Giorgio Marchini

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.

Ultrasound biomicroscopic and conventional ultrasonographic study of ocular dimensions in primary angle-closure glaucoma

OBJECTIVE To determine the biometric findings of ocular structures in primary angle-closure glaucoma (PACG). DESIGN An observational case series with comparisons among three groups (patients with acute/intermittent PACG [A/I-PACG], patients with chronic PACG [C-PACG], and normal subjects [N]). PARTICIPANTS A total of 54 white patients with PACG (13 male, 41 female) were studied: 10 with acute, 22 with intermittent, and 22 with chronic types of PACG. Forty-two normal white subjects (11 male, 31 female) were studied as control subjects. Only one eye was considered in each patient or subject. TESTING Ultrasound biomicroscopy (UBM) and standardized A-scan ultrasonography (immersion technique) were performed in each patient during the same session or within 1 to 3 days. MAIN OUTCOME MEASURES The following A-scan parameters were measured: anterior chamber depth (ACD), lens thickness (LT), axial length (AL), lens/axial length factor (LAF), and relative lens position (RLP). Ten UBM parameters were measured, the most important of which were anterior chamber angle, trabecular-ciliary process distance (TCPD), angle opening distance at 500 microm from the scleral spur (AOD 500), and scleral-ciliary process angle (SCPA). RESULTS Compared to normal subjects, the patients with PACG presented a shorter AL (A/I-PACG = 22.31 +/- 0.83 mm, C-PACG = 22.27 +/- 0.94 mm, N = 23.38 +/- 1.23 mm), a shallower ACD (A/I-PACG = 2.41 +/- 0.25 mm, C-PACG = 2.77 +/- 0.31 mm, N = 3.33 +/- 0.31 mm), a thicker lens (A/I-PACG = 5.10 +/- 0.33 mm, C-PACG = 4.92 +/- 0.27 mm, N = 4.60 +/- 0.53 mm), and a more anteriorly located lens (RLP values, A/I-PACG = 2.22 +/- 0.12, C-PACG = 2.34 +/- 0.16, N = 2.41 +/- 0.15). The LAF values in A/I-PACG, C-PACG, and N were 2.28 +/- 012, 2.20 +/- 0.11, and 1.97 +/- 0.12, respectively. Anterior chamber angle (A/I-PACG = 11.72 +/- 8.84, C-PACG = 19.87 +/- 9.83, N = 31.29 +/- 9.18 degrees) and SCPA (A/I-PACG = 28.71 +/- 4.02, C-PACG = 30.87 +/- 6.04, N = 53.13 +/- 9.58 degrees) were narrower, TCPD (A/I-PACG = 0.61 +/- 0.12 mm, C-PACG = 0.71 +/- 0.14 mm, N = 1.08 +/- 0.22 mm) and AOD 500 shorter (A/I-PACG = 0.13 +/- 0.09 mm, C-PACG = 0.21 +/- 0.10 mm, N = 0.36 +/- 0.11 mm) in patients with PACG. All the biometric differences proved statistically significant using the one-way analysis-of-variance test. CONCLUSIONS In patients with PACG, the anterior segment is more crowded because of the presence of a thicker, more anteriorly located lens. The UBM confirms this crowding of the anterior segment, showing the forward rotation of the ciliary processes. A gradual progressive shift in anatomic characteristics is discernible on passing from normal to chronic PACG and then to acute/intermittent PACG eyes.

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.

Ultrasound biomicroscopy and intraocular-pressure-lowering mechanisms of deep sclerectomy with reticulated hyaluronic acid implant

