Reflectance feedback control of photocoagulation in vivo.

OBJECTIVE: The objective of this research was to build a real-time feedback system that controlled lesion size. Two-dimensional reflectance images were acquired with a charge-coupled device camera during irradiation, and argon laser exposure was ended when parameters of the image reached prespecified values. METHODS: The real-time feedback control system was tested by creating lesions at different power levels in pigmented rabbits. Laser exposure time was controlled by monitoring the central reflectance. RESULTS: Results of feedback-controlled lesions formed in vivo in pigmented rabbits are presented. An ability to produce uniform lesions despite variation in tissue absorption or changes in laser power is demonstrated. CONCLUSIONS: Reflectance control of photocoagulation is possible; incorporation of feedback during photocoagulation has numerous therapeutic and safety benefits over current ballistic delivery.

Maintaining the cornea and the general physiological environment in visual neurophysiology experiments.

Neurophysiologists have been investigating the responses of neurons in the visual system for the past half-century using monkeys and cats that are anesthetized and paralyzed, with the non-blinking eyelids open for prolonged periods of time. Impermeable plastic contact lenses have been used to prevent dehydration of the corneal epithelium, which would otherwise occur in minutes. Unfortunately, such lenses rapidly introduce a variety of abnormal states that lead to clouding of the cornea, degradation of the retinal image, and premature termination of the experiment. To extend the viability of such preparations, a new protocol for maintenance of corneal health has been developed. The protocol uses rigid gas permeable contact lenses designed to maximize gas transmission, rigorous sterile methods, and a variety of methods for sustaining and monitoring the overall physiology of the animal. The effectiveness of the protocol was evaluated clinically by ophthalmoscopy before, during, and after the experiments, which lasted 8-10 days. Histopathology and quantitative histology were performed on the corneas following the experiment. Our observations showed that this protocol permits continuous contact lens wear without adversely affecting the corneas. Thus, it is possible to collect data 24 h each day, for the entire duration of the experiment.

Initial in vivo results of a hybrid retinal photocoagulation system.

We describe initial in vivo experimental results of a new hybrid digital and analog design for retinal tracking and laser beam control. An overview of the design is given. The results show in vivo tracking rates which exceed the equivalent of 38 degrees/s in the eye. A robotically assisted lesion pattern is created for laser surgery to treat conditions such as diabetic retinopathy and retinal breaks.

Chronic measurement of epidural pressure with an induction-powered oscillator transducer.

An induction-powered oscillator transducer (IPOT) was designed for the chronic measurement of epidural pressure. The transducer was completely implantable so all pressure measurements were made through the intact skin. The IPOT had a linear pressure range from -50 to +200 cm H2O, was sensitive to 1 mm H2O and had a zero drift of less than 1 mm H2O/day under full load. Zero drift was minimized by using a hermetically-sealed metal bellows transducing element which was chemically treated to prevent corrosion and creep. The correlation between epidural pressure and intraventricular pressure was determined during the first 24 hours after implantation in six dogs. Epidural pressure was found to be a linear function of intraventricular fluid pressure. Epidural pressure and intraventricular pressure were essential equal provided the epidural wedge pressure was minimized by proper insertion of the transducer. The correlation between epidural pressure and intraventricular pressure was determined after chronic implantation in five dogs. Epidural pressure was a linear function of intraventricular pressure in the chronically implanted dogs, but epidural pressure was not equal to intraventricular pressure. After chronic implantation, the epidural pressure transducer was not responsive to changes in intraventricular pressure because of mechanical changes in the dura. The dura became stiff and non-compliant. Maximum correlation between epidural pressure and intraventricular fluid pressure in chronic implantations will depend on judicious material selection and mechanical design at the transducer-dura interface.

Corneal photocoagulation with continuous wave and pulsed holmium: YAG radiation.

In this study, the effectiveness of pulsed and continuous wave (CW) holmium: YAG lasers in coagulating in vitro pig corneas was analyzed. With the CW laser, irradiance and exposure time were varied; irradiance, from 162 to 324 W/cm2 and exposure time, from 200 to 800 ms. With the pulsed laser, number of pulses and radiant exposure were varied; number of pulses per lesion, from 4 to 30 and radiant exposure, from 10 to 25 J/cm2. Laser-induced corneal damage was determined by analyzing histological cross sections of each lesion. Depth and diameter of the lesions were plotted against the varying laser parameters. Light and birefringent photomicrographs of typical lesion histology show that the pulsed laser significantly damaged superficial layers of the cornea and could not achieve the coagulation depths produced by the CW laser. Additional histology demonstrates that minimal surface damage (intrastromal coagulation) occurred when the CW laser beam was delivered with a sapphire-tipped contact probe. The results provide empirical data on the sensitivity of each parameter in producing a range of coagulation end points. In addition, the experimental results describe trends between the parameters of either laser and the extent of coagulation.

Real-time algorithm for retinal tracking.

