Area Of Fluorescein Leakage Research Articles

Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study System for Evaluation of Stereoscopic Color Fundus Photographs and Fluorescein Angiograms

To describe the procedures and reproducibility for grading stereoscopic color fundus photographs and fluorescein angiograms of participants in the SCORE Study. Standardized stereoscopic fundus photographs and fluorescein angiograms taken at 84 clinical centers were evaluated by graders at a central reading center. Type of retinal vein occlusion (RVO), area of retinal thickening, and area of retinal hemorrhage are evaluated from fundus photographs; area of fluorescein leakage and area of capillary nonperfusion are measured on fluorescein angiography. Temporal reproducibility consisted of annual regrading of a randomly selected dedicated subset of fundus photographs (60 subjects) and fluorescein angiograms (40 subjects) for 3 successive years. Contemporaneous reproducibility involved monthly regrading of a 5% random selection of recently evaluated fundus photographs (n = 73). The intergrader agreement for RVO type and presence of retinal thickening was greater than 90% in the 3 annual regrades. The intraclass correlation (ICC) for area of retinal thickening in the 3 years ranged from 0.39 to 0.64 and for area of retinal hemorrhage, 0.87 to 0.96. The ICC for area of fluorescein leakage ranged from 0.66 to 0.75 and for capillary nonperfusion, 0.94 to 0.97. The contemporaneous reproducibility results were similar to those of temporal reproducibility for all variables except area of retinal thickening (ICC, 0.84). The fundus photography and fluorescein angiography grading procedures for the SCORE Study are reproducible and can be used for multicenter longitudinal studies of RVO. A systematic temporal drift occurred in evaluating area of retinal thickening.

SCORE Study Report 3: Study Design and Baseline Characteristics

To describe the baseline characteristics of the participants in the Standard Care versus COrticosteroid for REtinal Vein Occlusion (SCORE) Study and to compare with cohorts from other retinal vein occlusion trials. The design of the SCORE Study is also described. Two, multicenter, Phase III, randomized clinical trials, one involving participants with central retinal vein occlusion (CRVO) and one involving participants with branch retinal vein occlusion (BRVO). A total of 682 participants, including 271 with CRVO and 411 with BRVO. Demographic and study eye characteristics are summarized and compared between the CRVO and BRVO study participants. Baseline ophthalmic characteristics, including visual acuity and duration of macular edema before enrollment, and medical history characteristics, including diabetes mellitus and hypertension. In the CRVO trial, at baseline, mean visual acuity letter score was 51 ( approximately 20/100), mean optical coherence tomography (OCT)-measured central subfield thickness was 595 microns, mean area of retinal thickening in the macular grid on color photography was 12.3 disc areas (DA), and mean area of fluorescein leakage was 11.0 DA. In the BRVO trial, at baseline, mean visual acuity letter score was 57 ( approximately 20/80), mean OCT-measured central subfield thickness was 491 microns, mean area of retinal thickening in the macular grid on color photography was 7.5 DA, and the mean area of fluorescein leakage was 6.1 DA. Differences observed in baseline visual acuity, OCT-measured retinal thickness, area of retinal thickening on color photography, and area of fluorescein leakage support the evaluation of CRVO and BRVO in separate trials. The authors have no proprietary or commercial interest in any of the materials discussed in this article.

EFFECT OF FOCAL/GRID PHOTOCOAGULATION ON VISUAL ACUITY AND RETINAL THICKENING IN EYES WITH NON–CENTER-INVOLVED DIABETIC MACULAR EDEMA

To report visual acuity and anatomic changes from baseline to 12 months after modified Early Treatment Diabetic Retinopathy Study (ETDRS)-style (focal/grid) photocoagulation in eyes with non-center-involved (non-CI) clinically significant macular edema. Visual acuity, optical coherence tomography, fluorescein angiography, and fundus photography data were analyzed from eyes with non-CI clinically significant macular edema treated with modified ETDRS-style (focal/grid) photocoagulation in a Diabetic Retinopathy Clinical Research Network trial. Among the 22 eyes (of 22 patients) with 12-month follow-up, median visual acuity letter score remained within 1 letter of baseline over 12 months. The median central subfield retinal thickness decreased by 10 mum, median total macular volume decreased by 0.2 mm, and median fluorescein leakage area within the grid decreased by 0.7 disk areas. We are unaware of any other systematic evaluation of eyes with non-CI clinically significant macular edema since the ETDRS. Focal/grid laser in these non-CI eyes was associated with relatively stable visual acuity and retinal thickness measurements, and decreased fluorescein leakage area at 1 year. One-year visual acuity results are consistent with those published by the ETDRS, despite the intervening significant differences in the management of diabetes. Although this was a small study without a concurrent control group, the ETDRS recommendation to consider focal/grid laser in eyes with non-CI clinically significant macular edema still seems appropriate.

