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    Research update: 513

    The latest research highlights for 5 October 2021


    Result of intravitreal aflibercept injection for myopic choroidal neovascularization

    BMC Ophthalmol. 2021 Sep 22;21(1):342. 

    Shih-Lin Chen, Pei-Ling Tang, Tsung-Tien Wu

    Background: The current study aimed to evaluate the efficacy of intravitreal aflibercept injections as the primary treatment for subfoveal/juxtafoveal myopic choroidal neovascularization (CNV) by using optical coherence tomography (OCT). Optical coherence tomography angiography (OCTA) was further used for some patients to detect the changes of CNV after treatment.

    Methods: In the present study, 21 treatment-naive eyes of 21 patients with subfoveal/juxtafoveal myopic CNV received primary intravitreal aflibercept injections and were under follow-up for a minimum duration of 12 months. Among the 21 patients, 12 underwent OCTA to evaluate the changes in central foveal thickness, selected CNV area, and flow area.

    Results: The mean best-corrected visual acuity (BCVA) pertaining to all the patients significantly improved from the baseline value of 0.7 to 0.3 logMAR after treatment for 12 months (P = 0.001). However, the improvements in the median BCVA after treatment for three and 12 months were not statistically significant in the younger group (< 50 years), compared to the older group (≥ 50 years). One aflibercept injection resolved the CNV in 47.6% (10/21) of the patients. The younger group displayed greater improvement in the median central foveal thickness, compared to the older group. OCTA revealed interlacing or disorganized pattern at the level of the outer retinal layer in 12 subjects with myopic CNV. After 3 months of treatment, both groups displayed a decrease in the size of the selected CNV area and flow area. The interlacing group displayed a trend towards better anatomical improvements.

    Conclusion: Intravitreal aflibercept injection provides long-term improvement in visual acuity in patients with myopic CNV. Eyes with the interlacing pattern on OCTA displayed a greater decrease in size and flow after aflibercept injection.

    DOI: 10.1186/s12886-021-02088-x

    Exploration of real-world outcomes and treatment patterns in patients treated with anti-vascular endothelial growth factors for neovascular age-related macular degeneration in Sweden

    Acta Ophthalmol. 2021 Sep 20.

    Marion Schroeder, Inger Westborg, Caroline Fluur, Rasmus Olsen, Monica Lövestam-Adrian 

    Purpose: To analyse and compare the number and interval of anti-vascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (nAMD), as well as the visual development in patients followed up for one to three years in clinical practice and during different index periods.

    Methods: This observational study included treatment-naïve eyes with nAMD from the Swedish Macula Register that started treatment between 2007 and 2017, stratified by different index periods (2007-2010, 2011-2013, 2014-2015 and 2016-2017) and by follow-up cohorts for each index period of one, two or three years (cohorts 1-3). Their intravitreal anti-VEGF treatment was assessed by number of injections, injection intervals, visual acuity (VA) and near VA change.

    Results: From the earliest index period 2007-2010 to the latest 2016-2017, the number of injections increased for the comparable follow-up time; 6.2 ± 1.4 versus 8.3 ± 2.0 injections after 1 year of treatment, 4.8 ± 1.6 versus 6.7 ± 2.4 during year 2. The last injection interval was 73 ± 34 days after 1, 71 ± 33 after 2 and 67 ± 32 after 3 years of follow-up for the index period 2014-2015. For the same period, the percentage of eyes with at least two consecutive 12-16 weeks of injection interval over 1-, 2- and 3-year follow-up increased from 5.2%, 15.0%, to 17.5% respectively. Baseline VA for eyes indexed 2016-2017 increased and presented with 62.1 ± 13.4 letters compared with 57.7 ± 13.5 letters in 2007-2010; p < 0.0001.

    Conclusions: From the earliest to the latest index periods, the number of injections increased for the comparable follow-up time. Accordingly, baseline VA and near VA and their outcomes improved continuously.

    DOI: 10.1111/aos.15025

    Comparison of Intravitreal Dexamethasone Implant and Ranibizumab in Vitrectomized Eyes with Diabetic Macular Edema

    J Ophthalmol. 2021 Sep 10;2021:8882539.

