Various Forms Of Glaucoma Research Articles

Protective Effects of 7,8-Dihydroxyflavone on Retinal Ganglion and RGC-5 Cells Against Excitotoxic and Oxidative Stress

A preferential loss of retinal ganglion cells (RGCs) is observed in glaucoma and optic neuritis. Loss of tropomyosin-related kinase receptor B (TrkB)-mediated signaling has been implicated in this degeneration. Our study indicates that 7,8-dihydroxyflavone (7,8 DHF) robustly upregulates the TrkB signaling in the primary rat RGCs and the retinal neuronal precursor RGC-5 cell line by promoting phosphorylation of TrkB receptor, leading to enhanced TrkB receptor tyrosine kinase activity. The flavonoid derivative 7,8 DHF acts a potent TrkB agonist and upregulates the downstream AKT and MAPK/ERK survival signaling pathways in a TrkB-dependent manner in both primary rat RGCs as well as the RGC-5 cell line. Excitotoxicity and oxidative injury have been alleged in the specific RGC degeneration in various forms of glaucoma. A novel finding of this study is that treatment with 7,8 DHF protects these cells significantly from excitotoxic and oxidative stress-induced apoptosis and cell death. 7,8 DHF also promotes neuritogenesis by stimulating neurite outgrowth, suggesting a possible therapeutic strategy for protection of RGCs in various optic neuropathies.

Medical and surgical outcomes in childhood glaucoma: A population-based study

To describe the clinical and surgical outcomes among patients younger than 20 years of age diagnosed with glaucoma in a defined population during a 40-year period. The medical records of all patients (<20 years) diagnosed with glaucoma in Olmsted County, Minnesota, from January 1, 1965, through December 31, 2004, were retrospectively reviewed. Thirty children (45 eyes) were diagnosed with various forms of glaucoma during the 40-year study period. During a mean follow-up of 12.5 years (range, 7 days to 32 years), 18 (60%) of the 30 children underwent a mean of 2.7 surgeries (range, 1 to 10), including 6 (20%) patients whose sole surgery consisted of enucleation or evisceration for a blind, painful eye. Twenty-eight (93%) of the 30 children required medical management during the follow-up period, including 14 (47%) treated before their first surgery. At the final follow-up examination, 11 (37%) had a visual acuity of 20/200 or worse. The 10-year Kaplan-Meier risk of vision decreasing less than 20/200 in all glaucoma patients was 22.7% (95% CI, 0-40.9), and patients requiring any glaucoma surgery was 68.3% (95% CI, 42.4-82.6). In this population-based study of children diagnosed with glaucoma during a 40-year period, most patients required surgery, with few being successfully controlled by medications alone. A poor visual outcome or the loss of an eye was relatively common.

Evidence for RPGRIP1 gene as risk factor for primary open angle glaucoma

Glaucoma is a genetically heterogeneous disorder and is the second cause of blindness worldwide owing to the progressive degeneration of retinal ganglion neurons. Very few genes causing glaucoma were identified to this date. In this study, we screened 10 candidate genes of glaucoma between the D14S261 and D14S121 markers of chromosome 14q11, a critical region previously linked to primary open-angle glaucoma (POAG). Mutation analyses of two large cohorts of patients with POAG, normal tension glaucoma (NTG) and juvenile open-angle glaucoma (JOAG), and control subjects, found only association of non-synonymous heterozygous variants of the retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1) with POAG, NTG and JOAG. The 20 non-synonymous variants identified in RPGRIP1 were all distinct from variants causing photoreceptor dystrophies and were found throughout all but one domain (RPGR-interacting domain) of RPGRIP1. Among them, 14 missense variants clustered within or around the C2 domains of RPGRIP1. Yeast two-hybrid analyses of a subset of the missense mutations within the C2 domains of RPGRIP1 shows that five of them (p.R598Q, p.A635G, p.T806I, p.A837G and p.I838V) decrease the association of the C2 domains with nephrocystin-4 (NPHPH). When considering only these five confirmed C2-domain mutations, the association remains statistically significant (P=0.001). Altogether, the data support that heterozygous non-synonymous variants of RPGRIP1 may cause or increase the susceptibility to various forms of glaucoma and that among other factors, physical impairment of the interaction of RPGRIP1with different proteins may contribute to the pathogenesis of forms of glaucoma.

