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    Research Update 559


    Salvageable waste associated with intravitreal injections: a local medical waste management approach.

    Clinical & Experimental Ophthalmology. 2022 Nov 1

    Rogerson T, Dedina L, Goggin M, Chan WO.

    Background: Healthcare waste management is a globally challenging issue with an increased prevalence of disposable, single use materials in developed countries and a rapidly ageing population continuing to drive an increase in the use of medical resources. One manifestation of this within ophthalmology is the increasing number of intravitreal injections given for conditions such as age-related macular degeneration and diabetic macular oedema.

    Methods: A prospective controlled cohort study was performed over five weeks in 2021 during which two sites were selected to compare different approaches to sorting the waste generated by intravitreal injections. At Site A all waste associated with these injections was placed in standard hospital waste bins. Site B was the intervention arm where a real-time sorting of waste occurred. The number of injections given and waste amounts were recorded.

    Results: 116 and 286 injections were given at Sites A and B respectively over the study period. Site A generated an average of 470.7 g of waste per injection compared to 175.1 g at our intervention site. This represents a 62.8% reduction (p<0.001). At Site B, where waste was sorted, a total of 50.1 kg of medical waste was generated from these injections during the study period of which 33.8kg (67.5%) was salvageable.

    Discussion: This is the first quantification of the medical waste associated with intravitreal injections, a burgeoning treatment for macular degeneration and diabetic retinopathy amongst other conditions. This study demonstrates a significant reduction in the amount of medical waste produced using an easily implementable real-world methodology. This article is protected by copyright. All rights reserved.

    DOI: 10.1111/ceo.14187


    Lipid profile and future risk of exudative age-related macular degeneration development: a nationwide cohort study from South Korea.

    Science Reports. 2022 Nov 5

    Hwang S, Kang SW, Choi J, Son KY, Lim DH, Shin DW, Kim K, Kim SJ.

    This nationwide population-based cohort study evaluated the association between lipid profiles and the future risk of exudative age-related macular degeneration (AMD) using authorized clinical data provided by the Korean National Health Insurance Service. A total of 6,129,616 subjects over 50 years of age who participated in the Korean National Health Screening Program in 2013 or 2014 were included. Data on risk factors, including age, sex, comorbidities, behavioral factors, and baseline lipid profiles, including total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels were collected. Patients were followed-up patients until December 2018, and incident cases of exudative AMD were identified using registered diagnostic codes. During an average follow-up period of 4.91 years, 18,803 patients were newly diagnosed with exudative AMD. Compared to the lowest HDL cholesterol quartile group, the highest HDL cholesterol quartile group had a greater risk of future exudative AMD development with a hazard ratio (95% confidence interval) of 1.13 (1.08-1.18) in the fully adjusted model. The highest TG quartile group had a lower risk of exudative AMD than the lowest TG quartile group, with a hazard ratio (95% confidence interval) of 0.84 (0.81-0.88). High HDL cholesterol and low TG levels were prospectively associated with exudative AMD incidence.

    DOI: 10.1038/s41598-022-23607-w


    Impact of intravitreal ranibizumab, aflibercept and bevacizumab on retinal ganglion cell and nerve fibre layer thickness in Neovascular age-related macular degeneration.

    Acta Ophthalmologica. 2022 Nov 8

    Abu Dail Y, Seitz B, Sideroudi H, Abdin AD.

    Purpose: To compare the effects of monotherapy with intravitreal ranibizumab, aflibercept and bevacizumab on retinal ganglion cell layer (RGCL) and retinal nerve fibre layer (RNFL) in patients with naïve neovascular age-related macular degeneration (nAMD).

    Methods: This is a retrospective cohort study with three-groups comparison. 83 patients and 97 eyes on continuous monotherapy with an intravitreal anti-vascular endothelial growth factor (anti-VEGF) were followed for 24 months and divided into three groups according to anti-VEGF (aflibercept: 25 eyes, ranibizumab: 34 eyes, bevacizumab: 38 eyes). Main outcome measures included: RGCL and RNFL thickness, best corrected visual acuity (BCVA), central macular thickness (CMT), macular volume (MV) and the presence of intraretinal fluids (IRF), subretinal fluids (SRF) and retinal pigment epithelial atrophy (RPE-atrophy). All outcome measures were recorded at the time of the first injection, 1 and 2 years after treatment and compared longitudinally and between groups.

