Selective laser trabeculoplasty in the treatment of pseudoexfoliation glaucoma in patients allergic to all anti-glaucoma drops

Secondary chronic open-angle glaucoma associated with pseudoexfoliation (PEX) syndrome accounts for approximately 25% of all glaucomas and represents the most common identifiable cause of glaucoma overall. Selective laser trabeculoplasty (SLT) is effective in reducing intraocular pressure (IOP) in glaucomatous patients and has the advantage of preserving surrounding structures. We report here SLT treatment of a 82 year old female with a secondary developed open-angle pseudoexfoliation glaucoma allergic to all anti glaucoma eye drops especially those which contain bensalconium chloridum as preservative. Since patient was allergic also to methyl-cellulose, we performed SLT with water as a mediator. Patient had PEX syndrome for 10 years, immature cataracts on both eyes, and best corrected visual acuity (BCVA) 0.7 on the right and 0.2 on the left eye. We have monitored intraocular pressure (IOP), the changes in the visual field and optic nerve. Preoperative IOP was 28 mmHg on the right and 30 mmHg on the left eye. The follow up period was 24 months with time points for measured parameters every 3 months. After 18 months IOP remained in the normal values (average 17 mmHg) on the right eye, but on the left eye it increased up to 28 mmHg. SLT re-treatment was carried out on the left eye and the IOP stabilized again on the values between 16-18mmHg. There were no significant change in the visual field and optic nerve configuration before and after SLT (C/D value for right eye: 0.3-0.4; C/D left eye: 0.5). Based on this case report, SLT seems to be very effective treatment for maintaining regular IOP in patient with PEX who is allergic to all types of medications.     

Experimental Glaucoma Induced by Ocular Injection of Magnetic Microspheres

Progress in understanding the pathophysiology, and providing novel treatments for glaucoma is dependent on good animal models of the disease. We present here a protocol for elevating intraocular pressure (IOP) in the rat, by injecting magnetic microspheres into the anterior chamber of the eye. The use of magnetic particles allows the user to manipulate the beads into the iridocorneal angle, thus providing a very effective blockade of fluid outflow from the trabecular meshwork. This leads to long-lasting IOP rises, and eventually neuronal death in the ganglion cell layer (GCL) as well as optic nerve pathology, as seen in patients with the disease. This method is simple to perform, as it does not require machinery, specialist surgical skills, or many hours of practice to perfect. Furthermore, the pressure elevations are very robust, and reinjection of the magnetic microspheres is not usually required unlike in some other models using plastic beads. Additionally, we believe this method is suitable for adaptation for the mouse eye.     

Pharmacotherapies for glaucoma

Glaucoma is a group of progressive optic neuropathies in which the axons in the optic nerve are injured, retinal ganglion cell numbers are reduced and vision is gradually and permanently lost. The only approved and effective way to treat glaucoma is to reduce the intraocular pressure (IOP). This is usually accomplished by surgical and/or pharmacological means. Drugs designed to reduce IOP target one or more of the parameters that maintain it. These parameters (collectively known as aqueous humor dynamics) are the production rate of aqueous humor, the pressure in the episcleral veins and the drainage of aqueous humor through the trabecular or uveoscleral outflow pathways. Intraocular pressure lowering drugs can be classified as inflow or outflow depending on whether they reduce aqueous humor inflow into the anterior chamber or improve aqueous humor outflow from the anterior chamber. Inflow drugs, like β adrenergic antagonists and carbonic anhydrase inhibitors, reduce the rate of aqueous humor production. Outflow drugs, like prostaglandin analogs, cholinergic agonists and sympathomimetics, increase the rate of drainage through the uveoscleral outflow pathway and/or increase the facility of outflow through the trabecular meshwork. Some drugs have mixed inflow/outflow effects. This review summarizes the pharmacological treatments for glaucoma in use today and some new drugs showing potential for use in the future.     

