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    Research Update 588


    Effect of socioeconomic deprivation as determined by the English deprivation deciles on the progression of diabetic retinopathy and maculopathy: a multivariate case-control analysis of 88 910 patients attending a South-East London diabetic eye screening service.

    British journal of ophthalmology. 2023 Jun 28:

    Giannakis P, Nderitu P, Nunez do Rio JM, Webster L, Mann S, Hopkins D, Cardoso MJ, Modat M, Bergeles C, Jackson TL.

    Purpose: To determine associations between deprivation using the Index of Multiple Deprivation (IMD and individual IMD subdomains) with incident referable diabetic retinopathy/maculopathy (termed rDR).

    Methods: Anonymised demographic and screening data collected by the South-East London Diabetic Eye Screening Programme were extracted from September 2013 to December 2019. Multivariable Cox proportional models were used to explore the association between the IMD, IMD subdomains and rDR.

    Results: From 118 508 people with diabetes who attended during the study period, 88 910 (75%) were eligible. The mean (± SD) age was 59.6 (±14.7) years; 53.94% were male, 52.58% identified as white, 94.28% had type 2 diabetes and the average duration of diabetes was 5.81 (±6.9) years; rDR occurred in 7113 patients (8.00%). Known risk factors of younger age, Black ethnicity, type 2 diabetes, more severe baseline DR and diabetes duration conferred a higher risk of incident rDR. After adjusting for these known risk factors, the multivariable analysis did not show a significant association between IMD (decile 1 vs decile 10) and rDR (HR: 1.08, 95% CI: 0.87 to 1.34, p=0.511). However, high deprivation (decile 1) in three IMD subdomains was associated with rDR, namely living environment (HR: 1.64, 95% CI: 1.12 to 2.41, p=0.011), education skills (HR: 1.64, 95% CI: 1.12 to 2.41, p=0.011) and income (HR: 1.19, 95% CI: 1.02 to 1.38, p=0.024).

    Conclusion: IMD subdomains allow for the detection of associations between aspects of deprivation and rDR, which may be missed when using the aggregate IMD. The generalisation of these findings outside the UK population requires corroboration internationally.

    DOI: 10.1136/bjo-2023-323402


    Role of sleep-disordered breathing in age-related macular degeneration.

    BMJ open ophthalmology. 2023 May;8

    Fang WY, Rama Raj P, Wu,Abbott C, Luu CD, Naughton M, Guymer RH.

    Aims: To examine the association between obstructive sleep apnoea (OSA) and age-related macular degeneration (AMD), and the subphenotype of AMD with reticular pseudodrusen (RPD).

    Methods: Case-control study with 351 participants (211 AMD and 140 controls) using the Epworth Sleepiness Scale (ESS) and the STOP-BANG Questionnaire (SBQ) validated sleep questionnaires. Participant risk of having moderate-to-severe OSA was determined using a binary risk scale based on the ESS and SBQ combined and an ordinal risk scale based on the SBQ. A prior diagnosis of OSA and whether receiving assisted breathing treatment was also ascertained. Retinal imaging allowed AMD and RPD determination.

    Results: Higher risk of moderate-to-severe OSA according to the binary and ordinal scales was not associated with the presence of AMD (p≥0.519) nor AMD with RPD (p≥0.551). Per point increase in ESS or SBQ questionnaire score was also not associated with AMD nor AMD with RPD (p≥0.252). However, being on assisted breathing treatment for diagnosed OSA was significantly associated with a higher likelihood of having AMD with RPD, but not all AMD, (OR 3.70; p=0.042 and OR 2.70; p=0.149, respectively), when compared with those without diagnosed OSA on treatment.

    Conclusions: Formally diagnosed OSA undergoing treatment, increased the likelihood of having AMD with RPD, but not overall AMD compared with those who were not undergoing treatment. Risk-based OSA questionnaires showed no difference in risk for all AMD or AMD with RPD. Future research, using formal sleep studies could further explore the potential role of nocturnal hypoxia in AMD.

    DOI: 10.1136/bmjophth-2022-001203


    Longitudinal microvascular and neuronal retinal evaluation in patients with diabetes mellitus type 1 and 2 and good glycemic control.

    Retina (Philadelphia, Pa.) 2023 Jun 27.

    Vujosevic S, Toma C, Villani E, Nucci P, Brambilla M, Torti E, Prof FL, De Cillà S.

    Purpose: To evaluate microvascular and neuronal changes over 3 years in patients with type 1/2 diabetes mellitus (DM1/DM2), good metabolic control and no signs of diabetic retinopathy (DR).

