Pigmentary glaucoma

Pigmentary glaucoma is one of the more common forms of secondary open angle glaucoma. It typically affects younger individuals, being more common among myopes, Caucasian men and persons with a family history of glaucoma. It is characterized by pigment dispersion throughout the anterior segment. The biomicroscopic signs of this condition include iris transillumination defects, Krukenberg spindles, and a dense uniform trabecular meshwork pigment band, oftentimes with a discernable pigmented Schwalbe's line (Sampoalesi line). In addition, pigment deposition may be observed on the anterior iris surface, zonules and the crystalline lens. The development of pigmentary glaucoma moves through a continuum of stages. It is advocated that posterior bowing of the iris (reverse pupillary block) results in iridozonular contact, causing release of iris pigment, i.e. pigmentary dispersion syndrome. Pigment accumulation within the trabecular meshwork leads to endothelial cell damage and loss, resulting in trabecular collapse. The trabecular meshwork support beams collapse and fuse, leading to decreased outflow facility, elevated IOP and glaucoma. Present day management includes antiglaucoma medications, trabeculoplasty, laser iridotomy for those patients with concave iris contour and filtering surgery.     

In vivo non-contact measurement of human iris elasticity by optical coherence elastography

Quantifying the mechanical properties of the iris can offer valuable insights into the pathophysiology of primary angle closure glaucoma. However, current techniques for iris elastography remain ex vivo with limited clinical applications. This article describes a proposition for a non-contact and non-invasive air-puff optical coherence elastography (OCE) system that can evaluate iris elasticity in vivo. Ten eyes recruited from seven subjects underwent OCE imaging acquisition under three different illumination conditions. The Young's modulus of each eye was detected and shown to be inversely proportional to the iris length, indicating a relationship between mechanical properties and morphology of the iris. With its noninvasive and high-resolution features, this air-puff system shows great potential for applications in clinical ophthalmology.     

Corneal thickness in pseudoexfoliative glaucoma

Measurements of central cornea thickness (CCT) have a very important value in glaucoma patients; if the central cornea is thinner than it suggests, then the intraocular pressure is falsely low. This study compares the central cornea thickness between patients with pseudoexfoliative glaucoma, open angle glaucoma, angle closure glaucoma and control group. This study included 34 patients with pseudoexfoliative glaucoma, 31 patient with open angle laucoma, 28 patients with angle closure laucoma and 36 normal subjects in a control group. Patients in all groups and also normal subjects in control group had no other corneal disorders, no history of trauma, corneal surgery and were not patients with contacts lens use. Patients with pseudoexfoliative glaucoma and also patients with open angle glaucoma had significantly lower values of central cornea thickness compared with normal subjects in control group. Tomey EM 3000 is a non contact specular microscope which was used to measure central corneal thickness in this study. Pachymetry is an important method for diagnoses of glaucoma and for examination of the intraocular pressure in glaucoma patients, because values of the central corneal thickness affect the exact intraocular pressure readings.     

Treatment of glaucoma by prostaglandin agonists and beta‐blockers in combination directly reduces pro‐fibrotic gene expression in trabecular meshwork

Prostaglandin analogues (PG), beta‐blockers (BB) or their combination (PG+BB) are used primarily to reduce the intraocular pressure (IOP) pathologically associated with glaucoma. Since, fibrosis of the trabecular meshwork (TM) is a major aetiological factor in glaucoma, we studied the effect of these drugs on fibrosis‐associated gene expression in TM of primary glaucoma patients. In the present study, TM and iris of primary open‐angle (n = 32) and angle‐closure (n = 37) glaucoma patients were obtained surgically during trabeculectomy and categorized based on the type of IOP‐lowering medications use as PG, BB or PG+BB. mRNA expression of pro‐fibrotic and anti‐fibrotic genes was quantified using qPCR in these tissues. The gene expression levels of pro‐fibrotic genes were significantly lower in PG+BB as compared to other groups. These observations and underlying signalling validated in vitro in human TM cells also showed reduced fibrotic gene and protein expression levels following PG+BB treatment. In conclusion, it is observed that PG+BB combination rather than their lone use renders a reduced fibrotic status in TM. This further suggests that IOP‐lowering medications, in combination, would also modulate fibrosis‐associated molecular changes in the TM, which may be beneficial for maintaining aqueous out‐flow mechanisms over the clinical treatment duration.     

