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    Research update: 512

    The latest research highlights for 27 September 2021


    Non-immediate drug hypersensitivity reactions secondary to intravitreal anti-vascular endothelial growth factors

    Graefes Arch Clin Exp Ophthalmol. 2021 Sep 16.

    E Moret, A Ambresin, C Gianniou, J Bijon, C Besse-Hayat, S Bogiatzi, D Hohl, F Spertini, I Mantel  

    Purpose: To describe a series of non-immediate drug hypersensitivity reactions after intravitreal anti-vascular endothelial growth factors (anti-VEGFs).

    Patients and methods: Retrospective report of 6 patients with cutaneous non-immediate drug hypersensitivity reactions following intravitreal anti-VEGF injections, 4 after ranibizumab, 1 after bevacizumab and 1 after aflibercept.

    Results: Clinical manifestations ranged from mild maculopapular rash, purpura to severe generalized erythroderma, with or without systemic involvement such as microscopic hematuria and proteinuria or fever. In two out of the six patients, reintroduction of either the same or an alternative anti-VEGF drug did induce a recurrence of the drug hypersensitivity reaction, while 4 patients showed no recurrence.

    Conclusion: Cutaneous non-immediate drug hypersensitivity reactions secondary to intravitreal anti-VEGF may occur. Continuation of the same drug or switch to another anti-VEGF may either induce recurrence or be well supported by the patient. The decision of drug discontinuation should be guided by the severity of the disease.

    DOI: 10.1007/s00417-021-05353-3

    12-month outcomes of ranibizumab versus aflibercept for macular oedema in central retinal vein occlusion: data from the FRB! registry

    Acta Ophthalmol.2021 Sep 13.

    Mateusz Niedzwiecki, Adrian Hunt, Vuong Nguyen, Hemal Mehta, Catherine Creuzot-Garcher, Pierre-Henry Gabrielle, Martin Guillemin, Samantha Fraser-Bell, Jennifer Arnold, Ian L McAllister, Mark Gillies, Daniel Barthelmes  

    Purpose: To compare 12-month treatment outcomes of eyes receiving aflibercept or ranibizumab for macular oedema secondary to central retinal vein occlusion (CRVO) in routine clinical practice.

    Methods: 296 treatment-naïve eyes receiving either aflibercept (171 eyes, 2 mg) or ranibizumab (125 eyes, 0.5 mg) for macular oedema secondary to CRVO were recruited retrospectively from centres using the prospectively designed FRB! registry. The primary outcome measure was the mean change in LogMAR letter scores of visual acuity (VA). Secondary outcomes included change in central subfield thickness (CST), injections and visits, time to first grading of inactivity, switching and non-completion from baseline to 12 months.

    Results: Baseline VA (SD) was somewhat better in aflibercept- versus ranibizumab-treated eyes (42.5 ± 25.5 letters versus 36.9 ± 26 letters; p = 0.07) with similar CST (614 (240) μm versus 616 (234) μm: p = 0.95). The 12-month adjusted mean (95%CI) VA change was +16.6 (12.9, 20.4) letters for aflibercept versus +9.8 (5.5, 14.1) letters for ranibizumab (p = 0.001). The mean (95%CI) adjusted change in CST was significantly greater in aflibercept- versus ranibizumab-treated eyes: -304 (-276, -333) µm versus -252 (-220, -282) µm (p < 0.001). Both groups had a median (Q1, Q3) of 7 (5, 9) injections and 10 (8,13) visits. Aflibercept-treated eyes became inactive sooner than ranibizumab (p = 0.02). Switching occurred more commonly from ranibizumab (26 eyes, 21%) than from aflibercept (9 eyes, 5%) (p < 0.001).

    Conclusion: Both aflibercept and ranibizumab improved VA and reduced CST in eyes with CRVO in routine clinical practice, with aflibercept showing significantly greater improvements in this comparative analysis.

    DOI: 10.1111/aos.15014

    Inhibition of Complement C3 in Geographic Atrophy with NGM621: Phase 1 Dose-Escalation Study Results

    Am J Ophthalmol.2021 Sep 9;S0002-9394(21)00441-4. 

    Charles C Wykoff, Vrinda Hershberger, David Eichenbaum, Erin Henry, Husam S Younis, Priya Chandra, Nancy Yuan, Mark Solloway, Alex DePaoli  

    Purpose: To evaluate the safety and tolerability of single and multiple intravitreal injections of NGM621 in patients with geographic atrophy (GA) and to characterize the pharmacokinetics and immunogenic potential.

