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Detection of gonioscopically occludable angles and primary angle closure glaucoma by estimation of limbal chamber depth in Asians: modified grading scheme.

AIM: To evaluate the performance of limbal chamber depth estimation as a means of detecting occludable drainage angles and primary angle closure, with or without glaucoma, in an east Asian population, and determine whether an augmented grading scheme would enhance test performance. METHOD: A two phase, cross sectional, community based study was conducted on rural and urban areas of Hövsgöl and Omnögobi provinces, Mongolia. 1800 subjects aged 40 to 93 years were selected and 1717 (95%) of these were examined. Depth of the anterior chamber at the temporal limbus was graded as a percentage fraction of peripheral corneal thickness. An "occludable" angle was one in which the trabecular meshwork was seen in less than 90 degrees of the angle circumference by gonioscopy. Primary angle closure (PAC) was diagnosed in subjects with an occludable angle and either raised pressure or peripheral anterior synechiae. PAC with glaucoma (PACG) was diagnosed in cases with an occludable angle combined with glaucomatous optic neuropathy and consistent visual morbidity. RESULTS: Occludable angles were identified in 140 subjects, 28 of these had PACG. The 15% grade (equivalent to the traditional "grade 1") yielded sensitivity and specificity of 84% and 86% respectively for the detection of occludable angles. The 5% grade gave sensitivity of 91% and specificity of 93% for the detection of PACG. The interobserver agreement for this augmented grading scheme was good (weighted kappa 0.76). CONCLUSIONS: The traditional limbal chamber depth grading scheme offers good performance for detecting occludable drainage angles in this population. The augmented scheme gives enhanced performance in detection of established PACG. The augmented scheme has potential for good interobserver agreement.

Adult↗

Effect of cataract extraction and posterior chamber lens implantation on outflow facility and its response to pilocarpine in Korean subjects.

AIM: To investigate the effect of the lens on outflow facility in Korean patients with cataracts. METHODS: Intraocular pressure was measured by Goldmann applanation tonometry in 42 patients with cataracts and outflow facility was determined by tonography preoperatively, before and after instillation of pilocarpine. All patients received clear corneal phacoemulsification and silicone foldable intraocular lens implantation within the capsular bag by one surgeon. Two months after surgery, slit lamp examination and gonioscopy were performed and intraocular pressure and outflow facility were again determined. Statistical analysis was carried out using the Student's paired t test. RESULTS: There were no anterior chamber reactions and no visible trabecular meshwork damage 2 months after surgery. Intraocular pressure 2 months after lens extraction decreased by a mean of 2.4 (SE 0.4) mm Hg (p<0.001) compared with the preoperative value; postoperative outflow facility with and without pilocarpine increased by 0.080 (0.019) microl/min/mm Hg (p<0.001) and 0.045 (0.014) microl/min/mm Hg (p<0.001), respectively, at 2 months compared with preoperative values. The facility response to pilocarpine after lens extraction, relative to the baseline value and preoperative response, increased by 10.7 (7.1)% which was not statistically significant (p>0.1). CONCLUSION: Lens extraction causes a reduction in intraocular pressure and an increase in outflow facility in Korean subjects. Pilocarpine causes an increase in outflow facility which persists after cataract extraction and posterior chamber lens implantation.

Adult↗

Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy.

