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Laser trabeculostimulation in open-angle glaucoma: a new trial. Part I.

We describe herein a new trial to stimulate trabecular meshwork tissue and thereby increase outflow facility. The efficacy of our laser trabeculostimulation (LTS) was compared with that of conventional laser trabeculoplasty (LTP), since LTP causes shrinkage and cicatrization of the meshwork tissue, thus limiting the reduction of postoperative intraocular pressure (IOP). The mean preoperative IOP of 40 eyes was 24.9 +/- 6.8 mm Hg (mean +/- SD). LTS was applied with a 50-microns spot, a power setting of 50 mW and an exposure time of 1 s. With LTS, the IOP decreased but then increased afterward. Results indicate that low power (50 mW) is effective if used for a longer duration. Our LTS can be applied repeatedly and used in addition to conventional LTP. Although our LTS was less effective than LTP, the trial may lead to the development of another useful treatment modality.

Adult↗

Laser therapy for open angle glaucoma.

Fort-five phakic eyes with open angle glaucoma received argon laser therapy to the trabecular meshwork (laser goniotherapy). The average IOP dropped from 27.5 to 20.3 mm Hg in 22 eyes that were followed up for seven to fourteen months. Tonographic data obtained from 13 eyes prior to and approximately one month after laser treatment demonstrated a 50% increase in the facility of aqueous outflow. Several eyes experienced hypertensive episodes following treatment, in which the IOP increased as high as 60 mm Hg on one occasion. Two eyes developed prolonged uveitis with peripheral anterior synechiae formation. Laser goniotherapy appears to be a beneficial mode of therapy for open angle glaucoma in many patients. Longer follow-up is needed, however, and its role in secondary and aphakic glaucomas needs to be defined.

Follow-Up Studies↗

Congenital glaucoma unresponsive to conventional therapy: a clinicopathological case presentation.

A clinicopathological case report of a black male with congenital glaucoma is presented. The child died at age three months of the Sudden Infant Death Syndrome. The clinical course was characterized by persistent corneal clouding and elevated intraocular pressure in spite of vigorous medical and surgical therapy. Histopathological findings included corneal enlargement, marked hypoplasia of the canal of Schlemm, poorly developed scleral spur, insertion of the ciliary musculature directly into the trabecular meshwork anterior to the scleral spur, and anterior displacement of the iris root. There was also anomalous dispersion of the sphincter muscle of the iris from the pupillary margin almost to the iris root, and attachment of some ciliary processes to the posterior surface of the iris. A poor clinical response to conventional glaucoma therapy, including trabeculotomy, goniotomy, trabeculectomy and medical therapy, supports the belief that the marked hypoplasia of Schlemm's canal was a major factor contributing to the elevated intraocular pressure. Furthermore, the multiplicity of abnormalities of anterior chamber angle structures suggests that some cases of congenital glaucoma may result from an early and extensive disorder in the formation of anterior segment tissues.

Autopsy↗

Long term follow-up of the argon laser trabeculoplasty in eyes treated 180 degrees and 360 degrees of the trabeculum.

The results obtained with the Argon Laser Trabeculoplasty (ALT) on 196 eyes with an average follow-up period of 5.24 years (maximum 9 years) have been reviewed. Of the 123 eyes treated with 75-115 burns in the 360 degrees of the trabecular meshwork, 71 eyes were successful with a follow-up of 64.3 +/- 28.3 months (mean +/- SD). This treatment reduced the previous anti-glaucomatous medical treatment in 35 eyes (28.5%). The remaining 73 eyes were treated with 40-60 burns in 180 degrees of the trabeculum, 38.4% (28 eyes) were successful therapeutically with a follow-up of 56.5 +/- 23.1 months. The treatment reduced the additional medical treatment in 9 eyes (12.3%). The comparison of these results and the survival curves of both groups showed statistically significant differences in favour of the treatment on 360 degrees of the trabeculum.

Aged↗

Alterations of ocular nitric oxide synthase in human glaucoma.

