Thermosensitive chitosan-gelatin-based hydrogel containing curcumin-loaded nanoparticles and latanoprost as a dual-drug delivery system for glaucoma treatment.

Elevated intraocular pressure (IOP) in glaucoma is due to impairment of aqueous humor drainage via the uveoscleral or trabecular outflow pathway. Latanoprost reduces IOP by increasing the uveoscleral outflow. Despite its potency, long-term daily application of it may cause undesirable side effects and many require more than one medication for IOP control. Recent studies have suggested that oxidative stress in the trabecular meshwork (TM) play an important role in the pathogenesis of impaired trabecular outflow facility. Curcumin, a natural phenolic compound, possesses anti-oxidant and anti-inflammation properties. In this study, we developed a thermosensitive hydrogel containing latanoprost and curcumin-loaded nanoparticles (CUR-NPs), and evaluated its possible therapeutic effects with cultured human TM cells under oxidative stress. The results demonstrated that 20 µM of CUR-NPs might be the optimal concentration to treat TM cells without causing cytotoxicity. Using the newly developed system, both latanoprost and CUR-NPs displayed a sustained-release profile. Treatment with this hydrogel containing CUR-NPs effectively decreased the oxidative stress-mediated damage in TM cells via decreasing inflammation-related gene expression, mitochondrial reactive oxygen stress (ROS) production and apoptosis level. The in vivo biocompatibility revealed no signs of inflammation or damage after topical application of developed hydrogel in rabbits. These results suggest that this dual-drug delivery system might enhance both trabecular and uveoscleral outflow and is promising to develop into a novel treatment for glaucoma.

Role of the water-drinking test in medically treated primary open angle glaucoma patients.

PURPOSE: The water-drinking test (WDT) has recently re-emerged as a possible way to determine the competency of the trabecular meshwork. We performed a prospective interventional study to test the hypothesis that the WDT could be useful in assessing fluctuations in patients undergoing treatment for primary open angle glaucoma (POAG). METHODS: We included 122 patients; 62 on medical treatment for POAG (n=123 eyes) and 60 controls (n=120 eyes). The study group had been on intraocular pressures (IOP) lowering treatment continuously for at least 3months with stable IOP. The WDT was performed during fasting and was considered positive if it fluctuated ≥6mmHg. RESULTS: The patients on medical treatment had a mean age of 50.56±18.45 years vs. 51.35±11.22 for the controls (P=0.34); with 71% being female in the study group and 77% in the control group. In the study group; 52% were on beta blockers (n=64), 27% combination of two or more medications (n=33), 19% prostaglandin analogues (n=24) and 2% alpha agonists (n=2). The WDT was positive in 17.07% (n=21) in the study group and 2.5% (n=3) in the control group (P=0.0001). The mean fluctuation was 7.14±2.15mmHg in the study group and 6.00±0mmHg in the controls (P=0.33). A positive WDT was found in 33.33% (n=11) of those on combination therapy; 12.5% (n=3) prostaglandin analogues and 10.94% (n=7) beta blockers (P=0.03). Combination therapy had the highest positive WDT fluctuation (7.54±2.87) followed by prostaglandin analogues (7.00±1.00) and beta blockers (6.57±0.78) with a P value of 0.44. CONCLUSIONS: The WDT can identify significant fluctuations in eyes with POAG that are medically treated.

Reactive oxygen species, oxidative stress, glaucoma and hyperbaric oxygen therapy.

