Stefan Sacu

Neovascular Age-related Macular Degeneration: Intraocular Cytokines and Growth Factors and the Influence of Therapy with Ranibizumab

PURPOSE To investigate concentrations of growth factors and inflammatory cytokines in eyes with neovascular age-related macular degeneration (AMD) before and during therapy with intravitreal ranibizumab and to identify associations with disease activity. DESIGN Prospective clinical trial. PARTICIPANTS AND CONTROLS Twenty-eight eyes of patients with neovascular AMD were compared with 28 eyes of age-matched patients with cataract as control. METHODS Ranibizumab was administered intravitreously once at baseline, and retreatments were given at monthly visits if optical coherence tomography (OCT) revealed macular edema or vision loss had occurred. Aqueous humor samples were taken each time intravitreal interventions were performed. Follow-up was 12 months. Luminex (Luminex Inc., Austin, TX) multiplex assays were used for measurement of 29 different growth factors and cytokines, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). MAIN OUTCOME MEASURES Differences in the concentrations of growth factors and inflammatory cytokines in eyes with neovascular AMD compared with control eyes and the influence of therapy with intravitreal ranibizumab. RESULTS A significantly increased expression of VEGF (P = 0.033) and a significantly decreased expression of PDGF (P = 0.038) were measured in the aqueous humor of eyes with neovascular AMD. Furthermore, a significant decrease of VEGF (P<0.001) was observed after intravitreal injection of ranibizumab along with significant changes in visual acuity and central retinal thickness (P = 0.039 and P<0.001). During follow-up with a flexible regimen, a correlation was identified between increased VEGF levels and persistent or recurrent macular edema. Changes in PDGF levels were strongly associated with alterations in VEGF concentration. CONCLUSIONS Vascular endothelial growth factor and PDGF-AA seemed to be associated with disease activity of neovascular AMD. Intravitreal anti-angiogenic treatment with ranibizumab resulted in significantly decreased intraocular VEGF expression below physiologic levels compared with controls. This effect was measurable as long as 4 weeks after each injection and was prolonged by consecutive retreatment. With recurrence after discontinuation of treatment, VEGF levels increased again.

Effects Of Lutein Supplementation On Macular Pigment Optical Density And Visual Acuity In Patients With Age-related Macular Degeneration

PURPOSE There is evidence from several large-scale clinical trials that reduced intake of lutein, a major component of the macular pigment, is a risk factor for the development of AMD. In the present study (LISA; Lutein Intervention Study Austria) it was hypothesized that lutein supplementation increases macular pigment optical density (MPOD). In addition, an investigation was conducted into whether lutein supplementation improves visual acuity (VA) and macular function (mean differential light threshold; MDLT), as assessed with microperimetry. METHODS One hundred twenty-six patients with AMD (AREDS [Age-related Eye Disease Study] stages 2, 3, and 4) were included in this randomized (2:1), placebo-controlled, double-masked parallel group study. Lutein or placebo was administered for 6 months. MPOD was measured with a custom-built reflectometer. VA was assessed with ETDRS (Early Treatment Diabetic Retinopathy Study) charts, and MDLT was assessed with a microperimeter. RESULTS Lutein significantly increased MPOD by 27.9% ± 2.9% (P < 0.001 versus placebo). No significant effect of lutein supplementation on MDLT or VA was seen, although a tendency toward an increase was seen for both parameters (MDLT, P = 0.096 versus placebo; VA, P = 0.070 versus placebo). A significant correlation was found, however, between the increase in MPOD after 6 months and the increase in MDLT after 6 months (r = 0.25, P = 0.027), as well as between the increase in MPOD after 6 months and the increase in VA after 6 months (r = 0.27, P = 0.013). CONCLUSIONS The present study demonstrates that lutein supplementation increases MPOD, as assessed with an objective METHOD The correlation between the change in MPOD and the change in VA and MDLT indicates that patients who show a pronounced increase in MPOD also benefit in terms of visual function. (ClinicalTrials.gov number, NCT00879671.).

