Luciano Bonomi

Vascular risk factors for primary open angle glaucoma: The Egna-Neumarkt Study

OBJECTIVE To assess the impact of vascular risk factors on the prevalence of primary open angle glaucoma. DESIGN Population-based cross-sectional study. PARTICIPANTS Four thousand two hundred ninety-seven patients more than 40 years of age underwent a complete ocular examination in the context of the Egna-Neumarkt Glaucoma Study. INTERVENTION Ocular examinations were performed by trained, quality-controlled ophthalmologists according to a predefined standardized protocol including medical interview, blood pressure reading, applanation tonometry, computerized perimetry, and optic nerve head examination. MAIN OUTCOME MEASURES Prevalences of ocular hypertension, primary open-angle glaucoma, normal-tension glaucoma, and other types of glaucoma were determined. Correlation coefficients were calculated for the association between systemic blood pressure and age-adjusted intraocular pressure (IOP) and between age and both intraocular and systemic blood pressures. Odds ratios were computed to assess the risk of primary open-angle glaucoma and normal-tension glaucoma in relation to systemic hypertension or antihypertensive medication, blood pressure levels, diastolic perfusion pressure, and a number of other cardiovascular risk factors. RESULTS A positive correlation was found between systemic blood pressure and IOP, and an association was found between diagnosis of primary open-angle glaucoma and systemic hypertension. Lower diastolic perfusion pressure is associated with a marked, progressive increase in the frequency of hypertensive glaucoma. No relationship was found between systemic diseases of vascular origin and glaucoma. CONCLUSIONS Our data are in line with those reported in other recent epidemiologic studies and show that reduced diastolic perfusion pressure is an important risk factor for primary open-angle glaucoma.

Prevalence of glaucoma and intraocular pressure distribution in a defined population: The Egna-Neumarkt study

OBJECTIVE The purpose of the study is to assess the prevalence of various types of glaucoma and to determine the intraocular pressure (IOP) distribution in a defined population in an Italian rural community. DESIGN A cross-sectional epidemiologic study in a defined population was planned. After the screening examination, the subjects with suspected glaucoma were re-examined at the screening center in order to confirm the diagnosis. All cases that still proved suspect after the second examination underwent a third phase of investigations at the Ophthalmologic Division of Bolzano Hospital, and were classified as healthy or definitely glaucomatous. PARTICIPANTS All subjects residing in the Egna-Neumarkt area of Alto Adige region (Northern Italy) and over 40 years of age were invited to undergo an ophthalmologic examination. INTERVENTION Each subject was examined according to a standard protocol, including computerized perimetry, applanation tonometry, evaluation of anterior chamber depth and optic disc, and a medical history interview. The diagnosis of glaucoma was based on the presence of at least two of the following criteria: IOP > or = 22 mmHg, glaucomatous optic disc abnormalities, and glaucomatous visual field defects. Ocular hypertension was defined as IOP > or = 22 mmHg without visual field or glaucomatous optic disc abnormalities. MAIN OUTCOME MEASURES Participation rate, mean IOP, prevalence of glaucoma (primary open-angle glaucoma, primary angle-closure glaucoma, normal-tension glaucoma, secondary glaucoma), and ocular hypertension were determined. RESULTS Of a total of 5816, 4297 subjects were examined (73.9% overall participation rate). Intraocular pressure showed a Gaussian-like distribution curve skewed to the right. Mean IOP increased with age, and was slightly higher in men (15.14 mmHg) than in women (14.94 mmHg). The overall prevalences of ocular hypertension, primary open-angle glaucoma, primary angle-closure glaucoma, and normal-tension glaucoma were 2.1%, 1.4%, 0.6%, and 0.6%, respectively. Only 28 of 210 patients with glaucoma or ocular hypertension had been diagnosed prior to the screening. CONCLUSIONS The distribution of IOP and the prevalence of the different types of glaucoma were similar to those found in other white populations.

Epidemiology of angle-closure glaucoma: Prevalence, clinical types, and association with peripheral anterior chamber depth in the Egna-Neumarkt glaucoma study

