Burden Of Injections Research Articles

Extended Injection Intervals after Switching from Ranibizumab to Aflibercept in Macular Edema due to Central Retinal Vein Occlusion.

Purpose To assess treatment interval extension after switching from ranibizumab to aflibercept intravitreal injections in macular edema (ME) due to central retinal vein occlusion (CRVO) with an insufficient response or frequent recurrences to initial treatment. Methods CRVO eyes treated with ranibizumab injections on a treat-and-extend (TAE) basis with an insufficient response or frequent recurrences were switched to aflibercept. Primary endpoint was the change in injection intervals before and after the switch. Results Eleven eyes were included in this retrospective bicentric study. Before switching, patients received a mean number of 15.3 ranibizumab injections (range, 6–34) during a mean follow-up of 23.4 months (range, 6–57). After switching to aflibercept, patients received a mean number of 12.4 injections (range, 6–20) during a mean follow-up of 25.5 months (range, 16–38). Treatment interval could be extended from 6.1 (range, 4–8) to 11 weeks (range, 8–16) (p=0.001) corresponding to a mean extension of injection interval of +4.9 weeks. Conclusion In case of insufficient response or frequent recurrences of ME due to CRVO in patients treated with ranibizumab on a TAE basis, switching to aflibercept could allow extending treatment intervals, which could reduce the injection burden for these patients.

When and How to Incorporate Steroids for Persistent Diabetic Macular Edema: A Discussion of Real-World Treatment Optimization Strategies.

In the United States, diabetic macular edema (DME) is the leading cause of vision loss among people with diabetic retinopathy. Despite the availability of different therapies for DME, up to half of patients with DME show some persistent edema after anti-vascular endothelial growth factor (VEGF) treatment alone, leaving these patients at high risk for vision loss. However, dosing in a similar fashion to that of pivotal anti-VEGF trials is difficult because of real-life challenges faced in clinical practice. This is particularly true for DME, in that the frequency and burden of anti-VEGF injections are a major challenge to patient care. Research evaluating anti-VEGF therapies has shaped the treatment paradigms for patients with DME, and similar benefits have also been noted in clinical trials evaluating the use of intravitreal steroids. Treatment with a long-term intravitreal corticosteroid, which requires fewer injections than treatment with most short-acting therapies, has been found to reduce inflammation and improve vision in a percentage of patients. This roundtable discussion, which took place during the 2018 annual meeting of the Vit-Buckle Society, reviews the current treatment paradigms for DME and evaluates how to customize and optimize treatment strategies geared toward individualized patient care. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:S5-S15.].

Real-World Results of Aflibercept versus Ranibizumab for the Treatment of Exudative AMD Using a Fixed Regimen

Intravitreal injections of antivascular endothelial growth factors have been considered a milestone in the treatment of neovascular age-related macular degeneration (nAMD). However, the increasing incidence of AMD and the burden of visits and injections overcharge both the patient and the healthcare systems. Real-world solutions depend on treatment protocols aimed at optimizing the number of clinical visits while guaranteeing good functional outcomes. We performed a retrospective analysis of 72 eyes from 63 naïve patients diagnosed with nAMD that underwent a fixed intravitreal protocol consisting of bimonthly injections after a three-month loading dose, with either Aflibercept or Ranibizumab (no predefined criteria for treatment selection). Best corrected visual acuity (BCVA) and optical coherence tomography were analyzed at baseline and during follow-up clinical visits (months 3, 6, 12, and 18). From the included participants, 42 followed a fixed regimen with Aflibercept and 30 with Ranibizumab. At the 12-month visit, there was not a statistically significant difference in the mean change of BCVA between the two groups (p=0.121); however, the mean difference in the central retinal thickness was significantly superior in the Aflibercept group (-142.2 versus -51.5, p=0.011). The described fixed regimen seems to be efficient in the treatment of nAMD in a clinical practice setting.

Assessing patient acceptance of laser pretreatment to reduce injection burden in diabetic macular edema: a large scale postal survey

ObjectiveTo canvass views about whether argon laser pretreatment to ischemic areas of retina would be acceptable if it resulted in a reduced burden of intravitreal injections. MethodA postal survey was mailed to all 813 patients under the care of the diabetic eye clinic at Singleton Hospital with 10 questions, explanatory information, and a stamp-addressed envelope available for returning completed questionnaires. ResultsPatients were strongly supportive (9.14 out of 10) of the idea of undergoing laser pretreatment if it meant less injections were needed for diabetic macular edema. ConclusionThis is the first time any survey has analyzed patient attitude to laser pretreatment and showed that patients were strongly in favour if it was found to reduce the need for intravitreal injections.

