First-line therapy with latanoprost 0.005% results in improved ocular circulation in newly diagnosed primary open-angle glaucoma patients: a prospective, 6-month, open-label study.

PURPOSE: To evaluate the effect of latanoprost 0.005% on the optic nerve head (ONH) and retinal circulation of newly diagnosed and previously untreated primary open-angle glaucoma (POAG) patients. METHODS: Twenty-two newly diagnosed and previously untreated POAG patients (mean age+/-SD: 68.38+/-11.92 years) were included in this longitudinal open-label study. Patients were treated with latanoprost 0.005% once a day. Intraocular pressure (IOP), systemic blood pressure (BP), mean ocular perfusion pressure (MOPP), and ocular perfusion parameters 'volume', 'velocity', and 'flow' measured at the optic nerve head (ONH) and retina by means of Heidelberg Retina Flowmeter system were evaluated during a 6-month follow-up period. RESULTS: Treatment with latanoprost 0.005% resulted in a significant decrease in IOP (P<0.0001) and increase in MOPP (P<0.0001). After correcting for changes in MOPP, the blood velocity measured at the ONH level was significantly higher after 6 months of treatment than at baseline (P=0.0310). In addition, blood volume and flow measured at the peripapillary retina level improved after 3 and 6 months of treatment (P=0.0170; P=0.0260, and P=0.0170; P=0.0240 respectively). CONCLUSION: Previously untreated POAG patients exhibit reduced IOP, increased MOPP and improved ocular perfusion at the ONH and retina levels when treated with Latanoprost 0.005%. These effects could be beneficial for glaucoma patients suffering from ocular vascular dysregulation.

Some dissociating factors in the analysis of structural and functional progressive damage in open-angle glaucoma.

AIM: To identify the presence, and origin, of any "dissociating factors" inherent to the techniques for evaluating progression that mask the relationship between structural and functional progression in open-angle glaucoma (OAG). METHODS: 23 patients (14 with OAG and 9 with ocular hypertension (OHT)) who had received serial Heidelberg Retina Tomograph (HRT II) and Humphrey Field Analyser (HFA) examinations for >or=5 years (mean 78.4 months (SD 9.5), range 60-101 months) were identified. Evidence of progressive disease was retrospectively evaluated in one eye of each patient using the Topographic Change Analysis (TCA) and Glaucoma Progression Analysis (GPA) for the HRT II and HFA, respectively. RESULTS: Six patients were stable by both techniques; four exhibited both structural and functional progression; seven exhibited structural progression, only, and six showed functional progression, only. Three types of dissociating factors were identified. TCA failed to identify progressive structural damage in the presence of advanced optic nerve head damage. GPA failed to identify progressive functional damage at stimulus locations, with sensitivities exhibiting test-retest variability beyond the maximum stimulus luminance of the perimeter, and where a perimetric learning effect was apparent. CONCLUSION: The three dissociating factors accounted for nine of the 13 patients who exhibited a lack of concordance between structural and functional progressive damage.

Subjective and objective performance of the Lenstec KH-3500 "accommodative" intraocular lens.

AIM: To determine whether eyes implanted with the Lenstec KH-3500 "accommodative" intraocular lenses (IOLs) have improved subjective and objective focusing performance compared to a standard monofocal IOLs. METHODS: 28 participants were implanted monocularly with a KH-3500 "accommodative" IOL and 20 controls with a Softec1 IOL. Outcome measures of refraction, visual acuity, subjective amplitude of accommodation, objective accommodative stimulus response curve, aberrometry, and Scheimpflug imaging were taken at approximately 3 weeks and repeated after 6 months. RESULTS: Best corrected acuity with the KH-3500 was 0.06 (SD 0.13) logMAR at distance and 0.58 (0.20) logMAR at near. Accommodation was 0.39 (0.53) D measured objectively and 3.1 (1.6) D subjectively. Higher order aberrations were 0.87 (0.85) microm and lower order were 0.24 (0.39) microm. Posterior subcapsular light scatter was 0.95% (1.37%) greater than IOL clarity. In comparison, all control group measures were similar except objective (0.17 (0.13) D; p = 0.032) and subjective (2.0 (0.9) D; p = 0.009) amplitude of accommodation. Six months following surgery, posterior subcapsular scatter had increased (p<0.01) in the KH-3500 implanted subjects and near word acuity had decreased (p<0.05). CONCLUSIONS: The objective accommodating effects of the KH-3500 IOL appear to be limited, although the subjective and objective accommodative range is significantly increased compared to control subjects implanted with conventional IOLs. However, this "accommodative" ability of the lens appears to have decreased by 6 months post-surgery.