This review examines the role of oxidative stress in damage to cells of the trabecular meshwork and associated impaired aqueous drainage as well as damage to retinal ganglion cells and associated visual field losses. Consideration is given to the interaction between vascular and mechanical explanations for pathological changes in glaucoma. For example, elevated intraocular pressure (IOP) forces may contribute to ischaemia but there is increasing evidence that altered blood flow in a wider sense is also involved. Both vascular and mechanical theories are involved through fluctuations in intraocular pressure and dysregulation of blood flow. Retinal function is very sensitive to changes in haemoglobin oxygen concentration and the associated variations in the production of reactive oxygen species. Reperfusion injury and production of reactive oxygen species occurs when IOP is elevated or blood pressure is low and beyond the capacity for blood flow autoregulation to maintain appropriate oxygen concentration. Activities such as those associated with postural changes, muscular effort, eye wiping and rubbing which cause IOP fluctuation, may have significant vascular, mechanical, reperfusion and oxidative stress consequences. Hyperbaric oxygen therapy exposes the eye to increased oxygen concentration and the risk of oxidative damage in susceptible individuals. However, oxygen concentration in aqueous humour, and the risk of damage to trabecular meshwork cells may be greater if hyperbaric oxygen is delivered by a hood which exposes the anterior ocular surface to higher than normal oxygen levels. Oronasal mask delivery of hyperbaric oxygen therapy appears to be indicated in these cases.

The protective effects of silibinin in the treatment of streptozotocin-induced diabetic osteoporosis in rats.

Diabetic osteoporosis (DO) is a complication of diabetes mellitus. Our previous study showed that silibinin can attenuate high glucose mediated human bone marrow stem cells dysfunction through antioxidant effect. However, no study has yet investigated the effect of silibinin in diabetic rats. Therefore, we assessed the effects of silibinin on bone characteristics in streptozotocin-induced diabetic rats. The aim of our study was to determine whether providing silibinin in the different supplementation could prevent bone loss in diabetic rats or not. Rats were randomly divided into four groups: (1) control group (CG) (n=10); (2) diabetic group (DG) (n=10); (3) diabetic group with 50mgkg-1day-1 of silibinin orally (DG-50) (n=10); and (4) diabetic group with 100mgkg-1day-1 of silibinin orally (DG-100) (n=10). 12 weeks after streptozotocin (STZ) injection, the femora from all rats were assessed and oxidative stress was evaluated. Bone mineral density was significantly decreased in diabetic rats; these effects were prevented by treatment with silibinin (100mgkg-1day-1 orally). Similarly, in the DG and DG-50 groups, changes in microarchitecture of femoral metaphysis assessed by microcomputed tomography demonstrated simultaneous existence of diabetic osteoporosis; these impairments were prevented by silibinin (100mgkg-1day-1 orally). In conclusion, silibinin supplementation may have potential use as a possible therapy for maintaining skeletal health and these results can enhance the understanding of diabetic osteoporosis induced by diabetes.

Life under pressure: The role of ocular cribriform cells in preventing glaucoma.

Primary open-angle glaucoma is a multifactorial blinding disease often impacting the two pressure-sensitive regions of the eye: the conventional outflow pathway and the optic nerve head (ONH). The connective tissues that span these two openings in the globe are the trabecular meshwork of the conventional outflow pathway and the lamina cribrosa of the ONH. Resident cribiform cells of these two regions are responsible for actively remodeling and maintaining their connective tissues. In glaucoma, aberrant maintenance of the juxtacanalicular tissues (JCT) of the conventional outflow pathway results in ocular hypertension and pathological remodeling of the lamina cribrosa results in ONH cupping, damaging retinal ganglion cell axons. Interestingly, cells cultured from the lamina cribrosa and the JCT of the trabecular meshwork have similarities regarding gene expression, protein production, plus cellular responses to growth factors and mechanical stimuli. This review compares and contrasts the current knowledge of these two cell types, whose health is critical for protecting the eye from glaucomatous changes. In response to pressure gradients across their respective cribiform tissues, the goal is to better understand and differentiate healthy from pathological behavior of these two cell types.

Tetramethylpyrazine (TMP), an Active Ingredient of Chinese Herb Medicine Chuanxiong, Attenuates the Degeneration of Trabecular Meshwork through SDF-1/CXCR4 Axis.

