Repeated intravitreal bevacizumab (Avastin(®)) treatment of persistent new vessels in proliferative diabetic retinopathy after complete panretinal photocoagulation.

PURPOSE: To evaluate the effect of repeated intravitreal injections of bevacizumab (Avastin(®)) in patients with proliferative diabetic retinopathy and persistent new vessels after panretinal photocoagulation. METHODS: In this prospective study we investigated 11 eyes of 10 diabetic patients with persistent new vessels after previous complete panretinal photocoagulation. Complete ophthalmological examinations were performed at baseline and during monthly follow-up visits until the final follow-up at 6 months. Colour fundus photography, fluorescein angiography (FA) and macular optical coherence tomography (OCT) were performed. The area of leakage (mm²) found in the FA was used to demonstrate the effect of bevacizumab on retinal new vessels. Patients received 1.0 mg of intravitreal bevacizumab at baseline and at each of the monthly follow-up visits when reappearance of retinal new vessels was documented. RESULTS: At the 1-week follow-up visit, 73% of the treated eyes showed complete regression of retinal new vessels. Eight eyes were assigned to retreatments at the 3-month follow-up because of the reappearance of retinal new vessels. After 6 months, 36% of the eyes were found to have reappearance of retinal new vessels. The retreatment rate was 1.9 ± 0.7 and the mean interval to retreatment was 2.9 ± 1.0 months. The mean leakage area decreased from 7.2 ± 2.6 mm² at baseline to 1.2 ± 0.9 mm² at the final follow-up visit. BCVA increased from 59.2 ± 14.6 Early Treatment Diabetic Retinopathy Study (ETDRS) score (range 40-80) to 70.7 ± 8.5 at the final visit (p = 0.017). CONCLUSION: Intravitreal bevacizumab led to a significant reduction of retinal new vessels for a mean period of 2.9 months. A 3-monthly retreatment regime might be a valid method to control retinal new vessels in diabetic patients with persistent new vessels.

Angiogenic and inflammatory markers in the intraocular fluid of eyes with diabetic macular edema and influence of therapy with bevacizumab.

PURPOSE: The purpose of this study was to determine the concentrations of angiogenic and inflammatory markers in human eyes with diffuse diabetic macular edema before and during therapy with intravitreal bevacizumab and their association with disease activity. METHODS: In a prospective clinical trial, 10 eyes of 10 consecutive patients with vision loss because of diabetic macular edema were compared with 10 eyes of 10 age-matched controls. Bevacizumab was administered at baseline; retreatments were given monthly according to disease activity. During a follow-up of 6 months, aqueous humor samples were taken each time intravitreal therapy was administered. A multiplex assay was used for measurement of 12 different growth factors and cytokines. RESULTS: Aqueous humor of eyes with diabetic macular edema demonstrated a significantly increased expression of monocyte chemoattractant protein-1 and interleukin-8 and higher, but not significant, levels of interleukin-6 and vascular endothelial growth factor. Intravitreal therapy with bevacizumab resulted in a significant decrease of vascular endothelial growth factor below physiologic levels. This change was not associated with clinical disease activity as measured by visual acuity and central retinal thickness. CONCLUSION: Eyes with diabetic macular edema showed a different profile of monocyte chemoattractant protein-1 and interleukin-8 as compared with controls. The intraocular vascular endothelial growth factor expression decreased significantly after the first intravitreal injection of bevacizumab; this reduction was prolonged by consecutive monthly retreatment.

Choroidal blood flow and progression of age-related macular degeneration in the fellow eye in patients with unilateral choroidal neovascularization.

