Efficacy and safety of fixed combinations of latanoprost/timolol and dorzolamide/timolol in open-angle glaucoma or ocular hypertension.

AIMS: To compare intraocular pressure (IOP) reductions with fixed-combination (FC) latanoprost/timolol once daily in the evening vsFC dorzolamide/timolol twice daily. METHODS: This evaluator-masked, multicentre, controlled clinical trial randomized subjects with primary open-angle glaucoma or ocular hypertension with IOP insufficiently responsive to beta-blocker therapy (screening IOP>21 and <37 mm Hg) to FC latanoprost-timolol (N=135) or FC dorzolamide/timolol (N=135). At screening, baseline, and after 4 and 12 weeks of therapy, IOP was measured three times at 0800, 1200, and 1600 hours. Adverse events were recorded at each visit. The primary efficacy end point was whether either FC could be shown to be inferior to the other with respect to change in mean daytime IOP from baseline to week 12. RESULTS: Mean daytime IOP levels were similar at baseline. Mean reductions in daytime IOP from baseline to week 12 were -9.7 mm Hg for FC latanoprost-timolol and -9.5 mm Hg for FC dorzolamide/timolol. The difference between FC latanoprost/timolol-FC dorzolamide-timolol was -0.2 mm Hg (95% confidence interval (CI), -0.8 to -0.4 mm Hg). The upper bound of the 95% CI was <1.5 mm Hg, indicating that neither FC is inferior to the other. However, a significantly greater percentage of subjects treated with FC latanoprost/timolol achieved IOP levels

Surgical approaches to cavernous haemangiomas of the orbit.

Cavernous haemangiomas are the most common orbital masses and the second most common cause of unilateral proptosis after thyroid ophthalmopathy. We retrospectively analysed 19 patients with retrobulbar cavernous haemangiomas, 9 of whom had lateral orbitotomy to remove retrobulbar cavernous haemangiomas located superior (n=4), inferior (n=2) or lateral (n=3) to the optic nerve. Seven patients had lateral orbitotomy together with an anterior medial approach to gain access to retrobulbar cavernous haemangiomas located medially to the optic nerve in the posterior half of the orbit. An anterior approach was used in 3 patient with an anteriorly located cavernous haemangioma. We describe here the planning of surgical treatment based on the site of the lesion.

Corneal thickness and functional damage in patients with ocular hypertension.

PURPOSE: To correlate functional damage over time detected by standard automated perimetry (SAP) and frequency doubling technology (FDT) with central corneal thickness (CCT) in patients with ocular hypertension (OHT). METHODS: Seventy-eight OHT patients underwent CCT measurements, SAP, and FDT (the latter two also after 12 and 18 months). Patients were divided into three equally sized groups of 26 patients each: thin (< 540 microm), normal (540-580 microm), and thick cornea (> 580 microm). The frequency of abnormal FDT and SAP results was analyzed over time (Pearson chi2 test). RESULTS: Six of 26 patients with thin corneas (23.1%) presented an abnormal FDT test at baseline, compared to 1 of 26 (3.8%) in the normal thickness cornea group and 1 of 26 (3.8%) in the thick cornea group. After 12 months, the abnormal FDT tests were as follows, respectively: 9 of 26 (34.6%), 2 of 26 (7.7%), and 2 of 26 (7.7%). For SAP the abnormal results were as follows, respectively: 8 (30.1%), 5 (19.2%), and 2 (7.7%). After 18 months, the abnormal FDT tests were as follows, respectively: 16 (61.5%), 5 (19.2%), and 5 (19.2%). For SAP, the abnormal results were as follows, respectively: 10 (38.5%), 5 (19.2%), and 2 (7.7%). CONCLUSIONS: OHT patients with thinner corneas have a greater risk of developing functional damage over time.

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.

GDx in glaucoma.

The purpose of this paper is to review the clinical applications of GDx in the diagnosis and follow-up of glaucoma. The limits and potential of GDx technology are discussed.

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.

Experimental short-term tolerance to perfluorodecalin in the rabbit eye: a histopathological study.

PURPOSE: Perfluorocarbon liquids are largely used in vitreoretinal surgery, but their permanence into the eye is considered harmful and early withdrawal is routinely performed by most of the surgeons. We undertook this investigation to evaluate the effects of Perfluorodecalin (PFD) tamponade following vitrectomy in the rabbit eye. METHODS: Twenty-four rabbits underwent vitrectomy of the right eye according with a standard procedure. Eighteen rabbits received PFD and 6 control rabbits received Balanced Salt Solution (BSS) as vitreous substitute. The eyes were examined with light microscopy and transmission electron microscopy after two, four and six days after tamponade and thirty days after the withdrawal of PFD. RESULTS: The tamponade lasting four or more days caused irreversible retinal damage involving the photoreceptors and retinal pigment epithelium. Peculiar impressions were formed in the inner retina at the site of the gravitational effect of PFD droplets. CONCLUSIONS: Based on the results of this study we suggest that the tamponade with PFD lasting more than two days is detrimental to the retina, at least in the case of the rabbit. Damage seems to be related only to the high specific gravity of PFD.

