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[Theoretical and physical aspects of excimer laser trabeculotomy (ELT) ab interno with the AIDA laser with a wave length of 308 mm].

Ablation of tissue structures containing and surrounded by water differs from tissue ablation at a surface, not only theoretically, but also in terms of outcome. In contrast to the situation often observed with surface ablation, it is shown that the trabecular meshwork in the anterior chamber of the eye can be ablated cleanly and accurately with the 308 nm Excimer laser without causing collateral thermal damage. The reason for this is that in the trabecular meshwork, the ratio of radiation-absorbing tissue to water--which absorbs very little energy--is very small. A marked cooling effect thus results, which permits the development of only a very small amount of collateral thermal damage at the boundaries of the ablation zone.

Biophysical Phenomena↗

Microvascular injection studies in rubeosis iridis and neovascular glaucoma.

Microvascular silicone injection, tissue clearing, and histologic examination were used to demonstrate the origin, distribution, and interconnections of newly formed iris and chamber angle blood vessels in four eyes with rubeosis iridis and neovascular glaucoma associated with diabetic retinopathy and central retinal vessel occlusion. The newly formed iris vessels that formed either a tight, evenly distributed (diabetic) or loose, irregularly distributed (central vessel occlusion) network in the iris originated from the normal iris arteries that were branches of either the major arterial circle or of the perforating branches of the anterior ciliary arteries, and drained into the normal iris and ciliary body veins and occasionally into the paralimbal episcleral veins. These newly formed iris vessels appeared to shunt intravascular fluid from arteries to veins. The newly formed anterior chamber angle vessels that formed tufts and arcades at the trabecular meshwork also originated from the roots of the iris arteries and the ciliary body arteries and connected with the peripheral neovascular iris network. In addition, the circumferentially running angle vessels that coursed within the trabecular meshwork branched into and coursed within a fibrosed Schlemm's canal and into two of its intrascleral collector channels. No open communication between these newly formed vessels and the Schlemm's canal-aqueous outflow system was seen.

Arteriovenous Anastomosis↗

Erbium: YAG laser trabecular ablation (LTA) in the surgical treatment of glaucoma.

BACKGROUND AND OBJECTIVE: Laser trabecular ablation (LTA) aims to remove trabecular tissue and to open Schlemm's canal in order to improve outflow facility in glaucomatous eyes. The purpose of our study was to investigate the pressure-reducing effect of LTA in chronic open-angle glaucoma 1 year following laser surgery. STUDY DESIGN/MATERIALS AND METHODS: Eleven eyes of 11 patients with chronic open-angle glaucoma were treated by circumscribed laser ablation of the trabecular meshwork. We used an Erbium:YAG laser (2.94 microm) with a quartz fiber contact endoprobe (320 microm core-diameter, 385 microm coating-diameter) applying 11-30 single neighbouring laser pulses (5-7 mJ) to the trabecular meshwork by an ab-interno approach. Laser procedure was gonioscopically visualized. RESULTS: Mean maximum intraocular pressure (IOP) of all 11 patients before LTA was 36 mmHg and dropped down to 22 mmHg after a mean follow-up of 12 months following LTA; this represents an IOP decrease of 38% (P=0.008). The average number of medications per eye dropped from 2.8 to 1.5 per eye (P=0.021). CONCLUSION: Although IOP lowering effect of Erbium:YAG laser trabecular ablation did not prove as effective as in filtering procedures, LTA might be a valuable alternative in glaucoma surgery especially in order to avoid conjunctival scarring and postoperative hypotony.

Aged↗

Membrane formation in the chamber angle after failure of argon laser trabeculoplasty: analysis of risk factors.

AIM: Membrane formation in the chamber angle induced by argon laser trabeculoplasty (ALT) can be a cause of treatment failure. Identification of risk factors for membrane formation was the primary aim of this retrospective study. METHODS: Semithin sections of trabeculectomy specimens obtained in a 2 year period were examined by light microscopy. 122 eyes which were treated with one or more ALTs before trabeculectomy were identified. In 46 eyes, a sufficient amount of trabecular meshwork was obtained to permit morphological analysis. RESULTS: Eyes treated with ALT had a significantly higher incidence of membrane formation (p=0.001). In 23/46 specimens a cellular and collagenous membrane was observed covering the entire trabecular meshwork. In 14/23 specimens (61%), this membrane was readily visible at low power magnification (x40). Comparison of these eyes with those without membrane formation revealed a significant difference in the number of ALTs (mean 2.07 (SD 0.73) v 1.48 (0.59); p=0.026) and in preoperative IOP (32.0 (9. 7) v 26.2 (8.4) mm Hg; p=0.04). CONCLUSIONS: Membrane formation in the chamber angle is a frequent cause of ALT failure. The major risk factor is the number of ALTs performed.

