Pressure-cornea-vascular index (PCVI) for predicting disease progression in normal tension glaucoma

It has been shown that the pressure-to-cornea index (PCI), which estimates the relative effects of intraocular pressure (IOP) and central corneal thickness (CCT), may differentiate between glaucoma and non-glaucoma states. The authors investigated the utility of the pressure-cornea-vascular index (PCVI) in predicting field-progression in patients with normal tension glaucoma (NTG).

Repeatability of nerve fiber layer thickness measurements in patients with glaucoma and without glaucoma using spectral-domain and time-domain OCT

The aim of this work is to assess the repeatability of spectral-domain-OCT (SD-OCT) retinal nerve fiber layer thickness (RNFL) thickness measurements in a non-glaucoma group and patients with glaucoma and to compare these results to conventional time-domain-OCT (TD-OCT).

Compliance and knowledge about glaucoma in patients at tertiary glaucoma units

To document the rate of self-reported compliance and glaucoma-related knowledge in Swiss patients and to identify risk factors for their poor compliance. This was an observational study, including a total of 200 consecutive patients already under glaucoma medication in two Swiss tertiary glaucoma clinics (Geneva and Bern). Personal characteristics, presence of systemic disease, compliance with glaucoma medication, attitude to the ophthalmologist, and glaucoma-related attitudes were ascertained by means of a predetermined questionnaire with 40 questions. Patients were subsequently assessed for the ability to correctly instil placebo eye drops. Non-compliance with glaucoma medication was defined as omitting more than two doses a week as reported by the patient. Logistic regression was used to evaluate how patient characteristics and knowledge about the disease were related to compliance. Overall, 81% (n = 162) of patients reported to be compliant. Forgetfulness was the most frequently cited reason for non-compliance with dosing regimen (63%). Although 90.5% (n = 181) of patients believed glaucoma medication to be efficient, only 28% (n = 56) could correctly define glaucoma. Factors positively associated with compliance were 'knowledge of glaucoma' [adjusted odds ratio (OR) 4.77 (95% CI 1.36-16.70)] and 'getting help for administration of drops' [OR 2.95 (1.25-6.94)]. These findings indicate that despite the comparatively high compliance rate among glaucoma patients, knowledge of glaucoma remains poor in long-term glaucoma sufferers. Improving knowledge about the disease is important since it is positively associated with compliance in our study.

Interleukin-6 is an efficacious marker of axonal transport disruption during experimental glaucoma and stimulates neuritogenesis in cultured retinal ganglion cells

It is increasingly recognised that chronically activated glia contribute to the pathology of various neurodegenerative diseases, including glaucoma. One means by which this can occur is through the release of neurotoxic, proinflammatory factors. In the current study, we therefore investigated the spatio-temporal patterns of expression of three such cytokines, IL-1β, TNFα and IL-6, in a validated rat model of experimental glaucoma. First, only weak evidence was found for increased expression of IL-1β and TNFα following induction of ocular hypertension. Second, and much more striking, was that robust evidence was uncovered showing IL-6 to be synthesised by injured retinal ganglion cells following elevation of intraocular pressure and transported in an orthograde fashion along the nerve, accumulating at sites of axonal disruption in the optic nerve head. Verification that IL-6 represents a novel marker of disrupted axonal transport in this model was obtained by performing double labelling immunofluorescence with recognised markers of fast axonal transport. The stimulus for IL-6 synthesis and axonal transport during experimental glaucoma arose from axonal injury rather than ocular hypertension, as the response was identical after optic nerve crush and bilateral occlusion of the carotid arteries, each of which is independent of elevated intraocular pressure. Moreover, the response of IL-6 was not a generalised feature of the gp130 family of cytokines, as it was not mimicked by another family member, ciliary neurotrophic factor. Finally, further study suggested that IL-6 may be an early part of the endogenous regenerative response as the cytokine colocalised with growth-associated membrane phosphoprotein-43 in some putative regenerating axons, and potently stimulated neuritogenesis in retinal ganglion cells in culture, an effect that was additive to that of ciliary neurotrophic factor. These data comprise clear evidence that IL-6 is actively involved in the attempt of injured retinal ganglion cells to regenerate their axons.

