Comparing the effectiveness of bevacizumab to ranibizumab in patients with exudative age-related macular degeneration. The BRAMD study

Purpose: To compare the effectiveness of bevacizumab and ranibizumab in the treatment of exudative age-related macular degeneration (AMD). Design: Multicentre, randomized, controlled, double-masked clinical trial in 327 patients. The noninferiority margin was 4 letters. Patients: Patients ≥ 60 years of age with primary or recurrent sub- or juxtafoveal choroidal neovascularization (CNV) secondary to AMD with a total area of CNV < 12 disc areas and a best corrected visual acuity (BCVA) score between 20 and 78 letters on an EDTRS like chart in the study eye. Methods: Monthly intravitreal injections with 1.25 mg bevacizumab or 0.5 mg ranibizumab were given during one year. Intention to treat with last observation carried forward analysis was performed. Main Outcome Measures: Primary outcome was the change in BCVA in the study eye from baseline to 12 months. Results: The mean gain in BCVA was 5.1 (±14.1) letters in the bevacizumab group (n = 161) and 6.4 (±12.2) letters in the ranibizumab group (n = 166) (p = 0.37). The lower limit of the 95% confidence interval of the difference in BCVA gain was 3.72. The response to bevacizumab was more varied; 24% of patients showed a gain of ≥15 letters, 11% a loss of ≥15 letters and 65% a gain or loss < 15 letters compared to 19%, 5% and 76% respectively for ranibizumab (p = 0.038). No significant differences in absolute CRT and CRT change (p = 0.13) or in the presence of subretinal or intraretinal fluid (p = 0.14 and 0.10, respectively) were observed. However, the presence of any fluid on SD-OCT (subretinal and/or intraretinal) differed significantly (p = 0.020), with definite fluid on SD-OCT in 45% of the patients for bevacizumab versus 31% for ranibizumab. The occurrence of serious adverse events and adverse events was similar, with 34 SAEs and 256 AEs in the bevacizumab group and 37 SAEs and 299 AEs in the ranibizumab group (p = 0.87 and p = 0.48, respectively). Conclusions: Bevacizumab was not inferior to ranibizumab. The response to bevacizumab was more varied with higher percentages of both gainers and losers and more frequently observed retinal fluid on SD-OCT at 12 months when compared to the ranibizumab group. Trial Registration: Trialregister.nl NTR1704

Comparing the effectiveness and costs of Bevacizumab to Ranibizumab in patients with Diabetic Macular Edema: A randomized clinical trial (the BRDME study)

Background: The effectiveness of ranibizumab in the treatment of diabetic macular edema has been proven with large clinical trials. For bevacizumab only two clinical trials have been published and a head-to-head comparison is lacking to date. However, if proved non-inferior to ranibizumab, use of the off-label bevacizumab could reduce costs enormously without a loss in visual acuity. A cost-effectiveness study has been designed to substantiate this hypothesis. Aim: To compare the effectiveness and costs of 1.25 mg of bevacizumab to 0.5 mg ranibizumab given as monthly intravitreal injections during 6 months in patients with diabetic macular edema. It is hypothesized that bevacizumab is non-inferior to ranibizumab regarding its effectiveness. Design: This is a randomized, controlled, double masked, clinical trial in 246 patients in seven academic trial centres in The Netherlands. Outcomes: The primary outcome measure is the change in best-corrected visual acuity (BCVA) in the study eye from baseline to month 6. Secondary outcomes are the proportions of patients with a gain or loss of 15 letters or more or a BCVA of 20/40 or more at 6 months, the change in leakage on fluorescein angiography and the change in foveal thickness by optical coherence tomography at 6 months, the number of adverse events in 6 months, and the costs per quality adjusted life-year of the two treatments

Periorbital necrotising fasciitis due to Cryptococcus neoformans in a healthy young man

A case report is presented of a healthy 25-year-old man who developed a periorbital necrotising fasciitis after a trivial trauma with a wooden splinter. Necrotising fasciitis of the eyelids occurs rarely. Cryptococcus neoformans is not described as a causative factor of necrotizing fasciitis. Cryptococcus neoformans usually infects patients with immunodeficiencies, diabetes mellitus or steroid therapy. This patient was healthy and developed a periorbital necrotising fasciitis due to Cryptococcus neoformans

