Needle size in intravitreal injections - pain evaluation of a randomized clinical trial.

PURPOSE: To evaluate the influence of the needle size used for intravitreal (IVT) injections on patients' pain experience in a randomized, double-armed, single-blinded, clinical trial. METHODS: Patients included were randomized to have an IVT injection performed with a 27-gauge needle (group 1) or with a 30-gauge needle (group 2). The topical anaesthesia before the injection was standardized. Immediately after the injection, patients were asked to grade their pain using the visual analogue scale (VAS) and the Wong-Baker FACES scale. The main outcome measure was the pain score assessment. Cofactors analysed were patients' demographics (age and gender) and clinical characteristics (such as the number of previous IVT injections). In addition, scaled surgeon's questionnaires to assess the IVT injection procedure were evaluated. For statistical analysis, a regression model was used. RESULTS: The data of 208 patients (group 1: 104 patients; group 2: 104 patients) were analysed. There was no significant difference in the VAS pain scores (p > 0.18) and in the Wong-Baker pain scores (p > 0.59) between both treatment groups. Gender (p = 0.0288) and the number of previous IVT injections (p = 0.0028) significantly influenced the VAS pain scores (p < 0.05). Female patients and patients with a history of previous IVT injections had higher pain scores. The surgeon's questionnaire showed an overall preference towards the use of a 30-gauge needle for IVT injections. CONCLUSION: The use of a 30-gauge needle for IVT injections showed no significant effect in pain relief compared to the use of a 27-gauge needle. However, a 30-gauge needle was preferred by all surgeons.

Impact of visceral fat and pro-inflammatory factors on the pathogenesis of age-related macular degeneration.

PURPOSE: Previous studies have indicated that the immune system is involved in the pathogenesis of the AMD. Increased visceral fat, in addition, has a pro-inflammatory effect on the organism by producing or influencing different kinds of inflammatory factors. The aim of this study is to determine the relationship of body fat distribution in patients with age-related macula degeneration in comparison to a control group in the Austrian population. METHODS: In this case-control study, body weight and height, and body mass index (BMI) were measured for each subject in 54 patients with exudative AMD and compared to 46 gender- and age-matched healthy control subjects. Body composition and abdominal fat areas were measured using dual-energy X-ray absorptiometry (DEXA). Data on age, gender distribution, smoking history and systemic diseases, respectively, were compared. The inflammatory markers CRP, tumour necrosis factor-alpha (TNF-alpha), leptin, amyloid A, amyloid beta and interleukin-6 (IL-6) were assayed by ELISA (R&D). RESULTS: DEXA revealed central-abdominal-to-total body fat ratio of 0.073 +/- 0.011 in AMD patients compared to 0.061 +/- 0.013 in the controls (p <0.001; d = 0.98). The calculation of BMI has provided a significant result (p =0.045). U-test results for Aß1-42, IL-6, SAA and CRP each were significant (p < 0.05), with higher values in AMD patients. Leptin, TNF-alpha and Aß1-40 showed no significant differences between the groups. CONCLUSION: Our results suggest that abdominal fat distribution is significantly associated with age-related macular degeneration. Analysis of patients with exudative AMD revealed higher levels of CRP, amyloid ß1-42, IL-6 and amyloid alpha.

Choroidal thickness in patients with reticular pseudodrusen using 3D 1060-nm OCT maps.

PURPOSE: To map and analyze choroidal thickness (ChT) in AMD patients with reticular pseudodrusen (RPD) using three-dimensional (3D) 1060-nm optical coherence tomography (OCT). METHODS: Fifty eyes from 25 patients with RPD were grouped according to the severity of AMD and the presence of RPD. All patients were imaged by high-speed (60,000 A-scans/s) 3D 1060-nm OCT over a 36 × 36° field of view. Choroidal thickness maps were automatically generated and compared with RPD areas visualized by fundus autofluorescence and infrared imaging. Retinal thickness maps, ChT maps, Haller's and Sattler's layer thickness were statistically analyzed between groups. RESULTS: The mean ± SD (micrometers) subfoveal ChT was 201 ± 88 µm, 145 ± 48 µm, and 271 ± 130 µm for dry AMD with RPD, wet AMD with RPD, and eyes with wet AMD and no RPD, respectively. Choroidal thickness maps demonstrated the most significant choroidal thinning within eyes with wet AMD and RPD. Sattler's and Haller's layer thickness differed across the Early Treatment Diabetic Retinopathy Study grid when compared between eyes with and without RPD. Within eyes with RPD, ChT maps visualized that ChT was thicker below RDP areas than non-RPD areas. CONCLUSIONS: The 3D 1060-nm OCT choroidal maps over a large field of view offer noninvasive visualization for demonstrating local thickening correlation with RPD within each eye and overall thinning owing to AMD severity and RPD. This choroidal thinning was most striking in Sattler's layer, suggesting a choroidopathy of this vascular layer.

