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Biomedical subjects

N Orzalesi

Publications and source records attributed to N Orzalesi.

At least 19 recordsLinked to original sources

Circadian variations in central corneal thickness and intraocular pressure in patients with glaucoma.

AIM: To analyse 24 hour variations in intraocular pressure (IOP) and central corneal thickness (CCT) in a group of glaucomatous patients. METHODS: 30 patients with primary open angle glaucoma were hospitalised and underwent circadian evaluations (at 8 pm, midnight, 4 am, 8 am, noon, and 4 pm) of supine and sitting IOP, respectively, measured using a Perkins and a Goldmann tonometer, and CCT measured using an ultrasonic pachymeter (the mean value of three measurements within 5 mum). All patients were treated with timolol 0.5% twice daily and latanoprost 0.005% once daily. RESULTS: Mean supine IOP was 15.3 (SD 3.7) mm Hg (range 10-25), with circadian fluctuations of 7.3 (3.3) mm Hg. Mean sitting IOP was 15.1 (3.9) mm Hg (range 8-26), with circadian fluctuations of 5.4 (3.1) mm Hg. Mean CCT was 534 (39) microm (range 443-637 microm) with circadian fluctuations of 16.5 (6.2) microm (range 6-31 microm). Both the within patient and within time point fluctuations in CCT were statistically significant (p<0.0001, ANOVA). CONCLUSIONS: The authors found considerable fluctuations in 24 hour IOP. The circadian fluctuations in CCT were small and, although statistically significant, did not seem to interfere with the circadian IOP assessment.

Aged↗

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.

Adult↗

Intraobserver and interobserver reproducibility in the evaluation of ultrasonic pachymetry measurements of central corneal thickness.

PURPOSE: To assess reproducibility of central corneal thickness (CCT) measurement by means of ultrasonic pachymetry. METHODS: Fifty one volunteers underwent three sessions of CCT measurements, each consisting of three CCT measurements, performed by each of three different observers. Intra- and interobserver reproducibility was calculated by means of intraclass correlation coefficient (ICC). The expected range of variability between two independent evaluations was calculated using scatter plots of each test-retest difference against their mean. The standard deviation of the mean differences in the test-retest scores was used to describe the differences in the score spread. RESULTS: The ICC ranges of the intra- and interobserver evaluations were 0.95-0.97 and 0.89-0.95 respectively; the expected variability was < or = +/-1% and < or = +/- 2% respectively (95% confidence interval). CONCLUSIONS: The measurement of CCT by means of ultrasonic pachymetry is highly reproducible.

Aged↗

Clinical ability of Heidelberg retinal tomograph examination to detect glaucomatous visual field changes.

PURPOSE: To determine the agreement between Heidelberg Retinal Tomograph (HRT; Heidelberg Instruments, Heidelberg, Germany) and visual field examinations in differentiating normal from glaucomatous eyes and to evaluate the sensitivity and specificity of HRT optic disc examination in detecting eyes with glaucomatous damage. STUDY DESIGN: Cross-sectional study. PARTICIPANTS: Three hundred fifty-nine patients, for a total of 359 eyes (55 normal, 209 with ocular hypertension [OHT], and 95 with primary open-angle glaucoma). INTERVENTION: Optic disc imaging by HRT, using a 10 degrees angle view; a mean of three repeated images were analyzed using version 2.01 software. The optic disc was classified as "normal/glaucomatous" on the basis of multivariate discriminant analysis and cumulative frequency distribution (ranked-segment distribution curves). The visual field was examined using the DS 30 II program (Humphrey perimeter, Zeiss Humphrey System, Dublin, CA), with a glaucomatous visual field being defined on the basis of an abnormal glaucoma hemifield test and a statistically significant corrected pattern standard deviation less than 4 dB. MAIN OUTCOME MEASURES: Agreement between HRT and visual field examinations calculated by means of the kappa statistic and the sensitivity and specificity of HRT examination. RESULTS: The agreement between the visual field-based and HRT definition of glaucoma was fair to poor, with a kappa statistic of between 0.48 and 0.28. The sensitivity and specificity of the HRT examination were, respectively, 80% and 65%, according to Mikelberg's analysis, and, respectively, 31% to 53% and 90% to 92%, according to the analysis based on cumulative curves of normality. CONCLUSIONS: In a broad clinical setting including normal, OHT, and glaucoma patients, the HRT and visual field tests have fair to poor agreement in detecting glaucoma. The HRT demonstrated a lack of specificity when using Mikelberg's multivariate discriminant analysis and a lack of sensitivity when using cumulative frequency distribution (ranked-segment distribution) curves. These values did not change when normal or OHT patients were excluded from the analysis. In the clinical setting, caution should be used when interpreting HRT results on the basis of multivariate discriminant analysis or cumulative frequency distribution curves.

