Stefano Miglior

Risk Factors for Glaucoma Onset and Progression

In this review, we distinguish among risk factors associated with the development of open-angle glaucoma in individuals with healthy eyes, predictive determinants for the development of open-angle glaucoma in subjects with ocular hypertension, and prognostic factors for the progression of open-angle glaucoma in individuals who already have the disease. We primarily reviewed recent longitudinal population-based epidemiological studies, prospectively planned clinical trials, and cohort studies. Risk factors consistently associated with the development of open-angle glaucoma in individuals with healthy eyes include older age and an approximately 1 mm Hg increase in intraocular pressure (IOP) at baseline. Family history for open-angle glaucoma may be associated with the development of open-angle glaucoma as well. Predictive factors for the development of open-angle glaucoma in individuals with ocular hypertension may be older age, thinner central corneal thickness, higher cup-to-disk ratios of the optic disc, and higher pattern standard deviation values on the Humphrey automated perimeter at baseline. Given multi-center trials that showed similar predictive factors for the development of open-angle glaucoma in individuals with ocular hypertension, a calculator is available to clinicians for assessing the 5-year likelihood of developing open-angle glaucoma in ocular hypertensive patients with certain characteristics. Prognostic factors for the progression of open-angle glaucoma in individuals who already have the condition include older age at baseline, higher IOP at baseline, and thinner central conreal thickness. Self-report of diabetes may be associated with open-angle glaucoma progression. In conclusion, the only modifiable factor associated with open-angle glaucoma that has been consistently identified is elevated baseline IOP. Future research needs to evaluate the importance of others modifiable factors such as IOP fluctuation or nutritional factors.

Intraobserver and interobserver reproducibility in the evaluation of optic disc stereometric parameters by Heidelberg Retina Tomograph

PURPOSE To assess intraobserver and interobserver reproducibility of the measurement of stereometric parameters of the optic disc by means of the Heidelberg Retina Tomograph I (HRT). STUDY DESIGN Observational study, with interobserver variability. PARTICIPANTS Fifty-five volunteers (healthy subjects and patients with glaucoma). METHODS HRT examination of the optic disc was repeated on 3 consecutive days on 1 eye of each of the 55 subjects. During each session, five single images were randomly acquired by two independent observers. One mean topography image (MTI), based on three single images, was then built at each session. For the intraobserver intraimage evaluation, the two observers traced their own contour line on one randomly chosen MTI. This procedure was repeated three times. For the intraobserver interimage and interobserver intra/interimage evaluations, the two observers traced their own contour line on the MTI of the first session, which was then automatically superimposed on the MTIs of the other two sessions. MAIN OUTCOME MEASURES Reproducibility of the 12 stereometric parameters was calculated for each observer by means of the intraclass correlation coefficient (ICC). The expected range of variability between two independent evaluations was calculated by the scatter-plots of each test-retest difference versus their mean. The standard deviation of the mean test-retest score differences was used to describe the spread of score differences. RESULTS The ICC ranged between 0.79 and 0.99 for intraobserver intraimage and between 0.56 and 1 for intraobserver interimage evaluation. The ICC ranged between 0.54 and 0.99 for interobserver intraimage and between 0.65 and 0.97 for the interobserver interimage evaluation. ICC was almost perfect to perfect for planimetric measures (0.81 < ICC < or = 1), substantial to almost perfect for volumetric and cup measures (0.61 < ICC < or = 0.99), and moderate to almost perfect for retinal nerve fiber layer related measures (0.41 < ICC < 0.99). The expected variability was low (95% confidence interval, < +/-9%). Interimage evaluation showed a higher variability than intraimage evaluation in both of interobserver (P = 0.012) and intraobserver evaluation (P = 0.028 and P = 0.031 for the two observers). CONCLUSIONS Measurement of optic disc stereometric parameters by HRT is highly reproducible. However, the use of retinal nerve fiber layer-related parameters should be taken cautiously. The image acquisition-induced variability seems larger than the operator-induced variability.

The European glaucoma prevention study design and baseline description of the participants.