AIM: To determine clear cut echocardiographic criteria for isolated ventricular non-compaction (IVNC), a cardiomyopathy as yet "unclassified" by the World Health Organization. The disease is not widely known and its diagnosis mostly missed. METHODS AND RESULTS: In seven out of a series of 34 patients with IVNC the in vivo echocardiographic characteristics were validated against the anatomical examination of the heart removed after death in four and due to heart transplantation in three patients. Four morphological criteria diagnostic for IVNC were found. (1) Coexisting cardiac abnormalities were absent (by definition). (2) A two layer structure was seen, with a compacted thin epicardial band and a much thicker non-compacted endocardial layer of trabecular meshwork with deep endomyocardial spaces. A maximal end systolic ratio of non-compacted to compacted layers of > 2 is diagnostic. (3) The predominant localisation of the pathology was to mid-lateral (seven of seven patients), apical (six), and mid-inferior (seven) areas. The pathological preparations confirmed the echocardiographic findings. Concomitant regional hypokinesia was not confined to the non-compacted segments. (4) There was colour Doppler evidence of deep perfused intertrabecular recesses. CONCLUSIONS: Four clear cut echocardiographic diagnostic criteria were established. It is suggested that the WHO classification of cardiomyopathies be reconsidered to include IVNC as a distinct cardiomyopathy.

Adult↗

A novel Asp380Ala mutation in the GLC1A/myocilin gene in a family with juvenile onset primary open angle glaucoma.

Glaucoma describes a clinically and genetically heterogeneous group of diseases that result in optic neuropathy and progressive loss of visual fields. A gene for juvenile onset primary open angle glaucoma JOAG) has recently been mapped to 1q21-31. Mutations in the trabecular meshwork induced glucocorticoid response gene (TIGR, also known as myocilin or the GLC1A locus) have been found to cause both juvenile and later onset primary open angle glaucoma. Family TCD-POAG1 is a Spanish kindred, which segregates JOAG in an autosomal dominant fashion. This family was found to be linked to the previously identified GLC1A locus on chromosome 1q. Direct sequencing of the TIGR/myocilin gene showed a heterozygous A to C transition in codon 380, resulting in the substitution of alanine for aspartic acid (Asp380Ala). This substitution created a StyI restriction site, which segregated with the JOAG phenotype and permitted rapid screening of all members of the family. This restriction site was not present in 60 controls.

Adolescent↗

Novel TIGR/MYOC mutations in families with juvenile onset primary open angle glaucoma.

Mutations in the trabecular meshwork induced glucocorticoid response protein (TIGR) or myocilin (MYOC) has recently been shown to cause juvenile onset primary open angle glaucoma (JOAG). In this study, we identified two new mutations (Asp380Ala and Ser502Pro) in two British families and another (Pro370Leu) in a French-Canadian family. These mutations were not present in a total of 106 normal chromosomes. In another Turkish family with JOAG, we also detected a sequence variant that was proven to be an amino acid polymorphism (Arg76Lys). No other sequence changes were found in the entire coding region and splice junctions of the TIGR/MYOC gene in this family. However, it is still possible that mutations either in the TIGR promoter or in another neighbouring gene could cause glaucoma in this JOAG family. Our results confirm the role of the TIGR/MYOC gene in the aetiology of the JOAG phenotype.

Adolescent↗

Inhibition of NHE-1 Na+/H+ exchanger by natriuretic peptides in ocular nonpigmented ciliary epithelium.

The natriuretic peptides (NPs) atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) display hypotensive effects in the mammalian eye by lowering the intraocular pressure (IOP), a function that is mediated by the bilayer ocular ciliary epithelium (CE), in conjunction with the trabecular meshwork. ANP regulates Na(+)/H(+) exchanger (NHE) activity, and inhibitors of NHE have been shown to lower IOP. We examined whether NPs influence the NHE activity of the CE, which is comprised of pigmented (PE) and nonpigmented (NPE) epithelial cells, by directly recording the rate of intracellular pH (pH(i)) recovery from its inner NPE cell layer. NPs inhibited, in a dose-dependent manner (1-100 nM), the rate of pH(i) recovery with the order of potency CNP > ANP > BNP, indicative that this inhibition is mediated by the presence of NPR type B receptors. 8-Bromo-cGMP (8-BrcGMP), a nonhydrolyzable analog of cGMP, mimicked NPs in inhibiting the rate of Na(+)-dependent pH(i) recovery. In contrast, ethylisopropyl amiloride (EIPA, 100 nM) or amiloride (10 microM) completely abolished the pH(i) recovery by NHE. 18alpha-Glycyrrhetinic acid (18alpha-GA), a gap junction blocker, attenuated the inhibitory effect of CNP on the rate of pH(i) recovery, suggesting that NHE activity in both cell layers of the CE is coregulated. This interpretation was supported, in part, by the coexpression of NHE-1 isoform mRNA in both NPE and PE cells. The mechanism by which the inhibitory effect of NPs on NHE-1 activity might influence the net solute movement or fluid transport by the bilayer CE remains to be determined.