Beneficial effects of small-incision cataract surgery in patients demonstrating reduced ocular blood flow characteristics.

PURPOSE: To investigate intraocular pressure (IOP) and ocular haemodynamics following small incision cataract surgery. METHODS: Systemic and ocular haemodynamics, and IOP, were measured pre-operatively and 1 month post-operatively, in 25 eyes of 25 patients (mean age 72.6+/-7.9 years) scheduled for small incision cataract surgery and intraocular lens implantation; these values were compared to an untreated age-matched healthy group (n=25, mean age 72.3+/-5.0 years). For each eye, the Ocular Blood Flow Analyser (OBFA, Paradigm Inc., UT, USA) was used to obtain measurements of IOP, pulsatile ocular blood flow (POBF), pulse volume (PV), ocular pulse amplitude (PA), and pulse rate (PR). Systemic blood pressure measurements were obtained at each visit. Pre- and post-operative values for the cataract group were compared using repeated measures analysis of variance, and compared to the normal group using analysis of variance. RESULTS: Pre-operatively, IOP was significantly higher in the cataract group compared to the age-matched normal control group (P<0.001). Cataract surgery resulted in a significant 16.7% reduction in IOP (P=0.001). Consequently, the post-operative IOP in the cataract group was similar to that of the normal group (P>0.05). Both pre- and post-operative POBF and PV values for the cataract group were significantly lower than for the normal age-matched group (P<0.0125). Small incision cataract surgery led to an 8.3% post-operative increase in POBF (P=0.0118) and 15.5% increase in PV (P<0.001). No changes in PA or PR were evident. CONCLUSION: These data suggest that cataract patients exhibit higher IOP and reduced ocular perfusion characteristics compared to an age-matched normal healthy group. Following cataract surgery, IOP reduced and ocular pulsatility improved.

Plasma vascular endothelial growth factor, soluble VEGF receptor FLT-1, and von Willebrand factor in glaucoma.

AIM: To investigate plasma indices of vascular permeability (vascular endothelial growth factor, VEGF-also an index of angiogenesis, as well as the soluble receptor for VEGF, sFlt-1) and endothelial damage/dysfunction (von Willebrand factor, vWf) in glaucoma. METHODS: Citrated plasma was assayed for VEGF, sFlt-1, and vWf (all ELISA) in a cross sectional study of 50 patients (20 male; mean age 63.9 years, SD 10.5) with glaucoma: 26 had normal tension glaucoma (NTG) and 24 had primary open angle glaucoma (POAG), who were compared with 26 healthy controls (mean age 73.4 years, SD 9.2). RESULTS: Median (interquartile range, IQR) levels of VEGF were significantly elevated in patients with NTG and POAG compared to healthy controls (Kruskal-Wallis test, p<0.001). Similarly, mean (SD) vWF levels were abnormal in NTG and POAG compared to healthy controls (one way ANOVA, p<0.001). Median levels of sFlt-1 were significantly lower in patients with NTG and POAG, when compared to healthy controls (Kruskal-Wallis test, p<0.001; p<0.05 with Tukey's post hoc test for controls v POAG). There were no significant differences in VEGF, sFlt-1 or vWf levels between the NTG and POAG groups (Tukey's test, all p=NS). In both NTG and POAG groups, there was a significant correlation between VEGF and sFlt-1 (Spearman, NTG: r=0.6517, p=0.001; POAG: r=0.6017, p=0.008). There were no significant correlations between VEGF and sFlt-1, or with vWf among the controls. CONCLUSIONS: The pathogenesis of optic nerve damage in both NTG and POAG may be associated with abnormal vascular permeability and endothelial damage/dysfunction, as indicated by abnormal plasma VEGF and vWf levels in these patients.

