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Comparison of laser trabeculostimulation with laser trabeculoplasty in open-angle glaucoma.

We compared a new method, laser trabeculostimulation (LTS), with laser trabeculoplasty (LTP). The technique LTS stimulates trabecular meshwork tissue and thereby increases the outflow facility. The method LTP causes shrinkage and cicatrization of the meshwork tissue, thus limiting the reduction in postoperative intraocular pressure (IOP). The mean preoperative IOP of 40 eyes was 24.9 +/- 6.8 mmHg (mean +/- standard deviation). The LTS was applied with a 50-microns spot size, a power setting of 50mW, and an exposure time of 1 sec. With LTS, the IOP decreased and then increased afterward. Low power (50mW) was effective if used for a longer duration. The LTS can be applied repeatedly and used in addition to conventional LTP. The overall effect achieved with LTS was less than that with LTP, but it is possible to reduce IOP by selecting more reasonable parameters, e.g., a laser setting of 200mW, a 50 microns spot size and a 0.5 to 1-sec duration.

Adult↗

Integrins in human anterior chamber angle.

BACKGROUND: Integrins, which are composed of an alpha and beta subunit, are capable of binding to a number of extracellular matrix proteins and, hence, affect cell adhesion and proliferation. METHODS: The distribution of the integrin beta (beta 1, beta 3-beta 5) and alpha (alpha 1-6 and alpha v) subunits in human anterior chamber angle was studied in eyes from subjects aged 9 months to 81 years using the indirect immunofluorescence technique. RESULTS: Immunoreaction for the beta 1 subunit was found throughout the trabecular meshwork (TM), in the cribriform layer, and in the endothelial lining of Schlemm's canal (SC). Labelling for the alpha 3 subunit was found in the TM and the cribriform layer only. In infant eyes the alpha 5 subunit was present in all three areas with the highest concentration in the cribriform layer, whereas no reaction was observed in adult eyes. The alpha 6 subunit was localized to the endothelium of SC only. Immunoreaction for the alpha v subunit was present in the TM and the cribriform layer of infants and young adults. CONCLUSION: The present results suggest the presence of several integrin heterodimers, acting as potential receptors for laminin, collagen, fibronectin, and vitronectin, in the anterior chamber angle.

Adolescent↗

Pathological study of cases with secondary open-angle glaucoma due to sarcoidosis.

PURPOSE: To investigate the cause of secondary open-angle glaucoma due to sarcoidosis. DESIGN: Observational case series studied by histological methods. METHODS: Seven trabeculectomy specimens from six patients with secondary open-angle glaucoma due to ocular sarcoidosis (trabeculectomy group) and anterior parts of seven autopsy eyes from four patients (autopsy eye group) diagnosed as confirmed sarcoidosis were processed for light and transmission electron microscopy. Pathological changes of outflow routes were investigated. RESULTS: Granulomata were found in three eyes of the trabeculectomy group and in three eyes of the autopsy eye group. Part of the Schlemm canal was occluded and replaced by fibrotic tissue and it became narrow in four eyes of the trabeculectomy group and three eyes of the autopsy eye group. The spaces of the trabecular meshwork appeared wide, even in the area close to granulomata and peripheral anterior synechia of the iris. Infiltration of lymphocytes, monocytes, and macrophages around the Schlemm canal was found in all eyes of the trabeculectomy group and in four eyes of the autopsy eye group. The infiltration of these cells was observed not only in the inner wall, but also in the posterior outer wall of the Schlemm canal and the collector channels. CONCLUSION: "Schlemm canalitis" is proposed from the results of inflammatory cell infiltration around the wall of the canal. The occlusion of the Schlemm canal by granulomata or fibrotic tissue replacement of the canal may play an important role in secondary open-angle glaucoma due to sarcoidosis.

Adult↗

Innervation of the porcine ciliary muscle and outflow region.

The porcine eye serves as a model to study various functions of the aqueous outflow system. To compare these data with the primate eye, a detailed investigation of the distribution of contractile properties and of the innervation of the outflow region was conducted in the porcine eye. In all quadrants of the anterior eye segment, elastic fibres connected the ciliary muscle (CM) with the well-developed scleral spur (ScS) and also partly with the corneoscleral trabecular meshwork (TM) and the loops of the collecting outflow channels. Immunohistochemistry with antibodies against smooth muscle alpha-actin revealed intense staining of the CM and some myofibroblasts in the ScS and outer TM. In addition to a few cholinergic and aminergic nerve fibres in the outflow region, numerous substance P- and calcitonin-gene related peptide-positive nerve fibres and nerve endings were found near the outflow loops of the porcine TM. Although the porcine CM serves rather as a tensor choroideae muscle than as a muscle for accommodation, the innervation and morphology of the collecting outflow channel loops and of the expanded TM between the ScS and the cornea showed close similarities to the primate eye.