Involvement of inflammation, degradation, and apoptosis in a mouse model of glaucoma

Glaucoma is a common cause of blindness affecting at least 66 million people worldwide. Pigmentary glaucoma is one of the most common forms of secondary glaucoma, and its pathogenesis remains unclear. Interleukin-18 (IL-18) is an important regulator of innate and acquired immune responses and plays an important role in inflammatory/autoimmunity diseases. Using the DBA/2J mouse as an animal model of human pigmentary glaucoma, we demonstrated for the first time that the expression of the IL-18 protein and gene in the iris/ciliary body and level of IL-18 protein in the aqueous humor of DBA/2J mice are dramatically increased with age. This increase precedes the onset of clinical evidence of pigmentary glaucoma, implying a pathogenic role of inflammation/immunity in this disease. We also observed that activated NF-kappaB and phosphorylated MAPK are increased in the iris/ciliary body of DBA/2J mice, suggesting that both signaling pathways may be involved in IL-18 mediated pathogenesis of pigmentary glaucoma in the eyes of DBA/2J mice. In addition, matrix metalloproteinase-2 (MMP-2) expression in the iris/ciliary body and the activity of MMP-2 in the aqueous humor are increased whereas tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) expression in the iris/ciliary body is decreased, indicating that the degradation process is involved in this mouse model of pigmentary glaucoma. Furthermore, the expressions of apoptosis-related genes, caspase-8, Fas, FADD, FAP, and FAF, and the activity of caspase-3 are increased in the iris/ciliary body of DBA/2J mice. Elucidation of biochemical and molecular mechanisms of IL-18 participation in the pathogenesis of pigmentary glaucoma should provide approaches for developing improved and targeted treatments to ameliorate this blinding disease. The possibility that altered IL-18 expression in the eye of DBA/2J mice initiates and/or amplifies the pathogenesis of pigmentary glaucoma requires further investigation.     

T-Helper1/T-Helper2 Cytokine Imbalance in the Iris of Patients with Glaucoma

The mechanistic study of glaucoma pathogenesis has shifted to seeking to understand the effects of immune responses on retinal ganglion cell damage and protection. Cytokines mediate the biological effects of the immune system, and our previous study revealed an imbalance of T-helper (Th) 1-derived and Th2-derived cytokines in the serum of patients with glaucoma. In this study, we collected irises from normal individuals and patients with primary open-angle closure (POAG) or chronic angle-closure glaucoma (CACG). We used real-time polymerase chain reaction (PCR) to measure the expression of Th1 (interleukin (IL)-2, interferon-gamma (IFN-γ)), Th2 (IL-4, IL-6, IL-10), and Th3 (transforming growth factor-beta (TGF-β)) cytokines. We then performed immunohistochemical staining to characterize the localization of the upregulated cytokines in iris cryosections. We observed an upward trend in the expression of IL-2 and IFN-γ and a downward trend in IL-6 expression in the iris of POAG and CACG patients. Expression of TGF-β also increased. Immunohistochemistry revealed that IL-2 expression in POAG and CACG patients was localized in the anterior surface of the blood vessel wall in the stroma of the iris, in the cytoplasm of some cells, in the anterior epithelium, and in the posterior pigment epithelium. These findings indicate that immune status differed between the iris tissues of POAG and CACG patients and those of normal individuals. A T-helper cytokine imbalance may modulate the immune microenvironment in glaucomatous eyes and thus influence optic neuropathy.     

Specular microscopy in glaucoma patients

The endothelial cells are one of the most important structures in a donor cornea. Morphology and concentration of endothelial cells must be carefully evaluated with a specular microscope before transplantation. The aim of this study is to evaluate the status of corneal endothelium in glaucoma patients. Prospective study included 50 patients suffering from glaucoma and 50 patients in control group. Patients had no corneal disease, ocular inflammation, previous trauma or ocular surgery. Patients were not contact lens wearers. They were also analyzed in groups according to type of glaucoma. Specular microscopy was performed on central corneas. This study showed that patients with glaucoma have lower central corneal endothelial cell density than those without glaucoma of the same age group. Also, patients with pseudoexfoliative glaucoma had lower values of central endothelial cell density comparing to patients with open angle or angle closure glaucoma.     

Familial glaucoma iridogoniodysplasia maps to a 6p25 region implicated in primary congenital glaucoma and iridogoniodysgenesis anomaly.

