Glaucoma: an area of darkness.

This review of Primary Open Angle Glaucoma looks at the management of the condition today. It does this by looking at the following areas: (a) the size of the problem; (b) the position of IOP, with respect to its elevation and fluctuation; (c) optic nerve head changes; and (d) visual function changes. In doing so, it contrasts what is known now with ideas and concepts that were prevalent at the time of the two previous Bowman lecturers, Duke Elder and Drance, as well as noting concepts about the disease that were current at the time of William Bowman. The review concludes by suggesting challenges in this area that lie ahead.

The morphology of the optic nerve head in the Singaporean Chinese population (the Tanjong Pagar study): part 1--Optic nerve head morphology.

BACKGROUND/AIMS: To investigate the correlation between optic disc parameters and their association with demographic variables in a Chinese population. METHODS: Disc data were obtained from 929 subjects aged > or = 40 years from the Tanjong Pagar glaucoma survey of Singapore, using a novel planimetric method of sequential stereo-photographs. Biometric data (refractive error, keratometry, axial length, anterior chamber depth, lens thickness) were used to calculate ocular magnification. Camera magnification was quantified with a model eye. A "normal" dataset of 622 subjects was generated by exclusion of subjects with abnormal results on psychophysical testing, an occludable angle or an intraocular pressure > 97.5th percentile in either eye. RESULTS: Median disc area (DA), cup area (CA), and rim area (RA) were 2.09 (range 1.28-4.01) mm2, 0.69 (0.01-1.90) mm2 and 1.38 (0.82-2.50) mm2, respectively. There was strong evidence of an association between DA and RA (Spearman's rho 0.624, p<0.001). DA and RA were significantly greater in men (median DA = 2.20; range 1.30-3.56; median RA, 1.45; range 0.85-2.30) than women (median DA, 2.00; range 1.28-4.01; median RA, 1.36; range 0.82-2.49, p<0.001). DA increased with age (Spearman's rho 0.115, p = 0.004), while RA was unrelated (rho -0.041; p = 0.308). CONCLUSIONS: The morphometric characteristics of optic discs in Chinese Singaporeans are very similar to those described in other groups, with the temporal sector rim having the smallest area. Disc and rim areas vary with sex (men > women). Disc area (but not that of the rim) increases with age.

The morphology of the optic nerve head in the Singaporean Chinese population (the Tanjong Pagar study): part 2--Biometric and systemic associations.

BACKGROUND/AIMS: To investigate the association of biometric and systemic variables with optic disc characteristics in Chinese Singaporean adults. METHODS: Ocular, biometric and medical data including intraocular pressure, refractive error, keratometry, axial length (AL), anterior chamber depth, corneal and lens thickness as well as optic disc data (using planimetry of stereo-photographs) were obtained from 622 normal subjects aged > or = 40 years from the Tanjong Pagar glaucoma survey of Singapore. RESULTS: Disc area (DA) was positively associated with AL and height but was unrelated to corneal thickness. Following adjustment for IOP and sex, DA remained positively associated with AL, height and age. Neuroretinal rim area (RA) was also significantly and positively associated with AL and also with height. RA was negatively associated with IOP and was unrelated to blood pressure, history of diabetes, myocardial infarction, stroke or migraine. CONCLUSIONS: These data on a Chinese Singaporean population identify height and axial length of the globe as significantly associated with rim area of the disc. These features should be taken into account in statistical assessments of optic nerve head morphometry. This may improve the discriminative ability of image analysis to detect glaucomatous changes. In addition, we identified a statistically significant but small inverse association between rim area and IOP within the normal statistical range.

Direct costs of glaucoma and severity of the disease: a multinational long term study of resource utilisation in Europe.

