Sequence and expression of complement factor H gene cluster variants and their roles in age-related macular degeneration risk

Purpose: To investigate how potentially functional genetic variants are coinherited on each of four common complement factor H (CFH) and CFH-related gene haplotypes and to measure expression of these genes in eye and liver tissues.

Methods: We sequenced the CFH region in four individuals (one homozygote for each of four common CFH region haplotypes) to identify all genetic variants. We studied associations between the haplotypes and AMD phenotypes in 2157 cases and 1150 controls. We examined RNA-seq profiles in macular and peripheral retina and retinal pigment epithelium/choroid/sclera (RCS) from eight eye donors and three liver samples.

Results: The haplotypic coinheritance of potentially functional variants (including missense variants, novel splice sites, and the CFHR3–CFHR1 deletion) was described for the four common haplotypes. Expression of the short and long CFH transcripts differed markedly between the retina and liver. We found no expression of any of the five CFH-related genes in the retina or RCS, in contrast to the liver, which is the main source of the circulating proteins.

Conclusions: We identified all genetic variants on common CFH region haplotypes and described their coinheritance. Understanding their functional effects will be key to developing and stratifying AMD therapies. The small scale of our expression study prevented us from investigating the relationships between CFH region haplotypes and their expression, and it will take time and collaboration to develop epidemiologic-scale studies. However, the striking difference between systemic and ocular expression of complement regulators shown in this study suggests important implications for the development of intraocular and systemic treatments.

The design and implementation of a study to investigate the effectiveness of community vs hospital eye service follow-up for patients with neovascular age-related macular degeneration with quiescent disease

Introduction
Standard treatment for neovascular age-related macular degeneration (nAMD) is intravitreal injections of anti-VEGF drugs. Following multiple injections, nAMD lesions often become quiescent but there is a high risk of reactivation, and regular review by hospital ophthalmologists is the norm. The present trial examines the feasibility of community optometrists making lesion reactivation decisions.

Methods
The Effectiveness of Community vs Hospital Eye Service (ECHoES) trial is a virtual trial; lesion reactivation decisions were made about vignettes that comprised clinical data, colour fundus photographs, and optical coherence tomograms displayed on a web-based platform. Participants were either hospital ophthalmologists or community optometrists. All participants were provided with webinar training on the disease, its management, and assessment of the retinal imaging outputs. In a balanced design, 96 participants each assessed 42 vignettes; a total of 288 vignettes were assessed seven times by each professional group.The primary outcome is a participant's judgement of lesion reactivation compared with a reference standard. Secondary outcomes are the frequency of sight threatening errors; judgements about specific lesion components; participant-rated confidence in their decisions about the primary outcome; cost effectiveness of follow-up by optometrists rather than ophthalmologists.

Discussion
This trial addresses an important question for the NHS, namely whether, with appropriate training, community optometrists can make retreatment decisions for patients with nAMD to the same standard as hospital ophthalmologists. The trial employed a novel approach as participation was entirely through a web-based application; the trial required very few resources compared with those that would have been needed for a conventional randomised controlled clinical trial.

Retinal pigment epithelium tears after intravitreal injection of ranibizumab for predominantly classic neovascular membranes secondary to age-related macular degeneration.

PURPOSE: Retinal pigment epithelium (RPE) tear is an extremely rare complication in patients with classic neovascular membranes without RPE detachment. We evaluate their incidence and functional outcome following treatment with intravitreal ranibizumab. METHODS: Observational study of 72 consecutive patients (74 eyes) treated at Jules Gonin University Eye Hospital, Lausanne, with intravitreal ranibizumab 0.5 mg for classic choroidal neovascularization (CNV) between March 2006 and February 2008. Best-corrected visual acuity (BCVA), fundus examination and optical coherence tomography were recorded monthly; fluorescein angiography was performed at baseline and repeated at least every 3 months. RESULTS: RPE tears occurred in four (5.4%) eyes temporal to the fovea, after a mean of four injections (range 3-6). Mean baseline BCVA was 0.25 decimal equivalent (logMAR 0.67) and improved despite the RPE tear to 0.6 decimal equivalent (logMAR 0.22). CONCLUSION: RPE tears following intravitreal ranibizumab injections for classic CNV can occur in about 5% of patients, even in the absence of baseline RPE detachment. Nevertheless, vision may improve provided the fovea is not involved.

Recurrent uveitis, cystoid macular edema and pericarditis in Lyme disease.

Lyme disease has been associated with many systemic and ocular complications. The authors' patient, a 26-year-old man, developed recurrent pars planitis with two episodes of acute pericarditis. Extensive medical investigations were negative except for a highly positive western blot for Borrelia burgdorferi. Specific antibiotic treatment for Lyme disease was followed by a long lasting period without any relapse.

Evaluación terapéutica del bevacizumab, intravítreo, en el tratamiento del edema macular diabético difuso.

Tesis (Doctor en Medicina) UANL, 2011.

