ABSTRACT
Introduction: Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries and one of the leading causes of blindness. In this work, we evaluated color vision and the pupil light reflex (PLR) to assess visual function in patients with early and neovascular AMD (NVAMD) compared with the control group. Methods: We recruited 34 early patients with dry AMD and classified them into two groups following AREDS: 13 patients with NVAMD and 24 healthy controls. Controls and patients with early dry AMD had visual acuity (VA) best or equal to 20/25 (0.098 logMAR). Color vision was assessed in controls and patients with early dry AMD using the Cambridge Color Test (CCT) 2.0 through the Trivector protocol. The PLR was evaluated using a Ganzfeld, controlled by the RETI-port system. The stimuli consisted of 1s blue (470 nm) and red (631 nm) light flashes presented alternately at 2-min intervals. To assess the cone contribution, we used a red flash at 2.4 log cd.m-2, with a blue background at 0.78 log cd.m-2. For rods, we used 470-nm flashes at -3 log cd.m-2, and for the melanopsin function of ipRGCs, we used 470 nm at 2.4 log cd.m-2. Results: Patients with early dry AMD had reduced color discrimination in all three axes: protan (p = 0.0087), deutan (p = 0.0180), and tritan (p = 0.0095) when compared with the control group. The PLR has also been affected in patients with early dry AMD and patients with NVAMD. The amplitude for the melanopsin-driven response was smaller in patients with early dry AMD (p = 0.0485) and NVAMD (p = 0.0035) than in the control group. The melanopsin function was lower in patients with NVAMD (p = 0.0290) than the control group. For the rod-driven response, the latency was lower in the NVAMD group (p = 0.0041) than in the control group. No changes were found in cone-driven responses between the control and AMD groups. Conclusion: Patients with early dry AMD present diffusely acquired color vision alteration detected by CCT. Rods and melanopsin contributions for PLR are affected in NVAMD. The CCT and the PLR may be considered sensitive tests to evaluate and monitor functional changes in patients with AMD.
ABSTRACT
Background: Age-related macular degeneration (AMD) is a multifactorial disease and one of the main causes of blindness in people over 50 years old. The etiology and pathophysiology of AMD are not well understood. The aim of this study was to investigate whether the rs1143627 variant allele of IL1B, which encodes Interleukin (IL)-1ß, a key cytokine, mediates immune and inflammatory responses.Methods: A case-control study was conducted with 397 AMD patients and 402 controls in Brazil. IL1B genotyping was carried out with TaqMan® genotyping assay. Differences in IL1B allele frequencies and genotypes were evaluated between patients and controls and between wet and dry subgroups of AMD. Relationships between allele presence/genotype and disease risk are reported as odds ratios (ORs) with 95% confidence intervals (CIs).Results: Genotype proportions for the rs1143627 variant allele of IL1B were similar between AMD patients and controls (p = .21), with 84.38% of AMD patients and 79.60% of the controls carrying the variant allele. We observed a trend toward the variant allele being associated with AMD risk (OR = 1.38, 95% CI 0.95-2.03, p = .08), as well as a trend toward the variant allele being associated with increased risk for wet AMD in particular (OR = 1.23, 95% CI 0.96-1.56, p = .08).Conclusions: The rs1443627 variant was not associated with AMD risk in this Brazilian population sample. Larger studies are warranted to determine whether the trends observed in this study reflect a relationship between this variant and risk of AMD, especially wet AMD.
Subject(s)
Interleukin-1beta/genetics , Macular Degeneration/genetics , Polymorphism, Single Nucleotide/genetics , Aged , Aged, 80 and over , Brazil/epidemiology , Case-Control Studies , Female , Gene Frequency , Genotyping Techniques , Humans , Macular Degeneration/epidemiology , Male , Middle Aged , Odds Ratio , Ophthalmoscopy , Risk Factors , Slit Lamp Microscopy , Tomography, Optical Coherence , Visual Acuity/physiologyABSTRACT
Objetivos: presentar una revisión acerca de la terapia génica y los fármacos en estudios preclínicos como nuevos y posibles blancos de tratamiento farmacológicos para la degeneración macular relacionada a la edad neovascular y el estado de los estudios clínicos de los mismos. Diseño del estudio: revisión de tema. Métodos: se realizó una búsqueda de la literatura electrónica disponible en EMBASE, PUBMED y Google Scholar acerca del tema y se complementa con la información encontrada en www.clinicaltrials.gov y la plataforma de registros internacionales de ensayos clínicos de la OMS. Conclusiones: la terapia génica vinculada a la degeneración macular asociada a la edad neovascular muestra un avance científico importante en el campo de la farmacología ocular pudiendo proporcionar eficacia tras una sola inyección de un vector que puede expresar continuamente una proteína elegida. Existen estudios pre-clínicos que sugieren nuevos y diversos blancos farmacológicos para la degeneración macular relacionada a la edad mostrando un perfil de seguridad y eficacia significativo.
