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    Research update: 530

    The latest research highlights for 21 March 2022.


    Association of plasma ω-3 fatty acids with early age-related macular degeneration in the Multi-Ethnic Study of Atherosclerosis (MESA).

    7. Retina. 2022 Mar 9.

    Karger AB, Guan W, Nomura SO, Weir NL, Klein BEK, Burke GL, Johnson WC, Tsai MY.

    Purpose: To examine the association between omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and age-related macular degeneration (AMD) in the Multi-ethnic Study of Atherosclerosis (MESA) cohort.

    Methods: MESA is a multi-center, prospective cohort study designed to identify risk factors for cardiovascular disease in four ethnic groups. 6,814 participants of white, African American, Hispanic/Latino, and Chinese descent, ages 45 – 84 years, were recruited, with those found to have cardiovascular disease excluded. Our study population included all MESA participants with baseline PUFA measurements and retinal photography at exam 5 (n = 3,772). Fundus photographs were assessed for AMD using a standard grading protocol. Relative risk regression (log-link) determined associations between PUFA levels and AMD.

    Results: There was a significant association between increasing DHA levels and increasing DHA + EPA levels with reduced risk for early AMD (n = 214 participants with early AMD, of which n = 99 (46.3%) are non-white). EPA levels alone were not significantly associated with AMD.

    Conclusion: Our analysis suggests increasing levels of DHA are associated with reduced risk for early AMD in a multi-ethnic cohort. This represents the first racially diverse study demonstrating an association between omega-3 PUFAs and AMD risk.

    DOI: 10.1097


    Serum 25-hydroxy vitamin D levels in age-related macular degeneration.

    International Journal of Retina and Vitreous. 2022 Mar 7

    Pérez Serena A(1)(2), Martínez Betancourt DP(3), González Del Valle F(4), Ruiz-Moreno JM(5)(6).

    Background: The aim of this study was to determine the 25-hydroxy vitamin D (25(OH)D) levels in age-related macular degeneration (AMD) patients.

    Methods: Age-related macular degeneration (AMD) patients were classified into four groups: early AMD (N = 10), intermediate AMD (N = 12), advanced atrophic AMD (N = 19) and advanced neovascular AMD (N = 52) after undergoing fundus photography. Serum 25(OH)D levels of all subjects were evaluated. From a random control group of 326 patients whose 25(OH)D levels had been measured, a group of 93 were selected to match the age range of the AMD group. We measured 25(OH)D levels during the same period to rule out seasonal variation.

    Results: A total of 93 AMD patients (36 males and 57 females) and 93 healthy individuals (39 males and 54 females) were enrolled in this study with the mean age of 78.96 ± 8.46 vs. 78.80 ± 8.35, respectively. The patients affected by AMD had statistically significant lower 25(OH)D levels (15 ± 10 ng/mL) than the healthy subjects control group (21 ± 14 ng/mL) (p = 0.004). However, the median 25(OH)D levels in early AMD, intermediate AMD, advanced atrophic AMD and advanced neovascular AMD (12.5 ± 7.3; 15 ± 11; 15 ± 8 and 17 ± 11.5, respectively) were not statistically significant (p = 0.442).

    Conclusion: This study shows that patients affected by AMD had lower vitamin D levels compared to healthy subjects. Further research is necessary to investigate the possible association between 25(OH)D levels and AMD.

    DOI: 10.1186/s40942-022-00368-2


    Drivers of and Barriers to Adherence to Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema Treatment Management Plans: A Multi-National Qualitative Study.

    Patient Prefer Adherence. 2022 Mar 3

    Giocanti-Aurégan A, García-Layana A, Peto T, Gentile B, Chi GC, Mirt M, Kosmas CE, Lambert J, Lanar S, Lewis HB, Holekamp NM.

    Purpose: Neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) patients treated with intravitreally injected anti-vascular endothelial growth factor (anti-VEGF) monotherapies achieve lower vision improvements compared with patients in clinical trials. This qualitative research study aimed to better understand the real-world anti-VEGF treatment experience from nAMD and DME patients’, caregivers’, and retina specialists’ perspectives.

    Methods: One-time, semi-structured, individual interviews were conducted with adult patients with nAMD or DME treated with anti-VEGF injections for ≥12 months, their caregivers, and experienced retina specialists. Interview transcripts were analyzed qualitatively using a thematic analysis approach.

    Results: A total of 49 nAMD and 46 DME patients, 47 nAMD and 33 DME caregivers, and 62 retina specialists were interviewed in the USA, Canada, France, Germany, Italy and Spain. Most (79%) patients and caregivers reported disruptions to their routine on the day before, the day of, or the day after anti-VEGF injection. Seven nAMD patients (14%) and 14 DME patients (30%) reported having missed an injection visit. The most frequently reported driver for adherence for patients was the doctor-patient relationship (n=66, 70%), whereas for caregivers, it was the ease of booking an appointment (n=25, 32%). Retina specialists reported patient education on the treatment (n=28, 45%) as the most important driver. Treatment barriers could be grouped into four categories: tolerability, clinical factors, logistical parameters and human factors. The most frequently reported barrier to adherence for patients and caregivers was related to side effects (pain/discomfort/irritation: n=63, 67% of patients; n=52, 66% of caregivers), whereas for retina specialists it was logistical parameters (travel logistics: n=44, 71%).