BACKGROUND: A traditional Chinese medicine, Tetramethylpyrazine (TMP), has been prescribed as a complementary treatment for glaucoma to improve patient prognosis. However, the pharmacological mechanism of action of TMP is poorly understood. In previous studies, we demonstrated that TMP exerts potent inhibitory effects on neovascularization, suppresses the tumorigenic behavior of glioma cells, and protects neural cells by regulating CXCR4 expression. Here, we further investigated whether the SDF-1/CXCR4 pathway is also involved in the TMP-mediated activity in trabecular meshwork cells. METHODOLOGY/PRINCIPAL FINDINGS: CXCR4 expression was examined by quantitative real-time PCR in trabecular and iris specimens from 54 primary open-angle glaucoma (POAG) patients who required surgery and 19 non-glaucomatous donors. Our data revealed markedly elevated CXCR4 expression in the trabecular meshwork of POAG patients compared with that of controls. Consistently, CXCR4 expression was much higher in glaucomatous trabecular meshwork cells than in normal trabecular meshwork cells. Using RT-PCR and western blot assays, we determined that glaucoma-related cytokines and dexamethasone (DEX) also significantly up-regulated CXCR4 expression in primary human trabecular meshwork (PHTM) cells. Moreover, the TGF-ß1-mediated induction of CXCR4 expression in PHTM cells was markedly down-regulated by TMP compared with control treatment (PBS) and the CXCR4 antagonist AMD3100. In addition, TMP could counteract the TGF-ß1-induced effects on stress fiber accumulation and expansion of PHTM cells. TMP markedly suppressed the migration of PHTM cells stimulated by TGF-ß1 in transwell and scratch wound assays. TMP also suppressed the extracellular matrix (ECM) accumulation induced by TGF-ß2. CONCLUSIONS: Our findings demonstrate that CXCR4 might be involved in the pathogenetic changes in the trabecular meshwork of patients with POAG. Additionally, TMP might exert its beneficial effects in POAG patients by down-regulating CXCR4 expression.

The Function of Matricellular Proteins in the Lamina Cribrosa and Trabecular Meshwork in Glaucoma.

PURPOSE: To review the current literature regarding the role of matricellular proteins in glaucoma, specifically in the lamina cribrosa (LC) region of the optic nerve head (ONH) and the trabecular meshwork (TM). METHODS: A literature search was performed for published articles describing the expression and function of matricellular proteins such as thrombospondin (TSP), connective tissue growth factor (CTGF), secreted protein acidic and rich in cysteine (SPARC), and periostin in glaucoma. RESULTS: In glaucoma, there are characteristic extracellular matrix (ECM) changes associated with optic disc cupping in the ONH and subsequent visual field defects. Matricellular proteins are a family of nonstructural secreted glycoproteins, which enable cells to communicate with their surrounding ECM, including CTGF, also known as CCN2, TSPs, SPARC, periostin, osteonectin, and tenascin-C and -X, and other ECM proteins. Such proteins appear to play a role in fibrosis and increased ECM deposition. Importantly, most are widely expressed in tissues particularly in the TM and ONH, and deficiency of TSP1 and SPARC has been shown to lower intraocular pressure in mouse models of glaucoma through enhanced outflow facility. CONCLUSION: This article highlights the role of matricellular proteins in glaucoma pathology. The potential role of these proteins in glaucoma is emerging as some have an association with the pathophysiology of the TM and LC region and might therefore be potential targets for therapeutic intervention in glaucoma.

Analysis of a method for establishing a model with more stable chronic glaucoma in rhesus monkeys.

