Short term efficacy and safety in glaucoma patients changed to the latanoprost 0.005%/timolol maleate 0.5% fixed combination from monotherapies and adjunctive therapies.

AIMS: To evaluate efficacy and safety in patients with ocular hypertension or open angle glaucoma changed to latanoprost/timolol fixed combination (LTFC). METHODS: A prospective, multicentre, historical control in which qualified patients had their previous therapy substituted by LTFC and were followed for at least 2 months. RESULTS: In 1676 patients LTFC was continued in 93% throughout the observation period. In all patients LTFC reduced the intraocular pressure (IOP) from 20.6 (SD 3.8) to 17.7 (3.0) mm Hg (p<0.001) compared to previous monotherapies including latanoprost, timolol, alpha agonists or carbonic anhydrase inhibitors (CAI). LTFC provided more efficacy after changing from adjunctive therapies including: a beta blocker added to either CAI, alpha agonist, or pilocarpine, or CAI added to an alpha agonist, or latanoprost added to either CAI, alpha agonist, or beta blocker (unfixed combination), and travoprost added to timolol (p<0.007). LTFC was as effective as latanoprost used with dorzolamide/timolol fixed combination (-0.9 mm Hg, p = 0.1792). The most common reason to discontinue therapy was lack of efficacy (n = 70, 4%) and adverse event (n = 17, 1%). CONCLUSION: In a clinical setting, patients who have their monotherapy or adjunctive therapy substituted with LTFC may experience reduced IOP, good tolerability, and continuation of therapy for the first 2-3 months of treatment.

Blue-on-yellow perimetry with a scanning laser ophthalmoscope: small alterations in the central macula with aging.

The sensitivity of short-wavelength-sensitive (SWS) cone pathways was measured in the central fields of 74 normal subjects, aged 17-86 yr, with healthy maculas. The new fundus perimetry technique used a research scanning laser ophthalmoscope with a small entrance pupil to present blue static perimetry targets on a bright yellow background. Simultaneous infrared imaging aided target positioning and rapid assessment of potential pathology in elderly subjects. Targets were positioned peripheral to fixation, avoiding both the SWS-cone-free area and the peak macular pigment, determined in 11 subjects. Sensitivity declined 0.019 log unit per decade, while intraindividual variability across loci increased. The nasal-temporal asymmetry remained constant. Sensitivity of older subjects was relatively less for the most central targets but was unrelated to transmission through macular pigment. Retinal changes with age occur to differing extents or at differing rates and are readily detectable in the central macula.

Infrared scanning laser tomography of macular cysts.

OBJECTIVE: To perform three-dimensional, noninvasive, quantitative analysis of cystoid macular edema and macular cysts using infrared scanning laser tomography and to correlate findings with visual acuity (VA) as a basis for interventional studies. DESIGN: Cross-sectional, nonrandomized study. PARTICIPANTS: Seventeen patients (29-86 years of age) with macular cysts associated with a broad spectrum of diseases. INTERVENTION: Confocal infrared imaging with scanning laser tomography with the TopSS (790 nm) (Laser Diagnostic Technologies, San Diego, CA) with digitized images was used to perform three-dimensional, quantitative analysis of cysts in the central 5 degrees of the macula. MAIN OUTCOME MEASURES: Measurements of macular cyst number, area, volume, depth, slope, height of the surrounding macular elevation, and correlation with VA. RESULTS: Scanning laser tomography detected macular cysts in all patients. The number per patient ranged from 1 through 15. Cysts were accompanied by surrounding macular elevation in 16 patients (mean macular height, 216 microm). The area covered by cysts in the central 5 degrees was 0.087 to 0.969 mm2, and volume was 0.007 to 0.549 mm3. Visual acuity was significantly poorer in patients with greater cyst area (P = 0.0007), cyst volume (P = 0.0009), macular thickening (P = 0.0002), and cyst depth (P = 0.0013). Cyst number, average slope, and maximum slope, however, did not correlate significantly with VA. Grouping of macular cysts according to macular height and average cyst depth revealed that cysts in a more thickened retina were significantly deeper, had steeper slopes, and corresponded to worse VA. Macular height and average cyst depth were highly associated with each other, suggesting that in eyes with surrounding macular edema, cysts were deeper and may reflect more widespread tissue destruction. Individual confocal tomographic images provided additional information. Neither ophthalmoscopy nor fluorescein angiography delineated features such as retinal folds that suggested vitreous traction or changes in deeper layers that suggested occult choroidal new vessels. CONCLUSIONS: Infrared scanning laser tomography is a rapid and noninvasive imaging method that provides quantitative analysis of macular cysts in addition to qualitative information not seen clinically. Because poor VA is related to severe involvement of the central retina, scanning laser tomography could provide an objective outcome measure for interventional studies.