Purpose: To evaluate the anatomic characteristics and intraocular pressure (IOP) lowering mechanisms of deep sclerectomy with reticulated hyaluronic acid implant (DS with RHAI) using ultrasound biomicroscopy (UBM). Setting: Eye Clinic, Department of Neurological and Vision Sciences, University of Verona, Verona, Italy. Methods: Thirty patients with primary open‐angle glaucoma not controlled by medical therapy had DS with RHAI in 1 eye. A complete ocular examination and UBM study were performed 1, 3, 6, and 12 months postoperatively and thereafter at 6 month intervals. Eleven parameters were evaluated, the most important of which were IOP, surgical success in lowering IOP to 21 mm Hg or less with or without additional medical therapy, UBM appearance of the site of DS with RHAI, size of the decompression space, presence of a filtering bleb and supraciliary hypoechoic area, and scleral reflectivity around the decompression space. Results: After a mean follow‐up of 11.4 months ± 4.7 (SD), the mean percentage reduction in IOP compared to preoperatively was 38% (from 26 ± 4.5 mm Hg to 16.2 ± 3.8 mm Hg; P = .0001). Twenty‐four patients (80%) had an IOP less than 21 mm Hg; however, 7 of these eyes (23%) required additional IOP‐lowering medical therapy. The operation failed in 6 patients (20%) despite additional therapy. Ultrasound biomicroscopy revealed a reduction in the size of the decompression space from 6 months postoperatively and its disappearance in 2 cases. The difference in size at the last follow‐up and at 1 month postoperatively (maximum length 2.41 ± 1.02 mm versus 3.53 ± 0.51 mm) was significant (P = .0001). At the last examination, a filtering bleb was present in 18 patients (60%), a supraciliary hypoechoic area in 18 (60%), and hyporeflectivity of the scleral tissue around the decompression space in 14 (47%). These 3 UBM characteristics were detected singly and in various combinations. The simultaneous presence of all 3 characteristics in the same eye correlated significantly with a higher surgical success rate (P = .004). Conclusions: Ultrasound biomicroscopy showed that filtering bleb formation was frequent in eyes having DS with RHAI but that it was not the only surgically induced IOP‐lowering mechanism. Increased uveoscleral and transscleral filtration may be equally important.

Reproducibility and repeatability of foveal avascular zone measurements in healthy subjects by optical coherence tomography angiography

Background/aims To assess the reproducibility and repeatability of foveal avascular zone (FAZ) area measurements using optical coherence tomography angiography (OCT-A) in healthy subjects. Methods Sixty healthy volunteers (60 eyes) were subjected to FAZ area measurements by means of high speed and high resolution spectral-domain OCT (SD-OCT) XR Avanti with the split-spectrum amplitude decorrelation angiography algorithm by two experienced examiners in two different sessions. Results The mean±SD age of the subjects was 28.9±7.6 years. Overall FAZ areas measured by the first and second observer were 0.251±0.096 mm2 and 0.252±0.096 mm2, respectively. Within subjects, the coefficients of variations were 1.83% (95% CI 1.51% to 2.20%) and 1.86% (95% CI 1.33% to 2.43%) for the first and second observers, respectively. The coefficient of repeatability average measurements of FAZ area were 0.015 mm2 and 0.013 mm2 for the first and second observers, respectively. The intraclass correlation coefficient values were 0.997 (95% CI 0.995 to 0.998) and 0.998 (95% CI 0.996 to 0.999) for the first and second observers, respectively. Inter- and intraobserver concordance correlation coefficients ranged from 0.994 (95% CI 0.990 to 0.977) to 0.999 (95% CI 0.997 to 0.999) and from 0.997 (95% CI 0.995 to 0.998) to 0.996 (95% CI 0.994 to 0.998), respectively. Conclusions FAZ area measurements by means of OCT-A showed excellent reproducibility and repeatability in healthy eyes. OCT-A is a non-invasive diagnostic method, and its reliability makes it an interesting potential diagnostic tool for disease detection and follow-up in retinal pathologies involving foveal microcirculation.

Ultrasound biomicroscopic changes during accommodation in eyes with accommodating intraocular lenses: Pilot study and hypothesis for the mechanism of accommodation

Purpose: To document ciliary body constriction and movement with the Crystalens® AT‐45 intraocular lens (IOL) (eyeonics) using ultrasound biomicroscopy. Setting: Eye Clinic, Department of Neurological and Visual Sciences, University of Verona, Verona, Italy. Methods: Patients with no preexisting ocular conditions other than cataract who agreed to return for follow‐up were considered. Twenty eyes of 14 patients with a best corrected visual acuity of 5/10 or worse and a refractive error (spherical equivalent) of ±1.0 diopter (D) had implantation of a Crystalens AT‐45 accommodating IOL. Six patients had bilateral implantation. Ultrasound biomicroscopy was performed postoperatively at 1 and 6 months. Before and during accommodation, the anterior chamber depth (ACD) was measured to assess the endothelium–IOL distance and measure the scleral–ciliary process angle to determine whether there was anterior rotation of the ciliary body. The uncorrected distance acuity, best corrected distance acuity, uncorrected near acuity, distance corrected near acuity, best corrected near acuity, and accommodative amplitude were determined. Analysis was done to determine whether there was a correlation between the accommodative amplitude and the percentage variation in the ACD and scleral–ciliary process angle. Results: All surgical procedures were uneventful. The mean uncorrected distance acuity at 1 month was 0.8 ± 0.14 (SD) and remained stable at 6 months. Three of 20 eyes (15%) and 8 of 20 eyes (40%) had a Jaeger acuity of J1 and J3, respectively, without additional power correction. During accommodation, the mean reduction in ACD was 0.32 ± 0.16 mm at 1 month and 0.33 ± 0.25 mm at 6 months. The mean narrowing of the scleral–ciliary process angle was 4.32 ± 1.87 degrees at 1 month and 4.43 ± 1.85 degrees at 6 months. There was a correlation between accommodative amplitude and a decrease in the ACD (r = 0.404) and a decrease in scleral–ciliary process angle (r = 0.773). Conclusions: Anterior displacement of the Crystalens IOL and corresponding anterior rotation of the ciliary body occurred during near vision. The IOL displacement and rotation were proportional to the accommodation capacity.

