Visual consequences of refractive errors in the general population.

OBJECTIVE: To study the frequency and causes of visual impairment in relation to refractive error. DESIGN: Population-based cohort study. PARTICIPANTS: A total of 6597 participants from Rotterdam Study I (baseline and 4 follow-up examinations) and 2579 participants from Rotterdam Study II (baseline and 2 follow-up examinations), all 55 years or older, were included. METHODS: Participants underwent an extensive ophthalmic examination, including best-corrected visual acuity and objective refraction, fundus photography, visual field perimetry, and optical coherence tomography imaging of macula and optic disc. We calculated cumulative risks and odds ratios of visual impairment for various refractive error categories and determined causes by using all screening information as well as medical records. MAIN OUTCOME MEASURES: Unilateral and bilateral low vision (World Health Organization [WHO] criteria, VA < 0.3 and VA ≥ 0.05; United States (US) criteria, VA < 0.5 and VA ≥ 0.1) and blindness (WHO criteria, VA < 0.05; US criteria, VA < 0.1). RESULTS: Cumulative risks of visual impairment ranged from virtually 0 in all refractive error categories at 55 years of age to 9.5% (standard error, 0.01) for emmetropia and 15.3% (standard error, 0.06) for high hyperopia to 33.7% (standard error, 0.08) for high myopia at 85 years of age. The major causes of visual impairment in highly hyperopic persons were age-related macular degeneration (AMD), cataract, and combined causes (each 25%); in highly myopic persons, the major cause was myopic macular degeneration (38.9%). The major causes of visual impairment for the other refractive error categories were AMD and cataract. Compared with those with emmetropia, those with high myopia had a significantly increased lifetime risk of visual impairment; those with -6 diopters (D) or less and -10 D or more had an odds ratio (OR) risk of 3.4 (95% confidence interval [CI], 1.4-8.2) of visual impairment; those with less than -10 D had an OR of 22.0 (95% CI, 9.2-52.6). CONCLUSIONS: Of all refractive errors, high myopia has the most severe visual consequences. Irreversible macular pathologic features are the most common cause of visual impairment in this group.

Aberration in myeloid-derived pro-angiogenic cells in type-2 diabetes mellitus; implication for diabetic retinopathy?

Purpose: Diabetic retinopathy (DR) is a major microvascular complication of type 2 diabetes mellitus (T2DM). Myelomonocytic proangiogenic cells (PAC) have been implicated in DR pathogenesis, but their functional and developmental abnormalities are unclear. In this study we assessed PAC characteristics from healthy controls, T2DM patients with DR (DR) and without (NoDR) in order to determine the consequence of the diabetic condition on PAC phenotype and function, and whether these differ between DR and NoDR patients. Methods: PAC were generated by culturing PBMC on fibronectin coating and then immunophenotyped using flow cytometry. Furthermore, cells were sorted based on CD14, CD105, and CD133 expression and added to an in vitro 3-D endothelial tubule formation assay, containing GFP-expressing human retinal endothelial cells (REC), pericytes, and pro-angiogenic growth factors. Tubule formation was quantified by fluorescence microscopy and image analysis. Moreover, sorted populations were analyzed for angiogenic mediator production using a multiplex assay. Results: The expression of CD16, CD105 and CD31, but not CD133, was lower in PAC from T2DM patients with or without DR. Myeloid and non-myeloid T2DM-derived sorted populations increased REC angiogenesis in vitro as compared to control cultures. They also showed increased S100A8 secretion, decreased VEGF-A secretion, and similar levels of IL-8, HGF, and IL-3 as compared to healthy control (HC)-derived cell populations. Conclusion: T2DM PAC are phenotypically and functionally altered compared to PAC from HC. Differences between DR and NoDR PAC are limited. We propose that impaired T2DM PAC provide inadequate vascular support and promote compensatory, albeit pathological, retinal neovascularization.

Altered Functionality of Lipoprotein(a) Impacts on Angiogenesis in Diabetic Retinopathy.

