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1.
Phase II/III Clinical Trial of Sub-Tenon Injection of Triamcinolone Acetonide (WP-0508ST) for Diabetic Macular Edema.
Ogura, Y, Shimura, M, Iida, T, Sakamoto, T, Yoshimura, N, Yamada, M, Ishibashi, T
Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde. 2019;(3):161-169
Abstract
PURPOSE To assess the efficacy and safety of sub-Tenon injection of triamcinolone acetonide (WP-0508ST) for the patients with diabetic macular edema (DME). METHODS This multicenter, randomized, double-masked, comparative, controlled study was performed in 95 patients with DME. The patients were randomly divided into 20 mg WP-0508ST, 40 mg WP-0508ST, and control groups. RESULTS A significant improvement in central macular thickness (CMT) was observed (p < 0.001) at 12 weeks after a single sub-Tenon injection of 20 mg WP-0508ST. The 40 mg group also demonstrated improvement in CMT, but the difference was not significant. In addition, the best-corrected visual acuity was improved in both the 20 mg and 40 mg groups at 12 weeks. The major side effects were increased intraocular pressure (9.4% in the 20 mg group and 13.3% in the 40 mg group) and lenticular opacity (6.3% in the 20 mg group and 10.0% in the 40 mg group). However, none of the patients with increased intraocular pressure required surgery. CONCLUSION The efficacy and tolerability of WP-0508ST in the treatment of DME were confirmed, and 20 mg was determined to be the optimal dose.
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2.
Efficacy of Ranibizumab in Eyes with Diabetic Macular Edema and Macular Nonperfusion in RIDE and RISE.
Reddy, RK, Pieramici, DJ, Gune, S, Ghanekar, A, Lu, N, Quezada-Ruiz, C, Baumal, CR
Ophthalmology. 2018;(10):1568-1574
Abstract
PURPOSE To determine whether there are baseline characteristics that distinguish patients with diabetic macular edema (DME) with coexisting macular nonperfusion (MNP) at baseline and assess these patients' potential to achieve favorable visual acuity (VA), anatomic, and diabetic retinopathy (DR) outcomes over 24 months. DESIGN Post hoc analysis of RIDE/RISE, 2 phase 3, parallel, randomized, multicenter, double-masked trials (ClinicalTrials.gov: NCT00473382; NCT00473330). PARTICIPANTS Study eyes with best-corrected VA (BCVA)/fluorescein angiogram (FA) data at baseline. METHODS To measure MNP, the Early Treatment for Diabetic Retinopathy Study (ETDRS) grid was overlaid on FAs of the macula. The MNP area was calculated by estimating the percentage of capillary loss in the central, inner, and outer subfields and converting into disc areas (DAs) using a software algorithm. Summary statistics and P values, respectively, were provided for all outcomes and comparisons of interest. MAIN OUTCOME MEASURES Baseline characteristics; MNP area, BCVA, and central subfield thickness (CST) at months 12 and 24; and incidence of study eyes with ≥2-step DR improvement at months 3, 6, 12, 18, and 24. RESULTS Baseline MNP was detected in 28.2%, 25.8%, and 26.3% of study eyes in the ranibizumab 0.3 mg (n = 213), ranibizumab 0.5 mg (n = 225), and sham (n = 228) arms, respectively. At baseline, patients with MNP were younger and had shorter diabetes duration, worse vision, increased CST, and worse DR severity (P values < 0.01 vs. those without MNP). In the ranibizumab 0.3 mg arm, eyes with baseline MNP had lower mean baseline BCVA (53.4 vs. 57.2 ETDRS letters for those without baseline MNP; P = 0.05), but mean BCVA gain at month 24 was comparable (+15.6 vs. +13.4 ETDRS letters, respectively; P = 0.2). Eyes with baseline MNP had increased CST at baseline, but experienced a greater decrease in CST by month 24. The proportion of eyes with ≥2-step DR improvement was greater for eyes with versus without baseline MNP in each ranibizumab arm. CONCLUSIONS Despite having worse vision/increased CST versus those without baseline MNP, eyes with concurrent DME and baseline MNP entering RIDE/RISE experienced robust VA and anatomic improvement with ranibizumab and therefore should not be excluded from therapy.
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3.
Appearance of Far Peripheral Retina in Normal Eyes by Ultra-widefield Fluorescein Angiography.