Long-term effect of optic edge design in an acrylic intraocular lens on posterior capsule opacification

Purpose: To compare the posterior capsule opacification (PCO) inhibiting effect of the sharp posterior optic edge design of the Sensar OptiEdge AR40e intraocular lens (IOL) with that of the double‐round edge design of the Sensar AR40 IOL over a period of 3 years. Setting: Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. Methods: Fifty‐three patients with bilateral age‐related cataract (106 eyes) were included in this randomized prospective bilateral patient‐ and examiner‐masked clinical trial with intraindividual comparison. Each study patient had cataract surgery in both eyes and received a Sensar AR40 IOL (anterior and posterior round optic edges) in 1 eye and a Sensar OptiEdge AR40e IOL (round anterior and sharp posterior optic edge) in the other eye. Follow‐up examinations were at 1 week, 1 and 6 months, and 1, 2, and 3 years. Digital retroillumination images were taken of each eye. The amount of PCO was assessed subjectively at the slitlamp and objectively using automated image‐analysis software (AQUA) 1, 2, and 3 years after surgery. Results: The sharp‐edged AR40e lens showed significantly less regeneratory and fibrotic PCO 1, 2, and 3 years after surgery. The mean AQUA PCO score was 2.18 for the AR40 and 1.00 for the AR40e lens after 1 year; 2.94 and 1.56 after 2 years, and estimated at 3.13 and 1.77, respectively, after 3 years (scale 0 to 10; P<.001). The neodymium:YAG laser capsulotomy rate was significantly higher in the AR40 group. The AR40e lens also led to less peripheral fibrotic PCO. There was no significant difference in complaints concerning edge glare between the groups. Conclusion: Compared with the AR40 IOL, the sharp posterior optic edge design of the Sensar OptiEdge AR40e IOL led to significantly less PCO 1, 2, and 3 years postoperatively. In contrast with most past studies on PCO‐preventative factors, this study varied only 1 parameter, namely the optic edge design, and the main outcome measure (PCO) was assessed with an objective image‐analysis system.

A Systematic Comparison of Spectral-Domain Optical Coherence Tomography and Fundus Autofluorescence in Patients with Geographic Atrophy

PURPOSE To evaluate spectral-domain optical coherence tomography (SD-OCT) in providing reliable and reproducible parameters for grading geographic atrophy (GA) compared with fundus autofluorescence (FAF) images acquired by confocal scanning laser ophthalmoscopy (cSLO). DESIGN Prospective observational study. PARTICIPANTS A total of 81 eyes of 42 patients with GA. METHODS Patients with atrophic age-related macular degeneration (AMD) were enrolled on the basis of total GA lesion size ranging from 0.5 to 7 disc areas and best-corrected visual acuity of at least 20/200. A novel combined cSLO-SD-OCT system (Spectralis HRA-OCT, Heidelberg Engineering, Heidelberg, Germany) was used to grade foveal involvement and to manually measure disease extent at the level of the outer neurosensory layers and retinal pigment epithelium (RPE) at the site of GA lesions. Two readers of the Vienna Reading Center graded all obtained volume stacks (20×20 degrees), and the results were correlated to FAF. MAIN OUTCOME MEASURES Choroidal signal enhancements and alterations of the RPE, external limiting membrane (ELM), and outer plexiform layer by SD-OCT. These parameters were compared with the lesion measured with severely decreased FAF. RESULTS Foveal involvement or sparing was definitely identified in 75 of 81 eyes based on SD-OCT by both graders (inter-grader agreement: κ=0.6, P < 0.01). In FAF, inter-grader agreement regarding foveal involvement was lower (48/81 eyes, inter-grader agreement: κ=0.3, P < 0.01). Severely decreased FAF was measured over a mean area of 8.97 mm(2) for grader 1 (G1) and 9.54 mm(2) for grader 2 (G2), consistent with the mean SD-OCT quantification of the sub-RPE choroidal signal enhancement (8.9 mm(2) [G1] -9.4 mm(2) [G2]) and ELM loss with 8.7 mm(2) (G1) -10.2 mm(2) (G2). In contrast, complete morphologic absence of the RPE layer by SD-OCT was significantly smaller than the GA size in FAF (R(2)=0.400). Inter-reader agreement was highest regarding complete choroidal signal enhancement (0.98) and ELM loss (0.98). CONCLUSIONS Absence of FAF in GA lesions is consistent with morphologic RPE loss or advanced RPE disruption and is associated with alterations of the outer retinal layers as identified by SD-OCT. Lesion size is precisely determinable by SD-OCT, and foveal involvement is more accurate by SD-OCT than by FAF.

