Daniel Palanker

Femtosecond laser capsulotomy.

PURPOSE: To evaluate a femtosecond laser system to create the capsulotomy. SETTING: 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. DESIGN: Experimental and clinical study. METHODS: 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. RESULTS: 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 μm ± 26 (SD) for the laser technique and 337 ± 258 μm for the manual technique. The mean deviation from circularity was 6% and 20%, respectively. The center of the laser capsulotomies was within 77 ± 47 μm 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 μJ, 121 ± 16 mN for 6 μJ, and 113 ± 23 mN for 10 μJ. The strength of the manual capsulorhexes was 65 ± 21 mN. CONCLUSION: The femtosecond laser produced capsulotomies that were more precise, accurate, reproducible, and stronger than those created with the conventional manual technique. Financial Disclosure: The authors have equity interest in OptiMedica Corp., which manufactures the femtosecond laser cataract system.

Photovoltaic retinal prosthesis with high pixel density

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/mm2, two orders of magnitude below the ocular safety limit. Neural responses were elicited by illuminating a single 70 μm bipolar pixel, demonstrating the possibility of a fully-integrated photovoltaic retinal prosthesis with high pixel density.

Femtosecond Laser–Assisted Cataract Surgery with Integrated Optical Coherence Tomography

An image-guided, femtosecond laser can create precisely placed, accurate cuts in the eye to improve cataract surgery. The Power of Light As Star Wars fans know, a lightsaber fares better against the Dark Force than does a metal sword. Ophthalmologists, who battle the darkening forces of eye disease, have also learned this lesson, replacing steel scalpels with lasers for creating precise, controlled incisions in the eye. Laser-assisted in situ keratomileusis—commonly known as LASIK surgery—corrects myopia (nearsightedness) and other refractive errors in millions of people each year. Now, Palanker et al. used this approach to devise a more precise, reproducible and automated way to remove cataracts. The authors combine the precise cuts of a laser with the imaging sophistication of optical coherence tomography, a method that uses interference of coherent light scattered by biological tissues to create three-dimensional images of their internal structure. On the basis of the individual patient’s eye anatomy, the laser system calculates the optimal set of cutting patterns for cataract removal and directs the laser to execute these slices, resulting in fast, clean surgery. Two light-based methods made this surgical advance possible. The first, the femtosecond laser, is ideal for use deep inside a fragile eye. Unlike longer pulse lasers, which melt and boil their targets away, producing significant collateral damage to adjacent structures, femtosecond light pulses can turn the material in the focal spot into ionized plasma, allowing dissection of transparent tissues without heat accumulation and minimal disturbance to the surroundings. The resulting cut is smooth and precise. The second method—optical coherence tomography (OCT)—takes advantage of slight variations in the refractive properties of living tissues. Coherent light scattered by structures within the eye allows reconstruction of a 3D image of the live tissue. Palanker et al.’s instrument uses this imaging technique to map the cornea, iris and crystalline lens within the patient’s eye and precisely position the various laser cuts. The laser makes a circular opening in the lens capsule (the membrane that surrounds the lens itself), sections the opaque lens into small pieces that are easily removed, and carves a partial incision in the cornea for later completion of surgery and insertion of the artificial lens under sterile conditions. The laser-created edges in the lens capsule are stronger than those made manually, so they better resist damage when the opaque lens is removed or the new lens is implanted. All the laser cuts are produced without perforating the cornea, so that the procedure can be performed outside the operating room. The laser can also be used to cut the corneal surface for correction of astigmatism and for creating a port for surgical instruments in the operating room. Although the new instrument plans and performs incisions much more accurately than do currently available tools, a surgeon still must remove the lens manually. The benefits of the more precise surgical incisions on visual acuity in patients with various types of intraocular lenses will need to be ascertained in a larger prospective trial, although the preliminary data in the paper are promising and indicate that the laser procedure is safe for ocular tissues. This new instrument will arm surgeons with a precise and automated lightsaber with which to battle the darkening forces of cataracts. 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.

Semiautomated patterned scanning laser for retinal photocoagulation.

