Selective laser trabeculoplasty: stimulating the meshwork to mend its ways.
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[A case of Rubinstein-Taybi syndrome suspected with goniodysgenetic glaucoma].
We reported a case of Rubinstein-Taybi syndrome suspected in association with goniodysgenetic glaucoma, and studied using light and electron microscopy the anterior chamber angle tissues obtained surgically by trabeculectomy. The patient was 31-year old male, who had a systemic appearance of Rubinstein-Taybi syndrome with dwarfism, mental retardation, antimongoloid slant, flat-broad based thumbs, low set ears, high arched plate except for whorl of dermatographism. In addition to these malformations, goniodysgenetic glaucoma was also present which is characterized by underdevelopment of the angle recess and invisible ciliary body band in gonioscopic examination. The histopathological studies of the specimens revealed the presence of a compact tissue filled with a large amount of collagen fibers with few cells in the juxta-canalicular tissue of Schlemm's canal. There were 3 to 4 layers of trabecular sheets of corneoscleral meshwork at the anterior chamber side of the compact tissue. We conclude that the presence of the compact tissue under Schlemm's canal represents goniodysgenesis, underdevelopment of the trabecular meshwork, which is the primary cause of the glaucoma in this case.
Adult↗
Obstruction of aqueous humor outflow by cross-linked polyacrylamide microgels in bovine, monkey, and human eyes.
PURPOSE: Orcolon, a synthetic viscoelastic, may have contributed to refractory intraocular pressure (IOP) elevation after intracameral injection in some patients. Cross-linked polyacrylamide (microgels), an altered form of the polymer, was investigated as an etiologic candidate. METHODS: Four adult rhesus monkeys underwent anterior chamber exchange with mock aqueous humor containing microgels in one eye and a vehicle in the other. Outflow facility (perfusion) and IOP (applanation) were determined before and at various times thereafter. Facility also was determined before and after microgel or vehicle infusion into organ-cultured individual human (n = 9) and paired calf (n = 6) anterior segments. Representative monkey and human eyes were examined by light and electron microscopy. RESULTS: In the microgel-infused monkey eyes, IOP was consistently higher, by approximately 5 mmHg for approximately 1 month. In all three species, microgel infusion acutely decreased facility by approximately 50% to 80%. In the living monkeys where longer-term observation and retesting were possible, a facility reduction of approximately 40% to 50% persisted for at least 1 to 2 months, and rechallenge again produced an acute 80% facility decrease and subsequent 10-mmHg IOP rise. Results of electron microscopic examination in human and monkey eyes showed accumulation of microgels in the cribriform meshwork and beneath the inner wall of Schlemm's canal, with no cellular alterations or inflammatory infiltrate. CONCLUSIONS: Cross-linked polyacrylamide microgels can produce an acute and longstanding obstruction of trabecular drainage experimentally, and might therefore do so clinically.
Acrylic Resins↗
Pharmacologic trabeculocanalotomy. Facilitating aqueous outflow by assaulting the meshwork cytoskeleton, junctional complexes, and extracellular matrix.
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Animals↗
[Destruction of the sinusotrabecular meshwork in primary glaucoma].
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Adult↗
The anatomy of the rabbit aqueous outflow pathway.
The morphology of the filtration angle and pathway of aqueous outflow was studied in 10 pigmented rabbits using light and electron microscopic techniques. The following conclusions were arrived at: Numerous pectinate ligaments were found to cross the rabbit filtration angle. However, large spaces between these ligaments allows aqueous access to the peripheral portion of the angle and then to the trabeculum. The drainage of aqueous filtered through the meshwork is served by a plexus of 1 to 4 channels, which contain giant vacuoles along their internal and external walls. A single layer of endothelial cells was found covering all meridians of the entire trabeculum from the termination of the cornea to the filtration angle recess. This layer, here termed the trabecular endothelial layer, is a continuation of the corneal endothelium, and it is accompanied by the posterior limiting lamina (Descemet's membrane) for its full length. The aqueous passes through the trabecular endothelial layer by an intracellular route that possibly requires energy. The presence of the trabecular endothelial layer in the rabbit may explain the variation that is known to exist between human and rabbit in responses to pharmaceutical agents. The physiology of the rabbit trabecular endothelial layer needs to be investigated to determine the suitability of this species as an animal model for the human glaucomatous conditions caused by the presence of such a layer.
