Objective: To demonstrate optical coherence tomography for high-resolution, noninvasive imaging of the human retina. Optical coherence tomography is a new imaging technique analogous to ultrasound B scan that can provide cross-sectional images of the retina with micrometer-scale resolution. Design: Survey optical coherence tomographic examination of the retina, including the macula and optic nerve head in normal human subjects. Settings Research laboratory. Participants: Convenience sample of normal human subjects. Main Outcome Measures: Correlation of optical coherence retinal tomographs with known normal retinal anatomy. Results: Optical coherence tomographs can discriminate the cross-sectional morphologic features of the fovea and optic disc, the layered structure of the retina, and normal anatomic variations in retinal and retinal nerve fiber layer thicknesses with 10- μm depth resolution. Conclusion: Optical coherence tomography is a potentially useful technique for high depth resolution, cross-sectional examination of the fundus.

Optical Coherence Tomography of the Human Retina

Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration.

Background Angiogenesis is a key aspect of the wet form of age-related neovascular (AMD), the leading cause of blindness in the elderly population. Substantial evidence indicated that vascular endothelial growth factor (VEGF)-A is a major mediator of angiogenesis and vascular leakage in wet AMD. VEGF-A is the prototype member of a gene family that includes also PlGF, VEGF-B, VEGF-C, VEGF-D and the orf virus-encoded VEGF-E. Several isoforms of VEGF-A can be generated due to alternative mRNA splicing. Various VEGF inhibitors have been clinically developed. Among these, ranibizumab is a high affinity recombinant Fab that neutralizes all isoforms of VEGF-A. The article briefly reviews the biology of VEGF and then focuses on the path that led to clinical development of ranibizumab. Results The safety and efficacy of ranibizumab in the treatment of neovascular AMD have been evaluated in two large phase III, multicenter, randomized, double-masked, controlled pivotal trials in different neovascular AMD patient populations. Combined, the trial results indicate that ranibizumab results not only in a slowing down of vision loss but also in a significant proportion of patients experiencing a clinically meaningful vision gain. The visual acuity benefit over control was observed regardless of CNV lesion type. Furthermore, the benefit was associated with a low rate of serious adverse events. Conclusions Ranibizumab represents a novel therapy that, for the first time, appears to have the potential to enable many AMD patients to obtain a meaningful and sustained gain of vision. On June 30 2006, ranibizumab was approved by the US Food and Drug Administration for the treatment of wet AMD.

Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration.

Purpose:To describe the short-term anatomical and visual acuity responses after intravitreal injection of bevacizumab (Avastin, Genentech) in patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).Methods:We conducted a retrospective study of patients wi

Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration.

Objective To evaluate the clinical outcome of an intravitreal injection of triamcinolone acetonide as treatment of diffuse diabetic macular edema. Participants This prospective, interventional, clinical case series study included 20 patients (26 eyes) who received an intravitreal injection of 25 mg of triamcinolone acetonide for treatment of diffuse diabetic macular edema. Mean ± SD follow-up time was 6.64 ± 6.10 months. The study group was compared with a control group of 16 patients who underwent macular grid laser coagulation. Main Outcome Measures Visual acuity and intraocular pressure. Results In the study group, visual acuity improved significantly (P Conclusion Intravitreal injection of 25 mg of triamcinolone acetonide may be beneficial for improving visual acuity in patients with clinically significant diffuse diabetic macular edema.

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Intravitreal injection of triamcinolone for diffuse diabetic macular edema.

Intravitreal triamcinolone for uveitic cystoid macular edema: an optical coherence tomography study.

PURPOSE
To study real-world ranibizumab therapy for treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) and to benchmark standards of care.


DESIGN
Multicenter, national nAMD database study.


PARTICIPANTS
A total of 92 976 treatment episodes from 12 951 eyes of 11 135 patients.