Scanning laser reflectometry of retinal and subretinal tissues.

Measurements of the human ocular fundus that make use of the light returning through the pupil are called reflectometry. Early reflectometry studies were limited by poor light return from the retina and strong reflections from the anterior surface of the eye. Artifacts produced misleading results in diseases like age-related macular degeneration. Novel laser sources, scanning, confocal optics, and digital imaging provide improved sampling of the signal from the tissues of interest: photoreceptors and retinal pigment epithelial cells. A wider range of wavelengths is now compared, including the near infrared. Reflectometry now provides functional mapping, even in severe pathology.

Multiply scattered light tomography and confocal imaging: detecting neovascularization in age-related macular degeneration.

A novel technique, Multiply Scattered Light Tomography (MSLT), and confocal Infrared Imaging are used to provide diagnostic information using a comfortable, rapid, and noninvasive method. We investigated these techniques in detecting neovascularization in age-related macular degeneration. The MSLT used a Vertical Cavity Surface Emitting Laser (VCSEL) at 850 nm, while the confocal imaging technique used either the VCSEL or a 790 nm laser diode. Both were implemented into the topographical scanning system (TopSS, Laser Diagnostic Technologies, Inc.) Confocal imaging with both lasers provided different information about neovascularization as a function of focal plane, and different also from MSLT.

Infrared imaging of cystoid macular edema.

BACKGROUND: Cystoid macular edema (CME), a cause of central visual loss, is described in various pathologies. Typically, the fluorescein angiogram confirms the diagnosis and provides qualitative information as to the extent of leakage. This study was performed to investigate the features of cysts and quantify the extent of CME using non-invasive infrared imaging. METHODS: Eighteen eyes of 16 successive patients with CME in association with a broad spectrum of diseases were included in the study. The diagnosis of CME was established clinically and confirmed by fluorescein angiography. Digital infrared imaging was performed with a research scanning laser ophthalmoscope with different apertures, providing direct confocal and indirect imaging modes, to discriminate superficial features from deeper ones and to emphasize sources of multiple laterally scattered light. RESULTS: CME was easily detected with infrared imaging in all eyes. Confocal mode visualized the cysts themselves, while indirect mode emphasized borders. Large central cysts were detected as distinct, non-confluent structures. In addition, folds detected with infrared imaging in the macula in 12 of the 18 eyes were not always observed clinically. CONCLUSION: Infrared imaging provides a quick and safe diagnostic tool for patients with CME. The cystoid structures are readily localized and quantified, useful for monitoring CME. Despite differences in the pathophysiology, cysts did not differ qualitatively in a variety of diseases with infrared imaging.

Spatial extent of pigment epithelial detachments in age-related macular degeneration.

