Search

Glaucoma, one of the leading causes of irreversible blindness worldwide, is a complex and heterogenous disease. While environmental factors are important, it is well-recognized that the disease has a strong heritable component. With the advent of large-cohort genome wide association studies, a myriad of genetic risk loci has been linked to different forms of glaucoma. Animal models have been an indispensable tool in characterizing these loci, especially if they lie within coding regions in the genome. Not only do these models connect genotype to phenotype, advancing our understanding of glaucoma pathogenesis in the process, they also have valuable utility as a platform for the pre-clinical testing of potential therapies. In this review, we will outline genetic models used for studying the major forms of glaucoma, including primary open angle glaucoma, normal tension glaucoma, primary angle closure glaucoma, pigmentary glaucoma, pseudoexfoliation glaucoma, and early onset glaucoma, including congenital and developmental glaucoma, and how studying these models have helped shed light on human glaucoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Glaucoma is a heterogeneous group of progressive diseases that leads to irreversible blindness. Secondary glaucoma refers to glaucoma caused by a known underlying condition. Pseudoexfoliation and pigment dispersion syndromes are common causes of secondary glaucoma. Their respective deposits may obstruct the trabecular meshwork, leading to aqueous humor outflow resistance, ocular hypertension, and optic neuropathy. There are no disease-specific interventions available for either. Pseudoexfoliation syndrome is characterized by fibrillar deposits (pseudoexfoliative material) on anterior segment structures. Over a decade of multiomics analyses taken together with the current knowledge on pseudoexfoliative glaucoma warrant a re-think of mechanistic possibilities. We propose that the presence of nucleation centers (e.g., vitamin D binding protein), crosslinking enzymes (e.g., transglutaminase 2), aberrant extracellular matrix, flawed endocytosis, and abnormal aqueous-blood barrier contribute to the formation of proteolytically resistant pseudoexfoliative material. Pigment dispersion syndrome is characterized by abnormal iridolenticular contact that disrupts iris pigment epithelium and liberates melanin granules. Iris melanogenesis is aberrant in this condition. Cytotoxic melanogenesis intermediates leak out of melanosomes and cause iris melanocyte and pigment epithelium cell death. Targeting melanogenesis can likely decrease the risk of pigmentary glaucoma. Skin and melanoma research provides insights into potential therapeutics. We propose that specific prostanoid agonists and fenofibrates may reduce melanogenesis by inhibiting cholesterol internalization and de novo synthesis. Additionally, melatonin is a potent melanogenesis suppressor, antioxidant, and hypotensive agent, rendering it a valuable agent for pigmentary glaucoma. In pseudoexfoliative glaucoma, where environmental insults drive pseudoexfoliative material formation, melatonin's antioxidant and hypotensive properties may offer adjunct therapeutic benefits. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology., (© 2023 The Authors. WIREs Mechanisms of Disease published by Wiley Periodicals LLC.)

In this paper, the authors present a case report of a 46-year-old patient with decompensated pigmentary glaucoma and anterior uveitis after unilateral implantation of a BrightOcular artificial cosmetic iris (Stellar Devices, New York, USA). Postoperatively, there was a decrease of endothelial cells (ECD) down to 1216 cells/mm2, a uveal reaction in the anterior chamber and a significant decompensation of intraocular pressure (IOP). During the first examination at our clinic, the explantation of the artificial cosmetic iris was indicated. However, despite all warnings, the patient repeatedly refused this procedure. The patient later decided to undergo the artificial cosmetic iris explantation due to persistent elevation of IOP with intense eye pain. The cosmetic iris implant was removed almost five months after its implantation. Postoperatively, the anterior uveitis resolved, but there was a further decrease in ECD of 130 cells/mm2 and also an increase in IOP, despite maximal antiglaucoma therapy. Nearly one month after removal of the artificial cosmetic iris, the patient underwent implantation of the Express P50 drainage shunt (Alcon Inc, Fort Worth, TX, USA). After the drainage procedure, IOP was normalized and remained within physiological limits during the first year after surgery. Thereafter, there was a recurrence of elevated IOP, which subsided to normal, after initiation of a combination of two antiglaucoma therapies. Four years after surgery the eye was quiescent, ECD stationary, the optic nerve head was stable, and the visual field remained within the physiological norm. This case report highlights a potentially harmful procedure that is presented as a relatively safe alternative for an iris colour change, representing a deceptive marketing strategy for companies trading in these implants.