Aged↗

Antithrombin III, a serpin family protease inhibitor, is a major heparin binding protein in porcine aqueous humor.

Our hypothesis is that the proteins in aqueous humor may be involved in the regulation of outflow facility through the trabecular meshwork and uveoscleral meshwork. In this study, we analyzed the profile of heparin-binding proteins present in porcine aqueous humor to identify and characterize secretory proteins with a binding affinity for heparin. A single step involving heparin-sepharose affinity chromatography of porcine aqueous humor yielded a approximately 60 kDa protein as the major heparin-binding species. This protein was specifically eluted from the column by heparin. The N-terminal sequence and immunological cross reactivity of this protein confirmed its identity as antithrombin III. Aqueous humor from different species, as well as cells from human trabecular meshwork, Schlemm's canal, and lens epithelium, contained detectable amounts of antithrombin III. Based on its known anticoagulative function in endothelial cells and effects on the production of prostacyclin, it is reasonable to speculate that antithrombin III present in aqueous humor might influence the physiology of the trabecular and uveoscleral meshwork and thereby regulate intraocular pressure.

Amino Acid Sequence↗

Distribution and characterization of sulfated proteoglycans in the human trabecular tissue.

The distribution of proteoglycans in the trabecular tissue of human eyes was evaluated histochemically, using Cupromeronic Blue in combination with a series of enzyme digestions and nitrous acid treatment. Within the extracellular matrix of the trabecular meshwork, many Cupromeronic Blue-positive filaments were observed in association with collagen fibrils, basal lamina, a basal lamina-like material and a fine fibrillar-like material. Pretreatment with chondroitinase AC reduced the staining associated with the collagen fibrils, whereas filament staining in this location was completely eliminated by pretreatment with chondroitinase ABC. Nitrous acid treatment eliminated almost all the filament staining associated with the basal lamina and basal lamina-like material. When the tissue was treated with chondroitinase AC, chondroitinase ABC or nitrous acid, filament staining associated with the fine fibrillar-like material was reduced. After a combined treatment with nitrous acid followed by incubation with chondroitinase ABC, all filament staining in the trabecular meshwork was eliminated. These results are consistent with an interpretation that human trabecular tissue contains three distinct types of sulfated proteoglycans, namely chondroitin sulfate, dermatan sulfate and heparan sulfate-type proteoglycans. Proteoglycans containing chondroitin sulfate and dermatan sulfate are present in association with collagen fibrils. Proteoglycans of heparan sulfate-type are associated with the basal lamina and the basal lamina-like material. Chondroitin sulfate, dermatan sulfate and heparan sulfate-type proteoglycans are present in association with the fine fibrillar-like component. The basal lamina, basal lamina-like material and fine fibrillar-like components associated with these negatively charged proteoglycans may be important contributors to aqueous outflow resistance in the juxtacanalicular connective tissue.

Adult↗

Blood-aqueous barrier in pseudoexfoliation syndrome: evaluation by immunohistochemical staining of endogenous albumin.

BACKGROUND: Alterations of the integrity of the blood-aqueous barrier (BAB) are frequent findings in eyes with pseudoexfoliation syndrome (PSX). METHODS: Immunohistochemical staining for the demonstration of albumin was used to analyze the BAB in 10 eyes with PSX without previous intraocular surgery and in 10 age-matched normal control eyes. RESULTS: In eyes with PSX, small amounts of albumin were detected along the anterior surface of the iris in 7, in the anterior chamber in 1, along the ciliary epithelium in 4, and in the trabecular meshwork in 9 of 10 eyes. PSX material was also immunoreactive. In the 10 normal control eyes, albumin was detected anterior to the iris stroma in 1 eye, in the anterior chamber in 2 eyes, in the trabecular meshwork in 1 eye, but not internal to the ciliary epithelium. CONCLUSIONS: Our findings indicate that impairment of the BAB in PSX can be localized at the level of the iris and, less frequently or to a lesser extent, at the level of the ciliary body.

Aged↗

Hydrocortisone-induced DNA endoreplication in human trabecular cells in vitro.