Lu, J, Mai, G, Luo, Y, Li, M, Cao, D, Wang, X, Yan, H, Sadda, SR, Lu, L
American journal of ophthalmology. 2017;:84-90
Abstract
PURPOSE To characterize the appearance of the far peripheral retina of normal eyes using ultra-widefield fluorescein angiography (UWFA). DESIGN Cross-sectional study. METHODS This study enrolled 101 eyes with best-corrected visual acuity ≥20/20, with refractive error <3.00 diopters, and without visible retinal pathologic changes under a slit lamp-based condensing lens. The far peripheral retina was detected by UWFA. Ciliary body thickness (CBT) at 3 mm (CBT1) and 2 mm (CBT2) posterior to the scleral spur was measured by ultrasound biomicroscopy. RESULTS In the far peripheral retina, granular background fluorescence (GB) appeared in all eyes (100%), a mottled fluorescent band (MB) appeared in 44 eyes (43.6%), and retinal vascular leakage (VL) appeared in 20 eyes (19.8%). According to peripheral angiographic findings, the eyes were allocated into 3 groups: Group 1 (MB- and VL-), Group 2 (MB+ and VL-), and Group 3 (MB-/+ and VL+). Ultrasound biomicroscopy showed ciliary body edema and exudates in Group 3. The mean CBT1 (mm) and CBT2 (mm) of Group 3 were greater than those of Group 1 and Group 2 (0.315 ± 0.037 vs 0.240 ± 0.019 vs 0.251 ± 0.030; 0.571 ± 0.084 vs 0.375 ± 0.051 vs 0.410 ± 0.050, P < .001 for both CBT1 and CBT2). The mean CBT1 and CBT2 showed no difference between Group 1 and Group 2 (P = .575 for CBT1; P = .150 for CBT2). CONCLUSIONS Normal peripheral retinas generally show granular background fluorescence, with or without a mottled fluorescent band.
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4.
Combined Fundus Autofluorescence and Near Infrared Reflectance as Prognostic Biomarkers for Visual Acuity in Foveal-Sparing Geographic Atrophy.
Lindner, M, Nadal, J, Mauschitz, MM, Lüning, A, Czauderna, J, Pfau, M, Schmitz-Valckenberg, S, Holz, FG, Schmid, M, Fleckenstein, M
Investigative ophthalmology & visual science. 2017;(6):BIO61-BIO67
Abstract
PURPOSE To identify predictors of best corrected visual acuity (BCVA) in eyes with foveal-sparing geographic atrophy (GA) secondary to age-related macular degeneration (AMD). METHODS Best corrected visual acuity (Early Treatment Diabetic Retinopathy Study charts); serial fundus autofluorescence; and near-infrared reflectance images of patients participating in the FAM (NCT00393692) and DSGA (NCT02051998) studies were analyzed. The sizes of GA and spared fovea, and the minimal linear dimension of intact retinal pigment epithelium ("bridge") between the residual foveal island and the surrounding retina were quantified and associations with BCVA were assessed by local regression curves and mixed effects models. RESULTS A total of 65 eyes (51 patients, aged 75.68 ± 8.41 years) were included. Median time between baseline and last visit with detectable foveal sparing was 18 (quartiles: 12, 33) months. Median BCVA was 0.30 (0.20, 0.52) logMAR at baseline and 0.4 (0.3, 0.7) logMAR at follow-up. Local regression curves suggested no linear association of BCVA with GA size, sparing size or bridge size. Most contrasting values for BCVA were observed for >1.5 mm2 foveal-sparing size and for 400 μm bridge size. Employing these values as cutoff levels, mixed effects modeling revealed that both anatomic parameters, but not time, significantly impacted BCVA. CONCLUSIONS During the review period eyes with foveal-sparing GA were likely to maintain the baseline BCVA. There was no linear correlation of BCVA with foveal-sparing size. Yet, BCVA was worse if the spared foveal area was <1.5 mm2 or if the bridge was smaller than 400 μm in width. These findings add to the understanding of the natural history of foveal-sparing GA and may support future clinical trial designs.
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5.
The Clinical Importance of Changes in Diabetic Retinopathy Severity Score.
