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Biomedical subjects

W F March

Publications and source records attributed to W F March.

At least 19 recordsLinked to original sources

Raman spectroscopy in ophthalmology: from experimental tool to applications in vivo.

Raman spectroscopy is a qualitative and quantitative optical technique for determining the molecular composition of matter. Improvements in spectroscopic instruments, especially the modality to detect low light level signals extended the Raman technique to biomedical applications, even in delicate structures like the eye. The purpose of this paper was to make an inventory of performed applications of Raman spectroscopy in biomedical science and especially in ophthalmology. A literature search was done using Medline, Current Contents, a patent server on the Internet, and references found in articles and patents. This search revealed a variety of Raman techniques and applications in biomedical research, and an increasing flow of articles starting in the late 1970s on Raman spectroscopy in ophthalmology. This increase in literature about Raman spectroscopy in ophthalmology feeds the expectation that this valuable technique will be introduced in the future into clinical practice.

Animals↗

Noninvasive Raman spectroscopic identification of intraocular lens material in the living human eye.

PURPOSE: To develop a safe noninvasive technique for identifying the material of intraocular lenses (IOLs) implanted in patients. SETTING: Center for Biomedical Engineering and the Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas, USA. METHODS: Raman spectroscopy was used to noninvasively identify the type of IOL implanted after previous cataract surgery in 9 eyes of 6 patients who were legally blind as a result of eye disease. Three IOLs were characterized: poly(methyl methacrylate) (PMMA) (n = 5), acrylic (n = 3), and silicone (n = 1). Confocal Raman spectroscopy was used with a laser power of 95 microW and exposure time of 1 second. RESULTS: Distinct spectral peaks associated with each type of IOL were obtained. These included spectra peaks at 2840 cm(-1), 2946 cm(-1), and 3000 cm(-1) for PMMA; 2917 cm(-1), 2939 cm(-1), and 3055 cm(-1) for acrylic; and 2900 cm(-1), 2961 cm(-1), and 3048 cm(-1) for silicone. The procedure was well accepted by patients, and there were no complications. CONCLUSIONS: The specific Raman spectra of the IOLs allowed for noninvasive determination of IOL material with the use of a safe light dose and an exposure time of 1 second.

Acrylic Resins↗

The long-term safety and efficacy of brinzolamide 1.0% (azopt) in patients with primary open-angle glaucoma or ocular hypertension. The Brinzolamide Long-Term Therapy Study Group.

PURPOSE: Oral carbonic anhydrase inhibitors used to treat glaucoma have significant systemic side effects. Brinzolamide 1.0%, a new topical ocular carbonic anhydrase inhibitor, is effective apparently without significant systemic side effects. This study was performed to establish the long-term safety and efficacy of brinzolamide 1.0% two and three times daily for primary open-angle glaucoma and ocular hypertension. METHODS: An 18-month, multicenter, double-masked, parallel, controlled study was conducted. Patients were randomized to brinzolamide two or three times daily or timolol 0.5% twice daily in a 2:2:1 ratio (n = 150, 153, and 75, respectively). Intraocular pressure was measured at 8:00 AM at eligibility and months 1, 3, 6, 9, 12, 15, and 18. Efficacy was based on intraocular pressure reduction from baseline. Safety was also evaluated. RESULTS: All regimens produced clinically relevant and statistically significant (P<.05) intraocular pressure reductions from baseline. Mean changes in intraocular pressure trough measurements ranged from -2.7 to -3.9 mm Hg with brinzolamide twice-daily dosing and -2.8 to -3.8 mm Hg three times daily dosing compared with -4.7 to -5.6 mm Hg with timolol. The intraocular pressure reductions with brinzolamide two and three times daily were clinically and statistically equivalent. One hundred forty-four patients were discontinued from the study after randomization with the most common reasons being the occurrence of an adverse event (46), inadequate intraocular pressure control (23), patient decision unrelated to study medication (11), lost to follow-up (16), and noncompliance (9). Adverse events were nonserious and resolved without sequelae. There were no clinically relevant changes in safety parameters. Brinzolamide produced less ocular discomfort (burning/stinging) than timolol, and total carbonic anhydrase inhibition levels remained below that known to cause systemic side effects. CONCLUSION: Brinzolamide produced significant and equivalent reductions in intraocular pressure when dosed two and three times daily for 18 months. Brinzolamide was safe and well tolerated by patients, with minimal ocular discomfort.