Purpose: The DBA/2J (D2) mouse is an established model of pigmentary glaucoma, a type of primary open angle glaucoma. Prior studies have documented defects in flash electroretinogram (ERG) responses in D2 mice, but the origin of those defects is not clear. The purpose of this study was to understand the origin of these A-wave and B-wave changes in D2 ERGs., Materials and Methods: To accomplish this, we analyzed the differences between 9-month-old DBA/2J- Gpnmb+ (D2-control) and D2 mouse eyes in relation to ERG responses, intraocular pressure (IOP), outer nuclear layer thickness, and pupil area., Results: D2 scotopic ERGs showed lower A-wave amplitude and longer implicit time as well as a significant rightward shift in the intensity-response curve. D2 IOP increased at approximately seven months of age and had a weak correlation with the ERG A-wave sensitivity. Outer nuclear layer thickness was not significantly different in D2s compared to D2-control retinas. D2 mouse pupils also showed abnormal pupillary shape and no dilation following treatment with tropicamide eye drops. The pupil size moderately correlated with the A-wave sensitivity and this was pharmacologically replicated in C57Bl/6J mice following administration of pilocarpine to constrict the pupils. However, pilocarpine treatment did not affect ERG amplitudes., Conclusions: These data suggest that the smaller pupil sizes prevented light from reaching the photoreceptors and thus contributed to reduced ERG sensitivity in D2 mice. The reduced ERG A-wave amplitude in D2 mice likely results from dysfunctional photoreceptor responses.

Pigment dispersion syndrome (PDS) represents a clinical spectrum of a relatively common and usually underdiagnosed phenomenon produced by spontaneous pigment dispersion from the iris into the anterior segment. PDS is often bilateral, has no gender predisposition, and presents at a young age, particularly in myopes. Although most patients experiencing an episode of pigment dispersion are asymptomatic, extreme photophobia, ocular pain, redness, and blurred vision may occur. Other characteristic signs are iridolenticular contact, concave iris configuration, 360° peripheral iris transillumination, and pigment deposition on the anterior chamber angle or the corneal endothelium (Krukenberg spindle). Early PDS diagnosis is crucial to detect patients with pigment-related ocular hypertension (POHT) that can eventually lead to pigmentary glaucoma (PG). The latter represents a sight-threatening condition in which mechanical, environmental, and genetic factors contribute to optic nerve damage. In this review, we update the pathogenic mechanisms involved in the clinical spectrum of the disease. We describe its clinical presentation, ophthalmologic manifestations, and complications, including the factors influencing the development of POHT and PG. Because PDS has variable clinical presentations that lead to misdiagnoses, we emphasize the differential diagnosis and the actual therapeutic strategies according to disease status., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Glaucoma is a blinding optic neuropathy, the main risk factor for which is increased intraocular pressure (IOP). The trabecular meshwork, located within the iridocorneal angle, is the main pathway for drainage of aqueous humor (AH) out of the eye, and its dysfunction is responsible for the IOP elevation. The trabecular meshwork is a complex, fenestrated, three-dimensional structure composed of trabecular meshwork cells (TMC) interdigitated into a multilayered organization within the extracellular matrix (ECM). The purpose of this literature review is to provide an overview of current understanding of the trabecular meshwork and its pathophysiology in glaucoma. Thus, we will present the main anatomical and cellular bases for the regulation of aqueous humor outflow resistance, the pathophysiological mechanisms involved in trabecular dysfunction in the various types of glaucoma, as well as current and future therapeutic strategies targeting the trabecular meshwork., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Purpose Methods Results Conclusion Prospective investigation to determine the prevalence of ocular melanosis in adult Cairn Terriers within the United Kingdom using a previously established staging scheme.Ophthalmic assessment was performed on adult Cairn Terriers, recruited from various geographic locations within the United Kingdom. Examination included gonioscopy, rebound tonometry, slit lamp biomicroscopy, and indirect ophthalmoscopy, performed by one examiner (AM).A total of 93 dogs were examined, including 52 females and 41 males, aged between 15 months and 16 years 4 months. Sixty of 93 dogs (64.5%) were >7 years of age. Nine of 93 dogs (9.6%) demonstrated changes consistent with ocular melanosis. Four of 9 (44.4%) had Stage 1 disease and 5 of 9 (55.6%), Stage 2. Stages 3 or 4 were not identified in any dogs. Mean intraocular pressures in affected and unaffected dogs were 14.7 mmHg (range 12–17 mmHg) and 12.8 mmHg (range 5–21 mmHg), respectively. Incomplete pupil dilation was noted in affected dogs following pharmacologic mydriasis.Ocular melanosis was identified in approximately 10% of examined dogs, over half were dogs of breeding age (<7 years of age). It is possible that Grade 1 disease could go undetected, prior to obvious scleral pigment accumulation (Grade 2 disease). It is therefore recommended that dogs undergoing pre‐breeding screens have pre‐dilation assessment of the anterior segment using slit lamp biomicroscopy with subsequent gonioscopy to clearly assess for circumferential thickening of the iris base that might otherwise go undetected. Additionally, regular reassessment of breeding dogs is advised as disease progression could be rapid. [ABSTRACT FROM AUTHOR]