Actins↗

Identification of a gene that causes primary open angle glaucoma.

Glaucoma is a major cause of blindness and is characterized by progressive degeneration of the optic nerve and is usually associated with elevated intraocular pressure. Analyses of sequence tagged site (STS) content and haplotype sharing between families affected with chromosome 1q-linked open angle glaucoma (GLC1A) were used to prioritize candidate genes for mutation screening. A gene encoding a trabecular meshwork protein (TIGR) mapped to the narrowest disease interval by STS content and radiation hybrid mapping. Thirteen glaucoma patients were found to have one of three mutations in this gene (3.9 percent of the population studied). One of these mutations was also found in a control individual (0.2 percent). Identification of these mutations will aid in early diagnosis, which is essential for optimal application of existing therapies.

Base Sequence↗

The prostanoid EP2 receptor agonist butaprost increases uveoscleral outflow in the cynomolgus monkey.

PURPOSE: To investigate the ocular hypotensive effect of the prostanoid EP2 receptor agonist butaprost and to establish its mechanism of action. METHODS: All experiments were performed in cynomolgus monkeys after topical application of butaprost (0.1%). The effects of butaprost on aqueous humor flow were determined by fluorophotometry. Total outflow facility was measured by the two-level, constant-pressure perfusion method, and uveoscleral outflow was determined by perfusion of FITC-labeled dextran through the anterior chamber. Effects on ocular morphology were studied after tissue fixation with transcardial perfusion by paraformaldehyde and immersion fixation of the globe, in animals subjected to long-term treatment with butaprost. Conscious ocular normotensive monkeys and monkeys with unilateral ocular hypertension were used for intraocular pressure (IOP) studies. RESULTS: Butaprost had no significant effect on aqueous humor flow or total outflow facility in ocular normotensive monkeys. Uveoscleral outflow was significantly higher in the butaprost treated eyes than in vehicle treated eyes, 1.03 +/- 0.20 vs. 0.53 +/- 0.18 microL.min(-1). After a 1-year treatment with butaprost, the morphology of the ciliary muscle was changed, showing increased spaces between ciliary muscle bundles and the apparent formation of new outflow channels. In many instances, changes were observed in the trabecular meshwork as well. Butaprost, in a single 0.1% dose, decreased IOP significantly in ocular normotensive monkeys and reduced IOP in laser-induced glaucomatous monkey eyes to the same level as that in the ocular normotensive contralateral eyes. CONCLUSIONS: The prostanoid EP2 receptor agonist butaprost appears to lower IOP by increasing uveoscleral outflow, according to both physiological and morphologic findings. Although the prostanoid EP2 receptor is structurally and functionally distinct from the FP receptor, the effects of EP2 and FP receptor stimulation on aqueous humor outflow are similar.

Administration, Topical↗

Long-term clinical results of selective laser trabeculoplasty in the treatment of primary open angle glaucoma.

PURPOSE: To investigate the long-term efficacy of selective laser trabeculoplasty (SLT) in primary open-angle glaucoma, the authors performed a non-randomized, prospective, non-comparative clinical case series. METHODS: Fifty-two eyes of 52 patients (19 male, 33 female) with primary open angle glaucoma were treated with SLT. Patients were treated with the Coherent Selecta 7000 (Coherent, Palo Alto, CA, USA) frequency-doubled q-switched Nd:YAG laser (532 nm). A total of approximately 50 non-overlapping spots were placed over 180 degrees of the trabecular meshwork at energy levels ranging from 0.6 to 1.4 mJ per pulse. After surgery, patients were maintained with the drug regimen identical to that before treatment. RESULTS: After 1 year the average reduction in intraocular pressure (IOP) from the baseline was 24.3% (6.0 mmHg), after 2 years 27.8% (6.12 mmHg), after 3 years 24.5% (5.53 mmHg), and after 4 years 29.3% (6.33 mmHg). A Kaplan-Meier survival analysis revealed a 1-year success rate of 60%, a 2-year success rate of 53%, a 3-year success rate of 44%, and a 4-year success rate of 44%. CONCLUSIONS: Despite a declining success rate, SLT is an effective method to lower IOP over an extended period of time.