Administration, Topical↗

Intraocular lens glucose sensor.

Ocular spectroscopy, which is the use of the eye to monitor optically the concentration of metabolites in the body, has been successfully applied to monitor aqueous humor glucose concentration. In the United States, 1.7 million intraocular lenses are currently implanted yearly. Because patients with diabetes are more likely to develop cataracts at an earlier age, a relatively high proportion of the patients receiving intraocular lenses have diabetes. Last year, 110,000 patients with diabetes received intraocular lens implants of various materials. We have successfully polymerized a fluorescent complex within a hydrogel intraocular lens that responds well to glucose concentration.

Animals↗

Identification of intraocular lens materials using confocal Raman spectroscopy.

PURPOSE: To develop and test a noninvasive method to identify intraocular lens (IOL) materials in vitro. SETTING: Center for Biomedical Engineering and the Department of Ophthalmology, University of Texas Medical Branch, Galveston, Texas, USA. METHODS: A laser confocal Raman spectroscopy system (Conforam) was used for the noninvasive assessment of Raman spectra in the lower and the higher spectral regions (299.1 to 1833.7 cm-1 and 2633.8 to 3819.6 cm-1, respectively) of 4 IOL materials: silicone, poly(methyl methacrylate) (PMMA), acrylic, and hydrogel. RESULTS: Each lens material showed a distinctive spectrum in both the higher and the lower spectral regions. Most materials had unique peaks and a distinct profile using 1 mW of laser power and a 1 second exposure time. All materials still had a unique spectrum in both the higher and the lower region that allowed 1 material to be distinguished from the others. CONCLUSIONS: A Conforam differentiated silicone, PMMA, acrylic, and hydrogel lenses in vitro. Raman spectroscopy using the Conforam may provide a fast, safe, and reliable noninvasive method to gain information about the material of an implanted IOL and the stability of lens materials and their coatings.

Acrylates↗

Non-invasive assessment of ocular pharmacokinetics using Confocal Raman Spectroscopy.

A Laser Scanning Confocal Raman Spectroscopy (LSCRS) system was applied for the non-invasive quantification of the transport of a drug through the rabbit cornea in vivo. Employing LSCRS, the changes in the amplitude of a drug-specific Raman signal were assessed over time in the tearfilm and corneal epithelium of the living rabbit eye (n = 6), after topical application of 25 microL Trusopt 2%. This allowed for quantification of pharmacokinetic variables. The effect of the drug on corneal hydration was also monitored. LSCRS demonstrated adequate sensitivity and reproducibility, for continuous real-time monitoring of the Trusopt concentration. Each concentration-time curve had a bi-phasic trend; the rapid initial phase (t<8 min.) corresponds to the nonproductive losses of Trusopt from the tears (k10 = 0.24+/-0.04 min(-1), and the slower later phase (t>20 min.) is the result of transfer of the drug from the corneal epithelium to the stroma (k23 = 0.0047+/-0.0004 min(-1). Drug absorption into the corneal epithelium occurred at a rate of k12 = 0.034+/-0.006 min(-1). Trusopt caused an acute dehydrating effect, with a maximum decrease in corneal hydration of approximately 15% at approximately 60 min. following application of the drug. LSCRS has the specificity, sensitivity, reproducibility and spatial resolution for employment as a potentially valuable tool for the study of ocular pharmacokinetics.

Animals↗

In vivo confocal Raman spectroscopy of the human cornea.

