Philip House

The critical role of the conjunctiva in glaucoma filtration surgery

This review considers the critical role of the conjunctiva in determining the success or failure of glaucoma filtration surgery. Glaucoma filtration surgery can be defined as an attempt to lower intraocular pressure (IOP) by the surgical formation of an artificial drainage pathway from the anterior chamber to the subconjunctival space. Many types of glaucoma filtration surgery have been developed since the first attempts almost 180 years ago. The wide range of new techniques and devices currently under investigation is testament to the limitations of current techniques and the need for improved therapeutic outcomes. Whilst great attention has been paid to surgical techniques and devices to create the drainage pathway, relatively little attention has been given to address the question of why drainage from such artificial pathways is often problematic. This is in contrast to normal drainage pathways which last a lifetime. Furthermore, the consequences of potential changes in aqueous humour properties induced by glaucoma filtration surgery have not been sufficiently addressed. The mechanisms by which aqueous fluid is drained from the subconjunctival space after filtration surgery have also received relatively little attention. We propose that factors such as the degree of tissue damage during surgery, the surrounding tissue reaction to any surgical implant, and the degree of disruption of normal aqueous properties, are all factors which influence the successful formation of long term drainage channels from the conjunctiva, and that these channels are the key to successful filtration surgery. In recent years it has been suggested that the rate of fluid drainage from the subconjunctival space is actually the determining factor in the resultant IOP reduction. Improved knowledge of aqueous humour induced changes in such drainage pathways has the potential to significantly improve the surgical management of glaucoma. We describe for the first time a novel type of drainage surgery which attempts to minimise surgical trauma to the overlying conjunctiva. The rationale is that a healthy conjunctiva allows drainage channels to form and less opportunity for inflammation and scar tissue formation which are a frequent cause of failure in glaucoma filtration surgery. Successful drainage over extended periods of time has been demonstrated in monkey and rabbit eyes. Long lasting drainage pathways were clearly associated with the presence of lymphatic drainage pathways. A new philosophy in glaucoma drainage surgery is proposed in which minimisation of surgical trauma to the conjunctiva and the encouragement of the development of conjunctival drainage pathways, particularly lymphatic pathways, are central pillars to a successful outcome in glaucoma filtration surgery.

Cerebrospinal fluid pressure and the eye

Cerebrospinal fluid pressure (CSFP) interacts with intraocular pressure (IOP) and blood pressure to exert a major influence upon the eye, particularly the optic nerve head region. There is increased interest regarding the influence of CSFP upon disorders affecting this region, in particular glaucoma and idiopathic intracranial hypertension. Additionally, a high proportion of astronauts develop features similar to idiopathic intracranial hypertension that persist for years after returning to Earth. The factors that affect the CSFP influence upon the optic nerve and globe are likely to influence the outcome of various ophthalmic disorders.

Spatial modeling of visual field data for assessing glaucoma progression.

PURPOSE In order to reduce noise and account for spatial correlation, we applied disease mapping techniques to visual field (VF) data. We compared our calculated rates of progression to other established techniques. METHODS Conditional autoregressive (CAR) priors, weighted to account for physiologic correlations, were employed to describe spatial and spatiotemporal correlation over the VF. Our model is extended to account for several physiologic features, such as the nerve fibers serving adjacent loci on the VF not mapping to the adjacent optic disc regions, the presence of the blind spot, and large measurement fluctuation. The models were applied to VFs from 194 eyes and fitted within a Bayesian framework using Metropolis-Hastings algorithms. RESULTS Our method (SPROG for Spatial PROGgression) showed progression in 42% of eyes. Using a clinical reference, our method had the best receiver operating characteristics compared with the point-wise linear regression methods. Because our model intrinsically accounts for the large variation of VF data, by adjusting for spatial correlation, the effects of outliers are minimized, and spurious trends are avoided. CONCLUSIONS by using CAR priors, we have modeled the spatial correlation in the eye. combining this with physiologic information, we are able to provide a novel method for VF analysis. model diagnostics, sensitivity, and specificity show our model to be apparently superior to CURRENT POINT-wise linear regression methods. (http://www.anzctr.org.au number, ACTRN12608000274370.).

Visual field of high-pass resolution perimetry in normal subjects.

PurposeTo investigate the properties of the visual field of high-pass resolution perimetry in normal subjects. MethodsFour centers collected normative data for high-pass resolution perimetry. In two of the centers the subjects were stratified by age. One eye was tested per subject using high-pass resolution perimetry (Ophthimus®). We tested 640 normal subjects and describe their visual field results by test location. We also analyzed the data by concentric zone, age, and by testing center. ResultsThe individual test location averages confirmed a reduction in resolution with eccentricity. Resolution thresholds increased with age by 0.025 dB per year (P < 0.001). The mean ring size increased by about 1 dB from age 20 to 70. Among centers there were significant differences in the means and the change in threshold with age (P = 0.009). ConclusionThe normal visual field of high-pass resolution perimetry is characterized by an increase in threshold with eccentricity. We found significant differences among the centers that were likely due to multiple factors including differences in subject selection criteria. Whether such differences occur with other perimetric techniques is unknown.