Pilocarpine-induced shift of an accommodating intraocular lens: AT-45 Crystalens

Purpose: To measure the shift of an accommodating plate‐haptic intraocular lens (IOL) along the visual axis induced by ciliary muscle contraction after application of pilocarpine. Setting: Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. Methods: Fifty‐four eyes of 28 patients with age‐related cataract comprised this prospective study. Each patient received an AT‐45 silicone accommodating IOL (Crystalens, Eyeonics Corp.) after standardized cataract surgery. In a subgroup of 24 eyes, capsular bag fibrosis was reduced by extensive polishing of the anterior capsule with a slit cannula. Assessment included measurements of anterior chamber depth, assessed with partial coherence interferometry, before and after application of pilocarpine 2% and evaluation of near visual acuity 1 month and 3 months postoperatively. Results: A slight backward shift of the IOL of 151 μm in the nonpolished group (P<.001) and 122 μm in the polished group (P<.005) could be detected after application of pilocarpine. Polishing the capsule did not influence IOL shift. The median near visual acuity with distance correction 1 month and 3 months postoperatively was J5 and J4, respectively, in the nonpolished group and J6 at both times in the polished group. Conclusions: Pilocarpine induced a counterproductive active backward shift of the AT‐45 IOL. Polishing of the capsular bag had no impact on accommodative ability. The reading performance of patients with the AT‐45 IOL patients at 1 and 3 months was not significantly different from that of with a standard IOL under similar testing methods.

Intravitreal bevacizumab (Avastin) therapy versus photodynamic therapy plus intravitreal triamcinolone for neovascular age-related macular degeneration: 6-month results of a prospective, randomised, controlled clinical study

Aims: To compare functional and anatomical outcomes of intravitreal bevacizumab (Avastin) and verteporfin (photodynamic) therapy (PDT) combined with intravitreal triamcinolone (IVTA) in patients with neovascular age-related macular degeneration (AMD). Methods: Twenty-eight patients with neovascular AMD were enrolled in a prospective, randomised, controlled clinical trial. All patients randomly assigned to 1 mg intravitreal bevacizumab (0.04 ml) received three initial treatments at 4-week intervals. In further follow-up retreatment was based on optical coherence tomography (OCT). Patients randomly assigned to standard PDT received a same-day intravitreal injection of 4 mg triamcinolone (Kenalog). Retreatment was based on fluorescein angiography at 3-month intervals. Functional and anatomical results were evaluated using the Early Treatment Diabetic Retinopathy Study protocol vision charts, fluorescein angiography and OCT. Results: In the bevacizumab-treated group mean visual acuity (VA) improved to a 2.2 line gain at 6 months follow-up. Eyes treated in the PDT plus IVTA group had a stable mean VA at month 6 compared with baseline. There was a statistically significant difference (p = 0.03, analysis of variance (ANOVA)) between both groups as early as one day after initial treatment. The reduction in central retinal thickness (CRT) showed no significant difference between both groups (p = 0.3, ANOVA). Mean CRT was reduced from 357 μm at baseline to 239 μm at month 6 in bevacizumab-treated patients and from 326 μm to 222 μm, respectively, in PDT plus IVTA-treated patients. No significant local or systemic safety concerns were detected up to month 6. Conclusion: Intravitreal bevacizumab showed promising 6-month results in patients with neovascular AMD. Functional outcomes appear not only to be dependent on a reduction in CRT but also on the treatment modality used.