    Design: Multicenter, open-label, single- and multiple-dose phase 1 study.

    Methods: Fifteen patients enrolled at 4 sites in the United States. Participants had GA secondary to age-related macular degeneration, lesion size ≥2.5 mm2 and best-corrected visual acuity of 4 to 54 letters (20/80 to 20/800 Snellen equivalent) in the study eye and no history of choroidal neovascularization in either eye. Patients who met eligibility criteria were treated in a single ascending-dose phase (2 mg, 7.5 mg, 15 mg) or received 2 doses NGM621 15 mg 4 weeks apart in the multidose phase and were followed for 12 weeks (85 days). Assessments included adverse events, best-corrected visual acuity, low luminance visual acuity, vital signs, clinical laboratory evaluations, GA lesion area as measured by fundus autofluorescence, spectral domain optical coherence tomography, and pharmacokinetic, immunogenicity, and pharmacodynamic assessments.

    Results: All 15 participants completed the 12-week study. There were no serious adverse events and no drug-related adverse events, and no choroidal neovascularization developed in either eye. Mean visual acuity and GA lesion area appeared stable through week 12 for all cohorts. Pharmacokinetic analyses indicated that NGM621 serum exposures appeared to be dose proportional, and no antidrug antibodies were identified at any of the evaluated time points.

    Conclusions: In this small, open-labelled, 12-week phase 1 study, NGM621 was safe and tolerable when administered intravitreally up to 15 mg.

    DOI: 10.1016/j.ajo.2021.08.018


    Photobiomodulation Therapy for Age-Related Macular Degeneration and Diabetic Retinopathy: A Review

    Clin Ophthalmol.2021 Sep 2;15:3709-3720. 

    Justin C Muste, Matthew W Russell, Rishi P Singh 

    Purpose: Photobiomodulation therapy (PBT) has emerged as a possible treatment for age-related macular degeneration (AMD) and diabetic retinopathy (DR). This review seeks to summarize the application of PBT in AMD and DR.

    Methods: The National Clinical Trial (NCT) database and PubMed were queried using a literature search strategy and reviewed by the authors.

    Results: Fourteen studies examining the application of PBT for AMD and nine studies examining the application of PBT for diabetic macular edema (DME) were extracted from 60 candidate publications.

    Discussion: Despite notable methodological differences between studies, PBT has been reported to treat certain DR and AMD patients. DR patients with center involving DME and VA ≥ 20/25 have demonstrated response to treatment. AMD patients at Age-Related Eye Disease Study Stages 2-4 with VA ≥20/200 have also shown response to treatment. Results of major clinical trials are pending.

    Conclusion: PBT remains an emergent therapy with possible applications in DR and AMD. Further, high powered studies monitored by a neutral party with standard devices, treatment delivery and treatment timing are needed.

    DOI: 10.2147/OPTH.S272327


    The short-term compliance and concordance to in clinic testing for tablet-based home monitoring in age-related macular degeneration

    Am J Ophthalmol.2021 Sep 9;S0002-9394(21)00442-6. 

    Selwyn M Prea, George Y X Kong, Robyn H Guymer, Pyrawy Sharangan, Elizabeth K Baglin, Algis J Vingrys 

    Purpose: This study determines the short-term compliance to regular home monitoring of macular retinal sensitivity (RS) in intermediate age-related macular degeneration (iAMD). We also compare home-based outcomes with in-clinic outcomes determined using 1. the same tablet device under supervision and 2. the Macular Integrity Assessment (MaIA) microperimeter.

    Design: Single-centre longitudinal compliance and reliability study.

    Methods: Seventy-three participants with iAMD were trained to perform macular field testing with the Melbourne Rapid Fields-macular (MRF-m) iPad application. Volunteers were asked to retur 6 weekly tests from home, guided by audio instructions. We determined compliance to weekly testing and surveyed for factors that limited compliance. Test reliability (false positive, false negative) and retinal sensitivity (RS) were compared to in-clinic assays (MaIA). Data are shown as mean ±[standard deviation] or median[quartile 1-3 range]. Group comparisons were achieved with bootstrap to define the 95% confidence limits.

    Results: Fifty-nine participants submitted 6 home exams with a median inter-test interval of 8.0 [7.0-17] days. Compliance to weekly testing (7 days ±24 hours) was 55%. The main barrier to compliance was IT logistic reasons. Of 694 home exams submitted, 96% were reliable (FP<25%). The mean RS returned by the tablet was significantly higher (+3.2 dB, p<0.05) compared to the MaIA.

