Impact of the COVID-19 pandemic’s first wave on the care and treatment situation of intravitreal injections in a German metropolitan region

Purpose This study aims to evaluate the impact of the first coronavirus 2019 (COVID-19) wave in 2020 on patients scheduled for intravitreal injections (IVI) in a German metropolitan region. Methods We performed a multicentre prospective survey and retrospective analysis of the records of patients treated with intravitreal injections during the 20-week period from March to July 2020 in all four hospital eye departments in the city of Hamburg using a questionnaire (on treatment adherence, SarsCoV2-related personal, familial and social data) and treatment data. Results A total of 1038 patients (2472 IVI, 1231 eyes) and 818 questionnaires were evaluated. Longer duration of therapy, lower visual acuity (VA) of the treated and higher VA of the fellow untreated eye was were associated with a higher probability of visit cancellation. Every additional year of life posed a 2.6% lower risk of noncompliance. A COVID-19 infection in the family environment displayed a 5.5-fold chance of visit cancellation. Patients treated for neovascular age-related macular degeneration (nAMD) had a 36% reduced risk of visit cancellation compared to patients with diabetic macular oedema (DME). Conclusion A long preceding treatment period, low VA of the treated eye, high VA of the untreated eye, COVID-19 in the family and DME were identified as risk factors for IVI visit cancellations during the COVID-19 pandemic. Compliance to treatment might be improved in the future by taking these risk factors into account when scheduling patients for IVI during the exceptional circumstances of a pandemic.

On elevation of intraocular pressure after intravitreal injections

The aim of this work is to emphasize the need to take into account several important biomechanical factors (biometrical parameters of patient, s eyes accuracy of tonometers) as well as the design of the procedure when interpreting clinical data of immediate IOP elevation after intravitreal injections

Treatment results of nondamaging retinal laser therapy in diabetic macular edema

Background: Subthreshold nondamaging retinal laser therapy (NRT) provides a greater safety profile than conventional laser methods, but more data is needed on the efficacy and safety of subthreshold NRT in diabetic macular edema. Purpose: To evaluate the efficacy and safety of NRT for the treatment of clinically significant macular edema (CSME) that is partially responsive or resistant to intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment. Methods: This was a retrospective case series study. Fifty eyes of 38 diabetic patients with CSME previously treated with at least 6-monthly intravitreal bevacizumab injections with/without intravitreal Ozurdex therapy were evaluated. The patients received 577-nm yellow wavelength laser therapy with PASCAL laser system (Topcon Medical Laser Systems, Santa Clara, CA, USA). Best-corrected visual acuity (BCVA) and central subfield thickness (CST) were evaluated before and 1, 3, 6, 12 and 24 months after laser treatment. Results: Baseline mean CST was 368.06 ± 86.9 µm. The mean CST values at the 1-, 3-, 6-, 12-, and 24-month visits were 336.93 ± 79.8, 352.40 ± 113.5, 336.36 ± 109.3, 325.10 ± 104 µm, and 310.08 ± 84.7 µm, respectively. The mean CST decreased significantly at the first ( p = 0.002) and second year visits ( p < 0.001) when compared with pretreatment values. Although visual acuity was improved at the first year compared with baseline, this difference was not statistically significant ( p = 0.03). There was no significant difference in visual acuities between pretreatment and posttreatment visits. During 24-month follow-up, while 37 eyes were treated with [mean: 5.7 ± 3.4 (1–14)] intravitreal anti-VEGF injections, 3 eyes were administered single-dose intravitreal steroids. Additional intravitreal injections were not required in 10 (20%) eyes. Conclusion: NRT is effective by itself or in combination with anti-VEGF agents in diabetic macular edema that is partially responsive or resistant to previous intravitreal injections. T role in treating this disorder should be assessed in more detail with prospective controlled studies.

Treatment of Bilateral Endogenous Aspergillus Endophthalmitis with Multiple Intravitreal Voriconazole Injections with Good Visual Outcome

Endogenous endophthalmitis caused by <i>Aspergillus</i> species tends to be very aggressive, often leading to devastating visual outcomes. Historically, intravitreal amphotericin injections have played a central role in management, but with variable visual outcomes and a risk of toxicity. Limited reports suggest that use of intravitreal voriconazole is a safe and efficacious alternative, though these cases were treated with only few intravitreal injections. Here, we report a case of bilateral endogenous <i>Aspergillus</i> endophthalmitis treated with 8 intravitreal voriconazole injections in the right eye and 11 in the left eye with good best-corrected final visual outcome (20/50 right eye and 20/40 left eye).