OBJECTIVE: To quantify the spatial extent of pigment epithelial detachment (PED) associated with age-related macular degeneration (AMD) using a rapid, noninvasive method. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: The authors tested 32 eyes of 21 patients (13 women and 8 men) with AMD 56 to 91 years of age (mean = 72.8 years). The authors retested seven eyes of six patients. INTERVENTION: Three-dimensional imaging and quantification of PED were performed in each subject using confocal infrared imaging (790 nm) with a Topographic Scanning System (TopSS). The data consisted of a series of 32 images within a 3-mm-depth range requiring 0.9 second. Three-dimensional calculations were made from the series. MAIN OUTCOME MEASURE: Height, diameter, area, volume, and slope of each PED were obtained with two calculation methods. The Ellipse Method used a graphics tool to draw elliptical borders circumscribing the region of interest in the image. The software automatically calculated the values for all parameters for the region inside the ellipse, with the retinal reference plane adjusted to match the height of the surrounding retina. The User-Defined Region Method differed in that the region of interest was drawn manually. RESULTS: PEDs were easily detected in all patients using the TopSS. Maximum height of all PEDs above the reference plane ranged from 0.204 to 1.818 mm (mean = 0.57 mm). The diameter was 0.501 to 5.151 mm (mean = 2.711 mm), area was 0.179 to 20.402 mm2 (mean = 6.585 mm2), and volume was 0.012 to 13.981 mm3 (mean = 2.173 mm3). Intraobserver variability was low, with correlations between first and second measurements for the first visit ranging from r = 0.906 to 0.997 for slope and diameter, respectively. CONCLUSIONS: Three-dimensional analysis with the TopSS provides objective outcome measures not obtainable with typical clinical methods such as fundus photography and angiography. Height and volume are crucial in determining whether neovascularization is worsening or persistent after photocoagulation. More longitudinal data are needed to determine whether tomographic data reduce the need for angiography. Unique to scanning laser tomography, exudative features were imaged at different depths.

Foveal cone photopigment distribution: small alterations associated with macular pigment distribution.

PURPOSE: To map the photopigment distribution of central foveal cones in healthy adult subjects before potential onset of age-related macular degeneration. To compare alterations in cone photopigment distribution to those of macular pigment and examine those loci for subretinal changes. METHODS: Eleven healthy subjects (age range, 31-59 years) underwent reflectometry with a scanning laser ophthalmoscope. The difference in cone photopigment density in the fovea was mapped for the long-wavelength- and middle-wavelength-sensitive cones, using 594-nm light. Macular pigment was mapped with 488-nm and 514-nm light. Subretinal changes were investigated with infrared imaging (830-860 nm). RESULTS: Most subjects had small alterations in the regularity of their foveal cone photopigment distribution. Alterations were spatially related to macular pigment alterations but not to the presence of subretinal defects. Subjects were classified into three groups according to the type of alterations in the regularity of pigment distributions: central peak of photopigment and macular pigment, small foveal alterations, and broad distribution with missing central peak of photopigment or macular pigment. The resultant groups differed significantly in age, 43, 46, and 59 years, for groups 1, 2, and 3, respectively (P < 0.05). CONCLUSIONS: Small alterations in the distributions of foveal cone photopigment or macular pigment were found that varied among the subjects. Larger alterations in older subjects may indicate changes in foveal architecture with age, including potential vulnerability of central cones before the onset of clinically significant changes in the retinal pigment epithelium.

Quantitative analysis of macular holes with scanning laser tomography.