Comparación de grosor macular y grado de miopía en grupo de pacientes de la Fundación Oftalmológica Nacional

OBJETIVOS: Comparar las medidas de grosor macular, medido por HD-OCT Cirrus®, en pacientes de la Fundación Oftalmológica Nacional con miopía baja y alta. MÉTODOS: Estudio transversal analítico, en el que se incluyeron pacientes con miopía alta, definida como defecto esférico mayor a – 6.0 dioptrías (D), y pacientes con miopía baja, definida como defecto esférico entre -1.00 D y -6.00 D; a los que se le realizó mapa de grosores maculares con el HD-OCT Cirrus®, y se compararon las medias de los grosores (1, 3 y 6 mm). RESULTADOS: Un total de 128 ojos de pacientes entre 12 y 80 años fueron incluidos; 64 ojos en grupo de miopes bajos y 64 ojos en grupo de miopes altos. La media de edad fue: 37.3 y 38.4 años, y el defecto esférico promedio fue de 2.2 D y 11.5 D, respectivamente. El promedio de grosores en mácula interna (319.9 vs. 307.87 micras, P=0.002), y mácula externa (276.08 vs. 270.23 micras, P=0.047) fue significativamente mayor en el grupo de miopía baja que en el de miopía alta. Sin embargo la media del grosor macular central (1 mm) no tuvo diferencia (261.25 vs. 262 micras P=0.891). CONCLUSIÓN: Este estudio muestra que el grosor macular de 3 y 6 mm centrales es más delgado en miopes altos, pero en 1 mm central es similar que en miopes bajos. En los pacientes estudiados no se encontró diferencia en grosores maculares según género o subgrupos de edad.

Grosor macular luego de tratamiento con Ranibizumab o Bevacizumab en degeneración macular relacionada con la edad

Introducción: El manejo actual de la degeneración macular relacionada con la edad (DMRE) neovascular está basado en la terapia antiangiogénica con inhibidores del factor de crecimiento vascular endotelial (VEGF) entre los cuales se encuentra el Ranibizumab y el Bevacizumab. El seguimiento se hace mediante medidas funcionales (agudeza visual) y anatómicas (grosor macular por tomografía óptica coherente). Objetivo: comparar el comportamiento del grosor macular luego del tratamiento con cada medicamento Metodología: es un estudio descriptivo multicéntrico, para comparar los cambios de grosor macular por OCT y la agudeza visual a los 3, 6, 9, 12, 18 y 24 meses luego del tratamiento con Bevacizumab y Ranibizumab. Resultados: Se incluyeron 127 ojos (93 tratados con Bevacizumab y 34 tratados Ranibizumab). El grosor macular central inicial fue de 241 micras en el primer grupo y 242.5 en el segundo. Éste disminuyó con respecto al inicial 24.5 y 18 micras a los 3 meses, 15 y 11.5 a los 6 meses respectivamente. Al año aumentó 3 y 5 micras y a los 2 años disminuyó 13 y aumentó 21 micras respectivamente. No hubo diferencias estadísticamente significativas en los grosores entre los grupos. Discusión: Los grosores maculares centrales, del promedio de los 3 y 6 mm de la fóvea se mantuvieron estables durante los 2 años de seguimiento. La agudeza visual también se mantuvo estable en ambos grupos. No se encontró correlación entre la agudeza visual y el grosor macular

Asociación entre degeneración macular relacionada con la edad y la hipertensión arterial Bogotá 2014

Estudio Casos y Controles 1:1 que busca la relación entre la DMRE e HTA. Se estudian otras variables. Muestra de 400 pacientes, edad promedio 66,9 años +/-9,2 años. HTA y DM OR 2,315 y OR 4,626. Oclusión vascular OR 13,549 (IC 95% 3,023-60,724).

Association of complement factor H Y402H polymorphism and age-related macular degeneration in Brazilian patients

Purpose: The aim of this study was investigate the association between complement Factor H polymorphism (Y402H) and age-related macular degeneration (AMD) in Brazilian patients. Methods: Patients with AMD aged 50 or more and age-matched healthy controls were enrolled in the study. Genomic DNA was isolated from leucocytes of patients and controls; the Y402H polymorphism of complement Factor H gene (CFH) was determined by polymerase chain reaction directed sequencing. Results: The frequency of 1277C allele of Factor H was 56.30% in patients with AMD compared with 36.51% in controls (p-value = 0.001). The genotypic distribution differed significantly between the two groups (1277CC 36.98%, 1277CT 38.65% and 1277TT 24.37% for AMD group; 1277CC 13.16%, 1277CT 46.71% and 1277TT 40.13% for controls, p-value = 0.001). The odds ratio for patients with AMD carrying only one 1277C allele was 1.36 and for those carrying two 1277C alleles was 4.63, when compared to the control group. Conclusions: These results suggest the Y402H polymorphism of CFH is a risk factor to the development of AMD in Brazilian patients. This is in accordance with findings from the majority of previous study population in Europe and North American.