    Methods: In this prospective, longitudinal study, 20 DM1, 48 DM2 and 24 controls underwent macular OCT ant OCT-A at baseline and after 3 years. Following parameters were considered: thickness of the central macula (CMT), retinal nerve fiber layer (NFL), ganglion cell (GCL+/GCL++) complex; perfusion and vessel density (PD/VD) and fractal dimension (FD) at the superficial and deep capillary plexuses (SCP/DCP); choriocapillaris flow deficits (CC-FD); foveal avascular zone (FAZ) metrics. MATLAB and ImageJ were used for OCT-A scans analyses.

    Results: Mean HbA1c was 7.4 ± 0.8% in DM1 and 7.2 ± 0.8% in DM2 at baseline, with no change at 3 years. No eye developed DR. In longitudinal analyses, PD at SCP (p=0.03) and FAZ area and perimeter (p<0.0001) significantly increased in DM2 compared to other groups. No longitudinal changes occurred in OCT parameters. In comparisons within groups, DM2 had a significant thinning of GCL++ in the outer ring, decreased PD at DCP and CC-FD, an increase in FAZ perimeter and area in DCP; DM1 had an increase in FAZ perimeter in DCP (p<0.001 for all comparisons).

    Conclusion: Longitudinal data showed significant microvascular retinal changes in DM2. No changes were detected in neuronal parameters and in DM1. Longer and larger studies are needed to confirm these preliminary data.

    DOI: 10.1097/IAE.0000000000003880

    Retina and RPE lipid profile changes associated with ABCA4 associated Stargardt’s maculopathy.

    Pharmacology & therapeutics. 2023 Jun 27:

    Farnoodian M, Bose D, Barone F, Nelson LM, Boyle M, Jun B, Do K, Gordon W, Guerin MK, Perera R, Cogliati T, Sharma R, Books BP, Bazan N, Bharti K.

    Stargardt maculopathy, caused predominantly by mutations in the ABCA4 gene, is characterized by an accumulation of non-degradable visual pigment derivative, lipofuscin, in the retinal pigment epithelium (RPE) – resulting in RPE atrophy. RPE is a monolayer tissue located adjacent to retinal photoreceptors and regulates their health and functioning; RPE atrophy triggers photoreceptor cell death and vision loss in Stargardt patients. Previously, ABCA4 mutations in photoreceptors were thought to be the major contributor to lipid homeostasis defects in the eye. Recently, we demonstrated that ABCA4 loss of function in the RPE leads to cell-autonomous lipid homeostasis defects. Our work underscores that an incomplete understanding of lipid metabolism and lipid-mediated signaling in the retina and RPE are potential causes for lacking treatments for this disease. Here we report altered lipidomic in mouse and human Stargardt models. This work provides the basis for therapeutics that aim to restore lipid homeostasis in the retina and the RPE.

    DOI: 10.1016/j.pharmthera.2023.108482


    Retinal Thickness Deviation: A New OCT Parameter for Assessing Diabetic Macular Edema.

    Journal of clinical medicine. 2023 Jun 11;

    Marolo P, Borrelli E, Gelormini F, Boscia G, Parisi G, Fallico M, Barresi C, Lari G, Berni A, Bandello F, Reibaldi M.

    (1) Purpose: To determine the “retinal thickness deviation” (RTD) in diabetic macular edema (DME) eyes treated with intravitreal therapy and to establish associations between RTD and best-corrected visual acuity (BCVA).

    (2) Methods: We conducted a retrospective study, including consecutive patients with DME eyes undergoing intravitreal therapy with two years of follow-up. BCVA and central subfield thickness (CST) were collected at baseline and at 12 months and 24 months of follow-up. RTD was calculated as the absolute difference between measured and normative CST values at each time point. Linear regression analyses were performed between RTD and BCVA and between CST and BCVA.

     (3) Results: One hundred and four eyes were included in the analysis. The RTD was 177.0 (117.2) μm at baseline, 97.0 (99.7) μm at 12 months and 89.9 (75.3) μm at 24 months of follow-up (p < 0.001). RTD showed a moderate association with BCVA at baseline (R2 = 0.134, p < 0.001) and 12 months (R2 = 0.197, p < 0.001) and a substantial association at 24 months (R2 = 0.272, p < 0.001). The CST showed a moderate association with BCVA at baseline (R2 = 0.132, p < 0.001) and 12 months (R2 = 0.136, p < 0.001), while the association was weak at 24 months (R2 = 0.065, p = 0.009). (4) Conclusions: RTD showed a good association with visual outcome in patients with DME eyes undergoing intravitreal treatment.

