Vascular Response to Sildenafil Citrate in Aging and Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) - the leading cause of vision loss in the elderly - share many risks factors as atherosclerosis, which exhibits loss of vascular compliance resulting from aging and oxidative stress. Here, we attempt to explore choroidal and retinal vascular compliance in patients with AMD by evaluating dynamic vascular changes using live ocular imaging following treatment with oral sildenafil citrate, a phosphodiesterase type 5 (PDE5) inhibitor and potent vasodilator. Enhanced-depth imaging optical coherence tomography (EDI-OCT) and OCT angiography (OCT-A) were performed on 46 eyes of 23 subjects, including 15 patients with non-exudative AMD in one eye and exudative AMD in the fellow eye, and 8 age-matched control subjects. Choroidal thickness, choroidal vascularity, and retinal vessel density were measured across the central macula at 1 and 3 hours after a 100 mg oral dose of sildenafil citrate. Baseline choroidal thickness was 172.1 ± 60.0 μm in non-exudative AMD eyes, 196.4 ± 89.8 μm in exudative AMD eyes, and 207.4 ± 77.7 μm in control eyes, with no difference between the 3 groups (P = 0.116). After sildenafil, choroidal thickness increased by 6.0% to 9.0% at 1 and 3 hours in all groups (P = 0.001-0.014). Eyes from older subjects were associated with choroidal thinning at baseline (P = 0.005) and showed less choroidal expansion at 1 hour and 3 hours after sildenafil (P = 0.001) regardless of AMD status (P = 0.666). The choroidal thickening appeared to be primarily attributed to expansion of the stroma rather than luminal component. Retinal vascular density remained unchanged after sildenafil in all 3 groups (P = 0.281-0.587). Together, our studies suggest that vascular response of the choroid to sildenafil decreases with age, but is not affected by the presence of non-exudative or exudative AMD, providing insight into changes in vessel compliance in aging and AMD

Expression profile of inflammatory cytokines in aqueous from glaucomatous eyes

PURPOSE: To determine the proinflammatory cytokine profile of aqueous humor from glaucomatous eyes. METHODS: Aqueous humor samples were prospectively collected from 38 eyes (26 primary open angle glaucoma [POAG] and 12 primary angle closure glaucoma [PACG] eyes) of 37 medically treated glaucoma patients and 23 cataract subjects recruited in an institutional setting in this case-controlled study. The main outcome measure was to quantify the levels of 29 inflammatory cytokines in the aqueous of glaucoma and cataract subjects using a multiplexed cytokine analysis. Data on patient demographics, duration of glaucoma, preoperative intraocular pressure (IOP) as well as duration of anti-glaucoma therapy were also collected for correlation analysis. RESULTS: Mean duration of glaucoma was 53.8 months (range 1-360 months). Aqueous obtained from the glaucoma patients showed increased concentration of interleukin (IL)-9 (p=0.032), IL-12 (p=0.003), interferon (IFN)-α (p=0.034), IFN-γ (p=0.002), monokine induced by interferon-gamma (MIG or CXCL9) (p=0.006), and IL-10 (p=0.050), compared to the cataract group. The POAG group had higher IL-12 (p=0.011), IFN-γ (p=0.005), and CXCL9 (p=0.047) levels than controls, while the PACG group had higher interleukin-8 (CXCL8) (p=0.015) and CXCL9 (p=0.023) levels than the controls. No significant correlation was observed between aqueous cytokine level and preoperative IOP and duration of glaucoma. Duration of topical Timolol and Alphagan therapy correlated negatively with CXCL8 (r=-0.588, p=0.035), respectively. CONCLUSIONS: Primary glaucoma is associated with an aqueous inflammatory response and this is different between POAG and PACG groups. Duration of glaucoma treatment may have an effect on cytokine profile in the aqueous.Published versio

Plasma lipoprotein subfraction concentrations are associated with lipid metabolism and age-related macular degeneration

10.1194/jlr.M073684Journal of Lipid Research5891785-179

Lens status influences the association between CFH polymorphisms and age-related macular degeneration: Findings from two population-based studies in Singapore

10.1371/journal.pone.0119570PLoS ONE103e011957

Erratum in: Three-Year Outcomes of Neovascular Age-Related Macular Degeneration in Eyes That Do Not Develop Macular Atrophy or Subretinal Fibrosis