A prospective, randomised, multicenter trial for surgical treatment of central retinal vein occlusion: results of the Radial Optic Neurotomy for Central Vein Occlusion (ROVO) study group.

BACKGROUND: To compare the surgical outcomes and evaluate the effectiveness of two treatments for central retinal vein occlusion (CRVO), radial optic neurotomy (RON) and intravitreal triamcinolone (IVT), in comparison to natural history. METHODS: A prospective, placebo-controlled, randomised and multi-center study. Patients with CRVO were treated in three groups - with either RON, a single intravitreal injection of 4 mg triamcinolone acetonide, or a placebo treatment. The main outcome measures were change of VA (visual acuity) and proportion of eyes with a significant improvement (defined as > 3 lines logMAR scale) of VA from baseline to month 12. RESULTS: Ninety patients were included. Due to insufficient data, seven were excluded. Forty-seven percent (n = 18) of patients treated with RON showed an increase in VA, in comparison to 10 % (n = 2) of placebo-treated patients, and 20 % (n = 5) of patients treated with IVT. Significantly more patients showed an improvement in VA following RON than in the placebo group (p = 0.009). Significantly more patients showed an improvement in VA following RON than in the IVT group (p = 0.034). No significant difference was found when directly comparing improvement in VA following IVT and placebo (p = 0.667) treatment.Significantly (p = 0.007) more patients in the placebo group (35 %, n = 7) showed a deterioration (defined as > 3 lines LogMAR scale) in VA than patients in the RON group (8 %, n = 3). CONCLUSION: Our study showed that following treatment with RON, patients with CRVO display a significantly better long-term VA than untreated patients and patients treated with a single dose of IVT.

Comparing treatment of neovascular age-related macular degeneration with sequential intravitreal Avastin and Macugen versus intravitreal mono-therapy--a pilot study.

PURPOSE: To examine if the sequential treatment of Avastin and Macugen is safe and more efficient than the mono-therapies in a prospective randomized masked pilot study. MATERIALS AND METHODS: Subjects with exudative age-related macular degeneration were randomized to receive three intravitreal injections of either 1 mg of Avastin, 0.3 mg Macugen, or first 1 mg Avastin followed by retreatment of 0.3 mg Macugen. Follow-up examinations were performed after 1, 6, 12 weeks, and 6 months. RESULTS: Forty-eight subjects were included (13:18:17). Avastin resulted in lasting significant changes in visual acuity at 6 weeks, increase in contrast sensitivity at 6 weeks, and a significant decrease in macular thickness after 6 and 12 weeks. Macugen showed a significant decrease in retinal thickness after 6 weeks, but a significant decrease in visual acuity after 6 months, and a significant decrease in contrast sensitivity after 12 weeks and 6 months. The sequential treatment showed a decrease in retinal thickness after 1 and 12 weeks. CONCLUSION: Avastin alone is more effective in increasing visual acuity and contrast sensitivity and decreasing retinal thickness, than Macugen or the sequential treatment. We conclude that the sequential treatment of Avastin with Macugen is safe, but the single treatment of Avastin is more efficient.

Implication of CD21, CD35, and CD55 in the pathogenesis of age-related macular degeneration.

