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    Research update: 511

    The latest research highlights for 20 September 2021


    The Impact of Non-Ophthalmic Factors on Intravitreal Injections During the COVID-19 Lockdown.

    Clin Ophthalmol. 2021 Aug 28;15:3661-3668.

    Ashrafzadeh S, Gundlach BS, Tsui I.

    PURPOSE: Early on in the COVID-19 pandemic, it was difficult to know what factors would affect patient and physician decision-making regarding ophthalmic care utilization. The purpose of this study is to investigate the effect of non-ophthalmic factors on patient decision-making to receive intravitreal injections during the COVID-19 lockdown.

    PATIENTS AND METHODS: Data on patients who had intravitreal injection appointments at a tertiary care Veterans Health Administration clinic during a seven-week period (March 19, 2020-May 8, 2020) of the COVID-19 outbreak in Los Angeles County were collected and compared to patients who had intravitreal injection appointments during the same time period in 2019. Demographic characteristics, injection diagnoses, visual acuities, body mass indices, co-morbidities, and psychiatric conditions of patients and clinic volumes were tabulated and compared between the two time periods.

    RESULTS: There were 86 patients in the injection clinic in 2020 compared to 176 patients in 2019. The mean age and gender of patients in the injection clinic did not differ between 2019 and 2020. Compared to 2019, the number of patients who identified as Hispanic or Latino remained nearly the same, but the number of patients who identified as White, Black, or Asian or Pacific Islander decreased by nearly half. In 2020, a greater proportion of patients came to the injection clinic for neovascular age-related macular degeneration (56.5% vs 39.3%, p=0.017), but a decreased proportion of patients diagnosed with a heart condition (OR 0.57, 95% CI 0.33, 0.96), chronic obstructive pulmonary disease (OR 0.43, 95% CI 0.21, 0.91), or asthma (OR 0.09, 95% CI 0.01, 0.70) came to the injection clinic.

    CONCLUSION: The COVID-19 pandemic was associated with behavioral changes in eyecare utilization influenced by race and systemic co-morbidities. These data can be used to design and implement strategies to address disparities in essential ophthalmic care among vulnerable populations.

    DOI: 10.2147/OPTH.S314840

    Comparative Risk of Arterial Thromboembolic Events Between Aflibercept and Ranibizumab in Patients with Maculopathy: A Population-Based Retrospective Cohort Study.

    BioDrugs. 2021 Sep 8.

    Lee WA, Shao SC, Liao TC, Lin SJ, Lai CC, Lai EC.

    BACKGROUND: The increasing numbers of elderly patients and rising incidence of maculopathy raise concerns over arterial thromboembolic events (ATEs) with the use of intravitreal anti-vascular endothelial growth factor (VEGF) medications.

    OBJECTIVES: This study aimed to compare the risk of ATEs between aflibercept and ranibizumab for maculopathy.

    METHODS: We conducted a retrospective population-based cohort study analyzing Taiwan’s National Health Insurance Database during 2011-2017 to identify patients with maculopathy receiving intravitreal aflibercept or ranibizumab. The primary outcome was any hospitalization or emergency room visit because of ATEs, including ischemic heart disease (IHD), ischemic stroke (IS), and transient ischemic attack (TIA). The secondary outcome was mortality within 30 days after occurrence of ATE. We employed propensity score methods to generate more homogeneous groups for comparison.

    RESULTS: We included 5791 aflibercept users and 14,534 ranibizumab users in this study. Compared with the ranibizumab group, the aflibercept group was associated with a lower risk of ATE (hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.80-0.91), with HRs of 0.86 for IHD (95% CI 0.80-0.93), 0.87 for IS (95% CI 0.76-1.00), and 0.57 for TIA (95% CI 0.46-0.71). The risk of 30-day mortality after ATE (HR 1.39; 95% CI 0.80-2.43) and the risk of all-cause mortality (HR 1.02; 95% CI 0.89-1.17) in the aflibercept group was similar to that in the ranibizumab group.