Purpose: To report the 36-month treatment outcomes of eyes with neovascular age-related macular degeneration (nAMD) receiving vascular endothelial growth factor (VEGF) inhibitors in daily practice who did not develop either subretinal fibrosis (SRFi) or macular atrophy (MA). Methods: This is a retrospective analysis of data from the Fight Retinal Blindness registry. Treatment-naïve eyes starting intravitreal injection of VEGF inhibitors for nAMD from January 1, 2010, to September 1, 2017, and did not have SRFI and MA at baseline were tracked. Results: We identified 2478 eligible eyes, of which 1712 eyes did not develop SRFi or MA, 291 developed extrafoveal SRFI or MA, and 475 developed subfoveal SRFi or MA over 36 months. The estimated visual acuity stabilized from 6 months to 36 months in eyes that did not develop SRFI or MA with a mean (95% confidence interval [CI]) change in VA of -1 (-2, 0) letters, whereas eyes that developed extrafoveal (-3 [-5, -2] letters) or subfoveal (-10 [-11, -8] letters) SRFi or MA declined in vision in the same period. Eyes with no or extrafoveal SRFi or MA over 36 months were more likely to maintain their visual improvement from six months to 36 months (odds ratio [OR; 95% CI] = 2.3 [1.5, 3.3] for absence vs. subfoveal SRFi or MA, P ≤ 0.01 and OR = 2.0 [1.2, 3.4] for extrafoveal vs. subfoveal MA or SRFi, P = 0.01). Conclusions: Treatment-naïve nAMD eyes receiving VEGF inhibitors maintain their initial six-month visual improvement over three years if they do not develop SRFI or MA. Translational relevance: The nAMD is still a major cause of blindness despite antiangiogenic treatments. We found that eyes that did not develop subretinal fibrosis or macular atrophy maintained their initial vision improvement for at least three years, suggesting that identifying treatments for these complications is the final barrier to achieving excellent outcomes in nAMD

Three-Year Outcomes of Neovascular Age-Related Macular Degeneration in Eyes That Do Not Develop Macular Atrophy or Subretinal Fibrosis

Purpose: To report the 36-month treatment outcomes of eyes with neovascular age-related macular degeneration (nAMD) receiving vascular endothelial growth factor (VEGF) inhibitors in daily practice who did not develop either subretinal fibrosis (SRFi) or macular atrophy (MA). Methods: This is a retrospective analysis of data from the Fight Retinal Blindness registry. Treatment-naïve eyes starting intravitreal injection of VEGF inhibitors for nAMD from January 1, 2010, to September 1, 2017, and did not have SRFI and MA at baseline were tracked. Results: We identified 2478 eligible eyes, of which 1712 eyes did not develop SRFi or MA, 291 developed extrafoveal SRFI or MA, and 475 developed subfoveal SRFi or MA over 36 months. The estimated visual acuity stabilized from 6 months to 36 months in eyes that did not develop SRFI or MA with a mean (95% confidence interval [CI]) change in VA of -1 (-2, 0) letters, whereas eyes that developed extrafoveal (-3 [-5, -2] letters) or subfoveal (-10 [-11, -8] letters) SRFi or MA declined in vision in the same period. Eyes with no or extrafoveal SRFi or MA over 36 months were more likely to maintain their visual improvement from six months to 36 months (odds ratio [OR; 95% CI] = 2.3 [1.5, 3.3] for absence vs. subfoveal SRFi or MA, P ≤ 0.01 and OR = 2.0 [1.2, 3.4] for extrafoveal vs. subfoveal MA or SRFi, P = 0.01). Conclusions: Treatment-naïve nAMD eyes receiving VEGF inhibitors maintain their initial six-month visual improvement over three years if they do not develop SRFI or MA. Translational relevance: The nAMD is still a major cause of blindness despite antiangiogenic treatments. We found that eyes that did not develop subretinal fibrosis or macular atrophy maintained their initial vision improvement for at least three years, suggesting that identifying treatments for these complications is the final barrier to achieving excellent outcomes in nAMD

Clinical and Epidemiologic Research Ethnic Variation in Early Age-Related Macular Degeneration Lesions Between White Australians and Singaporean Asians