Animals↗

Aquaporins in complex tissues: distribution of aquaporins 1-5 in human and rat eye.

Multiple physiological fluid movements are involved in vision. Here we define the cellular and subcellular sites of aquaporin (AQP) water transport proteins in human and rat eyes by immunoblotting, high-resolution immunocytochemistry, and immunoelectron microscopy. AQP3 is abundant in bulbar conjunctival epithelium and glands but is only weakly present in corneal epithelium. In contrast, AQP5 is prominent in corneal epithelium and apical membranes of lacrimal acini. AQP1 is heavily expressed in scleral fibroblasts, corneal endothelium and keratocytes, and endothelium covering the trabecular meshwork and Schlemm's canal. Although AQP1 is plentiful in ciliary nonpigmented epithelium, it is not present in ciliary pigmented epithelium. Posterior and anterior epithelium of the iris and anterior lens epithelium also contain significant amounts of AQP1, but AQP0 (major intrinsic protein of the lens) is expressed in lens fiber cells. Retinal Müller cells and astrocytes exhibit notable concentrations of AQP4, whereas neurons and retinal pigment epithelium do not display aquaporin immunolabeling. These studies demonstrate selective expression of AQP1, AQP3, AQP4, and AQP5 in distinct ocular epithelia, predicting specific roles for each in the complex network through which water movements occur in the eye.

Animals↗

Aqueous humor dynamics in anesthetized rats infused with intracameral apraclonidine.

We studied the acute effects of the ocular hypotensive drug, apraclonidine (AP), on intraocular pressure (IOP) and aqueous humor dynamics of anesthetized rats during infusion-induced ocular hypertension. Two infusions were made into the anterior chamber of the eye: one was constant at a rate of 0.05 microl/min, the other was cyclic, at a rate of 0.25 microl/min, with the pump on for 4 min, then off for 4 min. Data were processed by complex demodulation and analysis of a second-order transfer function. This permitted separate calculations of resistive components (Ao), i.e., trabecular meshwork and uveoscleral outflows, and residual pressure (RP) estimating nonresistive components, i.e., aqueous synthesis and episcleral venous pressure. A balanced salt solution (BSS) and AP (0. 0005%) were tested. AP markedly delayed the within-group rise in IOP: 20 min for BSS vs. 60 min for AP (p < 0.001). IOP of AP rats was less than control for 100 min (p < 0.05). The infusions raised Ao in both groups (p < 0.05). AP initially had a transient inhibitory effect (p < 0.05). Infusions raised RP in both groups. AP had a strong inhibitory effect for the first 8 cycles (p < 0.05). These data document that the acute effects of AP in this in vivo rat model of ocular hypertension were to delay increases in IOP, mainly by reducing nonresistive components of aqueous humor dynamics. Transient inhibition of resistive mechanisms also occurred.

Adrenergic alpha-Agonists↗

One-year follow-up of selective laser trabeculoplasty in open-angle glaucoma.