Translational neuroprotection research in glaucoma: a review of definitions and principles

The maintenance of vision, through prevention and attenuation of neuronal injury in glaucoma, forms the basis of current clinical practice. Currently, the reduction of intraocular pressure is the only proven method to achieve these goals. Although this strategy enjoys considerable success, some patients progress to blindness; hence, additional management options are highly desirable. Several terms describing treatment modalities of neuronal diseases with potential applicability to glaucoma are used in the literature, including neuroprotection, neurorecovery, neurorescue and neuroregeneration. These phenomena have not been defined within a coherent framework. Here, we suggest a set of definitions, postulates and principles to form a foundation for the successful translation of novel glaucoma therapies from the laboratory to the clinic.

Estimation of axon counts in a rat model of glaucoma: comparison of fixed-pattern sampling with targeted sampling

Full axon counting of optic nerve cross-sections represents the most accurate method to quantify axonal damage, but such analysis is very labour intensive. Recently, a new method has been developed, termed targeted sampling, which combines the salient features of a grading scheme with axon counting. Preliminary findings revealed the method compared favourably with random sampling. The aim of the current study was to advance our understanding of the effect of sampling patterns on axon counts by comparing estimated axon counts from targeted sampling with those obtained from fixed-pattern sampling in a large collection of optic nerves with different severities of axonal injury.

Intravitreal bevacizumab (Avastin) in the treatment of neovascular glaucoma

PURPOSE: To describe a case series of neovascular glaucoma (NVG) caused by central retinal vein occlusion (CRVO) that was treated with intravitreal bevacizumab (IVB; Avastin). DESIGN: Retrospective interventional case series. METHODS: Six consecutive patients with NVG and a refractory, symptomatic elevation of intraocular pressure (IOP) and pronounced anterior segment congestion received IVB (1.25 mg/0.05 ml). Diode laser cyclophotocoagulation was carried out only if pressure was controlled insufficiently by topical medication. Follow-up examinations occurred at four to 16 weeks. RESULTS: IVB resulted in a marked regression of anterior segment neovascularization and relief of symptoms within 48 hours. IOP decreased substantially in three eyes; in the other three eyes, adjuvant cyclophotocoagulation was necessary. No side effects were observed. Panretinal photocoagulation (PRP) was performed as soon as feasible, five to 12 weeks after IVB treatment. CONCLUSION: IVB leads to a rapid regression of iris and angle neovascularization and should be investigated more thoroughly as an adjunct in the management of NVG.

Characterization of retinal damage in the episcleral vein cauterization rat glaucoma model

Episcleral vein cauterization (EVC) is used in rats to generate a glaucoma model with high intraocular pressure (IOP). The long-term retinal damage in this glaucoma model, however, has not been accurately quantified. We report the location and amount of retinal ganglion cell (RGC) damage caused by (EVC) induced IOP elevation in two rat strains. IOP was raised in one eye of Wistar (N = 5) and Brown-Norway(B-N)(N = 7) rats by EVC and monitored monthly until IOP in contralateral eyes equalized at 5 months post-surgery. Animals were maintained for 3.5-4.5 additional months. B-N rats (N = 7) that had no EVC served as controls for this strain. Scotopic flash ERGs were recorded at baseline and just prior to euthanasia. Automated counts of all retrogradely labeled RGCs in retinal flat-mounts were determined and compared between contralateral eyes. RGC density maps were constructed and RGC size distribution was determined. Oscillatory potentials in the group of eyes which had elevated IOP were decreased at the time of euthanasia, when IOP had returned to normal. The group of normal B-N rats had similar RGC counts between contralateral eyes. In the experimental group the mean number of RGCs was not significantly different between control and experimental eyes, but 1 of 5 Wistar and 2 of 7 B-N experimental eyes had at least 30% fewer RGCs than contralateral control eyes. Total retinal area in B-N experimental eyes was higher compared to contralateral eyes. Cumulative IOP exposure of the experimental eyes was modestly correlated with RGC loss while oscillatory potentials appeared to be inversely related to RGC loss. In retinas with extensive (> 30% RGC loss) but not complete damage, smaller cells were preserved better than larger ones. The above results indicate that RGC loss in both Wistar and B-N strains is variable after a prolonged elevation of IOP via EVC. Such variability despite equivalent IOP levels and ERG abnormalities, suggests unknown factors that can protect IOP-stressed RGCs. Identification and enhancement of such factors could prove useful for glaucoma therapy.