Therapeutic Effects of Intravitreal Bevacizumab Injection for Retinal Neovascularization Secondary to Proliferative Diabetic Retinopathy

Purpose: To evaluate the short-term effects of a single intravitreal injection of bevacizumab (Avastin) for the management of new vessels (NV) associated with proliferative diabetic retinopathy (PDR). Methods: A non-randomized study of 19 PDR patients (20 eyes) who had active NV was analyzed prospectively. Standardized ophthalmic evaluation was performed at baseline and at weeks 1, 4, and 8 after intravitreal injection of 1.25 mg of bevacizumab. The main outcome measures included changes in total area of fluorescein leakage from active NV and best corrected visual acuity (BCVA). Results: Twenty eyes of 19 patients (12 men [63.2%], 7 women [36.8%]) were included and all patients completed the 8-week study follow-up period. The mean age of participants was 47.0512.48 years. At baseline, NV area was 23.02. The area of active NV decreased significantly to 4.96, 1.11 and 4.55 (p0.49 at baseline to 0.560.47, 0.550.73 and 0.510.50 at weeks 1, 4, and 8, respectively. No significant adverse events were observed. Conclusions: Short-term results suggest that intravitreal injection of bevacizumab is associated with a rapid regression of retinal neovascularization secondary to PDR.

Panretinal photocoagulation versus PRP plus intravitreal bevacizumab for high‐risk proliferative diabetic retinopathy (IBeHi study)

To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab on best corrected visual acuity (BCVA) and total area of fluorescein leakage from active new vessels (NVs) in patients with high-risk proliferative diabetic retinopathy (PDR). We carried out a prospective study of patients with high-risk PDR and no prior laser treatment who were randomly assigned to receive PRP (PRP group) or PRP plus intravitreal injection of 1.5 mg of bevacizumab (PRP-plus group). In all patients, the PRP was administered at two time-points (weeks 1 and 3), with the intravitreal bevacizumab delivered at the end of the second laser episode in the PRP-plus group. Standardized ophthalmic evaluation including Early Treatment Diabetic Retinopathy Study BCVA as well as stereoscopic fundus photography and fluorescein angiography were performed at baseline and at weeks 4, 9 (+/- 1) and 16 (+/- 2). Main outcome measures included changes in BCVA and in total area of fluorescein leakage from active NVs. Twenty-two (n = 30 eyes) consecutive patients completed the 16-week follow-up. There was no significant difference between the PRP and PRP-plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active NVs or BCVA. No significant difference in BCVA was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-plus group compared with the PRP group at weeks 4, 9 and 16 (p < 0.001). No major adverse events were identified. In the short-term, the adjunctive use of intravitreal bevacizumab with PRP was associated with a greater reduction in the area of active leaking NVs than PRP alone in patients with high-risk PDR.

Intravenous Bevacizumab Causes Regression of Choroidal Neovascularization Secondary to Diseases Other Than Age-related Macular Degeneration

To investigate the safety, tolerability, and bioactivity of intravenous infusions of bevacizumab in patients with choroidal neovascularization (CNV) attributable to causes other than age-related macular degeneration. Nonrandomized clinical trial. Ten patients with CNV received infusions of 5 mg/kg of bevacizumab. The primary efficacy outcome measure was change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study letters read at 4 meters) at 24 weeks and secondary measures were changes from baseline in excess foveal thickness (center subfield thickness), area of fluorescein leakage, and area of CNV. Infusions were well tolerated and there were no ocular or systemic adverse events. At baseline, median VA was 25.5 letters read at 4 meters (20/80) and median foveal thickness was 346 mum. At the primary endpoint (24 weeks), median VA was 48.5 letters (20/32), representing four lines of improvement from baseline (P = .005), median foveal thickness was 248 mum representing a 72% reduction in excess foveal thickness (P = .007). Four of nine patients had complete elimination of fluorescein leakage, three had near complete elimination (reductions of 91%, 88%, and 87%), two had modest reductions, and one had no reduction. All patients except one showed a reduction in area of CNV with a median reduction of 43%. Despite the small number of patients studied, the marked improvement in VA accompanied by prominent reductions in foveal thickness, fluorescein leakage, and area of CNV suggest a beneficial effect. It may be worthwhile to consider further evaluation of systemic bevacizumab in young patients with CNV.

