Intraocular Hypertension Research Articles

The management of glaucoma and intraocular hypertension: current approaches and recent advances

In the last decade, numerous novel ocular hypotensive agents have been introduced for the control of intraocular pressure (IOP). Clinicians now have more options than ever in the selection of medical therapy for the treatment of glaucoma and ocular hypertension. When selecting an ocular hypotensive medication for their patients, clinicians should consider not only the IOP-lowering efficacy of an agent, but also the ability of the drug to allow patients to achieve target levels of IOP that are low enough to stop the progression of glaucomatous damage. Other considerations should include how well the drug controls diurnal IOP, the likelihood of serious adverse events, the versatility of the medication for use as an adjunctive agent, as well as other potential attributes (ie, neuroprotection).

Tratamiento de la hipertensión ocular infantil con colirio de brimonidina 0,2%

To evaluate the safety and efficacy of topical brimonidine 0.2% use in children. A descriptive study of twelve successive children (21 eyes) who needed topical treatment of intraocular hypertension, and where the use of b-blockers was contraindicated. During treatment we observed an average decrease of IOP of 5 SD 1.8 mmHg (21% of basal IOP), but found more common local symptoms, with stinging being complained of in 52.4% of cases. Somnolence was also complained of in two cases.

OCCULT WITH NO CLASSIC CHOROIDAL NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION TREATED BY INTRAVITREAL TRIAMCINOLONE AND PHOTODYNAMIC THERAPY WITH VERTEPORFIN

To examine combined treatment with intravitreal triamcinolone acetonide (IVT) and photodynamic therapy (PDT) for occult with no classic choroidal neovascularization (CNV) secondary to age-related macular degeneration. In this prospective, interventional case series, 11 eyes of 10 consecutive patients with occult with no classic CNV underwent a single injection (25 mg) of IVT followed 1 month later by PDT. Best-corrected visual acuity was measured by Early Treatment Diabetic Retinopathy Study (ETDRS) protocol refraction. Median best-corrected visual acuity was 20/160, 20/80, 20/80, 20/50, and 20/80 at baseline and 1, 3, 6, and 12 months, respectively. Best-corrected visual acuity at baseline was statistically different (P < 0.05) than best-corrected visual acuity at 1, 3, and 6 months. Of 11 eyes, 5 (45.5%), 7 (63.6%), 7 (63.6%), and 4 (36.3%) had improved best-corrected visual acuity of at least 3 ETDRS lines at 1, 3, 6, and 12 months, respectively, while 6 (54.5%), 9 (81.8%), 10 (91%), and 8 (73%) had improved best-corrected visual acuity of at least 2 ETDRS lines at 1, 3, 6, and 12 months, respectively. Two eyes (18%) lost >3 lines at 12 months. One eye had intraocular hypertension at 3 months and was treated with a combination of topical antiglaucomatous drugs. One eye developed a dense cataract at the last follow-up visit. No endophthalmitis, retinal detachment, or vitreous hemorrhage developed. Fluorescein leakage and retinal thickness reduced significantly after treatment. Improvement of best-corrected visual acuity and lack of fluorescein leakage suggest combination treatment with IVT and PDT for occult with no classic CNV merits further investigation.

Retinal Ganglion Cells and Supporting Elements in Culture

Elucidating the pathophysiology of glaucoma has traditionally relied on animal models of intraocular hypertension and optic nerve injury, which are closely related to the human disease with respect to tissue damage. However, cell culture models of retinal neurons (particularly retinal ganglion cells) and supporting cells (particularly retinal glia and lamina cribrosa cells), although less closely related to glaucoma pathophysiology, have particular advantages in understanding intracellular processes associated with glaucomatous optic neuropathy. Examples of studies which are more readily achievable with cultured cells include: 1) Isolation and separation of purified cells to help define the role of classes of cell types; 2) Transfection of genetic material to over-express or knockdown specific genes; 3) Fluorescent imaging of calcium concentrations, reactive oxygen species concentrations, mitochondrial membrane potential, cellular pH, and other measures of cellular physiology.