Effect of senescence on ocular blood flow in the retina, neuroretinal rim and lamina cribrosa, using scanning laser Doppler flowmetry.

PURPOSE: To determine the effects of age on blood flow measurements obtained using the scanning laser Doppler flowmeter (SLDF). METHOD: Using SLDF (Heidelberg retina flowmeter, Heidelberg Engineering, Germany) three 10 degrees images were taken of the superior temporal retina and three further images of the superior temporal neuroretinal rim in 15 young, healthy subjects (mean age 27.9 years +/- 6.2 years) and 15 mature, healthy subjects (mean age 65.2 years +/- 13.7 years). In addition, measurements were taken of the lamina cribrosa in 12 of the volunteers from each subject group (mean age 27.1 +/- 6.3 years and 64.8 +/- 13.2 years respectively). Using a 10 x 10 pixel measurement frame, blood flow readings were obtained at a predetermined position on the retina, neuroretinal rim and lamina cribrosa. Student's two-tailed unpaired t-tests were used to compare measures of blood flow, volume and velocity between the two subject groups (P < 0.05). In addition, linear regression analysis was used to assess the relationship between age and blood flow, volume and velocity at the retina, neuroretinal rim and lamina cribrosa. RESULTS: Retinal blood volume measured at the retina was significantly lower in the mature compared with the young subject group (P = 0.01). Mature subjects also exhibited reduced blood flow and velocity at the neuroretinal rim (P = 0.01 for both parameters) and lamina cribrosa (P = 0.008 and P = 0.01 respectively). Regression analysis revealed negative trends for all blood flow parameters in each of the anatomical areas with advancing age. Significant negative correlations were obtained for retinal blood volume (r = -0.455, P < 0.05), neuroretinal rim blood velocity (r = -0.359, P < 0.05) and lamina cribrosa blood volume (r = -0.475, P < 0.05). CONCLUSION: Capillary blood flow in the retina, neuroretinal rim and lamina cribrosa decreases with advancing age. This may be of consequence in the progression of chronic ocular diseases such as glaucoma, and should be considered in the longitudinal determination of change in disease monitoring.

Application of a local search strategy improves the detection of blood flow deficits in the neuroretinal rim of glaucoma patients using scanning laser Doppler flowmetry.

BACKGROUND/AIM: Blood flow measures acquired using the scanning laser Doppler flowmeter (SLDF) are known to be highly susceptible to spatial and temporal variations of physiological origin. The purpose of this study was to evaluate a local search strategy intended to overcome these intrinsic variations, thereby improving the detection of blood flow defects resulting from glaucoma. METHODS: The sample consisted of one eye of each of 15 glaucoma patients (aged 69.1 (SD 6.6) years) and 15 normal subjects (aged 65.2 (13.7) years). Three 10 degree images of the superior temporal retina and three images of the superior temporal rim were acquired using the Heidelberg retina flowmeter (HRF). Standard analysis was performed using a 10 x 10 pixel frame. For the search strategy the same frame was located within a 15 x 15 pixel window and manually repositioned in order to identify the highest and lowest local values of blood flow. Student's paired t test was used to identify differences between groups for the two methods (p<0.05). RESULTS: The standard strategy revealed no significant differences in blood flow measures between the subjects at either the retina or neuroretinal rim. With the search strategy there was also no difference in blood flow measures at the retina. At the neuroretinal rim, the search strategy demonstrated that the highest measured blood flow, volume, and velocity values were significantly lower for the glaucoma patients (p = 0.002, 0.02, and 0.002 respectively) while comparison of the lowest flow values showed that glaucoma patients had lower blood flow and velocity only (p = 0.023 and 0.021 respectively). CONCLUSIONS: Glaucoma patients exhibit reduced ocular blood flow at the neuroretinal rim, which seems to affect high velocity flow more profoundly than low velocity flow. When analysing perfusion images a local search strategy is recommend to identify the highest local blood flow values in order to optimise the ability to differentiate between subject groups.