Background: Ocular melanocytosis was originally described as pigmentary glaucoma and reported in seven dogs of the Cairn Terrier breed. Subsequently, the occurrence of this condition was reported in other breeds of dogs among them a Shih Tzu, recently described. With progression, black pigment spots in the sclera and episclera cover the ciliary cleft. Pigment particles can often be seen suspended in the aqueous and, as they sediment, cover the ventral drainage angle, causing secondary glaucoma. The aim of this study was to describe the clinical and sonographic findings of a Shih Tzu dog with melanocytosis and unilateral secondary glaucoma. Case: A 8-year-old, male, Shih Tzu dog, with a history of progressive darkening of the sclera for 5 years, was referred to the ophthalmological service. The patient underwent routine ophthalmic examination. Slit lamp biomicroscopy revealed anisocoria. In the right eye, diffuse pigmentation of the sclera was observed in almost the entire perilimbal region, and in the iris signs of advanced atrophy with tissue loss between 9 h and 12 h. Nevertheless, zonular ligaments could be observed in this region, as well as a large amount of pigment deposits in the ventral region of the ciliary cleft. Applanation tonometry showed intraocular pressure (IOP) of 14 mmHg. Fundoscopic examination did not reveal abnormal pigmentation, but attenuation of the retinal vessels and in the optic disc was observed. In the left eye, no change was observed to demonstrate the bilaterality of the disease. One month later, the patient returned to the ophthalmology service complaining of an increase in the size of the right eye. Ophthalmic examination revealed moderate buftalmia in the right eye, IOP of 30 mmHg and increased ocular melanosis. Treatment was instituted to control intraocular pressure. Fifteen days after the start of treatment, the IOP decreased to 18 mmHg and it was found that the ophthalmic signs had improved, with a decrease in ocular discomfort. Ultrasound examination showed an increase in the anteroposterior axis and expansion of the anterior chamber, with scattered hyperechogenic spots in the periphery. Ultrasound biomicroscopy (UBM) was performed, in which the presence of obstruction in the ciliary fissure and the presence of punctate echoes between the ciliary fissure and the iris were observed. Four months later, the ophthalmic signs were stable, as well as the IOP (20 mmHg). Currently, the animal is visual in both eyes and with a stable condition in the progression of the disease. Discussion: This condition also known as melanocytosis, pigmentary glaucoma or abnormal pigment deposition, involves the gradual accumulation of pigment-laden cells mainly, melanocytes but also melanophages, in the anterior segment structures including the iris and ciliary body. It is seen in dogs of the Cairn Terriers breed as a hereditary defect, but has been reported in other breeds. Recently the condition was reported in a Shih Tzu, however differently from our work where the condition was unilateral and with a controllable glaucoma. The disorder initially manifests clinically with a progressive bilateral dark peripheral thickening of the iris base, followed by scleral/episcleral plaques of pigment adjacent to the limbus. Signs increase slowly, with pigment clusters in the aqueous and pigmentation in the ventral iridocorneal angle and peripheral endothelium, symptoms are usually bilateral, although not always symmetrical. This is the 1st case of a Shih Tzu with melanocytosis and controlled secondary glaucoma, unilateral, reported in the literature. This is a disease that should be considered as a differential diagnosis of uveal melanomas and melanocytomas. [ABSTRACT FROM AUTHOR]