OBJECTIVE To assess the prevalence of primary angle-closure glaucoma (PACG), the frequency of its different clinical presentations, and its association with peripheral anterior chamber depth in a defined population in Northern Italy. DESIGN Cross-sectional epidemiologic study in a defined population. PARTICIPANTS All subjects resident in the Egna-Neumarkt area of the South Tyrol Region (Northern Italy) and more than 40 years of age were invited to undergo an ophthalmologic examination. INTERVENTION After the screening examination, subjects with suspected glaucoma were re-examined at the screening center to confirm the diagnosis. All cases that still proved suspect after the second examination underwent a third phase of investigations and were classified as healthy or as definitely glaucomatous. Each subject was examined according to a standard protocol, including medical history interview, refraction and visual acuity determination, ocular biomicroscopy, evaluation of peripheral anterior chamber depth by means of the Van Herick method, applanation tonometry, optic disc evaluation, and computerized perimetry. Gonioscopy was not performed during initial screening but only in all selected patients in the second and third phases of investigations. The diagnosis of PACG was made on the basis of the concomitant presence of at least two of the following criteria: intraocular pressure > or = 22 mmHg, glaucomatous optic disc abnormalities, glaucomatous visual field defects. In addition, biomicroscopic or gonioscopic evidence of angle closure was also necessary. MAIN OUTCOME MEASURES Percentage distribution of peripheral anterior chamber depths, prevalence of angle-closure glaucoma, and frequency of the different PACG clinical presentations. RESULTS Four thousand two hundred ninety-seven subjects were examined (73.9% overall participation rate). The peripheral depth of the anterior chamber according to the Van Herick method was grade 2 in 14.7%, grade 1 in 2.5%, and grade 0 in 0.3% of the population. The overall prevalence of angle-closure glaucoma was 0.6% (26 cases). Five of these were cases of previous acute attacks resolved by therapy, three were cases of chronic angle-closure after acute attacks, three were intermittent angle-closure glaucomas, and 15 were chronic angle-closure cases. CONCLUSIONS Occludable angles were more frequent than in other white populations previously studied. The prevalence of PACG is not as low as is usually believed; this type of glaucoma accounts for more than a quarter of all glaucomas found in the Egna-Neumarkt population. The most frequent clinical presentation is chronic angle-closure glaucoma.

Autonomic system activity and 24-hour blood pressure variations in subjects with normal- and high-tension glaucoma.

PurposeAs suggested by findings of abnormal responses to posture in patients with normal-tension glaucoma (NTG), cardiovascular autoregulation may also be defective in primary open-angle glaucoma (POAG). Patients and MethodsBoth 24-hour ambulatory blood pressure monitoring and the head-up tilt test were performed in 17 subjects with NTG and in 13 subjects with high-tension POAG (ht-POAG). These groups were compared with 17 age-matched healthy individuals. Subjects undergoing cardiovascular therapy were excluded. ResultsNo significant differences in diurnal and nocturnal blood pressure and heart rate were found between the groups. A significant reduction in diurnal heart rate variability was found in NTG (12.1 ± 2.8 bpm) compared with the ht-POAG (15.0 ± 2.4 bpm, P < 0.01) and control groups (15.8 ± 3.0 bpm, P = 0.01]). Nocturnal diastolic blood pressure variability was also reduced in NTG (6.9 ± 2.2 mm Hg) compared with controls (8.6 ± 2.3 mm Hg, P < 0.05]) as was heart rate variability (6.3 ± 1.4 vs 8.3 ± 2.6 in ht-POAG, P < 0.05), suggesting blunted blood pressure and heart rate modulation in NTG subjects. Spectral analysis of short-term heart rate variability showed a significant reduction of total power in the supine position (1064 ± 600 in NTG vs 1688 ± 889 ms2 in controls, P < 0.05]). This was not accompanied either by a physiological reduction in total power or in a high-frequency component during the passive orthostatic stimulus. These differences tend to become more prominent in the clinically more severe forms of NTG (as identified by scores based on the extent of optic disk excavation, visual field damage, and progression of disease). This would suggest a correlation between the extent of autonomic disorder and severity of glaucoma. The &agr; index (root-square of low-frequency heart rate to low-frequency blood pressure ratio) was lower in the supine position in NTG subjects (8.1 ± 3.1 vs 10.6 ± 3.3 ms/mm Hg in controls, P < 0.05), confirming the reduced baroreflex sensitivity. ConclusionsThe results confirm the hypothesis that dysfunction of autonomic control of the cardiovascular response may be a contributing pathogenetic factor in NTG, inducing a chronic ischemia of the optic nerve.

Comparison of the effects of nine beta-adrenergic blocking agents on intraocular pressure in rabbits

The intraocular pressure lowering effects of nine beta-adrenergic receptor blocking agents were compared using two different models of experimental ocular hypertension in rabbits. All the nine drugs possess, to different extents, a clear pressure-lowering action after topical administration into the conjunctival sac. For potency and duration of action, the best results were obtained with timolol and sotalol. Pindolol, oxprenolol, practolol, and propranolol are also fairly potent, while less impressive effects were produced by atenolol, butidrine, and metoprolol. With the exception of propranolol, all the drugs were well tolerated by the ocular tissues.