Animals↗
Reduced osteoblastic population and defective mineralization in osteopetrotic (op/op) mice.
Osteopetrotic (op/op) mice fail to exhibit bone remodeling because of a defective osteoclast formation due to a lack of macrophage colony-stimulating factor. In this study, we investigated the femora of op/op mice to clarify whether the osteoblastic population and bone mineralization are involved in osteoclasts or their bone resorption. The op/op mice extended the meshwork of trabecular bones from the chondro-osseous junction to the diaphyseal region. In the femoral metaphyses of op/op mice, intense alkaline phosphatase (ALPase)-positive osteoblasts were observed on the metaphyseal bone in close proximity to the erosion zone of the growth plates. Von Kossa's staining revealed scattered mineralized nodules and a fine meshwork of mineralized bone matrices while the wild-type littermates developed well-mineralized trabeculae parallel to the longitudinal axis. In contrast to the metaphysis, some op/op diaphyses showed flattened osteoblasts with weak ALPase-positivity, and the other diaphyses displayed bone surfaces without a covering by osteoblasts. It is likely, therefore, that the osteoblastic population and activity were lessened in the op/op diaphyses. Despite the osteopetrotic model, von Kossa's staining demonstrated patchy unmineralized areas in the op/op diaphyses, indicating that a lower population and/or the activity of osteoblasts resulted in defective mineralization in the bone. Transmission electron microscopy disclosed few osteoblasts on the diaphyseal bones, and instead, bone marrow cells and vascular endothelial cells were often attached to the unmineralized bone. Osteocytes were embedded in the unmineralized bone matrix. Thus, osteoclasts appear to be involved in the osteoblastic population and activity as well as subsequent bone mineralization.
Alkaline Phosphatase↗
Histology and fine structure of the iris and outflow system following latanoprost therapy.
Latanoprost therapy can lead to iris darkening in susceptible individuals, particularly those with hazel eyes. Concerns have been raised about whether latanoprost, and for that matter other prostanoids, may have a harmful effect on the iris. In addition, it is unknown whether latanoprost causes increased pigmentation of the outflow pathways that might eventually lead to blockage and a type of pigmentary glaucoma. The present study summarizes findings from the authors' own laboratories on the effects of latanoprost as seen by light and electron microscopy of the iris and outflow tissues and reviews the as yet limited, relevant literature. The findings support the proposal that latanoprost-induced eye color change is likely to be due to an increased amount of melanin within iris stromal melanocytes rather than any increase in melanocyte numbers, although many aspects of the darkening process remain obscure. No marked pathological changes were found in the latanoprost-treated iris; however, the numbers of specimens examined by us to date are still small (40 specimens in all) and those with latanoprost-induced darkening are even fewer (18). In the authors' experience, pigmentation of the outflow system in latanoprost-treated eyes was no greater than in eyes with primary open-angle glaucoma without prostanoid treatment, but there have been only limited numbers of trabeculectomy specimens examined. Concerns about latanoprost producing meshwork hyperpigmentation and pigmentary glaucoma are discussed.
Antihypertensive Agents↗
Scanning electron microscopy of trabeculectomy specimens from eyes with open-angle glaucoma.
We examined 13 trabeculectomy specimens from ten patients with open-angle glaucoma by scanning electron microscopy. The pores of the inner travecular meshwork were not obstructed by extracellular material in all specimens, a finding contrary to a recently published report.
Adolescent↗
The cells of the bovine outflow system in tissue culture.
Meshwork cells from the bovine outflow system were grown in culture and their growth characteristics and behaviour in vitro reported. The cells were studied by inverted phase microscopy and time-lapse cinephotomicrography. It was found that plating efficiency was highest for third and seventh passage cells. These cells reached confluence within 2 weeks when plated out at 7.5 X 10(3) cells cm-2 in a conventional culture medium containing 10% serum. Third passage cells were studied in greatest detail. These cells exhibited postconfluence contact inhibition of division. By 2 weeks postconfluence the division rate decreased 10-fold to a level of less than six divisions per thousand cells per day. The contact inhibition was not overcome by increasing the serum content of the medium. On the other hand, a 30-fold increased division rate could be produced after scratching the culture flask. Postconfluent contact-inhibited cultures were considered to be a better reflection of the behaviour and activities of meshwork cells in vivo than cultures which retain a high level of division.