Objectives: to review gene therapy and drugs in preclinical studies as potential new targets for pharmacological treatment for agerelated macular degeneration neovascular and the state of development clinical trials. Study design: literature review. Methods: a search of electronic literature available in EMBASE, PubMed and Google Scholar on the subject was performed and complemented with information found on www.clinicaltrials.gov and WHO platform of international clinical trials registers. Conclusions: the gene therapy linked to age-related macular degeneration shows a scientific important advance in the field of the ocular pharmacology being able to provide efficiency after a single injection of a vector that can express a chosen protein. There are preclinical studies that suggest new and different pharmacological targets for age-related macular degeneration showing a significant safety and efficacy profile.
Subject(s)
Macular Degeneration/therapy , Corneal Neovascularization/therapy , Eye Diseases/therapy , Macular Degeneration/drug therapyABSTRACT
Objetivos: Presentar una revisión de los nuevos y posibles objetivos de tratamiento farmacológicos para la degeneración macular relacionada a la edad neovascul r y el estado de los fármacos en estudios clínicos. Diseño del estudio: Revisión de tema. Métodos: Se realizó una búsqueda de la literatura electrónica disponible en EMBASE, PUBMED y Google Scholar acerca del tema, y se complementa con la información encontrada en www.clinicaltrials.gov y la plataforma de registros internacionales de ensayos clínicos de la O.M.S. Se procedió a sistematizar la información y se presenta en forma estructurada. Conclusiones: Las nuevas opciones terapéuticas para la degeneración macular relacionada la edad neovascular proporcionan múltiples objetivos farmacológicos, los cuales se alcanzan realizando modificaciones a moléculas ya elaboradas o con nuevos fármacos los cuales pueden actuar tanto como terapia adjunta a los actuales medicamentos antiangiogénicos (anti VEGF) mejorando su eficacia o con nuevas opciones sustitutivas. Meritorio destacar la vía de la tirosina-quinasa, la cual había sido abordada con los existentes anti VEGF, ahora se presentan nuevas opciones terapéuticas que actúan corriente abajo. Diversos fármacos se encuentran en estudios de efi cacia parcial, merecen especial mención Fovista® y conbercept de los cuales ya se encuentran en desarrollo estudios fase III.
Objectives: To present a review of new and potential targets for pharmacological treatment for neovascular age-related macular degeneration and the state of drugs in development of clinical studies. Study design: Literature review. Methods: A search of electronic literature available in EMBASE, PubMed and Google Scholar on the subject is made and compliments the information found on www.clinicaltrials. gov and platform of international clinical trials registers of the W.H.O. Conclusions: N ew therapeutic options for neovascular age-related macular degeneration provide multiple targets, which are achieved by performing modifi cations to a molecule already developed or new drugs which can act both as an adjunct to current anti VEGF improving efficiency or new alternative options. Meritorious note the tyrosine kinase way, on which previously it has acted with existing anti VEGF, now presents new therapeutic options that act downstream. Several drugs are in partial effi cacy studies, deserve special mention Fovista and conbercept of which already studies are in development phase III.
Subject(s)
Macular Degeneration/drug therapy , Vascular Endothelial Growth Factors , Macular Degeneration/diagnosisABSTRACT
BACKGROUND: Previous reports have described a decrease in retinal temperature and clinical improvement of wet age-related macular degeneration (AMD) after vitrectomy. We hypothesized that the retinal temperature decrease after vitrectomy plays a part in the suppression of wet AMD development. To test this hypothesis, we evaluated the temperature dependence of the expression of vascular endothelial growth factor-A (VEGF-A) and in vitro angiogen-esis in retinal pigment epithelium (RPE). RESULTS: We cultured ARPE-19 cells at 37, 35, 33 and 31°C and measured the expression of VEGF-A, VEGF-A splicing variants, and pigment epithelium-derived factor (PEDF). We performed an in vitro tube formation assay. The dehydrogenase activity was also evaluated at each temperature. Expression of VEGF-A significantly decreased with decreased temperature while PEDF expression did not. VEGF165 expression and in vitro angiogenesis also were temperature dependent. The dehydrogenase activity significantly decreased as the culture temperature decreased. CONCLUSIONS: RPE cultured under hypothermia that decreased cellular metabolism also had decreased VEGF-A and sustained PEDF expression, creating an anti-angiogenic environment. This mechanism may be associated with a beneficial effect after vitrectomy in patients with wet AMD.
Subject(s)
Humans , Serpins/metabolism , Vascular Endothelial Growth Factor A/metabolism , Eye Proteins/metabolism , Retinal Pigment Epithelium/metabolism , Hypothermia , Nerve Growth Factors/metabolism , Time Factors , RNA, Messenger/metabolism , Cell Line , Neovascularization, PhysiologicABSTRACT
A degeneração macular relacionada à idade (DMRI) representa a principal causa de cegueira legal em pacientes idosos no mundo ocidental. O presente artigo revisa os principais avanços no diagnóstico e tratamento da DMRI, servindo de auxílio para a atualização da comunidade médica quanto a esta doença (AU)
Age-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly in the Western world. In this regard, to promote the medical education about this disease, we present a review of AMD diagnostic and therapeutic approaches (AU)