The Effects of Intravitreal Agents on Systemic Vascular Diseases in Patients with Diabetic Retinopathy

Purpose: To assess the risk for cerebrovascular desease (CVD) and coronary artery disease (CAD) in diabetic patients who were treated with intravitreal anti-VEGF agents and compare the rates of CVD and CAD with diabetic controls. Methods: A retrospective chart review of diabetic patients was performed. The need for intravitreal injection and type of agent were noted. If clinically significant or center-involving diabetic macular edema (DME) were determined, intravitreal anti-VEGF agents were used. The CVD and/or CAD occurred within 6 months of the intravitreal injection were accepted as the main outcomes of the study. The records of diabetic patients who were followed up but not needed intravitreal injections were accepted as the control group of the study. Comparisons between these groups were performed.Results: The number of patients enrolled in the study was 9751 (5243 female, 4508 male patients). Of these patients, 1261 patients were received various intravitreal injections. Patients who had CVD history were divided into two groups according to whether they received intravitreal injection or not. There was statistically significant difference between these groups in terms of CVD history (p<0,001). There was statistically significant difference in the hazard of CVD between different anti-VEGF treatments (p<0,001). Patients who had CAD history were divided into two groups according to whether they received intravitreal injection or not. There was no statistically significant difference between these groups in terms of CAD history (p=0,31). Discussion: The risk for CVD was seen to increase with the intravitreal anti-VEGF treatment in diabetic patients. The rate of CVD was higher in patients who received intravitreal bevacizumab treatment.

Intravitreal injections as a leading cause of acute postoperative endophthalmitis—a regional survey in England

Background To evaluate the characteristics, treatment patterns and outcomes of acute postoperative endophthalmitis. Methods Patients presenting with acute postoperative endophthalmitis between January 2017 to December 2019 were identified from hospital records in this multicentre retrospective cohort study. Clinical records were reviewed for visual acuity (VA) at various timepoints, cause of endophthalmitis, microbiological results, treatments and complications. Results Forty-six eyes of 46 patients were included. Intravitreal injections were the leading cause of acute postoperative endophthalmitis (n = 29; 63%), followed by cataract surgery (n = 8; 17%), vitreoretinal surgery (n = 7; 15%), and secondary intraocular lens insertion (n = 2, 4%). The absolute risk of endophthalmitis was 0.024% (1:4132) for intravitreal injections, 0.016% (1:6096) for cataract surgery, and 0.072% (1:1385) for vitreoretinal surgery. The majority of patients (n = 38; 83%) had better VA at 6 months compared to presentation, although fewer (n = 13; 28%) maintained similar or better VA compared to before the precipitating surgery. Twenty-four cases yielded positive culture results, of which staphylococcus epidermidis was the most commonly isolated organism. Microbiological yield was not associated with better final visual outcomes. Patients who underwent therapeutic vitrectomy (n = 15; 33%) had poorer VA at presentation, but subsequently achieved visual outcomes comparable to those who received medical treatment alone. There was no difference in time to presentation, visual outcome and retinal detachment rates among the different causative procedures. Conclusion Intravitreal injections were the most common cause of endophthalmitis in our region, primarily because of their higher frequency compared to other intraocular procedures. In this cohort, the primary procedure had no effect on presentation, management or visual outcomes.

Pharmacokinetics of Pullulan–Dexamethasone Conjugates in Retinal Drug Delivery

The treatment of retinal diseases by intravitreal injections requires frequent administration unless drug delivery systems with long retention and controlled release are used. In this work, we focused on pullulan (≈67 kDa) conjugates of dexamethasone as therapeutic systems for intravitreal administration. The pullulan–dexamethasone conjugates self-assemble into negatively charged nanoparticles (average size 326 ± 29 nm). Intravitreal injections of pullulan and pullulan–dexamethasone were safe in mouse, rat and rabbit eyes. Fluorescently labeled pullulan particles showed prolonged retention in the vitreous and they were almost completely eliminated via aqueous humor outflow. Pullulan conjugates also distributed to the retina via Müller glial cells when tested in ex vivo retina explants and in vivo. Pharmacokinetic simulations showed that pullulan–dexamethasone conjugates may release free and active dexamethasone in the vitreous humor for over 16 days, even though a large fraction of dexamethasone may be eliminated from the eye as bound pullulan–dexamethasone. We conclude that pullulan based drug conjugates are promising intravitreal drug delivery systems as they may reduce injection frequency and deliver drugs into the retinal cells.