Adult↗

Myocilin Gln368stop mutation and advanced age as risk factors for late-onset primary open-angle glaucoma.

BACKGROUND: Juvenile open-angle glaucoma has been found to be associated with molecular defects in the myocilin (MYOC) gene. Most of the defects are missense mutations located in the third exon. The Gln368stop mutation has recently been found in several cases of late-onset primary open-angle glaucoma (POAG). OBJECTIVE: To study the effect of glaucoma risk in a relatively homogeneous genetic population. METHODS: A clinical study was performed in all living members of a 5-generation family. DNA analysis was performed for studying association with genetic markers and identifying the mutation. RESULTS: We identified the Gln368stop molecular defect in 19 patients with POAG, 5 patients with ocular hypertension, and 22 healthy carriers. We compared affected and unaffected carriers based on age at onset and last examination, respectively. Besides the presence of 3 young patients with POAG (<40 years old), the number of glaucomatous patients in the advanced age group increased. CONCLUSIONS: The penetrance of glaucoma increases with age in Gln368stop carriers, but some remain unaffected at advanced age and others are affected at an early age. This suggests that additional risk factors are operating within this family, which may be identified by a genome-wide linkage search in this large pedigree. CLINICAL RELEVANCE: The myocilin Gln368stop mutation shows a good genotype-phenotype correlation and should be investigated in all familiar cases of chronic POAG. This may be important for early diagnosis and periodical checkups of presymptomatic individuals belonging to these families.

Age Factors↗

A novel spontaneous missense mutation in VMD2 gene is a cause of a best macular dystrophy sporadic case.

PURPOSE: To report the molecular characterization of a novel VMD2 mutation causing a Best macular dystrophy sporadic case. METHODS: All family members underwent ophthalmologic examination and genetic testing by single strand conformation polymorphism analysis and direct sequencing of the VMD2 gene. RESULTS: A single T to G transition at nucleotide 663 was identified in one of the VMD2 gene copies of the patient, which results in a Cys to Trp substitution at position 221 in the corresponding protein (C221W). Sequence analysis of the VMD2 exon 6 of both parents of the patient did not reveal any mutation. CONCLUSION: These data confirm the involvement of the VMD2 gene in Best macular dystrophy onset, even in sporadic cases of the disease, pointing out the relevance of molecular analysis in the diagnosis of this degenerative retinal disease.

Amino Acid Substitution↗

Effect of timolol, latanoprost, and dorzolamide on circadian IOP in glaucoma or ocular hypertension.