BACKGROUND: Resource utilisation and direct costs associated with glaucoma progression in Europe are unknown. As population progressively ages, the economic impact of the disease will increase. METHODS: From a total of 1655 consecutive cases, the records of 194 patients were selected and stratified by disease severity. Record selection was based on diagnoses of primary open angle glaucoma, glaucoma suspect, ocular hypertension, or normal tension glaucoma; 5 years minimum follow up were required. Glaucoma severity was assessed using a six stage glaucoma staging system based on static threshold visual field parameters. Resource utilisation data were abstracted from the charts and unit costs were applied to estimate direct costs to the payer. Resource utilisation and estimated direct cost of treatment, per person year, were calculated. RESULTS: A statistically significant increasing linear trend (p = 0.018) in direct cost as disease severity worsened was demonstrated. The direct cost of treatment increased by an estimated 86 for each incremental step ranging from 455 euro per person year for stage 0 to 969 euro per person year for stage 4 disease. Medication costs ranged from 42% to 56% of total direct cost for all stages of disease. CONCLUSIONS: These results demonstrate for the first time in Europe that resource utilisation and direct medical costs of glaucoma management increase with worsening disease severity. Based on these findings, managing glaucoma and effectively delaying disease progression would be expected to significantly reduce the economic burden of this disease. These data are relevant to general practitioners and healthcare administrators who have a direct influence on the distribution of resources.

A practical approach to measuring the visual field component of fitness to drive.

AIMS: To determine the level of agreement between merged monocular visual field tests (the integrated visual field) and the binocular Esterman visual field test in classifying patients' visual status for UK legal fitness to drive. To examine the link between these two tests and the useful field of view (UFOV) test, a test which is considered to be a surrogate for the visual capability for safe driving. METHODS: Primary open angle glaucoma patients with bilateral overlapping visual field defects were recruited prospectively. Patients performed the bilateral monocular field tests (to generate the integrated visual field), the Esterman test and the UFOV test on the same visit. Patients were classified as "pass" or "fail" by both the integrated visual field and the Esterman test. UFOV risk scores were calculated for each patient. RESULTS: 65 patients were recruited. Substantial agreement was found between the integrated visual field and the Esterman test in classifying patients as "pass" or "fail" (kappa = 0.69). No patients classified as "pass" by the integrated visual field test were classified as "fail" by the Esterman test. Eight patients who were classified as "pass" by the Esterman test were classified as "fail" by the integrated visual field test. The UFOV risk characteristics of these eight patients suggested they were more similar to those of the 13 patients who were classified as "fail" by both the tests, than the 44 patients who were classified as "pass" by both tests. CONCLUSIONS: The integrated visual field test agrees well with the current method (Esterman) of classifying visual fields with regard to legal fitness to drive in the United Kingdom in patients with glaucoma; it appears superior to the current method in identifying those with reduced fitness to drive as measured by the UFOV. The integrated visual field test could perform a valuable screening or diagnostic role in the assessment of glaucoma patients' fitness to drive.

Interobserver agreement on visual field progression in glaucoma: a comparison of methods.

AIM: To examine the level of agreement between clinicians in assessing progressive deterioration in visual field series using two different methods of analysis. METHODS: Each visual field series satisfied the following criteria: more than 19 reliable fields, patient age over 40 years, macular threshold at least 30 dB. The first three fields in each series were excluded to minimise learning effects: the following 16 were studied. Five expert clinicians assessed the progression status of each series using both standard Humphrey printouts and pointwise linear regression (PROGRESSOR). The level of agreement between the clinicians was evaluated using a weighted kappa statistic. RESULTS: A total of 432 tests comprising 27 visual field series of 16 tests each were assessed by the clinicians. The level of agreement on progression status between the clinicians was always higher when they used PROGRESSOR (median kappa = 0.59) than when they used Humphrey printouts (median kappa = 0.32). This was statistically significant (p = 0.006, Wilcoxon matched pairs signed rank sum test). CONCLUSIONS: Agreement between expert clinicians about visual field progression status is poor when standard Humphrey printouts are used, even when the field series studied are long and consist solely of reliable fields. Under these ideal conditions, clinicians agree more closely about patients' visual field progression status when using PROGRESSOR than when inspecting series of Humphrey printouts.

Variability across the optic nerve head in scanning laser tomography.