Profile of preservative‐free TafluprostTM

AbstractProstaglandin analogues are the most commonly used treatment choice in various forms of glaucoma. They have gained their popularity mostly by their efficacy, once a day dosing and their high systemic tolerability. However, the topical tolerability of the glaucoma drugs are in general is an issue; not only on the basis of quality of life of the patients but also as a factor of adherence and overall success of the glaucoma therapy. Tafluprost is a novel prostaglandin analogue. It has a high affinity and potent agonistic activity for prostaglandin F receptor. In non‐clinical and clinical phase !/II/III studies, tafluprost has shown an excellent IOP‐lowering effect. As a difluorinated prostaglandin analogue Tafluprost has also unique stability which makes it suitable for preservative free formulation. In this formulation it is proven to be efficacious and safe. In patients having ocular surface problems with a preserved prostaglandin analogue, a switch to preservative free tafluprost has shown to significantly reduce both symptoms and signs of ocular surface disease. Preservative‐free formulations of glaucoma drugs, now available also as a prostaglandin analogue, are tools in our armamentarium to target our medical management of glaucoma to balanced long term efficacy and safety.

Anti-VEGF therapy for glaucoma

The role of antivascular endothelial growth factor (anti-VEGF) agents in treating various ophthalmic diseases is currently being investigated. There have been many advances in the understanding of how anti-VEGF agents work and speculation on when to implement them clinically for neovascular glaucoma. Recent studies exploring the utility of anti-VEGF agents for wound modulation after trabeculectomy reveal promising results. Anti-VEGF agents have been shown to be beneficial in treating neovascular glaucoma. Their use leads to regression of both iris and angle neovascularization, intraocular pressure control when the angle remains open and, in many cases, prompts symptomatic improvement. In addition, research on the wound modulatory properties of anti-VEGF agents has revealed a dose-dependent inhibition of fibroblast proliferation. Studies exploring the use of anti-VEGF agents at time of trabeculectomy or in bleb revision procedures suggest a beneficial effect on bleb survival and subsequent improvement in intraocular pressure control. Prospective randomized clinical trials are still needed. The recent use of anti-VEGF agents for neovascular glaucoma as well as wound modulation after trabeculectomy has shown great promise. Through future research, the antiangiogenic and antifibroblastic properties of anti-VEGF agents may prove to be beneficial in patients being treated for various forms of glaucoma.

Prevalence of Glaucoma in the Wroclaw Population. The Wroclaw Epidemiological Study

Purpose: Primarily to determine the prevalence of various types of glaucoma and ocular hypertension in Wroclaw inhabitants aged 40–79 years. The second aim of the study was to determine the number of undiagnosed glaucoma cases in this population. Methods: A representative group of the Wroclaw population (4853 people aged from 40 to 79 years) was recruited by a proportional simple random sampling selection with stratification. All participants underwent the first, screening-stage examination, which included a medical history interview, intraocular pressure (IOP) measurement, anterior chamber depth assessment by the Van Herrick technique, and optic nerve head (ONH) assessment by means of indirect ophthalmoscopy (Volk's lens), confocal scanning laser ophthalmoscopy with a Heidelberg Retinal Tomograph (HRT) and scanning laser polarimetry by the GDx Nerve Fiber Analyzer (GDx). The second stage, in glaucoma-suspect patients only, included best corrected visual acuity, static perimetry, 24-hour monitoring of IOP, gonioscopy, and full eye examination with mydriasis. Glaucoma was diagnosed by the presence of any two of the following: characteristic morphological changes in the optic disc, glaucomatous visual field abnormalities, and intraocular pressure greater than 21 mmHg. Results: The overall prevalence of glaucoma was 1.6% (79 subjects). The prevalence increased with age from 0.4% in subjects belonging to the age group 40–49 years to 4.6% in people aged between 70 and 79 years. The prevalence of definite primary open-angle glaucoma was 1.0% (49 subjects). Normal-pressure glaucoma was diagnosed in 13 subjects (0.3%). Ocular hypertension was diagnosed in 92 subjects (1.9%). Conclusion: The prevalence of the different types of glaucoma was similar to that found in other white populations. Among the subjects examined, 79 had various forms of glaucoma and 71% of them had not previously been diagnosed. Undiagnosed glaucoma is a serious public health problem in Poland.