PURPOSE: The authors recently reported that sites of outflow resistance and regulation in the human eye are highly enriched in the endothelial isoform of nitric oxide (NO) synthase (ecNOS). In vasculature, ecNOS activation is associated with altered vascular resistance and, in the stomach, defects in NO are associated with pathologic gastric hypertension. Because human glaucoma sometimes is associated with an increase in intraocular pressure and resistance changes in the aqueous outflow pathway (OP), the authors have investigated the possibility that alterations in NO or defects in NO-synthesizing tissues might exist in glaucomatous eyes. METHODS: Occurrence, distribution, and extent of sites of ocular NO production in the anterior segments of 16 normal eyes (10 patients) and 17 eyes (12 patients) with a history of primary open-angle glaucoma (POAG) were determined using the NO-indicator marker, NADPH-diaphorase (NADPH-d), which is known to colocalize with ecNOS immunoreactivity. Analysis of NADPH-d reactivity in tissues was combined with examination of overall cell distribution and use of neuron-specific markers. RESULTS: The ciliary muscle (CM) and OP of glaucomatous eyes showed marked differences in the amount and distribution of NADPH-d and alterations in gross structure. NADPH-d reactivity was decreased in trabecular meshwork (TM) and Schlemm's canal, and there was a marked reduction of anterior longitudinal CM fibers that insert near (and may normally regulate resistance in) the TM. CONCLUSION: Abnormalities in NO or NO-containing cells occur in POAG. These abnormalities may be causally related to glaucoma or may be a manifestation of the disease or its treatment. In either case, such alterations, together with recent pharmacologic studies showing that NO-mimicking nitrovasodilators alter IOP, indicate that NO has relevance to the course, treatment, or both, or some forms of this disease.

Aged↗

[Cofactorial glaucoma--causes].

The various types of glaucoma may be classified more accurately by studying the structure and physiology of the trabecular meshwork. Seen in this light, the development of glaucoma is linked to "extrinsic" and "intrinsic" factors. The intrinsic factors represent the predisposition to glaucoma; the secondary factors intervene in a secondary phase, creating a resistance to aqueous humor outflow. In so-called primary glaucoma the predisposition plays a decisive role, while the extrinsic factors are not so important. In cofactorial glaucoma the predisposition is only of slight significance, while the extrinsic factors are extremely important. In true secondary glaucoma predisposition plays a minimal role, while the extrinsic factors are all the more important. In correlated glaucomas the predisposition may be extremely relevant, but the extrinsic factors which represent the key causes are still unknown. Several types of glaucoma are described as examples.

Glaucoma↗

Variation of techniques on the results of argon laser trabeculoplasty.

Patients with uncontrolled open-angle glaucoma were treated with argon laser to the trabecular meshwork. These patients were divided into six groups. Each group of eyes had a slightly different technique of argon laser therapy. Except for one group, there was an adequate pressure lowering effect at the longest follow-up (-18 to -28%). Since the worst complication of argon laser trabeculoplasty is the immediate elevation in intraocular pressure with subsequent worsening of the field and/or disc, the immediate rise in intraocular pressure was measured and compared for each of the various techniques. In addition comparison was made when treating 180 degrees in one eye and 360 degrees in the other eye of 30 individuals having similar glaucomatous disease bilaterally. Little difference was noted between the two eyes.

Glaucoma, Open-Angle↗

Histopathology of Sanfilippo's syndrome.

A 19-year-old woman with Sanfilippo's syndrome had poor vision, a flat electroretinographic pattern, and fundus changes similar to those in retinitis pigmentosa. Histology of her eyes by phase-contrast and electron microscopy showed extensive intracellular accumulation of fibrillogranular and membranous lamellar vacuoles in cornea, trabecular meshwork, iris, lens, ciliary body, and sclera. Retinal ganglion cells, retinal pigment epithelium (RPE), and optic nerve glia were similarly involved. Retinal pigment epithelial hyperplasia and hypopigmentation, intraretinal RPE migration, vascular attenuation, and marked photoreceptor loss were notable and closely resembled that occurring in inherited retinitis pigmentosa. We assume that the patient's blindness was due to photoreceptor cell loss, since the ganglion cells and optic nerve seemed to be intact. Although the cause of photoreceptor loss is unclear, the massive storage of acid mucopolysaccharide and lipofuscin within the RPE might disturb its essential metabolic functions and lead to photoreceptor degeneration.