PURPOSE: Cardiovascular risk factors such as smoking, hypertension, and atherosclerosis seem to play an important role in the development of choroidal neovascularization (CNV). Recent studies have also provided evidence suggesting that choroidal and retinal blood flow is decreased in patients with AMD. On the basis of these results, the hypothesis for this study was that lower choroidal blood flow is associated with an increased risk of CNV in patients with AMD. METHODS: Forty-one patients with unilateral choroidal neovascular AMD were included in this observational longitudinal study. The fellow eyes of the patients served as study eyes. Subfoveal choroidal blood flow (FLOW) and fundus pulsation amplitude (FPA) were assessed with laser Doppler flowmetry and laser interferometry, respectively. A multivariate COX-regression model was used to test the hypothesis that low choroidal perfusion parameters are associated with the development of CNV. RESULTS: Of the 37 patients that were followed up until the end of the study, 17 developed CNV and 20 did not. The univariate COX-regression analysis shows that lower FLOW, systolic blood pressure, intraocular pressure, and FPA are risk factors for development of CNV. Moreover, the more advanced the AMD in the study eye, the higher the risk for CNV to develop in the fellow eye. Multivariate COX regression analysis indicated that only FLOW (P = 0.0071), FPA (P = 0.0068), and staging (P = 0.031) had statistically significant influences on the progression to CNV. CONCLUSIONS: The present study indicates that lower choroidal perfusion is a risk factor for the development of CNV in the fellow eye of patients with unilateral CNV.

Ocular haemodynamic changes after single treatment with photodynamic therapy assessed with non-invasive techniques.

PURPOSE: To investigate in patients with neovascular age-related macular degeneration (ARMD) the changes in ocular perfusion caused by single treatment with photodynamic therapy (PDT) by different non-invasive methods; to evaluate correlations between relative changes of ocular haemodynamic parameters after PDT among each other and compared to morphological parameters; and to assess this in relation to early changes of visual acuity. STUDY POPULATION: 17 consecutive patients with subfoveal choroidal neovascularization (CNV) caused by ARMD scheduled for PDT without previous PDT treatment (four patients with predominantly classic CNV and 13 patients with occult CNV). OBSERVATION PROCEDURES: best-corrected visual acuity (before PDT, 6 and 8 weeks after PDT), fundus photography, fluorescein angiography, haemodynamic measurements with laser Doppler flowmetry (LDF), laser interferometry and ocular blood flow (OBF) tonometry (baseline and 1, 2, 6 and 8 weeks after treatment). MAIN OUTCOME MEASURES: choroidal blood flow (CHBF), fundus pulsation amplitude (FPA), pulsatile ocular blood flow (POBF), visual acuity. Changes smaller than 20% were considered clinically irrelevant. RESULTS: Ocular haemodynamic parameters did not change significantly in the follow-up period. Changes of haemodynamic parameters showed no correlation to treatment spot, morphological changes or visual acuity. Changes of visual acuity were comparable to results of earlier studies. CONCLUSION: Single treatment with PDT did not modify ocular blood flow parameters above 20% as assessed with different non-invasive methods.

Effects of vitamin C on hyperoxia-induced reduction of retinal blood flow.

OBJECTIVE: Breathing of 100% oxygen causes vasoconstriction in retinal vessels paralleled by a decrease in blood flow. The mechanism underlying this effect is still unclear, but may be related to the increased generation of reactive oxygen species during hyperoxia. Thus, the purpose of the present study was to investigate whether vitamin C, an agent with strong antioxidative properties, modifies the retinal vasoconstrictor response to hyperoxia. METHODS: A randomized, double-masked, placebo controlled, two-way crossover study was performed in 12 healthy young volunteers. 100% oxygen was administered via a breathing mask for 12 min. Retinal blood flow was measured before and during oxygen breathing in the presence of either ascorbic acid (3 g) or placebo on two different study days. Retinal blood flow was determined based on measurement of retinal vessel diameters and red blood cell velocity. RESULTS: Breathing of 100% oxygen induced a pronounced reduction of retinal arterial (-7.6%+/-6.5%) and venous diameters (-12%+/-6%). Hyperoxia induced vasoconstriction was not altered by co-administration of vitamin C (-8.6%+/-4.8% in arteries and -15%+/-7% in veins). Likewise, RBV and retinal blood flow decreased in response to oxygen by -24%+/-53% and -38%+/-42%. Again, the reduction of retinal hemodynamic parameters was not altered by co-administration of vitamin C. CONCLUSIONS: Oxygen induced blood flow response in the human retina is not altered by a single dose of vitamin C in healthy, young subjects. Whether this indicates that ROS are not involved in hyperoxia induced vasoconstriction of retinal vessels or is related to other factors has yet to be determined.