PURPOSE: To compare the around-the-clock intraocular pressure (IOP) reduction induced by timolol 0.5%, latanoprost 0.005%, and dorzolamide in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). METHODS: In this crossover trial, 20 patients with POAG (n = 10) or OHT (n = 10) were treated with timolol, latanoprost, and dorzolamide for 1 month. The treatment sequence was randomized. All patients underwent measurements for four 24-hour tonometric curves: at baseline and after each 1-month period of treatment. The patients were admitted to the hospital, and IOP was measured by two well-trained evaluators masked to treatment assignment. Measurements were taken at 3, 6, and 9 AM and noon and at 3, 6, and 9 PM and midnight by handheld electronic tonometer (TonoPen XL; Bio-Rad, Glendale, CA) with the patient supine and sitting, and a Goldmann applanation tonometer (Haag-Streit, Bern, Switzerland) with the patient sitting at the slit lamp. Systemic blood pressure was recorded at the same times. The between-group differences were tested for significance by means of parametric analysis of variance. The circadian IOP curve of a small group of untreated healthy young subjects was also recorded using the same procedures. To compare the circadian IOP rhythms in the POAG-OHT and control groups, the acrophases for each subject were calculated. RESULTS: When Goldmann sitting values were considered, all the drugs significantly reduced IOP in comparison with baseline at all times, except for timolol at 3 AM. Latanoprost was more effective in lowering IOP than timolol at 3, 6, and 9 AM (P = 0.03), noon (P = 0.01), 9 PM, and midnight (P = 0.05) and was more effective than dorzolamide at 9 AM, noon (P = 0.03), and 3 and 6 PM (P = 0.04). Timolol was more effective than dorzolamide at 3 PM (P = 0.05), whereas dorzolamide performed better than timolol at midnight and 3 AM (P = 0.05). An ancillary finding of this study was that in the group of healthy subjects, the pattern of IOP curve was different that in patients with eye disease. CONCLUSIONS: Latanoprost seemed to lead to a fairly uniform circadian reduction in IOP, whereas timolol seemed to be less effective during the nighttime hours. Dorzolamide was less effective than latanoprost but led to a significant reduction in nocturnal IOP. The reason for the difference in the pattern of the IOP curve of healthy subjects is currently unknown and deserves further investigation.

Aged↗

Topical lomefloxacin 0.3% twice daily versus tobramycin 0.3% in acute bacterial conjunctivitis: A multicenter double-blind phase III study.

AIMS/BACKGROUND: To evaluate in a double-masked comparative, prospective, randomized multicenter trial the efficacy of lomefloxacin 0.3% eye drops twice daily and of tobramycin eye drops 4 times daily in patients with acute bacterial conjunctivitis. METHODS: Ninety-nine subjects were enrolled: 50 were treated with lomefloxacin 0.3% eye drops twice daily and 49 with tobramycin 0.3% eye drops 4 times daily. In all patients, conjunctival swabbing and assessment of objective signs and of subjective symptoms were performed. RESULTS: There was no statistical difference for any individual sign or symptom or for the sum score of either key or other signs and symptoms at any of the examination days. The sum score of both key and other signs and symptoms decreased in both groups at day 3-4 as compared to baseline values (p < 0.0001). The decrease in both these scores continued significantly from day 3-4 to day 7-8 (p < 0.05) and was similar in the two treatment groups (p > 0.4). The lowest resistance rate was seen in lomefloxacin (3.5%) and in neomycin (7.0%), while tobramycin showed resistance in 10 out of 88 resistance strains (11.4%). CONCLUSION: Both lomefloxacin 0.3% twice daily and tobramycin 0.3% administered 4 times daily were well tolerated and showed a high degree of clinical and microbiological efficacy in the treatment of acute bacterial conjunctivitis. Lomefloxacin caused less resistance than other antibiotics evaluated.

Acute Disease↗

A novel mutation in the GLC1A gene causes juvenile open-angle glaucoma in 4 families from the Italian region of Puglia.

BACKGROUND: Primary open-angle glaucoma encompasses a complex of potentially blinding ocular diseases characterized by a normal-appearing angle of the anterior chamber, a characteristic degeneration of the optic nerve with resultant typical visual field defects, and usually, an elevated intraocular pressure. It can be subdivided into 2 groups according to the age at onset: the more prevalent chronic open-angle glaucoma diagnosed after 40 years of age, and the less common juvenile form, which occurs between 3 years of age and early adulthood. A locus for primary open-angle glaucoma (GLC1A) has been mapped to a 3-centimorgan region of the long arm of chromosome 1 (1q23-25). Recently, the myocilin (MYOC) gene, located in this chromosomal interval, has been found mutated in several patients affected by primary open-angle glaucoma. OBJECTIVE: To describe the clinical and molecular genetic features of 4 pedigrees affected by autosomal dominant juvenile open-angle glaucoma, all from the Italian region of Puglia. METHODS: Clinical study, gonioscopy, automated perimetry, and DNA analysis were performed on several members of the 4 families. RESULTS: We identified a new molecular defect (1177GACA-->T) in the third exon of the GLC1A gene. This mutation is present in all affected persons and in 2 still phenotypically normal persons. CONCLUSION: Our results are important for diagnostic purposes because it is now possible to identify asymptomatic carriers, for whom clinical surveillance for the early detection and treatment of glaucoma may be suggested.