    CONCLUSION: The use of aflibercept in patients with maculopathy was associated with a lower risk of ATE than was the use of ranibizumab. There was no difference in mortality risk between the two groups. Our study could provide strong grounds for future prospective studies to confirm the findings.

    DOI: 10.1007/s40259-021-00497-4

    Intravitreal Dexamethasone Implant in Patients Who Did Not Complete Anti-VEGF Loading Dose During the COVID-19 Pandemic: a Retrospective Observational Study.

    Ophthalmol Ther. 2021 Sep 5:1-10.

    Scorcia V, Giannaccare G, Gatti V, Vaccaro S, Piccoli G, Villì A, Toro MD, Yu AC, Iovino C, Simonelli F, Carnevali A.

    INTRODUCTION: To compare the functional and anatomic outcomes between eyes in patients with diabetic macular edema (DME) who underwent a complete anti-vascular endothelial growth factor (VEGF) loading dose with aflibercept and those who were switched to dexamethasone intravitreal (DEX) implant after an incomplete anti-VEGF treatment regimen during the coronavirus disease 2019 (COVID-19) pandemic.

    METHODS: This was a retrospective and comparative study conducted on patients with DME. Main outcome measures were mean change in best corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 4.

    RESULTS: Forty-three eyes (23 eyes in the anti-VEGF group and 20 eyes in the DEX group) were included. Mean BCVA significantly improved from 37.7 ± 25.3 and 35.7 ± 22.0 letters at baseline to 45.4 (23.9) (mean adjusted BCVA improvement 7.6 ± 20.8 letters, p = 0.033) and 46.1 ± 26.0 (mean adjusted BCVA improvement 10.6 ± 15.9 letters, p = 0.049) at month 4 in the anti-VEGF and DEX groups, respectively, with no significant differences between study groups (mean adjusted BCVA difference 2.8 letters, 95% CI – 9.4 to 14.9 letters, p = 0.648). There were no statistically significant differences in the proportion of eyes that achieved a BCVA improvement of ≥ 5, ≥ 10, and ≥ 15 letters between groups. CRT was significantly reduced from baseline to month 4 in both DEX (mean adjusted CRT reduction 167.3 ± 148.2 µm, p = 0.012) and anti-VEGF groups (mean adjusted CRT reduction 109.9 ± 181.9 µm, p < 0.001), with no differences between them (mean adjusted CRT difference 56.1 µm, 95% CI – 46.0 to 158.2 µm, p = 0.273). Of 20 eyes in the DEX group, 16 (80.0%) and 9 (45.0%) eyes achieved a CRT reduction of ≥ 20% from baseline at 2 months and at 4 months, respectively.

    CONCLUSIONS: Our results seem to suggest that DEX implant can significantly improve both functional and anatomic clinical outcomes in patients who were unable to complete anti-VEGF loading dose during the COVID-19 pandemic.

    DOI: 10.1007/s40123-021-00395-6


    Prechoroidal cleft thickness correlates with disease activity in neovascular age-related macular degeneration.

    Graefes Arch Clin Exp Ophthalmol. 2021 Sep 7.

    Cozzi M, Monteduro D, Parrulli S, Ristoldo F, Corvi F, Zicarelli F, Staurenghi G, Invernizzi A.

    PURPOSE: The purpose of this study was to investigate the structural variations of the hyporeflective pocket of fluid (prechoroidal cleft) located between Bruch’s membrane and the hyperreflective material within the pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration (nAMD).

    METHODS: In this retrospective, observational case series study, patients diagnosed with nAMD and prechoroidal cleft associated with other activity signs of the macular neovascularization (MNV) were included. Structural optical coherence tomography (OCT) scans were evaluated to obtain anatomical measurements of prechoroidal cleft and PED at three different visits (T0, inactive MNV; T1, active MNV; T2, treated inactive MNV). The variations in size of the cleft and the PED were correlated with nAMD activity.