Strategies for reducing variance in laser Doppler flowmetry measurements.

BACKGROUND: Scattering of blood flow data as assessed with laser Doppler flowmetry (LDF) in humans is a problem in many studies using this technique. We set out to reduce variability in LDF data by eliminating the effect of the total returning light level (DC) on LDF parameters in the choroid through partial regression analysis. METHODS: In 20 healthy subjects, choroidal blood flow parameters were measured at different DC values using a portable confocal LDF device. We used two different strategies to reduce scattering of data eliminating the effect of yield, which is defined as DC/gain. On the one hand, we used a previously described method based on a third-order polynomial fit, which combines all obtained data. On the other hand, we applied a new method based on a linear fit for each individual subject. RESULTS: Variability of data during changes in DC is higher for LDF parameters volume and flow than for velocity. Both methods were successful in reducing scattering of LDF parameters with varying DC. CONCLUSIONS: The present study indicates that both methods to correct for changes in yield were successful in reducing the variability of LDF measurements. When systematic changes in DC occur after an intervention, one needs to be careful in interpreting the obtained data and it remains to be shown if either of the two techniques is capable of correcting for this effect. The approach presented here may, however, represent an effective, easily applicable and valid approach to reduce scattering of data from using LDF to assess blood flow in the posterior pole of the human eye.

Optical coherence tomography fast versus regular macular thickness mapping in diabetic retinopathy.

OBJECTIVE: The purpose of the study was to investigate if absolute values and reproducibility of thickness maps obtained from 2 optical coherence tomography (OCT) scanning protocols, regular high-resolution and fast low-density mode, differ in patients with diabetic macular edema. METHODS: A total of 26 consecutive patients undergoing fluorescein angiography and Stratus OCT scanning for the evaluation of diabetic macular edema at the Departments of Ophthalmology in Munich and Vienna were included. RESULTS: Retinal thickness of the central field of the thickness map measured by fast retinal thickness protocol was 287 +/- 97 and 290 +/- 113 microm by the regular protocol. This difference as well as that for all other fields was not statistically significant. Three times repeated measurements applying both OCT scanning modes in 10 patients yielded very good intrasession correlation coefficients between 0.70 and 0.99, with corresponding intrasession standard deviations ranging between 6 and 16 mum. The fast mode yielded slightly less reproducible values than the regular mode. Visual acuity did not influence the results. CONCLUSION: In practice both scanning modes can be interchanged and absolute values can be compared directly. Best reproducibility is obtained with higher sampling density even in patients with reduced visual acuity due to diabetic macular edema.

Photodynamic therapy with verteporfin and intravitreal triamcinolone acetonide in the treatment of neovascular age-related macular degeneration.

PURPOSE: To examine the efficacy of photodynamic therapy (PDT) with verteporfin and intravitreal triamcinolone acetonide in the treatment of neovascular age-related macular degeneration (AMD). DESIGN: Retrospective, interventional case series. METHODS: Sixty eyes of 56 patients with neovascular AMD were treated with PDT with verteporfin followed by an intravitreal injection of 4 mg triamcinolone acetonide. The main outcome measures were visual acuity (VA), retreatment frequency with PDT (and triamcinolone), and frequency of side effects. RESULTS: Mean follow-up was 15.9 months (range 12 to 30 months, median 15 months). Twenty-three (38.3%) of 60 eyes had a stable result at 12 months' follow-up (that is, loss/gain

Treatment frequency and visual outcome in subfoveal choroidal neovascularization related to pathologic myopia treated with photodynamic therapy.

