Background Ranibizumab — a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A — has been evaluated for the treatment of neovascular age-related macular degeneration. Methods In this multicenter, 2-year, double-blind, sham-controlled study, we randomly assigned patients with age-related macular degeneration with either minimally classic or occult (with no classic lesions) choroidal neovascularization to receive 24 monthly intravitreal injections of ranibizumab (either 0.3 mg or 0.5 mg) or sham injections. The primary end point was the proportion of patients losing fewer than 15 letters from baseline visual acuity at 12 months. Results We enrolled 716 patients in the study. At 12 months, 94.5% of the group given 0.3 mg of ranibizumab and 94.6% of those given 0.5 mg lost fewer than 15 letters, as compared with 62.2% of patients receiving sham injections (P<0.001 for both comparisons). Visual acuity improved by 15 or more letters in 24.8% of the 0.3-mg group and 33.8% of the 0.5-mg group, as compared with 5.0% of the sham-injection group (P<0.001 for both doses). Mean increases in visual acuity were 6.5 letters in the 0.3-mg group and 7.2 letters in the 0.5-mg group, as compared with a decrease of 10.4 letters in the sham-injection group (P<0.001 for both comparisons). The benefit in visual acuity was maintained at 24 months. During 24 months, presumed endophthalmitis was identified in five patients (1.0%) and serious uveitis in six patients (1.3%) given ranibizumab. Conclusions Intravitreal administration of ranibizumab for 2 years prevented vision loss and improved mean visual acuity, with low rates of serious adverse events, in patients with minimally classic or occult (with no classic lesions) choroidal neovascularization secondary to age-related macular degeneration. (ClinicalTrials.gov number, NCT00056836.)

/pdf/ranibizumab-for-neovascular-age-related-macular-degeneration-3277jvstyt.pdf

Ranibizumab for Neovascular Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. We report a genome-wide screen of 96 cases and 50 controls for polymorphisms associated with AMD. Among 116,204 single-nucleotide polymorphisms genotyped, an intronic and common variant in the complement factor H gene ( CFH ) is strongly associated with AMD (nominal P value -7 ). In individuals homozygous for the risk allele, the likelihood of AMD is increased by a factor of 7.4 (95% confidence interval 2.9 to 19). Resequencing revealed a polymorphism in linkage disequilibrium with the risk allele representing a tyrosine-histidine change at amino acid 402. This polymorphism is in a region of CFH that binds heparin and C-reactive protein. The CFH gene is located on chromosome 1 in a region repeatedly linked to AMD in family-based studies.

/pdf/complement-factor-h-polymorphism-in-age-related-macular-1je6ex4sfb.pdf

Complement Factor H Polymorphism in Age-Related Macular Degeneration

Of the 423 patients enrolled, 94.3% of those given 0.3 mg of ranibizumab and 96.4% of those given 0.5 mg lost fewer than 15 letters, as compared with 64.3% of those in the verteporfin group (P<0.001 for each comparison). Visual acuity improved by 15 letters or more in 35.7% of the 0.3-mg group and 40.3% of the 0.5-mg group, as compared with 5.6% of the verteporfin group (P<0.001 for each comparison). Mean visual acuity increased by 8.5 letters in the 0.3-mg group and 11.3 letters in the 0.5-mg group, as compared with a decrease of 9.5 letters in the verteporfin group (P<0.001 for each comparison). Among 140 patients treated with 0.5 mg of ranibizumab, presumed endophthalmitis occurred in 2 patients (1.4%) and serious uveitis in 1 (0.7%). Conclusions Ranibizumab was superior to verteporfin as intravitreal treatment of predominantly classic neovascular age-related macular degeneration, with low rates of serious ocular adverse events. Treatment improved visual acuity on average at 1 year. (ClinicalTrials. gov number, NCT00061594.)

/pdf/ranibizumab-versus-verteporfin-for-neovascular-age-related-zw3ei204oa.pdf

Ranibizumab versus Verteporfin for Neovascular Age-Related Macular Degeneration

https://www.thelancet.com/pdfs/journals/langlo/PIIS2214-109X(13)70145-1.pdf

Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis.

The cloning of genes encoding mammalian DNA binding transcription factors for RNA polymerase II has provided the opportunity to analyze the structure and function of these proteins. This review summarizes recent studies that define structural domains for DNA binding and transcriptional activation functions in sequence-specific transcription factors. The mechanisms by which these factors may activate transcriptional initiation and by which they may be regulated to achieve differential gene expression are also discussed.

https://science.sciencemag.org/content/sci/245/4916/371.full.pdf

Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins

had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Financial Disclosure: None. Funding/Support: This study was supported in part by an unrestricted grant from Research to Prevent Blindness, New York, NY, and grant NEI EY02698 to Paul Kaufman, MD, from the National Institutes of Health, Bethesda, Md. Acknowledgment: We thank Jon Peterson, CRA, for the rabbit photography.

https://jamanetwork.com/journals/jamaophthalmology/articlepdf/417655/ecr0506-3-1.pdf

Verteporfin photodynamic therapy of choroidal neovascularization secondary to ocular toxoplasmosis.

Preventing the Growth of Geographic Atrophy: An Important Therapeutic Target in Age-Related Macular Degeneration.

Pharmacotherapy of age-related macular degeneration

Background and objective To demonstrate the utility of widefield swept-source optical coherence tomography angiography (SS-OCTA) for the diagnosis and management of proliferative diabetic retinopathy (PDR). Patients and methods Consecutive patients with vision-threatening diabetic retinopathy were imaged with widefield SS-OCTA using the 12 mm × 12 mm scan pattern. Results Twenty-four eyes of 12 patients underwent SS-OCTA imaging. In all 24 eyes, the en face total retinal flow images detected areas of decreased retinal perfusion, and the en face vitreoretinal interface (VRI) slabs detected foci of retinal neovascularization (NV). NV was treated and followed using the VRI images. Conclusions Widefield SS-OCTA is a useful, noninvasive technology for the detection and monitoring of NV in PDR. Features of interest, such as areas of decreased retinal perfusion, increased retinal thickness, and NV, can be identified from different en face slabs extracted from a single 12 mm × 12 mm scan. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:474-484.].

Widefield Swept-Source Optical Coherence Tomography Angiography of Proliferative Diabetic Retinopathy

We present a geometric deformable model driven by dynamically updated probability fields. The shape is defined with the signed distance function, and the internal (smoothness) energy consists of a C1continuity constraint, a shape prior, and a term that forces the zero-level of the shape distance function towards a connected form. The image probability fields are estimated by our collaborative Conditional Random Field (CoCRF), which is updated during the evolution in an active learning manner: it infers class posteriors in pixels or regions with feature ambiguities by assessing the joint appearance of neighboring sites and using the classification confidence. We apply our method to Optical Coherence Tomography fundus images for the segmentation of geographic atrophies in dry age-related macular degeneration of the human eye.

Philip J. Rosenfeld

Papers

Verteporfin photodynamic therapy of choroidal neovascularization secondary to ocular toxoplasmosis.

Preventing the Growth of Geographic Atrophy: An Important Therapeutic Target in Age-Related Macular Degeneration.

Pharmacotherapy of age-related macular degeneration

Widefield Swept-Source Optical Coherence Tomography Angiography of Proliferative Diabetic Retinopathy

Geometric Deformable Model Driven by CoCRFs: Application to Optical Coherence Tomography