Trabeculectomy with mitomycin C in glaucoma associated with uveitis

The patients with uveitic glaucoma are at high risk for failure following drainage surgery because of young age of these patients, preoperative long-term control of inflammation and postoperative complications. Twenty-two trabeculectomies performed in 22 patients with uveitic glaucoma were retrospectively evaluated to analyze the effect of intraoperative application of mitomycin C (MMC). Success rates, postoperative levels of intraocular pressure (IOP) and postoperative complications were studied. After a mean follow-up of 10.6 months (range, 5-28 months), 15 patients (68.2%) achieved IOP of 21mmHg or less without antiglaucoma medications. There were statistically significant reduction in IOP postoperatively during the period studied (p < 0.001). Early postoperative complications included chorioidal detachment (9.1%), shallow anterior chamber (9.1%), hyphema (13.6%), macular edema (4.5%) and raised IOP (27.3%). Late postoperative complications included exacerbation of uveitis (4.5%), macular edema (4.5%), cataract (22.7%) and raised IOP (31.8%). The eyes with raised IOP needed additional antiglaucoma medication. The results of this retrospective and uncontrolled study suggest that intraoperative application of MMC may be a good option for enhancement of short-term trabeculectomy success rates in patients with uveitic glaucoma.     

Metal chelator combined with permeability enhancer ameliorates oxidative stress-associated neurodegeneration in rat eyes with elevated intraocular pressure

Because as many as half of glaucoma patients on intraocular pressure (IOP)-lowering therapy continue to experience optic nerve toxicity, it is imperative to find other effective therapies. Iron and calcium ions play key roles in oxidative stress, a hallmark of glaucoma. Therefore, we tested metal chelation by means of ethylenediaminetetraacetic acid (EDTA) combined with the permeability enhancer methylsulfonylmethane (MSM) applied topically on the eye to determine if this noninvasive treatment is neuroprotective in rat optic nerve and retinal ganglion cells exposed to oxidative stress induced by elevated IOP. Hyaluronic acid (HA) was injected into the anterior chamber of the rat eye to elevate the IOP. EDTA–MSM was applied topically to the eye for 3 months. Eyeballs and optic nerves were processed for histological assessment of cytoarchitecture. Protein–lipid aldehyde adducts and cyclooxygenase-2 (COX-2) were detected immunohistochemically. HA administration increased IOP and associated oxidative stress and inflammation. Elevated IOP was not affected by EDTA–MSM treatment. However, oxidative damage and inflammation were ameliorated as reflected by a decrease in formation of protein–lipid aldehyde adducts and COX-2 expression, respectively. Furthermore, EDTA–MSM treatment increased retinal ganglion cell survival and decreased demyelination of optic nerve compared with untreated eyes. Chelation treatment with EDTA–MSM ameliorates sequelae of IOP-induced toxicity without affecting IOP. Because most current therapies aim at reducing IOP and damage occurs even in the absence of elevated IOP, EDTA–MSM has the potential to work in conjunction with pressure-reducing therapies to alleviate damage to the optic nerve and retinal ganglion cells.     

超声乳化手术治疗慢性闭角型青光眼合并白内障的临床疗效分析

目的:探讨超声乳化手术治疗慢性闭角型青光眼合并白内障的临床效果。方法:慢性闭角型青光眼合并白内障64例(64眼)根据治疗方法的不同分为治疗组与对照组各32例,对照组采用传统小梁切除手术,治疗组采用超声乳化手术。结果:(1)两组术前视力对比无明显差异,治疗后视力情况都明显改善,同时组间对比有明显差异(P0.05)。(2)两组术前眼压比较无显著性差异,术后两组组间与组内对比都有明显差异(P0.05)。(3)两组术前前房深度比较无显著性差异,治疗后都有明显上升(P0.05),同时组间对比差异明显(P0.05)。(4)两组患者术中与术后都无严重并发症发生。结论:对于慢性闭角型青光眼合并白内障患者行超声乳化手术具备加深前房、控制眼压、提高视力的作用,同时安全性好,可作为标准治疗选择。     

Mapping Molecular Differences and Extracellular Matrix Gene Expression in Segmental Outflow Pathways of the Human Ocular Trabecular Meshwork