BACKGROUND: Selective laser trabeculoplasty (SLT) targets the pigmented trabecular meshwork (TM) cells without damage to the adjacent non-pigmented tissue. A study was conducted to evaluate the efficacy and safety of SLT in the treatment of uncontrolled open-angle glaucoma. METHODS: In a prospective non-randomized study 44 eyes of 31 patients with uncontrolled open-angle glaucoma were treated with a frequency-doubled, Q-switched Nd:YAG laser. A total of approximately 50 spots were placed over 180 degrees of the TM at energy levels ranging from 0.7 to 0.9 mJ. Intraocular pressure (IOP) was measured 1, 2, and 24 h, 1 and 2 weeks and 1, 2, 3, 6, 9, and 12 months after treatment. RESULTS: The average pre-operative IOP was 25.6 (SD 2.6) mm Hg (range 22-34). The mean IOP reduction from baseline at 24 h, 3, 6 and 12 months was 7.1 mm Hg (SD 3.5) or 27.6%; 4.2 mm Hg (SD 3.5) or 16.4%; 4.7 mm Hg (SD 4.2) or 18.6%, and 4.4 mm Hg (SD 3.8) or 17.1%, respectively. The percent of eyes with IOP reduction of 3 mm Hg or more at 3, 6 and 12 months was 66, 78 and 62%. A pressure spike of 8 mm Hg or more was detected in 4 eyes (9.1%). Anterior chamber reaction was seen 1 h after SLT and was mild to moderate in 16 eyes (40.4%) and marked in 3 eyes (6.8%). CONCLUSIONS: SLT has shown reasonable efficacy in lowering IOP over 1-year follow-up, but there was a tendency for IOP to increase with a longer follow-up. Long-term follow-up studies with a large sample size are needed to determine whether the IOP lowering effect is sustained over time, and to assess the efficacy of repeated SLT.

Aged↗

Eye lens crystallins: a component of intraocular pseudoexfoliative material.

Feeding experimental animals (19 pigs) with surplus sucrose and salt (NaCl) caused cataractous changes in lens tissue and triggered the formation of pseudoexfoliative material on the lens capsule. In the control animals (15 pigs) pseudoexfoliative material was absent. The avidin-biotin complex immunohistochemical method was applied to the pseudoexfoliative material obtained from 15 porcine experimental precataractous lenses and 1 spontaneously cataractous eye and revealed crystallins as a component of the intraocular pseudoexfoliative material. To prevent the development of both intraocular pseudoexfoliative material and crystallin-dependent glaucomatous changes in the trabecular meshwork of the eye, it is important to avoid any cataractogenic insult, including surplus sucrose and salt consumption, causing crystallin leakage from the lens.

Animals↗

Immunohistochemical localization of angiotensin-converting enzyme, angiotensin II and AT1 receptor in human ocular tissues.

We investigated the immunohistochemical distribution of 3 components of the renin-angiotensin system (RAS), angiotensin-converting enzyme (ACE), angiotensin II (AngII) and AT1 receptor (AT1), in the human eye. ACE and AngII were localized to nonpigmented epithelial cells of the ciliary body, to endothelial and epithelial cells of the cornea, to epithelial cells of the conjunctiva and to trabecular meshwork cells in the anterior part of the eye. In the posterior part of the eye, ACE and AngII were localized to ganglion cells, some cells in the inner nuclear layer, photoreceptor cells and to endothelial cells of the retinal and choroidal vessels. The overall intensity of AT1 immunoreactivity was weak in all ocular tissues, but the main localization was in ganglion cells. As a preliminary investigation, we were able to include 2 Alzheimer's disease (AD) cases. In AD, no differences from controls were found in the cellular distribution and staining intensity of all 3 antigens. The manifold localization sites of the observed antigens point to rather generalized functions of the RAS in human ocular tissues, such as regulatory effects on neuronal cells, vessels and vitreous humor homeostasis.

Aged↗

Association of E-cadherin gene 3'-UTR C/T polymorphism with primary open angle glaucoma.