Vitrectomy combined with cataract surgery and intraocular lens implantation

目的 探讨玻璃体切除联合白内障摘出及人工晶状体植入术的临床效果.方法对16例(17眼)玻璃体视网膜疾病伴有明显的白内障者实施了此联合手术.先行常规白内障囊外摘出术或晶状体超声乳化术,再行标准三通道闭合式玻璃体切除术,最后植入人工晶状体.结果术后随访2月～3年,平均13月.16眼术后视力均有不同程度提高,1眼增生性糖尿病性视网膜病变术后2月因继发新生血管性青光眼,行广泛视网膜冷凝后视力下降.术后早期16例(17眼)均有不同程度的角膜后弹力层皱褶,术后7～10 d消失.2例(2眼)术后有一过性眼压升高.1例(1眼)术后2月发生新生血管性青光眼.3例(3眼)术后后囊浑浊,未影响视力.结论此联合手术的临床效果良好,具有一定的优点,但应严格掌握适应证,并要求有熟练的手术技巧。

2-(1-Hexyn-1-yl)adenosine-induced intraocular hypertension is mediated via K+ channel opening through adenosine A2A receptor in rabbits

The present study was performed to clarify the mechanism of change in intraocular pressure by 2-(1-hexyn-1-yl)adenosine (2-H-Ado), a selective adenosine A2 receptor agonist, in rabbits. 2-H-Ado (0.1%, 50 μl)-induced ocular hypertension (Emax: 7.7 mm Hg) was inhibited by an adenosine A2A receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine, ATP-sensitive K+ channel blocker glibenclamide or 5-hydroxydecanoic acid, but not by an adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A2B receptor antagonist alloxazine or a cyclooxygenase inhibitor indomethacin. The outflow facility induced by 2-H-Ado seems to be independent of increase in intraocular pressure or ATP-sensitive K+ channel. In contrast, the recovery rate in intraocular pressure decreased by hypertonic saline was accelerated by 2-H-Ado, and this response was dependent on ATP-sensitive K+ channel. These results suggest that 2-H-Ado-induced ocular hypertension is mediated via K+ channel opening through adenosine A2A receptor, and this is probably due to aqueous formation, but independent of change in outflow facility or prostaglandin production.

The Economic Burden of Glaucoma and Ocular Hypertension

This paper reviews the burden and economic consequences of glaucoma upon healthcare systems and patients, especially elderly patients. An extensive review of the literature was conducted, primarily using MEDLINE, but also by examining selected article reference lists, relevant websites and the proceedings of specialised conferences. All relevant articles and documents were analysed. Glaucoma is characterised by destruction of the optic nerve. It is most often a continuous, chronic eye disease and the most frequent diagnosis is primary open angle glaucoma (POAG). POAG is mostly associated with intraocular hypertension which can be delayed by medication, surgery or laser therapy. The prevalence rate of glaucoma is about 1% in the population >50 years of age. The rate increases with age and is higher in Black and Hispanic populations. Glaucoma affects more than 67 million people worldwide. Cost-of-illness studies have shown the importance of this disease, on which more than pound300 million was spent in the UK in 2002. Most of the costs (45%) were associated with direct medical costs, but direct nonmedical costs (20%) and indirect costs (35%) were also not negligible. Recent economic studies have shown a dramatic increase in the number of patients with glaucoma receiving treatment but a reduction in use of surgical procedures to treat the condition, especially as first-line therapy. The greater part of medical expenditure is now on medication, with new, more potent, better tolerated, but more costly drugs replacing older and less expensive medications. Treatment costs are directly related to the severity of disease and the number of different treatments used; they are also negatively correlated with treatment efficacy in reducing intraocular pressure. However, long-term economic benefits that may be associated with use of more potent new drugs (by delaying institutionalisation) have never been documented. Glaucoma screening has also been found not to be cost effective, although these results should be reconsidered in the light of new data.