In this study, we utilized yellow-wavelength laser treatment and measured aqueous outflow facility to establish a model for chronic glaucoma in rhesus monkeys. We then compared the effects of photocoagulation resulting from exposure to the yellow laser or to a green laser. Twelve rhesus monkeys were used to establish the model, and the yellow and green lasers were utilized for 360° photocoagulation in the anterior-chamber angles of the right eye in all subjects. After certain periods of time before and after the creation of the glaucoma model, the cornea, aqueous humor, optic cup, intraocular pressure (IOP), outflow facility, retinal nerve fiber layer (RNFL), and pathology of the trabecular meshwork were analyzed. Both the yellow and green lasers caused an increase in IOP compared with before photocoagulation (18.6 ± 2.6 mm Hg and 16.1 ± 1.8 mm Hg, respectively), with an average photocoagulation from the yellow and green lasers of 39.2 ± 7.9 mm Hg and 30.3 ± 4.7 mm Hg, respectively (P < 0.01). However, the success rate of a second photocoagulation treatment in the yellow laser group was significantly higher than in the green laser group (P < 0.05). After the increase in IOP, both groups exhibited an inflammatory response in the anterior segment, enlarged cupping, and a decrease in the average thickness of the RNFL. However, the yellow laser caused less corneal edema than the green laser (P < 0.05), and the outflow facility of the two groups (0.33 ± 0.09 and 0.30 ± 0.07 µl/min/mm Hg for the yellow and green lasers, respectively) showed different degrees of differences (0.05 ± 0.02 and 0.07 ± 0.02 µl/min/mm Hg for the yellow and green lasers, respectively) into the abnormal range after photocoagulation. Pathological examination revealed that the depth of destruction of the trabecular meshwork appeared to be deeper in the yellow laser group than in the green laser group. In conclusion, application of a yellow laser combined with measuring aqueous outflow facility produced a glaucoma model with a minor inflammatory response and few IOP fluctuations.

Establishment of the ocular hypertension model using the common marmoset.

The purpose of this study was to establish an experimental glaucoma model in the common marmoset (Callithrix jacchus). Chronic intraocular pressure (IOP) elevation was induced by laser trabeculoplasty twice at 2-week intervals in the left eyes of 4 common marmosets. IOP was measured before and at 4, 7, 8, 11, 13 weeks after first laser treatment, and ophthalmoscopic examinations were also performed. At 13 weeks after laser treatment, each eye was enucleated, and retinal cross-sections and optic nerve were prepared for histological examination. Mean IOP values measured at the above 5 time points were over 40 mmHg in laser-treated eyes in 3 marmosets, but IOP in one marmoset was transiently increased to 26.6 mmHg at 7 weeks and then declined to the baseline level. In ophthalmoscopy, deepened and enlarged optic disc cupping, depending on the extent of IOP elevation and duration, were observed in laser-treated eyes of 3 marmosets with persistent IOP elevation, but there was no apparent change in the optic disc in the laser-treated eye of one marmoset with transient IOP elevation. Histological examination showed marked atrophy with deepened and enlarged cupping of optic disc, thinning of retinal nerve fiber layer and retinal ganglion loss in the retina, and axonal atrophy and loss in the optic nerve, depending on the extent of IOP elevation and duration. In conclusion, we succeeded in producing an experimental glaucoma model in the common marmoset, and this model may be useful in elucidating the pathophysiological mechanism for glaucoma.

[Multikinase inhibitors as a new approach in neovascular age-related macular degeneration (AMD) treatment: in vitro safety evaluations of axitinib, pazopanib and sorafenib for intraocular use]. / Multikinase-inhibitoren als therapeutischer ansatz bei neovaskulärer AMD: in-vitro-evaluation der sicherheit von axitinib, pazopanib und sorafenib zur intraokularen anwendung.

BACKGROUND: Multikinase inhibitors (MKI) interfere effectively at different levels of the neovascularisation cascade. Early clinical and experimental data suggest that MKIs represent a promising novel approach for the treatment of neovascular age-related macular degeneration (AMD). However, so far little is known about the biocompatibility of MKIs regarding human ocular cells. This in vitro study investigates and compares the biocompatibility of three MKIs, axitinib, pazopanib, and sorafenib regarding ocular cells of the anterior and posterior segments, as well as organ-cultured donor corneas. METHODS: Primary human optic nerve head astrocytes (ONHA), trabecular meshwork cells (TMC), and retinal pigment epithelium (RPE), human corneal endothelial and lens epithelial cells (CEC and LEC) were treated with different concentrations of axitinib, pazopanib, or sorafenib (0.1 to 100 µg/mL). To simulate oxidative stress, the cells were additionally co-incubated with 400 µM hydrogen peroxide. Induction of cell death and cellular viability were examined by live-dead assay and tetrazolium dye reduction assay (MTT). In addition, the influence of the three substances on human corneal endothelium was evaluated in seropositive donor corneas in organ culture by phase contrast microscopy. RESULTS: Up to a concentration of 7.5 mg/mL of the substances tested in any cell type examined, no toxic effects were found. Even after 10 days of incubation of organ-cultured donor corneas with 7.5 µg/mL, axitinib, pazopanib, or sorafenib, no evidence for endothelial toxicity was found. CONCLUSION: All three MKIs tested, axitinib, pazopanib, and sorafenib showed a good biocompatibility on the investigated ocular cells. Even under conditions of oxidative stress, there were no toxic effects up to a concentration of 7.5 µg/mL. Only at higher concentrations, there was a dose-dependent decrease in cellular viability and pronounced induction of cell death. These effects on cellular viability and induction of cell death appeared to be stronger with pazopanib, followed by sorafenib, than with axitinib.