PURPOSE: To investigate the feasibility of a confocal Raman spectroscopic technique for the noninvasive assessment of corneal hydration in vivo in two legally blind subjects. METHODS: A laser beam (632.8 nm; 15 mJ) was maintained on the cornea by using a microscope objective lens (x25 magnification, NA = 0.5, f = 10 mm) both for focusing the incident light as well as collecting the Raman backscattered light, in a 180 degrees backscatter configuration. An optical fiber, acting as the confocal pinhole for elimination of light from out-of-focus places, was coupled to a spectrometer that dispersed the collected light onto a sensitive array detector for rapid spectral data acquisition over a range from 2,890 to 3,590/cm(-1). Raman spectra were recorded from the anterior 100-150 microm of the cornea over a period before and after topical application of a mild dehydrating solution. The ratio between the amplitudes of the signals at 3,400/cm(-1) (OH-vibrational mode of water) and 2,940/cm(-1) (CH-vibrational mode of proteins) was used as a measure for corneal hydration. RESULTS: High signal-to-noise ratio (SNR = 25) Raman spectra were obtained from the human corneas by using 15 mJ of laser light energy. Qualitative changes in the hydration of the anteriormost part of the corneas could be observed as a result of the dehydrating agent. CONCLUSION: With adequate improvements in system safety, confocal Raman spectroscopy could potentially be applied clinically as a noninvasive tool for the assessment of corneal hydration in vivo.

Aged↗

The effects of betaxolol hydrochloride ophthalmic solution on intraocular pressures during transient microgravity.

BACKGROUND: Intraocular pressure (IOP) has been found to increase during microgravity. After peaking in the first few hours of orbital flight, IOP slowly decreases to a level that is slightly elevated above baseline IOP's. These modest elevations in IOP do not require treatment. Just as in 1-G, a clinically significant elevation of IOP that occurred during spaceflight would require treatment. We are not aware of previous studies of the efficacy of IOP lowering agents under conditions of microgravity. METHODS: This double-masked, placebo-controlled study measured the IOP's of 11 adult subjects (22 eyes) at baseline, preflight, and zero-gravity aboard the NASA KC-135 aircraft, and postflight. One eye of each of the subjects was treated with betaxolol hydrochloride ophthalmic solution 0.5%, while the contralateral eye was treated with normal saline placebo, for 7 d prior to parabolic flight. IOP's were measured by the Tono-Pen 2, a gravity independent tonometer. RESULTS: A modest, but statistically significant reduction of 2.4 mmHg in mean IOP was noted in betaxolol treated eyes at the time of preflight measurement. During zero-G, the mean IOP's of both betaxolol treated eyes and placebo treated eyes increased approximately 20% over preflight levels. Postflight IOP's were similar to preflight IOP's. CONCLUSIONS: The effect of betaxolol on the IOP of eyes treated with for 1 wk prior to exposure to microgravity was statistically significant, but may lack clinical significance in normal eyes. Further research needs to be done to determine the efficacy during microgravity of betaxolol and other agents, in subjects who have upper normal to slightly elevated IOP's at 1 G.

Adaptation, Physiological↗

Noninvasive assessment of the hydration gradient across the cornea using confocal Raman spectroscopy.

PURPOSE: The feasibility of Raman spectroscopy for the noninvasive assessment of axial corneal hydration was investigated. METHODS: A scanning confocal Raman spectroscopy system, with an axial resolution of 50 microns, was used to assess noninvasively the water (OH-bond) to protein (CH-bond) ratio as a measure of the hydration in collagen-based phantom media and rabbit corneas. RESULTS: Raman spectra with high signal-to-noise ratios were obtained under in vitro and in vivo conditions within a range of corneal hydration (H = 0.0-8.3 mg water/mg dry wt). The Raman intensity ratio OH/CH showed a strong correlation with the hydration of the phantom medium (R2 > 0.99) and the rabbit corneas (R2 > 0.95). A degree of reproducibility was seen in measurements performed at a specific depth within the cornea (SD = 1.2%-2.7%). Quantitatively, the spatially resolved corneal water content, as assessed with our method, showed an increasing gradient from the anterior to the posterior region, with a difference of approximately 0.9. Significant qualitative differences in the axial hydration gradient were observed between the in vitro and in vivo situation, caused by the presence of an intact tear-film in vivo. Characterization of the axial corneal hydration using Raman spectroscopy provided a reliable estimation of total corneal hydration compared with conventional measurements using pachymetry and lyophilization. CONCLUSIONS: The proposed noninvasive confocal Raman spectroscopic technique has the potential to assess the axial corneal water gradient with a degree of sensitivity and reproducibility.