PURPOSE: To determine a possible implication of CD21, CD35, and CD55 in the pathogenesis of age-related macular degeneration (AMD) by assessing the difference in expression rates of these factors on AMD patients and a control group. DESIGN: Case-control study. METHODS: Fifty unrelated AMD patients and 48 unrelated sex- and age-matched control subjects participated in this case-control study. Samples of fresh EDTA-blood were stained and flow cytometry was chosen to measure fluorescence emissions. The association between exudative AMD and CD21, CD35, and CD55 was evaluated from all patients who completed the study. RESULTS: Our study shows CD35 to be expressed in a significantly higher frequency in AMD patients on monocytes (P = .00586), lymphocytes (P = .000605), and granulocytes (P < .000033). In contrast, the expression rate of CD21 (P > .05) and CD55 (P > .05) are similar in both groups. CONCLUSION: More regulative factors of the complement system are involved in pathogenesis of AMD. Our study underlines the key role of the complement system in AMD and shows the involvement of the whole immune system through more regulative factors.

Epidermal growth factor: the driving force in initiation of RPE cell proliferation.

BACKGROUND: To analyze whether epidermal growth factor (EGF) exerts regulatory effects on proliferation and differentiation in ARPE19 cells after different incubation periods (24 vs. 48 h) for obtaining ideal conditions for feasible rejuvenation and autologous transplantation of retinal pigment epithelial cells (RPE cells). METHODS: To evaluate gene expression patterns of RPE-specific differentiation and proliferation markers as well as transcriptional and translational changes of beta-catenin (ß-catenin)-signaling markers by fluorescence activated cell sorting (FACS) and reverse transcription - polymerase chain reaction (RT-PCR) after 24 h of EGF treatment. RESULTS: After 24 h of EGF treatment, a significant decrease of retinal pigment epithelium-specific protein 65 (RPE 65), cellular retinaldehyde-binding protein (CRALBP) and cytokeratin 18 in ARPE-19 cells was scaled. In addition, an increase of cyclin D1 expression and a significant decrease of glycogen synthase kinase-3beta (GSK-3ß) and beta-catenin (ß-catenin) were equally observed after 24 and 48 h of EGF treatment. Cell-cycle studies revealed an increase of ARPE cells in S-G2/M phase after 24 h of EGF treatment. CONCLUSIONS: Our data demonstrate the induction of proliferation and upregulation of the ß-catenin signaling pathway by EGF even after 24 h of incubation. As ideal cell culture conditions are essential for maintaining RPE-specific phenotypes, short incubation times enhance RPE cell quality for feasible rejuvenation and subsequent autologous transplantation of RPE cells.

Genetic cardiovascular risk factors and age-related macular degeneration.

PURPOSE: To investigate the association between genetic cardiovascular risk factors and exudative age-related macular degeneration (AMD) in a White Austrian population. METHODS: Seventy-five unrelated AMD patients and 75 unrelated healthy, sex- and age-matched control patients were genotyped for the following 19 single nucleotide polymorphisms (SNPs) in 14 different genes: blood coagulation factor V (FV) R506Q, factor II (prothrombin) G20210A and factor XIII (FXIII) V34L; 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C; plasminogen activator inhibitor 1 (PAI-1) 4G/5G; endothelial protein C receptor (EPCR) 4600 A>G (A3 haplotype), 4678 G>C (A1 haplotype); apolipoprotein B (ApoB) R3500Q; apolipoprotein E (ApoE) E2/E3/E4; ß-fibrinogen -455 G>A; human platelet antigen 1 (HPA1) a/b; angiotensin-converting enzyme (ACE) I/D; endothelial nitric oxide synthase (eNOS) 786 T>C, 894 G>T; lymphotoxin alpha (LTA) 804 C>A and 9p21 rs10757278. Genotyping was carried out by polymerase chain reaction (PCR) followed by reverse hybridization (CVD StripAssays; ViennaLab Diagnostics, Vienna, Austria). RESULTS: No statistically significant association could be observed between AMD and the investigated genetic risk factors for cardiovascular disease (CVD). All factors seem to be uniformly distributed in the two groups of AMD patients and healthy controls. Two variables -ß-fibrinogen: -455 G>A (p = 0.0786) and apolipoprotein E4 (p = 0.0636) - were not as far from association as the others. CONCLUSION: Our data show that the 19 tested CVD risk markers do not play a significant role in AMD. ß-Fibrinogen and apolipoprotein E4 should be examined in a larger cohort.