INTRAVITREAL BEVACIZUMAB (AVASTIN) FOR PERSISTENT NEW VESSELS IN DIABETIC RETINOPATHY (IBEPE STUDY)

To evaluate the short-term fluorescein angiographic and visual acuity effects of a single intravitreal injection of bevacizumab (Avastin) for the management of persistent new vessels (NV) associated with diabetic retinopathy. A prospective, nonrandomized open-label study of diabetic patients with actively leaking NV refractory to laser treatment and best-corrected Early Treatment Diabetic Retinopathy Study visual acuity (BCVA) worse than 20/40. Standardized ophthalmic evaluation was performed at baseline and at weeks 1, 6, and 12 (+/-1) following intravitreal injection of 1.5 mg of bevacizumab. Main outcome measures include changes in total area of fluorescein leakage from active NV and BCVA. Fifteen consecutive patients (men, 9 [60%]; women, 6 [40%]) were included and all completed the 12-week follow-up period of the study. The mean +/- SD age of participants was 60.08 +/- 7.75 years (median, 59.5; range, 49-73 years). At baseline, mean +/- standard error of the mean (SEM) NV leakage area was 27.79 +/- 6.29 mm2. The mean +/- SEM area of active leaking NV decreased significantly to 5.43 +/- 2.18 mm2 and 5.50 +/- 1.24 mm2 (P < 0.05, Tukey multiple comparisons post-test) at 1 and 12 weeks postinjection, respectively; at week 6 no leakage was observed. The mean +/- SEM logMAR (Snellen equivalent) BCVA improved significantly from 0.90 (20/160) +/- 0.11 at baseline to 0.76 (20/125(+2)) +/- 0.12, 0.77 (20/125(+2)) +/- 0.11, and 0.77 (20/125(+2)) +/- 0.12 at weeks 1, 6, and 12, respectively (P < 0.05, Tukey multiple comparisons post-test). No major adverse events were observed. Intravitreal injection of bevacizumab achieved short-term reduction of fluorescein leakage from persistent active NV without loss of vision in patients with diabetic retinopathy. Further studies to investigate the role of anti-VEGF therapy with bevacizumab for the management of diabetic retinopathy refractory to laser treatment are warranted.

TWOFOLD ILLUMINATION PHOTODYNAMIC THERAPY SCHEME FOR SUBFOVEAL CHOROIDAL NEOVASCULARIZATION IN PATHOLOGIC MYOPIA

To compare the short-term efficacy and safety of standard verteporfin photodynamic therapy (PDT) to modified PDT regimen using a twofold illumination scheme for treating choroidal neovascularization in pathologic myopia. Randomized active-controlled clinical trial including 16 patients with subfoveal choroidal neovascularization caused by pathologic myopia and best-corrected visual acuity (BCVA) of 20/320 or better. Patients were randomly assigned (1:1) to standard PDT regimen (50 J/cm; n=8) or twofold illumination PDT scheme (50+50 J/cm; n=8). Comprehensive ophthalmic evaluation including fluorescein angiography was performed at baseline and at weeks 1, 12+/-2, and 24+/-2 following treatment. At week 12 follow-up examination, an additional treatment session with either standard or modified PDT regimens (as assigned at baseline) was applied to areas of fluorescein leakage if present. Changes in BCVA, retreatment rate, and incidence of adverse events were evaluated. All patients completed the 24-week study period. Baseline median BCVA was 20/100 and 20/100 for patients assigned to standard and modified PDT regimens, respectively. At week 24, median improvement in BCVA was significantly greater in patients submitted to twofold illumination PDT scheme (P=0.005; Mann-Whitney U test). Median change from baseline in BCVA (ETDRS lines) was +1.8 (P<0.05; Wilcoxon signed-rank test), +0.4, and +0.5 lines for patients submitted to standard PDT regimen, and +1.8 (P<0.05; Wilcoxon signed-rank test), +1.9 (P<0.05; Wilcoxon signed-rank test), and +2.4 (P<0.05; Wilcoxon signed-rank test) lines for patients submitted to twofold illumination PDT scheme at week 1, 12, and 24 follow-up examinations, respectively. An additional PDT session was performed in 7/8 patients assigned to standard PDT regimen, and in 4/8 patients assigned to modified PDT (P=0.28; Fisher exact test). No PDT-related complications were observed. Although the number of patients and length of follow-up in this study was limited, a better visual outcome and diminished retreatment rate were observed in patients assigned to twofold illumination PDT scheme in comparison to those submitted to standard PDT regimen. Larger studies with longer follow-up to look at twofold illumination PDT scheme versus standard one to confirm our preliminary results are warranted.