Outpatient management of traumatic hyphema in children: Prospective evaluation

Purpose To evaluate the clinical outcome of children with traumatic hyphema treated on an outpatient basis. Methods A prospective cases series. Thirty-five children with traumatic hyphema were treated as outpatients for the ocular injury from February 2002 to February 2003. Data regarding initial and final visual acuity, slit-lamp biomicroscopy, hyphema size,ophthalmoscopy, intraocular pressure, rebleeding, clearance time, and medical and surgical intervention were recorded. Results Thirty (85.7%) children were male, and the major cause of traumatic hyphema was domestic tools (14 cases, 40.0%). Twenty-four patients (68.6%) presented low grades of hyphema. Seventeen patients (48.6%) had intraocular pressures higher than 24 mm Hg. The most common lesions associated with traumatic hyphema were corneal injuries (16 cases, 45.7%). The median final visual acuity was 20/25. Unsatisfactory final visual acuity (worse than 20/30) was statistically associated with ocular posterior segment lesions ( P = 0.009) and grade of hyphema ( P = 0.004). The grade of hyphema was also related to intraocular hypertension ( P = 0.018) and time for hemorrhage absorption ( P < 0.001). Nine patients (25.7%) underwent surgical intervention. Rebleeding occurred in three patients (8.6%). Conclusions Outpatient management is a feasible option for children with hyphema. Associated posterior ocular segment injuries and hyphema of greater magnitude were related to the worst final visual acuities.

Phakic refractive lens experience in Spain

Purpose To evaluate the efficacy, predictability, and safety of a phakic refractive lens (PRL) for high myopia and hyperopia. Setting Instituto Oftalmológico Hoyos, Barcelona, Spain. Methods A PRL was implanted in 31 eyes (17 myopic, 14 hyperopic) with a mean preoperative spherical equivalent (SE) of −18.46 diopters (D) (range −11.85 to −26.00 D) for myopia and +7.77 D (range +5.25 to +11.00 D) for hyperopia. All eyes had a thorough ophthalmologic examination before and after surgery. The follow-up was at least 12 months. Results At 1 year, the mean postoperative SE in the myopic group was −0.22 D ± 0.87 (SD) and 82% were within ±1.00 D of the desired refraction. The mean postoperative SE in the hyperopic group was −0.38 ± 0.82 D, and 79% were within ±1.00 D. Snellen lines of visual acuity were gained in 65% of the myopic eyes (8 eyes gained 1 line, 3 eyes gained 2 lines), and no eye lost lines. In the hyperopic group, 1 eye gained 1 line of acuity and 1 eye lost 1 line. In the hyperopic group, complications included pupillary block in 2 eyes and pigment dispersion signs without intraocular hypertension in 1 eye. In the myopic group, 1 eye had a corticosteroid-induced intraocular pressure rise, 1 eye had a spot of anterior cortical lens opacity immediately after surgery that did not progress, and 3 eyes with the PRL model 100 had decentration that required replacement of the lens. Four patients (2 myopic, 2 hyperopic) reported night halos in both eyes. Conclusions Results indicate that PRL implantation to correct high myopia and hyperopia is a relatively rapid, safe, predictable, and stable method that in many cases also improves the best corrected visual acuity. Complications such as visually significant progressive cataract and pigmentary glaucoma were not observed.

Non-traumatic neurological emergencies: emergency neuroradiological interventions.