Oxidative stress and glaucoma: injury in the anterior segment of the eye.

The perturbation of the pro-oxidant/antioxidant balance can lead to increased oxidative damage, especially when the first line of antioxidant defense weakens with age. Chronic changes in the composition of factors present in aqueous or vitreous humor may induce alterations both in trabecular cells and in cells of the optic nerve head. Free radicals and reactive oxygen species are able to affect the cellularity of the human trabecular meshwork (HTM). These findings suggest that intraocular pressure increase, which characterizes most glaucomas, is related to oxidative and degenerative processes affecting the HTM and, more specifically, its endothelial cells. This supports the theory that glaucomatous damage is the pathophysiological consequence of oxidative stress. Glaucomatous subjects might have a genetic predisposition, rendering them more susceptible to reactive oxygen species-induced damage. It is likely that specific genetic factors contribute to both the elevation of IOP and susceptibility of the optic nerve/retinal ganglion cells (RGCs) to degeneration. Thus, oxidative stress plays a fundamental role during the arising of glaucoma-associated lesions, first in the HTM and then, when the balance between nitric oxide and endothelins is broken, in neuronal cell. Vascular damage and hypoxia, often associated with glaucoma, lead to apoptosis of RGCs and may also contribute to the induction of oxidative damage to the HTM. On the whole, these findings support the hypothesis that oxidative damage is an important step in the pathogenesis of primary open-angle glaucoma and might be a relevant target for both prevention and therapy.

Daidzein but not other phytoestrogens preserves bone architecture in ovariectomized female rats in vivo.

Ovariectomy of immature female rats, results in significant decrease of trabecular bone volume and in cortical bone thickness. Previously, we found that estradiol-17beta (E(2)) restored bone structure of ovariectomized (Ovx) female rats to values obtained in intact sham-operated female rats. E(2) also selectively stimulated creatine kinase (CK) specific activity a hormonal-genomic activity marker. In the present study, we compared the effects of E(2) and the phytoestrogens: daidzein (D), biochainin A (BA), genistein (G), carboxy-derivative of BA (cBA), and the SERM raloxifene (Ral) in Ovx, on both histological changes of bones and CK, when administered in multiple daily injections for 2.5 months. Bone from Ovx rats, showed significant disrupted architecture of the growth plate, with fewer proliferative cells and less chondroblasts. The metaphysis underneath the growth plate, contained less trabeculae but a significant increased number of adipocytes in the bone marrow. D like E(2) and Ral but not G, BA, or cBA, restored the morphology of the tibiae, similar to that of control sham-operated animals; the bony trabeculeae observed in the primary spongiosa was thicker, with almost no adipocytes in bone marrow. Ovariectomy resulted also in reduced CK, which in both epiphysis and diaphysis was stimulated by all estrogenic compounds tested. In summary, only D stimulated skeletal tissues growth and differentiation as effectively as E(2) or Ral, suggesting that under our experimental conditions, D is more effective in reversing menopausal changes than any of the other isolated phytoestrogens which cannot be considered as one entity.