Elevated intraocular pressure (IOP) is the primary risk factor for glaucoma, and lowering IOP remains the only effective treatment for glaucoma. The trabecular meshwork (TM) in the anterior chamber of the eye regulates IOP by generating resistance to aqueous humor outflow. Aqueous humor outflow is segmental, but molecular differences between high and low outflow regions of the TM are poorly understood. In this study, flow regions of the TM were characterized using fluorescent tracers and PCR arrays. Anterior segments from human donor eyes were perfused at physiological pressure in an ex vivo organ culture system. Fluorescently-labeled microspheres of various sizes were perfused into anterior segments to label flow regions. Actively perfused microspheres were segmentally distributed, whereas microspheres soaked passively into anterior segments uniformly labeled the TM and surrounding tissues with no apparent segmentation. Cell-tracker quantum dots (20 nm) were localized to the outer uveal and corneoscleral TM, whereas larger, modified microspheres (200 nm) localized throughout the TM layers and Schlemm’s canal. Distribution of fluorescent tracers demonstrated a variable labeling pattern on both a macro- and micro-scale. Quantitative PCR arrays allowed identification of a variety of extracellular matrix genes differentially expressed in high and low flow regions of the TM. Several collagen genes (COL16A1, COL4A2, COL6A1 and 2) and MMPs (1, 2, 3) were enriched in high, whereas COL15A1, and MMP16 were enriched in low flow regions. Matrix metalloproteinase activity was similar in high and low regions using a quantitative FRET peptide assay, whereas protein levels in tissues showed modest regional differences. These gene and protein differences across regions of the TM provide further evidence for a molecular basis of segmental flow routes within the aqueous outflow pathway. New insight into the molecular mechanisms of segmental aqueous outflow may aid in the design and delivery of improved treatments for glaucoma patients.     

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.     

Homozygous mutations in PXDN cause congenital cataract, corneal opacity, and developmental glaucoma

Anterior segment dysgenesis describes a group of heterogeneous developmental disorders that affect the anterior chamber of the eye and are associated with an increased risk of glaucoma. Here, we report homozygous mutations in peroxidasin (PXDN) in two consanguineous Pakistani families with congenital cataract-microcornea with mild to moderate corneal opacity and in a consanguineous Cambodian family with developmental glaucoma and severe corneal opacification. These results highlight the diverse ocular phenotypes caused by PXDN mutations, which are likely due to differences in genetic background and environmental factors. Peroxidasin is an extracellular matrix-associated protein with peroxidase catalytic activity, and we confirmed localization of the protein to the cornea and lens epithelial layers. Our findings imply that peroxidasin is essential for normal development of the anterior chamber of the eye, where it may have a structural role in supporting cornea and lens architecture as well as an enzymatic role as an antioxidant enzyme in protecting the lens, trabecular meshwork, and cornea against oxidative damage.     

Ischemic tolerance protects the rat retina from glaucomatous damage

Glaucoma is a leading cause of acquired blindness which may involve an ischemic-like insult to retinal ganglion cells and optic nerve head. We investigated the effect of a weekly application of brief ischemia pulses (ischemic conditioning) on the rat retinal damage induced by experimental glaucoma. Glaucoma was induced by weekly injections of chondroitin sulfate (CS) in the rat eye anterior chamber. Retinal ischemia was induced by increasing intraocular pressure to 120 mmHg for 5 min; this maneuver started after 6 weekly injections of vehicle or CS and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. Glaucoma was evaluated in terms of: i) intraocular pressure (IOP), ii) retinal function (electroretinogram (ERG)), iii) visual pathway function (visual evoked potentials, (VEPs)) iv) histology of the retina and optic nerve head. Retinal thiobarbituric acid substances levels were assessed as an index of lipid peroxidation. Ischemic conditioning significantly preserved ERG, VEPs, as well as retinal and optic nerve head structure from glaucomatous damage, without changes in IOP. Moreover, ischemia pulses abrogated the increase in lipid peroxidation induced by experimental glaucoma. These results indicate that induction of ischemic tolerance could constitute a fertile avenue for the development of new therapeutic strategies in glaucoma treatment.     

超声乳化联合房角分离治疗急性闭角型青光眼的临床观察

目的:观察和比较白内障超声乳化吸除人工晶状体植入术联合前房角分离术或小梁切除术治疗原发性急性闭角型青光眼合并白内障的临床疗效。方法:选择哈尔滨医科大学附属第一医院眼科医院2017年1月～2017年11月收治的原发性急性闭角型青光眼合并白内障患者62例,根据手术方式不同将其随机分为A、B两组,A组(31例,行Phaco+IOL联合前房角分离术);B组(31例,行Phaco+IOL联合小梁切除术)。分别观察两组患者术前术后最佳矫正视力(BCVA)、眼压(IOP)、前房深度(ACD)、角膜内皮细胞密度(ECD)的变化。结果:两组患者术后3天、3个月BCVA及IOP和术前比较均明显提高(P0.05),IOP控制至正常范围。且术后1周,A组视力恢复及眼压控制均优于B组(P0.05)。两组患者术后3月,ACD及ECD均较术前明显变化,ACD加深,ECD减少(P0.05),且A组ACD明显高于B组(P0.05)。结论:Phaco+IOL联合前房角分离术治疗急性闭角型青光眼合并白内障患者能有效降低眼压,在早期即可获得较好的临床效果。     