Genetics And Glaucoma

The recent advances of the human genome project have made genetic analysis of many human disorders possible. A genetic approach is especially productive when the quantity or accessibility of diseased tissues is limited. One aspect of the molecular approach that has been particularly important to glaucoma research is that only DNA from affected individuals and their relatives is required for analysis. Genetic approaches investigate the disease process at the DNA level and do not require samples of diseased tissues or even knowledge about how the disease may affect particular tissues. Collecting sufficient quantities of trabecular meshwork to perform biochemical and cellular studies, however, has been difficult. Moreover, tissue specimens taken from affected patients undergoing glaucoma surgery have been exposed to numerous medical and laser treatments that could obscure the initial abnormalities associated with the disease. Glaucoma research has been slowed because of the scarcity of trabecular meshwork and the inaccessibility of the retinal ganglion cells. Specific gene defects can be identified using DNA purified from lymphocytes obtained from a routine blood sample. The study of genes responsible for glaucoma will identify the role of specific protein products in the development of the disease without requiring direct access to ocular tissue. The identification of specific gene defects and the resulting abnormal protein products that are responsible for the various forms of glaucoma will help elucidate the underlying disease mechanisms. The identification and characterization of glaucoma susceptibility genes will also lead to new methods of diagnosis and treatment. The demonstration that the function of a particular enzyme or structural protein is impaired in glaucoma patients may lead to the development of new drug therapy. The identification of DNA sequence changes associated with the disease could form the basis of diagnostic tests useful for the identification of individuals at risk. The availability of such tests would provide a mechanism for early detection and treatment. Those individuals at risk who are identified early in the course of the disease and who begin therapy before significant damage to the optic nerve occurs will have the best chance of maintaining useful sight.

Gradual Painless Visual Loss: Glaucoma

Glaucoma is one of the leading causes of blindness in adult Americans. This disease remains undetected in one half of the people with this disease. Primary open angle glaucoma is the most common form of the disease. Patients at risk for glaucoma usually have one or more of the following characteristics: advanced age, diabetes, myopia, elevated intraocular pressure, large cup to disc ratio, and a positive family history of the disease. Presently in the United States, treatment for primary open angle glaucoma is usually medical. Six classes of glaucoma medications are available, all of which have side effects. The second most prevalent form of glaucoma is angle closure glaucoma, the treatment for which is usually surgical. Although a cure for the various forms of glaucoma does not exist, an awareness of the problem and early detection and treatment minimize the impact of the disease.

Safety and Efficacy of Mitomycin C Trabeculectomy in Southern India: A Short-term Pilot Study

Glaucoma is a major cause of blindness in developing nations. Medical and laser therapy have limitations in this environment. Filtration surgery alone often fails in young, darkly pigmented, individuals. The authors, therefore, evaluated the safety and efficacy of filtration surgery, using topical mitomycin C, in patients undergoing trabeculectomy in India. A short-term pilot study used mitomycin C at the time of trabeculectomy in a population of southern Indians with various forms of glaucoma. A single 5-minute intraoperative application of 0.4 mg/ml mitomycin C was given to 76 consecutive patients requiring filtration surgery for the control of intraocular pressure (IOP). All patients were admitted for 6 days and were seen at 6-week intervals for a minimum of 18 weeks. The mean preoperative IOP was 35.3 +/- 9.6 mmHg. Postoperative IOP control was attained in 93.4% of patients as defined by an IOP of 20 mmHg or less without additional glaucoma medications (or an IOP reduction > 25% if the preoperative IOP was < or = 20 mmHg). No corneal epithelial defects or wound leaks were seen. The major complications were cataract formation and a decreased visual acuity in ten (13%) eyes. Mitomycin C-aided trabeculectomy was highly successful in controlling IOP in this darkly pigmented population and may become an important adjunct in the treatment of glaucoma in developing countries.

Ultrasound Biomicroscopy in Pseudophakic Malignant Glaucoma

Malignant glaucoma (ciliary block glaucoma; aqueous misdirection glaucoma) is an incompletely understood, rare and serious complication of intraocular surgery. A woman with pseudophakic malignant glaucoma underwent successful neodymium: YAG (Nd:YAG) laser photodisruption of the anterior hyaloid face with resolution of the glaucoma. High-resolution ultrasound biomicroscopy was used to image the anterior segment and anterior chamber angle before and after laser surgery. Ultrasound biomicroscopy provided cross-sectional images of the iris, posterior chamber intraocular lens (IOL), and ciliary body and their relative positions before and after resolution of the malignant glaucoma. Anterior rotation of the ciliary body and anterior chamber shallowing normalized after rupture of the anterior hyaloid face. High-resolution ultrasound biomicroscopy provided images consistent with accepted concepts of the pathophysiology of this disease and offers great promise for the future elucidation of the anatomic mechanisms underlying various forms of glaucoma.