Reproducibility and comparison of retinal thickness and volume measurements in normal eyes determined with two different Cirrus OCT scanning protocols.

PURPOSE: To assess reproducibility and compare raster scanning protocols of Cirrus high-definition optical coherence tomography (Carl Zeiss Meditec, Dublin, CA). METHODS: Five hundred and twenty-eight computed tomography scans were performed in 17 healthy subjects. Four sessions were performed at each visit including two 200 × 200 and two 512 × 128 macular cube scans per session. The examined eye, observer, and order of scanning protocols in-between each session were randomly chosen. Reproducibility was described with intraclass correlation coefficients, coefficients of variance, intervisit, interrater, intersession intra-, and intersubject standard deviations. RESULTS: Intraclass correlation coefficients ranged from 80.4% to 97.8% and the coefficients of variance from 0.7% to 2.3% for retinal volume and retinal thickness measurements. Intersubject, intervisit, interrater, intersession, and intrasubject standard deviations ranged from 0 µm to 18.54 µm. Differences in retinal thickness between protocols were small (range 3.55 ± 1.95 µm to 0.81 ± 0.59 µm) but significant for the central (P < 0.0001), the outer superior (P = 0.0036), temporal (P = 0.0026), and nasal subfield (P < 0.0001). Average difference of retinal volume between protocols was 0.05 ± 0.04 mm (P = 0.0001). CONCLUSION: Both raster scanning protocols of the Cirrus optical coherence tomography showed excellent reproducibility of retinal thickness and volume measures. Significant differences between protocols for retinal thickness in four macula thickness map subfields and for retinal volume were found.

Serum VEGF and CFH in exudative age-related macular degeneration.

PURPOSE: To determine serum vascular endothelial growth factor 165 (VEGF165) levels and the association of the complement factor H gene (CFH) Y402H polymorphism in patients with exudative age-related macular degeneration (AMD) in comparison to unaffected control subjects. METHODS: Sixty-six AMD patients and 66 healthy age- and gender-matched controls were included in this case-control study. The serum VEGF165 was assayed by ELISA (R&D). Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Chi-squared tests were used regarding the polymorphism, a t-test regarding the VEGF-levels. RESULTS: Levels of serum VEGF165 were similar in both groups (p-value = 0.2112). Genotype frequency differed significantly between patients with exudative AMD and the healthy control group (p = 0.003136). The serum VEGF165 levels were similar irrespective of the presence of the CFH Y402H polymorphism (p = 0.4113) and independent of the specific genotype (p = 0.9634). CONCLUSION: In the present study, exudative AMD is not associated to serum VEGF165 levels; furthermore, our data does not establish a statistical link between VEGF165 and the CFH Y402H polymorphism.

Comparison of visual performance with blue light-filtering and ultraviolet light-filtering intraocular lenses.

PURPOSE: To compare the contrast sensitivity, glare, color perception, and visual acuity at different light intensities with yellow-tinted and clear intraocular lenses (IOLs) by different manufacturers. SETTING: Ludwig Boltzmann Institute of Retinology and Biomicroscopic Laser-Surgery, Department of Ophthalmology, Rudolf Foundation Clinic, Vienna, Austria. DESIGN: Comparative case series. METHODS: Eyes were randomized to 1 of the following IOLs: AF-1 (UY) (yellow tinted), AcrySof SN60AT (yellow tinted), AF-1 (UV) (clear), or AcrySof SA60AT (clear). One week and 2 months postoperatively, monocular contrast sensitivity function and color discrimination were tested and the corrected distance and near visual acuities were evaluated. All tests were performed under different light intensities (10 to 1000 lux). RESULTS: Of the 80 patients enrolled, 76 completed the study; there were 37 eyes in the yellow-tinted IOL group and 39 in the clear IOL group. There were no significant differences between yellow-tinted IOLs and clear IOLs except in color vision under mesopic conditions (10 lux). Patients with a yellow-tinted IOL made significantly more mistakes in the blue-light spectrum than patients with clear IOLs (P = .00015). There was no significant difference under photopic conditions (1000 lux). CONCLUSIONS: The yellow-tinted IOLs were equivalent to the clear IOLs in postoperative contrast sensitivity, visual acuity, and color perception under photopic conditions. Patients with yellow-tinted IOLs made statistically significantly more mistakes in the blue range under dim light than patients with clear IOLs.