Updates in Retinal Diseases 2018

Choroidal neovascularisation (CNV) is a major cause of vision loss. For more than 10 years, intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs have been used in the treatment of CNV. While effective, this treatment strategy is limited by the injection burden. Most patients require multiple injections and response levels can vary. Early diagnosis and treatment of CNV can increase the success rate of treatment. There is, therefore, considerable interest in identifying biomarkers both to identify patients most likely to respond to treatment and to facilitate early detection of the condition. In an expert interview, Maurizio Battaglia Parodi of the University Vita-Salute Milan, Italy, discusses the latest advances in CNV.

Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian stimulation in women undergoing in vitro fertilisation.

Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian stimulation in women undergoing in vitro fertilisation.

Subthreshold micropulse laser reduces anti-VEGF injection burden in patients with diabetic macular edema

To evaluate the efficacy of micropulse laser in the early treatment of diabetic macular edema (DME) and its associated burden of anti-vascular endothelial growth factor (VEGF) injections. This retrospective comparative study compared a group of 19 eyes with DME treated with micropulse laser to a matched control group of 19 eyes with DME treated with ranibizumab injections without micropulse laser. Recorded parameters included previous medical and ocular history, previous and subsequent ranibizumab injections administered for DME, visual acuity (VA), central macular thickness throughout the follow-up period, and the occurrence of any complications. The improvement in VA was comparable in both groups, at 12 months and at the final follow-up. Patients treated with micropulse laser required significantly fewer ranibizumab injections than their controls, both at 12 months (1.7 ± 2.3 vs 5.6 ± 2.1) and by the end of the follow-up (2.6 ± 3.3 vs 9.3 ± 5.1) (p<0.001 for both). No complications related to the micropulse laser were encountered. Micropulse laser is a safe and effective treatment for DME, which may achieve comparable improvement in VA along with a significant reduction in the burden of anti-VEGF injections. We suggest a treatment approach for its inclusion in the early stages of DME.

Rationale for, Initiation and Titration of the Basal Insulin/GLP-1RA Fixed-Ratio Combination Products, IDegLira and IGlarLixi, for the Management of Type 2 Diabetes.

Type 2 diabetes (T2D) is a progressive disease affecting glucose regulation and a major cause of morbidity and mortality globally. Many patients are not escalated up the treatment ladder appropriately despite failing to achieve glycemic control, with barriers such as fear of hypoglycemia, weight gain, and treatment burden recognized as factors. Exogenous basal insulin is titrated to address control of fasting plasma glucose and may preserve residual β-cell function, thus promoting a greater endogenous prandial insulin response. Native glucagon-like peptide-1 (GLP-1) is a peptide hormone secreted by the gut in response to nutrient ingestion; it increases insulin secretion, inhibits glucagon secretion, and prolongs gastric emptying, thereby lowering overall food intake. As its glucose-lowering action is glucose dependent, a GLP-1 receptor agonist (GLP-1RA) achieves these benefits with a lower risk of hypoglycemia compared with other diabetes therapies. Two products, an insulin degludec/liraglutide combination (IDegLira) and an insulin glargine/lixisenatide combination (IGlarLixi), were approved for use in adults with T2D by the US Food and Drug Administration in 2016. The efficacy and safety of these two basal insulin/GLP-1RA combination products were studied in the DUAL program (NCTs 01336023, 01392573, 01676116, 01618162, 01952145, and 02298192) and the LixiLan program (NCTs 02058160 and 02058147). Compared with basal insulin, insulin/GLP-1RA fixed-ratio combinations are superior at reducing HbA1c with weight neutrality or weight loss rather than weight gain, as well as reduced hypoglycemia rates, and reduced insulin-dose requirement with IDegLira. A combination of different medications may often be required to achieve glycemic control, and fixed-ratio combination products allow such therapies to be given in simple regimens. Clinical trial data for these products highlight the great potential of these agents, not merely their efficacy and safety but also their ease of use and decreased injection burden for patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-017-0287-y) contains supplementary material, which is available to authorized users.

Preprogrammed Long-Term Systemic Pulsatile Delivery of Parathyroid Hormone to Strengthen Bone.

Parathyroid hormone (PTH) is the only US Food and Drug Administration (FDA)-approved anabolic agent for the treatment of osteoporosis. The anabolic action of PTH depends on the mode of PTH administration. Pulsatile administration promotes bone formation, however continuous PTH exposure results in bone resorption. In addition, the therapeutic effect of PTH is optimal when the dose and duration fit the therapeutic window. Current PTH treatment requires daily injection, which is neither a convenient nor a favorable choice of patients. Here, an implantable and biodegradable device capable of long-term pulsatile delivery of PTH is developed as a patient-friendly alternative. The advanced materials and fabrication techniques developed in this work enable us to preprogram a pulsatile delivery device to systemically deliver 21 daily pulses of PTH that build bone in vivo. In addition, the device is biodegradable and absorbable in vivo so that no retraction procedure is needed. Therefore, this implantable and biodegradable pulsatile device holds promise to promote bone growth and treat various conditions of bone loss without the burden of daily injections or secondary surgeries.

