Is myopia a risk factor for glaucoma?

Controversy exists in the literature concerning the role of axial myopia as a risk factor for primary open-angle glaucoma. Epidemiologic evidence suggests that moderate and especially high myopia with a refractive error exceeding -6D is a risk factor for the development and the progression of glaucomatous optic neuropathy, with a twofold to threefold increased risk of glaucoma compared with that of nonmyopic subjects. This risk has been proven to be independent of other glaucoma risk factors and intraocular pressure (IOP). Myopic eyes have slightly although probably not clinically relevant, higher IOPs than emmetropic or hyperopic eyes. Selection bias could account for some of the reported association between glaucoma and myopia given that myopic subjects are likely to consult their ophthalmologist more frequently and glaucoma is underdiagnosed in myopic patients due to the great variability of their optic disc morphology, especially in high myopia, and the difficulty to interpret their visual field. The weakness of the fibroglial matrix of the nerve fibers at the optic disc together with the structural alterations in the lamina cribrosa and choroid, could contribute to the high susceptibility of the optic disc to IOP fluctuations and to increasing the risk of glaucomatous neuropathy, especially in high myopic eyes. Special attention will be given to patients with mild myopia who present with both elevated IOP levels and a positive family history. On the other hand, high myopic subjects should be screened for glaucoma at closer intervals. Moreover, after appropriate adjustments for deviations in central corneal thickness have been made, IOP greater than 17 mmHg must already be regarded as critical and initiation of medical treatment considered.     

Is early surgery for congenital cataract a risk factor for glaucoma?

AIMS: To estimate the risk of aphakic glaucoma after lensectomy for congenital cataract and its association with surgery within the first month of life. METHOD: A retrospective case notes review was conducted of all patients who had lensectomy for congenital cataract during their first year of life at Great Ormond Street Hospital between 1994 and 1997. Patients with pre-existing glaucoma, anterior segment dysgenesis, and Lowe syndrome were excluded. The risk of aphakic glaucoma after surgery was estimated using Kaplan-Meier survival analysis. RESULTS: 80 patients, undergoing 128 lensectomies were eligible. Of these, six patients (nine eyes) were lost to follow up. Based on eye count, the risk of glaucoma by 5 years after lensectomy was 15.6% (95% CI 10.2 to 23.4). Based on patient count, the 5 year risk of glaucoma in at least one eye following bilateral surgery was 25.1% (95% CI 15.1 to 40.0). The incidence of glaucoma remained at a constant level for the first 5 years after surgery. After early bilateral lensectomy, within the first month of life, the 5 year risk of glaucoma in at least one eye was 50% (95% CI 27.8 to 77.1) compared to 14.9% (95% CI 6.5 to 32.1) with surgery performed later (log rank test, p = 0.012). There was no significant difference (Kolmogorov-Smirnov test: unilateral lensectomy p = 0.587, bilateral lensectomy p = 0.369) in 5 year visual outcomes between eyes operated before and after 1 month of age. CONCLUSION: Bilateral lensectomy during the first month of life is associated with a higher risk of subsequent glaucoma than with surgery performed later. The reason for this is unclear but it may be prudent, in bilateral cases, to consider delaying surgery until the infant is 4 weeks old. As the incidence of glaucoma is similar for each year after surgery, long term glaucoma surveillance is mandatory.     

Neuroprotection in glaucoma - Is there a future role?

In glaucoma, the major cause of global irreversible blindness, there is an urgent need for treatment modalities that directly target the RGCs. The discovery of an alternative therapeutic approach, independent of IOP reduction, is highly sought after, due to the indirect nature and limited effectiveness of IOP lowering therapy in preventing RGC loss. Several mechanisms have been implicated in initiating the apoptotic cascade in glaucomatous retinopathy and numerous drugs have been shown to be neuroprotective in animal models of glaucoma. These mechanisms and their potential treatment include excitotoxicity, protein misfolding, mitochondrial dysfunction, oxidative stress, inflammation and neurotrophin deprivation. All of these mechanisms ultimately lead to programmed cell death with loss of RGCs. In this article we summarize the mechanisms involved in glaucomatous disease, highlight the rationale for neuroprotection in glaucoma management and review current potential neuroprotective strategies targeting RGCs from the laboratory to the clinic.     

Neuroprotection: a new treatment modality for glaucoma?

It is now commonly accepted that glaucoma is a neurodegenerative disease of the optic nerve. Thus, at any given time, there are neurons that, though still viable, are vulnerable to the hostile extracellular milieu and are therefore amenable to neuroprotective therapy. Neuroprotection refers to any intervention, either external to the optic nerve or internally, that will lead to an intracellular change in the balance between survival and death signals in favor of survival. Several potential sites and modalities for such intervention may exist. When designing neuroprotective therapy, ways must be sought to recruit the physiologic self-repair mechanisms awakened by the primary or secondary risk factors. These mechanisms appear to be insufficiently effective when in their natural state, but they may be simulated or boosted by appropriate therapeutic compounds or cells.     