Adult↗

[Fuchs' heterochromic cyclitis. Clinico-histopathologic findings of nodular iritis].

BACKGROUND: Despite the fact that in 1906 Fuchs described the first case of Fuchs' heterochromic cyclitis histopathologic reports of this disease are still rare. PATIENT AND METHODS: A clinicopathologic correlation of findings in Fuchs' heterochromic cyclitis is presented. In a patient with a history of Fuchs' heterochromic cyclitis for 15 years a secondary open-angle glaucoma developed. Several operations were performed including intracapsular cataract extraction, goniotrephanation (Elliot) and repeated cyclocryotherapy. The eye finally had to be enucleated because of a painful absolute glaucoma. RESULTS: Clinical hallmarks of Fuchs' heterochromic cyclitis in this patient include cataract formation and secondary open-angle glaucoma. Histology revealed accumulations of mononuclear cells on the surface of the iris and the corneal endothelium, as well as sparse inflammatory cells within the anterior chamber. The trabecular meshwork showed an infiltration of mononuclear inflammatory cells, chiefly lymphocytes and plasma cells. DISCUSSION: Accumulations of mononuclear cells on the surface of the iris, which histopathologically have not been described before, could represent the clinicopathologic correlate of Koeppe and Busacca nodules. Histologically, the cell deposits on the iris were similar to those in the anterior chamber and to larger corneal precipitates. It is supposed that the cells, which originally emigrated from the iris vessels, may form primary cell deposits on the iris surface or endothelium. Such iris precipitates may also be secondarily attracted by the endothelium in whole. An autoimmune-reaction against the corneal endothelium may be the underlying reason.

Adult↗

Axenfeld-Rieger syndrome: a theory of mechanism and distinctions from the iridocorneal endothelial syndrome.

Twenty-four patients with the diagnosis of Axenfeld's anomaly or Rieger's anomaly or syndrome were the subjects of a clinical study, which included specular microscopy of the corneal endothelium in 16 cases and fluorescein angiography of the iris in 5. Histopathologic material was obtained from ten eyes of eight of these patients (one enucleated eye and nine trabeculectomy specimens) and was studied by light and electron microscopy. The overlapping of ocular and nonocular defects in these patients prevented subclassification according to traditional criteria. Any attempted subdivision appears to have minimal clinical value, and a single classification for the disease spectrum is believed to be more practical. The collective term Axenfeld-Rieger (A-R) syndrome is proposed. A theory of mechanism for the ocular features of the A-R syndrome is postulated which involves a developmental arrest, late in gestation, of tissues derived from neural crest cells. This leads to retention of primordial endothelial tissue on the iris and across the anterior chamber angle, which produces the iridic changes and the peripheral tissue strands. Continued contraction of these membranes after birth explains the progressive changes noted in some patients. This primordial endothelium also produces excessive and atypical basement membrane, especially near the corneolimbal junction, which accounts for the prominent Schwalbe's line. The secondary glaucoma results from arrested development of the anterior chamber angle structures, characterized by incomplete maturation of the trabecular meshwork and Schlemm's canal and a high insertion of the iris. The ICE syndrome may be confused with the A-R syndrome on the basis of certain clinical and histopathologic similarities. Based on available evidence, however, it is postulated that the two entities are distinctly separate, in that the fundamental defect in the ICE syndrome is believed to be an abnormality of the corneal endothelium with secondary proliferation of a tissue layer over the anterior chamber angle and iris, while the A-R syndrome is thought to represent a developmental arrest with retention of a primordial membrane and other developmental defects.

Abnormalities, Multiple↗

Selective laser trabeculoplasty.