Triamcinolone as Adjunctive Treatment to Laser Panretinal Photocoagulation for Proliferative Diabetic Retinopathy

To evaluate intravitreal injection of triamcinolone acetonide before laser panretinal photocoagulation (PRP) in the treatment of proliferative diabetic retinopathy. This interventional case series included 9 patients with bilateral proliferative diabetic retinopathy. One eye received intravitreal triamcinolone before PRP (injected eye) and the other, PRP alone (control eye). The main outcome measures were the change in planimetric area of fluorescein leakage from retinal neovascularization and in central macular thickness on optical coherence tomography at 3, 6, 9, and 12 months. Secondary end points were change in vision, intraocular pressure, and cataract progression. All patients completed 9 months and 5 patients, 12 months of follow-up. Initial mean (SD) planimetric area of fluorescein leakage and central macular thickness were 7.22 (5.70) mm(2) and 372.11 (91.88) microm in injected eyes and 9.08 (6.17) mm(2) and 355.33 (115.23) microm in control eyes, respectively. At the 9- and 12-month intervals, the planimetric area of fluorescein leakage decreased by 86% and 88% in injected eyes and 33% and 50% in controls, respectively. Central macular thickness significantly decreased in injected eyes and increased in control eyes. Vision slightly improved in injected eyes and worsened in control eyes. Intravitreal injection of triamcinolone before PRP may be useful in improving the effects of PRP in eyes with proliferative diabetic retinopathy by reducing neovascularization and macular thickening.

Intravitreal Triamcinolone Acetonide in Refractory Pseudophakic Cystoid Macular Edema: Functional and Anatomic Results

To evaluate safety and efficacy of intravitreal triamcinolone acetonide (TAAC) injections in the treatment of refractory pseudophakic cystoid macular edema (CME). Seven eyes of six patients (age range: 50-74) with pseudophakic CME resistant to standard treatment received intravitreal injections of 4 mg of TAAC with all vehicle. Mean preinjection duration of CME was 18.3 months. A mean of 2.1+/-1.2 (range 1 to 4) treatments were performed in four eyes (57.1 %) when visual acuity deteriorated towards baseline levels. Visual acuity assessment, optical coherence tomography (OCT), and fluorescein angiography (FFA) were performed pre- and postoperatively to evaluate results of TAAC injections. Intraocular pressure (IOP) and complications related to treatment were assessed. After 11.1+/-3.9 months, mean best-corrected visual acuity (BCVA) increased (p =0.019) from 20/132 to a best value of 20/38. Mean macular thickness decreased from 517.29+/-146.98 mm to a best value of 263.71+/-83.13 mm (p=0.0018). Area of fluorescein leakage decreased (p<0.0001) from 11.84+/-0.93 mm2 at baseline to a minimal value of 3.86+/-0.98 mm2. The anatomic and functional improvement appeared after 1 month from the intravitreal injection and persisted through at least 3 months of follow-up. At the end of follow-up BCVA, macular thickness, and area of fluorescein leakage did not differ from baseline. Four eyes (57.1 %) developed IOP values higher than 21 mmHg, controlled by topical treatment. Two patients developed an endophthalmitis-like reaction. Intravitreal TAAC was relatively safe and effective in resistant cases of pseudophakic CME with a temporary beneficial effect on visual acuity and macular edema.