METHODS
Up to 5 years of routinely collected, anonymized data were extracted remotely from 14 United Kingdom centers to a central database using an electronic medical record (EMR) system. Participating centers used ranibizumab to treat nAMD using a loading phase of 3 monthly injections and a pro re nata retreatment regimen. The minimum data set defined before first patient data entry and mandated by the EMR system included age, Early Treatment Diabetic Retinopathy Study visual acuity (VA) at all visits, and injection episodes.


MAIN OUTCOME MEASURES
Baseline VA, change in VA, number of treatments and clinic visits, and baseline characteristics affecting VA change.


RESULTS
Information from more than 300 000 clinic visits (2.8 million data points) were collated. Mean age at first treatment was 79.1 years, with a female preponderance of 1.7:1. Mean VA (letters) for eyes followed up for at least 3 years from a baseline of 55 letters was 57 (+2) letters at 1 year, 56 (+1) letters at 2 years, and 53 (-2) letters at 3 years. The proportion of eyes that avoided moderate vision loss at years 1, 2, and 3 were 90%, 84%, and 82%, respectively. The proportion of eyes with VA of 20/40 or better were: baseline, 16%; year 1, 30%; year 2, 30%; and year 3, 29%. The median number of treatments for eyes followed up for at least 3 years in years 1, 2 and 3 was 5, 4, and 4, respectively, and the median number of outpatient visits was 9.2, 8.2, and 8.2, respectively. Baseline VA was related inversely to mean vision gain at 3 months. Older age was associated with lower presenting VA.


CONCLUSIONS
Real-world visual outcomes achieved at a large number of centers across the United Kingdom do not match the results achieved in most randomized trials, but they were delivered with substantially fewer injections and hospital visits. This study provides important benchmark results that should be of interest to patients, retina specialists, and commissioners of health care. This study demonstrates the EMR system's potential usefulness for future phase 4 and 5 clinical trials.

The Neovascular Age-Related Macular Degeneration Database: Multicenter Study of 92 976 Ranibizumab Injections

Purpose To determine the maximum size of molecule capable of freely diffusing across human retina, referred to as the retinal exclusion limit (REL), and the location of any sites of high resistance to diffusion. To assess the degree of interspecies variation in the REL of three animals commonly used to model human disease. Methods Trephines of human neuroretina were mounted in a modified Ussing chamber. FITC-dextrans of various molecular weights (MWT) were dissolved in phosphate-buffered saline, and the rate of transretinal diffusion was determined over 24 hours with a spectrophotometer. The theoretical REL was calculated by extrapolating the linear relationship between the rate of diffusion and log(MWT). In separate experiments to determine the sites of barrier to diffusion, FITC-dextrans with a MWT greater than the calculated REL were applied to either the inner or outer retinal surface, processed as frozen sections, and viewed with a fluorescence microscope. Experiments to determine the REL were repeated in bovine, porcine, and rabbit retina. Results The REL in human tissue was 76.5+/-1.5 kDa (6.11+/-0.04 nm). The inner and outer plexiform layers formed the sites of highest resistance to diffusion. The REL in pigs, cattle, and rabbits were 60 +/- 11.5, 78.5 +/- 20.5, and 86 +/- 30 kDa, respectively (5.68 +/- 0.45, 6.18 +/- 0.61, and 6.38 +/- 0.88 nm). Conclusions In humans, the inner and outer plexiform layers are sites of high resistance to the diffusion of large molecules, resulting in an REL of 76.5 kDa. There was only moderate interspecies variation in the REL of the animals studied, suggesting that they provide adequate models for the study of human transretinal macromolecular diffusion.

Richard J Antcliff

Papers

Intravitreal triamcinolone for uveitic cystoid macular edema: an optical coherence tomography study.

The Neovascular Age-Related Macular Degeneration Database: Multicenter Study of 92 976 Ranibizumab Injections

Human retinal molecular weight exclusion limit and estimate of species variation

Optical coherence tomography of melanocytoma.

The Neovascular Age-Related Macular Degeneration Database: Report 2: Incidence, Management, and Visual Outcomes of Second Treated Eyes