The Relationship between Intraocular Pressure and Glaucoma in a Defined Population

Purpose: To provide data on the prevalence of ocular hypertension and glaucoma and on the diagnostic validity of tonometry. Methods: In this cross-sectional, population-based study, 4,927 subjects over 40 years of age were examined. Each subject underwent a complete ocular examination as part of the Egna-Neumarkt Glaucoma Study. These examinations were carried out by trained, quality-controlled ophthalmologists, according to a predetermined standard protocol that included a medical interview, applanation tonometry, computerized perimetry, optic nerve head examination and other ocular measurements. The following data were recorded: mean IOP, prevalence of ocular hypertension, primary open-angle glaucoma and normal tension glaucoma. Sensitivity, specificity and the predictive value of the tonometric test, as well as the distribution of IOP in the different groups were also determined. Results: The overall prevalence of ocular hypertension, hypertensive primary open-angle glaucoma and normal tension glaucoma corresponded to 2.1, 1.4 and 0.6%, respectively. Other types of glaucoma accounted for a further 0.9%. The sensitivity and specificity of the tonometric test in recognizing glaucoma (cut-off between 21 and 22 mm Hg) were, respectively, 80.1 and 97.8%. The predictive values of the positivity and negativity of the test were 52.1 and 99.4%, respectively. Conclusions: The prevalence of ocular hypertension and glaucoma was similar to that found in several recent epidemiological studies. Tonometry alone is obviously not sufficient to ascertain or to exclude the presence of glaucoma; its diagnostic validity however is high and should never be underestimated. An elevated IOP is the main risk factor for glaucoma, with the degree of risk increasing as the level of IOP increases.

Effects of timolol maleate on tear flow in human eyes

Lacrimal function was studied in 30 patients treated for glaucoma, with 0.25% timolol eye drops. Rose bengal and fluorescein staining disclosed punctate epithelial defects in 11 eyes after one week. During the following weeks there defects disappeared spontaneously in most eyes. Schirmer tests (I and II), tear lysozyme and pre-corneal film break-up time were significantly decreased by the treatment, while tear immunoglobulins were unimpaired. The authors conclude that topical timolol treatment decreases tear production. This effect is quantitatively limited and does not appear dangerous for normal eyes, although it may become so for eyes with an originally low lacrimal secretion. An 30 Patienten, die wegen Glaukom mit 0,25% igen Timolol-Augentropfen behandelt wurden, wurde die Tränenfunktion untersucht. Rose bengal und Fluoreszein-Anfärbungen zeigten punktförmige Epitheldefekte in 11 Augen nach einer Woche Therapie. Während der folgenden Wochen verschwanden sie spontan in den meisten Fällen. Der Schirmer-Test (I und II), Tränen-Lysozyme und Aufbruchzeit waren signifikant herabgesetzt bei den behandelten Augen, während die Tränen-Immunoglobuline unverändert waren. Die Autoren schließen daraus, daß örtliche Anwendung von Timolol die Tränenproduktion herabsetzt. Dieser Effekt ist quantitativ begrenzt und scheint in normalen Augen keinen schädlichen Effekt zu haben. Er könnte jedoch gefährlich werden in Augen, die schon vorher eine niedrige Sekretion hatten.

Experimental corticosteroid ocular hypertension in the rabbit.

Weekly subconjunctival injections of 4mg repository betamethasone, repeated over three weeks, produced a sustained increase of intraocular pressure (IOP) in 96 % of the treated rabbits. Treatment was generally well tolerated and important systemic toxic effects were present only in a few animals. The ocular hypertension so obtained was constant, well reproducible and sensitive to antiglaucoma drugs. The authors believe they have developed an animal model which is very suitable for testing the pressure-lowering effect of drugs and for other studies on ocular hypertension and glaucoma.

HPR perimetry and Humphrey perimetry in glaucomatous children

Fifteen children aged less than 11 years, affected by congenital glaucoma, underwent visual field testing using two different methods: conventional computerized perimetry (24-2 Humphrey program) and High Pass Resolution perimetry (Ring test). The aim of the study was to discover which of the two perimetric techniques was more suitable for younger patient. Results showed that HPR perimetry is more suitable to children. Reasons include the short duration of the test (5 min), and the appearance like a pleasant game to 80% of the subjects tested. In addition it proved to be better than Humphrey test because of the minimal possibilities of memorisation with a reproducibility factor of 68% in our sample and because of the reliable results and satisfactory evaluation in 76% of the eyes examined.

Ocular hypotensive action of labetalol in rabbit and human eyes

The ocular hypotensive action of labetalol, a drug endowed with alpha- and beta-adrenergic receptor-blocking properties, was studied in both rabbit and human eyes. In the rabbit, using two different models of experimentally induced ocular hypertension, an impressive decrease of IOP was seen after topical administration of the drug. In this species labetalol was found to be at least as effective as timolol and more active than pilocarpine or propranolol. In human eyes suffering from glaucoma, however, its effectiveness was much less evident and clearly inferior to that of timolol.