Familial glaucoma iridogoniodysplasia (FGI) is a form of open-angle glaucoma in which developmental anomalies of the iris and irido-corneal angle are associated with a juvenile-onset glaucoma transmitted as an autosomal dominant trait. A single large family with this disorder was examined for genetic linkage to microsatellite markers. A peak LOD score of 11.63 at a recombination fraction of 0 was obtained with marker D6S967 mapping to chromosome 6p25. Haplotype analysis places the disease gene in a 6.4-cM interval between the markers D6S1713 and D6S1600. Two novel clinical appearances extend the phenotypic range and provide evidence of variable expressivity. The chromosome 6p25 region is now implicated in FGI, primary congenital glaucoma, and iridogoniodysgenesis anomaly. This may indicate the presence of a common causative gene or, alternatively, a cluster of genes involved in eye development/function.     

Clinical signs and differential diagnosis of iris melanoma

Iris melanoma is the rarest type of uveal melanomas. Only 4-5% of uveal melanomas occur on the iris. Although the iris can be easily examined due to its location, differentiation of melanocytic malformations such as naevi or melanomas is difficult for the examiner. According to publications by Rones and Zimmermann, histological examinations showed 22% of tumors to be malignant and 78% to be benign. This lead to iridectomy and iridocyclectomy as therapeutic solutions to gain ground over enucleation. Follow-up of the clinical signs, transillumination, ultrasonic biomicroscopy, iris fluorescein angiography and photo-documentation of the clinical signs can be of great help in diagnosis of pigmented iris tumours. Growth of the tumour, secondary glaucoma, hyphaema, significant vascularisation of the tumour and increasing extent of pigmentation can be signs of malignant behaviour.     

大草蛉成虫复眼的外部形态及其显微结构

用扫描电镜和光学显微镜观察了大草蛉Chrysopa pallens Ramber成虫复眼的外部形态及明、暗适应和性别对其显微结构的影响。结果发现：（1）其复眼呈半球形,位于头部两侧,略成“八”字形排列,单个复眼约由3 600个小眼组成,最前和最后小眼之间的夹角约为180°,最上和最下小眼之间的夹角约200°;（2）小眼主要由角膜、晶锥和6～8个小网膜细胞、基膜组成,外围环绕有2个初级虹膜色素细胞和6个次级虹膜色素细胞,基膜处有色素颗粒分布;（3）暗适应时,晶锥开裂程度较大,远端5～7个网膜细胞核向远端移动,与晶锥近端相接或接近,次级虹膜色素颗粒亦向远端移动包围晶锥;明适应时,晶锥开裂程度小或闭合,远端网膜细胞核向近端移动,透明带显现,大部分次级虹膜色素颗粒亦向近端移动分布在小网膜细胞柱周围,包被透明带;（4）在相同的明、暗适应下,雌、雄成虫复眼的显微结构无明显差异。结果表明大草蛉复眼为透明带明显的重叠象眼,其小眼不但具有次级虹膜色素颗粒纵向移动的常规调光机制,还存在晶锥开闭、远端网膜细胞核移动和基膜色素颗粒纵向扩散的调光新机制。     

Modeling passive mechanical interaction between aqueous humor and iris.

Certain forms of glaucoma are associated with displacement of the iris from its normal contour. We present here a mathematical model of the coupled aqueous humor-iris system that accountsfor the contribution of aqueous humor flow and passive iris deformability to the iris contour. The aqueous humor is modeled as a Newtonian fluid, and the iris is modeled as a linear elastic solid. The resulting coupled equation set is solved by the finite element method with mesh motion in response to iris displacement accomplished by tracking a pseudo-solid overlying the aqueous humor. The model is used to predict the iris contour in healthy and diseased eyes. The results compare favorably with clinical observations, supporting the hypothesis that passive iris deformation can produce the iris contours observed using ultrasound biomicroscopy.     