This article summarizes recent developments in the growing field of interventional neuroradiology for the treatment of acute cerebrovascular disease. We describe the possibilities in endovascular therapy of acute cerebral aneurysms using electrolytically detachable coils combined with trispan neck bridging devices and stent implantation to occlude acute wide neck aneurysms. Techniques and results of local intra-arterial thrombolytic therapy in acute stroke and central retinal artery occlusion are described and we discuss the potential for rapid, large-burden thrombus removal in cases of internal carotid artery thrombosis by rheolytic thrombectomy, percutaneous transluminal angioplasty and stent implantation. Emergency endovascular therapy using the transvenous approach to treat severe intracranial or intraocular hypertension and multifocal haemorrhagic venous infarction due to cerebral sinus thrombosis or dural fistulas is also described. In cases of acute bleeding of head and neck lesions following trauma, tumours after radiotherapy, arteriovenous malformations, epistaxis or from iatrogenic origin, angiography plays a major role in localizing the source of bleeding and occluding the damaged vessel during the same session using the same endovascular approach.

Topical non-preserved diclofenac therapy for keratoconjunctivitis sicca.

Keratoconjunctivitis sicca, regardless of origin, is associated with variable levels of inflammation of the ocular surface. Chronic inflammation induces and maintains the metaplastic changes that typically develop in the conjunctival epithelium of patients with this disease. Although inflammatory phenomena associated with KCS can be immunomediated and/or induced by local prostaglandin secretion, it is unknown which of the two mechanisms has the prevailing role in the genesis of injury. Nevertheless, it is reasonable to assume that inflammatory prostaglandins are liberated as a result of epithelial damage. In support of this hypothesis, a recent study demonstrated the efficacy of a therapy consisting of cycles of topically administered steroids in the treatment of KCS(4). However, the study also reported notable risks to other aspects of ocular structural health from the well known side effects of corticosteroids, e.g., intraocular hypertension and cataracts. A therapy with non-steroidal and non-preserved anti-inflammatory agents in association with tear substitutes could be an effective therapy for the reduction of inflammation of the ocular surface and its associated symptoms.

Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, April 29???May 4, 2001

Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, April 29???May 4, 2001

Sutureless phacotrabeculectomy. Interim results

To study the medium-term success rate of a simple surgical technique for combined operation of cataract and glaucoma. Of 50 patients with cataract and various types of glaucoma, 55 eyes underwent a combined operation for cataract and glaucoma and were followed up for at least 6.5 months. The phacoemulsification war performed through a scleral tunnel. After implantation of a foldable IOL an "inverse T" incision of the tunnel floor was performed to create a valve mechanism closure. In 45 eyes (83%) the intraocular pressure was controlled without medications during the follow-up time. In 10 cases (17%) a new glaucoma medication was introduced postoperatively. Following early postoperative complications were noticed: early intraocular hypertension (20.0%), wound leakage (20.0%), early intraocular hypotension (10.9%), hyphema (19.1%). No-stitch phacotrabeculectomy appears to be a safe and (medium-term) effective procedure for combined surgery of cataract and glaucoma.

Developing laser-induced glaucoma in rabbits.

An animal mode of glaucoma is necessary for the study of its pathogenesis and treatment. The purpose of this study was to create open-angle glaucoma using a laser in rabbits. The trabecular meshwork of anaesthetized, adult, pigmented and albino rabbits was ablated internally using a diode laser via a gonioscopy lens, or externally through the limbus. In albino rabbits we used Chinese ink to pigment the angle and methylcellulose to open the iridocorneal angle. The eyes were examined weekly and histological assessment was performed. The success rate of intra-ocular hypertension was low (15%) and a result of synechial angle closure. A narrow angle prevented access of the laser beam to the trabecular meshwork and promoted damage to the ciliary processes located on the posterior iris. Due to the unique anatomy of the rabbit eye, laser-induced glaucoma is difficult to achieve. To create a successful model it is necessary to widen the iridocorneal angle, selectively damage the trabecular meshwork and reduce inflammation.

Glycerol. Biochemistry, pharmacokinetics and clinical and practical applications.