Comparison of anterior chamber depth measurement methods in phakic and pseudophakic eyes

Purpose: To compare anterior chamber depth (ACD) measurements in phakic and pseudophakic eyes using a slit‐beam photographic technique (IOLMaster, Carl Zeiss Meditec AG) with those obtained with the laboratory prototype version of partial coherence interferometry (PCI) and with conventional applanation ultrasound in phakic eyes. Setting: Department of Ophthalmology, Vienna General Hospital, Vienna University, Vienna, Austria. Methods: Thirty‐three ACDs of 28 patients with age‐related cataract were measured preoperatively with a slit‐beam photographic technique (IOLMaster) and the prototype version of PCI. In 24 eyes, the ACD was also assessed with applanation ultrasound. In addition, 34 ACDs of 18 pseudophakic patients in a different study population were examined postoperatively with the IOLMaster and PCI. Results: The median ACD in the phakic eyes was 3.06 mm (range 1.93 to 3.90 mm) with the IOLMaster, 3.09 mm with PCI (range 1.49 to 4.06 mm), and 2.87 mm (range 2.18 to 3.33 mm) with applanation ultrasound. The precision was 0.005 mm for PCI and 0.015 mm for IOLMaster measurement. The median difference between the IOLMaster and PCI ACD biometry was 0.01 mm ± 0.14 (SD) (range −0.44 to 0.17 mm) (P = .71). In pseudophakic eyes, the 2 methods showed a median difference of −0.22 mm (range −0.45 to 1.99 mm) (P > .1) and did not correlate (r = 0.21; P > .2). Conclusions: In phakic eyes, the difference between IOLMaster and PCI measurements was small and not statistically significant. In pseudophakic eyes, the difference was larger and the methods did not correlate.

Correlation between the early morphological appearance of filtering blebs and outcome of trabeculectomy with mitomycin C

PurposeTo correlate the morphologic appearance of filtering blebs in the early postoperative period with the outcome of trabeculectomy with mitomycin C (MMC) during the first postoperative year. Patients and MethodsIn a prospective study, the morphologic appearance of filtering blebs after primary trabeculectomy with adjunctive MMC (0.1 mg/ml for 5 minutes intra-operatively) was classified; 49 eyes of 49 patients were examined preoperatively, 1 and 3 days, 1 and 2 weeks, 1, 3, 6, and 12 months postoperatively. Status of filtering bleb, intraocular pressure (IOP), and number of medications were recorded. ResultsOne year after surgery all patients had IOP ≤ 21; 6 patients received antiglaucoma medication. One eye required needling of the filtering bleb because of encapsulation. During the first postoperative year, eyes with conjunctival subepithelial micro cysts, observed in the first and the second postoperative week, had significantly lower mean IOP, than eyes without (11.1 mm Hg vs. 13.9 mm Hg; p:0.0043, ANOVA). Eyes with corkscrew vessels, observed in the first and the second postoperative week, had significantly higher mean IOP, than eyes without during the first postoperative year (13.4 mm Hg vs. 11.7 mm Hg; p:0.0141, ANOVA). ConclusionClassification of filtering blebs after trabeculectomy with MMC may help to disclose patients with an increased failure risk.