    Jia-Kang Wang , Tzu-Lun Huang, Pei-Yao Chang, Wei-Ting Ho, Yung-Ray Hsu , Fang-Ting Chen, Yun-Ju Chen 

    Purpose: This retrospective study aimed to compare the efficacy of intravitreal ranibizumab (IVR) and intravitreal dexamethasone implant (IDI) for pseudophakic vitrectomized eyes with diabetic macular edema (DME) in a single institution.

    Methods: Pseudophakic vitrectomized eyes with treatment-naïve center-involved DME were enrolled, with one eye in each patient. They were divided into two groups: one group receiving IDI every 3 to 4 months and another group receiving IVR using 3 monthly plus treat-and-extend injections, all with monthly follow-up for 6 months. Switch of intravitreal drugs or deferred macular laser was not allowed. Primary outcome measures included change in central foveal thickness (CFT) in 1 mm by spectral-domain optical coherence tomography and best-corrected visual acuity (BCVA) at Month 6.

    Results: Twenty-two eyes were included in the IDI group and 26 eyes in the IVR group. The baseline demographics, glycosylated hemoglobin level, intraocular pressure (IOP), BCVA, and CFT did not significantly differ (p > 0.05). Compared to baseline data, CFT decreased and BCVA improved significantly after either IDI or IVR at Month 6 (p < 0.05). Significantly better mean final BCVA (0.38 logMAR vs. 0.62 logMAR, p=0.04), more mean visual gain (-0.30 logMAR vs. -0.15 logMAR, p=0.02), lower mean final CFT (310.9 μm vs. 384.2 μm, p=0.04), and larger mean CFT decrease (-150.0 μm vs. -60.1 μm, p=0.03) were found in the IDI group compared to those in the IVR group. A smaller mean treatment number (2.6 vs. 5.6, p < 0.001) and higher rate of postinjection ocular hypertension requiring topical hypotensive agent therapy (27.3% vs. 0%, p=0.0002) were demonstrated in the IDI group than those in the IVR group.

    Conclusion: We concluded that IDI and IVR can both effectively treat vitrectomized eyes with DME. Dexamethasone implants had significantly better visual/anatomical improvement, smaller treatment number, and higher rate of elevated IOP after injection than IVR in pseudophakic vitrectomized eyes with DME in a 6-month period.

    DOI: 10.1155/2021/8882539


    Short-Term Results of Photobiomodulation Using Light-Emitting Diode Light of 670 nm in Eyes with Age-Related Macular Degeneration

    Photobiomodul Photomed Laser Surg. 2021 Sep;39(9):581-586.

    Rubens Camargo Siqueira, Laura Madureira Belíssimo, Tainara Souza Pinho, Lays Fernanda Nunes Dourado, Ana Paula Alves, Mayara Rodrigues Brandão de Paiva, Ubirajara Ajero, Armando da Silva Cunha 

    Objective: To evaluate the short-term result of retinal functional behavior in patients with dry age-related macular degeneration (AMD) corrected by photobiomodulation (PBM) with 670 nm light-emitting diode (LED) light.

    Materials and methods: Ten patients with dry AMD underwent a treatment consisting of nine PBM sessions with LED light of 670 nm with two cycles of 50 mW/cm2, producing 4 J/cm2 per dose in 88 sec. The studied eye was compared with the baseline (before therapy), and after nine PBM sessions, the following aspects were evaluated: best-corrected visual acuity (VA), retinal sensitivity, and characteristics of the correction area by the fundus automated perimetry using the Compass system. A functional and structural assessment of the retina was also performed using the multifocal electroretinography (ERG), optical coherence tomography (OCT), fluorescence retinography (FR), and autofluorescence (AF). All examinations were performed 1, 4, and 16 weeks after the therapy. The Chi-square and Student’s t-tests were used for comparisons. The analyses followed the 95% confidence level (p-value ≤0.05).