Glycerol is a naturally occurring 3-carbon alcohol in the human body. It is the structural backbone of triacylglycerol molecules, and can also be converted to a glycolytic substrate for subsequent metabolism. Serum glycerol concentrations approximate 0.05 mmol/L at rest, and can increase to 0.30 mmol/L during increased lipolysis associated with prolonged exercise or caloric restriction. When glycerol is ingested or infused at doses greater than 1.0 g/kg bodyweight, serum concentrations can increase to approximately 20 mmol/L, resulting in more than a 10 mOsmol/kg increase in serum osmolality. Glycerol infusion and ingestion have been used in research settings for almost 60 years, with widespread clinical use between 1961 and 1980 in the treatment of cerebral oedema resulting from acute ischaemic stroke, intraocular hypertension (glaucoma), intracranial hypertension, postural syncope and improved rehydration during acute gastrointestinal disease. Since 1987, glycerol ingestion with added fluid has been used to increase total body water (glycerol hyperhydration) by up to 700 ml, thereby providing benefits of improved thermoregulation and endurance during exercise or exposure to hot environments. Despite the small number of studies on glycerol hyperhydration and exercise, it appears to be an effective method of improving tolerance to exercise and other heat-related stressors.

Nerve growth factor (NGF) reduces and NGF antibody exacerbates retinal damage induced in rabbit by experimental ocular hypertension

It has been shown that intravitreal injection of NGF inhibits ganglion cell degeneration after optic nerve transection and ischemic injury. The aim of our study was to investigate the presence of NGF in aqueous humor and its involvement in retinal damage during ocular hypertension. We used an experimental model of ocular hypertension in rabbit. Before treatment and 4, 10 and 15 days after induction of hypertension, we evaluated histological retinal damage and NGF levels in aqueous humor using an immunoenzymatic assay. Polyclonal anti-NGF antibodies were injected intravitreally into one eye of each rabbit (n = 6), and the animals were killed after 4 days of hypertension. Another group of rabbits (n = 12) was injected retro-ocularly with NGF and killed after 10 or 15 days of treatment for histologic evaluation of the retina. Our data show that experimental ocular hypertension in adult rabbits induces retinal damage and enhances local NGF levels. The highest NGF value was found after 4 days of intraocular hypertension: high levels persisted, though to a lesser extent, for up to 15 days. Histological examination revealed that the number of retinal ganglion cells (RGC) remained unchanged during the first 4 days but decreased at 10 days. These studies also showed that retro-ocular administration of NGF reduced RGC loss, whereas intraocular injection of NGF antibodies, which inhibited the endogenous NGF, exacerbated the retinal insult. These findings demonstrate a protective effect of NGF on RGC damaged by ocular hypertension and prompt further investigations to evaluate a possible therapeutic use of NGF to retard RGC death in humans.

Mechanisms for Vasopressin Effects on Intraocular Pressure in Anesthetized Rats

Continuous intracameral infusions of a balanced salt solution (0.175 μl min−1) have been reported to raise intraocular pressure (IOP) in anesthetized rats. Palm et al. (1995) previously reported that this effect was attenuated significantly by inclusion of arginine-vasopressin (AVP, 10 ng 0.175 μl−1) in the infusate. This study used experimental and computer simulation methods to investigate factors underlying these changes in IOP. First, constant intracameral infusions of artificial cerebrospinal fluid (aCSF) at different fixed rates (0.049–0.35 μl min−1) were used to estimate the outflow resistance. Secondly, IOP responses were measured during an 2 hr intracameral infusion of either aCSF or AVP that was the sum of a small constant component (0.05 μl min−1) and a larger periodic component (0.25 μl min−1, cycling for 4 min on, then 4 min off); the mean infusion rate was 0.175 μl min−1. As shown previously for 0.175 μl min−1constant infusions, the periodic aCSF infusion induced a significant rise in IOP that was attenuated by AVP administration. Complex demodulation analysis and the estimated gain parameter of a second order transfer function fit to the periodic responses indicated that outflow resistance increased significantly during the infusions in both aCSF and AVP groups, but that the indices of resistance did not differ significantly between aCSF and AVP infused eyes. This finding implies that changes in outflow resistance do not explain the difference in IOP responses to intracameral aCSF and AVP. The two responses differed significantly, though, in damping factors, such that the aCSF responses were considerably more underdamped than the AVP responses. It is hypothesized that aCSF-induced increase in IOP reflects both (1) a small component reflecting increased outflow resistance and (2) a larger non-resistive component. Since the non-resistive component is insensitive to pretreatment with acetazolamide, it is suggested that the aCSF-induced elevation in IOP reflects primarily vascular perfusion changes that are reduced by local vasoconstrictor actions of AVP. The latter mechanism likely maintains vascular perfusion of the globe when intraocular hypertension develops.

