David C Broadway

Glaucoma and vasospasm

AIMS/BACKGROUND To study the vasoactivity of glaucoma patients with four previously described and distinct disc appearances potentially representative of primary open angle glaucoma subgroups. METHODS Patients with pure examples of four glaucomatous optic disc types—focal ischaemic, myopic glaucomatous, senile sclerotic, and those with generalised cup enlargement, were selected. A detailed ophthalmic, systemic, drug, and smoking history was taken from the patients who, in addition, underwent assessment of peripheral vasospasm with a laser Doppler flowmeter. Differences between the groups were evaluated using an analysis of variance, Student’s t test, Pearson’s χ2 test, Fisher’s exact test together with Spearman’s and Pearson’s correlation tests. RESULTS 38 patients with focal ischaemic, 37 with myopic glaucomatous, 24 with senile sclerotic, and 24 with discs characterised by generalised cup enlargement met the selection criteria. The group of patients with focal ischaemic discs contained more women (66% versus 32%–50% in the other three groups; p=0.01) and had a higher prevalence of vasospasm (63% versus 25%–49%; p=0.01), migraine (32% versus 8%–19%; p=0.02), and cold extremities (66% versus 17%–30%; p=0.00003). The group of patients with senile sclerotic discs had a higher prevalence of systemic cardiovascular disease (58% versus 21%–30% in the other three groups; p=0.01) and thyroid disease (21% cf 0%–8%; p=0.01) and although their mean age was greater (76 years cf 55–65 years; p<0.00001) the findings were independent of age. Smoking was unrelated to optic disc type. CONCLUSION Vasospasm, previously associated with normal tension glaucoma, and generalised cardiovascular disease both appear to be specific risk factors for the development of particular subgroups of glaucoma and may be independent of absolute intraocular pressure levels exerting effects in patients with both “normal” or “raised” intraocular pressure. The simple assessment as to whether a glaucoma patient suffers from colder extremities than average appeared to be better at distinguishing the focal ischaemic type of glaucoma than the more complex determination of vasospasm using the laser Doppler flowmeter.

Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial

BACKGROUND Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. METHODS In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. FINDINGS We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. INTERPRETATION This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period. FUNDING Pfizer, UK National Institute for Health Research Biomedical Research Centre.

Adverse effects of topical antiglaucomatous medications on the conjunctiva.

With selected patients glaucoma filtration surgery is highly successful. However, there is growing evidence that chronic topical medical therapy has a deleterious effect on surgical outcome. It has been suspected that topical drugs exert an adverse effect on the conjunctiva which results in altered postoperative wound healing. In this review the effect of previous topical antiglaucoma medication on the conjunctiva and the outcome of subsequent glaucoma filtration surgery are discussed.

Racial differences in the results of glaucoma filtration surgery: are racial differences in the conjunctival cell profile important?

Conjunctival biopsies were obtained at the time of filtration surgery from 90 patients with glaucoma; 45 of these patients were black and 45 white. Forty nine of the patients (25 black, 24 white) had undergone a primary trabeculectomy. Comparisons between black and white patients were made with respect to the results of surgery and differences in conjunctival cell profile. In agreement with many authors, trabeculectomy was found to be less successful in black patients (67% compared with 80%), although this finding was not statistically significant by survival analysis. In addition, conjunctiva from black patients was found to contain a greater number of macrophages and a smaller number of both mast cells and goblet cells in comparison with white patients. There was a tendency for conjunctiva from black patients to contain more fibroblasts. Conjunctiva obtained from the patients whose filtration surgery subsequently failed was found to contain more fibroblasts, macrophages, and basal epithelial pale cells. A greater number of conjunctival macrophages and possibly fibroblasts in black patients may partially explain the tendency for a lower success rate of filtration surgery in this group of patients.

Pigment dispersion syndrome and pigmentary glaucoma--a major review.

Pigment dispersion syndrome (PDS) is an interesting condition that can lead to secondary open angle glaucoma. Pigmentary glaucoma is primarily a disease of young people, myopes and men. PDS is characterized by the presence of Krukenberg spindles, iris trans‐illumination defects, trabecular meshwork pigmentation and backward bowing of the iris. Posterior bowing of the iris causes rubbing of the pigmented iris epithelium against lens structures, liberation of pigment and trabecular meshwork changes that result in reduced aqueous outflow with the risk of glaucoma. Peripheral laser iridotomy can reverse backward bowing of the iris and may prevent progression of pigmentary glaucoma.