Abstract Background Glaucoma is a leading cause of visual disability and blindness. Release of iris pigment within the eye, pigment dispersion syndrome (PDS), can lead to one type of glaucoma known as pigmentary glaucoma. PDS has a genetic component, however, the genes involved with this condition are largely unknown. We sought to discover genes that cause PDS by testing cohorts of patients and controls for mutations using a tiered analysis of exome data. Results Our primary analysis evaluated melanosome-related genes that cause dispersion of iris pigment in mice (TYRP1, GPNMB, LYST, DCT, and MITF). We identified rare mutations, but they were not statistically enriched in PDS patients. Our secondary analyses examined PMEL (previously linked with PDS), MRAP, and 19 other genes. Four MRAP mutations were identified in PDS cases but not in controls (p = 0.016). Immunohistochemical analysis of human donor eyes revealed abundant MRAP protein in the iris, the source of pigment in PDS. However, analysis of MRAP in additional cohorts (415 cases and 1645 controls) did not support an association with PDS. We also did not confirm a link between PMEL and PDS in our cohorts due to lack of reported mutations and similar frequency of the variants in PDS patients as in control subjects. Conclusions We did not detect a statistical enrichment of mutations in melanosome-related genes in human PDS patients and we found conflicting data about the likely pathogenicity of MRAP mutations. PDS may have a complex genetic basis that is not easily unraveled with exome analyses.

Purpose: The aim of this study was to evaluate the biomechanical properties of the cornea in different types of glaucoma and the relationship between corneal biomechanics and demographic and clinical parameters. Materials and Methods: Primary open-angle glaucoma (POAG), pseudoexfoliative glaucoma (PEG) and pigmentary glaucoma (PG) cases and healthy subjects as a control group were included in this retrospective observational study. Detailed ophthalmological examination was performed, computerized perimetry and optical coherence tomography (OCT) data were recorded in all cases. Corneal biomechanical properties were evaluated with Corvis ST® (Oculus, Wetzlar, Germany). Results: Forty-eight glaucoma cases (25 POAG, 15 PEG, 8 PG; 48 eyes) with a mean age of 61.4±11.4 years and 51 healthy volunteers (51 eyes) with a mean age of 45.2±9.9 years were included in the study. First applanation velocity (A1V) and deformation amplitude (DA) were lower in POAG cases than in other groups. In addition, the stiffness parameter (SP-A1) in the 1st applanation was higher in the POAG group compared to the control and PEG groups.. In glaucoma cases, a positive correlation was found between age and stress strain index, and an inverse relationship between glaucoma duration and SP-A1 Conclusion: The cornea was more resistant to deformation in POAG cases compared to PEG and PG cases and healthy corneas. There was no difference in corneal biomechanics between PEG and PG cases, and between these cases and the control group.. [ABSTRACT FROM AUTHOR]

Purpose/Aim: Glaucomatous optic neuropathy (GON) remains the world's leading cause of irreversible blindness. Treatments including topical medications are directed at reducing intraocular pressure (IOP), the most significant risk factor for GON. Current medications, while generally effective, are limited by insufficient response and side-effects in some patients. In search of a more targeted therapy that acts downstream of existing medications that has a potential for a lower side effect profile, our laboratory has identified Stanniocalcin-1 (STC-1), a multifunctional hormone, as an effector molecule in latanoprost-mediated IOP reduction with similar IOP-lowering efficacy as latanoprost in normotensive mice. Materials and methods: To investigate whether STC-1 can also reduce IOP in ocular hypertensive mice, we used a steroid-induced ocular hypertensive mouse model characterized by trabecular meshwork dysfunction as well as the DBA/2J mouse as an inherited model of pigment dispersion and secondary angle closure. Steroid-induced ocular hypertension was induced by weekly injections of dexamethasone into the conjunctival fornix of wild-type C57BL/6J mice (6–8 months old). After confirmation of the steroid response, mice were administered STC-1 or phosphate buffered saline (PBS) topically once daily for six weeks. For DBA/2J mice (14 months old), after baseline IOP measurements, mice were treated topically once daily with STC-1 or PBS for 5 days and IOP was assessed twice daily. Results: In steroid-induced ocular hypertensive mice, STC-1 lowered IOP by 26% (P <.001, week three) and maintained this level of IOP reduction throughout the remainder of the treatment period (P <.001, week six). In DBA/2J mice, STC-1 lowered IOP by 37% (P <.001). Conclusions: Together, these data show that STC-1 reduced IOP in two models of ocular hypertension with different mechanisms of outflow obstruction. [ABSTRACT FROM AUTHOR]

