing the use of this laser in in vitro retinal surgery with endolaser techniques. Currently, because of the lack of a delivery and focusing system for the 193-nm argon fluoride beam and its absorption by biologic liquids, this laser is used exclusively in ophthalmology for topical applications, such as corneal sculpting. This new method resolves these problems in a unique way with impressive results. Specifically, it was shown that, with this needle-guided excimer laser, it is possible to remove retinal tissue accurately without detectable damage to surrounding cells. Applications of this new technique in retinal surgery are discussed.

    View details for Web of Science ID A1992JE50900004

    View details for PubMedID 1634334

  • EFFECT OF THE ARF EXCIMER LASER ON HUMAN ENAMEL LASERS IN SURGERY AND MEDICINE Feuerstein, O., Palanker, D., FUXBRUNNER, A., Lewis, A., Deutsch, D. 1992; 12 (5): 471-477

    Abstract

    Human enamel surface was irradiated with ArF excimer laser and examined under light microscopy and scanning electron microscopy (SEM). Enamel surface was irradiated at three different areas with different energy fluences. It is demonstrated that the ArF excimer laser causes ablation of the calcified hard enamel tissue. Ablation curves were measured. There was no significant difference found in the etch depth between the three different areas of enamel surface. The morphology of the irradiated areas seen under the SEM was found to be dependent on energy fluence. It changed with increase in energy fluence from being etched to forming a smooth, fused, glaze-like surface and then at very high energy fluences producing a rough surface. The influence of the laser irradiation was confined to the irradiated area only, with no visible heat damage to the surroundings. These results suggest that excimer laser could be applied in a controlled and defined manner for tooth enamel treatments in dentistry.

    View details for Web of Science ID A1992JQ31500002

    View details for PubMedID 1405998

  • Statistical Approach for Subwavelength Measurements with a Conventional Light Microscope. Biophysical Journal Palanker D., Lewis A. 1991; 60: 1147-1155
  • TECHNIQUE FOR CELLULAR MICROSURGERY USING THE 193-NM EXCIMER LASER LASERS IN SURGERY AND MEDICINE Palanker, D., OHAD, S., Lewis, A., Simon, A., SHENKAR, J., Penchas, S., Laufer, N. 1991; 11 (6): 580-586

    Abstract

    A new cell surgery technique has been developed to produce well-defined alterations in cells and tissue without detectable heating and/or other structural damage in the surroundings. The technique involves the use of an argon fluoride excimer laser, in the deep ultraviolet (UV) region of the spectrum at 193 nm, which is guided through a glass pipette filled with a positive air pressure. To demonstrate the method, holes were drilled in the zona pellucida of mouse oocytes. The diameter of the drilled hole was determined by the pipette tip size, and its depth by an energy emitted per pulse and number of pulses. Scanning electron microscopy of the drilled mouse oocytes showed uniform, round, well-circumscribed holes with sharp edges. Oocytes that had their zona pellucida drilled with this new method fertilized in vitro and developed to the blastocyst stage in a rate similar to that of control group. These results demonstrate the nonperturbing nature of this cold laser microsurgical procedure. In addition to the extension of our results for clinical in vitro fertilization purposes, such as enhancement of fertilization and embryo biopsy, there are wide-ranging possible uses of our method in fundamental and applied investigations that require submicron accuracy in cellular alteration.

    View details for Web of Science ID A1991GR70300012

    View details for PubMedID 1753851

  • [Aggregation of cardiolipin liposomes induced by monovalent cations]. Biofizika Atsagortsian, A. Z., Vasiukov, A. E., Palanker, D. V., Nadzharian, G. N. 1989; 34 (1): 49-53

    Abstract

    Monovalent ion induced aggregation of the cardiolipin bilayer liposomes is studied. Derived threshold concentrations (Ck) stimulating fast aggregation testify that the order of effectiveness for monovalent cations to cause this process is: H+ greater than Na+ greater than Li+ greater than K+. The Ck is shown to be nonmonotonously dependent on the temperature discovering a maximum in the range approximately 30-40 degrees C. It is also shown that the liposomes preliminary temperature processing for two hours at approximately 70 degrees C as well as the liposomes incubation for several days at approximately 5 degrees C affect the Ck value. In both cases a considerable Ck increase is accompanied by almost two-fold increase of the lipid oxidation index. The studied process is reversible to both electrolyte concentration dilution and temperature changes. However, unlike the phosphatidylserine (PS) and phosphatidic acid (PA) liposomes the observed changes in the cardiolipin case proceeding considerably slower possibly indicate that the potential must be lower in its depth than that in the case of PS and/or PA.

    View details for PubMedID 2730931

  • The Effect of the Discreteness of Charge on the Potential Distribution in the Phospholipid Membrane. Proceedings of the Academy of Sciences of the Armenian Republic. Physical Series Atsagortsjan A., Palanker D., Nadjarjan G.N 1987; 22 (5): 266-272

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