OBJECTIVE: The purpose of the study is to establish objective, quantitative, and reproducible three-dimensional analysis for macular holes with scanning laser tomography and to correlate measurements with visual acuity. DESIGN: The authors performed a cross-sectional, nonrandomized study. PARTICIPANTS: The authors examined 28 full-thickness macular holes of 23 patients aged 61 to 84 years. INTERVENTION: Confocal infrared imaging with scanning laser tomography using the TopSS (790 nm, 10 degrees field) three-dimensional measurements and macular hole analysis were performed. MAIN OUTCOME MEASURES: Area, depth, and volume parameters for both macular holes and rims were obtained in two ways: (1) reference plane for analysis equal to height of the retina (offset surface distance [OSD] 0) or (2) equal to height of the surrounding edematous rim of the hole (OSD user). Correlation of measurements with visual acuity and groups of macular holes was performed. Reproducibility from three image series per subject and intraobserver variability from ten measurements in four subjects were computed. RESULTS: Scanning laser tomography could detect macular hole and rim features in all subjects. Infrared images provided clinically useful information that may help explain macular hole pathophysiology. Based on quantitative, three-dimensional measurements, holes were assigned to four groups: large, small, shallow, and average. Groups varied significantly (P < 0.05) for the majority of measurements. Visual acuity correlated significantly (P < 0.05) with macular hole volume, depth, slope, and rim height with OSD user only, but not with hole area. Holes computed with OSD user were deeper and of greater volume. Reproducibility was excellent for hole area, slope, and rim area; good for hole volume and depth; variable for rim volume; and improved with OSD user. Intraobserver variability was low in each group. CONCLUSIONS: Scanning laser tomography is a reproducible three-dimensional imaging technique providing objective and quantitative clinical information in assessing, grouping, and managing macular holes. By setting the OSD to rim height, additional information of rim height and hole volume was provided and correlated with visual acuity. In addition, more reliable differences among macular hole groups were found. Axial measurements such as macular hole depth, volume, and rim height may be more important for visual acuity than hole area indicating their possible predictive value for outcome measures.

Angioscotometry with the scanning laser ophthalmoscope. Comparison of the effect of different wavelengths.

PURPOSE: Angioscotomas are scotomata caused by vessel shadows. Their extent may be influenced by physiological and pharmacologic conditions and disease. In this study, the authors quantified angioscotomas in normal subjects using a fundus perimetry technique with a scanning laser ophthalmoscope. They further investigated the influence of two different wavelengths on scotoma depth. METHODS: For blue-on-yellow perimetry, the authors used two different lasers--an argon laser (lambda = 458 nm) for stimuli and a low background and a HeNE (lambda = 594 nm) for a superimposed yellow background. For red-on-red perimetry, the authors used another HeNe laser (lambda = 633 nm). Fundus illumination was provided by an infrared light. Five healthy subjects were examined. Twenty-one to 24 stimuli (200 msec duration, 0.4 degree x 0.4 degree) were presented at different intensities in randomized order in a 5 degrees x 2.5 degrees retinal test field, directly inferior and adjacent to the disk. RESULTS: The depth of scotomas caused by major vessels varied in all subjects and depended on perimetry condition. To quantify the influence of vessels on sensitivity, the authors analyzed psychometric functions for stimuli projected on the vessels and for those far from the vessels. The authors found a significant difference for targets on the vessel compared to those far, which was more pronounced for the blue-on-yellow condition. CONCLUSIONS: Angioscotomas are detected better with blue targets on a yellow background than with red-on-red perimetry. The greater light absorption by hemoglobin and oxyhemoglobin at short wavelengths compared to longer wavelengths is not compensated for by visual mechanisms.

[Retinal vessels before and after photocoagulation in diabetic retinopathy. Determining the diameter using digitized color fundus slides]. / Retinale Gefässe vor und nach Photokoagulation bei diabetischer Retinopathie. Durchmesserbestimmungen mittels digitalisierter Farbdiapositive.

BACKGROUND: Retinal vessel diameter is an important parameter in blood flow analysis. Despite modern digital image technology, most clinical studies investigate diameters subjectively using projected fundus slides or negatives. In the present study we used a technique to examine vessel diameters by digital image analysis of color fundus slides. We investigated in a retrospective manner diameter changes in twenty diabetic patients before and after panretinal laser coagulation. MATERIAL AND METHODS: Color fundus slides were digitized by a new high resolution scanning device. The resulting images consisted in three channels (red, green, blue). Since vessel contrast was the highest in the green channel, we assessed grey value profiles perpendicular to the vessels in the green channel. Diameters were measured at the half-height of the profile. RESULTS: After panretinal laser coagulation, average venous diameter was decreased, whereas arterial diameter remained unchanged. There was no significant relation between the diameter change and the number of laser burns or the presence of neovascularization. CONCLUSIONS: Splitting digitized images into color planes enables objective measurements of retinal diameters in conventional color slides.