Effects of novel ethacrynic acid derivatives on human trabecular meshwork cell shape, actin cytoskeletal organization, and transcellular fluid flow.

To determine efficacy and therapeutic index in the context of ocular hypotensive activity of the new ethacrynic acid (ECA) derivatives of the series (SA8,248 and SA8,389), 9,000 series (SA9,000, SA9,622 and SA9,995) and ticrynafen, we undertook a comparative evaluation of the dose-dependent effects of these compounds on human trabecular meshwork (HTM) cell shape, actin cytoskeletal organization, focal adhesions and transcellular fluid flow. Responses were either scored using an arbitrary scale of 1-5 or quantified. Compounds of the 9000 series (SA9,995>SA9,000>SA9,622) were found to be 14- to 20-fold more potent than ECA, ticrynafen or analogs from the 8,000 series (SA8,389>SA8,248) in terms of ability to induce cell shape alterations in HTM cells. Similarly, compounds of the 9,000 series (SA9,995>SA9,622>SA9,000) were found to be much stronger (2 to 20 fold) than ECA, ticrynafen or analogs of the 8000 series in terms of affecting decreases in actin stress fiber content in HTM cells. Analogs of the 9000 series (SA9,622>SA9,995>SA9,000) were also observed to be 8 to 10 fold more potent than ECA (SA8,389>ECA>SA8,248>ticrynafen) at eliciting decreases in cellular focal adhesions. Interestingly, analogs of the 9000 series (SA9,000>SA9,622>SA9,995) and SA8,248 demonstrated a huge increase (by many folds) in transcellular fluid flow of HTM cell monolayers as compared to ECA and ticrynafen. Collectively, these analyses revealed that the structural modification of ECA improves its ocular hypotensive efficacy, indicating that the SA9,000 series compounds might be promising novel ocular hypotensive drugs.

Configuration of the drainage angle, intraocular pressure, and optic disc cupping in subjects with chronic angle-closure glaucoma.

OBJECTIVE: To investigate the relationship between drainage angle configuration with untreated intraocular pressure (IOP) and optic disc cupping in subjects with chronic angle-closure glaucoma (CACG). DESIGN: Prospective, observational study. PARTICIPANTS: Two hundred seventy-five Asian subjects with CACG who participated in a randomized controlled trial that investigated the IOP-reducing effect of latanoprost and timolol. METHODS: Chronic angle-closure glaucoma was defined as the presence of glaucomatous optic neuropathy (with or without a visual field defect), an anterior chamber angle in which the pigmented trabecular meshwork was not visible for at least 180 degrees on gonioscopy, and evidence of peripheral anterior synechiae (PAS) in association with elevated IOP of 21 mmHg or more. Static and dynamic gonioscopy were performed, the angles were graded in each quadrant according to the Shaffer scheme, and the number of clock hours of PAS was recorded. The untreated IOP and vertical cup-to-disc ratio were correlated with mean angle width and extent of PAS. MAIN OUTCOME MEASURES: Mean angle width, clock hours of PAS, IOP, and vertical cup-to-disc ratio. RESULTS: Most subjects were female (75%), and the mean age was 62.9+/-9.4 years. The mean angle width was 0.77+/-0.53 and the mean number of clock hours of PAS was 4.77+/-3.2 hours. Untreated IOP correlated with angle width (r = -0.23; P<0.001) and clock hours of PAS (r = 0.22; P<0.001). Vertical cup-to-disc ratio also correlated with angle width (r = -0.17; P = 0.004) and PAS (r = 0.28; P<0.001). Performing a multiple linear regression using baseline IOP as the outcome variable with age, gender, clock hours of PAS, and angle width as predictors, there was a 0.39-mmHg (95% confidence interval, 0.15-0.63) increase in baseline untreated IOP for each unit increase in clock hours of PAS (P = 0.002). CONCLUSIONS: In subjects with CACG, the extent of PAS and a narrower width of the drainage angle were associated with higher untreated IOP and a larger vertical cup-to-disc ratio.

Clinical signs of the pigment dispersion syndrome in blacks.