    Results: The mean age was 79 ± 7 years. The RGCL thickness, MV, CMT and the presence of IRF and SRF decreased significantly within all three medication groups (p < 0.05 for all) with no significant difference between groups over the 2-year follow-up period (p > 0.10 for all). The decrease in RNFL thickness was not significant within or between the groups after a 2-year follow-up (p > 0.055 for all). RPE-atrophy increased significantly after 2 years in all three groups (p < 0.028 for all) with no significant difference between groups at all three time points (p > 0.307 for all). BCVA was comparable between the three groups over the 2-year follow-up period (p > 0.22 for all).

    Conclusions: Monotherapy with intravitreal aflibercept, bevacizumab and ranibizumab was associated with comparable significant decreases in RGCL thickness, CMT, MV, IRF and SRF in naïve nAMD patients during the first 2 years of treatment. Furthermore, no significant differences either in BCVA or RNFL thickness were observed between the three intravitreal anti-VEFGs during the first 2 years of treatment.

    DOI: 10.1111/aos.15283

    Metformin therapy as a strategy to compensate anti-VEGF resistance in patients with diabetic macular edema.

    Medicine (Baltimore). 2022 Oct 21

    Uwimana A, Ma C, Chen S, Ma X.

    Diabetic macular edema (DME) is the complication of diabetic retinopathy, the leading cause of vision loss among diabetic patients. Metformin is the main antidiabetic treatment. It is preferable for its great anti-angiogenic and anti-inflammatory effects. Anti-vascular endothelial growth factor (VEGF) therapy is the preferable treatment for DME despite its lack of convincing results in some patients. To assess whether the combination of metformin and anti-VEGF drugs may decrease the risk of anti-VEGF resistance among DME patients. We included DME patients with a central retinal thickness (CRT) ≥ 250 μm who consecutively underwent at least 3 anti-VEGF therapies from January 1, 2020, to December 30, 2021. Anti-VEGF resistance was defined as persistent macular edema with decreased CRT ≤ 25% after 3 anti-VEGF injections. 109 patients were considered for this research, of whom 65 (59.6%) were resistant to anti-VEGF therapy. The mean CRT of the non-metformin group decreased from 344.88 ± 129.48 to 318.29 ± 123.23 (20.85%) and from 415.64 ± 144.26 to 277.11 ± 99.25 (31.51%) (P = .031) in the metformin group. Moreover, the metformin group had fewer resistant patients than the non-metformin, 24 (45.3%) versus 41 (73.2%). Furthermore, a considerable gain in visual acuity was observed in both groups, with a BCVA gain of 40.41% in the metformin group and 39.9% in the non-metformin group. Metformin may be combined with an anti-VEGF drug to minimize the risk of anti-VEGF resistance among DME patients. Moreover, it can serve to design effective therapeutic deliveries.

    DOI: 10.1097/MD.0000000000031266


    A five-year follow-up of ABCA4 carriers showing deterioration of retinal function and increased structural changes.

    Molecular Vision. 2022 Oct 1

    Kjellström U, Andréasson S.

    Purpose: To investigate whether the reduced retinal function and morphological retinal changes previously demonstrated in ABCA4 carriers had remained stationary or had deteriorated over time at 5-year follow-up to further explore if carriers of an autosomal recessive trait also express a weak phenotype, although this is not expected for an autosomal recessive disorder.

    Methods: Thirteen ABCA4 carriers from a previous study that included parents to patients with well known genetically verified ABCA4-associated retinal degenerations were reexamined 5 years after the initial examination. As novel genes and new variants in already established genes are continuously reported, all subjects underwent renewed genetic testing with a next-generation sequencing (NGS) panel that included 288 genes associated with retinal dystrophies and an analysis of deep intronic mutations and copy number variations in the ABCA4 gene. Moreover, to evaluate any changes in retinal function and/or structure over time, clinical reassessment with Goldmann perimetry, visual acuity testing, fundus photography, fundus autofluorescence (FAF) imaging, optical coherence tomography (OCT), full-field electroretinography (ffERG), and multifocal ERG (mfERG) were performed 5 years after the initial investigation. The values of the ffERG parameters were compared between the two time points (the measurements obtained in the initial study versus the measurements at 5-year follow-up) and with the controls. The mfERG results of the carriers were compared with those of the controls.