Poly(1,3-trimethylene carbonate) networks as a resorbable scleral buckle

Currently non-resorbable scleral buckles are used to repair a retinal detachment in the eye. In contrast to a non-resorbable implant, a resorbable implant will disappear after it has fulfilled its function. PTMC scleral buckles were implanted in six rabbits and explanted 10 weeks later. Histological analysis showed a mild tissue response, the degradation rate was up to 9.2 μm/day. Based on these results, it is expected that PTMC is a suitable material for scleral buckle application

Pentosidine accumulates in the aging vitreous body: A gender effect

The human vitreous body undergoes structural changes with aging. This can be followed by a posterior vitreous detachment, which can result in ocular pathology. As in many collagenous tissues, age-related changes in the vitreous could be caused by the formation of advanced glycation end products (AGEs). The goal of this study was to find out whether the AGE pentosidine accumulates in the human vitreous with aging. With this data we were able to estimate the half-life of vitreous collagen. Furthermore, we analyzed whether there was a gender difference in pentosidine accumulation, as this was seen in other tissues as well. Using high performance liquid chromatography, pentosidine contents were determined in whole vitreous bodies and in separate parts of vitreous bodies, which were all obtained from human donor eyes. Our results show that pentosidine accumulates in the human vitreous. From the rate of accumulation we could roughly estimate that vitreous collagen has as a similar or shorter half-life compared to skin collagen. This supports the concept of collagen turnover in the vitreous. In general, the female vitreous experiences a faster pentosidine accumulation than the male vitreous, and most of the pentosidine accumulation in the former occurs after 50 years of age. © 2009 Elsevier Ltd. All rights reserved

Design and Validation of a Method to Determine the Position of the Fovea by Using the Nerve-Head to Fovea Distance of the Fellow Eye

<p>Purpose: To measure the nerve-head to fovea distance (NFD) on fundus photographs in fellow eyes, and to compare the NFD between fellow eyes.</p><p>Methods: Diabetic patients without retinopathy, (n = 183) who were screened by fundus photography at the University Medical Center Groningen, the Netherlands from January 1st 2005 until January 1st 2006 were included. The NFD was measured in left and right eyes both from the center and from the rim of the nerve-head. To determine inter-and intra-observer agreement, repeated measurements by one observer (n = 3) were performed on all photographs and by two observers on 60 photographs (30 paired eyes). The effect of age, gender, and refractive error on NFD was analysed.</p><p>Results: The correlation of NFDs between the left and the right eye was 0.958 when measured from the center of the nerve head (mean difference 0.0078 mm. +/- SD 0.079 (95% limits of agreement -0.147-0.163)) and 0.963 when measured from the rim (mean difference 0.0056 +/- SD 0.073 (95% limits of agreement -0.137-0.149)). Using the NFD between fellow eyes interchangeably, resulted in a standard error of 0.153 mm. Intra- and inter-observer variability was small. We found a significant effect of age (center of the nerve-head (P = 0.006) and rim of the nerve head (P = 0.003)) and refractive error (center of nerve-head (P</p><p>Conclusions: The NFD in one eye provides a confident, reproducible, and valid method to address the position of the fovea in the fellow eye. We recommend using the NFD measured from the center of the nerve-head since the standard error by this method was smallest. Age and refractive error have an effect on NFD.</p>

Mature enzymatic collagen cross-links, hydroxylysylpyridinoline and lysylpyridinoline, in the aging human vitreous

Purpose. The vitreous body of the human eye undergoes progressive morphologic changes with aging. Since the enzymatic collagen cross-links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are known to be important for the integrity of the collagen matrix, the presence in the vitreous on aging was studied. Methods. Vitreous bodies (VBs; n = 143) from 119 donors (age 4-80 years; mean ± SD, 54.3 ± 17.0 years) were carefully dissected. After weighing and freeze-drying, all samples were analyzed by high performance liquid chromatography. Left and right eyes of 24 donors were compared and, for age-related phenomena, 119 single eyes were used. Results. Within one donor, no significant differences were found between left and right eyes. On aging, VB wet weight (4.42 ± 0.84 g) accumulates until 35 years and decreases thereafter. Collagen content (0.30 ± 0.14 mg), HP per triple helix (TH; 0.55 ± 0.18), and (HP plus LP)/TH (0.61 ± 0.19) increase until 50 years followed by a decrease, whereas LP/TH (0.057 ± 0.018) accumulates until 50 years and remains constant thereafter. The ratio between HP and LP (range, 0.42-31.0; median, 10.0) is constant over time. Conclusions. The accumulation of enzymatic collagen cross-links until 50 years is consistent with collagen maturation and possible collagen synthesis in the human vitreous body. The decline of collagen cross-links after 50 years is consistent with collagen breakdown