Citation: Joachim N, Mitchell P, Younan C, et al. Ethnic variation in early age-related macular degeneration lesions between white Australians and Singaporean Asians. Invest Ophthalmol Vis Sci. 2014;55:4421-4429. DOI:10.1167/iovs.14-14476 PURPOSE. We compared early age-related macular degeneration (AMD) lesion characteristics between white Australians and Singaporean Asians. METHODS. Participants of the Blue Mountains Eye Study (BMES; whites, n ¼ 3508) and the Singapore Epidemiology of Eye Disease Study (SEED; Malay, n ¼ 3280, Indian, n ¼ 3400, and Chinese, n ¼ 3353) underwent examinations, including retinal photography. The AMD lesions were assessed following the Wisconsin AMD grading protocol by the same photographic grader. Prevalence and characteristics of early AMD lesions were compared between the BMES and the SEED. The associations between ethnicity and early AMD lesion types were analyzed using logistic regression models adjusting for age, sex, smoking status, lipids, and genetic polymorphisms associated with AMD. RESULTS. After age-standardization to the BMES population, the prevalence of distinct soft drusen was significantly higher in Singaporeans compared to Australians (23.9%, 95% confidence interval [CI] 22.9-25.0 vs. 6.2%, 95% CI 5.3-7.0), with an adjusted odds ratio (OR) of 4.6 (95% CI 3.4-6.0). In contrast, the prevalence of indistinct soft or reticular drusen was significantly lower in Singaporeans compared to Australians (6.5%, 95% CI 5.9-7.1 vs. 8.3%, 95% CI 7.4-9.3, with nonsignificant adjusted OR of 1.2, 95% CI 0.8-1.7). Soft drusen of any type were present frequently at the inner and outer macula (within a zone ‡500 to <3000 lm radius from the foveal center) among Singaporeans, while among Australians soft drusen were present more frequently at the central macula (<500 lm radius). CONCLUSIONS. Singaporean Asians had a milder spectrum of early AMD lesions and lesion characteristics (predominantly distinct soft drusen and noncentral location) compared to white Australians

Conversion to aflibercept for diabetic macular edema unresponsive to ranibizumab or bevacizumab

Background: The purpose of this study was to determine if eyes with diabetic macular edema (DME) unresponsive to ranibizumab or bevacizumab would benefit from conversion to aflibercept. Methods: This study was conducted as a retrospective chart review of subjects with DME unresponsive to ranibizumab and/or bevacizumab and subsequently converted to aflibercept. Results: In total, 21 eyes from 19 subjects of mean age 62±15 years were included. The majority of subjects were male (63%). The median number of ranibizumab or bevacizumab injections before switching to aflibercept was six, and the median number of aflibercept injections after switching was three. Median follow-up was 5 months after the switch. Mean central foveal thickness (CFT) was 453.52±143.39 mm immediately prior to the switch. Morphologically, intraretinal cysts were present in all cases. Mean CFT after the first injection decreased significantly to 362.57±92.82 mm (Wilcoxon signed-rank test; P<0.001). At the end of follow-up, the mean CFT was 324.17±98.76 mm (P<0.001). Mean visual acuity was 0.42±0.23 logMAR just prior to the switch, 0.39±0.31 logMAR after one aflibercept injection, and 0.37±0.22 log-MAR at the end of follow-up. The final visual acuity was significantly better than visual acuity before the switch (P=0.04). Conclusion: Eyes with DME unresponsive to multiple ranibizumab/bevacizumab injections demonstrate anatomical and visual improvement on conversion to aflibercept

Human pharyngeal microbiota in age-related macular degeneration.

BACKGROUND: While the aetiology of age-related macular degeneration (AMD)-a major blinding disease-remains unknown, the disease is strongly associated with variants in the complement factor H (CFH) gene. CFH variants also confer susceptibility to invasive infection with several bacterial colonizers of the nasopharyngeal mucosa. This shared susceptibility locus implicates complement deregulation as a common disease mechanism, and suggests the possibility that microbial interactions with host complement may trigger AMD. In this study, we address this possibility by testing the hypothesis that AMD is associated with specific microbial colonization of the human nasopharynx. RESULTS: High-throughput Illumina sequencing of the V3-V6 region of the microbial 16S ribosomal RNA gene was used to comprehensively and accurately describe the human pharyngeal microbiome, at genus level, in 245 AMD patients and 386 controls. Based on mean and differential microbial abundance analyses, we determined an overview of the pharyngeal microbiota, as well as candidate genera (Prevotella and Gemella) suggesting an association towards AMD health and disease conditions. CONCLUSIONS: Utilizing an extensive study population from Singapore, our results provided an accurate description of the pharyngeal microbiota profiles in AMD health and disease conditions. Through identification of candidate genera that are different between conditions, we provide preliminary evidence for the existence of microbial triggers for AMD. Ethical approval for this study was obtained through the Singapore Health Clinical Institutional Review Board, reference numbers R799/63/2010 and 2010/585/A