    RESULTS: Twenty-nine eyes from 27 patients were included. The subfoveal measurements showed a significant increase of prechoroidal cleft height and width from T0 to T1 (P < 0.05) and a subsequent decrease of the cleft height after treatment with anti-VEGF agents (P = 0.004). A similar significant trend was observed for the greatest prechoroidal cleft height and width, obtained assessing the whole OCT raster. In the multivariate analysis, the cleft height was significantly affected by both time (P = 0.001) and PED height (P < 0.0001). By contrast, the effect of fibrovascular tissue size within the PED was not significant. Visual acuity did not correlate with prechoroidal cleft size.

    CONCLUSION: Prechoroidal cleft increased in association with MNV reactivation and decreased after treatment. Our results suggest that prechoroidal cleft could represent an accumulation of fluid actively exudating from the MNV and should be considered a sign of nAMD activity.

    DOI: 10.1007/s00417-021-05384-w


    Associations of systemic health and medication use with the enlargement rate of geographic atrophy in age-related macular degeneration.

    Br J Ophthalmol. 2021 Sep 6:bjophthalmol-2021-319426.

    Shen LL, Xie Y, Sun M, Ahluwalia A, Park MM, Young BK, Del Priore LV.

    BACKGROUND: The associations of geographic atrophy (GA) progression with systemic health status and medication use are unclear.

    METHODS: We manually delineated GA in 318 eyes in the Age-Related Eye Disease Study. We calculated GA perimeter-adjusted growth rate as the ratio between GA area growth rate and mean GA perimeter between the first and last visit for each eye (mean follow-up=5.3 years). Patients’ history of systemic health and medications was collected through questionnaires administered at study enrolment. We evaluated the associations between GA perimeter-adjusted growth rate and 27 systemic health factors using univariable and multivariable linear mixed-effects regression models.

    RESULTS: In the univariable model, GA perimeter-adjusted growth rate was associated with GA in the fellow eye at any visit (p=0.002), hypertension history (p=0.03), cholesterol-lowering medication use (p<0.001), beta-blocker use (p=0.02), diuretic use (p<0.001) and thyroid hormone use (p=0.03). Among the six factors, GA in the fellow eye at any visit (p=0.008), cholesterol-lowering medication use (p=0.002), and diuretic use (p<0.001) were independently associated with higher GA perimeter-adjusted growth rate in the multivariable model. GA perimeter-adjusted growth rate was 51.1% higher in patients with versus without cholesterol-lowering medication use history and was 37.8% higher in patients with versus without diuretic use history.

    CONCLUSIONS: GA growth rate may be associated with the fellow eye status, cholesterol-lowering medication use, and diuretic use. These possible associations do not infer causal relationships, and future prospective studies are required to investigate the relationships further.

    DOI: 10.1136/bjophthalmol-2021-319426

    Cross-sectional study evaluating burden and depressive symptoms in family carers of persons with age-related macular degeneration in Australia.

    BMJ Open. 2021 Sep 8;11(9):e048658.

    Jin I, Tang D, Gengaroli J, Nicholson Perry K, Burlutsky G, Craig A, Liew G, Mitchell P, Gopinath B.

    OBJECTIVES: We aimed to analyse the degree of carer burden and depressive symptoms in family carers of persons with age-related macular degeneration (AMD) and explore the factors independently associated with carer burden and depressive symptoms.

    METHODS: Cross-sectional study using self-administered and interviewer-administered surveys, involving 96 family carer-care recipient pairs. Participants were identified from tertiary ophthalmology clinics in Sydney, Australia, as well as the Macular Disease Foundation of Australia database. Logistic regression, Pearson and Spearman correlation analyses were used to investigate associations of explanatory factors (family caregiving experience, carer fatigue, carer quality of life and care-recipient level of dependency) with study outcomes-carer burden and depressive symptoms.