BackgroundThe molecular mechanisms causing pigment dispersion syndrome (PDS) and the pathway(s) by which it progresses to pigmentary glaucoma are not known. Mutations in two melanosomal protein genes (Tyrp1(b) and Gpnmb(R150X)) are responsible for pigment dispersing iris disease, which progresses to intraocular pressure (IOP) elevation and subsequent glaucoma in DBA/2J mice. Melanosomal defects along with ocular immune abnormalities play a role in the propagation of pigment dispersion and progression to IOP elevation. Here, we tested the role of specific immune components in the progression of the iris disease and high IOP.ResultsWe tested the role of NK cells in disease etiology by genetically modifying the B6.D2-Gpnmb(R150X) Tyrp1(b) strain, which develops the same iris disease as DBA/2J mice. Our findings demonstrate that neither diminishing NK mediated cytotoxic activity (Prf1 mutation) nor NK cell depletion (Il2rg mutation) has any influence on the severity or timing of Gpnmb(R150X) Tyrp1(b) mediated iris disease. Since DBA/2J mice are deficient in CD94, an important immune modulator that often acts as an immune suppressor, we generated DBA/2J mice sufficient in CD94. Sufficiency of CD94 failed to alter either the iris disease or the subsequent IOP elevation. Additionally CD94 status had no detected effect on glaucomatous optic nerve damage.ConclusionOur previous data implicate immune components in the manifestation of pigment dispersion and/or IOP elevation in DBA/2J mice. The current study eliminates important immune components, specifically NK cells and CD94 deficiency, as critical in the progression of iris disease and glaucoma. This narrows the field of possible immune components responsible for disease progression.

Background: Glaucoma is a leading cause of visual disability and blindness. Release of iris pigment within the eye, pigment dispersion syndrome (PDS), can lead to one type of glaucoma known as pigmentary glaucoma. PDS has a genetic component, however, the genes involved with this condition are largely unknown. We sought to discover genes that cause PDS by testing cohorts of patients and controls for mutations using a tiered analysis of exome data. Results: Our primary analysis evaluated melanosome-related genes that cause dispersion of iris pigment in mice (TYRP1, GPNMB, LYST, DCT, and MITF). We identified rare mutations, but they were not statistically enriched in PDS patients. Our secondary analyses examined PMEL (previously linked with PDS), MRAP, and 19 other genes. Four MRAP mutations were identified in PDS cases but not in controls (p = 0.016). Immunohistochemical analysis of human donor eyes revealed abundant MRAP protein in the iris, the source of pigment in PDS. However, analysis of MRAP in additional cohorts (415 cases and 1645 controls) did not support an association with PDS. We also did not confirm a link between PMEL and PDS in our cohorts due to lack of reported mutations and similar frequency of the variants in PDS patients as in control subjects. Conclusions: We did not detect a statistical enrichment of mutations in melanosome-related genes in human PDS patients and we found conflicting data about the likely pathogenicity of MRAP mutations. PDS may have a complex genetic basis that is not easily unraveled with exome analyses. [ABSTRACT FROM AUTHOR]

Pigment dispersion syndrome (PDS) is a clinical entity that is characterized with anomalous irido-zonular contact leading pigment dispersion throughout the anterior segment. Clinical presentation includes pigmented cells on the corneal endothelium, an increased pigmentation of the trabecular meshwork, and mid-periphery transillumination defects of iris. The syndrome is usually bilateral and more common in myopic individuals and young male adults. Also it can be associated with ocular hypertension or glaucoma. Pigmentary glaucoma (PG) is a kind of secondary open-angle glaucoma and is caused by occlusion of trabecular meshwork by pigmentary cells and reduction in the aqueous humor efflux. In this review, we will discuss clinical characteristics, pathogenesis and current management of PDS and PG. [ABSTRACT FROM AUTHOR]