Adult↗

The anterior chamber angles in Nigerians.

The anatomic configuration of the anterior chamber angles in 240 newly diagnosed cases of primary glaucoma in Nigerian adults 30 years and above have been studied. The gonioscopic features in eyes of glaucoma patients 30 years and over have been compared to 250 subjects without glaucoma. Closed angles (Scheie grade 0 or 1) was found in 15.0% of cases compared to 1.6% of controls. There was a statistical significant difference in the distribution of angle width between the 2 groups (X2 = 71.47, P < 0.0001). Grade angle 0 was not found in the control group, subjects with closed angles in the controls had at least grade 1 angle width. Anterior iris insertion characterized the anterior chamber angles in eyes of subjects in the glaucoma group occurring in 14.2% compared to 3.2% of eyes in the control group. This difference was statistically significant (X2 = 18.79, P < 0.0001). 38.8% of eyes with glaucoma were considered to have occludable angles compared to 10.4% of control eyes, a difference also statistically significant (X2 = 53.52, P < 0.0001). Trabecular meshwork pigmentation and peripheral iris curvature did not occur differently in the two groups. Mean central anterior chamber depth (CACD) was shallower in cases than in controls. This difference was statistically significant P = 0.002. The mean depth was shallower in female cases than male cases. It decreased with age in subjects with glaucoma and those without. The mean CACD increases with increasing angle width. Just over half of subjects with closed angles have mean CACD less than 2.5 mm. The other subjects with angle closure glaucoma with higher CACD may have plateau iris. Closed angles, anterior iris insertion and shallower central anterior chamber depth are statistically significantly associated with eyes glaucoma. Increased pigmentation and peripherally convex iris curvature were not significantly associated with eyes glaucoma.

Adult↗

Acute haptic-induced pigmentary glaucoma with an AcrySof intraocular lens.

A 49-year-old man had uneventful endocapsular phacoemulsification with in-the-bag implantation of an AcrySof SA60AT single-piece intraocular lens (IOL) (Alcon) in the right eye. Twenty-seven days postoperatively, he presented with ocular pain, intraocular pressure of 48 mm Hg, 360 degrees of hyperpigmentation of the trabecular meshwork, and iris pigment epithelial atrophy in the region of the upper temporal haptic, which had dislocated into the sulcus. The patient made an excellent recovery following IOL removal and exchange. Scanning electron microscopy of the explanted IOL demonstrated that the haptic had a rough lateral surface and anterolateral edge. We do not think this IOL should be implanted in the sulcus placement of the heptics. In this article, we report the case of a patient with an AcrySof SA60ATIOL (Alcon) who developed acute pigmentary glaucoma when the inferior haptic slipped out of the bag and came into contact with the pigmented iris and ciliary body.

Acrylic Resins↗

Morphological changes in glaucomatous eyes and the role of TGFbeta2 for the pathogenesis of the disease.

This review summarizes the Ernst H. Bárány Prize Lecture given at the XVI. meeting 2004 of the International Society of Eye Research in Sydney, Australia. The article describes the author's early studies starting with the determination of the site of aqueous humour outflow resistance and its regulation through ciliary muscle contraction, which were performed in collaborations with Bárány. It continues with the qualitative and quantitative evaluation of the trabecular meshwork (TM) changes seen in different kinds of glaucoma diseases. A comparison of correlations between meshwork pathology, IOP, and axon loss in the optic nerve between eyes with pseudoexfoliation glaucoma (PEXG) and primary open angle glaucoma (POAG) indicates that in the secondary glaucoma (PEXG) optic neuropathy is mainly induced by an increase in IOP. In eyes with POAG, the correlations point towards a more complex pathogenesis of the disease. Common factors might be involved in both the TM and the optic nerve changes. In vitro studies performed in cell cultures of human TM cells and optic nerve astrocytes as well as organ culture studies of the anterior eye segment indicate that TGFbeta2 might be one of the factors involved in the development of POAG. The paper is primarily focused on studies performed by the author and complete reference to other previous or contemporary studies is therefore not given as the purpose is not to present a comprehensive review article.

