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Biomedical subjects

D E Gaasterland

Publications and source records attributed to D E Gaasterland.

At least 37 records · Page 2Linked to original sources

Threshold for lens damage during Q-switched Nd:YAG laser iridectomy. A study of rhesus monkey eyes.

Clinical and pathologic examinations were performed after 18 iridectomies had been created in six eyes of three rhesus monkeys using increasing Q-switched neodymium (Nd):YAG laser energy, pulses per burst, and number of bursts. Treatment parameters bracketed the threshold for lens damage during iridectomy. Iridectomy with one or two bursts of one or two Q-switched pulses at 5 to 6.2 mJ per pulse was achieved without lens damage. Slight increase of pulse energy or an increase to three pulses per burst (without pulse energy increase) caused local damage to the underlying lens. Marked increase of any of the treatment parameters caused slightly larger iridectomies and slightly larger, localized damage of the underlying lens. Synechiae developed between the monkey posterior iris surface at the iridectomy and the damaged area in 80% of the lens lesions. In monkeys, the small pulsed laser iridectomies created with pulses of energies up to 6.5 mJ became occluded during the healing process.

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Endothelial damage thresholds for retrocorneal Q-switched neodymium:YAG laser pulses in monkeys.

Laser pulses were focused within 1 mm of the rhesus monkey corneal endothelium using the Coherent Model 9900 laser at energies of 3, 6, 9, and 12 mJ. Sixteen slightly off-axis pulses were applied with no contact lens on the eye. Corneal damage was studied clinically and by scanning electron microscopy. Q-switched pulses of 12 mJ or less are not likely to damage the cornea if focused more than 0.75 mm from the endothelium. The retrocorneal focal distance for a 50% incidence of endothelial damage for 6, 9, and 12 mJ pulses was found to be less than 0.5 mm. For 3 mJ pulses, it was less than 0.25 mm. The severe early effect of suprathreshold pulses is edema of endothelial cells in a 0.2- to 0.6-mm diameter circular zone surrounding a small central pit through Descemet's membrane. At two months, irregular enlargement of endothelial cells surrounding and partially covering the persistent pit exists at sites of severe damage. The extent of the longer-term change is proportional to the severity of the original insult, but in no case was there clinically significant, persistent damage in the healed corneas.

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Endothelial damage from retrocorneal mode-locked neodymium:YAG laser pulses in monkeys.

Laser pulses were focused 0.85 to 1.60 mm from the rhesus monkey corneal endothelium using a mode-locked laser at 3.3 and 4.5 mJ. Sixteen slightly off-axis pulses were applied with no contact lens on the eye. Corneal damage was studied clinically and by scanning electron microscopy. The retrocorneal distance for a 50% incidence of endothelial damage (LD 50 = lesion distance, 50%) for 3.3 mJ mode-locked pulses was found to be 1.60 mm. All mode-locked pulses of 4.5 mJ focused 0.85 to 1.60 mJ from the endothelium caused damage. In comparison, Q-switched pulses of 12 mJ or less are not likely to damage the cornea if focused more than 0.75 mm from the endothelium. The severe, early effect of mode-locked pulses is edema of endothelial cells in a 0.2- to 0.3-mm diameter circular zone surrounding a 0.1-mm diameter denuded zone with a small central break of Descemet's membrane. By two months, mild and moderate lesions heal with little or no distortion of the endothelial mosaic. Irregular enlargement of endothelial cells surrounding and covering the previously denuded area of severe lesions is caused by both mode-locked and Q-switched treatment. In no case was there clinically significant, persistent damage in the healed monkey corneas.

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Long-term effects of Q-switched ruby laser on monkey anterior chamber angle.