AIM: To characterise measurement variability in scanning laser tomography of the optic nerve head. METHODS: 21 normal and 21 glaucoma subjects underwent same and separate day test-retest Heidelberg retina tomograph imaging by the same and different operators. RESULTS: Rim area was most reproducible among parameters. Its variability tended to be highest temporally and increased (p<0.05) with testing involving different operators and visits. Nature of regional variability differed between glaucoma and normal eyes and between standard and 320 micro m reference planes. CONCLUSIONS: Rim area is reproducible and potentially useful as a marker of progression. Pattern of variability and the influence of different reference planes, disease, operators, and visits should be considered when evaluating progression.

The phenotype of normal tension glaucoma patients with and without OPA1 polymorphisms.

AIM: Polymorphisms in OPA1, the gene responsible for autosomal dominant optic atrophy, were recently found to be strongly associated with normal tension glaucoma (NTG). The aim of this study was to determine whether OPA1 polymorphisms affect the phenotype of NTG patients. METHODS: A retrospective analysis was performed of 108 well characterised NTG patients who had been genotyped for OPA1 variations, and who had previously undergone automated perimetry and Heidelberg retina tomography (HRT). 25 NTG patients had the at-risk OPA1 genotype (IVS 8 +4 C/T; +32 T/C) and 83 NTG patients did not. Differences between groups were sought in a wide range of structural, psychophysical, and demographic factors. These included sex, age at diagnosis, family history of glaucoma, history of ischaemic risk factors and vasospasm, laterality of glaucoma, presenting and highest diurnal intraocular pressure (IOP), initial cup-disc (CD) ratio, baseline visual field global indices, and optic disc parameters as measured by HRT. For a subgroup of patients with at least 5 years of follow up and 10 visual field tests, pointwise linear regression analysis (PROGRESSOR for Windows software) was applied to the visual field series. RESULTS: There was no significant difference in the two groups with respect to sex, age at diagnosis, family history of glaucoma, history of ischaemic risk factors and vasospasm, or laterality of glaucoma. The comparison of IOP, CD ratio and visual field global indices, MD and CPSD in the two groups showed no significant difference. There were no differences in the mean values for any of the HRT parameters analysed. For the subgroup of patients with at least 5 years of follow up, there was also no significant difference in the number of patients with progressing locations, the mean number of progressing locations per subject, the mean slope of the progressing locations or the mean slope for whole visual field. CONCLUSIONS: The absence of phenotypic differences in normal tension glaucoma patients with and without the OPA1 polymorphisms IVS 8 +4 C/T; +32 T/C suggest that these OPA1 polymorphisms do not underlie any major phenotypic diversity in these patients.

Effect of treatment by medicine or surgery on intraocular pressure and pulsatile ocular blood flow in normal-pressure glaucoma.

PURPOSE: To study the effect of trabeculectomy and monotherapy with topical betaxolol, brimonidine and latanoprost on intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) in patients with normal-pressure glaucoma (NPG). METHODS: In this retrospective study NPG patients attending the glaucoma research unit at Moorfields Eye Hospital were reviewed. Patients treated by surgery or topical medication (betaxolol, brimonidine or latanoprost) who had pre- and post-treatment IOP and POBF measurements were studied. For those patients who were having treatment to both eyes, one eye was selected at random for analysis. RESULTS: A total of 147 patients were reviewed. Forty-three eyes were receiving betaxolol 0.5%, 58 eyes latanoprost 0.005%, 23 eyes brimonidine 0.2% and 23 eyes had undergone trabeculectomy surgery. There were more female than male patients in all four groups, and the groups were similar with regards age. Pre-treatment IOP and POBF values were similar among the groups ( P=0.27, P=0.08 respectively). Post-treatment IOP values tended to be lower than pre-treatment values for all four groups. All groups had an increased POBF except for betaxolol, where POBF decreased. CONCLUSION: Patients treated by trabeculectomy and those receiving topical latanoprost and brimonidine had lower IOP and higher POBF following treatment. The betaxolol-treated group, despite a slight decrease in IOP, had a decreased POBF. Lowering IOP by treatment may not necessarily be associated with an increase in POBF.

Use of high spatial resolution perimetry to identify scotomata not apparent with conventional perimetry in the nasal field of glaucomatous subjects.