BACKGROUND: The purpose of this study was to examine the influence of treatment frequency on visual acuity of patients with PDT treatment for subfoveal predominantly classic CNV related to pathological myopia. DESIGN: Retrospective case series. METHODS: Thirty-seven patients with subfoveal predominantly classic CNV caused by pathologic myopia and treated with PDT were included. All patients received a full ophthalmic examination, including best-corrected visual acuity, slit-lamp biomicroscopy, fundus photography and fluorescein angiography, before first treatment and every 3 months thereafter. Photodynamic therapy was performed according to standard protocol. Main outcome measurements were visual acuity and treatment frequency. RESULTS: The number of treatments received was 3.35+/-1.83 (average: 1-7). In 12 eyes (32.43%); the BCVA was stable or increased during the entire follow-up period. In eight eyes (21.62%), the BCVA decreased and did not return to the baseline values. A transient loss of visual acuity (over 3-9 months) with subsequent improvement in visual function was found in 68% (17 eyes). A gain of three or more lines compared with lowest BCVA was found in 56% (14 eyes). The number of treatments did not correlate with baseline BCVA, greatest linear dimension of CNV at baseline or with the change of BCVA from baseline. In cases with transient worsening of BCVA, the recovery of visual acuity correlated significantly with the number of treatments (r=-0.522, P<0.05; Spearman rank correlation) received. CONCLUSION: Visual acuity recovery correlates with the number of PDT re-treatments; in many cases, an improvement in visual function after temporary decrease of BCVA can be observed after re-treatment according to current treatment guidelines. The number of PDT treatments has no negative effect on the visual outcome in subfoveal CNVs caused by pathological myopia.

Choroidal hemodynamic changes during isometric exercise in patients with inactive central serous chorioretinopathy.

PURPOSE: Imaging studies suggest that the choroidal vasculature may be altered in central serous chorioretinopathy. Little is known, however, about the regulation of ocular blood flow in patients with central serous chorioretinopathy (CSC). The hypothesis for the present study was that choroidal blood flow changes during an increase in ocular perfusion pressure induced by isometric exercise may be altered in CSC. METHODS: An observer-masked, two-cohort study was performed in 14 nonsmoking patients with chronic-relapsing but inactive CSC and in 14 healthy nonsmoking volunteers. Both groups were matched for age and sex. Subfoveal choroidal blood flow (CBF) was assessed with laser Doppler flowmetry, and ocular perfusion pressure (OPP) was calculated from mean arterial pressure (MAP) and intraocular pressure (IOP). Changes of CBF during isometric exercise over a period of 6 minutes were measured. RESULTS: Whereas the increase of MAP, the pulse rate, and the OPP were comparable between the two study groups, subfoveal CBF increased significantly more in the group of patients with CSC (P < 0.001). IOP remained unchanged in both groups during isometric exercise. At an 85% increase in OPP, subfoveal CBF was approximately twice as high in the patients with CSC compared with the healthy control group. CONCLUSIONS: The data indicate an abnormal subfoveal CBF regulation in patients with relapsing CSC compared with age-matched, nonsmoking, healthy volunteers during isometric exercise.

Seven years of HAART impact on ophthalmic management of HIV-infected patients.

PURPOSE: The widespread use of highly active antiretroviral therapy (HAART) has changed the clinical picture of HIV-associated eye disease. We evaluated the incidence of ocular manifestations of HIV infection since the introduction of HAART. METHODS: Between January 1996 and December 2002, we examined 539 HIV-infected patients in our hospital. Follow-up of the patients was performed in case of ophthalmologic symptoms, regardless of current immunologic status, or for screening. RESULTS: A total of 217 patients (40.3%) had HIV-associated eye disease. Of these patients, 42.0% had no eye symptoms. Fifty-eight (10.8%) of the 539 patients had cytomegalovirus (CMV) retinitis, most of whom had CMV retinitis before receiving HAART. Four patients developed immune-recovery uveitis. A total of 145 patients (26.9%) had HIV-related microangiopathy and 96 (17.8%) had dry-eye syndrome. CONCLUSION: The introduction of HAART had a major impact on the medical history of patients with HIV-related eye disease with improved survival time and decreased morbidity.

Effect of laser photocoagulation on the retinal vessel diameter in branch and macular vein occlusion.