Repeatability and reproducibility of retinal thickness measurements by optical coherence tomography in age-related macular degeneration.

PURPOSE: To evaluate the repeatability and reproducibility of retinal thickness measurements in exudative age-related macular degeneration (AMD) using Stratus optical coherence tomography (OCT) (Carl Zeiss Meditec, Inc., Dublin, CA). DESIGN: Prospective, observational case series. PARTICIPANTS: A total of 200 eyes of 200 subjects with exudative AMD. METHODS: Macular thickness and fast macular thickness programs of Stratus OCT were performed twice by the same examiners or 2 different examiners. The sequence of examiners was randomized 1:1:1:1. The variability of 1-mm subfield central retinal thickness (CRT), center point thickness (CPT), and retinal volume (RV) was calculated. MAIN OUTCOME MEASURES: Interobserver and intraobserver variability of retinal thickness measurements. RESULTS: Ninety-nine patients/eyes were enrolled in study arm 1 (repeated by the same examiner), and 101 patients/eyes were enrolled in study arm 2 (repeated by different examiners). Values of CPT, CRT, and RV were well correlated (interclass correlation coefficient, 0.71-0.93) in both study arms, revealing better results for the macular thickness program than for the fast macular thickness program. Threshold algorithm line failures were significantly correlated to the absolute differences of 2 repeated measurements for CPT, CRT, and RV but not with manually corrected maximum retinal thickness (MRT). Maximum retinal thickness was significantly influenced by the examiner performing the measurement. Age, lesion composition, examiner performing OCT examination, and sequence of examination had no significant influence. CONCLUSIONS: The repeatability and reproducibility of retinal thickness measurements were high, presenting better results for CRT and RV versus CPT, and for the macular thickness program versus the fast macular thickness program. The reliability of retinal thickness measurement was most frequently affected by algorithm line failures and fixation problems. A possible solution may be manually corrected measurement, such as MRT.

Fusarium endophthalmitis following refractive lens exchange for correction of high myopia.

We report a case of Fusarium endophthalmitis following refractive lens exchange (RLE) for the correction of high myopia that was initially diagnosed as lens-induced uveitis. Endophthalmitis is a rare but often devastating complication of intraocular lens surgery. In contrast to cataract surgery, in which the potential increase in visual acuity clearly outweighs the potential risks involved in the procedure, RLE has all the potential risks of conventional cataract surgery and the indication for surgery, "no more glasses or contact lenses," is not that straightforward.

Retinal angiomatous proliferation: morphological changes assessed by Stratus and Cirrus OCT.

BACKGROUND AND OBJECTIVE: Spectral domain optical coherence tomography (SD-OCT) should be used to examine lesions containing retinal angiomatous proliferation (RAP) to achieve a better understanding of the origin of this pathology. PATIENTS AND METHODS: In this prospective, observational case series, patients with RAP underwent retinal thickness imaging with Stratus OCT and cube 200 X 200 imaging with Cirrus OCT. RESULTS: A total of 12 eyes from 11 patients were included in the study. Of these, eight eyes had stage III RAP and four eyes had stage II RAP. Cirrus OCT detected the hyperreflective area corresponding to the neovascularization in all 12 eyes and Stratus OCT detected this pathology in 10 of the 12 eyes. All stage III lesions contained a retinal pigment epithelial break, which was more visible in the 200 x 200 scans obtained from Cirrus OCT compared with six radial scan lines obtained from Stratus OCT. CONCLUSION: Cirrus OCT had considerable advantages compared with Stratus OCT, particularly in investigation of juxtafoveal pathology.

Activation of the beta-catenin signaling pathway and its impact on RPE cell cycle.