Sleep disorders: a risk factor for normal-tension glaucoma?

PURPOSE: To determine the prevalence of sleep-related symptoms and sleep-related breathing disorders by polysomnography in patients with normal-tension glaucoma (NTG). PATIENTS AND METHODS: This comparative case series included 23 patients with NTG, 14 NTG suspects, and 30 comparison patients without NTG. A sleep history was obtained and determined to be positive or negative. Polysomnography was offered for patients with a positive sleep history. Prevalence of a positive sleep history and prevalence of sleep disorders were the main outcome measures. RESULTS: The NTG, NTG suspect, and comparison groups did not differ with respect to age, body mass index, systemic disease, gender, or race. Thirteen (57%) of 23 patients with NTG, 6 (43%) of 14 NTG suspects, and 1 (3%) of 30 comparison patients had a positive sleep history (P = 0.001). Nine of 13 patients with NTG and four of six NTG suspects with a positive sleep history chose to undergo polysomnography. Seven (78%) of nine patients with NTG and all four NTG suspects undergoing polysomnography were diagnosed with a sleep disorder. Five patients with NTG had sleep apnea and two had sleep hypopnea. Two NTG suspects had sleep apnea; one had sleep hypopnea; and one had upper airway resistance syndrome. The one comparison patient with a positive sleep history had upper airway resistance syndrome by polysomnography. CONCLUSIONS: Sleep-disturbed breathing may be a risk factor for NTG. Although we do not provide evidence for a cause-and-effect relationship, various physiologic factors produced by sleep-disturbed breathing may play a significant role in the pathogenesis of this optic neuropathy. We recommend obtaining a sleep history from patients with NTG and performing polysomnography in those patients with sleep disturbance symptoms.     

Modulating the immune system: a vaccine for glaucoma?

Glaucomatous neuropathy, like other neurodegenerative diseases, is a multi-dimensional disease in which various molecular and cellular factors contribute to the pathological process. These factors, while not initially causative, are key elements in disease progression and may continue to contribute even after the primary pathology is alleviated. An entire field of research of neuroprotection and restoration has opened up as part of the search for additional ways of slowing disease progression. We have proposed, on the basis of experimental evidence, that a vaccine could be a means of recruiting the immune system to help eliminate many of the factors associated with glaucomatous neurodegeneration and thus prevent disease progression, though not its onset. This immune defence involves lymphocytes, resident and infiltrating innate immune cells, the microglia, and macrophages. The antigens of choice are synthetic antigens, such as glatiramer acetate, that weakly cross-react with self-antigens in the retina and optic nerves. The vaccine induces a beneficial immune response that recruits immune effector cells to counteract or neutralize many of the compounds and factors that contribute to ongoing destruction, and in addition supports cell renewal and repair.     

Is glaucoma blindness a disease of deprivation and ignorance? A case–control study for late presentation of glaucoma in India

Aim:

The aim was to identify the presenting symptoms and social risk factors for late presentation of primary glaucoma in newly diagnosed cases.

Materials and Methods:

It was a case-control study in a tertiary eye care center in Maharashtra, India. Newly diagnosed patients with primary glaucoma were classified as cases (late presenters) where there was no perception of light in one eye or severe visual field loss affecting an area within 20° of fixation or a cup–disc (C:D) ratio ≥0.8 and controls (early presenters), presenting relative scotoma within 20° of fixation or a C:D ratio <0.8, but >0.5. All patients underwent a comprehensive ocular examination including gonioscopy, perimetry, and detailed family and social history. Occupation, education, and socioeconomic status were graded. SPSS version 12.0 was used, and univariate and multivariate logistic regression analysis was performed.

Results:

Gradual progressive painless loss of vision was the commonest symptom (175, 87.5%). Primary angle closure glaucoma was more common in females (P = 0.001) and lower socioeconomic groups (P = 0.05). Patients who were less educated were more likely to have late presentation of glaucoma (P < 0.001, odds ratio = 0.07; 95% CI, 0.02–0.25). Knowledge of family history of glaucoma (P = 0.80, odds ratio = 1.16; 95% CI, 0.36–3.71) and eye clinic attendance in past 2 years still resulted in late presentation (P = 0.45, odds ratio = 1.34, 95% CI, 0.63–2.82).

Conclusion:

Lack of education and awareness of glaucoma were major risk factors for late presentation.     

Maintaining mitochondrial membrane impermeability. an opportunity for new therapy in glaucoma?