OBJECTIVES The European Glaucoma Prevention Study seeks to evaluate the efficacy of reducing intraocular pressure (IOP), with dorzolamide to prevent or delay patients affected by ocular hypertension from developing primary open-angle glaucoma. DESIGN Randomized, double-blinded, controlled clinical trial. PARTICIPANTS Patients (age > or =30 years) were enrolled from 18 European centers. The patients fulfilled a series of inclusion criteria including the measurements of IOP (22-29 mmHg), two normal and reliable visual fields (VFs) (on the basis of mean defect and corrected pattern standard deviation/corrected loss of variance of standard 30/II Humphrey or Octopus perimetry), and normal optic disc as determined by the Optic Disc Reading Center (vertical and horizontal cup-to-disc ratios; asymmetry between the two eyes < or =0.4). INTERVENTION Patients were randomized to the treatment with dorzolamide or a placebo. MAIN OUTCOME MEASURES End points are VF and/or optic disc changes. A VF change during the follow-up must be confirmed by two further positive tests. Optic disc change is defined by the agreement of two out of three independent observers evaluating optic disc stereo-slides. RESULTS One thousand seventy-seven subjects were randomized between January 1, 1997 and May 31, 1999. The mean age was 57.03 +/- 10.3 years; 54.41% were women and 99.9% were Caucasian. Mean IOP was 23.6 +/- 1.6 mmHg in both eyes. Mean visual acuity was 0.97 +/- 0.11 in both eyes; mean refraction was 0.23 +/- 1.76 diopters in the right eye and 0.18 +/- 1.79 diopters in the left eye. Previous use of medication for ocular hypertension was reported by 38.4% of the patients, systemic hypertension by 28.1%, cardiovascular diseases by 12.9%, and diabetes mellitus by 4.7%. The qualifying VFs were normal and reliable according to protocol criteria. CONCLUSIONS The mean IOP of the patients enrolled in the European Glaucoma Prevention Study is consistent with the estimated mean IOP (within the range of 22-29 mmHg) found in a large sample of the European population. The European Glaucoma Prevention Study should be able to better address the clinical question of whether pharmacological reduction of IOP (by means of dorzolamide) in ocular hypertension patients at moderate risk for developing primary open-angle glaucoma effectively lowers the incidence of primary open-angle glaucoma.

Microperimetry of localized retinal nerve fiber layer defects

The aim of this study was to determine the sensitivity of retinal areas involved in a localized retinal nerve fiber layer (RNFL) defect and to assess correlations between microperimetry and the standard full threshold central 30 deg visual field test. Twenty-five patients with focal RNFL defects, evaluated by means of Argon-blue scanning laser ophthalmoscopy (SLO), underwent an automated 30 deg central visual field examination and a microperimetry with SLO. Microperimetry was performed according to standard procedures (infrared laser for fundus imaging; HeNe laser for 10 candles/m2 background illumination, fixation aid and generation of stimuli; manual fundus tracking). The size of stimuli was Goldmann III with 0.1 sec duration. In eyes with focal RNFL defects a deep microperimetric scotoma of at least 5 dB was found in 12 cases and a mild scotoma (1-4 dB) in 13 cases. These scotomas were mainly located throughout the whole defect or grouped in the temporal or nasal sides of the defect and were characterized by sharp and well-defined borders. With automated perimetry, a scotoma, defined by a single point depression of at least 10 dB or a depression of at least 5 dB in two or more contiguous points corresponding to the RNFL, defect, was found in only 14 out of 25 eyes with microperimetric defect. Focal RNFL defects correspond to localized areas of depressed retinal sensitivity as evaluated by microperimetry. The close correspondence between structural and microperimetric findings suggests that, in hypertensive eyes also, localized RNFL defects correspond to visual dysfunction possibly associated with substantial atrophy of ganglion cells.

Relationship between morphometric optic disc parameters, sex and axial length

Optic disc correlations were evaluated in normal eyes by means of computer-aided morphometry. Two hundred and thirty-five subjects (144 women and 91 men) entered the study. One eye per patient was randomly chosen for statistical analysis. Disc area (P < 0.05) and axial length (P < 0.0001) were statistically different between sexes. There was a correlation between axial length and both disc area (r for females = 0.55, P < 0.00001; r for males = 0.35, P < 0.0007) and refraction (r for females = 0.40, P < 0.00001; r for males = 0.50, P < 0.00001). The main findings of this investigation were that disc area is greater in male than in female eyes (thus clinically confirming the Ishis and Quigleys previous observations of autopsy eyes) on the basis of axial length difference between the two sexes, and that disc size correlated with axial length. Disagreements in disc measurements reported in previous studies may be caused by differences in the male/female ratios of their samples.

Reproducibility of Retinal Nerve Fiber Layer Evaluation by Dynamic Scanning Laser Ophthalmoscopy

Scanning laser ophthalmoscopy is a laser-based image acquisition technique, which greatly improves the quality of the examination of the fundus and the retinal nerve fiber layer. To assess retinal nerve fiber layer imaging by scanning laser ophthalmoscopy and evaluate intra- and interobserver reproducibility in the classification of retinal nerve fiber layer defects, three independent observers evaluated on two separate occasions the videotaped images of 150 eyes of 80 consecutive patients with ocular hypertension or glaucoma. Ophthalmoscopy was performed using argon blue light (488 nm), confocal apertures of 3 to 1 mm, and 40-degree and 20-degree field angles. Of 150 eyes, 20 (13.3%) were excluded from the study because of the poor quality of the images (clinically significant cataract or myopic peripapillary atrophy). The retinal nerve fiber layer was evaluated qualitatively according to a standard classification: normal pattern, slit, wedge, and diffuse defects. Intraobserver reproducibility, evaluated by kappa statistic, was excellent (> or = 0.75): observer A = 0.78 (95% confidence limits, 0.67-0.88); observer B = 0.84 (95% confidence limits, 0.72-0.96); and observer C = 0.79 (95% confidence limits, 0.67-0.91). Interobserver reproducibility was also excellent in all cases: observers A-B = 0.84 (95% confidence limits, 0.71-0.98); observers A-C = 0.76 (95% confidence limits, 0.65-0.87); and observers B-C = 0.80 (95% confidence limits, 0.69-0.92). Kappa values ranged between 0.59 and 0.69 for intraobserver reproducibility and between 0.55 and 0.69 for interobserver reproducibility when using only those eyes in which abnormalities were noted by at least one observer.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation between the progression of optic disc and visual field changes in glaucoma