    Conclusions: Home monitoring produces reliable results that differ from in-clinic tests due to test design. This should not impact self-monitoring once an at-home baseline is established, but these differences will affect comparisons to in-clinic outcomes. Reasonable compliance to weekly testing was achieved. Improved IT support might lead to better compliance.

    DOI: 10.1016/j.ajo.2021.09.003


    Nonexudative morphologic changes of neovascularization on optical coherence tomography angiography as predictive factors for exudative recurrence in age-related macular degeneration

    Graefes Arch Clin Exp Ophthalmol.2021 Sep 13.

    Han Joo Cho, Jaemin Kim, Seung Kwan Nah, Jihyun Lee, Chul Gu Kim, Jong Woo Kim 

    Purpose: To evaluate morphologic changes of choroidal neovascularization (CNV) on optical coherence tomography angiography (OCTA) during the nonexudative period and to correlate the features and timing of recurrence in neovascular age-related macular degeneration. (AMD).

    Methods: Two hundred thirty-eight eyes with type 1 CNV were retrospectively reviewed. For cases with exudative recurrence, OCTA images were tracked for analysis between the recurrences. Qualitative parameters of morphologic changes of CNV on OCTA, including tiny branching vessels, anastomotic loops, peripheral vascular arcade, and perilesional halo, were correlated with the features of exudative recurrence.

    Results: Exudative recurrence was identified in 163 cases, and among them, nonexudative morphological changes in CNV were identified using OCTA in 45 cases. For the cases with nonexudative changes on OCTA, exudative recurrence eventually developed within 0.5-3.5 months (mean, 2.3 ± 2.0 months) after identifying morphologic changes OCTA. The following changes in CNV were revealed on OCTA: tiny branching vessels in 53.3% (24/45) of cases, anastomotic loops in 40.0% (18/45), peripheral vascular arcades in 44.4% (20/45), and perilesional halo in 35.6% (16/45). Among the morphologic parameters, development of tiny branching vessels was significantly associated with early exudative recurrence (1.5 ± 1.2 months, p = 0.019), higher incidence of intraretinal fluid (IRF) (p = 0.016), and subretinal or subretinal pigment epithelial hemorrhage (p = 0.023) at recurrence, compared with other morphologic changes.

    Conclusion: Development of tiny branching vessels of CNV on OCTA during the nonexudative period was associated with early exudative recurrence, including IRF or hemorrhage. Identifying the nonexudative changes of CNV on OCTA might predict exudative recurrence and provide additional parameters for monitoring neovascular AMD.

    DOI: 10.1007/s00417-021-05405-8

    The Diagnostic Capability of Swept Source OCT Angiography in Treatment-Naive Exudative Neovascular Age-Related Macular Degeneration

    J Ophthalmol.2021 Feb 16;2021:6695918. 

    Daniel Ahmed, Martin Stattin, Anna-Maria Haas, Stefan Kickinger, Maximilian Gabriel, Alexandra Graf, Katharina Krepler, Siamak Ansari-Shahrezaei  

    Purpose: To evaluate the capability of swept source-optical coherence tomography angiography (SS-OCTA) in the detection and localization of treatment-naive macular neovascularization (MNV) secondary to exudative neovascular age-related macular degeneration (nAMD).

    Methods: In this prospective, observational case series, 158 eyes of 142 patients were diagnosed with exudative nAMD using fluorescein (FA) and indocyanine green angiography (ICGA) and evaluated by SS-OCTA in a tertiary retina center (Rudolf Foundation Hospital Vienna, Austria). The main outcome measure was the sensitivity of SS-OCTA compared to the standard multimodal imaging approach. Secondary outcome measure was the anatomic analysis of MNV in relation to the retinal pigment epithelium.

    Results: En-face SS-OCTA confirmed a MNV in 126 eyes (sensitivity: 79.8%), leaving 32 eyes (20.2%) undetected. In 23 of these 32 eyes (71.9%), abnormal flow in cross-sectional SS-OCTA B-scans was identified, giving an overall SS-OCTA sensitivity of 94.3%. Eyes with a pigment epithelium detachment (PED) ≥ 300 μm had a smaller probability for correct MNV detection (p=0.015). Type 1 MNV showed a trend (p=0.051) towards smaller probability for the correct detection compared to all other subtypes. Other relevant factors for the nondetection of MNV in SS-OCTA were image artifacts present in 3 of 32 eyes (9.4%). SS-OCTA confirmed the anatomic localization of 93 in 126 MNVs as compared to FA (sensitivity: 73.8%). There was no influence of age, gender, pseudophakia, visual acuity, central foveal thickness, or subfoveal choroidal thickness on the detection rate of MNV.