AIM: To examine whether high spatial resolution perimetry (HSRP) could identify fine scale scotomata which may not be apparent with conventional perimetry. The HSRP was performed in the nasal field, as this location is a recognised site for the early occurrence of glaucomatous defects. METHOD: 16 early glaucoma eyes, 17 glaucoma suspect eyes, and 20 age matched healthy control eyes underwent conventional automated perimetry using the 24-2 program of the Humphrey field analyser (HFA) and HSRP. The HSRP was performed in the nasal field by testing 9 x 9 degrees of 100 tested points separated by 1 degree and the results compared with the HFA 24-2 program. RESULTS: Mean HSRP thresholds were significantly abnormal in the suspect and glaucoma eyes, with elevated levels of asymmetry between the superior and inferior nasal field. Overall, 7/17 (41%) suspect eyes (95% confidence interval 5/17 (29%) to 7/17 (41%)) had nasal scotomata on HSRP, although their HFA 24-2 fields failed to identify any defects. In glaucomatous eyes, 15/16 (94%) eyes had HSRP scotomata (95% CI 14/16 (88%) to 15/16 (94%)). In 12 these coexisted with HFA 24-2 defects at the same location, while in three eyes only HSRP identified scotomata in the nasal field. CONCLUSION: HSRP can identify scotoma in glaucomatous eyes in the nasal field which may be missed with the lower spatial resolution of conventional perimetry.

Optic disc changes following trabeculectomy: longitudinal and localisation of change.

AIMS: To determine whether there were any changes in the optic disc at 2 years after trabeculectomy. To determine the factors that most influenced change and whether change was localised to any region of the optic disc. METHODS: 95 patients undergoing routine trabeculectomy as part of the ongoing Moorfields/MRC 5-fluorouracil trial were recruited into the study. Eyes were imaged preoperatively (4 (SD 3) weeks) with the Heidelberg retina tomograph (HRT, Heidelberg Engineering), and at 3 months (SD 2 weeks), 1 year (SD 1 month), and 2 years (SD 1 month) after surgery. Parameters investigated for change were rim area, rim volume, and maximum cup depth. The predefined segment analysis available on the HRT analysis software was used to determine segmental change. RESULTS: The images of 70 patients were analysed. Intraocular pressure reduced from 22.25 (SD 3.76) mm Hg, at the time of preoperative imaging to 15.27 (SD 4.96) mm Hg at 3 months, 14.38 (SD 3.89) mm Hg at 1 year, and 13.80 (SD 3.54) mm Hg at 2 years after trabeculectomy. An increase in rim area and rim volume was present at all time points after surgery, but was only found to be statistically significant at 2 years after surgery. Maximum depth of cup reduced by month 3 and month 12, but showed a slight increase at 2 years after surgery, although this was still lower than the preoperative measure. Segmental analysis found a significant change in rim volume in the nasal, inferonasal, superonasal, and superotemporal regions at 2 years after surgery. No significant regional localisation for change was found at any other time point or in any other parameter investigated. CONCLUSIONS: Reversal of disc cupping is present at 2 years after trabeculectomy. The factor most influencing change is reduction of intraocular pressure. Segmental analysis showed that change in rim volume was greatest in the nasal, inferonasal, superonasal and superotemporal regions at 2 years.

Glaucoma surgery with or without adjunctive antiproliferatives in normal tension glaucoma: 2 Visual field progression.