The concept of retinal photocoagulation was introduced by Meyer-Schwickerath for the treatment of diabetic retinopathy in the 1950s and used with some success in the 1960s. The xenon arc photocoagulator utilized for this purpose was large, polychromatic, inefficient, and difficult to operate, prompting a search for a better method of treatment. Further progress was achieved when ruby,1 argon ion,2 and krypton ion3 lasers were coupled to a slit lamp with an articulating arm containing mirrors.4 A contact lens, aiming beam, and movable joystick were used to place the laser beam on the retina. These innovations allowed for creating single laser spots of variable size, power, and duration on the retina with a high degree of precision and ushered in the modern era of retinal laser photocoagulation in the 1970s. The techniques enabled by these devices, termed focal photocoagulation, grid photocoagulation, and panretinal photocoagulation, were refined and shown to be effective in the treatment of proliferative diabetic retinopathy and advanced forms of nonproliferative diabetic retinopathy associated with macular edema in large, prospective, multicenter, randomized trials—the DRS and ETDRS.5,6 These trials validated the efficacy and institutionalized the indications and parameters for treatment that have remained the gold standard since that time. Patients with high risk proliferative diabetic retinopathy who undergo panretinal photocoagulation typically receive between 1,200 and 1,500 laser spots in two to four sessions of 10 minutes to 20 minutes each over the course of 2 weeks to 4 weeks. Because the spots are delivered individually, treatments are time consuming and tedious for the patient and physician alike and can be painful, especially in the retinal periphery. Focal photocoagulation and grid photocoagulation for macular edema are less painful and time consuming, because the spots are applied more posteriorly and are fewer in number, but still are tedious and require a considerable degree of patient cooperation and physician skill to achieve a successful outcome and avoid complications. Until now, little has changed in the general design of the devices used for retinal photocoagulation aside from the substitution of fiber-optic cables for articulating arms and the use of air-cooled solid state lasers rather than water-cooled gas tubes. These innovations have had limited or no impact from the standpoint of the patient or physician on the technique of treatments and clinical outcomes. We reasoned that greater precision and safety in retinal photocoagulation might be achieved by delivering a multiplicity of spots in a pattern created by a scanner rather than as a series of individually placed lesions. We also wondered whether the pattern application time and patient discomfort could be further reduced by using shorter pulses than the conventional 100 milliseconds to 200 milliseconds recommended in the DRS and ETDRS.5,6 Prior efforts toward improvement in retinal photocoagulation systems were principally directed toward (1) fully automated systems with retinal stabilization based on eye tracking7–10 and (2) determination of the optimal dose in each spot using the tissue reflectance– based feedback systems.11 Automated systems required acquisition of an image of the retina before the treatment, planning and aligning all treatment locations with reference to the retinal image, and treating all of these locations automatically. Complex retinal tracking systems were also required in these approaches to ensure alignment between planned treatment locations defined on the acquired image and actual sites on the retina.7–10 The complexity of these fully automated systems hampered the introduction of

Effect of Pulse Duration on Size and Character of the Lesion in Retinal Photocoagulation

OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSIONS 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. CLINICAL RELEVANCE 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.

Healing of Retinal Photocoagulation Lesions

PURPOSE To systematically assess the changes in retinal morphology during the healing of retinal photocoagulation lesions of various clinical grades. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Tissue Damage by Pulsed Electrical Stimulation

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 mum to 1 mm, pulse duration from 6 mus 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 mum, and scaled as 1/r2 for electrodes smaller than 200 mum. 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 mus. 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.

Photovoltaic restoration of sight with high visual acuity.

Patients with retinal degeneration lose sight due to the gradual demise of photoreceptors. Electrical stimulation of surviving retinal neurons provides an alternative route for the delivery of visual information. We demonstrate that subretinal implants with 70-μm-wide photovoltaic pixels provide highly localized stimulation of retinal neurons in rats. The electrical receptive fields recorded in retinal ganglion cells were similar in size to the natural visual receptive fields. Similarly to normal vision, the retinal response to prosthetic stimulation exhibited flicker fusion at high frequencies, adaptation to static images and nonlinear spatial summation. In rats with retinal degeneration, these photovoltaic arrays elicited retinal responses with a spatial resolution of 64 ± 11 μm, corresponding to half of the normal visual acuity in healthy rats. The ease of implantation of these wireless and modular arrays, combined with their high resolution, opens the door to the functional restoration of sight in patients blinded by retinal degeneration.

Near-field infrared imaging with a microfabricated solid immersion lens

We report imaging in the infrared with a microfabricated solid immersion lens. The integrated 15-μm-diameter lens and cantilever are fabricated from single-crystal silicon and scanned in contact with a sample to obtain an image. We demonstrate a focused spot size of λ/5 and an effective numerical aperture of 2.5 with λ=9.3 μm light. The total power transmitted through the lens is a factor of 103 greater than through a metal aperture giving the same spatial resolution. Two 1.0 μm holes in a metal film separated by 3.0 μm are imaged with the solid immersion lens in transmission and shown to be resolved.

The chick chorioallantoic membrane as a model tissue for surgical retinal research and simulation.

Purpose: 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. Methods: 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. Results: The CAM’s ease of use, low cost, and anatomic structure make it a convenient model for surgical retinal and retinal vascular modeling. Conclusion: 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.