In an attempt to clarify whether pulsed lasers might be able to cause permanent fistulas from the anterior chamber to the interior of the canal of Schlemm, slightly suprathreshold, low energy, small diameter Q-switched ruby laser pulses were applied to the trabecular meshwork of nine eyes of six rhesus monkeys. Clinical examinations during the next 2 months disclosed no adverse effect on the cornea, iris, lens, or retina. There was transient mild inflammation in five eyes. Intraocular pressure was not changed significantly; the facility determined by perfusion of the anterior chambers at 2 months was normal. Light microscopy and scanning electron microscopy show localized trabecular lesions; some are slightly indented, but there is no persistent penetration to Schlemm's canal. Endothelial cells, confluent with those of the cornea, cover the inner (anterior chamber) surface of the lesions. Cross-sections through the center of a lesion show that trabecular meshwork and Schlemm's canal have been obliterated by the treatment and healing; these changes are similar to those previously seen after argon laser monkey trabecular treatment. In the untreated areas, between pulsed laser application sites, trabecular meshwork and Schlemm's canal are normal by light microscopic and scanning electron microscopic examination. Any effect on IOP from this particular type of pulsed laser treatment of the trabecular meshwork is probably not due to trabeculopuncture and flow of fluid through the fistula.

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Laser-induced primate glaucoma. I. Progression of cupping.

Sustained intraocular pressure elevations were induced in 15 monkey eyes by argon laser photocoagulation of the trabecular meshwork. Large fluctuations of IOP resulted. Posttreatment gonioscopy revealed an open angle with scattered low peripheral anterior synechiae. Optic disc cupping progressed during pressure elevations, manifested first as posterior bowing of the optic nerve head and peripapillary tissues. Reversal of this early phase of cupping occurred in eight eyes during spontaneous normalization of IOP. In most eyes, as cupping evolved from saucerization to a deeper cup, the cup remained round. In four eyes, focal sloping of the cup to the inferotemporal rim occurred with nerve fiber layer defects. Total cupping with undermining of the rim occurred in five eyes with prolonged IOP elevation. Laser-induced primate glaucoma has features in common with juvenile human glaucoma and is a useful model for the study of cupping of the optic nerve head.

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Threshold for retinal damage associated with the use of high-power neodymium-YAG lasers in the vitreous.

Ultrashort, Q-switched or mode-locked, neodymium-YAG laser pulses focused within 2 mm of the retina caused reproducible retinal damage in four eyes of two monkeys and in four eyes of three rabbits. The distance of the laser focus from the retina for clinically observed threshold retinal damage was characterized for pulse energies up to 9 mJ. For the 2- to 6-mJ pulse energies necessary to rupture vitreal membranes in clear media in rabbits, the high-power laser pulses could not be focused within 2 mm of the retina without substantial risk of damaging the underlying retina. These laser pulses did not rupture vitreal membranes in hazy ocular media that prevented precise focusing. The retinal damage was somewhat greater than expected for retinal absorption of 1.06-micron laser energy, suggesting that secondary effects such as self-focusing and shock waves emanating from the focus may be important.

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Long-term ocular effects of osmotic modification of the blood-brain barrier in monkeys. I. Clinical examinations; aqueous ascorbate and protein.

The blood-aqueous humor barrier in adult rhesus monkeys was opened by intracarotid infusion of a 25% mannitol solution. Each monkey had one to four infusions into the same artery, with at least one week between subsequent procedures. The monkeys were observed clinically for 3 to 212 days. Within an hour pigmented cells and protein accumulated in the aqueous humor of the mannitol-treated eyes. Hypotony developed within a day. Aqueous flare and cells cleared within 2 weeks. Hypotony resolved in 8 to 12 weeks. More than one half of the monkeys had transient anisocoria. In some, the pupil in the treated eye was miotic; in others it was dilated. Direct and consensual pupil responses to light remained intact in untreated eyes and in treated eyes with mydriasis. About one fourth of the monkeys developed edema of the ipsilateral optic disk. This correlated with hypotony. No monkey developed cataract, corneal opacity, or vitreous or retinal change. The aqueous protein concentration was slightly above normal a month or more after the carotid infusions, but was considerably less than plasma protein concentration. Posterior and anterior aqueous ascorbate concentrations in treated eyes were slightly below normal, but far greater than plasma concentration, indicating that ascorbate active transport by the ciliary epithelium was essentially intact despite the widespread, permanent structural alteration that had been caused by the mannitol treatment.

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Episcleral venous pressure: a comparison of invasive and noninvasive measurements.