OBJECTIVE: To investigate the response of retinal vessel diameters to photocoagulation treatment and their role for the success of laser treatment in patients with retinal vein occlusion. METHODS: The study included 14 patients with branch vein occlusion or macular vein occlusion. The ophthalmologic examination included best-corrected visual acuity, biomicroscopy, fundus photography, and fluorescein angiography. Retinal vessel diameters were quantified before and after laser photocoagulation using a retinal vessel analyzer. MAIN OUTCOME MEASURE: Retinal vessel diameters. RESULTS: In cases manifesting macular vein occlusions, no significant change of the vessel diameter in any vessel was observed during the follow-up period. In the group with branch vein occlusion, all vessels tended to constrict after the laser photocoagulation. The effect of laser treatment on retinal vessel diameters was significant for superotemporal (P =.045, analysis of variance [ANOVA]) and inferotemporal branch veins (P =.03, ANOVA). Vasoconstriction was more pronounced in the occluded branch veins (P =.009, ANOVA) compared with the nonaffected veins (P =.12; ANOVA). The change of visual acuity after 3 months was correlated with the change of vessel diameter 3 months after laser treatment for occluded venular branches (r = 0.78, P =.02, linear regression). There was no correlation between the number of laser burns and the change of vessel diameters in the affected veins in this period (r = 0.12, P =.75, linear regression). CONCLUSIONS: Our results show that retinal photocoagulation in patients with branch vein occlusion has a vasoconstrictive effect on occluded veins. The correlation between the change in visual acuity and the change in vessel diameter indicates that branch vein constriction after photocoagulation may be an early indicator of the success of laser treatment.

Topical fundus pulsation measurement in patients with active central serous chorioretinopathy.

OBJECTIVE: To determine regional pulsatile choroidal blood flow using laser interferometry in patients with active central serous chorioretinopathy (CSC). METHOD: The study compared an equally sized age-, sex-, and refractive error-matched control group of healthy volunteers obtained from the Department of Clinical Pharmacology with 18 consecutive patients who had newly diagnosed active, unilateral CSC obtained from the University of Vienna Eye Clinic, Vienna, Austria. MAIN OUTCOME MEASURES: Regional fundus pulsation amplitude as assessed using laser interferometry. RESULTS: The median age of the patients was 40 years; the male-female ratio was 16:2. Foveal fundus pulsation amplitude was significantly higher in eyes with CSC (mean [SD], 5.5 [1.7] micro m) than in the eyes of the control subjects (4.1 [1.1] micro m; P =.005). In addition, eyes with CSC had a significantly higher variability in fundus pulsation amplitude (mean [SD], 48% [20%]) assessed at different fundus locations around the leak than the controls did (20% [9%]; P<.001). CONCLUSIONS: To our knowledge, this is the first study that measures topical fundus pulsations in patients who have active, unilateral CSC. These data indicate a generally increased foveal pulsatile choroidal blood flow and an abnormal distribution of fundus pulsation amplitude in the area close to the leak. Whether these findings reinforce the concept that choroidal perfusion abnormalities play a role in the pathogenesis of CSC remains to be established.

Ocular surface changes and tear film alterations associated with sun gazing during a solar eclipse.

PURPOSE: A solar eclipse occurred in central Europe on August 11th, 1999. Following the eclipse, patients with ocular symptoms were investigated. Gazing at the sun without protection is liable to damage the retina. Our attention was focused on changes of the ocular surface and the tear film. METHODS: Forty-three patients were investigated within one week after the solar eclipse as baseline. 33 of them were followed up one year later. Visual acuity and the central visual-field were measured, and the ocular surface and the fundus were examined using a slit lamp. The quality of the lacrimal tear film was examined using Schirmer's test for the aqueous layer, break-up time for the mucous layer and interference observation for the lipid layer, measured by a slit lamp and a tearoscope. RESULTS: At the baseline 19 patients had non-specific visual problems. Pathological alterations of the tear film were seen in all three tear-film layers: Schirmer's test was pathological in 87%, break-up time decreased in 85%, the interference pattern of the lipid layer changed in 67% and there were changes in 87% using the tearoscope. One year later the non specific visual disorders had disappeared. Schirmer's test did not reveal much change from the baseline: 51% pathological, 24% remained pathological in break-up-time and the lipid layer was normalized except in 9%. Using the tearoscope, lipids were better than grade 3 in all patients. CONCLUSION: After gazing at a solar eclipse the ocular surface and tear film changed. While the aqueous layer remained pathological in many patients, the lipid layer and the mucous layer recovered spontaneously.