Apoptosis may contribute to retinal ganglion cell loss in glaucoma and glaucoma models. Recent research has suggested that mitochondrially dependent apoptosis signaling may contribute to apoptosis in a rat model of glaucoma involving chronic increases in intraocular pressure. In some forms of apoptosis, mitochondrially dependent signaling involves increases in mitochondrial membrane permeability and the mitochondrial release of factors that signal for cell degradation. Opening of a multi-protein, mitochondrial megapore is one factor that contributes to the increased permeability and some anti-apoptotic proteins, particularly BCL-2 and BCL-X(L), bind at the megapore and facilitate megapore closure and reduce increases in mitochondrial membrane permeability. Phosphorylated protein kinase B (Akt) serves as an integrator for cellular survival signals and facilitates the megapore actions of BCL-2 and BCL-X(L), which could protect retinal ganglion cells against insults that induce apoptosis. Several anti-apoptotic agents are being evaluated for use in glaucoma, including brimonidine and propargylamines, which oppose mitochondrially dependent apoptosis through pathways involving phosphorylated Akt.     

Is the nasal optic disc sector important for morphometric glaucoma diagnosis?

BACKGROUND/AIM: Since the central retinal vessel trunk usually located in the nasal optic disc sector can render difficult the delineation of the neuroretinal rim and optic disc, the aim of this study was to evaluate whether the nasal region of the optic nerve head is important, or can be left out, for the morphometric glaucoma diagnosis. METHODS: The clinical observational study included 1337 patients with primary or secondary open angle glaucoma and 649 normal subjects. The glaucoma group was divided into 1187 patients with glaucomatous visual field defects ("perimetric glaucoma"), and into 150 patients with optic nerve head changes and normal visual fields ("preperimetric glaucoma"). Colour stereo optic disc photographs were morphometrically evaluated. RESULTS: Highest diagnostic power for the separation between the normal group and the perimetric glaucoma group, and for the differentiation between the normal group and the preperimetric glaucoma group, had the sum of inferotemporal rim area plus superotemporal rim area, the sum of inferotemporal rim area plus superotemporal rim area plus temporal rim area, and the inferotemporal rim area as single parameter. The lowest diagnostic precision had the nasal rim area as single parameter or in combination with rim measurements in other disc sectors. CONCLUSION: Excluding the nasal optic disc sector does not markedly decrease the diagnostic power of morphometric optic disc analysis in glaucoma diagnosis. It may have importance for an automated computerised morphometric detection of glaucomatous optic nerve damage.     

Is canaloplasty with mitomycin c a safe procedure in myopic glaucoma?

Graefe's Archive for Clinical and Experimental Ophthalmology - Myopic glaucoma patients display a considerable risk of complications following antiglaucomatous filtering surgery, e.g.,...     

Cystoid macular edema in a pseudophakic patient after several glaucoma procedures. Is local therapy with bimatoprost the reason?

BACKGROUND: Prostaglandin-like drugs such as latanoprost (Xalatan), travoprost (Travatan) and bimatoprost (Lumigan) lower the intraocular pressure by improving the outflow of aqueous humor via the uveoscleral pathway. Up to now there is no report about a macular edema after the topical use of Lumigan eye drops in a pseudophakic patient with an intact posterior capsule. PATIENT: A 69-year-old pseudophakic patient with a 14-year history of glaucoma in pseudoexfoliation syndrome, revealed a cystoid macular edema after local treatment with bimatoprost . 6 months earlier a phakoemulsification followed by the insertion of a posterior intraocular lens was performed on the left eye. Due to an elevated intraocular pressure after the surgery, which could not be controlled either by several eyedrops, or by three more operations (one viscocanalostomy with mitomycin c, two cyclophotocoagulations), therefore, a final attempt with bimatoprost (Lumigan) was started. Two weeks later the patient complained of blurred vision, caused by a cystoid macular edema. RESULTS: After discontinuation of bimatoprost and initiation of a local and systemic anti-inflammatory therapy, the edema resolved and visual acuity recovered. CONCLUSION: Bimatoprost (Lumigan) , a synthetic prostamid is similar to human prostaglandins, especially to prostaglandin F (2alpha.) Although it does not bind to the same receptor, its side effects are comparable to those of common prostaglandin analogues. So far there are no reports about the manifestation of a macular edema after using bimatoprost in pseudophakic eyes with an intact posterior capsule. Even if three more operations followed the cataract surgery, we suspect that bimatoprost eyedrops can be held responsible for this. Therefore they should be used with great care and in clear indications, particularly in pseudophakic patients.     

Is neurovascular coupling of relevance in glaucoma?

Rapid development of functional neuroimaging techniques have brought about a growing interest for neurovascular coupling in neuroresearch, which, in turn, has prompted similar research in ophthalmology. There are now hints that neurovascular coupling is disturbed in glaucoma. The contact of the nerve terminals to the cortical blood vessels is mostly realized through astrocytes. A major defining property of glaucoma, cupping of the optic disk, implies tissue remodeling of the optic nerve head and involves an astrocytic responses. A malfunction of the astrocytes in glaucoma may lead not only to the hallmark of glaucoma-cupping and death of retinal ganglion cells-but also to an accompanying or even preceding disturbance in ocular neurovascular coupling. This article is a short overview of research published in this field so far.