Introduction: Pigmentary Glaucoma (PG) and Pigment Dispersion Syndrome (PDS) are two different spectrums of a single disease. Since the disease is seen in younger population and is rapidly progressive blinding disease, therefore early diagnosis and treatment will reduce the burden of the disease and improve the quality of life. Aim: The aim of this study was to evaluate clinical characteristics of PDS and PG patients in eastern part of Uttar Pradesh. Materials and Methods: This was a two years (1st January 2018 to 31st December 2019) hospital-based retrospective cross-sectional study of patients who attended the glaucoma clinic. Diagnosis of PDS was made when they had normal optic disc, normal visual field {with or without increased Intra Ocular Pressure (IOP)} and at least two of the following three signs were found clinically: Krukenberg spindle, homogenous moderate-to-heavy (≥Spaeth 2+) Trabecular Meshwork (TM) pigmentation, and any degree of zonular and/or lenticular pigment granule dusting. Patients with PDS were diagnosed with PG, if they had two or more of the following findings: initial IOP >21 mmHg, glaucomatous optic nerve damage or glaucomatous visual field loss. Various parameters such as influence of demographics, IOP, Best-Corrected Visual Acuity (BCVA), Central Corneal Thickness (CCT), Mean Deviation (MD), Visual Field Index (VFI %), spherical equivalent and clinical finding of anterior segment of study patients were analysed. Mean, standard deviation and percentage were calculated using GraphPad Instat version 3.0. Results: Among 40 patients, nine eyes of the six patients had myopia of -0.5D or greater, with mean refractive error of -3.55±4.72 spherical equivalent. The average baseline IOP in study patients (PDS+PG), was 30.21±11.42 mmHg. Twenty four (60%) patients, either in one or both eyes had glaucoma, secondary to PDS at the initial diagnosis. Thirty three (82.5%) patients had Krukenberg spindles. Homogeneous TM pigmentation was seen in all patients. Typical spoke-like radial Iris Transillumination Defects (ITDs) were not observed in any of the patients except in one patient, who had isolated short slitlike trans-illumination defects in iris crypts. Conclusion: It can be concluded that PDS patients with normal optic disc and visual field and raised IOP, should be started prophylactic treatment and needs to be monitored more closely. Thus, the finding of PDS in Indians should alert the ophthalmologist to look for glaucoma during the initial examination. [ABSTRACT FROM AUTHOR]

Laser applications on iris for the treatment of glaucoma include laser iridotomy (LI) and laser peripheral iridoplasty (LPI). LI is a simple and effective modality for treatment of closed-angle glaucoma with pupillary block. LPI is an easy and effective treatment for closed angle in situations in which LI either cannot be performed or does not repair the appositional angle closure because mechanisms other than pupillary block are present. The aim of this review is to summarize the indications, technique details, and complications of laser applications on iris for the treatment of glaucoma. (Turk J Ophthalmol 2013; 43: 190-4)

Background Single nucleotide polymorphisms (SNPs) within the LOXL1 gene are associated with pseudoesfoliation syndrome and pseudoesfoliation glaucoma. The aim of our study is to investigate a potential involvement of LOXL1 gene in the pathogenesis of pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG). Methods A cohort of Caucasian origin of 84 unrelated and clinically well-characterised patients with PDS/PG and 200 control subjects were included in the study. Genomic DNA from whole blood was extracted and the coding and regulatory regions of LOXL1 gene were risequenced in both patients and controls to identify unknown sequence variations. Genotype and haplotype analysis were performed with UNPHASED software. The expression levels of LOXL1 were determined on c-DNA from peripheral blood lymphocytes by quantitative realtime RT-PCR. Results A significant allele association was detected for SNP rs2304722 within the fifth intron of LOXL1 (Odds ratio (OR = 2.43, p-value = 3,05e-2). Haplotype analysis revealed the existence of risk and protective haplotypes associated with PG-PDS (OR = 3.35; p-value = 1.00e-5 and OR = 3.35; p-value = 1.00e-4, respectively). Expression analysis suggests that associated haplotypes can regulate the expression level LOXL1. Conclusions Haplotypes of LOXL1 are associated with PG-PDS independently from rs1048661, leading to a differential expression of the transcript. [ABSTRACT FROM AUTHOR]

Laser applications on iris for the treatment of glaucoma include laser iridotomy (LI) and laser peripheral iridoplasty (LPI). LI is a simple and effective modality for treatment of closed-angle glaucoma with pupillary block. LPI is an easy and effective treatment for closed angle in situations in which LI either cannot be performed or does not repair the appositional angle closure because mechanisms other than pupillary block are present. The aim of this review is to summarize the indications, technique details, and complications of laser applications on iris for the treatment of glaucoma. [ABSTRACT FROM AUTHOR]

Background: Ocular melanosis of Cairn terrier dogs is an inherited defect characterized by progressive pigmentation of both eyes which can result in glaucoma and blindness. Pedigree analysis suggests the trait has an autosomal dominant mode of inheritance. We selected 11 potential candidate genes and used an exclusion analysis approach to investigate the likelihood that one of the candidate gene loci contained the Cairn terrier-ocular melanosis locus. Results: Two polymorphic loci were identified within or close to each candidate gene. Genotyping of at least 10 ocular melanosis Cairn terriers for each marker showed that there was no single shared allele for either of the two polymorphic markers identified in ASIP, COMT, GPNMB, GSK3B, LYST, MC1R, MITF, SILV, TYR, TYRP1,and TYRP2. This is strong evidence to exclude each locus as the site of the ocular melanosis mutation (probability of a false exclusion calculated for each gene ranged from 1.59 × 10-4 to 1 × 10-9). Conclusions: None of the 11 potential candidate genes selected are likely to be the gene locus for ocular melanosis in Cairn terriers. [ABSTRACT FROM AUTHOR]