PURPOSE: To investigate the effect of EGF, IGF-1, and VEGF on ARPE19 cell proliferation and differentiation. METHODS: The gene expression of RPE-specific differentiation and proliferation markers and the transcriptional and translational activity of beta-catenin signaling markers were measured by flow cytometry and RT-PCR. RESULTS: The data showed a significant decrease in RPE65, CRALBP, and cytokeratin 18 in ARPE-19 cells stimulated with EGF and IGF-1. In addition, a significant decrease in GSK-3beta and beta-catenin was observed that was paralleled by an increase in cyclin D1 expression. Cell cycle studies revealed an increase in ARPE cells in the S-G(2)/M-phase after treatment with EGF or IGF-1. VEGF, on the other hand, led to a reduction in cyclin D1 and to an increase in GSK 3beta and beta-catenin expression which was paralleled by an increase in RPE-specific differentiation markers. CONCLUSIONS: The data demonstrate the induction of proliferation by EGF and IGF-1 and upregulation of the beta-catenin signaling pathway in ARPE-19 cells. The data suggest that activation of the beta-catenin signaling pathway may be key in activating ARPE-19 cells by different growth factors.

Advantages of using a ray-traced, three-dimensional rendering system for spectral domain Cirrus HD-OCT to visualize subtle structures of the vitreoretinal interface.

BACKGROUND AND OBJECTIVE: To create a ray-traced, three-dimensional display system for Cirrus high-definition optical coherence tomography (Carl Zeiss Meditec, Inc., Dublin, CA) that improves the visualization of subtle structures of the vitreoretinal interface. PATIENTS AND METHODS: High-definition optical coherence tomography (HD-OCT) data for epiretinal membranes (17 eyes), macular holes (11 eyes), and posterior vitreal detachments (17 eyes) were collected. A display system that visualizes the acquired data using ray-tracing algorithms was designed and compared with the Cirrus HD-OCT 2.0 advanced visualization software system. The area around the vitreoretinal interface was visualized using a 100-microm-thick internal limiting membrane (ILM) fitted slab as well as ILM and retinal pigment epithelium surface reconstructions. RESULTS: Subtle structures could be visualized more distinctly using the ray-traced, three-dimensional rendering software. CONCLUSION: A ray-traced visualization system improves the visualization of subtle structures in and around the vitreoretinal interface.

Quality of the threshold algorithm in age-related macular degeneration: Stratus versus Cirrus OCT.

PURPOSE: Automatically generated measurements of the retinal volume or the central retinal thickness are based on correctly set threshold lines on the retinal surface and the retinal pigment epithelium. The purpose of this study was to compare the accuracy of threshold algorithm lines of Stratus optical coherence tomography (OCT) with those of Cirrus OCT. METHODS: A consecutive series of patients at least 50 years of age with exudative age-related macular degeneration was included. Stratus OCT (retinal thickness program) and Cirrus OCT (macular cube 512 x 128) were performed by the same examiner, the sequence of the examinations was randomized. Two independent examiners evaluated the positioning of the threshold algorithm lines and performed a grading of the failures. Logistic regression analysis was applied for evaluation of the failure rate. RESULTS: One hundred four patients were included. For the entire OCT examination (6 scans Stratus OCT, 128 scans Cirrus OCT) algorithm line failures were detected in 69.2% of the Stratus OCT and in 25% of the Cirrus OCT examinations, with the difference reaching statistical significance (P < 0.001). The median failure grade was 1 (0-6) for Stratus and 0 (0-5.15) for Cirrus OCT. Age, measurement sequence, and investigator did not influence the error rates. CONCLUSIONS: With Cirrus OCT automatically performed and therefore objective measurements of central retinal thickness and retinal volume were provided correctly in 69.2% of the scans. Furthermore, this latest software version offers the possibility of manual correction of false positioned algorithm lines (ClinicalTrials.gov number, NCT00568191).

Anecortave acetate for fibrotic lesions with presence of residual peripheral activity in age-related macular degeneration.

We retrospectively examined the efficacy of a single juxtascleral anecortave acetate depot injection for the treatment of fibrotic choroidal neovascular lesions with presence of residual peripheral activity in age related macular degeneration in 20 consecutive patients who rejected intravitreal treatment. As a second line-therapy of classic and occult fibrotic lesions with active peripheral zones, anecortave seems to be a vision conserving therapeutic option.