视网膜激光光凝与复合式小梁切除术治疗新生血管性青光眼的临床疗效对比

目的:观察和比较视网膜激光光凝与复合式小梁切除术治疗新生血管性青光眼(NVG)的临床疗效和安全性。方法:选择2013年1月~2015年6月我院收治的新生血管性青光眼患者85例,随机分为两组,观察组采用视网膜激光光凝术治疗,对照组采用复合式小梁切除术治疗,比较两组的临床疗效和并发症的发生情况。结果:两组术后眼压均较治疗前明显降低(P0.05),且观察组明显低于对照组(P0.05);两组术后视力、虹膜新生血管退化情况相比差异无明显统计学意义(P0.05);观察组术中、术后前房出血发生率均明显低于对照组(P0.05)。结论:视网膜激光光凝与复合式小梁切除术对新生血管性青光眼均有较好的治疗效果,复合式小梁切除术对患者眼压控制效果更好,安全性更高。     

Diagnosis and treatment of glaucoma; a review of recent developments

Tonography is helpful in the diagnosis of doubtful cases of chronic simple glaucoma. If also gives a good indication of the status of the disease in a given eye. The most useful miotic in the treatment of glaucoma is still pilocarpine. Carbachol is more potent but must be used in an anhydrous base ointment or in a solution of a wetting agent. DFP (diisopropyl fluorophosphate) produces undesirable side effects because of the hyperreactivity of the ciliary body and iris sphincter which it causes. These can be partly overcome by using pilocarpine first. Diamox is a carbonic anhydrase inhibitor that is effective when given orally. In many cases it produces at least a temporary lowering of tension in glaucomatous eyes, apparently by reducing the secretion of intraocular fluid. Its ultimate value in glaucoma remains to be seen. The cyclodiathermy operation which has been modified somewhat by Weekers has had a recent increase in use but the long-term results have been somewhat disappointing. The importance of early operation in narrow angle glaucoma is becoming more and more apparent. Following iridectomy the wound should be tightly sutured to insure the prompt reformation of the anterior chamber.     

DIAGNOSIS AND TREATMENT OF GLAUCOMA—A Review of Recent Developments

Tonography is helpful in the diagnosis of doubtful cases of chronic simple glaucoma. If also gives a good indication of the status of the disease in a given eye.The most useful miotic in the treatment of glaucoma is still pilocarpine. Carbachol is more potent but must be used in an anhydrous base ointment or in a solution of a wetting agent. DFP (diisopropyl fluorophosphate) produces undesirable side effects because of the hyperreactivity of the ciliary body and iris sphincter which it causes. These can be partly overcome by using pilocarpine first. Diamox is a carbonic anhydrase inhibitor that is effective when given orally. In many cases it produces at least a temporary lowering of tension in glaucomatous eyes, apparently by reducing the secretion of intraocular fluid. Its ultimate value in glaucoma remains to be seen.The cyclodiathermy operation which has been modified somewhat by Weekers has had a recent increase in use but the long-term results have been somewhat disappointing.The importance of early operation in narrow angle glaucoma is becoming more and more apparent. Following iridectomy the wound should be tightly sutured to insure the prompt reformation of the anterior chamber.     

Current uses of ophthalmic lasers.

Current laser treatments are quick, relatively painless, and well tolerated. Some ophthalmic techniques can be performed only by laser while others have a lower morbidity than alternative treatments. Peripheral retinal photocoagulation and focal photocoagulation now offer greatly improved visual prognosis for diabetic patients with proliferative diabetic retinopathy or diabetic macular disease. Selected cases of macular degeneration may be treated by focal laser photocoagulation. The role of lasers in treating sub-retinal neovascular membranes is limited by the extent and location of the membrane at presentation and the high risk of recurrence after treatment. Patients with distorted vision must be referred urgently for specialist ophthalmic assessment. Flat retinal holes and tears may be sealed by laser therapy, thus preventing retinal detachment. Short pulsed neodymium-YAG photodisruptive capsulotomy effectively clears the visual axis of thickened posterior lens capsule after cataract surgery. Short pulsed neodymium-YAG photodisruptive iridotomy may be used to treat and prevent angle closure glaucoma. Laser trabeculoplasty aids the control of open angle glaucoma. Research is continuing into the role of other lasers in managing open angle glaucoma and of photoablative lasers in treating refractive errors and superficial corneal disorders.     