Effects of intravitreous sodium hydrosulfide on intraocular pressure and retinopathy in ocular hypertensive rats

We investigated the possible neuroprotectant and intraocular pressure (IOP) lowering effects of intravitreous injection of sodium hydrosulfide (NaSH) in a rodent model of experimental glaucoma. Glaucoma currently is treated by controlling IOP using medications and/or surgery. These methods are not entirely adequate for all patients. We divided 24 rats into three groups. For the control group, the right eye was treated with intravitreous saline. For the glaucoma group, ocular hypertension was induced by photocoagulating three episcleral veins and the limbal plexus of the right eye using an argon laser, then saline was injected into the vitreous of these eyes during the third week. For the NaSH group, rats were treated with intravenous NaSH 3 weeks after photocoagulation. IOP was measured each week during the 6 week experimental period. Coagulating the episcleral veins rapidly increased the IOP of rat eyes. Intravitreous injection of NaSH significantly reduced IOP. Intravitreous NaSH prevented degeneration of the retina and decreased the number of apoptotic cells. Intravitreous NaSH appeared to reduce IOP and to prevent IOP induced retinopathy in rats.     

兔先天性青光眼的临床研究

目的 总结兔先天性青光眼的临床特点。方法 对先天性青光眼兔和正常兔进行临床观察,研究其在眼压、眼球结构、视功能方面的变化。结果 青光眼兔的眼压明显升高,角膜直径变大,前房变深,眼轴变长,房角变宽,眼底视乳头损害明显,视觉诱发电位明显异常。结论 兔先天性青光眼的房水排泄障碍部位可能在小梁,兔眼球壁对高眼压的耐受力弱,在高眼压下容易出现眼球扩张,视功能损害。     

The Effect of Zeaxanthin on the Visual Acuity of Zebrafish

Oral supplementation of carotenoids such as zeaxanthin or lutein which naturally occur in human retina have been shown to improve vision and prevent progression of damage to advanced AMD in some studies. The zebrafish eye shares many physiological similarities with the human eye and is increasingly being used as model for vision research. We hypothesized that injection of zeaxanthin into the zebrafish eye would improve the visual acuity of the zebrafish over time. Visual acuity, calculated in cycles per degree, was measured in adult zebrafish to establish a consistent baseline using the optokinetic response. Zeaxanthin dissolved into phosphate buffered saline (PBS) or PBS only was injected into the anterior chamber of the right and left eyes of the Zebrafish. Visual acuities were measured at 1 week and 3, 8 and 12 weeks post-injection to compare to baseline values. Repeated measures ANOVA was used to compare visual acuities between fish injected with PBS and zeaxanthin. A significant improvement in visual acuity, 14% better than before the injection (baseline levels), was observed one week after injection with zeaxanthin (p = 0.04). This improvement peaked at more than 30% for some fish a few weeks after the injection and improvement in vision persisted at 3 weeks after injection (p = 0.006). The enhanced visual function was not significantly better than baseline at 8 weeks (p = 0.19) and returned to baseline levels 12 weeks after the initial injection (p = 0.50). Zeaxanthin can improve visual acuity in zebrafish eyes. Further studies are required to develop a better understanding of the role zeaxanthin and other carotenoids play during normal visual function.     

单切口和双切口联合手术对闭角型青光眼合并白内障患者视力、IOP及CCT的影响

目的:探讨单切口和双切口联合手术对闭角型青光眼合并白内障患者视力、眼压(IOP)及中央前房深度(CCT)的影响。方法:选择2013年6月至2016年6月我院收治的90例闭角型青光眼合并白内障患者,随机分为观察组和对照组,每组各45例。对照组采用单切口手术治疗,观察组采用双切口手术治疗。观察并比较两组患者治疗前后角膜内皮细胞密度、面积、最佳矫正视力、裸眼视力、IOP以及术后并发症的发生率。结果:与术前比较,两组患者术后角膜内皮细胞密度均升高,且观察组高于对照组,差异具有统计学意义(P0.05);与术前比较,两组患者术后角膜内皮细胞面积均减小,且观察组小于对照组,差异具有统计学意义(P0.05);与术前比较,两组患者术后最佳矫正视力、裸眼视力均升高,且观察组高于对照组,差异具有统计学意义(P0.05);与术前比较,两组患者术后IOP均降低,且观察组低于对照组,差异具有统计学意义(P0.05);与术前比较,两组患者术后CCT均升高,且观察组高于对照组,差异具有统计学意义(P0.05);观察组术后并发症总发生率低于对照组(P0.05)。结论:双切口手术治疗闭角型青光眼合并白内障的效果显著,能够有效改善患者视力、IOP及CCT水平,且安全性高,值得临床推广。     