    Results: The BCVA significantly improved, from an average of 1.1 to 0.98 LogMAR (p = 0.01). The visual field examination, according to the parameters of mean deviation, standard deviation, and index of deviation of background perimeter, showed a significant improvement of -12.6% to -10.6%, 10.54% to 9.89%, and 56% to 60%, respectively (p = 0.02, 0.03, and 0.02, respectively). No participant had an adverse effect during the follow-up period; neither did any participant experience abnormalities in OCT, ERG, FR, and AF findings.

    Conclusions: In this short-term study, the PBM technique in patients with dry AMD showed the potential to improve VA and macular perimetry without causing significant adverse events. A larger number of patients and a longer follow-up will be necessary to further assess the success of this technique in these patients.

    DOI: 10.1089/photob.2021.0005


    Choroidal Imaging Biomarkers to Predict Highly Responsive and Resistant Cases Treated with Standardised Anti-Vascular Endothelial Growth Factor Regimen in Neovascular Age-Related Macular Degeneration 

    Retina. 2021 Oct 1;41(10):2115-2121.

    Mahima Jhingan , Melina Cavichini, Manuel Amador, Kunny Dans, Dirk-Uwe Bartsch, Lingyun Cheng, Jay Chhablani, William R Freeman 

    Purpose: To determine structural predictors of treatment response in neovascular age-related macular degeneration analyzing optical coherence tomography (OCT)-related biomarkers.

    Methods: A retrospective review of patients undergoing treatment for neovascular age-related macular degeneration at a tertiary institute was performed at presentation. High-intensity regimen included eyes on long-term anti-vascular endothelial growth factor treatment with the inability to extend beyond a month without a relapse and needed double the dose of medication (n = 25). Low-intensity regimen had eyes that went into long-term remission after at least three injections and remained dry for more than a year until the last visit (n = 20). Multimodal imaging including fluorescein angiogram, OCT, and comprehensive ocular evaluation were done. Choroidal vascularity index, total choroidal area, luminal area, subfoveal choroidal thickness, choriocapillaris thickness and Haller and Sattler layer thickness were analyzed for statistical significance.

    Results: The groups had no significant difference at baseline in age, gender, incidence of reticular pseudodrusen, polypoidal choroidal vasculopathy feature on OCT, type of choroidal neovascular membrane, and geographic atrophy. Multinomial logistic regression revealed that thicker subfoveal choroidal thickness and larger total choroidal area were the significant predictors of poor response to anti-vascular endothelial growth factor treatment (E = 0.02; P = 0.02; E = 1.82; P = 0.0075).

    Conclusion: Thicker subfoveal choroidal thickness and higher total choroidal area are useful variables to predict a poor treatment response.

    DOI: 10.1097/IAE.0000000000003156

    Optical coherence tomography angiography features of macular neovascularization in wet age-related macular degeneration: A cross-sectional study

    Ann Med Surg (Lond). 2021 Sep 8;70:102826.

    Mahjoub Ahmed, Ben Mrad Syrine, Ben Abdesslem Nadia  , Mahjoub Anis, Zinelabidine Karim, Ghorbel Mohamed, Mahjoub Hachemi, Krifa Fethi, Knani Leila 

    Background: OCT-A is a recent imaging technique allowing a non-invasive assessment of the retinal and choroidal microvasculature, providing valuable data for the diagnosis and monitoring of wet AMD. We aim to determine the diagnosis accuracy, describe the morphological features, and assess the clinical activity of MNV in wet AMD using OCT-A.

    Materials and methods: We conducted a descriptive cross-sectional study over a 15-month period. We enrolled patients with treatment-naive and treated MNV secondary to wet AMD. Macular OCT-A images were obtained using a swept-source OCT-A device (Triton SS-OCT, Topcon, Tokyo, Japan). Morphologic characteristics and semi-automated measurements were analyzed on the en face projection OCT-Angiograms. For the qualitative analysis, determined the sensitivity of detection of the MNV using OCTA. When detected, we described its shape, branching pattern, anastomoses and loops, and vessel termination. We looked for the halo sign and the feeder vessel. We then defined the lesion’s “pattern” reflecting its exudative activity. For the quantitative analysis, we measured the lesion’s area in square millimeters, when its borders were clearly defined.