Is the role of trabeculectomy in glaucoma management changing?

BACKGROUND: In recent years there have been significant developments in the diagnosis and treatment of glaucoma. We conducted a study to determine whether there has been an associated change in trabeculectomy rates in England over this period. METHODS: Figures for the total number of trabeculectomies and cataract operations performed in England for each year from 1989/90 to 1999/2000 were obtained from the Department of Health, Hospital Episode Statistics Division. RESULTS: The available data show that the number of trabeculectomies and cataract operations increased year on year from 1990/91 until 1995/96. Since then, the number of cataract procedures has continued to rise dramatically, whereas the number of trabeculectomies has fallen progressively by 7%, 23%, 37% and 53% in the last 4 years. CONCLUSION: The perceived need for surgical intervention would appear to have been delayed or prevented. We postulate that several factors underlie this trend and that there are a number of implications regarding the future management of glaucoma patients.

The SITA perimetric threshold algorithms in glaucoma.

PURPOSE: To determine the within-visit between-algorithm and the within-algorithm between-visit differences in sensitivity for the SITA Standard, SITA Fast, FASTPAC, and Full Threshold algorithms in stable primary open angle glaucoma. METHODS: One designated eye from each of 29 patients (age 67.3 +/- 10.2 years; mean +/- SD) experienced in automated perimetry was examined with the four algorithms on each of three visits, using the Humphrey Field Analyzer 750 and Program 30-2. RESULTS: The group mean Mean Sensitivity was 1.0 dB greater for SITA Standard than Full Threshold (P < 0.001), 0.7 dB greater for SITA Standard than FASTPAC (P < 0.001), 1.6 dB greater for SITA Fast than FASTPAC (P < 0.001), and 0.9 dB greater for SITA Fast than SITA Standard (P < 0.001). The higher pointwise sensitivity for SITA Fast compared to Full Threshold, FASTPAC, and SITA Standard increased with increase in defect depth. The examination duration for SITA Standard was 53% of that for Full Threshold and 50% shorter for SITA Fast compared to FASTPAC (P < 0.001), regardless of age (P = 0.932). The examination duration increased with increase in severity of field loss (P < 0.001), and this increase was proportionately greater for both SITA algorithms (P < 0.001), particularly SITA Fast. The Total and Pattern Deviation probability analyses of both SITA algorithms yielded a statistically greater defect than Full Threshold or FASTPAC (P < 0.001). The within-algorithm between-visit differences were similar between SITA Standard and Full Threshold and between SITA Fast and FASTPAC. CONCLUSIONS: Both SITA algorithms produce a marginally higher differential light sensitivity compared to existing algorithms but with a statistically deeper defect and a marked reduction in examination duration.

Between-algorithm, between-individual differences in normal perimetric sensitivity: full threshold, FASTPAC, and SITA. Swedish Interactive Threshold algorithm.