雷珠单抗联合Ahmed青光眼阀植入术对新生血管性青光眼患者眼动脉血流动力学和血清VEGF、PDGF的影响

摘要 目的：观察雷珠单抗联合Ahmed青光眼阀植入术治疗新生血管性青光眼（NVG）的疗效及对眼动脉血流动力学和血清血管内皮生长因子（VEGF）、血小板衍生生长因子（PDGF）的影响。方法：选择2018年4月~2021年2月期间华中科技大学同济医学院附属协和医院眼科收治的NVG患者60例94眼,采用随机数字表法将患者分为对照组和研究组,分别为30例48眼和30例46眼。对照组患者予以Ahmed青光眼阀植入术,研究组眼内注射雷珠单抗一周后再行Ahmed青光眼阀植入术,观察治疗效果,对比两组眼动脉血流动力学和血清VEGF、PDGF,观察虹膜与前房角新生血管消退率及并发症发生率。结果：研究组的疗效明显优于对照组（P<0.05）。研究组治疗后3个月血流阻力系数（RI）低于对照组,收缩期峰值流速（PSV）、舒张末期流速（EDV）高于对照组（P<0.05）。治疗后3个月两组VEGF、PDGF均下降,且研究组低于对照组（P<0.05）。治疗后3个月两组眼压下降,视力升高,且研究组的改善程度优于对照组（P<0.05）,研究组虹膜与前房角新生血管消退率高于对照组（P<0.05）。研究组的并发症发生率少于对照组（P<0.05）。结论：NVG采用Ahmed青光眼阀植入术联合雷珠单抗治疗,可有效恢复视力、眼压,具有更好的疗效,这可能与联合治疗可改善眼动脉血流动力学及血清VEGF、PDGF水平有关。     

Cyclic nucleotides in experimental glaucoma

cAMP and cGMP contents were studied in various eye tissues of rabbits with experimental glaucoma induced by chronic intravenous adrenaline administration. Cyclic nucleotide level was measured in the retina, choroid, iris and ciliary body. An increase in the tissue cAMP level was found especially in the iris and ciliary body. An increase in tissue cAMP content is explained by an enhanced beta-adrenergic regulation in the eyes of rabbits with experimental glaucoma. No consistent changes were found in cGMP content in eye tissues.     

Confirmation of linkage to 1q21-31 in a Danish autosomal dominant juvenile-onset glaucoma family and evidence of genetic heterogeneity

Autosomal dominant juvenile-onset open-angle glaucoma has been mapped to 1q21-31 in a number of American families. Our study confirms linkage in a Danish five-generation dominant juvenile-onset glaucoma family with a maximum two-point lod score of 6.67 at the D1S210 locus. Multipoint linkage analysis in a nine-generation Swedish family with dominant juvenile-onset glaucoma and iris hypoplasia excludes linkage to the region of approximately 18 cM between loci D1S104 and D1S218, shown to contain the previously mapped glaucoma gene. This study thus provides support for genetic heterogeneity with respect to dominant juvenile-onset glaucoma.     

Genetic context determines susceptibility to intraocular pressure elevation in a mouse pigmentary glaucoma

Background  

DBA/2J (D2) mice develop an age-related form of glaucoma. Their eyes progressively develop iris pigment dispersion and iris atrophy followed by increased intraocular pressure (IOP) and glaucomatous optic nerve damage. Mutant alleles of the Gpnmb and Tyrp1 genes are necessary for the iris disease, but it is unknown whether alleles of other D2 gene(s) are necessary for the distinct later stages of disease. We initiated a study of congenic strains to further define the genetic requirements and disease mechanisms of the D2 glaucoma.     

The mouse anterior chamber angle and trabecular meshwork develop without cell death

Background

The iridocorneal angle forms in the mammalian eye from undifferentiated mesenchyme between the root of the iris and cornea. A major component is the trabecular meshwork, consisting of extracellular matrix organized into a network of beams, covered in trabecular endothelial cells. Between the beams, channels lead to Schlemm's canal for the drainage of aqueous humor from the eye into the blood stream. Abnormal development of the iridocorneal angle that interferes with ocular fluid drainage can lead to glaucoma in humans. Little is known about the precise mechanisms underlying angle development. There are two main hypotheses. The first proposes that morphogenesis involves mainly cell differentiation, matrix deposition and assembly of the originally continuous mesenchymal mass into beams, channels and Schlemm's canal. The second, based primarily on rat studies, proposes that cell death and macrophages play an important role in forming channels and beams. Mice provide a potentially useful model to understand the origin and development of angle structures and how defective development leads to glaucoma. Few studies have assessed the normal structure and development of the mouse angle. We used light and electron microscopy and a cell death assay to define the sequence of events underlying formation of the angle structures in mice.

Results

The mouse angle structures and developmental sequence are similar to those in humans. Cell death was not detectable during the period of trabecular channel and beam formation.

Conclusions

These results support morphogenic mechanisms involving organization of cellular and extracellular matrix components without cell death or atrophy.