BACKGROUND: Reduction of intraocular pressure by 20-30% with glaucoma drainage surgery slows disease progression in normal tension glaucoma (NTG). It is not clear whether adjunctive antiproliferative agents are necessary or safe in eyes at low risk for scarring. METHOD: 61 eyes of 61 white patients with NTG who had undergone a primary guarded fistulising procedure were reviewed. 20 eyes had no antiproliferatives (nil), 29 had peroperative 5-fluorouracil (5-FU), and 12 had peroperative mitomycin C (MMC). Pointwise linear regression analysis (PROGRESSOR for Windows software) was applied to their visual field series starting with the first visual field following surgery and adding subsequent visual fields one at a time. Progression of visual field loss was defined as the appearance of a regression slope 1 dB per year or more with a significance of p<0.01 at one or more visual field locations which remained consistent with the addition of two of three successive visual fields. Time updated covariate analysis was used to determine the relation between variables that changed with time, such as IOP, and the risk of progression. RESULTS: The median percentage IOP reduction was 24.4 for the nil group, 38.0 for the 5-FU group, and 47.5 for the MMC group (p=0.001). There was a statistically significant relation between percentage change in IOP and risk of visual field progression in the subsequent 6 month period for all patients analysed as one group, hazard ratio = -0.021 (p=0.002). There was a statistically significantly increase in the risk of visual field progression for the MMC group compared with the 5-FU group, hazard ratio = 1.51 (p=0.02). CONCLUSION: In NTG patients, the IOP reduction produced by drainage surgery reduces the risk that visual field progression may be reduced after drainage surgery; this is related to the level of IOP reduction. The percentage drop in IOP during a given time is related to the risk of subsequent visual field progression. However, the use of MMC is associated with a greater risk of visual field progression despite a greater fall in IOP. This visual field deterioration may be related to the functional loss produced by late postoperative complications which have been reported at a higher rate in this group. The use of adjunctive perioperative 5-FU should maintain a suitable target IOP with preservation of visual function without the additional complications and associated visual deterioration seen with adjunctive MMC.

The ability of the GDx nerve fibre analyser neural network to diagnose glaucoma.

PURPOSE: To evaluate the neural network used by the GDx in a group of normal subjects, patients with ocular hypertension (OHT) and patients with normal-pressure glaucoma (NPG). METHODS: The GDx neural network produces a "number" that indicates the likelihood that glaucoma is present. This number was compared in three groups representing different stages of health and disease, namely, normal controls (n = 101), OHT (n = 102) and NPG (105). The GDx number's ability to differentiate between normal and glaucoma individuals was then investigated. We also studied the relationship between the GDx number and retinal nerve fibre layer (RNFL) average thickness and visual field status to examine how well the GDx number reflects disease severity. RESULTS: The GDx number was significantly different among the groups (P < 0.01); it was highest in NPG and lowest in normal controls. The GDx number differentiated between glaucoma and normal with sensitivity of 92.3% and specificity of 96%. When combined with the parameter of RNFL average thickness, sensitivity and specificity were 88.5% and 100% respectively. In NPG a significant correlation was found between the GDx number and RNFL average thickness(rho = -0.88, P < 0.001) and visual field mean deviation (rho = -0.64, P < 0.001). CONCLUSION: The GDx number is able to differentiate between groups of normal, OHT and NPG subjects. Its close relationship with RNFL average thickness and visual field status in glaucoma indicates that it is able to reflect disease severity. Furthermore, its measured ability to distinguish between normal individuals and those with glaucoma demonstrates potential for use in glaucoma diagnosis.

Glaucomatous optic disc changes in the contralateral eye of unilateral normal pressure glaucoma patients.

OBJECTIVE: To evaluate the optic disc for structural abnormalities in the contralateral eye of unilateral normal pressure glaucoma patients. DESIGN: Cross-sectional study. PARTICIPANTS: Fifty-three unilateral normal pressure glaucoma patients. TESTING: Optic disc imaging with the Heidelberg Retina Tomograph (HRT). MAIN OUTCOME MEASURES: Optic disc structural parameters. RESULTS: Of the contralateral (normal visual field) eyes, 79.2% were found to have an abnormal optic disc by HRT analysis. Of the glaucomatous (abnormal visual field) eyes, 94.3% were found to have an abnormal disc. The patterns of disc abnormality were defined as marked or moderate diffuse thinning of the neuroretinal rim (NRR) or broad or narrow focal thinning of the NRR. The most common pattern in the contralateral eyes was moderate diffuse thinning of the NRR (45.2%). The most frequently abnormal segments were the nasal superior (73. 8%) followed by the nasal inferior and the global NRR parameter (both 54.8%). CONCLUSIONS: A high frequency of NRR thinning was found in the contralateral (normal visual field) eyes of unilateral normal pressure glaucoma patients by HRT analysis. Knowing whether these abnormalities predict future progression to the development of visual field abnormality must wait until longitudinal studies are completed. If a disc abnormality is shown to predict future field loss, then early identification will allow early treatment.