Long-term topical timolol and blood lipids: the Blue Mountains Eye Study.

Objectives: To examine whether an association exists between long‐term use of topical timolol and blood lipids, including high‐density lipoprotein cholesterol (HDLC), cholesterol, and triglycerides, among participants of the Blue Mountains Eye Study. Methods: From 1992 through 1994, a detailed medical and eye examination was performed in 3,654 people aged 49 years or older, representing 82% of permanent residents in two postcode areas west of Sydney. Glaucoma and ocular hypertension were diagnosed, and an ophthalmic history was taken, including use of topical timolol. Fasting blood tests were performed in 89% of subjects. Lipid levels were compared in subjects using topical timolol for at least 1 year with those not using timolol, after excluding people using oral &bgr;‐blockers, topical &bgr;1‐selective agents, or oral lipidlowering medications. Results: Analyses compared blood lipids of 63 people who had used topical timolol for at least 1 year with 2,597 nonusers. No statistically significant differences were found in any blood lipid mean levels between treated and untreated people, after multivariate adjustment. However, subgroup analyses of men and women separately showed that male timolol users had a mean value of HDL‐C 0.13 mmol/L (11%) lower then the mean value of male nonusers, while female timolol users had a mean value of HDL‐C 0.09 mmol/L (5%) higher than the mean for female nonusers. There were no statistically significant associations between timolol treatment duration and HDL‐C or other lipid levels. Previously reported adverse effects of oral &bgr;‐blockers on blood lipid levels were confirmed. Conclusions: These population‐based data suggest that long‐term administration of topical timolol for glaucoma or ocular hypertension can cause adverse effects on HDL‐C in men, but not in women. The magnitude of the effect in men was similar to that previously described in a number of short‐term studies.

Photoplethysmographic measurement of various retinal vascular pulsation parameters and measurement of the venous phase delay.

PURPOSE Retinal vein pulsation properties are altered by glaucoma, intracranial pressure (ICP) changes, and retinal venous occlusion, but measurements are limited to threshold measures or manual observation from video frames. We developed an objective retinal vessel pulsation measurement technique, assessed its repeatability, and used it to determine the phase relations between retinal arteries and veins. METHODS Twenty-three eyes of 20 glaucoma patients had video photograph recordings from their optic nerve and peripapillary retina. A modified photoplethysmographic system using video recordings taken through an ophthalmodynamometer and timed to the cardiac cycle was used. Aligned video frames of vessel segments were analyzed for blood column light absorbance, and waveform analysis was applied. Coefficient of variation (COV) was calculated from data series using recordings taken within ±1 unit ophthalmodynamometric force of each other. The time in cardiac cycles and seconds of the peak (dilation) and trough (constriction) points of the retinal arterial and vein pulse waveforms were measured. RESULTS Mean vein peak time COV was 3.4%, and arterial peak time COV was 4.4%. Lower vein peak occurred at 0.044 cardiac cycles (0.040 seconds) after the arterial peak (P = 0.0001), with upper vein peak an insignificant 0.019 cardiac cycles later. No difference in COV for any parameter was found between upper or lower hemiveins. Mean vein amplitude COV was 12.6%, and mean downslope COV was 17.7%. CONCLUSIONS This technique demonstrates a small retinal venous phase lag behind arterial pulse. It is objective and applicable to any eye with clear ocular media and has moderate to high reproducibility. ( http://www.anzctr.org.au number, ACTRN12608000274370.).

Intraocular pressure reduction is associated with reduced venous pulsation pressure

Purpose To explore whether alterations in intraocular pressure (IOP) affect vein pulsation properties using ophthalmodynamometric measures of vein pulsation pressure. Patients and Methods Glaucoma patients had two retinal vein pulsation pressure (VPP) measurements from upper and lower hemiveins performed by ophthalmodynamometry at least 3 months apart. All subjects had VPP and IOP recorded at two visits, with standard automated perimetry, central corneal thickness (CCT) recorded at the initial visit. Where venous pulsation was spontaneous ophthalmodynamometry could not be performed and VPP was considered equal to IOP. Change in VPP was calculated and binarized with reduction in pressure scored 1 and no change or increase scored as 0. Data analysis used a mixed logistic regression model with change in VPP as response variable and change in IOP, visual field loss (mean deviation), CCT and time interval as explanatory variables. Results 31 subjects (20 females) with mean age 60 years (sd 11) were examined with change in VPP being significantly associated with change in IOP (odds ratio 1.6/mmHg, 95% CI 1.2 to 2.1 in the glaucoma patients but not suspect patients (p = 0.0005). Conclusion Change in VPP is strongly associated with change in IOP such that a reduced intraocular pressure is associated with a subsequent reduction in VPP. This indicates that reduced IOP alters some retinal vein properties however the nature and time course of these changes is not known.