Animals↗
Repair in the rabbit outflow system.
An in vivo study was conducted to study repair processes in the injured rabbit outflow system. A uniform injury was produced by raising intraocular pressure (IOP) manometrically to 70 mmHg for 1 h. The recovery process, which was followed clinically for 8 weeks and morphologically for 6 weeks, led to the re-establishment of normal meshwork architecture within this period. The morphological studies included light microscopy, autoradiography and electron microscopy. The initial lesion consisted of large deficits in the meshwork with breakdown of cell-to-cell connections, loss of extracellular materials and disruption of the vessels of the aqueous plexus. There was a significant lowering of IOP in the first week of recovery, which thereafter climbed back to normal. Also in the first week the meshwork became infiltrated with inflammatory cells which cleared by 4 weeks. There was some meshwork cell death by either necrosis or apoptosis. The majority of meshwork cells became activated within the first few days and remained activated for at least the first 2 weeks. Tritiated proline incorporation was maximal between 1 and 2 weeks. Tritiated thymidine labelling was seen throughout, but only after the inflammation subsided was it clear that meshwork cells in all regions of the meshwork were proliferating. Our study provided no evidence that normal meshwork cells have a basal proliferative turnover level. Our injury model involved complete repair of the outflow tissues and that required meshwork cells to become activated, mobilise, undertake synthetic activity and proliferate. This is the first example, other than argon laser trabeculoplasty, where meshwork cells in vivo have been induced to divide. Possible therapeutic implications for glaucoma are discussed.
Animals↗
Factors influencing intraocular pressure in cultured human anterior segments.
PURPOSE: To determine why variations in intraocular pressure (IOP) occur in cultured human anterior segments despite a constant rate of infusion of culture medium. Two types of variations occur: an initial elevation of IOP and small changes in baseline IOP. METHODS: Anterior segments from human eyes were placed in perfusion organ culture. In cultures with initially high IOP, eyes were fixed at the high IOP level and histologic examination performed. In other cultures with high initial IOP, effluent medium was collected and subsequently reinfused after IOP had decreased to baseline. In cultures with stable baseline IOP, cell fragments from monolayer-cultured cells, or human genomic DNA, were infused at concentrations equivalent to 30,000 to 300,000 cells. RESULTS: Electron microscopy of initially high-pressure cultures revealed scattered cell debris throughout the meshwork in greater amounts than found in eyes without initially high IOP. Reinfusion of effluent media from cultures with high initial pressures caused elevation of IOP. Centrifugation of effluent media lessened this elevation of IOP. In cultures with stable baseline IOP, infusion of cell fragments or genomic DNA raised IOP in a dose-dependent manner, with elevation of IOP for a minimum of 24 hours. CONCLUSIONS: Cell debris can elevate IOP during the initial culture period, and after baseline pressures are established. Cell fragments and DNA increase IOP in a dose-dependent manner. The variations in baseline IOP seen during culture are probably caused by cell fragments and debris from dying cells in the meshwork, ciliary body, and other anterior segment tissues.
Aged↗
Clearance of debris from the iris through the drainage angle of the rabbit's eye.
The fate of particulate material on entering the drainage angle of the rabbit's eye was investigated by transmission electron microscopy. The infiltrate was produced by photocoagulation of the iris. Initially it consisted of plasma, connective tissue and cellular debris, fibrin, and red blood cells. Later, free melanin granules, polymorphs, macrophages, and iris clump cells were all seen to enter the drainage system. Native meshwork cells were found to be active phagocytes and began to degrade various components of the infiltrate within 2 hours of the formation of the iris lesions. Corneal endothelial cells, the cells which cover the iris pillars, and the adventitial cells of the ciliary body were less active but were also phagocytic.
Animals↗
N-ethylmaleimide increases the facility of aqueous outflow of excised monkey and calf eyes.
Freshly enucleated eyes were quantitatively perfused via the anterior chamber at 15 mm Hg pressure with various concentrations of the sulfhydryl (-SH) agent. N-ethylmaleimide (NEM). In the monkey eye a dosage of 9.4 mM NEM produced a 108% increase in facility of outflow. In calf eyes a dosage of NEM of 4.7 mM or greater also produced a significant increase in outflow facility. At the threshold dosage of 4.7 mM NEM there was only slight (12%) inhibition of glycolysis in the calf meshwork, which was excised after perfusion. The results suggest that the effect of NEM on outflow facility is not caused by a metabolic inhibitory action. We propose that alteration of cell membrane -SH groups in the outflow pathways can influence aqueous outflow resistance.