    Conclusion: This study highlights the importance of the doctor-patient relationship and patient education as key drivers, and treatment tolerability and logistics as key barriers to treatment adherence. Improved doctor-patient relationship/communication and patient education together with new therapies offering convenience, long-acting effectiveness, and better tolerability may improve treatment adherence.

    DOI: 10.2147/PPA.S347713


    Sleep and eye disease: A review.

    Clinical and Experimental Ophthalmology. 2022 Mar 9.

    Lee SSY, Nilagiri VK, Mackey DA.

    There is a growing body of literature on the effects of sleep disorders, in particular obstructive sleep apnoea (OSA), on ocular health, with consistent evidence of an increased risk of floppy eyelid syndrome, non-arteritic anterior ischaemic optic neuropathy, diabetic macular oedema, and other retinal vasculature changes in individuals with OSA. However, reports on OSA’s associations with glaucoma, papilloedema, diabetic retinopathy, central serous chorioretinopathy, and keratoconus have been conflicting, while links between OSA and age-related macular degeneration have only been described fairly recently. Despite numerous suggestions that OSA treatment may reduce risk of these eye diseases, well-designed studies to support these claims are lacking. In particular, the ocular hypertensive effects of continuous positive airway pressure (CPAP) therapy for OSA requires further investigation into its potential impact on glaucoma risk and management. Reports of ocular surface complications secondary to leaking CPAP masks highlights the importance of ensuring good mask fit. Poor sleep habits have also been linked with increased myopia risk; however, the evidence on this association remains weak. This article is protected by copyright. All rights reserved.

    DOI: 10.1111/ceo.14071

    Dark Adaptation and Its Role in Age-Related Macular Degeneration.

    Journal of Clinical Medicine. 2022 Mar 1

    Nigalye AK, Hess K, Pundlik SJ, Jeffrey BG, Cukras CA, Husain D.

    Dark adaptation (DA) refers to the slow recovery of visual sensitivity in darkness following exposure to intense or prolonged illumination, which bleaches a significant amount of the rhodopsin. This natural process also offers an opportunity to understand cellular function in the outer retina and evaluate for presence of disease. How our eyes adapt to darkness can be a key indicator of retinal health, which can be altered in the presence of certain diseases, such as age-related macular degeneration (AMD). A specific focus on clinical aspects of DA measurement and its significance to furthering our understanding of AMD has revealed essential findings underlying the pathobiology of the disease. The process of dark adaptation involves phototransduction taking place mainly between the photoreceptor outer segments and the retinal pigment epithelial (RPE) layer. DA occurs over a large range of luminance and is modulated by both cone and rod photoreceptors. In the photopic ranges, rods are saturated and cone cells adapt to the high luminance levels. However, under scotopic ranges, cones are unable to respond to the dim luminance and rods modulate the responses to lower levels of light as they can respond to even a single photon. Since the cone visual cycle is also based on the Muller cells, measuring the impairment in rod-based dark adaptation is thought to be particularly relevant to diseases such as AMD, which involves both photoreceptors and RPE. Dark adaptation parameters are metrics derived from curve-fitting dark adaptation sensitivities over time and can represent specific cellular function. Parameters such as the cone-rod break (CRB) and rod intercept time (RIT) are particularly sensitive to changes in the outer retina. There is some structural and functional continuum between normal aging and the AMD pathology. Many studies have shown an increase of the rod intercept time (RIT), i.e., delays in rod-mediated DA in AMD patients with increasing disease severity determined by increased drusen grade, pigment changes and the presence of subretinal drusenoid deposits (SDD) and association with certain morphological features in the peripheral retina. Specifications of spatial testing location, repeatability of the testing, ease and availability of the testing device in clinical settings, and test duration in elderly population are also important. We provide a detailed overview in light of all these factors.

    DOI: 10.3390/jcm11051358


    Anti-retinal IgG antibodies in patients with early and advanced type 2 macular telangiectasia.

    Experimental Eye Research. 2022 Mar 7

    McLenachan S, Balaratnasingam C, Heath Jeffery RC, Chen SC, Zhang D, Chan G, Dolz-Marco R, Bacci T, Lo J, Wiffen S, Yannuzzi LA, Chen FK.