Primary monolayer cultures of trabecular cells and organ cultures of trabecular meshwork, obtained from normal eyes of human subjects (age range, 40 to 70 yr) were exposed to hydrocortisone at concentrations ranging from 10(-4) M to 10(-6) M for periods up to 4 weeks. Phase-contrast microscopy of cultured cells showed an increase in the size of the nuclei (up to three times) and in the extent of the cell cytoplasm compared to those in control cultures, and vesicular structures frequently accumulated in the cytoplasm. Microdensitometry of Feulgen-stained cell nuclei indicated that the cells of the trabecular meshwork in vivo have predominantly diploid levels (2C) of DNA. Many nuclei in the trabecular cell cultures were polyploid and contained DNA values of 4C, 8C, and 16C. Cultures which had been exposed to hydrocortisone showed a significant shift toward the higher DNA classes, in contrast to the untreated control cultures; the average increase in the amount of DNA per nucleus was 36%. We discuss the relevance of these findings to the disease glaucoma in man.

Adult↗

Low-dose trabeculoplasty.

We treated 21 eyes (18 patients) with open-angle glaucoma by low-dose laser trabeculoplasty consisting of 25 laser burns spaced over one quadrant (90 degrees) of the trabecular meshwork. After one month these eyes showed an average decreased in intraocular pressure of 6.86 +/- 2.95 mm Hg. Sixteen eyes underwent a second treatment consisting of an additional 25 laser burns spaced over a second quadrant of the trabecular meshwork. Intraocular pressure decreased an additional 3.56 +/- 2.94 mm Hg in these eyes. Although low-dose trabeculoplasty decreases intraocular pressure by an amount similar to that achieved with standard laser trabeculoplasty treatment protocols, additional study is needed to determine whether complications are reduced and whether the beneficial effect is sustained over a long period of follow-up.

Glaucoma, Open-Angle↗

Melanocytomalytic glaucoma in eyes with necrotic iris melanocytoma.

OBJECTIVE: Iris melanocytoma, although histologically benign, may undergo spontaneous necrosis with the resultant pigment dispersion causing secondary open-angle glaucoma. The authors describe the clinical findings in three patients with this syndrome and review the current literature. DESIGN: The study design was a small case series. PARTICIPANTS: Three patients with secondary glaucoma caused by a necrotic iris melanocytoma participated. INTERVENTION: Clinical records and pathologic preparations were reviewed. The diagnosis of iris melanocytoma was confirmed by histopathologic examination in all three cases. RESULTS: All patients had intrinsically pigmented localized iris tumors and pigmentation of the angle. Hyperchromic heterochromia iridum was noticeable in all patients. In two instances, a central crater in the lesion signified tumor necrosis. Two patients were treated successfully by surgical resection of the iris tumor and the glaucoma resolved. One patient was treated with enucleation. In all patients, histopathologic analysis disclosed extensively necrotic tumor comprised of maximally pigmented nevus cells with bland nuclei and infiltration of the trabecular meshwork by melanophages. CONCLUSION: Secondary glaucoma may result from obstruction of the trabecular meshwork with necrotic iris melanocytoma. Resection of the tumor may relieve the glaucoma.

Adult↗

Clinicopathologic features of Chandler's syndrome.

The clinicopathologic features of Chandler's syndrome are elucidated based on a study of nine patients. Keratoplasty, trabeculectomy and/or iris specimens were studied by light, electron and, in six cases, specular microscopy. The prominent pathologic features were abnormalities of the endothelially-derived cells lining the posterior corneal surface, the inner surface of the trabecular meshwork, and the anterior iris surface. In all four corneal buttons, the endothelium was diffusely attenuated and focally absent, and posterior collagen layers were present. Extension of the endothelial cell layer and Descemet's membrane deposition over the trabecular meshwork were observed in two trabeculectomy specimens, and similar proliferation onto the anterior surface of the iris was evident in four iris specimens. Other abnormalities of the endothelial cells included increased intracytoplasmic filaments. These pathologic alterations are consistent with the concept of Chandler's syndrome as representing one variant of the iridocorneal endothelial (ICE) syndrome. Interestingly, although both endothelial proliferative and degenerative responses can be observed in Chandler's syndrome, their occurrence within the same eye is apparently not simultaneous.

Adult↗

Comparison of long-term outcomes of selective laser trabeculoplasty versus argon laser trabeculoplasty in open-angle glaucoma.