A two centre study of the dose-response relation for transscleral diode laser cyclophotocoagulation in refractory glaucoma

Background/aims: Transscleral diode laser cyclophotocoagulation (“cyclodiode”) is widely used to treat refractory glaucoma. The main aims of this study were to investigate the dose-response relation of cyclodiode and to evaluate possible predictive factors that would help establish optimum treatment parameters. Methods: A retrospective analysis of the case notes of 263 eyes of 238 consecutive patients who underwent transscleral diode laser cyclophotocoagulation at two centres was undertaken. Results: Mean intraocular pressure (IOP) decreased significantly from 40.7 mm Hg (SD 13.7) before cyclodiode therapy to 17.7 mm Hg (SD 10.9) post-treatment, a reduction of 52.6% (p = 0.0001). Following cyclodiode, 89% of patients achieved an IOP of less than 22 mm Hg or a greater than 30% drop in IOP. Hypotony occurred in 9.5% of patients, 76% of whom had neovascular glaucoma. A linear dose relation response was found for the 122 eyes with neovascular glaucoma (p = 0.001) but not for the group as a whole. Treatment failure was associated with male sex (multivariate regression analysis, p = 0.008) and low mean energy per treatment session (univariate analysis alone, p = 0.016). High pretreatment IOP (p = 0.031) and high mean energy per treatment episode (p = 0.001) appeared to be associated with the occurrence of hypotony, although multivariate analysis did not support this finding. Conclusion: Cyclodiode therapy is highly effective but there is a significant risk of hypotony, which may be reduced by applying lower energy in cases of very high pretreatment IOP and in neovascular glaucoma. The dose-response association remains unpredictable, although a linear relation was found for neovascular glaucoma.

Effect of corneal parameters on measurements using the pulsatile ocular blood flow tonograph and Goldmann applanation tonometer

Aims: To investigate the effect of central corneal thickness and corneal curvature on intraocular pressure measurements using the pulsatile ocular blood flow tonograph and the Goldmann applanation tonometer, and to assess the agreement between the pulsatile ocular blood flow tonograph and the Goldmann applanation tonometer in intraocular pressure measurement. Methods: 479 subjects underwent intraocular pressure measurements with the Goldmann applanation tonometer and the pulsatile ocular blood flow tonograph. Of these, 334 patients underwent additional measurement of central corneal thickness with an ultrasonic pachymeter and corneal curvature measurement with a keratometer. Results: The intraocular pressure measurements obtained with both the Goldmann applanation tonometer and the pulsatile ocular blood flow tonograph varied with central corneal thickness and mean keratometric reading. Intraocular pressure measured using the Goldmann applanation tonometer increased by 0.027 mm Hg per µm increase in central corneal thickness. Intraocular pressure measured using the pulsatile ocular blood flow tonograph increased by 0.048 mm Hg per μm increase in central corneal thickness. For an increase of 1 mm of mean corneal curvature there was rise in intraocular pressure of 1.14 mm Hg measured by the Goldmann applanation tonometer and of 2.6 mm Hg measured by the pulsatile ocular blood flow tonograph. When compared to the Goldmann applanation tonometer, the pulsatile ocular blood flow tonograph underestimated at low intraocular pressure and overestimated at higher intraocular pressure. Conclusion: Central corneal thickness and corneal curvature affected measurements obtained with the pulsatile ocular blood flow tonograph more than they affected measurements obtained with the Goldmann applanation tonometer.

Trabeculectomy in the 21st century: a multicenter analysis.