PURPOSE: E-cadherin (E-CDH) is one of the most important cell surface glycoproteins involved in cell morphogenesis. In primary open angle glaucoma (POAG), the extracellular matrixes of trabecular meshwork and lamina cribrosa in the optic nerve head are out of balance. We suspected that E-CDH by way of metalloproteinases is closely related to POAG. We therefore investigated the relationship between CDH-1 gene 3' untranslated region (3'-UTR) polymorphism and POAG patients in order to support this hypothesis. PATIENTS AND METHODS: We enrolled 60 POAG patients and 103 healthy volunteers from the Department of Ophthalmology at the China Medical University Hospital, Taichung, Taiwan, ROC. None of the control subjects had a history of eye disease and all underwent the same examination as the POAG patients. PCR-based analysis of the restriction fragment length polymorphism was used to test the CDH-1 gene 3'-UTR polymorphism. All statistical analyses were performed by the chi(2) test. RESULT: There was a significant difference in the distribution of the CDH-1 gene 3'-UTR C/T polymorphism between POAG patients and the normal controls (p <0.000). The odds ratio of the 'C' allele was al so significantly different between both groups (odds ratio = 5.510, 95% confidence interval = 3.171-9.574). CONCLUSION: CDH-1 is closely related to metalloproteinase and plays an important but not well-understood role in the onset and progression of POAG. The exact role of CDH-1 in POAG could be resolved by the posttranslated products of the gene and the protein-protein interaction of the gene products in the future.

3' Untranslated Regions↗

Localization of M3 muscarinic receptor subtype and mRNA in the human eye.

Cholinergic agents used to lower intraocular pressure in the medical management of glaucoma act on muscarinic receptors in the eye. Recently, subtypes of muscarinic receptors have been recognized in many tissues including the eye. To localize the M3 muscarinic receptor subtype and m3 messenger RNA (mRNA) in the human eye, we used in vitro ligand binding and in situ hybridization techniques on post-mortem sections. We used an M3 antagonist, [3H]-4-DAMP ([3H]-4-diphenylacetoxy-N-methylpiperidine methiodide) to identify M3-binding sites and a [35S]-labelled oligonucleotide probe to detect and localize m3 mRNA. M3 and m3 mRNA were both localized in the ciliary muscle, ciliary epithelium, iris, corneal epithelium and anterior lens epithelium. The m3 transcript was also detected in the trabecular meshwork and corneal endothelium.

Acetylcholine↗

Biphasic intraocular pressure response to laser irradiation of the iris in rabbits.

The possibility of an acute increase in intraocular pressure (IOP) following laser iridotomy is well known. However, little attention has been paid to the hypotony after laser irradiation of the iris. We performed this study to evaluate the effect of laser irradiation of the iris on the IOP in pigmented rabbits. IOP, aqueous flare values, and aqueous prostaglandin E2 levels were measured before and 1, 4, 12, and 24 h after argon laser treatment. The IOP showed a prolonged reduction for 24 h following an initial transient increase. Flare values and aqueous prostaglandin E2 levels reached a peak 1 h after laser treatment, followed by a progressive reduction. Argon laser peripheral iridoplasty that can separate the iris from the trabecular meshwork by the mechanical force resulting from a contraction burn is used sometimes in treating angle-closure glaucoma. Our results showed that the laser irradiation of the iris itself can cause ocular hypotony, so that this phenomenon may be another explanation of the IOP response after peripheral iridoplasty.

Animals↗

Effect of dapiprazole, an alpha-adrenergic blocking agent, on aqueous humor dynamics in pigmentary glaucoma.