Uveitic glaucoma and Rosai-Dorfman disease (sinus histiocytosis)

PURPOSE: To report a novel association of uveitic glaucoma with Rosai-Dorfman disease. METHODS: Case report. RESULTS: A 67-year-old Caucasian woman presented with a chronic bilateral granulomatous uveitis which did not respond to conventional topical steroid therapy. She also had raised intraocular pressures, glaucomatous optic disc changes and diffuse nodular fibrous skin lesions. Subsequent skin biopsy immuno-cytochemistry showed S-100 staining, consistent with Rosai-Dorfman disease. The uveitis and glaucoma were highly resistant to standard medical treatments, but completely resolved together with the systemic features of the disease after six months. CONCLUSIONS: Rosai-Dorfman disease has not previously been reported to cause uveitic glaucoma and should be considered in non-responsive cases presenting with a rash. The disease is entirely self-limiting and early diagnosis may therefore avoid unnecessary trabeculectomy and/or systemic immune suppression.

Long-term outcome of trans-scleral diode laser cyclophotocoagulation in refractory glaucoma

BACKGROUND: Long-term outcome and complications of diode laser cyclophotocoagulation (DCPC) may be important, since eyes, once treated with DCPC, are less likely to be subjected to other types of interventions in the further follow-up. METHODS: Retrospective review of 131 eyes of 127 patients treated from 2000 through 2004. Success was defined as intraocular pressure (IOP) at last visit 6-21 mm Hg; hypotony: IOP glaucoma, and patients were significantly younger. All eyes had refractory glaucomas on maximal medication, neovascular glaucoma (NVG) representing the largest subgroup (61%). IOP decreased from 36.9 (10.7) mm Hg pretreatment to 15.3 (10.4) mm Hg at the end of FU. Success was noted in 69.5% (91 eyes), failure (non-response) in 13%. Hypotony occurred in 17.6% eyes, of which 74% had NVG. Hypotony developed after mean 19.3 (11.0) months, range 6 to 36; with 96% of these eyes having received only 1 or 2 treatments; delivered energy did not differ from that in the successful eyes. CONCLUSIONS: DCPC is an efficient treatment for refractory glaucoma. Hypotony, the most common complication, may develop as late as 36 months post-treatment. Diagnostic category and age seem to influence the outcome stronger than laser protocol and delivered energy.

Novel pressure-to-cornea index in glaucoma

BACKGROUND: Several conversion tables and formulas have been suggested to correct applanation intraocular pressure (IOP) for central corneal thickness (CCT). CCT is also thought to represent an independent glaucoma risk factor. In an attempt to integrate IOP and CCT into a unified risk factor and avoid uncertain correction for tonometric inaccuracy, a new pressure-to-cornea index (PCI) is proposed. METHODS: PCI (IOP/CCT(3)) was defined as the ratio between untreated IOP and CCT(3) in mm (ultrasound pachymetry). PCI distribution in 220 normal controls, 53 patients with normal-tension glaucoma (NTG), 76 with ocular hypertension (OHT), and 89 with primary open-angle glaucoma (POAG) was investigated. PCI's ability to discriminate between glaucoma (NTG+POAG) and non-glaucoma (controls+OHT) was compared with that of three published formulae for correcting IOP for CCT. Receiver operating characteristic (ROC) curves were built. RESULTS: Mean PCI values were: Controls 92.0 (SD 24.8), NTG 129.1 (SD 25.8), OHT 134.0 (SD 26.5), POAG 173.6 (SD 40.9). To minimise IOP bias, eyes within the same 2 mm Hg range between 16 and 29 mm Hg (16-17, 18-19, etc) were separately compared: control and NTG eyes as well as OHT and POAG eyes differed significantly. PCI demonstrated a larger area under the ROC curve (AUC) and significantly higher sensitivity at fixed 80% and 90% specificities compared with each of the correction formulas; optimum PCI cut-off value 133.8. CONCLUSIONS: A PCI range of 120-140 is proposed as the upper limit of "normality", 120 being the cut-off value for eyes with untreated pressures or=22 mm Hg. PCI may reflect individual susceptibility to a given IOP level, and thus represent a glaucoma risk factor. Longitudinal studies are needed to prove its prognostic value.