Primary pigment dispersion syndrome (PPDS) is a bilateral condition that occurs in anatomically predisposed individuals. PPDS may evolve into pigmentary glaucoma, but it is difficult to predict which patients will progress. Secondary pigment dispersion is more often unilateral and acquired as a result of surgery, trauma, or intraocular tumor, but can likewise lead to pigmentary glaucoma. We report two cases of patients with bilateral PPDS who developed secondary pigment dispersion and pigmentary glaucoma in one eye. Patients with PPDS who acquire a secondary mechanism of pigment dispersion may be at an increased risk of progression to pigmentary glaucoma, presumably due to an increased burden of liberated pigment. In addition to regular surveillance for progression to glaucoma from PPDS, secondary causes of pigmentary dispersion in these eyes should be considered when patients present with grossly asymmetric findings. When secondary pigment dispersion is identified in eyes with PPDS, we recommend prompt intervention to alleviate the cause of secondary pigment dispersion and/or aggressive control of intraocular pressure to limit glaucomatous damage. [ABSTRACT FROM AUTHOR]

Purpose: To report two Japanese cases of pigmentary glaucoma (PG) treated with laser peripheral iridotomy (LPI) that were followed for 15 and 16 years, respectively. Methods: The medical records of two patients with PG who were successfully treated with LPI were reviewed. Changes in the intraocular pressure (IOP) were followed. Results: Case 1 was that of a 35-year-old man with LPI who underwent argon laser trabeculoplasty twice. He required ocular hypotensive drugs to maintain the IOP at normal levels. Case 2 involved a 36-year-old man with LPI who required ocular hypotensive drugs to maintain his IOP at the low-teen level. The IOP of both patients was unstable during the first 6-8 years following the LPI, but showed a decrease at each annual follow-up examination up to the age of 50 years. Conclusions: Although only two cases were followed, we conclude that the long-term effects of LPI may play a role, at least partly, in stabilizing the IOP at the low-teen level. Both patients were relatively young at the time of the LPI, and age may have been a factor in the stabilization process. Our findings confirm similar findings in Western countries. [ABSTRACT FROM AUTHOR]

The article investigates the interconnection between microglial activation and the increase in intraocular pressure (IOP) and retinal ganglion (RGC) cell death. Vision loss caused by glaucoma is attributed to retinal ganglion cell apoptosis. IOP is an important risk factor for glaucoma. The methodology involved mice divided into glaucoma and control models. Their eyes were observed using a biomicroscope and a microneedle system estimated IOP. The results indicated that RGC loss was due to activated microlagia and IOP caused retinal microglial activation.

Pigment dispersion syndrome (PDS) is an interesting condition that can lead to secondary open angle glaucoma. Pigmentary glaucoma is primarily a disease of young people, myopes and men. PDS is characterized by the presence of Krukenberg spindles, iris trans-illumination defects, trabecular meshwork pigmentation and backward bowing of the iris. Posterior bowing of the iris causes rubbing of the pigmented iris epithelium against lens structures, liberation of pigment and trabecular meshwork changes that result in reduced aqueous outflow with the risk of glaucoma. Peripheral laser iridotomy can reverse backward bowing of the iris and may prevent progression of pigmentary glaucoma. [ABSTRACT FROM AUTHOR]

Objective To describe the clinical features of ocular melanosis in Cairn Terriers. Animal studied One hundred and fourteen Cairn Terriers diagnosed with ocular melanosis. Procedure(s) A complete eye examination was performed on each dog. Four dogs (and two unaffected control dogs) underwent a high frequency ultrasound examination of the anterior segment. The pedigrees of affected dogs were analyzed. Results Forty-four (38.6%) dogs were male and 67 (58.7%) female; the sex of three dogs (2.6%) was not provided. A four-stage grading system of the ocular changes was developed. There was a variable age of onset, and the earliest change was a dark-colored thickening of the iris root. This was followed by the development of episcleral/scleral pigment plaques, release of pigment into the aqueous and deposition in the drainage apparatus, particularly ventrally. Secondary glaucoma developed in the most severely affected dogs. A slow progression of pigmentation in the tapetal fundus was observed and in some dogs pigment on the surface of the optic nerve head was seen. Three dogs developed uveal melanocytic neoplasms. Pedigree analysis suggested a possible autosomal dominant mode of inheritance. Conclusions Ocular melanosis is an inherited, probably autosomal-dominant condition with a variable age of onset and rate of progression. It results in a thickening and pigmentation of the iris, release of pigmented material into the aqueous, pigment deposition in the sclera/episclera, and to a lesser extent posterior segment pigment deposition. Following extensive pigment deposition in the aqueous drainage pathways it can result in secondary glaucoma. [ABSTRACT FROM AUTHOR]

