Intravitreal therapy is widely recognized as a major milestone in ophthalmology being one of the most commonly performed ocular procedures (). The spread of coronavirus disease (COVID-19) still represents an important public health problem worldwide (; ). This novel virus infection, is causing a significant downsizing of non-urgent treatments provided for ocular disorders (; , ), including intravitreal therapy ().
Since diabetic retinopathy (DR) still remains the leading cause of blindness among working-age adults (), ophthalmologists should be aware of the potential negative effects of COVID-19 restrictions in the management of diabetic patients in the next months.
The global COVID-19 pandemic led many governments from different nations to adopt protective and strict measures to reduce its spread. In these unprecedented circumstances, many healthcare systems are overwhelmed and under stress.
In this scenario, there is an urgent need to support ophthalmologists who are treating patients with intravitreal injections in decision-making protocols. In order to provide continuity of care, and to reduce the risk of contamination, series of protection measures have been proposed (; ; ). Nevertheless, many patients cannot receive a prompt therapy due to all public health restriction measures. During COVID-19 outbreak Carnevali et al. proposed treatment priority levels to treat the most urgent patients, although a drop of 91.7% of the injections performed compared to the same period of 2019 was registered ().
Diabetic patients are considered at high risk for COVID-19 complications and should not be exposed to avoidable risks, including the injections procedure itself. However, continuation of care, where possible, is important to avoid irreversible vision loss.
For non-monocular patients with diabetic macular edema (DME), postponement (>4–6 months) of appointments has been proposed (). As recently reported, postponing treatment in patients with good visual acuity does not affect the prognosis at 1 year, regardless of whether the DME was treated or not (). Conversely, in patients with more advanced DR and worse visual acuity, a delay in treatments could cause irreversible visual loss (; ).
Anti-vascular endothelial growth factor (VEGF) injections represent generally a first-line therapy for several retinal disorders including DME (; ; ; ), but monthly injections are needed at least during the loading dose (). Of note, intravitreal dexamethasone (DEX) implant 0.7 mg (Ozurdex®, Allergan, Inc. Irvine, CA, United States) is considered a valid alternative for both refractory to anti-VEGF treatment eyes and treatment naïve ones (; ). Intravitreal DEX implant releases active ingredients within the vitreous chamber over a 3–6 months period, and its efficacy and safety in various retinal diseases have been proved in clinical trials and real-life studies (; ). Several authors also reported significant anatomical and functional effects of DEX implant in vitrectomized eyes in different conditions (; ; ). Corticosteroids have multiple levels of action, modifying tight junction integrity, inhibiting different molecules involved in vascular permeability and inflammation processes including interleukin-6, stroma-derived factor-1, Intercellular adhesion molecule-1, as well as VEGF ().
All these mechanisms of action work in aggregate, resulting in decreased macular edema and VEGF production, fibrin deposition, capillary leakage and migration of inflammatory cells (). There is evidence that oxidative stress, ischemia and inflammation promote the initiation and progression of DR (), further supporting the role of DEX implant in controlling the progression of the DME ().
Cataract progression and intraocular pressure rise are the most common side effects, but often rather easily manageable (; ). Additionally, several optical coherence tomography (OCT) biomarkers were identified as functional outcome predictors in DME eyes treated with DEX implant including the presence of submacular fluid, absence of hyperreflective intraretinal foci and integrity of the ellipsoid zone ().
On this background, a good selection of patients with DME who can benefit from observation or a single intravitreal DEX injection rather than monthly anti-VEGF injections, could be of great importance in reducing the burden of injections of clinics and hospitals. Treating eligible subjects with DME showing the previously mentioned OCT biomarkers, could indeed reduce the burden of care delivery for patients and health system. Considering that the IOP increase after the injection is typically noticed within the first 2 weeks, IOP lowering eye drops together with a post-injection visit should be taken into account for patients with high risk for glaucoma.
Almost one year is gone since the WHO declared the global pandemic and new more contagious virus variants are now emerging. Physicians may be dealing with this emergency status for the next 1 or 2 years.
In our opinion, by tailoring the treatment to patients in most need, equity can be considered the ethical value that support the decisionmaking by the treating provider.
Although an evidence-based clinical practice guideline for intravitreal injections is not yet available, we believe that these considerations about management of diabetic patients with DME, could be useful for ophthalmologists from most affected countries who will be under public health COVID-19 measures and restrictions for the next months. Saving costs, resources and time is an important goal for all health workers who are facing this common enemy in first line.
Statements
Author contributions
CI wrote the first draft of the manuscript. EP, GG, VS, and AC checked and revised the draft manuscript. All authors contributed read, revised, and approved the submitted version.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Summary
Keywords
COVID-19, intravitreal injection, diabetic macular edema, dexamethason implant, pandemic (COVID19)
Citation
Iovino C, Peiretti E, Giannaccare G, Scorcia V and Carnevali A (2021) Evolving Treatment Paradigm in the Management of Diabetic Macular Edema in the Era of COVID-19. Front. Pharmacol. 12:670468. doi: 10.3389/fphar.2021.670468
Received
21 February 2021
Accepted
10 March 2021
Published
12 April 2021
Volume
12 - 2021
Edited by
Mario Damiano Toro, Medical University of Lublin, Poland
Reviewed by
Sibel Demirel, Ankara University, Turkey
Dinah Zur, Tel Aviv Sourasky Medical Center, Israel
Updates
Copyright
© 2021 Iovino, Peiretti, Giannaccare, Scorcia and Carnevali.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Adriano Carnevali, adrianocarnevali@live.it
This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology
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