Noninvasive (pressure chamber) measurements of episcleral venous pressure were followed by invasive (direct cannulation) measurements at the same venous site in seven eyes of four anesthetized rhesus monkeys. There were three definite effects on the vein caused by the pressure chamber that could be used as endpoints: (1) slight indentation; (2) intermittent collapse; and (3) sustained collapse of the vein lumen. The mean pressure in the chamber corresponding to these endpoints was 9.9 +/- 0.9, 23.5 +/- 2.9, and 31.4 +/- 4.0 mmHg (+/- SE), respectively. After the chamber was removed, the pressure in the veins determined by cannulation measurements at the same sites was 11.3 +/- 0.5 mmHg (+/- SE). Therefore, the first endpoint with the pressure chamber (slight indentation) correlates most closely and slightly underestimates the cannulated pressure. Endpoints defined by partial or complete venous collapse overestimates the venous pressure. Simultaneous measurements with the chamber and a cannula show a rise of local venous pressure caused by the chamber.

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Ocular involvement in xeroderma pigmentosum.

A 37-year-old, white woman with xeroderma pigmentosum had reduced vision for many years because of primary and secondary corneal epithelial edema and stromal haze. Corneal grafting was required, but was not successful. Numerous primary dermal tumors of various types involving the lids of both eyes had been excised surgically or treated by freezing with liquid nitrogen. Squamous cell carcinomas involving the limbal area of the globe and adjacent tissues were excised from the left eye at age 12, the right eye at age 32, and the left eye (again) at age 36. The right limbal tumor soon recurred and invaded the orbit despite radiation treatment; this required right orbital exenteration. The second left limbal tumor recurred one year later, soon after the recurrence of a left lower lid basal cell carcinoma. Left orbital exenteration was required. Corneal graft failures and recurrent ocular squamous cell carcinoma involving the eye in xeroderma pigmentosum can be difficult management problems.

Adolescent↗

Short-term effects of Q-switched ruby laser on monkey anterior chamber angle.

Three Q-switched ruby laser pulses were applied to the trabecular meshwork of 10 monkey eyes. Pulse energies ranging from 20 to 110 mJ were studied. The spot size ranged from 100 to 200 micrometer (in air), and the pulse durations was 28 sec. Gonioscopic examinations showed a graded response from no appreciable change at 20 mJ per pulse to marked disruption of anterior chamber angle structures at 100 mJ or more per pulse. Perfusions done within an hour of treatment showed no consistent alteration of the outflow facility. Scanning electron microscopy demonstrated the graded anterior chamber angle response. No disruption of the angle structures was seen after the 20 mJ treatment, but discrete trabecular damage occurred after treatments with 25 mJ. After pulses equal to or greater than 45 mJ the anterior chamber angle structures were markedly altered. The power density causing extensive tissue disruption was equal to or greater than 150 X 10(8) watts/cm2. In each specimen with an identifiable trabecular lesion, tissue debris and endothelial edema were found on the adjacent inner surface of the cornea. Tearing of Descemet's membrane next to the trabecular meshwork occurred with the 100 mJ pulses.

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Ocular irritation from high-dose methotrexate therapy: pharmacokinetics of drug in the tear film.

Four of 13 patients receiving intermittent high-dose methotrexate therapy experienced recurrent symptoms of ocular irritation (burning, pruritus, "dry eyes") two to seven days after chemotherapy. Ophthalmic examination was unremarkable in symptomatic individuals except for decreased reflex production of tears in some patients. Pharmacokinetic studies of a group of these patients revealed concentrations of methotrexate in tears equivalent to those in plasma at 24 and 48 hours after treatment; these concentrations reached 1 X 10(-5) M during the infusion of methotrexate. The occurrence of acidic lacrimal secretions, pH 6.5 in one symptomatic patient, may have contributed to decreased solubility of methotrexate in the fluid of the conjunctival sac.

Adolescent↗

Experimental ciliochoroidal detachment. Effect on intraocular pressure and aqueous humor flow.