Glaucoma describes a group of diseases that kill retinal ganglion cells. There are different types of glaucoma, and each appears to be genetically heterogeneous. Different glaucoma genes have been identified, but these genes account for only a small proportion of glaucoma. Most glaucoma cases appear to be multifactorial, and are likely affected by multiple interacting loci. A number of genetic susceptibility factors have been suggested to contribute to glaucoma. These factors fit into two broad groups, those affecting intraocular pressure and those important in modulating retinal ganglion cell viability. Defining the complex genetics of glaucoma will require significant further study of the human disease and animal models. Genetic approaches are essential and will be enhanced by recently developed genomic and proteomic technologies. These technologies will provide valuable clues about pathogenesis for subsequent testing. In this review, we focus on endogenous genetic susceptibility factors and on how experimental studies will be valuable for dissecting the multifactorial complexity of their interactions. [ABSTRACT FROM AUTHOR]

Purpose: To study the effect of exercise on the configuration of the anterior chamber angle in healthy persons. Methods: Both eyes of 22 healthy persons were scanned by Ultrasound Biomicroscopy. Before and after 10 minutes of exercise the anterior chamber angle and the area of the peripheral anterior chamber were measured on the scannings. Results: After exercise the anterior chamber angle/peripheral area increases in all eyes due to changes in the iris configuration. The myopic group shows the largest change. Conclusion: Reverse pupillary block (iris concavity) is not pathognomonic in pigmentary glaucoma, it occurs in all normal eyes after exercise, most pronounced in myopics. Consequently, the difference between physiological and pathological reverse pupillary block has to be clarified. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the racial heritage of a group of African-Americans who exhibit the pigment dispersion syndrome (PDS). Subjects and Methods: Ten unrelated African-American PDS patients (age range 13–59) from a primary eye care population in Chicago, Illinois, USA, were interviewed to determine their racial heritage. Since Caucasian and Native American heritage were commonly reported, 101 unaffected African-American control subjects (age range 18–55) were also interviewed to determine the reported frequency of these specific racial heritage characteristics. Results: Some degree of Caucasian heritage was reported by 100% of the PDS subjects and by 46.5% of controls. Native American heritage was reported by 90% of the PDS subjects and by 71.3% of controls. Based on these data, the PDS subjects were significantly more likely to report Caucasian heritage (Fisher's exact test, P=0.001) but they were not significantly more likely to report Native American heritage ( P=0.282). In addition, the PDS subjects were significantly more likely to report Caucasian heritage from both parents ( P=0.024) and more likely to report a combination of both Caucasian and Native American heritage ( P=0.0006) than corresponding controls. In general, the PDS subjects had `light' or `medium' complexions. Conclusion: Results from this analysis are consistent with the hypothesis that non-African heritage, particularly Caucasian, is likely to be prevalent in the background of African-Americans who exhibit PDS. It is suggested that non-African heritage may not only be important for the transference of PDS causing genes, but it may also influence factors such as degree of iris pigmentation and rigidity which could influence iris contour and the subsequent expression of PDS in those who are genetically predisposed. Further investigation is needed to study the factors that influence the expression and severity of PDS among African-Americans, a population which traditionally has been considered to be rarely affected by this condition. [ABSTRACT FROM AUTHOR]

Pigment dispersion syndrome (PDS) is a well-known clinical entity usually discovered during routine examination of an otherwise healthy adult eye and is associated with the development of pigmentary glaucoma. It's characteristic feature includes loss of iris contour and loss of pigment granules from the iris. A 55 year old female presented with complaints of painless, gradually progressive diminution of vision in both eyes. On ocular examination, both eyes showed pigment deposition on the corneal endothelium in a vertical spindle-shaped distribution suggestive of Krukenberg's spindle. On gonioscopy, there was presence of heavy pigmentation on the trabecular meshwork (Sampaolesi line).Regular IOP monitoring of this patient was advised for early detection of pigmentary glaucoma. [ABSTRACT FROM AUTHOR]