BACKGROUND: The pigment dispersion syndrome (PDS) is considered rare in blacks, and minimal literature exists concerning the condition in this patient population. The diagnosis of PDS in blacks may present unique challenges because some of the typical clinical signs that are present in whites, including iris transillumination defects, posterior iris bowing, and noticeable anterior iris stromal pigment dusting, may not occur as commonly. Diagnosis can be particularly difficult when neither these signs nor significant corneal endothelial pigmentation exists. Although zonular and peripheral lens pigment has been found to be consistently present in whites with PDS, attention has not been given to this as a potentially important diagnostic sign in blacks. METHODS: From among a primary care population, we identified and studied 7 patients (13 eyes) who exhibited moderate to heavy trabecular meshwork (TM) pigmentation, as well as zonule and/or peripheral lens pigmentation. Patients were identified during routine clinical care provided by one of the authors, as well as from notification by other practitioners. All patients received complete eye examination and other signs of PDS were looked for. RESULTS: Four males and 3 females were identified, their average age being 37 years (range = 15 to 51) at the time of their initial identification. All but one patient was myopic (average approximately -2.50 D spherical equivalent). Iris transillumination defects were present in only one eye of one patient, and no eyes showed overt posterior iris bowing, although the iris contours were usually flat and the anterior chambers appeared relatively deep. Corneal endothelial pigmentation was frequently barely detectable and could not be relied on as a predictor of trabecular meshwork or lenticular pigmentation. Glaucoma, or a suspicion of glaucoma due to increased intraocular pressure (IOP) or cupping, was common among the group. Using heavy TM pigmentation as well as any degree of zonular and/or peripheral lenticular pigmentation as a criteria for the diagnosis of PDS, we calculated the prevalence of PDS among blacks in a nonreferred primary care population (> age 7) to be at least 15 cases per 10,000. CONCLUSIONS: More investigation is needed to study the clinical presentation of PDS in blacks because it may be substantially different than in whites. Zonular and peripheral lenticular pigmentation may be a particularly useful diagnostic sign of PDS in blacks, especially in those cases where other traditional signs, including iris transillumination defects, pronounced corneal endothelial pigmentation, posterior iris bowing, and visible anterior iris stromal pigment dusting, are absent. The "classic" variety of PDS may be more common among blacks than previously recognized.

Laser trabecular ablation (LTA).

As part of a pilot study for glaucoma surgery, the use of 3 infrared solid state lasers with 4 fiber optic delivery systems to ablate human trabecular meshwork was investigated. Laser trabecular ablation (LTA) was attempted with the Erbium:YAG (2.94 microns), Erbium:YSGG (2.79 microns), and Holmium:YSGG (2.1 microns) lasers. Laser energy was delivered as a single pulse (250 microseconds) by tissue fiber optic contact with low hydroxyl-fused silica (200 and 500 microns), zirconium fluoride (250 microns), or sapphire (250 microns) fiber optics. Total energy required and thermal effects decreased as laser wavelength increased. LTA was best achieved at 2.94 microns (4 mJ total energy; energy densities = 8.2-12.7 J/cm2; pulse length 250 microseconds) with average thermal damage zones of 5.3-10.3 +/- 1.3-2.4 microns (means +/- SDs) to contiguous structures. This finding has potential applications in the surgical treatment of open-angle and congenital glaucoma and may minimize failure rates seen in other types of surgery on the trabecular meshwork where disrupted trabecular meshwork is not removed.

Retinitis pigmentosa associated with glaucoma--clinical analysis.

A clinical analysis of Retinitis Pigmentosa (RP) was made in 2,789 eyes of 1,400 patients seen over a 5 year period (1983-1987), 64 eyes of 32 cases (2.3%) of RP associated with glaucoma were investigated. Of these 32 cases, the angle closure glaucoma was much more than the open angle glaucoma (30/2). More than half of the 32 cases were without cupping of disk, 5 cases did not have the glaucomatous damage to disk in spite of persistent elevated intraocular pressure for 0.5-5 yrs under the maximum medical therapy. 31 cases (97%) had subnormal blood pressure compared with the normal blood pressure value in different age groups. Histopathologic changes of the trabecular meshwork (TM) of 14 eyes showed a little bit more pigment cells in the TM than normal subjects, no typical features that would obstruct the outflow channels.