PURPOSE: To determine the between-algorithm differences in perimetric sensitivity for the Swedish Interactive Threshold algorithm (SITA) Standard, SITA Fast, FASTPAC, and Full Threshold algorithms; to determine the between-subject, between-algorithm differences in the magnitude of the normal variation in sensitivity. METHODS: The sample comprised 50 normal subjects (mean age, 52.9 +/- 18.5 years) experienced in automated perimetry. One randomly assigned eye was examined at three visits with Program 30-2 of the Humphrey Field Analyzer (HFA). The first visit was a familiarization session. A two-period crossover design with order randomization within visits was used over the second and third visits. SITA Standard, SITA Fast, and HFA 640 Full Threshold were administered during one visit. FASTPAC and HFA 750 Full Threshold were administered during the remaining visit. RESULTS: Group mean Mean Sensitivity was 0.8 dB higher for SITA Standard than for Full Threshold (P < 0.001) and 1.3 dB higher for SITA Fast than for Full Threshold (P < 0.001). A similar trend was found between SITA and FASTPAC. The group mean Mean Sensitivity for SITA Fast was 0.5 dB higher than for SITA Standard (P < 0.001). The pointwise between-algorithm difference in sensitivity was similar for all algorithms. The pointwise between-algorithm, between-subject variability was lower for SITA. The examination durations for SITA Fast and SITA Standard were half those for FASTPAC and Full Threshold; SITA Fast was 41% that of SITA Standard (P < 0.001). CONCLUSIONS: SITA produced marginally higher mean mean sensitivity compared with that of existing algorithms and markedly reduced examination duration. The reduced between-subject variability of SITA should result in narrower confidence limits for definition of normality.

Long-term follow-up of Molteno drains used in the treatment of glaucoma presenting in childhood.

PURPOSE AND METHODS: This study reviews the long-term follow-up (mean 11.2 years, range 9 months to 16 years 9 months) of Molteno drains used in the treatment of glaucoma presenting in childhood, in 34 eyes of 25 patients. RESULTS: Intraocular pressure control was achieved in 85% of eyes, and vision (where measurable) was maintained in 57% of eyes. Seventy-one per cent of eyes required further surgical intervention. Thirty-two per cent of these cases were for drain-related problems, which may be avoidable with the use of current surgical techniques. The remaining interventions were for associated ocular defects, and for problems caused by multiple surgical procedures and periods of high intraocular pressure during early childhood. CONCLUSIONS: Today the implants are used at an earlier stage in the disease process to try to obtain early and definitive IOP control and so help to optimise the long-term visual prognosis.

The effect of TGF-beta 1 and TGF-beta 2 on the proliferation of human Tenon's capsule fibroblasts in tissue culture.

This study examines the effect of transforming growth factor beta 1 and 2 (TGF-beta 1 and TGF-beta 2) on the proliferation of human Tenon's capsule fibroblasts in tissue culture. Both TGF-beta 1 and TGF-beta 2 were shown to stimulate proliferation at 1000 and 100 pg/ml concentrations. We discuss the significance of these findings with respect to wound healing following trabeculectomy, and postulate why some eyes are more at risk of failure than others.

Effect of TNF, IL-1, and IL-6 on the proliferation of human Tenon's capsule fibroblasts in tissue culture.

Trabeculectomy is a commonly performed procedure for primary open angle glaucoma and is successful in the majority of cases. However, certain factors including aphakia, previous surgery, secondary glaucomas, ethnic origin, and the long term use of topical antiglaucoma medications may be associated with a reduced success rate. The mechanism (or mechanisms) which influence clinical outcome following trabeculectomy remain elusive. Alterations in the composition of the conjunctiva or aqueous humour may be partly responsible for this effect, and this could be mediated by cytokines. In this study we found that tumour necrosis factor (TNF), and interleukin 1 (IL-1) were capable of stimulating the proliferation of Tenon's capsule fibroblasts in tissue culture. Interleukin 6 (IL-6) did not appear to have any effect. The relevance of this to wound healing following trabeculectomy is discussed.

Pilot study on the effect of topical adrenergic medications on human Tenon's capsule fibroblasts in tissue culture.