Ciliochoroidal detachments were produced in rhesus monkeys by injecting glutathione bicarbonate Ringer's solution, autologous serum, or silicone oil into the anterior suprachoroidal space. Silicone oil detachments, like sham operations, caused a transient 2 mm Hg reduction in intraocular pressure. Detachments with glutathione bicarbonate Ringer's solution or serum caused a 6 mm Hg reduction in intraocular pressure, which normalized in three weeks. Aqueous humor flow in serum-detached eyes was normal, indicating that the hypotonia does not result from reduced aqueous humor formation. Blood was present in Schlemm's canal in most eyes with hypotonia, which suggests that hypotonia is not the result of enhanced conventional aqueous humor outflow. Therefore, it is postulated that hypotonia might result from enhanced aqueous humor outflow from the anterior chamber into the suprachoroidal space and out of the eye through the emissarial channels of the sclera (uveoscleral outflow).

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Low-energy, Q-switched ruby laser iridotomies in Macaca mulatta.

Laser iridotomies have been pursued as a means of performing anterior segments surgery as a virtually noninvasive procedure. An ideal single laser pulse technique has been elusive. In this study, iridotomies in rhesus monkeys were produced with a single exposure to a Q-switched ruby laser pulse. The iridotomy formation was accompanied by acoustic wave generation, bubble formation, and explosive tissue disruption, evidence of a nonlinear laser-iris interaction. The average energies at which these iridotomies were produced ranged between 18 and 48 mJ, some of the lowest energies reported for a laser iridotomy. Corneal changes were observed both at the epithelium and at the endothelium in some, but not all, of the eyes exposed. The epithelial changes morphologically resembled nonlinear damage reported for transparent solids. Damage to physical materials has been attributed to stimulated Brillouin scattering, a mechanism that may also play a role at the cornea. Consideration of such phenomena should be a part of the clinical evaluation prior to exposure of a cornea to high-power laser pulses. Although the endothelial change was more difficult to analyze, a shock-wave effect could not be discounted.

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Sites of breakdown of the blood-aqueous barrier after paracentesis of the rhesus monkey eye.

Sites of breakdown of the blood-aqueous barrier following rapid paracentesis have been investigated in rhesus monkeys with two independent procedures. (1) The entrance of fluorescein into the anterior and posterior chambers following paracentesis was studied in vivo in normal eyes, in eyes with laser-induced experimental glaucoma, and in totally iridectomized eyes. (2) Scanning electron microscopy was used to study the ciliary body and trabecular meshwork regions in normal eyes and paracentetic eyes. These investigations show that the ciliary body, particularly the anterior pars plicata region, is a source of secondary aqueous humor protein. In addition, the study shows reflux of blood into Schlemm's canal and plasma movement across the inner wall into the anterior chamber.

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Rhesus monkey aqueous humor composition and a primate ocular perfusate.

The composition of rhesus monkey aqueous humor has been studied in large-volume, pooled samples. Replicate determinations of the concentrations of a number of constituents have been carried out for both aqueous humor and serum from large veins by means of automatic analyzing equipment. Since aqueous humor has been obtained by anterior chamber paracentesis, it is a mixture of anterior and posterior chamber aqueous. When compared to serum, the pooled aqueous contains an excess of chloride, bicarbonate, ascorbate, lactate, uric acid, and several neutral amino acids. Rhesus monkey aqueous humor is deficient in calcium, urea nitrogen, phosphates, glucose, protein, creatinine, iron, bilirubin, cholesterol, triglycerides, a number of serum enzymes, acidic and basic amino acids, and several neutral amino acids. Sodium, potassium, magnesium, and two neutral amino acids (cysteine and valine) are of equal concentration in aqueous humor and serum. Glutathione concentration is very low in both aqueous humor and serum. Pooled rhesus monkey aqueous humor and serum are isosmolar, with measured osmolality being about 303 mOsm. Based upon the chemical analysis, a new solution has been formulated to substitute for primate aqueous humor during anterior ocular perfusion. This new solution causes very little change in the physiologic integrity of the outflow pathways during prolonged, repeated perfusion. In this respect, its effects are very similar to those of pooled rhesus monkey aqueous humor during perfusion of rhesus monkey eyes. In contrast, perfusion of rhesus monkey eyes with glutathione-bicarbonate-Ringer's solution has been shown to cause progressive increase of the total facility. To minimize physiologic alterations during operative procedures, a solution similar to this new one could be formulated for irrigation of the inside of the human eye.

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