Assessment of diurnal tensional curve in early glaucoma damage

We know very little about the relationship between the diurnal intraocular pressure variations and the progression of visual field loss. A prospective study of 149 eyes of 149 patients suffering from intraocular hypertension has been carried out through a minimum period of five years. At least 4 years before the appearance of field defects, we detected significant oscillations of IOP in the 64% of the cases prone to develop visual field loss. Likewise, we have found a statistically significant relationship between the presence of defects in the RNFL (retinal nerve fiber layer) and the existence of significant oscillations of IOP.

Histopathological evaluation of retinal damage during intraocular hypertension in rabbit: involvement of ganglion cells and nerve fiber layer.

Current clinical tests do not detect glaucomatous signs until the onset of substantial retinal damage. Therefore animal models are required to investigate the very early histopathological alterations in glaucoma disease. We used an experimental model of intraocular hypertension to compare early changes in retinal ganglion cell (RGC) density with the thickness of the nerve fiber layer (NFL). Methylcellulose 2% was injected into the anterior chamber of 18 eyes of 18 New Zealand albino rabbits. Intraocular pressure was measured 6 h after the injection and thenceforth once a day using a Shiötz tonometer. Histopathological analysis was performed on days 4, 10, and 15 following the induction of hypertension (six eyes for each group). Sections from the upper temporal retina were stained with hematoxylin-eosin and immunohistochemically using a polyclonal antibody PGP 9.5 to identify RGC. An image analysis system was used to evaluate the RGC and the thickness of the NFL. We observed a significant increase in intraocular pressure until the end of the experiment. Histological analysis showed, after 10 days of ocular hypertension, a significant decrease in RGC density (P < 0.05) and a significant increase (P < 0.05) in glial cell density. We found a significant correlation between RGC loss and cell area at 4 days (P < 0.01; Cc = 0.86) and at 10 days (P < 0.002; Cc = 0.91) of intraocular hypertension. We did not observe a significant decrease in the NFL thickness until 10 days of intraocular hypertension. Our study confirms the size-dependent RGC loss during intraocular hypertension and shows no early decrease in NFL thickness.

Results of an epidemiological study on drug-treated intraocular hypertension in Belgium

Some epidemiological aspects of drug-treated intraocular hypertension in Belgium were established in 1992 from questionnaires filled in by 1513 patients who attended a sample of 209 pharmacies open to the public. The mean age of the patients was 67 years (range: 3–95). After standardization for age, the prevalence of diabetes mellitus among patients was found to be 1.7 times higher than in the general population. Family history of glaucoma and/or blindness was reported by 28% of the patients. Beta-blocker eye drops were used by 96% of the sample. An ophthalmologist was consulted more than four times a year by 24% of the patients who had been drug-treated for less than one year; the proportion, however, decreases to 11% for those treated for at least five years. The annual consumed dose of eye drops containing parasympathomimetics, beta-blockers, and epinephrine or dipivefrine was 12.4, 13.6, and 12.3 bottles, respectively, and that of ointments containing parasympathomimetics was 9.9 tubes. From these results and using sales figures, the prevalence of drug-treated intraocular hypertension was found to be 77 per 10,000 inhabitants (95% CI: 31–123).