Visual field test and optic disc evaluation are the standard examination techniques used to detect the onset and progression of glaucoma. This explorative study was performed to assess the temporal correlation between visual field and optic disc changes in eyes with ocular hypertension and well-established glaucoma. Eighty-six hypertensive and 16 glaucomatous eyes were followed up for a period of up to 9 years (average 4.4 yrs) using kinetic and computerized static perimetry and optic disc manual morphometry. Perimetric changes were based on a series of strict criteria and optic disc changes were based as a reduction in the baseline rim area/disc area ratio (R/D) measurement exceeding the 99% confidence interval for intraobserver reproducibility (7.7%). Optic disc changes were found prior to visual field changes in four hypertensive eyes, whereas visual field changes were found prior to disc changes in six glaucomatous eyes (p = 0.042). The results of our explorative study suggest that quantitative optic disc analysis may be more sensitive than visual field examination in detecting early glaucomatous changes, whereas visual field examination may be more sensitive than quantitative optic disc analysis in detecting glaucomatous progressions in eyes with well established glaucoma.

Efficacy and safety of travoprost/timolol vs dorzolamide/timolol in patients with open-angle glaucoma or ocular hypertension

Purpose: To compare the intraocular pressure- (IOP-) lowering efficacy of fixed combinations travoprost 0.004%/timolol 0.5% and dorzolamide 2%/timolol 0.5% in patients with ocular hypertension or open-angle glaucoma. Methods: In this prospective, multicenter, double-masked, randomized clinical trial, 319 qualifying patients received either travoprost/timolol once daily in the morning (n = 157) or dorzolamide/timolol twice daily (n = 162). IOP was assessed morning and evening at 2 and 6 weeks. The primary outcome measure was mean diurnal IOP. Results: Baseline mean IOP values were similar between groups. Mean pooled diurnal IOP was significantly lower in the travoprost/timolol group (16.5 mmHg ± 0.23) than in the dorzolamide/timolol group (17.3 mmHg ± 0.23; P = 0.011). Mean IOP was significantly lower in the travoprost/timolol group compared to the dorzolamide/timolol group at the 9 AM time point both at Week 2 (P = 0.006) and Week 6 (P = 0.002). The travoprost/timolol combination produced mean IOP reductions from baseline of 35.3% to 38.5%, while the dorzolamide/timolol combination produced mean IOP reductions from baseline of 32.5% to 34.5%. Conclusions: The fixed combination travoprost 0.004%/timolol 0.5% dosed once daily in the morning demonstrated superior mean diurnal IOP-lowering efficacy compared to dorzolamide 2%/timolol 0.5% dosed twice daily in patients with ocular hypertension or open-angle glaucoma.

Learning effect of short-wavelength automated perimetry in patients with ocular hypertension.

AimTo evaluate the learning effect of short-wavelength automated perimetry (SWAP) on a group of patients with ocular hypertension experienced with standard automated perimetry (SAP). MethodsThirty patients with ocular hypertension underwent 5 full-threshold SWAP tests at intervals of 7±2 days. The parameters investigated to detect a learning effect were duration, the perimetric indices, and the number of points with a P of <5% and 1% in the total and pattern deviation maps. Differences in learning effect were also evaluated by comparing the sensitivities of central, paracentral, and peripheral areas, hemifields and quadrants. ResultsLearning effects were demonstrated for mean defect (P<0.0001, analysis of variance), duration (P=0.0001), the number of points with P<5% in the pattern deviation map (P=0.003), and short fluctuations (P=0.03). The effect was greater in the peripheral than in central areas (P=0.04). Mean defect was the most sensitive parameter, for which the learning effect was statistically significant between the first and the fifth test. ConclusionsThe results of this study demonstrate a significant learning effect at full-threshold SWAP. This may limit the efficacy of this kind of perimetry in detecting early glaucoma, and should therefore be carefully considered when creating normative databases for new SWAP strategies.

Relationship between intraocular pressure and glaucoma onset and progression.

Open-angle glaucoma is a multifactorial disease, and among the several risk factors, a high intraocular pressure represents the most consistent and the only one that can be modified in order to provide a significant impact over the course of the disease. High intraocular pressure is significantly associated to the onset and the progression of open angle glaucoma, and the results of several randomised controlled clinical trials have consistently attributed a higher 10% higher risk for both the development and the progression of the disease to each higher single mmHg. Intraocular pressure has been studied in terms of mean value and short-term and long-term fluctuations. As of today the mean value represents the most significant factor whereas the importance of both short-term and long-term fluctuations is still debated.