Adolescent↗

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.

Adult↗

Laser treatment of feeder vessels in subfoveal choroidal neovascular membranes: a revisitation using dynamic indocyanine green angiography.

OBJECTIVE: This study aimed to determine whether the indocyanine green angiography (ICGA)-guided laser treatment of feeder vessels (FVs) may be useful in the management of the subfoveal choroidal neovascular membranes (CNVM) in patients with age-related macular degeneration (ARMD). DESIGN: Noncomparative case series. PARTICIPANTS: The authors considered a series of 15 patients with subfoveal CNVM in whom feeder vessels could be clearly detected by means of dynamic ICGA but not necessarily with fluorescein angiography (FA). On the basis of the indications of the pilot study, the authors also studied a second series of 16 patients with FVs smaller than 85 microm. INTERVENTION: Treatment of FV using argon green laser was performed. The ICGA was performed immediately after treatment, after 2, 7, 30 days, and then every 3 months, to assess FV closure. If an FV appeared to be still patent, it was immediately retreated and the follow-up was started again. The follow-up time ranged from 23 to 34 months for the pilot study and from 4 to 12 months for the second series. MAIN OUTCOME MEASURES: The obliteration of the membrane and change in visual acuity from baseline were measured. The effect on the treatment of the number and width of the FVs, and the size and location of the membrane, also was evaluated. RESULTS: In the pilot study, the CNVM was obliterated after the first treatment in only one patient, five patients needed more than one treatment, and obliteration failed in nine patients (40% success rate). The rate of success was affected by the width and number of the FVs. The success rate in the second series of 16 patients was higher (75%). CONCLUSIONS: The success of the laser treatment of FVs depends on their width, length, and number. Dynamic ICGA, which detects smaller FVs and makes it possible to control the laser effect and initiate immediate retreatment in the case of incomplete FV closure, should be considered mandatory for this type of treatment; a comparable success rate would have been unlikely using the other currently available methods of treating subfoveal CNVMs.

Aged↗

Scanning laser ophthalmoscopy of the optic disc at the level of the lamina cribrosa.

PURPOSE: To determine the suitability and reproducibility of optic disc morphometry performed on images focused at the level of the lamina cribrosa, obtained by means of the scanning laser ophthalmoscope (SLO). METHODS: Twenty-one eyes were imaged with argon blue and green, helium neon red and diode infrared laser sources of a scanning laser ophthalmoscope. Five images of the optic disc at the level of the lamina cribrosa were taken for each patient, digitized and traced by three trained observers, in order to identify the external contour of the optic disc and the inner edge of the neuroretinal rim. Dedicated software allowed the contours to be traced on the video and an estimate of the real sizes of optic disc parameters to be obtained according to Littman's equation. Standard deviation (SD) and coefficient of variation (CV) were used to determine the intra- and inter-observer reproducibility in measuring disc, dark annulus (DA), and reflective center (RC) areas, DA area/disc area (DA/D) and RC area/disc area (RC/D) ratios of each set of images taken with all laser wavelengths. RESULTS: A high contrast between the dark annulus of the lamina and the central highly reflective area was achieved at all laser wavelengths. The ranges of CVs for all of the observers, using all the laser wavelengths, were as follows: disc: 0.018-0.036; dark annulus: 0.015-0.039; reflective center: 0.014-0.031; DA/D: 0.005-0.01; RC/D: 0.007-0.018. No significant difference was observed between the measurements performed on the images acquired, using the different laser wavelengths. CONCLUSIONS: SLO imaging of the optic disc at the level of the lamina cribrosa proved to be suitable and highly reproducible at all laser wavelengths. The coefficients of variation of the measurements of optic disc parameters obtained using this technique are smaller than those obtained by means of conventional photographic methods.

Adult↗