    RESULTS: Over one in two family carers reported experiencing mild or moderate-severe burden. More than one in five and more than one in three family carers experienced depressive symptoms and substantial fatigue, respectively. High level of care-recipient dependency was associated with greater odds of moderate-severe and mild carer burden, multivariable-adjusted OR 8.42 (95% CI 1.88 to 37.60) and OR 4.26 (95% CI 1.35 to 13.43), respectively. High levels of fatigue were associated with threefold greater odds of the carer experiencing depressive symptoms, multivariable-adjusted OR 3.47 (95% CI 1.00 to 12.05).

    CONCLUSIONS: A substantial degree of morbidity is observed in family carers during the caregiving experience for patients with AMD. Level of dependency on the family carer and fatigue were independently associated with family carer burden and depressive symptoms.

    TRIAL REGISTRATION NUMBER: The trial registration number is ACTRN12616001461482. The results presented in this paper are Pre-results stage.

    DOI: 10.1136/bmjopen-2021-048658


    A case of bilateral pachychoroid disease: polypoidal choroidal vasculopathy in one eye and peripheral exudative hemorrhagic chorioretinopathy in contralateral eye.

    BMC Ophthalmol. 2021 Sep 4;21(1):320.

    Kitagawa Y, Shimada H, Kawamura A, Tanaka K, Mori R, Onoe H, Nakashizuka H.

    BACKGROUND: We report a case of bilateral pachychoroid disease manifesting polypoidal choroidal vasculopathy (PCV) with punctate hyperfluorescent spot (PHS) in one eye, and peripheral exudative hemorrhagic choroidal retinopathy (PEHCR) with central serous chorioretinopathy (CSC) and PHS in the contralateral eye.

    CASE PRESENTATION: A 51-year-old healthy woman presented with complaint of blurred vision in her right eye. Corrected visual acuity was 20/20 in the right and 24/20 in the left eye. Fundus examination was normal in the left eye. In the right eye, fundus finding of an orange-red nodular lesion and optical coherence tomography (OCT) finding of polypoidal lesions led to a diagnosis of PCV. Four aflibercept intravitreal injections were performed in her right eye. After treatment, indocyanine green angiography (ICGA) confirmed residual polypoidal lesions with branching vascular networks and PHS with choroidal vascular hyperpermeability. OCT showed PHS associated with small sharp-peaked retinal pigment epithelium (RPE) elevation in peripheral fundus and small RPE elevation in posterior fundus. Based on the above findings, PCV with PHS was finally diagnosed in the right eye. Posttreatment corrected visual acuity in the right eye was 20/20. She presented again 32 months later, with complaint of vision loss in her left eye. Left corrected visual acuity was 20/20, and fundus examination showed mild vitreous hemorrhage. Vitrectomy was performed. In temporal midperipheral fundus, fluorescein angiography revealed CSC, and OCT showed pachychoroid. ICGA depicted abnormal choroidal networks and PHS in peripheral fundus. Furthermore, polypoidal lesions were confirmed by OCT. Based on the above findings, PEHCR and CSC with PHS was finally diagnosed in the left eye. Postoperative corrected visual acuity in the left eye was 20/20, and aflibercept intravitreal injection was performed for prevention of recurrence of vitreous hemorrhage.

    CONCLUSIONS: This is the first case report of PCV with PHS in one eye, and PEHCR with CSC and PHS in the contralateral eye. This case suggests that PCV, PEHCR, and CSC may be linked pathologies of pachychoroid spectrum disease.

    DOI: 10.1186/s12886-021-02067-2


    Simulating Macular Degeneration to Investigate Activities of Daily Living: A Systematic Review.

    Front Neurosci. 2021 Aug 13;15:663062.

    Macnamara A, Chen C, Schinazi VR, Saredakis D, Loetscher T.