Selective laser trabeculoplasty (SLT) has been shown to be safe, well tolerated, and effective in intraocular pressure (IOP) reduction as therapy in several forms of open-angle glaucoma. The preservation of trabecular meshwork (TM) architecture and the demonstrated efficacy in lowering IOP make SLT a reasonable and safe alternative to argon laser trabeculoplasty (ALT). SLT may also be effective for cases of failed ALT and is a procedure that may also be repeatable, unlike ALT. SLT is also a simple technique for an ophthalmologist to learn as the large spot size eliminates the need to locate a particular zone of treatment on the TM. SLT has been demonstrated to be effective as primary treatment for open angle glaucoma and can be an effective adjunct in the early treatment of glaucoma. Furthermore, SLT can be considered as a primary treatment option in patients who cannot tolerate or who are noncompliant with their glaucoma medications, without interfering with the success of future surgery.

Glaucoma↗

Histochemical survey of the anterior segment of the normal human foetal and adult eye.

The distributions of the lysosomal enzymes [acid phosphatase (AP), N-acetyl-beta-D-glucosaminidase (NAG), beta-glucuronidase (beta-Gluc), beta-galactosidase (beta-Gal), dipeptidylpeptidase II (DPP II)] and of the membrane-bound proteases [aminopeptidase M (APM), aminopeptidase A (APA), gamma-glutamyltransferase (GGT), dipeptidylpeptidase IV (DPP IV)] were investigated in the normal human adult and foetal anterior segment by histochemical methods. The distribution of these hydrolases varied between ocular tissues. The most active enzymes in the adult corneal epithelium and endothelium were AP, beta-Gluc, NAG, beta-Gal and GGT; in the keratocytes, APM, APA, beta-Gluc and GGT predominated. The adult trabecular meshwork cells were stained by AP, beta-Gluc, NAG, APM, GGT, DPP II and DPP IV. The enzymes AP, beta-Gluc, APM and APA, however, displayed greater activity in the endothelium of Schlemm's canal. The adult ciliary epithelium stained strongly for all lysosomal hydrolases; GGT was the most active protease here. Differences in enzyme activity were noted in some tissues when foetal and adult anterior segments were compared. There appeared to be a decrease in the activity of some enzymes with age and post-mortem delay greater than 24 h. The function(s) of each enzyme and their possible roles in the respective tissues are discussed.

Aged↗

Pathophysiology of pigment dispersion syndrome and pigmentary glaucoma.

Pigmentary glaucoma results from zonular-pigment dispersion, primarily in young, myopic, white individuals. The concavity of the midperipheral iris allows iridozonular contact. Released pigment is carried to the trabecular meshwork where it resides: (1) benignly, not affecting the intraocular pressure, as in pigment dispersion syndrome; or (2) malignantly, elevating the intraocular pressure, as in pigmentary glaucoma. Small amounts of pigment are quickly phagocytized. If the particulate load is heavy, the cells migrate further along the outflow pathway. The flattening of the iris in pigmentary glaucoma patients receiving iridotomies, along with the backward flow of pigment observed during treatment, demonstrates a greater pressure in the anterior than the posterior chamber. This reverse pupillary block may be due to temporary ocular deformations caused by blinking, as small aqueous aliquots are forced into the anterior chamber. Flattening of the concave iris is the key to current and future management of these patients.

Ciliary Body↗

[Implant in Schlemm's canal. A new method for regulating intraocular pressure in patients with primary open-angle glaucoma?].

BACKGROUND: A surgical technique was developed using a Schlemm's canal implant to bypass the obstruction of outflow of the juxtacanalicular trabecular meshwork in patients with primary open-angle glaucoma. The implant device should also bridge healing processes after trabeculotomy and laser techniques. PATIENTS AND METHODS: An 8- to 15-mm-long silicone tube was implanted in each of two human autopsy eyes connecting the anterior chamber directly with Schlemm's canal. Serial sectioning was performed at two sections of 1-mm length. RESULTS: Implantation of the tube was technically uneventful. Histological examination showed no evidence of mechanical disruption of the endothelial lining of the inner wall of Schlemm's canal. CONCLUSION: These preliminary results demonstrate the possibility of shunting aqueous directly into Schlemm's canal using a silicone tube. A clinical study in a selected group of patients is planned.