Animals↗

Gonioscopic ab interno laser sclerostomy. A pilot study in glaucoma patients.

PURPOSE: The purpose of this study is to evaluate the safety and efficacy of gonioscopic ab interno laser sclerostomy (GLS) in patients with glaucoma. METHODS: The technique of GLS involves iontophoresis of methylene blue dye (1%) at the limbus to focally dye the sclera and to provide subsequent delivery of 10-microsecond pulsed laser energy to the dyed area through a goniolens. The laser emits at 660 nm, a wavelength that is maximally absorbed by the methylene blue dye. Patients were evaluated for fistula formation, intraocular pressure (IOP) reduction, and adverse sequelae. Thirty-eight treatments were performed in 35 eyes. RESULTS: Successful complete sclerostomies were achieved in 21 eyes (55%), which was associated with an acute mean reduction in IOP of 23 mmHg. Mean preoperative IOP for all patients was 35 mmHg, and 1 hour after treatment it was reduced to 18.5 mmHg. In 4 of the 38 treatments, there was no acute IOP reduction, and these eyes were judged as failures. The mean follow-up time was 8.2 months with a maximum follow-up of 15 months. By 9 months, 50% of patients had an IOP of 22 mmHg or lower. The number of antiglaucoma medications decreased from 3.1 to 1.7 for all eyes over the 15-month follow-up period. Hyphemas (13%) were the only major complication, and these resolved spontaneously. In only one case did the IOP increase after the procedure. CONCLUSION: The results of this trial indicate that GLS is technically feasible, and preliminary results of IOP control are promising.

Adult↗

Laser sclerostomy by pulsed-dye laser and goniolens.

We describe an ab-interno laser sclerostomy procedure using the method termed dye-enhanced ablation with a slit-lamp delivery system and special goniolens such that only the laser light beam penetrates the anterior chamber. The procedure uses a microsecond-pulsed-dye laser emitting at 666 nm and iontophoresis of methylene blue dye (absorption of 668 nm) into the sclera at the limbus to enhance the absorption of the laser light. We compared the number of pulses needed to perforate excised human sclera at pulse durations of 1.5, 20, and 300 microseconds. Pulse durations of 1.5 and 20 microseconds required 20 pulses or fewer to perforate excised human sclera with pulse energies of 75 to 100 mJ. The ab-interno laser sclerostomy procedure was performed in 54 eyes of Dutch-belted rabbits with pulse durations of 1.5 or 20 microseconds and a 100- or 200-microns incident spot diameter delivered using a CGF goniolens. Full-thickness fistulas were successfully created at both pulse durations in approximately 80% of eyes treated. A range of three to 25 pulses was required to perforate sclera with slightly fewer pulses and lower pulse energies at 1.5 microseconds compared with 20 microseconds. There were no significant complications from the procedure. This technique could permit filtration surgery to be performed on an outpatient basis.

Animals↗

Safety of high-energy neodymium:YAG laser pulses in YAG sclerostomy.

YAG sclerostomy was performed in 15 eyes of nine cynomolgus monkeys. Individual pulse energies ranged between 10 and 135 millijoules. Total pulse energy ranged between 2,000 and 36,000 millijoules in order to test the extreme range of energy that might be required. Both acute effects and chronic effects were studied in the corneal endothelium, the lens capsule, the iris, the ciliary body, the retina, and the sclera. Techniques included flat preparations of the corneal endothelium, paraffin sections for light microscopy, and scanning and transmission electron microscopy. Our conclusion is that individual pulse energies of up to 135 millijoules with a total of up to 36 joules of energy are safe in monkey eyes when performing YAG sclerostomy.

Animals↗

Silver oxide in YAG sclerostomy.

YAG sclerostomy is a filtering procedure performed entirely with the neodymium:YAG laser through a goniolens as an alternative to trabeculectomy in the treatment of glaucoma. Extremely large pulse powers have been required in the past to complete the procedure. We found that an injection of silver-stabilized protein intrasclerally prior to the procedure makes it possible to perform the procedure with low total power.

Animals↗