Ip, MS, Zhang, J, Ehrlich, JS
Ophthalmology. 2017;(5):596-603
Abstract
PURPOSE To investigate the clinical importance of changes in diabetic retinopathy severity score (DRSS) in patients with diabetic macular edema (DME) treated with intravitreal ranibizumab. DESIGN Post hoc analysis of the phase III RIDE and RISE studies of ranibizumab for treatment of DME. PARTICIPANTS Four hundred sixty-eight eyes treated with ranibizumab from randomization with gradable DRSS on baseline fundus photographs. METHODS Visual and anatomic outcomes were examined in eyes grouped according to DRSS change from baseline to month 24. MAIN OUTCOME MEASURES Mean best-corrected visual acuity (BCVA) letter score change, proportion of patients with 15 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letter score change, mean contrast sensitivity change, proportion of patients with resolved macular edema, and leakage on fluorescein angiography. RESULTS Most (56.8%) patients treated with ranibizumab experienced 1-step or more improvement in DRSS from baseline to month 24; 40.0% had no change, and 3.2% experienced DRSS worsening. Patients with DRSS stability or improvement had greater mean BCVA letter score changes (+15.1, +14.2, +11.3, and +11.2 letters for ≥3-step improvement, ≥2-step improvement, 1-step improvement, and no DRSS change, respectively) compared with +5.0 letters in patients who had any DRSS worsening. Best-corrected visual acuity letter score gain of 15 letters or more was more common in patients with 2-step or 3-step or more DRSS improvement (51.9% and 44.6%, respectively) compared with those with a 1-step DRSS improvement, no change, or worsening (37.9%, 39.6%, and 26.7%, respectively). A loss of 15 letters or more in BCVA was more common in patients with any DRSS worsening (13.3%) compared with patients who had stable or improved DRSS (0%-2.8%). Resolution of macular edema was more common in patients with DRSS improvement: 84.2%, 87.7%, and 92.3% of patients with 1-step, 2-step or more, and 3-step or more improvement in DRSS achieved central foveal thickness of 250 μm or less, compared with 65.2% and 53.3% of patients who had no DRSS change or any DRSS worsening. CONCLUSIONS These findings provide further support that improvement in DRSS is a clinically important outcome that should be evaluated as a measure of treatment effectiveness in future studies of diabetic eye disease.
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6.
Ultrawide angle fluorescein angiographic imaging: a comparison to conventional digital acquisition systems.
Friberg, TR, Gupta, A, Yu, J, Huang, L, Suner, I, Puliafito, CA, Schwartz, SD
Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye. 2008;(4):304-11
Abstract
BACKGROUND AND OBJECTIVE A prototype ultrawide field angiographic system and conventional technology were compared. PATIENTS AND METHODS Thirty subjects with diabetic retinopathy were imaged in three centers by conventional (Topcon Inc., Paramus, NJ, or Carl Zeiss Meditec, Dublin, CA) and ultrawide field (Optos P200A; Optos Inc., Dunfermline, Scotland) digital fluorescein angiography units. A calibrated grid was digitally placed on the images to facilitate measurements. Main outcome measures were field of view and the number of grid sectors displaying retinal ischemia and neovascularization. Secondary measures were image quality and patient satisfaction scores. RESULTS The P200A provided a significantly greater visual field extent of 8.7 +/- 1.6 disc diameters (DD) compared to the conventional systems (3.4 +/- 0.76 DD) (P < .001). Retinal ischemia was better revealed (16.9 +/- 15 vs 3.4 +/- 4.26 sectors) with the prototype, but image quality was superior with the conventional system. Patient satisfaction scores did not differ between systems. CONCLUSION A prototype ultrawide angle imaging system displayed significantly more diabetic retinal pathology in a single image than conventional systems.
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7.
[Limits of the confocal laser-scanning technique in measurements of time-resolved autofluorescence of the ocular fundus].