Ciliary Body↗

Microvessels of the human optic nerve head: ultrastructural and radioreceptorial changes in eyes with increased IOP.

BACKGROUND: Ultrastructural, morphological modifications in the microvessels of the optic nerve head were studied in human eyes with normal intraocular pressure (IOP), with slightly increased IOP, and with strongly increased IOP. Moreover, the distribution of beta-adrenergic receptors was analyzed in the same samples. METHODS: Six enucleated human eyes were studied. Small pieces of the optic nerve head and of iridocorneal angle (including trabecular meshwork) were dissected immediately after autopsy. The sections were studied with transmission electron microscopy and autoradiography. Radiolabelled pindolol was used to locate beta-adrenergic receptors topographically on fresh sections of human eye. RESULTS: Transmission electron microscopy demonstrated that elevated IOP induces ultrastructural modifications of the microvessels of the optic nerve head. Autoradiographic experiments showed the presence and distribution of beta-adrenergic receptors in the optic nerve head of eyes with both normal and increased IOP. INTERPRETATION: Increased IOP initially compresses the microvessels of the optic nerve head. The number of beta-adrenergic receptors increased markedly in the eyes with raised IOP. Further studies are needed to clarify the physiological and pathological roles of these receptors.

Aged↗

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.

Animals↗

Experimental glaucoma model in the rat induced by laser trabecular photocoagulation after an intracameral injection of India ink.

A simple and reproducible rodent glaucoma model is required to elucidate the pathophysiology of damage to the optic nerve. We developed chronically elevated intraocular pressure (IOP) unilaterally in rats by injecting india ink into the anterior chamber of one eye using a 30-gauge needle. One week later, trapped carbon particles in the chamber angle formed a black band along the corneal limbus in the injected eyes. We performed direct laser photocoagulation without a gonio lens, and selectively burned the trabecular meshwork. Intraocular pressure was measured every week and laser photocoagulation was repeated until mean IOP in the experimental eyes rose above 25 mmHg. Unilateral IOP elevation was attained in all rats within 4 weeks. Twelve weeks after ink injection, we sacrificed the rats and excised the eyes for histologic analysis. The anterior chamber angle showed peripheral anterior synechia caused by laser photocoagulation, and carbon particles were engulfed by macrophages that infiltrated the ciliary cleft. In the optic nerve head, a remarkable decrease in the nerve fiber layer and cavernous degeneration were observed, suggesting glaucomatous optic nerve damage. This experimental rodent model should facilitate the study of the complex mechanisms involved in glaucoma.

Animals↗

Juvenile open angle glaucoma: fine mapping of the TIGR gene to 1q24.3-q25.2 and mutation analysis.

Autosomal dominant juvenile open angle glaucoma (JOAG) is an early-onset form of primary open angle glaucoma (POAG), which has been linked to chromosome 1q21-q31. Recently, mutations in the trabecular meshwork inducible glucocorticoid response gene (TIGR), one of the candidate genes mapped in this region, were identified in glaucoma patients of several families. We screened for mutations of the TIGR gene in two German families with JOAG and in 100 unselected sporadic cases of POAG. In the first family we identified a Pro370Leu mutation and in the second family a Gly367Arg mutation cosegregating with the glaucoma phenotype. No pathogenic mutation was found in 100 sporadic cases but a Tyr347Tyr polymorphism was found in two patients. Furthermore, fluorescence in situ hybridization (FISH) analysis was used to map a TIGR-specific yeast artificial chromosome to 1q24.3-q25.2.

Adolescent↗

Retroperfusion studies of the aqueous outflow system. Part I: Evaluation of technique using N-ethyl maleimide.

PURPOSE: The goal of this study was to develop a new technique to deliver drugs or other agents to the lumen of the angular aqueous plexus/Schlemm's canal (AAP/SC) while bypassing the trabecular meshwork, thereby gaining insight into AAP/SC inner wall function. METHODS: The anterior chamber is held at a small negative pressure and fluid is allowed to flow retrograde from the limbal vessels, through the collector channels, and into the AAP/SC ("retroperfusion"). Facility measurements are combined with histologic and tracer studies in bovine eyes. RESULTS: (1) Retroperfusion with a saline solution does not alter facility or change outflow pathway morphology; (2) fluid is able to move retrograde from the scleral surface and enter the lumen of the AAP; and (3) retroperfusion with N-ethyl maleimide causes a dose-dependent increase in washout rate and concomitant inner wall breaks. CONCLUSIONS: It is hypothesized that the observed increase in washout is due to leakage of extracellular materials through breaks in the inner wall.