Purpose: Diabetic retinopathy (DR) is a complication of type 2 diabetes mellitus (T2DM). Lipoprotein(a) (Lp(a)) contributes to the progression of DR, but how is unclear. In homeostasis of the retinal microvasculature, myeloid-derived pro-angiogenic cells (PACs) also play a pivotal role, and fail to function properly in diabetic conditions. Here, we explored the putative contribution of Lp(a) from patients with T2DM with/without DR and healthy controls on inflammation and angiogenesis of retinal endothelial cells (RECs), and on PAC differentiation. Subsequently, we compared the lipid composition of Lp(a) from patients to that from healthy controls. Methods: Lp(a)/LDL obtained from patients and healthy controls were added to TNF-alpha-activated RECs. Expression of VCAM-1/ICAM-1 was measured using flowcytometry. Angiogenesis was determined in REC-pericyte co-cultures stimulated by pro-angiogenic growth factors. PAC differentiation from peripheral blood mononuclear cells was determined by measuring expression of PAC markers. The lipoprotein lipid composition was quantified using detailed lipidomics analysis. Results: Lp(a) from patients with DR (DR-Lp(a)) failed to block TNF-alpha-induced expression of VCAM-1/ICAM-1 in REC whereas Lp(a) from healthy controls (healthy control [HC]-Lp(a)) did. DR-Lp(a) increased REC angiogenesis more than HC-Lp(a) did. Lp(a) from patients without DR showed intermediate profiles. HC-Lp(a) reduced the expression of CD16 and CD105 in PAC, but T2DM-Lp(a) did not. Phosphatidylethanolamine content was lower in T2DM-Lp(a) than in HC-Lp(a). Conclusions: DR-Lp(a) does not show the anti-inflammatory capacity seen with HC-Lp(a), but increases REC angiogenesis, and affects PAC differentiation less than HC-Lp(a). These functional differences in Lp(a) in T2DM-related retinopathy are associated with alterations in the lipid composition as compared to healthy conditions.

Intra- and Intergrader Agreement for Detection of OCT Angiographic Characteristics Associated With Type 3 Neovascularization.

Purpose: To examine the intra- and intergrader agreement on morphologic characteristics of type 3 neovascularization on optical coherence tomography angiography (OCT-A). Methods: OCT-A images of 22 eyes from 21 patients with a new-onset, treatment-naive type 3 neovascularization were included in this cross-sectional retrospective agreement study. Each image was graded three times by two independent medical retina specialists to assess intra- and intergrader agreement. The graders scored the presence or absence of the following vascular and structural features: intraretinal neovascularization (IRN), subretinal neovascularization, sub-retinal pigment epithelium (RPE) neovascularization (SRPEN), retinal choroidal anastomosis (RCA), intraretinal cysts, subretinal fluid, and pigment epithelial detachment. Agreement was analyzed for each feature using Gwet's AC1, к statistics, and percentage of agreement. Results: The best agreement (AC1) was found for intraretinal neovascularization (withingrader1: 0.94; withingrader2: 0.93 and between: 1.00) and intraretinal cysts (withingrader1, 1.00; withingrader2, 0.97 and between, 1.00). The poorest intragrader agreements were observed for SRPEN (withingrader1, 0.54 and withingrader2, 0.36) and RCA (withingrader1, 0.45 and withingrader2, 0.52), and the poorest intergrader agreement was found for SRPEN, RCA, and pigment epithelial detachment (0.18, 0.37, and 0.15, respectively). Conclusions: Although the agreement values were high for intraretinal features, considerable grader variability was found for the vascular and structural features in the deeper retina or under the RPE. Clinicians should be careful to base therapeutic decisions on qualitative OCT-A assessment, because even well-trained specialists show a considerable grader variation in their subjective evaluation. Translational Relevance: The clinical value of OCT-A imaging largely depends on the agreement of subjective evaluations by ophthalmologists.

Detailed optical coherence tomography angiographic short-term response of type 3 neovascularization to combined treatment with photodynamic therapy and intravitreal bevacizumab.