    Type 2 idiopathic macular telangiectasia (MacTel-2) is a progressive adult-onset macular disease associated with bilateral perifoveal vascular changes, Muller cell degeneration and increased blood-retinal barrier permeability. The pathophysiological mechanisms of MacTel-2 remain unclear, however it was previously reported that anti-retinal antibodies in MacTel-2 patients was a significant feature of the disease. In this study, we aimed to compare the prevalence of anti-retinal antibodies in patients MacTel-2, healthy controls and patients with other retinal diseases. MacTel-2 patients diagnosed with multimodal imaging were enrolled and their disease severities were graded using spectral-domain optical coherence tomography. For comparison, patients with age-related macular degeneration (AMD), inherited retinal diseases (IRDs) or no retinal disease (healthy controls) were recruited as controls. Blood serum samples were screened for immunoglobulin G anti-retinal antibodies by western blotting, followed by densitometry analysis. Odds ratios (OR) with 95% confidence intervals (CI) were calculated and p < 0.05 considered statistically significant. Overall, anti-retinal antibody-positive cases were older (64 ± 15 vs 53 ± 17 years, p < 0.001) and females were more likely to develop anti-retinal antibodies (OR: 2.41, CI: 1.12-5.18). The frequency of anti-retinal antibody detection in MacTel-2 patients (n = 42, 36%) was not significantly different from healthy controls (n = 52, 25%) or IRDs patients (n = 18, 25%) and the majority of MacTel-2 patients had no anti-retinal antibodies. In contrast, the frequency of anti-retinal antibody detection was significantly higher in patients with AMD (n = 15, 73%, p < 0.001). The lack of a greater anti-retinal antibody frequency or specificity in the MacTel-2 cohort suggests that antibody mediated immunological mechanisms may play a less significant role in MacTel-2 disease pathogenesis.

    DOI: 10.1016/j.exer.2022.109024


    THE RAP STUDY, REPORT 5: REDISCOVERING MACULAR NEOVASCULARIZATION TYPE 3: Multimodal Imaging of Fellow Eyes over 24 months.

    50. Retina. 2022 Mar 1.

    Haj Najeeb B, Deak GG, Mylonas G, Sacu S, Gerendas BS, Schmidt-Erfurth U.

    Purpose: To explore the condition of fellow eyes of patients with macular neovascularization Type 3 (MNV3) and to verify whether the retinal-choroidal anastomosis (RCA) develops equally in all MNV types.

    Methods: The contralateral eyes of 94 patients with MNV3, 96 patients with MNV1, and 96 patients with MNV2 were included. Multimodal imaging was performed. The MNV3 stage including the development of fibrosis and RCA over 24 months was determined.

    Results: In the contralateral eyes of patients of the solitary (one lesion) MNV3 group, 32 eyes (42.1%) showed early/intermediate age-related macular degeneration, 25 eyes (33%) showed MNV3, and 11 eyes (14.5%) experienced fibrosis, of which 4 eyes (5.2%) had a RCA, 7 eyes (9.2%) had atrophy after resolved MNV3, and 1 eye (1.3%) developed MNV1. In the multifocal (more than one lesion) MNV3 group, 2 eyes (11.1%) showed early/intermediate age-related macular degeneration, 9 eyes (50%) showed 15 MNV3 lesions, and 4 eyes (22.2%) showed fibrosis, of which 2 eyes (11.1%) manifested with a RCA and 3 eyes (16.7%) showed atrophy after resolved MNV3. The number of eyes with a RCA accounted for 40% of all eyes with fibrosis. The count of simultaneous bilateral multifocal MNV3 was 5 (55.6%). In the MNV1 and MNV2 groups, no eye developed a RCA. The incidence of RCAs in the scarred eyes in MNV3 was significantly higher (P < 0.0001).

    Conclusion: Retinal-choroidal anastomosis is an exclusive clinical feature of MNV3. The development of the multifocal MNV3 is usually bilateral and simultaneous. The occurrence of fibrosis in MNV3 has decreased dramatically after the introduction of the antiangiogenic therapy.

    DOI: 10.1097/IAE.0000000000003330


    The effect of age-related macular degeneration on cognitive test performance.

    27. Sci Rep. 2022 Mar 8

    Macnamara A, Schinazi VR, Chen C, Coussens S, Loetscher T.

    The reliable assessment of cognitive functioning is critical to the study of brain-behaviour relationships. Yet conditions that are synchronous which ageing, including visual decline, are easily overlooked when interpreting cognitive test scores. The purpose of this study was to demonstrate the negative consequences of visual impairments on cognitive tests performance. Moderate to severe levels of age-related macular degeneration were simulated, with a set of goggles, in a sample of twenty-four normally sighted participants while they completed two cognitive tasks: a vision-dependent reaction time task and a vision-independent verbal fluency test. Performance on the reaction time task significantly decreased (p < 0.001) in the simulated age-related macular degeneration condition, by as much as 25 percentile ranks. In contrast, performance on the verbal fluency test were not statistically different between the simulated and normal vision conditions (p = 0.78). The findings highlight the importance of considering visual functioning when assessing cognitive function. When vision is not accounted for, low test scores may inaccurately indicate poor cognition. Such false attributions may have significant ramification for diagnosis and research on cognitive functioning.

    DOI: 10.1038/s41598-022-07924-8