Conventional retinal laser photocoagulation is presently performed by an ophthalmologist manually aiming a low-power laser beam at a desired site and firing a high-power laser for a preselected interval of time. To automate this process a retinal tracker must acquire a target, track small saccades, and identify loss of track during a large saccade. The authors successfully implemented a real-time algorithm that used a simple computer, video digitizing card, low light video camera, and fundus camera to perform rudimentary tracking on a photograph of a retina undergoing smooth circular motion. The algorithm tracked speeds up to 5 Hz, or 27 degrees/s, which equated to the retina moving in a 525 microns diameter circle.

Reflectance as an indirect measurement of the extent of laser-induced coagulation.

Two-dimensional reflectance images and surface thermal distributions were recorded during argon laser induced coagulation. During laser irradiation, coagulated egg yolk formed a white lesion. The whiteness, or reflectance caused by backscattering of light from the forming lesion, would be measured after a short delay from the onset of laser irradiation. In the experiments which covered exposure time from 4.5 to 17.0 s, we found that it started slowly, the reflectance increased rapidly once the surface temperature of the lesion reached approximately 90 degrees C. After this rapid rise, the reflectance began to taper off until no change in reflectance was recorded. There was a 0.98 correlation between lesion diameter measured from a two dimensional reflectance image and the lesion diameter that was measured microscopically. There was a 0.92 correlation between reflectance at the center of the lesion and microscopically measured depth of coagulation at the same point. However, the correlation between microscopically measured coagulation depth and width was only 0.88.

Preliminary results on reflectance feedback control of photocoagulation in vivo.

The size of therapeutic laser-induced retinal lesions is critical for effective treatment and minimal complications. Due to tissue variability, the size of a lesion that results from a given set of laser irradiation parameters cannot be predicted. Real time feedback control of lesion size is implemented based on two-dimensional reflectance images acquired during irradiation. Preliminary results of feedback controlled lesions formed in pigmented rabbits demonstrate an ability to produce uniform lesions despite variations in tissue absorption or changes in laser power.

Dynamic optical property changes: implications for reflectance feedback control of photocoagulation.

During laser treatment, coagulation affects the optical properties of the tissue. In particular, the formation of a white lesion significantly increases the scattering coefficient. This change in the optical properties in turn affects the laser light distribution in the tissue. The white lesion formed during photocoagulation of the retina has a dynamic effect upon reflection and fluence rate. This problem has been simulated on a model medium consisting of a thin absorbing layer covered with a 1 cm thick layer of albumin. The albumin layer is subdivided into coagulated (white) and uncoagulated (clear) layers. The optical properties of each layer have been determined and these values have been used to model light distribution in the medium. One-dimensional adding-doubling and three-dimensional Monte Carlo methods have provided light distributions in the medium for varying thicknesses of the coagulated albumin. Computed fluence reaching the absorbing layer decreased in the presence of a 275 microns or thicker coagulated layer. The coagulated layer attenuates light because it is highly scattering; however, this scattering also leads to a sub-surface peak in fluence rate at a level higher than the incident fluence. The latter effect outweighed the former for coagulated layer thicknesses less than 275 microns. Computed reflectance of argon laser light from a semi-infinite coagulated region initially increased linearly as a function of thickness. As the coagulation thickness increased beyond 4-5 optical depths, the reflectance approached a constant value, R infinity, at 9 optical depths (2 mm). Experimentally measured total reflectance is shown to be an inadequate indicator of the thickness of a lesion (finite coagulated volume); however, central reflectance from a lesion measured with a CCD camera confirmed the computed trends. These results provide a theoretical foundation for control of lesion thickness using reflectance images.

An automated laser system for eye surgery.

The use of lasers in ophthalmology is discussed, and the procedure and requirements of ophthalmic laser surgery are described. An overview of a proposed laser system for eye surgery is given, and its operation is described. Progress and research to date are reviewed.

Photocoagulation of the fovea.

The visual outcome, histopathology, and electrodiagnostic tests of a man with a malignant melanoma of the choroid who received foveal argon laser photocoagulation prior to enucleatiion are described. The low intensity foveal burn destroyed only the outer retinal layers and spared the inner retina. Vision was reduced to 20/50 immediately, but recovered to 20/30 after one day. The visually-evoked-potential (VEP) was altered in both amplitude and waveform by the small foveal burn. A patient with solar retinopathy and permanent visual loss demonstrated only waveform changes on VEP testing. Monkeys with mild experimental foveal burns demonstrated outer layer retinal damage and waveform changes on VEP testing. The retinal energy density threshold for argon laser photocoagulation of the fovea is lower than 0.13 joules/mm.2.

Optical properties of conjunctiva, sclera, and the ciliary body and their consequences for transscleral cyclophotocoagulation: erratum.

Corrections are given to the reported [Appl. Opt. 35, 3321 (1996)] units of the absorption and scattering coefficients mu (a) and mu (s), respectively. The corrections pertain to two figures, several tables, and the text describing results.

The effect of radial keratotomy in the rupture strength of pig eyes.