PURPOSE: To explore the short-term vascular and structural changes of type 3 neovascularization using optical coherence tomography angiography (OCT-A) when treated with a combination of photodynamic therapy (PDT) and intravitreal bevacizumab (IVB), and to evaluate the course of different sequences of the combined therapies. METHODS: Thirty eyes of 29 treatment-naïve patients with a type 3 neovascularization were included in this prospective observational cohort study. They were all treated with PDT and IVB 2 weeks apart, starting either with PDT (PDT-first group) or IVB (IVB-first group). Optical coherence tomography angiography (OCT-A) imaging was performed at week 0, 2, 4 and 18, and best corrected visual acuity (BCVA) at week 0 and 18. Vascular, structural and functional features were graded and analysed over time. RESULTS: In all patients, at all follow-up visits, vascular and structural features were significantly more often decreased or resolved than unchanged or increased. Best corrected visual acuity (BCVA) significantly improved at 18 weeks. Vascular, structural and functional outcomes were all slightly better in the PDT-first group compared to the IVB-first group, although not statistically significant. CONCLUSION: Combined treatment of PDT and IVB is effective in short-term for type 3 neovascularization based on vascular and structural features. Initial treatment with PDT tended to be more effective than with IVB.

Association of Axial Length With Risk of Uncorrectable Visual Impairment for Europeans With Myopia.

IMPORTANCE: Myopia (ie, nearsightedness) is becoming the most common eye disorder to cause blindness in younger persons in many parts of the world. Visual impairment due to myopia is associated with structural changes of the retina and the globe because of elongation of the eye axis. How axial length-a sum of the anterior chamber depth, lens thickness, and vitreous chamber depth-and myopia relate to the development of visual impairment over time is unknown. OBJECTIVES: To evaluate the association between axial length, spherical equivalent, and the risk of visual impairment and to make projections of visual impairment for regions with high prevalence rates. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study uses population-based data from the Rotterdam Study I (1990 to 1993), II (2000 to 2002), and III (2006 to 2008) and the Erasmus Rucphen Family Study (2002 to 2005) as well as case-control data from the Myopia Study (2010 to 2012) from the Netherlands. In total, 15 404 individuals with data on spherical equivalent and 9074 individuals with data on axial length were included in the study; right eyes were used for analyses. Data were analyzed from September 2014 to May 2016. MAIN OUTCOMES AND MEASURES: Visual impairment and blindness (defined according to the World Health Organization criteria as a visual acuity less than 0.3) and predicted rates of visual impairment specifically for persons with myopia. RESULTS: Of the 15 693 individuals included in this study, the mean (SD) age was 61.3 (11.4) years, and 8961 (57.1%) were female. Axial length ranged from 15.3 to 37.8 mm; 819 individuals had an axial length of 26 mm or greater. Spherical equivalent ranged from -25 to +14 diopters; 796 persons had high myopia (ie, a spherical equivalent of -6 diopters or less). The prevalence of visual impairment varied from 1.0% to 4.1% in the population-based studies, was 5.4% in the Myopia Study, and was 0.3% in controls. The prevalence of visual impairment rose with increasing axial length and spherical equivalent, with a cumulative incidence (SE) of visual impairment of 3.8% (1.3) for participants aged 75 years with an axial length of 24 to less than 26 mm and greater than 90% (8.1) with an axial length of 30 mm or greater. The cumulative risk (SE) of visual impairment was 5.7% (1.3) for participants aged 60 years and 39% (4.9) for those aged 75 years with a spherical equivalent of -6 diopters or less. Projections of these data suggest that visual impairment will increase 7- to 13-fold by 2055 in high-risk areas. CONCLUSIONS AND RELEVANCE: This study demonstrated that visual impairment is associated with axial length and spherical equivalent and may be unavoidable at the most extreme values in this population. Developing strategies to prevent the development of myopia and its complications could help to avoid an increase of visual impairment in the working-age population.