    Results: The renewed genetic testing confirmed the previously established ABCA4 mutations but also revealed the hypomorph ABCA4 variant c.5603A>T in five ABCA4 carriers. In three of them, the variant was found to be associated with known disease-causing alleles that always carry the c.5603A>T in cis. According to recent publications, the subjects could still be considered ABCA4 carriers because both variants are on the same allele. In the remaining two subjects, c.5603A>T could be in trans with the previously known ABCA4 variant, and the subjects were therefore excluded from the study since they could no longer be considered as carriers only. Statistical comparison of ffERG parameters showed significant reduction of the isolated rod, -as well as the combined rod-cone amplitudes over the five years of follow-up, but not compared with the controls. Concerning macular function, mfERG amplitudes were reduced for all rings in the carriers compared with the controls. Fundus photographs demonstrated morphological changes in 64% of the carriers, and 36% of them had further changes at follow-up. FAF images showed alterations in 55% of the carriers, with increased changes in 36% of them. Abnormalities on OCT were observed in 82% of the carriers, of whom 9% had newly found abnormalities at follow-up.

    Conclusions: At 5-year follow-up, the ABCA4 carriers, who previously demonstrated reduced macular function, presented with deterioration of general retinal function, including reduced isolated rod and mixed rod-cone ffERG responses combined with a slight increase in morphological changes in some subjects. This indicates that carriership of at least some ABCA4 variants may cause a condition similar to a subgroup of dry age-related macular degeneration (AMD). In the long run, this might be of importance concerning the possibilities to also treat this subgroup of AMD patients with future gene-based and pharmacological drugs targeting ABCA4-associated disorders.

    PMCID: PMC9603925


    Prevalence of Age-Related Macular Degeneration in the US in 2019.

    JAMA Ophthalmology. 2022 Nov 3

    Rein DB, Wittenborn JS, Burke-Conte Z, Gulia R, Robalik T, Ehrlich JR, Lundeen EA, Flaxman AD.

    NORC, University of Chicago, Chicago, Illinois. Institute for Health Metrics and Evaluation, University of Washington, Seattle. Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor. (4)Institute for Social Research, University of Michigan, Ann Arbor. Vision Health Initiative, Division of Diabetes Translation, US Centers for Disease Control and Prevention, Atlanta, Georgia.

    Importance: Age-related macular degeneration (AMD) is a leading cause of vision loss and blindness. AMD prevalence has not been estimated for the US in over a decade and early-stage AMD prevalence estimates are scarce and inconsistently measured.

    Objective: To produce estimates of early- and late-stage AMD prevalence overall and by age, gender, race and ethnicity, county, and state.

    Design, setting, and participants: The study team conducted a bayesian meta-regression analysis of relevant data sources containing information on the prevalence of AMD among different population groups in the US. DATA SOURCES: We included data from the American Community Survey (2019), the National Health and Nutrition Examination Survey (2005-2008), US Centers for Medicare & Medicaid Services claims for fee-for-service beneficiaries (2018), and population-based studies (2004-2016). STUDY SELECTION: We included all relevant data from the US Centers for Disease Control and Prevention’s Vision and Eye Health Surveillance System.

    Data extraction and synthesis: The prevalence of early- and late-stage AMD was estimated and stratified when possible by factors including county, age group, gender, and race and ethnicity. Data analysis occurred from June 2021 to April 2022.

    Main outcomes or measures: The prevalence of early- (defined as retinal pigment epithelium abnormalities or the presence of drusen 125 or more microns in diameter in either eye) and late-stage (defined as choroidal neovascularization and/or geographic atrophy in either eye) manifestations of AMD.

    Results: This study used data from nationally representative and local population-based studies that represent the populations in which they were conducted. For 2019, we estimated that there were 18.34 million people 40 years and older (95% uncertainty interval [UI], 15.30-22.03) living with early-stage AMD, corresponding to a crude prevalence rate of 11.64% (95% UI, 9.71-13.98). We estimated there were 1.49 million people 40 years and older (95% UI, 0.97-2.15) living with late-stage AMD, corresponding to a crude prevalence rate of 0.94% (95% UI, 0.62-1.36). Prevalence rates of early- and late-stage AMD varied by demographic characteristics and geography.

    Conclusions and relevance: We estimated a higher prevalence of early-stage AMD and a similar prevalence of late-stage AMD as compared with earlier studies. State-level and county-level AMD estimates may help guide public health practice.

    DOI: 10.1001/jamaophthalmol.2022.4401


    Retinal telangiectasia-like lesions in a 15-year-old female with Hereditary hemorrhagic telangiectasia – a case report.

    BMC Ophthalmology. 2022 Nov 7

    Ala A, Sørensen TL, Laugesen CS.