Local Tumor Control, Visual Acuity, and Survival After Hypofractionated Stereotactic Photon Radiotherapy of Choroidal Melanoma in 212 Patients Treated Between 1997 and 2007

PURPOSE To evaluate long-term local tumor control, visual acuity, and survival after hypofractionated linear accelerator-based stereotactic photon radiotherapy in patients with choroidal melanoma. METHODS AND MATERIALS Between 1997 and 2007, 212 patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at a linear accelerator with 6-MV photon beams at the Medical University of Vienna in five fractions over 7 days. Twenty-four patients received a total dose of 70 Gy (five fractions of 14 Gy), 158 a total dose of 60 Gy (five fractions of 12 Gy) and 30 patients a total dose of 50 Gy (five fractions of 10 Gy) applied on the 80% isodose. Ophthalmologic examinations were performed at baseline and every 3 months in the first 2 years, every 6 months until 5 years, and once a year thereafter until 10 years after radiotherapy. Assessment of visual acuity, routine ophthalmologic examinations, and measurement of tumor base dimension and height using standardized A-scan and B-scan echography were done at each visit. Funduscopy and fluorescein angiography were done when necessary to document tumor response. RESULTS Median tumor height and volume decreased from 4.8 mm and 270.7 mm3 at baseline to 2.6 mm and 86.6 mm3 at the last individual follow-up, respectively (p<0.001, p<0.001). Median visual acuity decreased from 0.55 at baseline to hand motion at the last individual follow-up (p<0.001). Local tumor control was 95.9% after 5 years and 92.6% after 10 years. Thirty-two patients developed metastatic disease, and 22 of these patients died during the follow-up period. CONCLUSION Hypofractionated stereotactic photon radiotherapy with 70 to 50 Gy delivered in five fractions in 7 days is sufficient to achieve excellent local tumor control in patients with malignant melanoma of the choroid. Disease outcome and vision are comparable to those achieved with proton beam radiotherapy. Decreasing the total dose below 60 Gy seems to be possible.

Effect of intraocular lens optic edge design and material on fibrotic capsule opacification and capsulorhexis contraction

Purpose: To examine the influence of intraocular lens (IOL) optic edge design and optic material on fibrosis of the anterior and peripheral posterior capsules and on capsulorhexis contraction. Setting: Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. Methods: This randomized controlled patient‐ and examiner‐masked study comprised 210 eyes of 105 patients with bilateral age‐related cataract. In Group 1 (n = 53), the Sensar® OptiEdge AR40e hydrophobic acrylic IOL with a sharp posterior optic edge was compared with the AR40 acrylic IOL with a round edge. In Group 2 (n = 52), the ClariFlex® OptiEdge silicone IOL with a sharp posterior optic edge was compared with the PhacoFlex SI‐40 silicone IOL with a round edge All IOLs were manufactured by Advanced Medical Optics, Inc. Standardized digital slitlamp images of anterior capsule opacification (ACO) and fibrotic posterior capsule opacification (PCO) were taken 1 year postoperatively, and digital retroillumination images were taken at 1 week and 1 year. The intensity of fibrotic PCO was graded subjectively (score 0 to 4), ACO was graded objectively (score 0% to 100%), and the capsulorhexis area (mm2) was determined objectively. Results: One year after surgery, the mean ACO score was 32% in eyes with the sharp‐edged acrylic IOL and 29% in eyes with the round‐edged acrylic IOL (P<.05). In the silicone group, the mean was 31% and 26%, respectively (P<.05). The mean fibrotic PCO score was lower in eyes with a sharp‐edged acrylic IOL than in eyes with a round‐edged acrylic IOL (0.26 and 0.93, respectively; P<.05) and in eyes with a sharp‐edged silicone IOL than in eyes with a round‐edged silicone IOL (0.24 and 0.82, respectively; P<.001). At 1 year, the mean capsulorhexis area was statistically significantly smaller in eyes with a sharp‐edged silicone IOL than in eyes with a round‐edged silicone IOL (P<.05). Conclusions: Acrylic and silicone IOLs with the sharp OptiEdge design led to significantly less fibrotic PCO but more ACO than round‐edged acrylic and silicone IOLs. The sharp‐edged silicone IOL caused significantly more capsulorhexis contraction than the round‐edged silicone IOL and both acrylic IOLs.