Photodynamic therapy with verteporfin for choroidal neovascularization in patients with diabetic retinopathy

PURPOSE: To report the use of photodynamic therapy (PDT) with verteporfin in three patients with choroidal neovascularization (CNV) from age-related macular degeneration and underlying diabetic retinopathy. The level of diabetic retinopathy would have excluded these patients from participation in previously reported randomized clinical trials evaluating PDT with verteporfin due to a theoretic concern of damage to the overlying retinal vasculature. DESIGN: Retrospective interventional case series. METHODS: Three patients from a referral practice with at least severe nonproliferative diabetic retinopathy and a history of clinically significant macular edema developed loss of vision from concurrent choroidal neovascularization evaluated with fundus photography and fluorescein angiography before and after PDT with verteporfin to identify adverse retinal vascular events. RESULTS: Four eyes in three patients had PDT using verteporfin. Three eyes received two treatments. With short follow-up, visual acuity remained stable in two eyes, improved from 20/400 to 20/320 in one eye, and decreased from 20/200 to 20/400 in one eye. Fluorescein angiograms at intervals from 2 weeks to 3 months after PDT showed no damage to the retinal vasculature or progression of the diabetic retinopathy, but did show a decreased area of fluorescein leakage from CNV. One eye that had new subretinal hemorrhage following treatment appeared to show new vasculopathy on initial evaluation of the post-treatment angiogram. Retrospective review suggested that the subretinal hemorrhage provided increased contrast to more easily visualize vasculopathy that was present before the PDT. CONCLUSIONS: Three patients with diabetic retinopathy undergoing a total of seven PDT treatments with verteporfin in four eyes had no new retinal vascular abnormalities develop. No other atypical responses of CNV to PDT were noted except new subretinal hemorrhage, providing increased contrast of the overlying vasculature, which gave the false impression of the development of new vasculopathy in one eye. Patients with diabetic retinopathy who have concurrent CNV for which PDT with verteporfin is recommended should be cautioned regarding the theoretical concerns of harming the retinal vasculature. Periodic surveillance for such concerns seems warranted until more experience is obtained.

Angiographic abnormalities of experimental autoimmune uveoretinitis.

Experimental autoimmune uveoretinitis (EAU) is an invaluable animal model for studying inflammatory eye disease in humans. Indocyanine green (ICG) is a fluorescent dye that can be used to image both retinal and choroidal vessels. This study was performed to examined the retinal and choroidal vascular abnormalities of a rat model of EAU using ICG and fluorescein as the contrast media to assess the suitability of this model for studying ICG angiographic abnormalities in inflammatory eye disease in humans. Twenty-six black-hooded Lister rats were inoculated with bovine retinal S-antigen plus adjuvant with or without Bordetella pertussis antigen. Fluorescein and ICG angiograms were performed at different stages of clinical disease with a scanning laser ophthalmoscope. EAU was more severe and primarily choroidal disease in rats given Bordetella pertussis, but no animals showed evidence of dye leakage from large choroidal vessels. There was frank leakage of indocyanine green from retinal vessels. Leakage of both fluorescein and ICG retinal vessels largely correlated with disease activity. Retinal pigment epithelial lesions either corresponded to areas of hypofluorescence on the ICG angiogram alone or were represented by areas of ICG hyperfluorescence that had overlying areas of fluorescein leakage from retinal capillaries. This study has demonstrated the vascular abnormalities of this model of EAU using ICG and fluorescein as the contrast media. The suitability of this method for studying ICG angiographic abnormalities in inflammatory eye disease in humans is encouraging.

Photocoagulation of central serous retinopathy. A preliminary report.

The recent demonstration of discrete areas of fluorescein leakage in central serous retinopathy has permitted a new therapeutic approach in carefully selected cases. The fluorescein leakage site in four patients whose symptoms had persisted from 3½ to 34 months were treated with minimal intensity laser photocoagulation. Resolution of the serous detachment of the macula was obtained in each case with consequent improvement in visual acuity. Serial fundus photographs and fluorescein studies are presented. The techniques employed and the hazards of this form of therapy are discussed. It is stressed that until additional confirmation of this work is obtained this therapeutic approach is not to be recommended for general use.