    Results: 70 eyes from 55 patients were enrolled in this study. Type 1 MNV was identified in 57,1% eyes, type 2 in 21,4%, mixed type 1 and2 in 1,4%, type 3 in 1,4% and unclassified fibrotic MNV in 18,6%. 55,7% were active and 44,3% were inactive. Sensitivity of detection was 85% for type 1 lesions, 100% for type 2, mixed and type 3 lesions, and 92% for unclassified fibrotic lesions. It was 84,6% for active lesions and 96,8% for inactive lesions. For each detected lesion, shape was well-defined (medusa, glomerulus, seafan), long liner vessels or ill-defined. Branching pattern was dense or loose. Anastomoses and vascular loops were numerous or few. Termination was in an anastomotic arcade or in a dead-tree aspect. Halo sign was present or absent and feeder vessel was detected or not. All types combined, 41,3% of the lesions were “pattern I” and 58,7% were pattern II. We reported a correlation rate of 84,8% between the lesion’s activity on MI and « pattern I » on OCT-A, and of 96,6% between absence of activity signs on MI and « pattern II » on OCT-A The mean area of inactive lesions was slightly larger than that of active lesions with respective values of 3.86 mm2 and 2.92 mm2.

    Conclusion: OCT-A is a non-invasive, safe, and reproducible retinal imaging technique with a high sensitivity of detection of MNV in AMD. It provides useful qualitative and quantitative data. The involvement of OCT-A in the treatment decision for MNV in AMD is linked to identifying the “pattern” of the lesion reflecting its active or inactive status.

    DOI: 10.1016/j.amsu.2021.102826


    Macular Hold Associated with Age-Related Macular Degeneration: Pathogenesis and Surgical Outcomes

    Retina. 2021 Oct 1;41(10):2079-2087.

    Kyoung Lae Kim, Jeong Mo Han, Min Seok Kim, Sang Jun Park, Seong-Woo Kim, Jae Hui Kim, Min Kim  , Christopher Seungkyu Lee, Hyun Goo Kang, Joo Yong Lee, Se Joon Woo 

    Purpose: To ascertain the pathogenesis of macular hole (MH) associated with age-related macular degeneration (AMD) and its surgical outcomes.

    Methods: Patients with full-thickness MH associated with AMD (higher grades than intermediate) were enrolled. The mechanism of MH formation and closure rate after vitrectomy (surgical outcome) were determined using optical coherence tomography imaging.

    Results: The mechanism of MH formation (35 eyes) associated with AMD was classified into four types: vitreomacular traction (42.9%), gradual retinal thinning caused by subretinal drusen or pigment epithelial detachment (22.9%), massive subretinal hemorrhage (20.0%), and combined (14.3%). In the 41 eyes that underwent vitrectomy, the logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.82 (0.10-2.30) preoperative to 0.69 (0.10-2.30) postoperative (P = 0.001). Successful closure of the MH was achieved in 33 eyes (80.5%) after vitrectomy. No significant association was observed between the closure rate of MH after vitrectomy and mechanism of MH formation (P = 0.083).

    Conclusion: The mechanism of MH formation associated with AMD was classified into four types and was not related to its surgical outcome. Considering visual improvement and surgical outcome after vitrectomy in our study, active surgical treatment can be considered for MH associated with AMD.

    DOI: 10.1097/IAE.0000000000003148


    Global Burden of Dry Age-Related Macular Degeneration: A Targeted Literature Review

    Clin Ther. 2021 Sep 18;S0149-2918(21)00310-6.

    Neil M Schultz, Shweta Bhardwaj, Claudia Barclay, Luis Gaspar, Jason Schwartz 

    Purpose: Age-related macular degeneration (AMD) is a leading cause of blindness, particularly in higher-income countries. Although dry AMD accounts for 85% to 90% of AMD cases, a comprehensive understanding of the global dry AMD burden is needed.