Scotoma size and reading speed in patients with subfoveal occult choroidal neovascularization in age-related macular degeneration.

PURPOSE: To investigate the correlation between reading speed and scotoma size in patients with subfoveal occult with no classic choroidal neovascularization (CNV) in age-related macular degeneration (AMD) participating at 2 of 28 centers in the Verteporfin in Photodynamic Therapy trial. DESIGN: Prospective, observational case series. PARTICIPANTS: Twenty-two eyes of 22 patients with occult with no classic CNV in AMD. METHODS: Patients' reading speed was examined using a German-language reading test (Radner Lesetest). Scotoma size was measured using the microperimetry program 2.01 of the Rodenstock Scanning Laser Ophthalmoscope. MAIN OUTCOME MEASURES: Reading acuity, reading speed, size of absolute (AS) and relative scotoma (RS). RESULTS: There was a significant correlation between the size of AS and reading speed (r = -0.48, P = 0.023), as well as AS and reading acuity (r = 0.52, P = 0.013). No correlation was seen between RS and reading speed or reading capacity. CONCLUSION: The size of absolute scotoma correlated significantly with reading capacity and reading speed and may influence these measures.

Evaluation of pulsatile choroidal blood flow in branch retinal vein occlusion.

BACKGROUND: The present study was undertaken to compare pulsatile choroidal blood flow in patients with branch retinal vein occlusion (BRVO) with the values in normal controls. METHODS: The study included male and female patients with manifest BRVO (n=16) and a healthy sex- and age-matched control group (n=36). Fundus pulsation amplitude (FPA) was measured in the fovea by laser interferometry to assess pulsatile choroidal blood flow. RESULTS: The FPA in eyes with BRVO (4.4 microm) was significantly higher than in the fellow eye (3.8 microm; P<0.0005). There was also a significant difference between the affected eye of the patients and the healthy control group (3.3 microm; P<0.0009). CONCLUSION: The increase in FPA indicates increased choroidal blood flow resulting from some local mechanisms compensating for the decrease in retinal blood flow.

Plate-haptic silicone intraocular lens implantation: long-term results.

PURPOSE: To present the 10- to 12-year functional and morphological results of in-the-bag implantation of a foldable, plate-haptic, silicone posterior chamber intraocular lens (IOL). SETTING: Department of Ophthalmology, University of Vienna Medical School, Vienna, Austria. METHODS: Between September 1987 and December 1989, 160 silicone posterior chamber IOLs (Staar AA-4203C) were implanted in the capsular bag through a 3.5 mm corneoscleral incision after a continuous curvilinear capsulorhexis was created. In spring 1999, 36 patients (38 eyes) could be included in a follow-up examination. RESULTS: The median follow-up was 10.5 years +/- 2 (SD). The mean visual acuity was 0.82 +/- 0.34. The mean refraction (spherical equivalent) was +0.57 diopter (D), an insignificant change from the mean at the first postoperative follow-up at 1 month (+0.40 D). Slitlamp examination showed mildly dispersed pigment on the IOL surface in 81.58% of cases. All IOLs had a Tyndall effect (clouding). In 84.21%, the effect was minimal, in 10.53% it was moderate, and in 5.26% it was more intense. Ninety-two percent of the IOLs were centered within 0.5 mm. Of the 22 cases of decentration (57.89%), 86.36% were toward the 12 o'clock position in the bag. The neodymium:YAG capsulotomy rate was 10.52%. There were no cases of IOL-related inflammation or a clinically significant cystoid macular edema. CONCLUSION: The 10- to 12-year results suggest favorable clinical results of implantation of Staar AA-4203C plate-haptic, silicone posterior chamber IOLs.