Animals↗
The effects of various levels of intraocular pressure on the rabbit's outflow system.
The effects of various levels of intraocular pressure on the morphology of the rabbit outflow system were investigated. In a total of 20 rabbits, intraocular pressure was maintained at various levels between 0-50 mmHg in the experimental eye and at 20 mmHg in the control eye for 1 hr. Flow rates into the eyes were measured by following the movement of a miniscus through a calibrated capillary tube. Progressive increase in pressure lead to distension and enlargement of the ciliary cleft. The meshwork tissues stretched and distended, and the vessels of the angular aqueous plexus had pressure-sensitive giant vacuoles of their endothelium. These vessels were prone to closure at pressures of 30 mmHg and greater. Difficulties associated with quantitation of giant vacuoles in this species were discussed.
Animals↗
Argon and low energy, pulsed Nd:YAG laser trabeculoplasty. A prospective, comparative clinical and morphological study.
Argon laser trabeculoplasty (ALT; 1.0 W, 0.1 sec, 50 microns) was performed in right eyes, and low energy, Q-switched Nd:YAG laser trabeculoplasty (Nd:YAGLT; 1.1-4.8 mJ/pulse) in left eyes of 14 patients with primary open-angle glaucoma and in one patient with juvenile glaucoma. The pre-laser intraocular pressure (IOP) was medically uncontrollable (IOP > 21 mmHg). The interocular pressure difference varied between 0 and 3 mmHg. In 9 patients IOP decreased to less than 22 mmHg (success) in both eyes. No statistically significant difference has been revealed with paired t-test in the degree of IOP decrease between ALT and Nd:YAGLT treated eyes during the 1-18 months' follow-up. Treatment variables of Nd:YAGLT had no statistically significant effect on the duration of the post-laser success with Cox-regression. In 4 patients both treatments were ineffective (IOP > 21 mmHg). In 2 patients ALT was successful but Nd:YAGLT was ineffective. In three cases of early bilateral laser failure (IOP > 21 mmHg at the first month visit) trabeculectomy was performed on both eyes in the third post-laser month. Following ALT the uveoscleral meshwork was severely destroyed in the area of the laser spots, and the surrounding collagen fibres were heat-damaged. The meshwork between the laser spots was covered by a membrane formed by migrating endothelial cells. In the uveoscleral meshwork Nd:YAGLT induced severe focal damage surrounded by circumscript shrinkage and scarring. The juxtacanalicular tissue remained free of laser induced damage. No endothelial membrane was present. The results suggest that low energy, Q-switched Nd:YAGLT may represent an alternative method of glaucoma laser surgery.
Adult↗
Effects of pilocarpine on the morphology of the human outflow apparatus.
The morphology of the outflow apparatus in human eyes which had been treated topically with either 2 or 4% pilocarpine on 4 occasions at 6-hourly intervals before enucleation was compared with an untreated control series of eyes from patients in a similar age range. In the pilocarpine-treated group the scleral spur was pulled posteriorly and internally, so that the angle formed by the scleral spur and the scleral sulcus was significantly greater in the treated than the untreated series. The change in attitude of the scleral spur produced widening of the spaces between the corneoscleral trabeculae and distension of the endothelial meshwork. It was shown from counts of giant vacuoles in the endothelium of Schlemm's canal that the incidence of giant vacuoles in the pilocarpine-treated group was greater than twice that in the controls. It would appear that pilocarpine produces alterations in the configuration of the outflow apparatus which would promote the drainage of aqueous humour.
Adult↗
The post-mortem vacuoles of Schlemm's canal.
A two-part study was conducted in which post-mortem changes were investigated in the baboon outflow system. It was found that the meshwork cells closest to the chamber angle were particularly susceptible to post-mortem advance. Post-mortem vacuoles developed in the endothelium of Schlemm's canal and by light microscopy these structures could be mistaken for giant vacuoles. On the other hand it was shown by electron microscopy that the giant vacuoles which have been implicated in the transendothelial transfer of aqueous humour and post-mortem vacuoles were distinct and separate entities.
Animals↗
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