    Background: Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome is a bleeding disorder that can affect all parts of the body including the eyes. Different ocular abnormalities have been described in relation to HHT, but the pathogenesis of retinal involvement is still unknown. A few cases have described chorioretinal abnormalities primarily occurring in elderly patients. In this study, we present a unique case of a young female with known HHT and a series of retinal fundus images including optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) with macular telangiectasia-like lesions.

    Case presentation: A young female genetically diagnosed with hereditary hemorrhagic telangiectasia (HHT), is regularly attending retinal screening since she is diagnosed with Type 1 diabetes. At one visit, abnormal retinal telangiectasia-like lesions in the macula, are observed. These abnormalities are monitored over an extended period of time with fundus imaging, and further investigated with OCT and OCTA. The patient has no visual complaints at any time and best-corrected visual acuity is 20/20 Snellen equivalent in both eyes.

    Conclusions: To the best of our knowledge, this is the first case to describe the occurrence of telangiectasia-like lesions in macula with secondary choriocapillaris atrophy in a patient diagnosed with HHT in such a young age.

    DOI: 10.1186/s12886-022-02658-7


    Outcome of cataract surgery in patients with retinitis pigmentosa.

    American Journal of Ophthalmology. 2022 Oct 14.

    Nguyen XT, Thiadens AAHJ, Fiocco M, Tan W, McKibbin M, Klaver CCCW, Meester-Smoor MA, Van Cauwenbergh C, Strubbe I, Vergaro A, Pott JR, Hoyng CB, Leroy BP, Zemaitiene R, Khan KN, Boon CJF.

    Purpose: To assess the visual outcome of cataract surgery in patients with retinitis pigmentosa (RP).

    Design: Retrospective, non-comparative clinical study.

    Methods: Preoperative, intraoperative and postoperative data of patients with RP undergoing cataract surgery were collected from several expertise centers across Europe. RESULTS: In total, 295 eyes of 225 patients were included in the study. The mean age at surgery of the first eye was 56.1 ± 17.9 years. Following surgery, best-corrected visual acuity (BCVA) improved significantly from 1.03 to 0.81 logMAR (i.e. 20/214 to 20/129 Snellen) in the first treated eye (-0.22 logMAR; 95% CI: -0.31 to -0.13; p < 0.001), and from 0.80 to 0.56 logMAR (i.e. 20/126 to 20/73 Snellen) in the second treated eye (-0.24 logMAR; 95% CI: -0.32 to -0.15; p < 0.001). Marked BCVA improvements (postoperative change in BCVA of ≥ 0.3 logMAR) were observed in 87 out of 226 patients (39%). Greater odds for marked visual improvements were observed in patients with moderate visual impairment or worse. The most common complications were zonular dialysis (n = 15; 5%), and (exacerbation of) cystoid macular edema (n = 14; 5%), respectively. Postoperative posterior capsular opacifications were present in 111 out of 295 (38%) eyes.

    Conclusion: Significant improvements in BCVA are observed in most patients with RP following cataract surgery. Baseline BCVA is a predictor for visual outcome. Preoperative evaluation should include the assessment of potential zonular insufficiency and the presence of CME, as they are relatively common, and may increase the risk for complications.

    DOI: 10.1016/j.ajo.2022.10.001


    C1q and the classical complement cascade in geographic atrophy secondary to age-related macular degeneration.

    International Journal of Retina and Vitreous. 2022 Nov 8

    Yednock T, Fong DS, Lad EM.

    Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is a retinal neurodegenerative disorder. Human genetic data support the complement system as a key component of pathogenesis in AMD, which has been further supported by pre-clinical and recent clinical studies. However, the involvement of the different complement pathways (classical, lectin, alternative), and thus the optimal complement inhibition target, has yet to be fully defined. There is evidence that C1q, the initiating molecule of the classical pathway, is a key driver of complement activity in AMD. C1q is expressed locally by infiltrating phagocytic cells and C1q-activating ligands are present at disease onset and continue to accumulate with disease progression. The accumulation of C1q on photoreceptor synapses with age and disease is consistent with its role in synapse elimination and neurodegeneration that has been observed in other neurodegenerative disorders. Furthermore, genetic deletion of C1q, local pharmacologic inhibition within the eye, or genetic deletion of downstream C4 prevents photoreceptor cell damage in mouse models. Hence, targeting the classical pathway in GA could provide a more specific therapeutic approach with potential for favorable efficacy and safety.

    DOI: 10.1186/s40942-022-00431-y