Adjuvants in Allergy: Elevating Efficacy

This symposium provided an overview of the current and future technologies and treatments used in the field of allergen immunotherapy (AIT). Prof Ralph Mösges explored the concept of pre-seasonal immunotherapy in overcoming the problem of recurrent allergy, focussing on the use of Pollinex® Quattro versus the use of symptomatic treatment according to current guidelines. The use and mechanisms of adjuvants was explored by Prof Randolf Brehler, who discussed the use of adjuvants in AIT including delivery systems, immunopotentiators, and targeted delivery systems to facilitate optimum immune responses with the potential of a lower injection burden and increased efficacy of treatment. Prof Thomas Kündig concluded the symposium with an overview of the future of AIT and the use of virus-like particles (VLP) in harnessing the innate immune system response to protect against allergens.

Comparison of Time to Retreatment and Visual Function Between Ranibizumab and Aflibercept in Age-Related Macular Degeneration

To compare time to retreatment and visual function between patients with treatment-naïve neovascular age-related macular degeneration (AMD) treated with either intravitreal ranibizumab (IVR) or intravitreal aflibercept (IVA) in routine clinical practice. Retrospective, interventional comparative case series. A total of 200 eyes of 197 patients with neovascular AMD. A total of 99 patients in the IVR group and 101 patients in the IVA group who met the inclusion criteria with 12months of follow-up were included in the present study. All patients received 3 consecutive monthly injections of 0.5mg/0.05mL ranibizumab or 2.0mg/0.05mL aflibercept as loading doses. Retreatment was allowed if evidence of clinical deterioration or the presence of intraretinal edema or subretinal fluid on spectral-domain optical coherence tomography examination performed at the 1-month follow-up was noted. The time to retreatment after the third injection during the loading phase to the first recurrence during the maintenance phase was compared between treatments using the Kaplan-Meier analysis. Functional and anatomic outcomes were also compared between the IVR and IVA groups. The median time to retreatment after the last induction dose was 5months in both groups. The proportion of IVR patients who required injection retreatment was not significantly higher than that of IVA patients (67.7% and 63.4%, respectively, at the 12-month follow up; log-rank test, P= .554). In both groups, significant improvements in postoperative best-corrected visual acuity (BCVA) compared with preoperative visual acuity was observed over the 12-month follow-up period (P< .05 for both). Central foveal thickness (CFT) decreased from the baseline values in both groups during the follow-up period (P < .001 for both). Although there was a trend toward greater BCVA improvements in the IVA group, no significant differences in BCVA or CFT were observed between the treatment groups. Both IVR and IVA were well tolerated and demonstrated efficacy in improving the visual acuityin treatment-naïve patients with AMD. Despite a trend toward greater BCVA improvements in the IVAgroup, a similar injection burden was observed following the loading phases of both ranibizumab andaflibercept.

Cost and carbon burden of long-acting injections: a sustainable evaluation.

Aims and method This study explores the economic cost and carbon footprint associated with current patterns of prescribing long-term flupentixol decanoate long-acting injections. We conducted an analysis of prescription data from a mental health trust followed by economic and carbon cost projections using local and national data.Results A reduction of £300 000 could be achieved across England by improving prescribing behaviour, which equates to £250 per patient per year and 170 000 kg CO2e. These savings are unlikely to be released as cash from the service, but will lead to higher-value service provision at the same or lower cost. Most of these carbon emissions are attributable to the carbon footprint of the appointment – 88 000 kg CO2e (including energy use and materials used) and the overprescribing of medication – 66 000 kg CO2e.Clinical implications Psychiatrists need to review their prescribing practice of long-acting injections to reduce their impact on the National Health Service financial budget and the environment.

The Future of Hemophilia Treatment: Longer-Acting Factor Concentrates versus Gene Therapy.

Gene therapy is the only novel technology that currently offers the prospect of a lasting cure for hemophilia and freedom from the burden of repeated injections. Recent data from a handful of patients who have undergone gene therapy for hemophilia B are very encouraging with a sustained factor IX (FIX) level of 0.05 IU/mL maintained for over 4 years. While this level is above the current usual target trough levels, it falls well short of the level that patients on prophylaxis with longer-acting products can expect. Prophylaxis is also associated with high peak levels, which permits patients to maintain an active lifestyle. A major barrier to widespread adoption of gene therapy is a high seroprevalence of antibodies to adeno-associated virus (AAV) vectors in the general population. Young children would be the best candidates for gene therapy in view of much lower seroprevalence to AAV in infants. A stable level of FIX early in life would prevent the onset of joint bleeds and the development of arthropathy. The recent experience with apolipoprotein tiparvovec (Glybera; uniQure, Amsterdam, the Netherlands) indicates that gene therapy is unlikely to prove to be a cheap therapeutic option. It is also quite possible that other new technologies that do not require viral vectors (such as stem cell therapy) may overtake gene therapy during development and make it redundant.