不同手术方式治疗青光眼的临床疗效比较

目的探讨单纯小梁切除术与复合式小梁切除术治疗青光眼的临床疗效。方法将2015年6月~2016年5月我院收治行手术治疗的74例青光眼患者作为研究对象,按手术方案不同分为两组,A组行单纯小梁切除术,B组行复合式小梁切除术,评价比较两组临床治疗效果。结果 B组浅前房发生率为5.40%明显低于A组的24.32%,功能性滤过泡率为91.89%明显高于A组的72.97%,眼压完全控制率为89.19%明显高于A组的64.86%,差异均有统计学意义(均P0.05)。结论复合式小梁切除术治疗青光眼的临床疗效较单纯小梁切除术更为显著。     

A passive pressure sensor for continuously measuring the intraocular pressure in glaucomatous patients

ObjectiveThe main risk factor for the development of glaucoma, a retinal disease leading to blindness, is an increase in the intraocular pressure (IOP). Reducing this IOP can be obtained by eye drops but unfortunately the disease can still progress because IOP increases are painless, can fluctuate and, thus remain undetected during a visit to an ophthalmologist. The “MATEO” ANR project aims to develop sensors embedded in a contact lens for continuously IOP monitoring.Materials and methodsPressure sensors were produced by MEMS technology and tested with pig eyes obtained at a local slaughterhouse. Solution was injected by 50 μL steps in the eye with a Hamilton syringe while IOP was monitored in parallel with a TonoVET system and an industrial pressure transducer inserted in the injection tubing system.ResultsOur first pressure sensor prototypes were generated and inserted in a lens compatible with eye application. A wireless system was developed to excite the sensor. At same time, it was recorded the data in components inserted into spectacles and a pocket recorder. In parallel, we showed that injecting a solution in the eye anterior chamber triggered an IOP increase smaller and more stable than injections in the posterior chamber. Finally, a direct correlation was observed between IOP measured on the corneal surface with the TonoVET and the pressure transducer placed close to eye injection point.DiscussionOur results indicate that our in vitro model on pig eyes is adequate to test our new lens sensor. Finally, the pressure sensor was successfully inserted in contact lens opening the way for their in vitro and in vivo preclinical validation.     

Allometry and Scaling of the Intraocular Pressure and Aqueous Humour Flow Rate in Vertebrate Eyes

In vertebrates, intraocular pressure (IOP) is required to maintain the eye into a shape allowing it to function as an optical instrument. It is sustained by the balance between the production of aqueous humour by the ciliary body and the resistance to its outflow from the eye. Dysregulation of the IOP is often pathological to vision. High IOP may lead to glaucoma, which is in man the second most prevalent cause of blindness. Here, we examine the importance of the IOP and rate of formation of aqueous humour in the development of vertebrate eyes by performing allometric and scaling analyses of the forces acting on the eye during head movement and the energy demands of the cornea, and testing the predictions of the models against a list of measurements in vertebrates collated through a systematic review. We show that the IOP has a weak dependence on body mass, and that in order to maintain the focal length of the eye, it needs to be an order of magnitude greater than the pressure drop across the eye resulting from gravity or head movement. This constitutes an evolutionary constraint that is common to all vertebrates. In animals with cornea-based optics, this constraint also represents a condition to maintain visual acuity. Estimated IOPs were found to increase with the evolution of terrestrial animals. The rate of formation of aqueous humour was found to be adjusted to the metabolic requirements of the cornea, scaling as Vac0.67, where V_ac is the volume of the anterior chamber. The present work highlights an interdependence between IOP and aqueous flow rate crucial to ocular function that must be considered to understand the evolution of the dioptric apparatus. It should also be taken into consideration in the prevention and treatment of glaucoma.