Gamma Knife Stereotactic Radiosurgery for Uveal Melanoma: Clinical Results after 2 Years

We report on 36 cases of uveal melanoma treated at our center between March 1993 and September 1995. There were 16 men and 20 women, aged 57 +/- 11 years. The choroid was affected in 35 patients and the ciliary-body in 1. The same preoperative and follow-up protocol was adopted for all cases. The procedure included fixation and positioning of the eye with a retrobulbar injection of long-lasting anesthetic and two extraocular muscle sutures, application of the frame, computed tomography scan localization, dose planning and treatment with the Gamma Knife. The patients were divided into three groups. Group A: 10 patients with a follow-up of 24 +/- 4 months, treated with a high dose (surface dose 58 +/- 9 Gy, maximum dose 81 +/- 15 Gy, mean dose 66 +/- 11 Gy). Group B: 9 patients with a follow-up of 16 +/- 2 months, treated with a lower dose (surface dose 41 +/- 3 Gy, maximum dose 76 +/- 10 Gy, mean dose 53 +/- 11 Gy). Group C: 17 patients with a follow-up of 6 +/- 3 months, treated with a lower dose (surface dose 42 +/- 3 Gy, maximum dose 72 +/- 16 Gy, mean dose: 54 +/- 6 Gy). In group A, we observed marked tumor regression in 9 cases, tumor recurrence in 1 case and severe complications in 5 cases (neovascular glaucoma and/or radiation retinopathy and/or radiation optic neuropathy). In group B, significant local control of the tumor was obtained with minor complications (cotton wool spots hard exudates, intraretinal hemorrhages). In group C, to date we have observed a regression of the tumor in 7 cases and 1 severe complication (neovascular glaucoma). Our data show that uveal melanomas may be adequately controlled by a high radiosurgical dosage (50-70 Gy), though there are significant side effects. Comparable levels of local tumor control may be obtainable using lower doses (40-45 Gy) which would hopefully reduce the rate of complications. However, a longer follow-up is needed for further validation of these results.

Evaluation of ocular surface disorders: a new diagnostic tool based on impression cytology and confocal laser scanning microscopy

Aim To provide a new tool for the evaluation of altered ocular surfaces by using a combination of impression cytology, laser scanning confocal microscopy and advanced image analysis. Methods The expression of keratin 3 (K3), keratin 12 (K12), keratin 19 (K19) and mucin 1 (MUC1) was analysed by immunofluorescence on both histological sections of nine corneoscleral buttons from normal donors comprising conjunctiva, limbus and cornea and impression cytology specimens from six healthy normal subjects (12 eyes) and 12 patients with chronic ocular surface disorders. Levels of fluorescence expression of the different markers were quantified through quantitative fluorescence immunohistochemistry (Q-FIHC). Results Impression cytology specimens from normal and diseased ocular surfaces showed distinct expression patterns for K12 and MUC1. Healthy corneas expressed only K12 (but not MUC1), while conjunctivalised corneas from patients with limbal stem cell deficiency (LSCD) were characterised by the presence of MUC1 and the disappearance of K12. Similar clear-cut results were not seen with the K3/K19 markers, which showed lack of specificity and overlapping signals in cornea and conjunctiva impression cytology specimens. Conclusions The ability of K12 and of the antibody against MUC1 to discriminate clearly between limbus/cornea and conjunctiva in impression cytology specimens could become a valuable diagnostic tool for ophthalmologists in order to evaluate alterations of the ocular surface and the grading of LSCD.

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.