    Methods: A targeted literature review was conducted in PubMed, MEDLINE, Embase, and the Cochrane Database of Systematic Reviews (1995-2019) to identify data on the epidemiology, management, and humanistic and economic burden of dry AMD in adults. A landscape analysis of patient-reported outcome (PRO) instruments in AMD was also conducted via searches in PubMed (1995-2019),, PROQOLID, PROLABELS, and health technology assessment reports (2008-2018).

    Findings: Thirty-seven of 4205 identified publications were included in the review. Dry AMD prevalence was 0.44% globally, varied across ethnic groups, and increased with age. Patients with dry AMD had higher risks of all-cause mortality (hazard ratio [HR] = 1.46; 95% CI, 0.99-2.16) and tobacco-related (HR = 2.86; 95% CI, 1.15-7.09) or cancer deaths (HR = 3.37; 95% CI, 1.56-7.29; P = 0.002) than those without dry AMD. Smoking, increasing age or cholesterol levels, and obesity are key risk factors for developing dry AMD. No treatment guidelines were identified for dry AMD specifically; management focuses on risk factor reduction and use of dietary supplements. In the United States and Italy, direct medical costs and health care resource utilization were lower in patients with dry versus wet AMD. Patients with dry AMD, particularly advanced disease, experienced significant visual function impairment. Dry AMD symptoms included reduced central vision, decreased ability to see at night, increased visual blurriness, distortion of straight lines and text, and faded color vision. Most PRO instruments used in AMD evaluations covered few, if any, of the identified symptoms reported by patients with dry AMD. Although the Quality of Life and Vision Function Questionnaire, 25-item National Eye Institute Vision Function Questionnaire, Low Vision Quality of Life, Impact of Vision Impairment-Very Low Vision, and Functional Reading Independence Index had strong content validity and psychometric properties in patients with dry AMD, they retained limited coverage of salient concepts.

    Implications: Despite dry AMD accounting for most AMD cases, there are substantial gaps in the published literature, particularly the humanistic and economic burden of disease and the lack of differentiation among dry, wet, or unspecified dry AMD. The significant burden of illness alludes to a high unmet need for tolerable and effective treatment options, as well as PRO instruments with more coverage of dry AMD symptoms and salient concepts.

    DOI: 10.1016/j.clinthera.2021.08.011

    Introduction of structured record keeping in age-related macular degeneration: a before and after study

    Clin Exp Optom. 2021 Sep 19;1-7.

    Angelica Ly, Barbara Zangerl, Michael Kalloniatis 

    Clinical relevance: Structured record keeping improves documentation in age-related macular degeneration; however, it may have a more limited effect on the management decisions of a group of already highly trained clinicians, especially in the context of other well-embedded clinical decision support tools.

    Background: Structured record keeping has been associated with a range of advantages including improved history taking and communication, reduced number of unnecessary referrals, and enhanced diagnostic accuracy. The aim of this study was to examine the impact of a structured record keeping, quality improvement tool on recording, reporting and management congruency.

    Methods: A before and after retrospective record review study was performed in a single academic, intermediate-tier care institute in New South Wales, Australia. The structured record keeping tool intervention captured 31 items in addition to the prior pre-existing medical record: six items relating to historical risk factors, two items relating to patient activation, 13 items signifying core clinical signs, five items for change analysis and five items regarding the ongoing patient management plan.

    Results: Two hundred medical records from 151 patients with age-related macular degeneration were analysed. There was a statistically significant improvement in the number of reports that explicitly specified the number of clinical structural risk factors (from 24 to 75%; Fisher’s exact p < 0.001) and risk of progression to advanced disease (from 71 to 84%; p = 0.041); however, this documentation had no statistically significant effect on the report-recommended management plan and/or the final report-recommended review period.

    Conclusion: Disease-specific, structured record keeping improves the outgoing documentation of key clinical signs and is effective in prompting the transposition of these signs into a quantified risk progression score. It has limited value in improving management consistency among a group of highly trained eye care staff.

    DOI: 10.1080/08164622.2021.1971490