Recent publications have suggested that the long term use of topical antiglaucoma medications may be detrimental to the outcome of trabeculectomy. In order to investigate this further, the effect of several adrenergic agents and a preservative on the proliferation and viability of human Tenon's capsule fibroblasts in tissue culture were examined. The following compounds were tested: adrenaline (Eppy 1% and pure adrenaline base 1%, Smith & Nephew Pharmaceuticals Ltd); dipivefrine hydrochloride (Propine 0.1% and pure dipivefrine hydrochloride 0.1% Allergan Ltd and Allergan Pharmaceuticals (Ireland) Ltd); benzalkonium chloride (pure benzalkonium chloride 0.01%, Sigma Chemical Company Ltd); the two adrenaline based preparations were also tested in the presence of an antioxidant. None of the tested compounds stimulated the proliferation of fibroblasts. The commercial products tested, their pure compounds, and the preservative all inhibited proliferation and had toxic effects on the cells. In the presence of antioxidant, commercial Eppy and pure adrenaline base appeared to have less effect on proliferation and toxicity. These findings are discussed with reference to the outcome of trabeculectomy.

Influence of apraclonidine and pilocarpine alone and in combination on post laser trabeculoplasty pressure rise.

Apraclonidine and pilocarpine have been shown to be effective in reducing the incidence of intraocular pressure (IOP) spikes following argon laser trabeculoplasty. An additional reduction in the incidence of acute pressure rise might theoretically be expected by combining these two effective agents. In a prospective randomised study we compared the ability of apraclonidine and pilocarpine alone and in combination to prevent post laser pressure spikes. Patients receiving regular pilocarpine to either eye were excluded. Seventy five eyes received either apraclonidine (26 eyes), pilocarpine (23 eyes), or both drugs (26 eyes). Apraclonidine 1% was instilled 1 hour before and immediately after, and pilocarpine 4% immediately after trabeculoplasty. IOP was measured before and at 1, 2, and 3 hours following trabeculoplasty. In only two (8%) eyes receiving combined treatment was a pressure rise observed. This frequency was significantly lower than that seen in eyes treated with apraclonidine alone (38%), or pilocarpine alone (39%). The mean fall in IOP at 1, 2, and 3 hours was significantly greater in those eyes receiving combined treatment than in the other two groups.

Intra-operative use of 5-fluorouracil in glaucoma filtering surgery.

This study reviews the outcome of 14 eyes considered to be at risk of surgical failure undergoing trabeculectomy with 5-Fluorouracil (5-FU). The antimetabolite was administered intra-operatively by placing a surgical sponge soaked in 5-FU (25 mg/ml) directly on the sclera under the conjunctival flap for 5 minutes. All eyes showed a reduction in intraocular pressure (IOP) at a mean follow-up of 18.5 weeks, and only one eye required topical antiglaucoma medication. Mean IOP reduction at final follow-up was 43.1%. No eyes showed any corneal problems associated with the intra-operative use of 5-FU. These results suggest that the intra-operative use of 5-Fluorouracil is an effective way of improving surgical success in at risk eyes. The early complications appear to be less than those associated with post-operative subconjunctival injections of 5-FU, but the long-term differences are still to be shown.

Choroidal melanoma presenting as vitreous haemorrhage.

Vitreous haemorrhage is an unusual presenting feature of malignant melanoma of the choroid. We describe three cases in which this occurred. The three tumours shared a number of common features: all were located in the peripheral choroid, were of a similar size and had a small herniation of tumour tissue through Bruch's membrane. We believe that vascular congestion caused by constriction of the tumour vasculature at the site of herniation is the most probable cause for the haemorrhage in these cases. We review the relevant literature and discuss some of the commoner differential diagnoses.

Bilateral optic nerve sheath meningiomas in a patient with neurofibromatosis type 2.

A 34-year-old woman who presented with hearing loss and tinnitus was found to have reduced vision bilaterally. Computed tomography scan revealed bilateral acoustic neuromas and bilateral optic nerve sheath meningiomas. The presence of bilateral acoustic neuromas fulfils the criteria for the diagnosis of central neurofibromatosis (neurofibromatosis type 2). Although this is the first report of bilateral optic nerve sheath meningioma in neurofibromatosis type 2, meningiomas are commoner in this dominantly inherited disorder, than in its absence and both forms of central nervous system tumour may be caused by loss of tumour suppressor genes on chromosome 22.