[Positive ibopamine provocative test in normal-tension glaucoma suspects]

BACKGROUND: Ibopamine is an alpha-adrenergic agent and causes an elevation of intraocular pressure in eyes with increased outflow resistance. It has been proposed as a test substance for the detection of early ocular hydrodynamic disorders. PATIENTS AND METHODS: A total of 64 normal-tension glaucoma suspect eyes without anti-hypertensive treatment were enrolled. A daily pressure curve was registered with measurements at 7:00 am, 8:00 am, 12:00 am, 17:00 pm using an applanation tonometer and a contour tonometer followed by instillation of ibopamine 2% in both eyes. Tonometry was performed every 15 minutes during the following hour. An IOP increase of > 2.0 mmHg was considered positive. RESULTS: The positive test group showed a significant pressure increase from 18.04 to 22.06 mmHg. Ocular pulse amplitude increased from 2.96 to 3.97 mmHg and was positively correlated with the pressure. Intraocular pressure was unchanged in the negative test group. Central corneal thickness was not significantly different in the two groups (p = 0.32). CONCLUSIONS: Ibopamine 2% eye drops have a positive pressure effect in 50% of suspected normal-tension glaucoma eyes and may differentiate between eyes with normal trabecular outflow capacity and eyes with increased resistance in the trabecular meshwork that are prone to pressure peaks and deterioration to glaucoma.

Increased plasma endothelin-1 levels in patients with progressive open angle glaucoma

AIM: To compare the plasma levels of endothelin-1 (ET-1) between patients with primary open angle glaucoma with visual field progression despite normal or normalised intraocular pressure and patients with stabile visual fields in a retrospective study. METHODS: The progressive group consisted of 16 primary open angle glaucoma patients and the group with stable visual field consisted of 15 patients. After a 30 minute rest in a supine position, venous blood was obtained for ET-1 dosing. Difference in the plasma level of ET-1 between two groups was compared by means of analysis of covariance (ANCOVA), including age, sex, and mean arterial blood pressure as covariates. RESULTS: ET-1 plasma levels were found to be significantly increased in patients with deteriorating (3.47 (SD 0.75) pg/ml) glaucoma when compared to those with stable (2.59 (SD 0.54) pg/ml) visual fields (p = 0.0007). CONCLUSIONS: Glaucoma patients with visual field progression in spite of normal or normalised intraocular pressure have been found to have increased plasma endothelin-1 levels. It remains to be determined if this is a secondary phenomenon or whether it may have a role in the progression of glaucomatous damage.

Comparison between confocal scanning laser tomography, scanning laser polarimetry and optical coherence tomography on the ability to detect localised retinal nerve fibre layer defects in glaucoma patients

BACKGROUND/AIM: To compare the ability of confocal scanning laser tomography (CSLT), scanning laser polarimetry (SLP) and optical coherence tomography (OCT) in recognising localised retinal nerve fibre layer (RNFL) defects. METHODS: 51 eyes from 43 patients with glaucoma were identified by two observers as having RNFL defects visible on optic disc photographs. 51 eyes of 32 normal subjects were used as controls. Three masked observers evaluated CSLT, SLP and OCT images to determine subjectively the presence of localised RNFL defects. RESULTS: Interobserver agreement was highest with OCT, followed by SLP and CSLT (mean kappa: 0.83, 0.69 and 0.64, respectively). RNFL defects were identified in 58.8% of CSLT, 66.7% of SLP and 54.9% of OCT (p = 0.02 between SLP and OCT) by at least two observers. In the controls, 94.1% of CSLT, 84.3% of SLP and 94.1% of OCT scans, respectively, were rated as normal (p = 0.02 between CSLT and SLP, and SLP and OCT). CONCLUSION: Approximately 20-40% of localised RNFL defects identified by colour optic disc photographs are not detected by CSLT, SPL or OCT. SLP showed a higher number of false-positive results than the other techniques, but also had a higher proportion of correctly identified RNFL defects in the glaucoma population.