Efficacy and safety of Bimatoprost as replacement for Latanoprost in patients with glaucoma or ocular hypertension: A uniocular switch study

PurposeTo assess the efficacy and safety of switching patients from bilateral latanoprost to bimatoprost in 1 eye while maintaining latanoprost in the fellow eye. Patients and MethodsThis prospective, open-label, multicenter, uniocular (within-eye control) study was conducted from March 2005 to February 2007; 105 patients with glaucoma or ocular hypertension were enrolled. At baseline, patients using bilateral latanoprost were switched to bimatoprost treatment in 1 eye (study eye) and continued latanoprost treatment in the fellow eye (control eye). At 12 weeks, patients were offered bilateral bimatoprost for 12 additional weeks. ResultsAt week 12, the mean difference in intraocular pressure (IOP) from baseline was −3.0 mm Hg in study eyes and −1.6 mm Hg in control eyes, which equates to a further −1.4 mm Hg (95% confidence limits: −1.9, −0.9) reduction in IOP in study eyes compared with control eyes (P<0.0001). Overall, 27% (28/104) more study eyes had ≥−2.5 mm Hg reduction in IOP than control eyes (P<0001). At week 24, the mean difference in IOP from baseline was −2.8 mm Hg for study eyes and for control eyes that had switched to bimatoprost. Conjunctival hyperemia occurred more frequently and was more severe in bimatoprost-treated eyes at week 12 than at baseline (P<0.001). No patients withdrew from treatment because of conjunctival hyperemia. ConclusionsClinically, these data suggest that switching patients from latanoprost to bimatoprost may result in further improvement in IOP control.

Relationship between intraocular pressure and glaucomatous optic neuropathy

The paper of Landers et al. was a retrospective case review of 739 new cases presenting to a tertiary referral practice with a diagnosis of glaucoma or ocular hypertension. Risk factors that might be associated with the diagnosis of glaucoma were analyzed in a univariate and multivariate way. The results showed a strong association between IOP and glaucoma (Fig. 1). The clear trend to increased risk with increased IOP is supported by Landers analysis, which gives a positive Mantel–Haenszel test for trend ( P < 0.05). The apparent weakening of the association with the multivariate analysis might be due in part to the very strong effect of age on risk (Fig. 2). This may be interpreted as being due to a longer exposure to the higher IOP of the ocular hypertension group leading to conversion to glaucoma. Sponsel chooses the dip in the graph for IOP of 24–29 mmHg to support his contention that IOP is weakly associated with glaucomatous damage. A similar comment could also be made for the drop in risk above 32 mmHg. We were surprised to see these results, but feel that it may be due to stochastic aberration or related to the study design. Patients in the study were not randomly selected. An undisclosed number of the glaucoma patients would have already been on treatment and details of wash out to reach the ‘native eye pressure’ are not given. Indeed, Landers et al. emphasize that their paper was designed to look at associated risk factors, rather than IOP. 2

Estimating thresholds in conventional and high-pass resolution perimetry using computer simulation.

High-pass resolution perimetry is a new technique that uses a vanishing optotype as the test stimulus. This type of stimulus is thought to produce steeper frequency-of-seeing curves than the stimulus used in conventional automated perimetry, resulting in a lower variability in threshold estimates. The purpose of this study was to compare the stimulus properties in both conventional and high-pass resolution perimetry in computer simulation experiments. The computer model contained stimulus-response data sets obtained from frequency-of-seeing experiments in 11 normal subjects tested with each perimetric technique at four retinal locations [(0 degrees , 30 degrees ), (0 degrees , 15 degrees ), (0 degrees , - 15 degrees ), and (0 degrees , - 30 degrees )]. We programmed eight staircase procedures varying from a coarse one with one reversal to an elaborate procedure with four reversals to look at the relationship between accuracy (the difference between the estimated and actual threshold) and efficiency (number of presentations required for estimate) with each technique. Threshold estimates were made 100 times for each location, strategy, perimetric technique, and subject. Our results showed that an increase in accuracy was always coupled with a decrease in efficiency and that the relationship between these two parameters was similar between the two techniques. Some evidence, however, is presented to show that compared to conventional perimetry relatively simple staircase procedures may be used with high-pass resolution perimetry to attain threshold estimates of similar accuracy.