Freshly enucleated pig eyes are significantly weakened following radial keratotomy surgery and are more susceptible to rupture under lateral or axial compression than their unoperated fellow eyes. Patients should be cautioned to restrict hazardous activity in the post-operative period to prevent disastrous globe rupture.

Rate process parameters of albumen.

Both egg white and egg yolk are excellent media for studying photocoagulation due to thermal response of tissue to laser light. They are readily available, consistently the same, and provide a standard biological medium for different labs to compare results. The irradiation parameters for laser coagulation of these media depend upon their optical properties and their temperature-dependent rate reactions. Estimates of the rate process damage coefficients were obtained from constant-temperature water bath experiments. The activation energy E for egg white was estimated to be 92,000 (cal/M*K] and the integration constant A was found to be 3.8 x 10(57) (second-1).

Optical model for light distribution during transscleral cyclophotocoagulation.

Transscleral cyclophotocoagulation (TSCPC) is currently performed clinically as an effective treatment for end-stage glaucoma. We develop a theoretical model for the analysis of optical attenuation phenomena during TSCPC as a basis for selection of an optimal wavelength. A multilayered Monte Carlo model was developed to calculate the fluence and the rate of heat generation in each tissue layer for the wavelengths of Nd:YAG, diode, ruby, krypton yellow, and argon lasers. Of the five wavelengths under study, our theoretical results suggest that the diode laser wavelength offers the best penetration through the conjunctiva, sclera, and ciliary muscle and highest absorption within the ciliary pigment epithelium.

Automated lesion placement in the rabbit eye.

BACKGROUND AND OBJECTIVE: The objective of this research was to build a prototype feedback control system to precisely place argon laser lesions on the retina for treatment of retinal disorders. STUDY DESIGN/MATERIALS, AND METHODS: The prototype feedback control system was tested by placing lesions at specific locations on the retina of pigmented rabbits to simulate the treatment of diabetic retinopathy, retinal breaks or tears, and a pre-programmed, two-dimensional array of lesions was placed at a specific site. RESULTS: Results of feedback-controlled lesion placement performed in vivo on pigmented rabbits are presented. The ability to place lesions with automated feedback control is demonstrated. CONCLUSION: Automated feedback control placement of argon laser lesions is possible at a reasonable cost and has numerous therapeutic and safety benefits over current ballistic delivery.

Infrared spectral sensitivity of Melanophila acuminata.

The spectral sensitivity of the pit organ of the beetle Melanophila acuminata (Coleoptera:Buprestidae) was measured using an ultrafast tunable infrared laser source and standard electrophysiological techniques. The pit organ may be classified as a broadband detector as the beetles responded to all infrared excitation wavelengths from 2 to 6&mgr;m. There was a decrease in response threshold and latency and an increase in the magnitude of the response in the region from 2.8 to 3.5&mgr;m, which corresponded to a region of decreased transmittance (increased absorbance) as measured by Fourier transform infrared spectroscopy. The implications of the correlation between spectral response and optical properties are discussed.

Use of an agent to reduce scattering in skin.

BACKGROUND AND OBJECTIVE: A method to increase light transport deeply into target areas of tissue would enhance both therapeutic and diagnostic laser applications. The effects of a hyperosmotic agent on the scattering properties of rat and hamster skin were investigated. STUDY DESIGN/MATERIALS AND METHODS: A hyperosmotic agent, glycerol, was applied in vitro and in vivo to rat and hamster skin to assess the changes in tissue optical properties. Changes in the reduced scattering coefficient after application of the agent in vitro to rat skin and after the skin has been rehydrated were assessed to evaluate the effect of the agent on tissue. RESULTS: Experimental results showed a transient change in the optical properties of in vitro rat skin. A 50% increase in transmittance and decrease in diffuse reflectance occurred within 5-10 min after the introduction of anhydrous glycerol. In addition, reduction of light scattering with this technique increased depth of visibility with optical coherence tomography. Injection of glycerol under the skin allowed in vivo visualization of blood vessels. CONCLUSIONS: The application of the agent reduces the amount of refractive mismatch found in the tissue and markedly reduces random scattering, thereby making the skin less turbid for visible wavelengths for a controlled period of time.

Investigation of the transduction mechanism of infrared detection in Melanophila acuminata: photo-thermal-mechanical hypothesis.

Differential phase optical low coherence reflectometry (OLCR) was used to detect sub-wavelength displacements in the infrared-sensitive thoracic pit organ of Melanophila acuminata (Coleoptera: Buprestidae) upon absorption of infrared radiation at 3.39 microm. The displacement had more complex morphology but similar amplitude ( approximately 100 nm at 1 W cm(-2)) when compared to the displacement measured from the exocuticle in an alternate region on the beetle's body. In addition, a simplified finite difference model was developed to predict the temperature distribution and resultant thermal expansion in the pit organ tissue. The experimental and model results were interpreted to help clarify the mechanism by which the sensilla in the pit organ convert infrared radiation to neural signals. The results of this paper are discussed in relation to the photo-thermal-mechanical transduction hypothesis. This is the first experimental examination of the transduction mechanism in Melanophila acuminata.