PURPOSE: In this investigation the authors studied the effect of dapiprazole, an alpha-adrenergic blocking agent, on aqueous humor dynamics in patients affected with pigmentary glaucoma. METHODS: Dapiprazole 0.5% eye drops were administered 3 times daily as adjunctive therapy to 16 pigmentary glaucoma patients in addition to timolol 0.5% eye drops twice daily. Computerized tonography was performed before and 3, 12 and 36 months after dapiprazole treatment. Sixteen sex- and age-matched pigmentary glaucoma patients treated with timolol 0.5% eye drops alone were used as a control group. RESULTS: After 36 months of follow-up, the dapiprazole-treated group showed a significant increase in total outflow facility (C, from 0.17 +/- 0.04 to 0.22 +/- 0.07 ml min-1 mm Hg-1; p = 0.010, paired t test) and Po/C ratio (Q) significantly decreased from 113.39 +/- 31.02 to 89.22 +/- 51.66 (p = 0.036, paired t test). CONCLUSIONS: Our results show that the introduction of dapiprazole in the therapy of pigmentary glaucoma may be useful in the long-term management of these patients. Its mechanism of action is likely to be due to iridoplegia; in fact, a decrease in the shedding of pigment occurs, with time, the outflow facility increases and the pigment clearance from the trabecular meshwork is enhanced.

Administration, Topical↗

[Specific pathological findings in trabeculectomy].

A quick embedding method for trabeculectomy specimens is desirable. It allows a comparison between the observations made during surgery and the histological material as long as the facts are remembered by the surgeon. Embedding by butoxy-ethanol-glycol-methacrylate proved to be adequate. It allows 1- to 2-mu thick sections. 39 trabeculectomy specimens were investigated in regard of topographical origin. In 26 of them, an exact localization was possible. Only 8 pieces contained Schlemm's canal or major parts of it. The others where cut more anteriorly and contained cornea and parts of the trabecular meshwork. The different topographical localization of the ectomized pieces did not influence the regulation of the intraocular tension in the early follow-up period. It is suggested that trabeculectomy does not give direct access to the aqueous to the cut ends of Schlemm's canal and to collector channels but rather by letting filter the aqueous externally along the scleral openings.

Aged↗

Secondary glaucoma accompanied with primary familial amyloidosis.

22 patients were diagnosed as having primary familial amyloidosis by the histological examination of biopsy specimens, clinical course of the disease, and family history, having a focus in the Nagano Prefecture in Japan. All patients belonged to the Andrade type of the neuropathy form in the primary familial amyloidosis. 15 out of 22 patients underwent ophthalmological examination, and secondary glaucoma, due to primary familial amyloidosis, was found in 4 patients. The clinical characteristic features of the secondary glaucoma were described as follows: (1) having the systemic symptoms of primary familial amyloidosis; (2) belonging to relatively older age groups and having a longer duration of the course of the disease; (3) having vitreous opacities; (4) having the wide open angle with pigment deposition in the gonioscopical examination; (5) having white flocculent materials in the pupillary margin, and (6) having flaky substances on the surface of the lens. The ophthalmological symptoms mentioned in 4, 5, and 6 were very similar to those of glaucoma capsulare. The tissue specimens obtained at the time of antiglaucoma surgery were subjected to light and electron microscopy. Amyloid fibrils were found in the iris and trabeculum, and the pathogenesis of secondary glaucoma was speculated to be a deposition of amyloid fibrils in the trabecular meshwork.

Adult↗

GH secretion in open-angle glaucoma.

Open-angle glaucoma is frequently observed in patients with acromegaly suggesting that the somatotropic hormone might facilitate a condition of glaucoma. The open-angle glaucoma patients studied, displayed higher plasma human growth hormone (HGH) levels than control subjects 60 min (30.3 +/- 1.7 against 16.8 +/- 2.7 ng/ml; p less than 0.001) and 90 min (19.0 +/- 1.9 against 9.3 +/- 1.2 ng/ml; p less than 0.001) after intravenous administration of arginine (25 g in 30 min). The authors support the hypothesis that the increased plasma HGH level may interfere with the regulation of ocular pressure by modifying the flow of aqueous humor from the eyeball via changes in the sclero-corneal trabecular meshwork; these changes are also found in diabetic subjects. The interplay between HGH and changes of carbohydrate metabolism (frequently occurring in glaucomatous patients) may be at the root of the variations of intraocular pressure in open-angle glaucoma.

Arginine↗