    Conclusions: SS-OCTA remains inferior to dye-based angiography in the detection rate of exudative nAMD consistent with type 1 MNV and a PED ≥300 µm. The capability to combine imaging modalities and distinguish the respective MNV subtype improves its diagnostic value.

    DOI: 10.1155/2021/6695918


    Incidence of Newly Registered Blindness From Age-Related Macular Degeneration in Australia Over a 21-Year Period: 1996-2016

    Asia Pac J Ophthalmol (Phila). 2021 Sep 16.

    Rachael C Heath Jeffery, Syed Aqif Mukhtar, Derrick Lopez, David B Preen, Ian L McAllister, David A Mackey, Nigel Morlet, William H Morgan, Fred K Chen

    Purpose: Report the age-standardized annual incidence of blindness registration due to age-related macular degeneration (AMD) in Australia in patients aged 50 years and older. Frequencies of photodynamic therapy (PDT) and intravitreal therapy (IVT) were examined.

    Design: Retrospective observational study.

    Setting: Registry of the Association for the Blind of Western Australia with best-corrected visual acuity worse than 20/200 in the better-seeing eye.

    Participants: Registering as blind aged 50 years or over.

    Measures: Annual age-standardized incidence of blindness over 3 time periods: 1996-2001 (pre-PDT), 2002-2007 (PDT era) and 2008-2016 (IVT era). The rates of PDT and IVT usage were assessed.

    Results: Age-standardized annual incidence of blindness rose during the PDT era, reaching 72.5 cases per 100,000 person-years in 2004. The incidence declined from 2007 onwards, reaching 8.2 cases per 100,000 person-years in 2016 (IVT era). The age at AMD blindness registration increased from 82.7 to 84.9 and 83.7 to 86.0 years from the PDT era to the IVT era in both male and females (P < 0.001) respectively. Over the same time period, PDT usage increased in 2002 and declined in 2006, whereas IVT usage increased from 2009 by 3745 per year.

    Conclusion: The increase in new blindness registrations due to AMD coincided with public funding of verteporfin for PDT, whereas the subsequent decline occurred when bevacizumab was used off-label and ranibizumab and aflibercept were publicly funded. An understanding of the effect of retinal therapy on public health measures may inform improvements in the allocation of limited resources.

    DOI: 10.1097/APO.0000000000000415


    Case Report: Multimodal Imaging of Acute Idiopathic Maculopathy in a Chinese Woman

    Optom Vis Sci. 2021 Sep 14. 

    Ke Zhang , Jian Liu, Deyong Jiang, Frank L Myers, Liang Zhou

    Significance: Acute idiopathic maculopathy is a rare disease with the characteristics of sudden, severe, unilateral central vision loss after a flu-like illness. The prognosis is generally good, and poor vision usually results from complications such as choroidal neovascularization or subfoveal pigment degeneration. Multimodal imaging is helpful in the diagnosis and follow-up of this disease.

    Purpose: We report a case of acute idiopathic maculopathy and present multimodal imaging results in the diagnosis of this condition.

    Case report: A 37-year-old Chinese woman noted a central scotoma in her right eye a day after a prodrome of flu-like symptoms. Best-corrected visual acuity of the right eye was 20/40. Multimodal imaging was performed, and a diagnosis of acute idiopathic maculopathy was made. The variable clinical appearance of acute idiopathic maculopathy on autofluorescence, near-infrared reflectance, and optical coherence tomography (OCT) was shown. The patient’s vision spontaneously recovered to 20/20 two weeks after the onset of the disease, but macular sensitivity, as measured by microperimetry, did not return to normal until 1 month. Retrobulbar injection of triamcinolone was done at 3 weeks to prevent retinal pigment epithelium hyperplasia and choroidal neovascularization. Written informed consent was obtained from the patient.

    Conclusions: Our findings suggest that near-infrared reflectance corresponds to the change of the outer retina and retinal pigment epithelium on OCT and complements autofluorescence in the diagnosis and follow-up of acute idiopathic maculopathy. Fundus autofluorescence, near-infrared reflectance, and OCT are recommended as routine examinations in this disease.

    DOI: 10.1097/OPX.0000000000001777