Patients' with type 2 diabetes willingness to pay for insulin therapy and clinical outcomes

ObjectivesThis study assessed patient preferences, using willingness to pay as a method to measure different treatment characteristics or attributes associated with injectable insulin therapy in patients with type 2 diabetes.Research...

Premixed insulin regimens in type 2 diabetes: pros.

Because of the increasing prevalence of type 2 diabetes, the need to intensify treatment to manage hyperglycemia is expanding. Premixed insulin regimens were designed to maximize patient convenience and reduce the number of daily injections required by providing both rapid-acting and intermediate-acting components in one formulation. Although the basal bolus insulin regimen is considered by many as "the golden standard" in reaching goals of glycemic control, proper use of intensified insulin regimens, such as basal bolus or premixed, will result in similar HbA1c reduction, hypoglycemic events, and weight gain. At the same number of daily insulin injections (2shots/day), the premixed regimen is associated with a significant 0.2% HbA1c decrease, as compared with the basal plus regimen (one shot of long-acting plus one shot of short-acting insulin). The choice of insulin regimen should consider the preferences, and resources of the individual and the family for adapting treatment to the patient needs. At last, the process of insulin initiation and intensification in type 2 diabetes must be carried out in the context of patient safety, minimizing the risk of hypoglycemia, weight gain, and injection burden.

Concentrated insulins: the new basal insulins.

IntroductionInsulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed.Areas coveredThis review highlights the published reports of the pharmacokinetic (PK) and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market.ConclusionHumulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration.

Abstract P1-10-04: A prospective study of patterns of chemotherapy, colony-stimulating factor use, and burden of colony-stimulating factor injections in patients with early-stage breast cancer

Abstract Background: Febrile neutropenia (FN) is a common side effect of myelosuppressive chemotherapy. Primary prophylaxis with colony-stimulating factors (CSFs) can reduce FN incidence and is recommended when a patient has a high risk of FN (&amp;gt; 20%). In the prophylactic setting, CSFs should be administered at least 24 hours after chemotherapy completion. Patient burden associated with CSF administration is not well understood. Here we describe current patterns of chemotherapy use and burden of CSF injections for patients with early-stage breast cancer (ESBC) in US clinical practice. Methods: This was a prospective cohort study of adult ESBC patients receiving their first chemotherapy course who had a high risk of FN based on high- or intermediate-risk chemotherapy regimen and individual FN risk factors. The burden associated with CSF injections was assessed via questionnaires among patients who received CSF, and a subset analysis of patient burden in the first cycle of chemotherapy is reported. Results: 598 patients completed the "burden of CSF injections" questionnaire following the first cycle of chemotherapy. Most patients were &amp;lt; 65 years old (76.8%), had a BMI &amp;lt; 30 kg/m2 (54.9%), and had few comorbidities (see table for additional characteristics and comorbidities). The three most common chemotherapy regimens received were ddAC-T (34.4%), TC (23.4%), and TCH (15.6%). 98.3% of patients received prophylaxis with CSF in the first chemotherapy cycle: 94.6% of these received pegfilgrastim, and 5.4% received filgrastim. Among all patients who received CSF, mean (SD) one-way travel time for a single CSF injection was 31 (25) minutes; mean (SD) time in office to receive a CSF injection was 41 (68) minutes. Across the first chemotherapy cycle, mean (SD) time missed from work for CSF administration was 3.1 (9.3) hours, and mean (SD) time missed from non-work activities was 5.5 (14.4) hours. 66.3% of patients had someone else assist them with travel to the clinic to receive CSF, of which 98.8% were helped by an unpaid caregiver. When patients were questioned about the subjective burden of CSF injections, 25.4% reported some degree of bother, and 15.9% reported at least moderate inconvenience. Conclusions: Among the high- and intermediate-risk regimens investigated here, dose-dense and taxane-based chemotherapy regimens were common. As many high-risk patients with ESBC receive primary prophylaxis with CSF, travel and time needed to receive CSF can contribute to patient and caregiver burden. Patient CharacteristicsN = 598 Age, mean (SD) years55.1 (11.3) BMI, mean (SD) kg/m230.7 (7.5) HER2+23.2% Luminal Aa52.0% Triple negative21.6% Stage at diagnosis 124.6% 253.7% 321.2% Missing0.5%Comorbidities &amp;gt; 10% Hypertension37.5% Hyperlipidemia24.7% