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Our two year experience with excimer laser photorefractive keratectomy for the correction of myopia on 160 eyes of 128 patients is described. All eyes were treated with a VISX Twenty- Twenty excimer laser, with the following parameters: radiant exposure 160 mJ/cm2, frequency 5 Hz, ablation zone diameter 5.0 to 5.5 mm, and stromal ablation rate 0.18 to 0.33 (mu) /pulse. A suction fixation ring was used in all cases either with nitrogen flow (79 eyes) or without nitrogen flow (81 eyes) across the cornea. Follow-up ranged from one month (152 eyes) to 24 months (12 eyes). The results are stable between 3 and 24 months with less than 0.25 D change in the mean postoperative spherical equivalents. In eyes with a follow-up of 6 to 24 months, 77% to 100% were 20/40 or better uncorrected, and 84% to 92% were corrected to within +/- 1 D of emmetropia. Further follow-up is needed to assess the long term safety and efficacy of the procedure.
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High speed shadow photography is performed on excimer laser ablated porcine corneas and rubber stoppers to capture the excimer laser induced shock waves at various time delays between 40 and 320 nanoseconds. The shock waves in air, nitrogen, and helium are recorded by tangentially illuminating the ablated surface with a tunable dye laser, the XeCl excimer laser pulse. The excimer laser ablates the specimen and excites the dye laser, which is then passed through an optical delay line before illuminating the specimen. The shadow of the shock wave produced during ablation is then cast on a screen and photographed with a CCD video camera. The system is pulsed at 30 times per second to allow a video recording of the shock wave at a fixed time delay. We conclude that high energy acoustic waves and gaseous particles are liberated during excimer laser corneal ablation, and dissipate on a submicrosecond time scale. The velocity of their dissipation is dependent on the atmospheric environment and can be increased two-fold when the ablation is performed in a helium atmosphere. Therefore, local temperature increases due to the liberation of high energy gases may be reduced by using helium during corneal photoablation.
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We have developed a simple instrument for making objective measurements of haze that develops following excimer laser ablation of the cornea. It consists of an appropriately modified slit-lamp microscope, with a fiber optic pickup, a filter system for wavelength selection, and a photomultiplier detector. The scattered intensity at 120 degree(s) from the forward direction is determined. Preliminary tests were made by measuring the haze following a deep photorefractive ablation on a rabbit cornea under conditions which ensured that rather severe haze would develop. The VISX Model 20/20 laser system was set to produce a 6.0 mm diameter, -15 D correction, with a central depth of 236 micrometers . Measurements were made on the normal cornea prior to ablation and at various times up to 114 days post-ablation and are compared to slit-lamp photographs. Scattering peaked two weeks post-ablation at a value approximately 40X that of the normal (unablated) cornea and gradually decreased to approximately 11X the normal value at 114 days.
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Cornea: Refractive Surgery, New Beam-Delivery System
This paper reports on our progress using an erodible mask to perform photorefractive keratectomy (PRK) for the correction of myopic astigmatism. We describe modifications to the mask, the mask eye cup and the surgical microscope aimed at simplifying the procedure and improving the ergonomics of the hardware. We report the clinical results of the post-op exam for 20 patients who have undergone PRK for myopic astigmatism under a Phase IIA study. The results compare favorably with an earlier Phase IIA study for performing PRK with a computer-controlled iris. Most important, the clinical data show the absence of any significant corneal haze and no significant decrease in spectacle corrected visual acuity. Although more long term follow-up is needed, the preliminary results support the safety and effectiveness of using an erodible mask to perform PRK for myopic astigmatism.
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Taking the functional block diagram of an ophthalmic laser surgical system presented by Taylor et al. in 1989, important technical features for the clinical use of the 193 nm excimer laser are presented.
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Replacing the gas ArF (193 nm) excimer laser with a solid state laser source in the far-UV spectrum region would eliminate the hazards of a gas laser and would reduce its size which is desirable for photo-refractive keratectomy (PRK). In this study, we investigated corneal reshaping using a frequency-quintupled (213 nm) pulsed (10 ns) Nd:YAG laser coupled to a computer-controlled optical scanning delivery system. Corneal topographic measurements showed myopic corrections ranging from 2.3 to 6.1 diopters. Post-operative examination with the slit-lamp and operating microscope demonstrated a smoothly ablated surface without corneal haze. Histological results showed a smoothly sloping surface without recognizable steps. The surface quality and cellular effects were similar to that of previously described excimer PRK. Our study demonstrated that a UV solid state laser coupled to an optical scanning delivery system is capable of reshaping the corneal surface with the advantage of producing customized, aspheric corrections without corneal haze which may improve the quality of vision following PRK.
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Vance M. Thompson M.D., Daniel S. Durrie M.D., John D. Hunkeler M.D., Art C. Hurt III, P. Michael Mann M.D., Theo Seiler, Michael C. King, Alex C. Sacharoff, David F. Muller
We describe the results of a 30 patient Phase I clinical trial using the Laser Thermokeratoplasty (LTK) treatment for correction of hyperopic astigmatism. We report the results for 29 patients who have reached 2 months post-operative. The average pre-op cylinder was reduced from -3.06 Diopters (D) to -1.21 D. Average spherical equivalent (SE) refractive error was reduced from +2.28 to +1.34 D. Six patients have reached 4 months post-op; the average cylinder of these patients has been reduced from -1.92 to -0.79 D while the average SE has been reduced from +1.29 to +0.31 D. Although patients had varying degrees of astigmatism pre-op, all treatments were performed with identical parameters (intended to correct a small amount of astigmatism) to enable us to determine the effect of the procedure without the influence of other factors such as varying zone diameter or laser fluence. The predictability and stability of the LTK procedure are supported by a recent study of 20 patients treated in Germany by Seiler for low to moderate degrees (2 - 4 D) of hyperopia. After 6 months post-op, 16 of 20 patients are within +/- 1 D of the attempted correction. Longer-term follow-up will be necessary to determine the ultimate refractive stability of the LTK procedure.
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A new system for non-contact laser photo thermal keratoplasty (LPTK) is revealed and demonstrated. This non-contact system alleviates or removes some of the undesirable characteristics associated with a variety of contact systems currently being pursued and practiced.
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A unique continuous wave (cw) holmium laser ((lambda) equals 2.09 micrometers , Rare Earth Medical) has been evaluated as a new heating modality for thermokeratoplasty. Thermokeratoplasty is a refractive surgical procedure for the correction of hyperopia which uses selective heating to reshape the cornea. The holmium laser is highly effective in this procedure due to the high absorption coefficient ((mu) a equals 27.55 cm-1) of the cornea at 2.09 micrometers . The depth of corneal photocoagulation has been evaluated with histological studies of enucleated porcine eyes that were irradiated with the cw Ho:YAG laser. Laser power and exposure time ranged from 300 mW to 800 mW and 100 ms to 800 ms, respectively. The laser was delivered to the eyes via a 600 micrometers low-OH optical fiber. Coagulation depth was determined by birefringence microscopy of the corneal sections. Our studies also compared the effects of contact and non-contact irradiation and found significant advantages with the contact mode. The optimal laser parameters determined from the histology studies were used for in vivo rabbit studies to quantify the refractive correction possible. One coagulation was placed on each of sixteen equiangular rays taken from a central, clear, optical zone in the cornea with a diameter of 7 mm. Refractive changes in the central cornea were quantified with a keratoscope. Initial procedures resulted in refractive changes up to five diopters. The keratoscope results showed a significant regression at three weeks post- operatively.
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Ophthalmic Measurements and New Optical System Design
This paper demonstrates the three-dimensional visualization of the ex vivo rabbit cornea. The cornea is an ideal test specimen to evaluate techniques for 3-D reconstruction and visualization of unstained, unfixed, transparent living tissues from a stack of optical sections. The 0.4 mm thick, transparent, specimen has been optically sectioned into 365 sections using a laser scanning confocal microscope with a water immersion objective. Isometric sampling resulted in near-cubic voxels which compensated for the reduced microscopic resolution in the z axis as compared to x and y resolution. This paper demonstrates the first three-dimensional visualization of the posterior stroma and the basal epithelium of the ex vivo rabbit cornea.
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In the STARE project (structured analysis of the retina) we are developing a system that will automatically diagnose images of the ocular fundus, compare sequential images for change, and make clinically significant measurements of lesions and anatomical structures in the images. Ophthalmologists need to compare color images, fluorescein angiograms, indocyanine angiograms, and scanning laser ophthalmoscopy for onset of disease and changes in lesions. The images are made from fundus cameras of different manufacture and at different magnification. Consequently we designed our system to register images of different magnification or appearance automatically.
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A new, nonapplanating, real-time slit scanning confocal microscope is described for the in vivo examination of the living human eye. This confocal microscope produces unique real- time video images of the in vivo human cornea. In contrast to other confocal microscopes designed for in vivo ocular imaging, which are based on either the Nipkow disk (pinholes) or the modified wide-field specular microscope (photographic system which is not real time), this new instrument produces single video frames which have superior resolution and contrast. This new real-time slit scanning confocal microscope produces en face, high contrast, high resolution, images of the wing cells, epithelial basal cells, corneal innervation, nuclei of stromal keratocytes, and the cell bodies of the stromal keratocytes in the posterior stromal region, and thus demonstrates its unique real-time imaging features. This real-time confocal microscope is based on a modular building block principle. This new microscope is equipped with water immersion microscope objectives which do not applanate the cornea; a polymer gel is used to optically couple the tip of the microscope objective to the eye.
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Concepts including the length of T-incisions are mainly based on empirical evaluation of the surgeons. We report on a holographic interferometric study of the effects of straight T- incisions of 5 mm, 10 mm, and 15 mm length using double-exposure holographic interferometry. A new classification of the central holographic interferometric fringe pattern including cross-like, parallel and convex fringes allows an objective qualitative analysis of 48 holographic interferograms of the corneas of six bovine eyes. The intraocular pressure is 1340 Pa with 10 Pa and 20 Pa pressure increase. T-incisions of 5 mm length of incision (incision depth 95%) change the holographic interferometric fringe pattern completely. An increase to 10 mm length of incision results in a change of holographic fringe pattern in 50% of the cases. With 15 mm length of incision only two types of holographic interferometric fringe pattern of the cornea can be seen: parallel fringes and irregular fringes indicating an instability of the cornea. This might be a reason for paradox flattening of the cornea in the unincised meridian.
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We present a new technique for coherent optical imaging of ocular structure based on optical coherence tomography (OCT). OCT is a noncontact, noninvasive, tomographic imaging technique with superior spatial resolution to ultrasound (< 20 micrometers ) and high sensitivity (100 dB dynamic range). We have used OCT to perform direct imaging of ocular structure in the anterior and posterior segments of human eyes in vitro and in vivo. In the anterior segment, we have measured corneal thickness and profile, anterior chamber depth and angle, and iris thickness and profile. These and other possible measurements have potential applications in diagnosis of pathologies of the cornea, angle, and iris, as well as in noncontact biometry for applications in cataract and corneal refractive surgeries. In the posterior segment, we have obtained high-resolution images of retinal structure in human subjects in vivo. These images demonstrate higher resolution than available with any other existing technique, and include characterization of optic disk morphology and topology. These measurements have potential applications in early diagnosis and assessment of glaucoma and other retinal diseases.
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To treat for some eye diseases by means of the modern methods of sight correction (microsurgical operation of keratotomy, contact lens fitting, etc.) it is necessary to know the exact shape of the anterior surface of a cornea (or the corneal topography). In order to use these methods successfully it is required that the optical power distribution be determined with the precision of 0.25 diopter. For this purpose at present special devices, keratoscopes, are usually used. A main disadvantage of these devices is a great sensitivity of measurement precision from displacements of eye relative to device. Therefore, in these keratoscopes the eye should be located relative to the apparatus very accurately, with the error less than 0.25 mm. This disadvantage decreases the possibilities of the keratoscopes. That is why the main problem of keratoscope designing is to eliminate the influence of eye alignment on the measurement precision.
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The study of insertion and deployment of foldable IOLs in cadaver eyes is enhanced by viewing the process from the posterior pole position. A video system was constructed to view IOL placement in sectioned eyes from the posterior position. All tissue used in this study were prepared using the VISUALEYESTM Surgical Practice System (Visitec Co., Sarasota, FL). This system allows for the precise placement and resection of the proximal third of the posterior segment of the globe. The remaining two-thirds of the globe is then placed onto the eye holder, which allows the tissue to be viewed from the posterior position. After the tissue has been prepared and attached to the fixation plate, the entire assembly is attached to the video system. A variety of intraocular procedures can then be performed utilizing this system. Both anterior and posterior views can be video taped for later analysis. Parameters such as IOL diameter, haptic length, positioning of the IOL within the eye and unfolding characteristics can be assessed using this system. This paper discusses the development of this device and presents examples of its use in the study of foldable IOL deployment.
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We describe the design and building of an apparatus which can be used to measure the central and peripheric visual fields of humans. It minimizes technician mistakes or subjective responses of the patient.
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The STORZTM TRUE VISTATM bifocal intraocular lens was evaluated in a laboratory setting and during clinical trials. The modulation transfer function and through focus response were measured in a simulated eye chamber for selection of optimal add zone size, location, power, and pupil dependency. Results indicate the optimal design to be an annular add power of +4 D having a 1.5 millimeter inner diameter and a 2.6 millimeter outer diameter. Optical performance was predicted using computer ray trace and Fourier analysis. Laboratory testing confirmed design performance achieved through the manufacturing process. Clinical results correlate well with through focus response but less well with modulation transfer function.
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Age-related macular degeneration is a disease that affects the retina in eye of the older adult, causing central visual field loss. This can result in reduced visual acuity. A magnified image effectively appears as if the visual field loss is small relative to that image. The magnification is provided by an ocular telephoto system consisting of a diffractive and refractive hybrid spectacle lens and a dual-purpose intraocular lens. Without the spectacle lens, the intraocular lens functions as an implant for the treatment of cataracts. With the spectacle the system assists the patient in visual near tasks, such as reading or writing. The application of diffractive optics on the spectacle permits the correction of optical aberrations while reducing the size and weight of the high-power spectacle lens.
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Spherical aberration for intraocular lenses is calculated based on surface contributions. The impact on image quality can be determined using a defined pupil function. Relationship between wavefront aberration and displacement of the best focal plane is discussed. The impact on ANSI Z80.7 power labelling is computed and found to be as great as 0.9 Diopters for standard lens types from the combination of media conversion error and spherical aberration. A pupil function is defined for solution of the Fresnel diffraction integral, in the Fraunhofer approximation, and is used to compute strehl ratio and modulation transfer function for symmetrical biconvex, convex plano and meniscus lenses in standard atmosphere and in situ. Results in air indicate best optical performance for convex plano lenses due to minimization of spherical aberration. In situ, all lenses analyzed performed approximately equally well. Use of this calculation technique for refractive bifocal IOL performance prediction is discussed.
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Laser lyses have been made for 41 cases of eyes having posterior capsular fold after extracystic cataract extraction and posterior chamber artificial intraocular lens implantation by applying a Nd:YAG laser. Laser energy of a single pulse is 0.4 to 1.1 mJ, and the total curative energy per eye averages 24.1 mJ. Visual improving rate after treatment reaches to 100%. The curative rate after one time is 63.4%, and at the most three treatments are required. No complication has been found, and no damage on the intraocular lens has been observed with a high power microscope. Knowing well and strictly indications and selecting a suitable laser energy and focusing precisely are beneficial to improving the curative effect.
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The effect of various laser parameters on the ablation rate and the resulting thermal damage on porcine scleral tissue by the Ho:YAG laser was tested. We compared the ablation rate and the thermal damage with varying fluences, fiber core diameters and pulse durations. A Ho:YAG laser operating at a wavelength of 2.1 micrometers at a repetition rate of 2 Hz was used. The ablation rate for the tissue was calculated as the ratio of the number of pulses needed to perforate the sample to the sample thickness (micrometers /pulse +/- standard deviation). The lateral thermal damage depths were quantified by ocular micrometry. Our results suggest that with the Ho:YAG (2.1 micrometers ) laser the ablation rate increases linearly with radiant exposure, but the change in radiant exposure does not significantly affect thermal damage. Different pulse durations generate small changes in ablation rate, but no change in thermal damage. An increase in the irradiated area enhances the ablation rate and thermal damage.
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Goniotomy is an effective treatment for primary infantile glaucoma. Unlike trabeculotomy, goniotomy facilitates the visualization of the trabecular meshwork and does not disturb the conjunctiva. Because a cloudy cornea may prevent a clear view of the anterior chamber angle through the operating microscope, we investigated whether an endoscope would improve visualization during goniotomy in pig cadaver eyes. We deepened the anterior chamber of each pig eye with viscoelastic material. A modified 23-gauge needle attached to an Olympus 0.8 mm diameter flexible fiberoptic endoscope entered the anterior chamber through a 3 mm limbal incision. The angle was clearly seen on a videoscreen as the needle approached and incised the trabecular pillars for 120 degree(s); the iris immediately fell back. Following the procedure, the eyes were fixed in formalin and sectioned for light microscopy, or fixed in 2% glutaraldehyde for scanning electron microscopy. Trabecular pillars were present from the iris root to Schwalbe's line in the untreated region of the anterior chamber angle. The treated area demonstrated incision of the trabecular pillars with opening of the underlying trabecular meshwork.
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A number of studies have supported the efficacy of transscleral cyclophotocoagulation in reducing intraocular pressure in human eyes that are refractory to medical or traditional surgical treatments. Due to its recent history, however, no information has yet been made available on optimal exposure parameters for this treatment modality. An 810 nm diode laser was used to examine lesion formation during transscleral irradiation and compared to those reported for the Nd:YAG laser. A large sector iridectomy was performed on the eye, and a slit lamp delivery system combined with a digital image acquisition system (time resolution of 17 milliseconds) were used to view the ciliary body before, during, and after cyclophotocoagulation. The data obtained provide a basis for an in-vivo examination of lesion morphology as well as the underlying mechanism of ciliary destruction using the two laser sources.
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A double beam spectrometer, which works in single photon counting technique, was developed for measuring the reflectance spectra at selected fundus sites in a wavelength range from 430 to 700 nm. By forming logarithmic difference spectra between the reflectance of the normal fundus and the fundus reflectance in different stages of glaucoma only substance or structure specific glaucomatous alterations appear. The approximation of logarithmic difference spectra is demonstrated by a linear model. The primary information in the modelling is only the relative spectral course of important fundus substances like oxyhemoglobin, melanin and xanthophyll. The influence of scattering is formulated as a wavelength-independent intensity, multiplied by a term, containing a power of the wavelength. Found by the spectra-deconvolution, a lack of oxyhemoglobin in the papillo-macular bundle is the first sign of a damaged microcirculation in case of relative losses of the visual field function. The reduced scattering intensity and the altered scattering exponent point to a thinning of the nerve fiber layer.
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Laser sclerectomy, a simple filtering procedure performed to alleviate high intraocular pressure in glaucoma patients, was taught to offer longer lasting effect and therefore improve the patient's outcome when compared with the standard trabeculectomy procedure. Recent clinical trials have shown that this was not the case and pharmacologic wound healing modulation is also required with this new procedure. Five-Fluorouracil (5-FU) is useful as an adjunct treatment for glaucoma filtering surgery. However, efficacy depends upon maintaining sustained drug levels, currently achieved by repeated daily injection of the drug for several weeks. To overcome this limitation, we designed a biodegradable implant for the sustained release of 5-FU. After laser sclerectomy, the implant is inserted through the same 1 mm wide conjunctival snip incision and positioned below the open channel. Implantation takes less than a minute. The implant releases the drug for over 15 days and totally biodegrades in less than 100 days. The combined laser surgery and implantation procedure show great potentials for the treatment of glaucoma.
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A THC:YAG (thulium, holmium, chromium-doped YAG crystal) was used to create sclerostomies in 71 glaucomatous eyes of 67 patients, for a total of 83 procedures. The laser is a long-pulsed (300 microsecond(s) ec), compact, self-contained, solid state laser operating in the near infrared (2.1 (mu) ). A 1 mm conjunctival stab incision was made 12 mm from the sclerostomy site to allow entry of a specially designed 22-gauge (712 (mu) ) optic probe that delivers energy at a right angle to the long axis of the fiber. Probe insertion produced minimal disturbance of the conjunctiva. Pulse energies of 80 to 120 mJ were used with a repetition rate of 5 pulses/sec. Total energy levels to produce full-thickness sclerostomies ranged from 1.4 to 7.2 J. Patients ranged in age from 9 to 90 years. Success was defined as postoperative intraocular pressure <EQ 22 mmHg, or a >= 30% reduction in intraocular pressure if preoperative pressure was <EQ 22 mmHg. One retreatment was permitted if needed in the surgeon's judgment. Success rate was 65% at 12 months and 56% at 21 months. Mean intraocular pressure of successful cases was 13.0 mmHg at 12 months. Success and failure were analyzed relative to patient risk factors.
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Since its introduction in 1973 by Beckmann et al., transscleral cyclophotocoagulation with the Nd:YAG laser has developed into a successful method in glaucoma therapy. It was initially performed with the aid of non-contact systems, whereby the laser beam was focused by means of a slit lamp. With the introduction of contact systems, for which purpose a number of different probes were employed, the treatment efficiency was found to be improved by a factor between 2 to 6. The transparency of the sclera increases as a function of the pressure exerted. Therefore, the pressure exerted by the contact probe is a critical factor in determining the transmission of laser radiation across the sclera and may in part explain the large differences which are reported in the literature with respect to the effectiveness of this treatment method.
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Laser induced retinal lesions are used to treat a variety of eye diseases such as diabetic retinopathy and retinal detachment. In this treatment, an argon laser beam is directed into the eye through the pupil onto the fundus where the heat resulting from the absorbed laser light coagulates the retinal tissue. This thermally damaged region is highly scattering and appears as a white disk. The size of the retinal lesions is critical for effective treatment and minimal complications. A real time feedback control system is implemented that monitors lesion growth using two-dimensional reflectance images acquired by a CCD camera. The camera views the lesion formation on axis with the coagulating laser beam. The reflectance images are acquired and processed as the lesion forms. When parameters of the reflectance images that are correlated to lesion dimensions meet certain preset thresholds, the laser is shuttered. Results of feedback controlled lesions formed in vivo in pigmented rabbits are presented. An ability to produce uniform lesions despite variation in the tissue absorption or changes in laser power is demonstrated. This lesion control system forms part of a larger automated system for retinal photocoagulation.
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Scleral indentation was induced in cadaver eyes by shrinkage of scleral collagen fibers using a pulsed solid state Ho:YAG (2.1 micrometers ) laser with fiber optic delivery. Applying Ho:YAG laser radiation permits control of the amount of laser induced buckling effect by selecting laser treatment parameters such as beam spot, radiant exposure, and number of pulses. With treatment using 11.3 +/- 1.2 J/cm2 laser radiant exposure and 5 pulses, laser induced scleral shrinkage affected only the external two-thirds of scleral tissue. No thermal damage or disruption was observed in subjacent retinal pigment epithelium, chorioid, or retina. Coupling of two appropriately selected lasers may allow laser induced scleral buckling and transscleral retinal photocoagulation using the same laser probe for retinal reattachment surgery.
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In the eye, the retinal nerve fibers transmit the visual signal from the photoreceptors to the brain. In certain diseases, i.e., glaucoma, these nerve fibers are damaged, resulting in impaired vision or blindness. The retinal nerve fiber layer consists of parallel structures of diameter smaller than the wavelength of light. Therefore, this qualifies it as a form birefringent structure, capable of changing the state of polarization of light double passing it. The amount of change in the state of polarization (retardation) can be assessed with a polarimeter and is proportional to the thickness of the nerve fiber layer at the measurement location. A scanning laser polarimeter (Nerve Fiber AnalyzerTM) is described that employs a low power near infra-red laser beam to illuminate the human retina. In normal eyes, a thick retinal nerve fiber layer was measured in the superior and inferior regions of the peripapillary retina. In glaucoma eyes, this normal nerve fiber layer thickness distribution was found to be disturbed. The measured retinal nerve fiber directions indicated that the retinal nerve fiber layer around the optic nerve head of a normal eye is radially symmetrical.
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Laser induced retinal lesions are used to treat a variety of eye diseases such as diabetic retinopathy and retinal detachment. An instrumentation system has been developed to track a specific lesion coordinate on the retinal surface and provide corrective signals to maintain laser position on the coordinate. High resolution retinal images are acquired via a CCD camera coupled to a fundus camera and video frame grabber. Optical filtering and histogram modification are used to enhance the retinal vessel network against the lighter retinal background. Six distinct retinal landmarks are tracked on the high contrast image obtained from the frame grabber using two-dimensional blood vessel templates. The frame grabber is hosted on a 486 PC. The PC performs correction signal calculations using an exhaustive search on selected image portions. An X and Y laser correction signal is derived from the landmark tracking information and provided to a pair of galvanometer steered mirrors via a data acquisition and control subsystem. This subsystem also responds to patient inputs and the system monitoring lesion growth. This paper begins with an overview of the robotic laser system design followed by implementation and testing of a development system for proof of concept. The paper concludes with specifications for a real time system.
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Nonenzymatic glycation alters collagen throughout the body, resulting in the histopathology that underlies diabetic disease in several organs. In the eye such changes in vitreous collagen could contribute to the progression of proliferative diabetic retinopathy by inducing vitreous degeneration. In this study, near infrared Fourier-transform Raman spectroscopy was performed on vitreous obtained at surgery from diabetic patients and from non-diabetic control subjects. The findings were compared to measurements obtained in untreated and glycated (in vitro) rat-tail tendon collagen, as well as demineralized chick bone, rich in crosslinks. The results demonstrated substantial changes in diabetic vitreous collagen not resulting from enzyme-mediated crosslinking, but most likely advanced nonenzymatic glycation. This approach appears to be useful as a means of characterizing the molecular changes induced by diabetes. Furthermore, this technique could be developed as a way of quantifying these changes in vivo in several tissues, so as to gauge the severity of disease and monitor the response to therapy.
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Malignant melanoma is the most prevalent and the most dangerous primary intraocular tumor. The most common treatment until recently was enucleation. In our experimental work we would like to present the use of hematoporphyrin derivative photodynamic therapy (HpD- PDT) in diagnosis and treatment of cancer. Eighteen eyes of rabbits were incubated intracamerally with amelanotic Greene melanoma tissue. The technique involves the administration of HpD and photoactivation of the tumor with violet light (406 nm) for diagnostic purposes and with red light (630 nm) to achieve selective destruction of cancer cells. After photoradiation the tumor showed blanching and shrinkage, we could also observe the tumor vasculature damage. Successfully treated tumors had large areas of necrosis with severely damaged blood vessels in histopathological examination. Results indicate that HpD- PDT is a very promising modern modality offering new diagnostic and treatment methods for melanoma.
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Although photoablation is considered to be a nonthermal mechanism of tissue removal, previous investigators have shown local temperature rises along the surface of corneal tissue following excimer laser photoablation. These temperature increases can be explained by a hot cloud of ionized gas (plasma) created by the products of ablation. Our study demonstrates that the plasma absorbs incident laser light energy and reduces the transmission and scatter of light at the ablated surface. The spectrum of light generated on the surface consists of a number of atomic lines and molecular bands, thereby verifying the presence of excited and ionized atoms and molecules. The magnitude of light scattering and absorption by the plasma increases with both energy density and the length of the incident pulse. Plasma shielding and absorption of incident light occurs for laser pulsewidths greater than several nanoseconds. The plasma emission spectrum is fairly independent of the atmospheric environment and of the type of material ablated, as long as the material is organic. This suggests that the plasma is created from the ablated material. The temporal decay function is multiexponential and dissipates within a fraction of a microsecond, precluding interaction of the plasma with subsequent pulses during excimer laser photoablation.
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Intraocular microsurgery relies on plasma generation with subsequent shock wave emission and cavitation bubble formation. To assess the potentials of photodisruption with picosecond pulses in comparison to the clinical techniques presently used, the shock wave characteristics and the bubble expension after optical breakdown with picosecond and nanosecond laser pulses were investigated by time resolved photography and acoustic measurements. Nd:YAG laser pulses with a wavelength of 1064 nm and a duration of 30 ps and 6 ns were focused into a water-filled glass cuvette. Their breakdown thresholds were 15 (mu) J and 200 (mu) J, respectively. Frequency doubled light from the same laser pulses was optically delayed between 2 ns and 136 ns and used as illumination source for photography. Since the individual events were well reproducible, the shock wave position and bubble wall position could be determined as a function of time. From the slope of these r(t) curves, the shock wave and bubble wall velocities were determined. The shock wave pressure p(r) was calculated from the shock velocity using the `jump conditions' of the shock front and the equation of state of water. The collateral effects of intraocular microsurgery can thus be considerably reduced by using ps-pulses, and with series of ps-pulses a `laser scalpel' may be realized which offers new applications of photodisruption.
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The proliferation of residual lens epithelial cells (LEC) is responsible for reopacification of the lens capsule and loss of visual acuity after cataract surgery. Photodynamic therapy (PDT) using Di-Hematoporphyrin Ether (DHE) was shown to kill cultured LEC. We studied 2 synthetic photodynamic drugs: Rose Bengal (RB) and Erythrosin B (EB) to determine the minimal PDT parameters. LEC located on the anterior capsule of freshly explanted rabbit lenses were subcultured for the following studies: (1) Dye uptake was evaluated by cellular fluorescence. The minimum concentrations for RB and EB after 1 minute of exposure were 1 (mu) g/ml, and 50 (mu) g/ml; (2) Cytotoxicity was evaluated by reculturing the cells, and was detectable with concentrations of 200 (mu) g/ml RB or 2000 (mu) g/ml EB; (3) The PDT effect was evaluated using concentrations of 1 to 25 (mu) g/ml of RB and 1 to 2000 (mu) g/ml of EB. The minimum parameters for PDT of cultured LEC were 0.5 (mu) g/ml of RB and 10 (mu) g/ml of EB with a 60 second 0.5 W/cm2 irradiation using a 514.5 nm Argon laser. To mimic the in vivo setting, LEC attached to the anterior lens capsule were incubated with EB to evaluate dye uptake. The minimum parameters were 100 (mu) g/ml and 7 minutes of exposure. RB was found most effective and may be useful, but EB was found safer and has potential for conjugation with LEC antibodies for the prevention of secondary cataracts.
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Laser operation is simulated by an eye model, and production and development of the plasma shock wave are investigated. According to the simulating experimental results, a physical mechanism hypothesis of the action upon the cured eye tissue and the influence on the surrounding tissues of the laser plasma shock wave during the operation is presented, and some accompanying phenomena are explained satisfactorily.
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It has been reported that thirty-five cases of congenital persistent pupillary membranes have been cut off by a Nd:YAG laser. Among these, twenty-two are single eye, and thirteen are double eyes. Visual improving rate reaches to 100% after the persistent membranes were cut off, and through making a weak vision therapy for six months, the rate of patients whose visions reach to 1.0 is 41.7%. No complications and lens damage are discovered.
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Keratoprostheses (KPro) are optical elements replacing a cornea that is opacified and which cannot be replaced by transplantation. This occurs, for example, after severe burn or in trachoma. The KPro that consists of an optical cylinder mounted on a supporting plate (haptics) is implanted approximately in the middle of the cornea. It is intended to restore vision, i.e., should give a sufficient visual acuity and a comfortable field of view. Failures are due to rejection (expulsion) and optical decentration of the prosthesis. Postoperative corrections of the refractive power are possible with spectacles. However, in view of the rapid expansion of corneal reshaping with the ArF excimer laser emitting at 193 nm, a direct correction of the anterior surface of the KPro can be envisaged. For that purpose, various designs are analyzed in terms of image magnification and field of view. The possibility of a postoperative adaptation of the keratoprostheses by photoablation with the ArF is then presented.
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To reattach the retina, in many instances, biological or synthetic belt-shaped exoplants are inserted in the orbit and tightened around the globe's equator to inwardly depress the sclera until its inner layers contact the retina. In deforming the globe these `buckling procedures' are thought to affect the eye's optical system and thus vision. A new non-contact optical technique was devised to quantify the refractive effect of the two most common techniques used in retinal detachment surgery.
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Refractive changes can be induced through modification of the anterior corneal surface. A method using an ultrashort pulsed infrared laser (Nd:YLF) and resulting in an intrastromal photoablation has been reported for that purpose. In this concept a well defined stromal volume is ablated or vaporized. After collapse of the bubbles that have been produced, the anterior surface of the cornea should flatten, leading to a lower myopic refraction of the eye. It has already been shown that there is less collateral tissue damage associated with picosecond than with nanosecond laser pulses. In this study, the acute and long term morphological as well as thermal effects of intrastromally applied picosecond laser pulses are investigated.
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The first generation of excimer lasers for refractive surgery have several functional and cost limitations. As a result, product developers are investigating several types of solidstate lasers for this application. Lasers under development include erbium, holmium, Ti:sapphire, short- pulse Nd:YAG, and frequency converted Nd:YAG. Laboratory tests have shown that all of these lasers can perform refractive surgery. The clinical and technical status of each of these lasers are presented in an overview of this emerging technology.