PURPOSE: To compare the long-term success rate of selective laser trabeculoplasty (SLT) versus argon laser trabeculoplasty (ALT). DESIGN: Retrospective chart review. PARTICIPANTS: One hundred ninety-five eyes of 195 patients with uncontrolled open-angle glaucoma (OAG), of which 154 eyes underwent ALT and 41 eyes underwent SLT and were followed up for a maximum of 5 years. INTERVENTION: The SLT patients were treated with the frequency-doubled q-switched neodymium:yytrium-aluminum-garnet laser (532 nm). Approximately 50 to 55 nonoverlapping spots were placed over 180 degrees of the trabecular meshwork at energy levels ranging from 0.6 to 1.0 mJ per pulse. The ALT patients were treated with the argon blue-green laser with between 45 to 55 adjacent, nonoverlapping spots over 180 degrees of the trabecular meshwork at 470 to 1150 mW of energy per pulse. MAIN OUTCOME MEASURES: The success rates were defined by criterion I and criterion II. Success by criterion I was defined as a decrease in intraocular pressure (IOP) of 3 mmHg or more with no additional medications, laser, or glaucoma surgery. Criterion II had the same requirements as criterion I, except that a 20% or more IOP reduction was required for success. RESULTS: The mean follow-up time was 37.4+/-14.7 months for patients in the SLT group and 33.6+/-17.0 months for patients in the ALT group. The long-term success rate was not significantly different between the ALT and SLT groups by either criterion (Kaplan-Meier survival analysis log-rank P = 0.20 by criterion I and P = 0.12 by criterion II). When comparing patients with and without previous ALT, there was not a statistically significant difference in the patients treated with SLT by either criterion (log-rank P = 0.37 by criterion I and P = 0.39 by criterion II). CONCLUSIONS: In eyes with primary OAG that are receiving maximally tolerated medical therapy, SLT was found to be as effective as ALT in lowering IOP over a 5-year period. However, long-term data reveal that many of the glaucoma patients treated with SLT and ALT required further medical or surgical intervention. Whether SLT has better long-term success than ALT in repeat laser trabeculoplasty treatments remains unclear.

Aged↗

Effects of Er:YAG laser trabecular ablation on outflow facility in cadaver porcine eyes.

BACKGROUND: Mid-infrared laser technology opens new perspectives in experimental glaucoma surgery. The aim of this study was to establish the effectiveness of Er:YAG laser photoablation of the trabecular meshwork in increasing outflow facility in cadaver porcine eyes. METHODS: Eye cups of 20 freshly enucleated cadaver porcine eyes were fixed in an anterior segment perfusion system, measuring outflow facility under constant pressure conditions (7-13 mmHg) over a period of 45 min. Trabecular ablation was performed using a pulsed Er:YAG (2.94 microns) laser. Radiation was delivered in a single 4-mJ pulse of 200 microseconds duration by means of an articulated zirconium fluoride optical fibre and a 320-microns quartz-fibre tip. RESULTS: Er:YAG laser treatment yielded reproducible ablation areas confined to the trabecular meshwork, with a diameter corresponding to that of the fibre tip. Collateral thermal damage extended up to a depth of 30 microns. Outflow facility measurements revealed an increase (mean +/- SD) from 0.128 +/- 0.041 microliter min-1 mmHg-1 in control eyes (n = 11) to 0.308 +/- 0.093 microliter min-1 mmHg-1 in treated ones (n = 9). CONCLUSION: Application of the photoablative Er:YAG laser technique in non-fistulating trabecular surgery produces patent trabecular perforation with minimal collateral tissue damage and effects a significant reduction (79%) in outflow resistance.

Animals↗

Lasers in the treatment of chronic simple glaucoma.

Basic biological effects of laser irradiation are given with respect to the treatment of chronic simple glaucoma. As for the irradiation of the trabecular meshwork, an ultrastructural analysis of what is happening in the method of Wise and Witter (1979) has been done (a). In comparison with the effect of an Argon-ion laser (pulse duration 0.2 s, pulse power 2.2 W) upon the trabecular meshwork of human autopsy eyes the effect of a Nd:YAG laser (pulse duration 10 ms, pulse energy 2 J) has been analysed in ultrastructure. After cyclodialysis by Q-switched laser pulses the routes of outflow of the aqueous humour from the suprachoroidal and supraciliary space have been marked using mercury sulfide red (b). Three ways of outflow could be identified: (1) Into the veins of the ciliary body (2) Into the vortex veins (3) Into the subarachnoidal space around the optic nerve. The last way represents a communication between the suprachoroidal space and the cerebrospinal fluid.