OBJECTIVE To evaluate the efficacy and safety of current trabeculectomy surgery in the United Kingdom. DESIGN Cross-sectional, multicenter, retrospective follow-up. PARTICIPANTS A total of 428 eyes of 395 patients. METHODS Consecutive trabeculectomy cases with open-angle glaucoma and no previous incisional glaucoma surgery from 9 glaucoma units were evaluated retrospectively. Follow-up was a minimum of 2 years. MAIN OUTCOME MEASURES Surgical success, intraocular pressure (IOP), visual acuity, complications, and interventions. Success was stratified according to IOP, use of hypotensive medications, bleb needling, and resuturing/revision for hypotony. Reoperation for glaucoma and loss of perception of light were classified as failures. RESULTS Antifibrotics were used in 400 cases (93%): mitomycin C (MMC) in 271 (63%), 5-fluorouracil (5-FU) in 129 (30%), and no antifibrotic in 28 (7%). At 2 years, IOP (mean ± standard deviation) was 12.4 ± 4 mmHg, and 342 patients (80%) achieved an IOP ≤ 21 mmHg and 20% reduction of preoperative IOP without IOP-lowering medication, whereas 374 patients (87%) achieved an IOP ≤ 21 mmHg and 20% reduction of preoperative IOP overall. An IOP ≤18 mmHg and 20% reduction of preoperative IOP were achieved by 337 trabeculectomies (78%) without IOP-lowering treatment and by 367 trabeculectomies (86%) including hypotensive medication. Postoperative treatments included suture manipulation in 184 patients (43%), resuturing or revision for hypotony in 30 patients (7%), bleb needling in 71 patients (17%), and cataract extraction in 111 of 363 patients (31%). Subconjunctival 5-FU injection was performed postoperatively in 119 patients (28%). Visual loss of >2 Snellen lines occurred in 24 of 428 patients (5.6%). A total of 31 of the 428 patients (7.2%) had late-onset hypotony (IOP <6 mmHg after 6 months). In 3 of these, visual acuity decreased by >2 Snellen lines. Bleb leaks were observed in 59 cases (14%), 56 (95%) of which occurred within 3 months. Two patients developed blebitis. Bleb-related endophthalmitis developed in 1 patient within 1 month postoperatively and in 1 patient at 3 years. There was an endophthalmitis associated with subsequent cataract surgery. CONCLUSIONS This survey shows that good trabeculectomy outcomes with low rates of surgical complications can be achieved, but intensive proactive postoperative care is required.

A comparison of healthy, ocular hypertensive, and glaucomatous optic disc topographic parameters.

PurposeTo compare the optic discs of 62 healthy individuals 68 patients who have ocular hypertension (OH), and 182 patients with primary open-angle glaucoma (132 high-tension glaucoma (HTG) and 50 normal-tension glaucoma (NTG)), and determine whether disc size exerted an influence on the group differentiation. Patients and MethodsStandard criteria were used to define glaucoma and normality. Ocular hypertension was defined as having raised intraocular pressure, a normal visual field, and a healthy optic disc/retinal nerve fiber layer (RNFL). The optic disc of one eye from each individual was analyzed using a confocal scanning laser ophthalmoscope (Heidelberg Retina Tomograph software version 1.11, Heidelberg Engineering, Heidelberg. Germany). Thirteen topographical, volumetric, and shape parameters were compared between the three diagnostic groups. In addition, the individuals were divided into subgroups on the basis of disc size to determine any effect of disc size on the differentiating ability of the confocal scanning laser ophthalmoscope. Differences between the groups were evaluated using an analysis of variance. ResultsGlaucomatous optic discs were found to differ from both healthy and OH discs, although no differences in disc area between the groups were identified. On the basis of disc size, differentiating the glaucomatous discs was best for midsized discs of 2 mm2 to 3 mm2. However, no difference was found between healthy and OH discs, even when allowing for disc size. ConclusionsOcular hypertensive optic discs (with a clinically normal appearance) could not be distinguished from healthy discs using a confocal scanning laser ophthalmoscopic technique. Glaucomatous optic discs were found to differ from both healthy and OH discs, with a limited effect of disc size.

Intraocular Pressure and Corneal Biomechanics in an Adult British Population: The EPIC-Norfolk Eye Study

PURPOSE To describe the distribution and determinants of intraocular pressure (IOP) and indices of corneal biomechanics in an adult British population. METHODS Goldmann-equivalent IOP (IOPg), corneal mechanical characteristics (corneal hysteresis, CH; corneal resistance factor, CRF), and IOP adjusted for corneal factors (IOPcc) were measured. Ocular biometric characteristics were also measured in 4184 consecutive individuals aged 48 to 91 years recruited from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Sociodemographic data were recorded with a standardized questionnaire. Blood pressure and anthropometric data were recorded by trained staff according to a standard protocol. RESULTS Mean IOP was similar to that reported in previous United Kingdom population studies (IOPg: 16.0 mm Hg, SD 3.68). These data confirmed systolic blood pressure as the major identifiable correlate of IOP. There was a significant positive association between IOP and axial length of the eye. The IOPg, but not IOPcc, was higher in the women than in the men. No difference in IOP between the different age groups was identified. CRF and CH varied with IOPg, age, sex, and axial length of the eye. CONCLUSIONS The study provided current population-based values for IOP and corneal biomechanical parameters. Mean IOP in this British population was very similar to levels previously reported over 40 years ago. There was no identifiable relationship between IOP and age within this cohort with an older age range, in contrast to previous studies. Systolic blood pressure was identified as the major correlate of IOP.