    DOI: 10.3390/jcm12123976


    Effect of the Mediterranean Diet on Progression of Dry Form of Age-related Macular Degeneration.

    In vivo (Athens, Greece) 2023 Jul-Aug;

    Gourgouli DM, Gourgouli I, Spai S, Gourgouli K, Tzorovili E, Skouroliakou M, Papakonstantinou D, Moschos MM.

    Background/Aim: The aim of this study was to investigate the possible effect of the Mediterranean diet (Med Diet) on the progression of age-related macular degeneration (AMD) in patients with early or intermediate stages of dry AMD.

    Patients And Methods: The present study included 164 patients with early or intermediate dry AMD. Data collected included demographics, anthropometric data, ophthalmic and medical history. AMD progression was evaluated using patients’ optical coherence tomography (OCT) and visual acuity. Using the MedDietScore, sample’s attachment to Med Diet was evaluated, and distinguished into high and low. The association of supplement intake and adherence to Med Diet with AMD progression was investigated using logistic regression.

    Results: Sample’s mean age was 73±7.4 years. A positive correlation was found between dietary supplementation and slowing of AMD progression, as well as between high adherence to Med Diet and slowing of AMD progression. In contrast, smokers had 51.4% higher risk of AMD progression (p=0.043). The rate of slowing AMD progression was higher in patients who followed Med Diet and received a dietary supplement, compared to patients who followed one or none of the aforementioned recommendations (p<0.001).

    Conclusion: Adherence to the Med Diet could have a positive effect on delaying AMD progression in advanced stages, both in patients receiving or not antioxidants. Therefore, our study proposes to strengthen recommendations to AMD patients to follow a Med Diet.

    DOI: 10.21873/invivo.13271 PMID: 37369498


    The role of the cytokine TNF-α in choroidal neovascularization: a systematic review.

    Eye (London, England)2023 Jun 28.


    TNF-α is a multifunctional cytokine produced by macrophages and T cells. This proinflammatory substance is considered to play a crucial role in the inflammatory process associated with age-related macular degeneration (AMD). The current review aimed to describe evidence for an association between TNF-α and AMD reported in various studies. The MEDLINE, Embase, PubMed and Global Health databases were systematically searched to identify studies that investigated the role of TNF-α in AMD. A total of 24 studies were deemed eligible for the review. To better understand and integrate the evidence, the studies were categorised into four major groups in relation to the role of TNF-α in AMD: (1) those examining biological signalling pathways through which TNF-α exerts its effect; (2) investigating levels of TNF-α; (3) exploring the genetics underlying the role of TNF-α; and (4) assessing anti-TNF-α agents as potential treatments for AMD. TNF-α is thought to directly contribute to choroidal neovascularization (CNV) enhancement and has been shown to exert its effect by augmenting the inflammatory response through other signalling pathways. Additionally, different genes have been found to be associated with activities linked to TNF-α in AMD. Overall, measurement of systemic and local levels of TNF-α has not yielded consistent findings, with variable conclusions for the role of anti-TNF-α agents in remission of AMD symptoms. The role of TNF-α in neovascular AMD is not clear, and not all anti-TNF-α agents are safe. The potential of this cytokine in atrophic AMD has not been examined. Future studies should address these unresolved questions.

    DOI: 10.1038/s41433-023-02634-5


    Pachychoroid disease associated with geographic atrophy and subretinal drusenoid deposits.

    Retina cases & brief reports. 2023 Jul 1;

    Manayath GJ, Verghese S, Narendran V.

    Purpose: To report an atypical case of pachychoroid spectrum disease associated with subretinal drusenoid deposits and geographic atrophy.

    Methods: Case report.

    Results: A 67-year-old woman presented for a routine examination. Her best-corrected visual acuity was 20/20 in both eyes. Based on fundus examination and multimodal imaging findings, the presence of subretinal drusenoid deposits and geographic atrophy was seen in the right eye, which was associated with pachychoroid. The left eye revealed two active polypoidal lesions suggestive of polypoidal choroidal vasculopathy with subretinal drusenoid deposits, geographic atrophy, and a thick choroid with dilated outer choroidal vessels. She underwent an intravitreal injection of ranibizumab followed by focal laser to the polypoidal lesion in the left eye. At 3-month posttreatment, her best-corrected visual acuity was maintained at 20/20 in the left eye, with a good anatomical outcome.

    Conclusion: This case highlights a previously unreported unique association of a pachychoroid disease spectrum with geographic atrophy and with subretinal drusenoid deposits.

    DOI: 10.1097/ICB.0000000000001226