Animals↗

One-year follow-up of laser trabeculoplasty using Q-switched frequency-doubled Nd:YAG laser of 523 nm wavelength.

BACKGROUND AND OBJECTIVE: To investigate clinical efficacy and safety of a new laser treatment of open angle glaucoma that targets pigmented cells in the trabecular meshwork for disruption. MATERIALS AND METHODS: The 16 eyes of chronic open angle glaucoma patients were treated in the method similar to argon laser trabeculoplasty using Q-switched, frequency-doubled Nd:YAG laser (523 nm). The treatment results were followed and analyzed for a one-year period. RESULTS: Mean intraocular pressure reduction of 3.81 mm Hg (15%) at 3 months, 3.94 mm Hg (16.1%) at 6 months, and 4.93 mm Hg (20.2%) at 12 months from the baseline were obtained. Slightly greater reductions were seen in the responder group that consisted of eyes showing 3 mm Hg or greater reduction. Adverse reactions were minimal and not significant. CONCLUSION: This new laser trabeculoplasty has shown reasonable efficacy and safety on a limited number of eyes over a one year duration.

Aged↗

Laser trabecular sclerosis for chronic hypotony after vitreoretinal surgery.

PURPOSE: To perform a pilot study of laser trabecular sclerosis (LTS) for chronic ocular hypotony after vitreoretinal surgery. DESIGN: Prospective noncomparative case series. PARTICIPANTS: Three patients with chronic hypotony after vitreoretinal procedures underwent LTS. All patients had undergone complex vitreoretinal surgery with attached retinas postoperatively but with persistent hypotony and poor vision. INTERVENTION: Laser trabecular sclerosis was performed in a fashion similar to laser trabeculoplasty, using a 100-microm spot, 800 to 1000 mW power at 0.1 seconds, and applying heavy confluent treatment in >/=1 sessions throughout the angle where trabecular meshwork was visible. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), best spectacle-corrected visual acuity, and complications were studied. RESULTS: In 1 patient, a single session of LTS was followed by an increase in IOP of approximately 4 mm, with subjective and objective improvement in vision. A second patient exhibited improvement in IOP and visual acuity after 3 sessions of LTS. A third patient underwent 3 sessions of LTS without improvement in IOP or vision. CONCLUSION: Given the limitations of this small series, including the lack of a randomized prospective design, it is not possible to determine the safety or efficacy of LTS, but this study does suggest that this procedure could play a therapeutic role in some patients with chronic symptomatic hypotony after complex intraocular surgery. Further study is warranted.

Adult↗

[Intracanalicular trabeculostomy with the Er:YAG laser].

PURPOSE: To develop a new ab externo technique for glaucoma trabecular surgery using the infrared Er:YAG laser radiation (2.9 micrometer) guided into Schlemm's canal by an optical fiber. MATERIAL AND METHODS: In order to create a drainage canal to the anterior chamber, a quartz fiber (core diameter: 100 micrometer) coupled to an Er:YAG laser was shielded by a metal canula (diameter: 280 micrometer) bent in conformance to the curvature of Schlemm's canal. A 45 degrees -mirror enabled the laser radiation to exit the canula perpendicular to the fiber axis. The complete surgery device was tested on agar medium and enucleated human eyes. RESULTS: Using the unshielded quartz fiber, eight pulses of 8 mJ (frequency: 7 Hz, pulse duration: 150 microseconds) were sufficient to perforate the trabecular meshwork of the human eye. Histology showed a rippled canal with 50 micrometer average diameter and a surrounding necrosis zone of 15-35 micrometer. The complete device could be easily inserted into Schlemm's canal similar to the classic trabeculostomy probe and a conical-shaped canal with a length of 2-3 mm could be created in agar medium within a few seconds. CONCLUSIONS: Initial experience in an experimental set-up show the ab externo creation of a draining canal between Schlemm's canal and the anterior chamber with only minimal irritation of the surrounding tissue. Further refinements of the laser parameters and the biomechanical set-up resulted in a new hand-held device with improved function. The Er:YAG laser intracanalicular trabeculostomy could become a new ab externo technique for minimal invasive therapy of open angle glaucoma.

Equipment Design↗