Schweitzer, D, Hammer, M, Schweitzer, F
Biomedizinische Technik. Biomedical engineering. 2005;(9):263-7
Abstract
GOAL: The 2-dimensional measurement of the time-dependent autofluorescence has in combination of confocal laser scanner technique and time correlated single photon counting the potential for the investigation of the metabolism state at the eye ground. It was to be examined, to what extent these measurements are influenced through the auto-fluorescence of the crystalline lens. MATERIAL AND METHOD The time-dependent auto-fluorescence was measured on eyes of 21 patients with age-related macular degeneration (AMD) and of 26 healthy subjects in 40 degrees fundus images. The experimental set-up used, was developed at the eye clinic of the University of Jena. In this scanning laser ophthalmoscope, the fundus was excited at 446 nm by pulses of 100 ps full width at half maximum and 40 MHz repetition rate. The auto-fluorescence was detected with a time resolution of 25 ps for wavelengths > 500 nm. The dynamic auto-fluorescence of each pixel was approximated by a tri-exponential model function. In order to determine the influence of the fluorescence of the crystalline lens, healthy eyes and eyes were compared with implanted artificial intra-ocular lenses. For comparison the frequency distributions were used, which the decay times t1, t2 and t3 in the fundus images had been calculated with. RESULTS Clear differences were shown in the frequency distributions of the fluorescence lifetimes between AMD-patients and healthy subjects, It resulted, however, from a crucial analysis that the fluorescence of the crystalline lens is not suppressed by the confocal laser scanning principle sufficiently. In particular the long lifetime t3 is overlapped by the fluorescence of the crystalline lens of about 4.6 ns. To the complete suppression of the influence of the lens fluorescence in measurements of the time-resolved fundus auto-fluorescence it is suggested to combine the confocal laser scanning technique with the principle of the aperture diaphragm division. CONCLUSION In order to be able to determine the capability of measurements of the time-dependent fundus auto-fluorescence as diagnostic tool exactly, the influence of the crystalline lens is to reduce through the combination of confocal laser scanning ophthalmoscopy with the principle of the aperture diaphragm division diversely.
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8.
Mapping the human blood-retinal barrier function.
Bernardes, R, Dias, J, Cunha-Vaz, J
IEEE transactions on bio-medical engineering. 2005;(1):106-16
Abstract
The aim of the work herein presented is to map blood-retinal barrier function by measuring retinal fluorescein leakage from the blood stream into the human vitreous using a confocal scanning laser ophthalmoscope (CSLO). Existing methods for the assessment of fluorescein leakage into the human vitreous are based on the qualitative evaluation of fluorescein angiographies (FA) and on volume measurements, as performed by the Fluorotron Master. A new procedure is presented capable of measuring fluorescein leakage into the vitreous while simultaneously imaging the retina. The present methodology computes the fluorescein leakage in a fully automated way, based on the three-dimensional fluorescence distribution in the human eye by using a single data acquisition. The processing includes signal filtering, volume alignment and profile deconvolution. The deconvolved profile obeys the established physical model. Representative cases shown are: a healthy eye; an eye with drusen from a nondiabetic person; a photocoagulated eye; and an eye with nonproliferative diabetic retinopathy. The results are in agreement with previous findings and go a step further by making possible its daily usage in a clinical setup based on currently available instrumentation.
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9.
Clinical evaluation of 'local contrast enhancement' for oral fluorescein angiograms.
Newsom, RS, Sinthanayothin, C, Boyce, J, Casswell, AG, Williamson, TH
Eye (London, England). 2000;:318-23
Abstract
PURPOSE To describe and assess the clinical impact of 'local contrast enhancement' on oral fluorescein angiograms. METHODS Oral fluorescein angiograms (OFA) were performed on 12 patients with a range of diabetic retinopathy. The digital images were processed using two enhancement techniques: histogram equalization, a widely available method; and 'local contrast enhancement'. Twelve control images and 24 enhanced images were randomised and subjectively graded for clarity between 1 and 100 on a visual analogue scale by two masked observers. A score of 50% was chosen as the cut-off for clinically useful images. RESULTS The mean score for the unenhanced images was 38.8% (SD 19.4); the histogram equalization performed better at 54.7% (SD 10.0) (p = 0.016) and 'local contrast enhancement' at 69.4% (SD 13.6) (p < 0.001). These results equate to a 14.7% improvement in comparison with histogram equalization and a 30.3% improvement with the 'local contrast enhancement' technique. All the 'local contrast enhancement' images were clinically useful, compared with 58.3% of the histogram equalization images (chi 2 2.08, p = 0.2), and 33.3% of the control images (chi 2 = 6.75, p = 0.01). CONCLUSION This pilot study has demonstrated the power of 'local contrast enhancement' techniques for low-contrast fluorescein angiograms. Using 'local contrast enhancement' oral fluorescein angiograms can give high-quality images and may allow safer patient investigation.