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The earliest laser application in medicine has occurred in ophthalmology. In 1965,the Shanghai Institute of Optics and Fine Mechanics, Academia Sinica, suy developed the first laser retina photocoagulator in China. It was an experimental prototype. Then the laser ophthalmic experiment for animal and for clinical demonstration were carried out at the Shanghai No. 6 People's Hospital. Since 1970 ,further effort has been made to improve the performances of this experimental system, and the ruby laser retina photocoagulator has been produced for clinic application. In 1972 ,a ruby laser photodisruptor was developed ,and was used for clinic peripheral iridectomy one year later. Since 1970,in addition to Shanghai,mo.st of the large cities of China,such as Beijing ,Shenyang,Guangzhou ,Hefei ,Chengdu and Xumou etc. successively started laser ophthalmology. Now the laser ophthalmology has become widespread medical application in China. The municipal hospitals of all provinces except Tibet and the suburban county hospitals have set up their laser ophthalmic clinics. As a regular medical technology ,laser has provided effective treatment for over thousand of the eye diseases patients every year. Among all cities of China , Shanghai is the leading and mo.st developed city in ophthalmology. 220 hospitals in Shanghai set up their laser clinics,and most of them has laser ophthalmic treatment divisions. Recently ,the Shanghai Research Center for Laser Medicine has been established in the Shanghai Second Medical University. The Center has assembled many famous laser medical experts and laser engineering experts. The ophthalmic laser application is its major effort.
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The Ohio State University (OSU) is one site of an FDA controlled investigational study to evaluate the safety and efficacy of excimer laser photorefractive keratectomy (PRK). This is a report of the current Phase III results at OSU for cases at 6 months post surgery as of 12/31/92.
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Scientists have searched every discipline to find effective methods of treating blindness, such as using aids based on conversion of the optical image, to auditory or tactile stimuli. However, the limited performance of such equipment and difficulties in training patients have seriously hampered practical applications. A great edification has been given by the discovery of Foerster (1929) and Krause & Schum (1931), who found that the electrical stimulation of the visual cortex evokes the perception of a small spot of light called `phosphene' in both blind and sighted subjects. According to this principle, it is possible to invite artificial vision by using stimulation with electrodes placed on the vision neural system, thereby developing a prosthesis for the blind that might be of value in reading and mobility. In fact, a number of investigators have already exploited this phenomena to produce a functional visual prosthesis, bringing about great advances in this area.
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Jean-Marie A. Parel, William Q. Jeffers, Gabriel Simon, Patrick Hostyn, Jean-Marc Legeais M.D., Francois Kuhne, Yoshiko Takesue M.D., Hiroyuki Shimada, Elena Barraquer, et al.
With their inherent precision and avoidance of tissue deformation, non-contact laser trephines may minimize graft postoperative astigmatism. Laser-cut corneal button geometry surpassed handheld and equaled Hanna and Krumeich vacuum held trephines, without significant endothelium or wound healing differences for linear cuts between laser and metal blades. To compare the laser with metal trephines, we performed 8 mm diameter grafts on 12 rabbits and 12 cats. A new laser system, using an advanced pulsed HF laser coupled to a computer controlled optical delivery system and equipped for quasi-instantaneous simultaneous 8-point corneal marking (200 ns) for precise suture placement at the 5.5 to 10.5 mm diameter and rapid corneal trephination (approximately equals 6 sec), or a new disposable sterile vacuum-assisted Hessburg-Barron (HB) trephine was used in each procedure. Circumferential keratotomies were more accurately and more easily performed with the laser. No statistical differences were found in wound strength and healing. The laser produced a slightly lower astigmatism. These initial results suggest the safety of HF laser corneal marking-trephination and its potential for PK procedures in humans.
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Ophthalmic Measurements and New Optical System Design
The effect of novel refractive surgical techniques on visual acuity and contrast sensitivity is normally determined by the outcome of human clinical trials. For example, ArF laser photorefractive keratoplasty follows an algorithm based on the patient's preoperative data for keratometry, refraction, pachometry, and ocular length all measured with ultrasound. A normalized ablation rate (which is function of the laser fluence), and the desired refractive correction are then used to calculate the ablation depth. On the day of surgery, the epithelium is mechanically removed and the bare cornea photoablated. Finally, the cornea may be medicated with a topical application of antibiotics and the eye is patched. On postoperative day 7, the epithelium is healed and visual acuity and keratometry are measured. With PRK, the theoretical outcome refraction should be within +/- 0.25 D. Thus far however, reproducibility is only of +/- 2 D. We believe the large discrepancy between theory and practice is due to several parameters that vary patient-to-patient.
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The effect of novel intraocular implants and refractive surgical techniques on visual acuity and contrast sensitivity is normally determined by the outcome of human clinical trials. Even if intraocular lenses (IOL) are optically `bench tested' prior to implantation, and their contribution to the patient's vision modeled by computer simulation, the clinical outcome is often poorer than mathematically predicted. This is due in large part to the approximations made in the schematic eye used for computation and the biological variables, such as iris geometry, the implant centration, and location with respect to the three-dimensional position of the visual axis and foveal plane. In vitro laboratory optical testing of novel IOLs and lens refractive procedures, such as capsular bag refilling and inflatable balloons, are non-existent. As animal experiments cannot resolve this dilemma, we took a new in vitro approach at assessing the vision of surgically modified and/or implanted human eyes. Using stock parts, a new optical instrument was built to measure the in situ optical resolution and OMTF of fresh cadaver eyes and to comparatively assess novel surgical techniques and implants by pre- and postoperative optical measurements of the retinal image.
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