Glaucoma, Open-Angle↗

Histopathology and molecular basis of iridogoniodysgenesis syndrome.

Iridogoniodysgenesis is an autosomal dominant disorder in which there are abnormalities in the development of the iris stroma and trabecular meshwork tissues commonly resulting in glaucoma. The unoperated eye from an affected member of a family with iridogoniodysgenesis syndrome (IGDS) was removed shortly after death. Histopathological studies showed an incomplete, normally positioned line of Schwalbe and iris stromal hypoplasia. The molecular basis underlying the disorder is a missense mutation in the RIEG gene at 4q25, mutations of which have been previously shown to cause Axenfeld-Rieger syndrome (ARS). Coupled with another report of a missense mutation of the RIEG gene in a family with IGDS, we suggest that these mutations may interfere less with gene function and thereby may be responsible for a milder phenotype than occurs in the more characteristic ARS.

Congenital Abnormalities↗

The TIGR gene, pathogenic mechanisms, and other recent advances in glaucoma genetics.

Important advances have been made within the past year in the area of glaucoma genetics, including the identification of the TIGR gene for adult as well as juvenile GLC1A glaucoma, a P450 gene for GLC3A congenital glaucoma, and a bicoidhomeobox transcription factor gene RIEG for developmental glaucoma. The cloning of TIGR as a candidate gene for glaucoma is based on its distinctive induction in human trabecular meshwork cells and tissues, its induction profile, and the expressed molecule's putative biologic properties. Results from several laboratories showing defects in the olfactomedin homology domain of the TIGR gene have generated particular interest concerning potential pathogenic mechanisms. Recent progress in glaucoma genetics has also included the identification of new loci in familial adult open-angle glaucoma, the identification of a locus associated with pigment dispersion syndrome, and the collection of new families for linkage analyses and clinical assessments. Taken together, these findings offer future prospects for improving diagnostic criteria, for understanding disease etiologies, and for developing improved therapeutic strategies.

Adolescent↗

Anterior chamber angle in the exfoliation syndrome.

The gonioscopic findings of 76 patients with the exfoliation syndrome were reviewed. A high frequency of narrowness of the anterior chamber (AC) angle was found (32%). 18% had angles considered occludable, and 14% had obvious angle-closure glaucoma as shown by the presence of peripheral anterior synechias (PAS). Increased pigmentation of the posterior trabecular meshwork (PTM) was noted in all cases. When this pigmentation was markedly asymmetrical, unilateral exfoliation with glaucoma was common in the more pigmented eye. In addition heavy angle pigmentation in the absence of exfoliation was noted in the fellow eye of patients with characteristic exfoliated material in the other eye. Increased pigmentation of the PTM may be the earliest detectable sign of the exfoliation syndrome (ES). The clinical significance of our estimating PTM pigmentation at the 12 o'clock position is discussed. In view of the accelerated optic nerve damage associated with the development of glaucoma secondary to ES, routine estimation of the pigmentation of the PTM at 12 o'clock is recommended in the hope of early detection of cases of otherwise inapparent ES.

Aged↗

Anatomic correlates of changing aqueous outflow facility in excised human eyes.

Five pairs of excised human eyes were examined for anatomic correlates of changes in aqueous outflow facility that result from changing the intraocular pressure (IOP) and from placing mechanical tension on the irido-corneal angle (lens depression). An increase in IOP from 0 to 40 mm Hg tended inconsistently to compress trabecular meshwork as a whole and to distend the juxtacanalicular tissue. The most constant and significant effect of increasing IOP, however, was to compress Schlemm's canal, thereby progressively diminishing its volume to its virtual collapse at 40 mm Hg IOP. Lens depression increased Schlemm's canal volume and partially prevented its collapse at high levels of IOP. The mean frequency of endothelial vacuoles was remarkably constant at IOPs from 2.5 to 40.0 mm Hg, with and without lens depression, but was significantly lower when the IOP was reduced to 0 mm Hg. When correlated with existing physiologic data, these anatomic findings suggest that Schlemm's canal collapse, but not vacuole frequency, is an important contributor to pressure-dependent changes in aqueous outflow facility.

Adult↗