Neovascular Age-related Macular Degeneration in the Very Old (=90 Years): Epidemiology, Adherence to Treatment, and Comparison of Efficacy

Purpose. To investigate neovascular age-related macular degeneration (AMD) in patients aged ≥90 years from several perspectives for a comprehensive overview: prevalence, presenting characteristics, treatment adherence, reasons for discontinuation, and efficacy of antivascular endothelial growth factor (VEGF) treatment comparing Ranibizumab and Aflibercept. Methods. In this retrospective chart review, we determined the prevalence and presenting characteristics by reviewing all data for patients referred to our department with treatment-naïve neovascular AMD. By looking at historical cohorts, we determined adherence to treatment, reasons for discontinuation, and treatment outcomes after loading dose, 12 months, and 24 months. Results. Patients aged ≥90 years constituted 7% of the patients. Treatment was discontinued in 51%, primarily because of death and treatment burden. Mean change in best-corrected visual acuity was 3.2, 1.5, and −2.2 ETDRS letters at 4, 12, and 24 months, respectively. Aflibercept was superior to Ranibizumab in visual and anatomic outcomes. After two years of treatment, patients losing ≥15 ETDRS letters made up 19% in the Aflibercept group and 26% in the Ranibizumab group. Conclusions. We propose that the very old patients with neovascular AMD may constitute a distinctive group warranting special attention and possibilities for individualized therapy. Possible differences between anti-VEGF agents need further investigations

Valsalva-Related Subretinal Hemorrhage as a Presenting Symptom of Polypoidal Choroidal Vasculopathy

Purpose. To describe a case of Valsalva-related subretinal hemorrhage as a presenting symptom of polypoidal choroidal vasculopathy (PCV). The patient refrained from treatment against our best advice, and thus this is also a rare case of the natural course of an untreated PCV. Methods. Case report. Results. A 66-year-old female with a respiratory infection coughed intensely until exhaustion, after which she developed visual symptoms on the right eye. Primary care ophthalmologist examined the patient on the same day of the onset of symptoms and referred her to our tertiary medical retinal service for detailed retinal diagnosis including fluorescein and indocyanine green angiography. The right eye had a large subretinal hemorrhage and pigment epithelium detachment in the lower temporal arcade with foveal involvement. Against our best advice, the patient refused treatment. In the following 9 months, the BCVA decreased from 68 to 55 ETDRS letters, the subretinal hemorrhage almost regressed, pigment epithelium detachments persisted, and macular edema, intraretinal cysts, and subretinal fibrosis developed. Conclusions. Although classic Valsalva retinopathy with preretinal hemorrhage in most cases can be managed by careful observation and no treatment, this case demonstrates that Valsalva-related subretinal hemorrhage needs different attention and approach

Effect of aging and lifestyle on photoreceptors and retinal pigment epithelium:cross-sectional study in a healthy Danish population

Photoreceptors and their supporting retinal pigment epithelium constitute the key functional parts of the retina. Here, a study was undertaken to show how aging and lifestyle factors affect the photoreceptor layer and the retinal pigment epithelium and Bruch’s membrane complex (RPE-BM) in vivo in a healthy Danish population using spectral-domain optical coherence tomography. This was a cross-sectional study of healthy humans aged ≥50 years. All participants were interviewed for medical history and lifestyle factors. Maculae of all participants were scanned using spectral-domain optical coherence tomography. The thickness of the photoreceptor layer and the RPE-BM was measured on one eye from each participant. In 150 eyes of 150 participants, it was found that aging was associated with a decrease in the thickness of the photoreceptor layer (−0.143 μm/year, P = 0.031) and an increase in the thickness of the RPE-BM layer (0.100 μm/year, P = 0.029) at the foveal minimum. Regarding lifestyle factors, alcohol intake or BMI were not associated with any significant trend, but physical inactivity and smoking had effects on the photoreceptor layer (decreased thickness) and the RPE-BM layer (increased thickness) indicating an accelerated aging process of the macula. Taken together, aging affects photoreceptors and the RPE-BM, and these aging trends are accelerated in smokers and the physically inactive

T-cell differentiation and CD56+ levels in polypoidal choroidal vasculopathy and neovascular age-related macular degeneration

Polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (AMD) are prevalent age-related diseases characterized by exudative changes in the macula. Although they share anatomical and clinical similarities, they are also distinctly characterized by their own features, e.g. vascular abnormalities in PCV and drusen-mediated progression in neovascular AMD. PCV remains etiologically uncharacterized, and ongoing discussion is whether PCV and neovascular AMD share the same etiology or constitute two substantially different diseases. In this study, we investigated T-cell differentiation and aging profile in human patients with PCV, patients with neovascular AMD, and age-matched healthy control individuals. Fresh venous blood was prepared for flow cytometry to investigate CD4+ and CD8+ T-cell differentiation (naïve, central memory, effector memory, effector memory CD45ra+), loss of differentiation markers CD27 and CD28, and expression of aging marker CD56. Patients with PCV were similar to the healthy controls in all aspects. In patients with neovascular AMD we found significantly accelerated T-cell differentiation (more CD28-CD27- cells) and aging (more CD56+ cells) in the CD8+ T-cell compartment. These findings suggest that PCV and neovascular AMD are etiologically different in terms of T cell immunity, and that neovascular AMD is associated with T-cell immunosenescence

Systemic frequencies of T helper 1 and T helper 17 cells in patients with age-related macular degeneration: A case-control study

Age-related macular degeneration (AMD) is a degenerative disease of the retina and a leading cause of irreversible vision loss. We investigated the systemic differences in the frequency of T helper (Th) 1 and Th17 cells in patients with non-exudative and exudative AMD and compared to age-matched controls. Flow cytometry was used to determine the systemic frequency of Th1 (CD4+CXCR3+IL12RB2+) and Th17 (CD4+CCR6+IL23R+) cells, and percentage of CD4+ T-cells expressing CXCR3, IL12RB2, CCR6, IL23R, and co-expressing CXCR3 and CCR6. The frequency of Th1 cells and CXCR3+ CD4+ T-cells was lower in patients with exudative AMD. A significant age-dependent decrement in Th1 was observed in controls, but not in non-exudative or exudative AMD. This may be related to the CXCR3+ CD4+ T-cells, which showed similar pattern in controls, but not in non-exudative or exudative AMD. No significant group differences were observed for the frequency of Th17 cells. Correlation networks found several differences between controls and AMD. These data suggests the involvement of the adaptive immune system in AMD and supports the notion of AMD as a systemic disease. Our observations warrant further investigation into the role of the adaptive immune system in the pathogenesis of AMD