Neodymium-YAG Laser Iridectomies in Glaucoma Associated With Closed or Occludable Angles

A review of our first 200 neodymium-YAG laser iridectomies performed over a two-year period in various forms of glaucoma showed patent iridectomies in 180 of 182 eyes (99% success) at the last examination (one to 26 months postoperatively). Both failures had preexisting chronic uveitis. Eighteen eyes were lost to follow-up. Complications included intraocular pressure increased more than 10 mm Hg in 54 eyes (30%), hemorrhage in 36 eyes (20%), iritis in 21 eyes (11.5%), posterior synechiae in 13 eyes (7%), corneal changes in seven eyes (4%), and pupillary distortion in six eyes (3%). With experience, fewer applications are required to penetrate the iris, and retreatment to obtain patency is less likely to be needed.

Argon Laser Trabeculoplasty in a Residency Program

The following article discusses the outcome of 60 eyes with various forms of glaucoma undergoing resident-performed argon laser trabeculoplasty (ALT). The majority (46/60) of eyes had primary open-angle glaucoma. Decrease in intraocular pressure (IOP) was not as great as reported in the literature. Our results suggest that initially treating 180 degrees of the angle is associated with improved overall results. ALT has proved to be a safe and effective alternative to conventional surgery for glaucoma in a residency training setting.

CONTROVERSY IN GLAUCOMA AND HLA

Early studies described the presence or absence of HLA associations in various forms of glaucoma. Recent reports from several countries indicate that there is no association between glaucoma and HLA.

Long-term results following goniotrepanation with a scleral flap (Elliot-Fronimopoulos)

The present paper reports on results obtained in 442 eyes which were followed up 3 to 9 years after goniotrepanation for various forms of glaucoma. The overall success rate in cases of primary glaucoma was 93 to 97%, with only a small number of intraoperative and postoperative complications; there were no severe complications such as visual field loss or endophthalmitis.

Klinische Einstellung und Langzeiterfahrungen mit Timolol*

The author reports the regulation of IOP in 31 patients using Timolol maleate. The patients were suffering from various forms of Glaucoma. It proved possible to stabilize IOP in 21 patients during clinical treatment. Follow-ups were continued for up to 31 weeks after discharge.

Progress in the treatment of glaucoma in my lifetime

A period of great progress in the diagnosis and treatment of glaucoma began in the 1920's with the development of gonioscopy apparatus and the slitlamp, and the first application of epinephrine in the treatment of the disease. With the development of precise methods for examination, differentiation among the various forms of glaucoma became possible, knowledge and theories regarding the nature and mechanisms of the disease became available, and medical and surgical approaches to treatment were developed with varying degrees of success. Major events and concepts in the management of glaucoma during the last 50 years are reviewed, including literature reports and the personal experiences of the authors and his colleagues.

Improvement of the co-efficient of outflow in glaucomatous eyes. Prolonged local treatment with epinephrine.

Epinephrine and other sympathomimetic amines have been used in the treatment of various forms of glaucoma for at least 30 years. Within the last 4 years uniform and reasonably stable preparations of racemic epinephrine bitartrate and l -epinephrine hydrochloride have become available widely for clinical use. When tonography was performed on patients in whom the intraocular pressure (IOP) had been lowered by the addition of one of these preparations to the therapeutic program, in the first few weeks the lowering of the pressure was in most cases the result of a reduction in the rate of production of aqueous humor. This effect has been described most recently by Becker and Ley. When the epinephrine treatment was continued for a period of weeks or months, a different effect was observed in that the pressure remained low and the facility of outflow (C) became larger. In a majority of the patients so treated,

Gonioscopy.

This book was commissioned by the Belgian Ophthalmological Society and is an excellent review of what is known of the filtration angle in the normal human subject and in the various forms of glaucoma. It is written in French, but contains an excellent bibliography of the world's literature. It is of interest to note that the majority of these references are to authors in this country. The first chapter deals with the anatomy of the normal angle. In the next chapter, the importance of the canal of Schlemm is considered, and various theories on the outflow of aqueous are enumerated. There is a good section on the aqueous veins. Noticeable for its absence is any reference to the work of Friedenwald, who, it will be remembered, was the first investigator to find efferent arteries to the canal of Schlemm. Chapter 3 deals with the technic of gonioscopy and chapter 4