Argon↗

Histopathological study of trabeculum after excimer laser trabeculectomy ab interno.

PURPOSE: To study the clinical manifestations and histopathologic changes of trabeculum after excimer laser trabeculectomy ab interno (ELT), and to investigate the mechanisms of ELT in reducing intraocular pressure. METHODS: ELT was performed on ten rabbit eyes and postoperative responses were documented. Corneoscleral tissue samples were harvested consecutively each week until the 5th postoperative week and these samples were examined under light and electrical microscopy. RESULTS: Mild stimulation signs were present postoperatively in nine of ten eyes, but no serious complications were experienced. Obvious inflammation was observed in one rabbit eye as a result of iris damage during the surgical manipulations. Local fractures on the trabecular meshwork and openings into Schlemm's canal were detected in all tissue samples under light microscope. Mitochondria were found to be turgescent and dilated like vacuoles and endoplasmic reticula were found to be dilated under electrical microscope in the early postoperative period. Later, all trabecular cells returned normal and no fibroblast cells were ever detected. CONCLUSIONS: Permanent openings through trabecular meshwork into the inner wall of Schlemm's canal can be created with ELT. The outflow resistance of aqueous humor can be reduced with these openings and intraocular pressure can be controlled thereafter.

Animals↗

Is primary open angle glaucoma caused by small proteins?

Primary open angle glaucoma is a disease which is characterized by a decreased facility of outflow of aqueous humor from the anterior segment of the eye. Analyses by gel exclusion chromatography of the aqueous humor of normal monkeys have shown that the proteins in this fluid range in size from approximately 40-200 kilodaltons. Although small proteins and peptides are seen in the aqueous humor by SDS gel electrophoresis, these smaller proteins appear to elute by column chromatography with the albumin peak. In the outflow of the aqueous humor, the trabecular meshwork may be an efficient sieve for proteins of intermediate size, but this tissue may be obstructed if the proteins present become too large or too small as a result of other disease processes in the eye. Primary open angle glaucoma may be the result of the inability of the trabecular meshwork to filter small proteins and polypeptides efficiently.

Animals↗

Fluorescence-labeled lectins, glycoconjugates, and the development of the mouse AOP.

The development of the aqueous outflow pathway (AOP) in early postnatal mouse eyes was examined for the presence of a variety of lectin receptors using fluorescein isothiocyanate (FITC) conjugated lectins, 1 micron araldite plastic sections, and computer-aided fluorescence photography. The trabecular meshwork anlage (days 1-4) was characterized by the presence of loosely arranged cells and an extracellular matrix that exhibited intense areas of Con A- and RCA-lectin staining, and absence of WGA- and LPA-lectin staining. By day 6, trabecular meshwork LPA- and WGA-positive materials were observed as focal areas of staining. By day 10, LPA- and WGA-positive materials were present as diffuse areas of staining, as the AOP differentiated into an organized and functional biological filter. The age-dependent pattern of LPA- and WGA-positive materials indicated that there were time-dependent points in the synthesis of glycoconjugates in the developing AOP. The results suggest: The composition and/or conformation of the glycoconjugates on cells and extracellular matrix changed as the AOP differentiated into a functional tissue. The use of FITC lectins as biological markers for studies of the AOP provided information on the potential role of glycoconjugates in the development of the normal AOP. Modification in the type, amount, and distribution of glycoconjugates may provide a basis for understanding the cellular mechanisms of abnormal development of the AOP, eg, congenital glaucoma.

Animals↗

Defects in cortisol-metabolizing enzymes in primary open-angle glaucoma.

Assays of cortisol-metabolizing enzymes in homogenates of human trabecular meshwork cells under optimal conditions revealed two defects in primary open-angle glaucoma (POAG): one is a marked increase in delta 4-reductase and the other is a decrease in 3-oxidoreductase. Experiments indicated that the differences in enzyme activities seen between POAG and nonPOAG trabecular meshwork derived cell homogenates were due to altered amounts of enzymes rather than to alterations in cofactor availability, pH, or endogenous activators or inhibitors. This clearly demonstrates an enzymatic defect(s) in POAG which may be the basis for the ocular hypertension and sensitivity to exogenous glucocorticoids seen in this disorder.

Glaucoma, Open-Angle↗