    PURPOSE: Investigating difficulties during activities of daily living is a fundamental first step for the development of vision-related intervention and rehabilitation strategies. One way to do this is through visual impairment simulations. The aim of this review is to synthesize and assess the types of simulation methods that have been used to simulate age-related macular degeneration (AMD) in normally sighted participants, during activities of daily living (e.g., reading, cleaning, and cooking).

    METHODS: We conducted a systematic literature search in five databases and a critical analysis of the advantages and disadvantages of various AMD simulation methods (following PRISMA guidelines). The review focuses on the suitability of each method for investigating activities of daily living, an assessment of clinical validation procedures, and an evaluation of the adaptation periods for participants.

    RESULTS: Nineteen studies met the criteria for inclusion. Contact lenses, computer manipulations, gaze contingent displays, and simulation glasses were the main forms of AMD simulation identified. The use of validation and adaptation procedures were reported in approximately two-thirds and half of studies, respectively.

    CONCLUSIONS: Synthesis of the methodology demonstrated that the choice of simulation has been, and should continue to be, guided by the nature of the study. While simulations may never completely replicate vision loss experienced during AMD, consistency in simulation methodology is critical for generating realistic behavioral responses under vision impairment simulation and limiting the influence of confounding factors. Researchers could also come to a consensus regarding the length and form of adaptation by exploring what is an adequate amount of time and type of training required to acclimatize participants to vision impairment simulations.

    DOI: 10.3389/fnins.2021.663062


    Discovery of Novel Genetic Risk Loci for Acute Central Serous Chorioretinopathy and Genetic Pleiotropic Effect with Age-Related Macular Degeneration.

    Front Cell Dev Biol. 2021 Aug 20;9:696885.

    Feng L, Chen S, Dai H, Dorajoo R, Liu J, Kong J, Yin X, Ren Y.

    BACKGROUND: Central serous chorioretinopathy (CSC) is a severe and heterogeneous chorioretinal disorder. Shared clinical manifestations between CSC and age-related macular degeneration (AMD) and the confirmation of CFH as genetic risk locus for both CSC and AMD suggest possible common pathophysiologic mechanisms between two diseases.

    METHODS: To advance the understanding of genetic susceptibility of CSC and further investigate genetic pleiotropy between CSC and AMD, we performed genetic association analysis of 38 AMD-associated single nucleotide polymorphisms (SNPs) in a Chinese CSC cohort, consisting of 464 patients and 548 matched healthy controls.

    RESULTS: Twelve SNPs were found to be associated with CSC at nominal significance (p < 0.05), and four SNPs on chromosomes 1, 4, and 15 showed strong associations whose evidences surpassed Bonferroni (BF)-corrected significance [rs1410996, odds ratios (OR) = 1.47, p = 2.37 × 10-5; rs1329428, OR = 1.40, p = 3.32 × 10-4; rs4698775, OR = 1.45, p = 2.20 × 10-4; and rs2043085, OR = 1.44, p = 1.91 × 10-4]. While the genetic risk effects of rs1410996 and rs1329428 (within the well-established locus CFH) are correlated (due to high LD), rs4698775 on chromosome 4 and rs2043085 on chromosome 15 are novel risk loci for CSC. Polygenetic risk score (PRS) constructed by using three independent SNPs (rs1410996, rs4698775, and rs2043085) showed highly significant association with CSC (p = 2.10 × 10-7), with the top 10% of subjects with high PRS showing 6.39 times higher risk than the bottom 10% of subjects with lowest PRS. Three SNPs were also found to be associated with clinic manifestations of CSC patients. In addition, by comparing the genetic effects (ORs) of these 38 SNPs between CSC and AMD, our study revealed significant, but complex genetic pleiotropic effect between the two diseases.

    CONCLUSION: By discovering two novel genetic risk loci and revealing significant genetic pleiotropic effect between CSC and AMD, the current study has provided novel insights into the role of genetic composition in the pathogenesis of CSC.

    DOI: 10.3389/fcell.2021.696885