Laser-induced glaucoma in rabbits.

Argon laser energy was applied to the trabecular meshwork of pigmented rabbits in an attempt to develop an animal model of 'glaucoma'. Laser energy was varied to determine the optimal level needed to produce sustained ocular hypertension. An initial response of ocular hypertension followed by hypotension was observed in all of the animals tested. Approximately half of the laser-treated rabbits developed a secondary buphthalmus and sustained ocular hypertension. In these animals outflow facility was decreased by approximately 60%. Histologic examination at 4- and 8 weeks after laser treatment demonstrated a wound-healing response resulting in closure of the intertrabecular spaces and obstruction of outflow to injected carbon particles. Optic nerve cupping and a loss of ganglion cells were also observed. Topical application of L-timolol (0.5%), pilocarpine (2.0%) and forskolin (1.0%) were found to be effective in decreasing intraocular pressure in the laser-treated, hypertensive eye with no significant effect in control non-laser-treated eyes, suggesting that this model can be a useful tool for screening potential antiglaucoma medications.

Pigmentary glaucoma: a clinical review of anterior segment pigment dispersal syndrome.

Sixty-eight cases (44 males, 24 females) of anterior segment pigment dispersal syndrome are reviewed. Five patients had no rise in intraocular pressure, 38 had ocular hypertension and 25 had glaucoma as shown by optic disc cupping and field loss. All cases had heavy deposition of pigment in the drainage angle together with Krukenberg spindles and/or light reflux through the iris. Other evidence of anterior segment pigment dispersal was common. The condition was commonest in young adult males, but could present at any age and in women. Medical treatment was often successful initially, but continued to control pressure in only 17 of 42 patients. Laser trabeculoplasty helped some patients. Drainage operations of various types were successful in 19 of 23 cases. Iris angiography showed evidence of vascular hypoperfusion of the iris which probably precedes pigment dispersal and suggests that the ultimate aetiology may be a congenital deficiency of the mesodermal support tissues of the iris. Some degree of iris stromal atrophy is also common and may become marked. Pigment dispersal from the pigment epithelium of the iris occurs in susceptible individuals and may be associated with the insertion of the dilator muscle. The term anterior segment pigment dispersal seems appropriate as the condition is limited to the anterior segment.

Effects of chondroitin sulfate on metabolism of trabecular meshwork.

Glycosaminoglycans are believed to play a role in the physiological functions of trabecular meshwork. The effects of chondroitin sulfate on the metabolism of trabecular meshwork were studied by replacing the aqueous humor in the right eye (experimental eye) of 12 albino rabbits with 0.3 ml of chondroitin-4-sulfate solution (10 mg ml-1 in glucose-supplemented phosphate buffered saline). The aqueous humor in the left eye (control eye) was replaced with the phosphate buffered saline-glucose solution in the same manner. The intracameral procedures were performed twice a week for four weeks (initial injection period), and then discontinued for another four weeks (resting period). No significant or prolonged increase in the intraocular pressure was observed during either period in any eyes. Subsequent intracameral injections performed after the resting period, however, caused an intraocular pressure elevation in 10 of the 12 experimental eyes. During this second injection period, the injections were carried out whenever the intraocular pressure of experimental eyes dropped to the control value. The pressure generally remained 5-10 mmHg above that of the control eyes for periods ranging from two days to four weeks. In the eyes with elevated intraocular pressure, light microscopy showed that the trabecular beams were compact and sclerotic and the intertrabecular spaces were narrower. Chamber angle tissues obtained from the eyes with elevated intraocular pressure incorporated more radioactive precursors into glycosaminoglycans than those from the control eyes. The synthesis of glycosaminoglycans and the metabolism of trabecular meshwork seemed to be modified by the long-term chondroitin sulfate treatment.