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.

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.

Temporal corneal phacoemulsification combined with separate-incision superior trabeculectomy vs standard phacotrabeculectomy. A comparative study.

The aim of the study was to compare functional and refractive outcome after temporal approach phacoemulsification combined with superior trabeculectomy against that of standard superior phacotrabeculectomy in patients affected by cataract and uncontrolled glaucoma. Fifty patients undergoing combined surgery were randomly allocated to receive either a standard superior phacotrabeculectomy (group A) or a temporal via clear cornea phacoemulsification combined with a separate superior trabeculectomy (group B). Short-term and long-term mean IOP reductions were similar in the two groups though, at 2 years, more patients in the standard phacotrabeculectomy group had need of medical therapy to control their ocular pressure (p = 0.04). Group B had less surgically induced astigmatism than group A (p = 0.05). There was no significant difference in ocular inflammation and complication rates between the 2 groups.

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.

Reproducibility of retinal nerve fiber layer evaluation by dynamics 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)

Risk factors for cortical, nuclear, posterior subcapsular and mixed cataract: a case-control study.

A case-control study was conducted to evaluate risk factors for cortical, nuclear, posterior subcapsular and mixed cataract. The 385 cases and 215 controls (age range 40-75 yrs) included in the study underwent a complete ophthalmological examination and laboratory blood tests, and were interviewed about behavioral variables, environmental exposure and their medical history. Lens opacity was classified using the 'Lens Opacity Classification System II' (LOCS II). On multivariate analysis, the risk factors for cortical cataract were the presence of diabetes for more than five years (OR = 3.7) and increased serum K+ and Na+ levels. A history of surgery under general anesthesia and the use of sedative drugs were associated with reduced risk (OR = 0.4). Posterior subcapsular cataract was associated with the use of steroids (OR = 18.2) and diabetes (OR = 8.1), and nuclear cataract with calcitonin (OR = 5.7) and milk intake (OR = 0.25). Mixed cataract was associated with a history of surgery under general anesthesia (OR = 0.5). Some of these results are consistent with the findings of similar studies performed in different geographical areas, others are not. The results suggest a possible role of electrolyte imbalance in the development of senile cataract.

Prevalence and causes of visual impairment in Italy.

This Italian study, based on the National Household Health Survey (NHHS), the Registry of the Blind and the Welfare lists of the Ministry of the Interior, was designed to estimate the prevalence of blindness and hypovision in Italy and describe its geographical distribution. In addition, a national sample of 29 763 Registry members was studied to describe causes of blindness. The prevalence from NHHS data was 4.3 per 1000 in 1983 and 4.5 in 1986-1987 (3.2 in the North, 4.6 in the Centre, 6.5 in the South). Welfare recipients were 112,783 in 1988, a prevalence of 2.0 per 1,000, but were fewer in Northern than in Southern regions (range 0.7-4.8). The Registry of the Blind had 80,918 members in 1984 (prevalence 1.4 per 1,000) and 106,000 in 1989 (prevalence 1.9): < 1 per 1,000 in the North and > 3 in the South. The most frequent causes of blindness among Registry members were retinal diseases (33%) and cataract (23%). The causes of preventable blindness were more frequently reported in Southern than in Northern Italy.

Subretinal neovascularization after naphthalene damage to the rabbit retina.

PURPOSE: To examine the retinotoxic effect of naphthalene, a powerful oxidative agent and a well-known cataractogenic agent. METHODS: A 10% solution of naphthalene dissolved in paraffin oil was given every other day by gavage to 31 pigmented rabbits for 5 weeks, at a dose of 1 g/kg body weight. Four rabbits who received only paraffin oil served as controls. The eyes were clinically followed up by means of ophthalmoscopy and retinal fluorangiography. At selected intervals, the eyes were examined with light microscopy and transmission electron microscopy. RESULTS: The first lesions were focal and appeared in the periphery of the fundus about 3 weeks after the beginning of treatment and tended to spread over the entire retina. Histologically, there was a degeneration of photoreceptors, accompanied by a reaction and proliferation of retinal pigment epithelium (RPE) that phagocytized the damaged visual cells. After about 3 months, the proliferation of RPE was followed by subretinal neovascularization (SRN). Both mature fenestrated and thick-walled non-fenestrated capillaries penetrated Bruch's membrane, enveloped by abundant fibrous extracellular matrix and accompanied by pericytes. As a consequence of this process, the retina was focally transformed into a "neovascular complex" in which a vascular plexus was intermingled with pseudo-acinar cavities lined by RPE. There were no signs of SRN at retinal fluorangiography, possibly because of the dense microenvironment of extracellular matrix and RPE cells of the neovascular complexes. CONCLUSIONS: Naphthalene degeneration of the rabbit retina appears to be a simple model of photoreceptor vulnerability in the first stages of SRN thereafter. The close chronologic and topographic relationship between the appearance of the anomalous vessels and RPE alteration and the close resemblance with previous models of experimental SRN may support the hypothesis of an experimental model of SRN triggered by the RPE.

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 Ishi's and Quigley's 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.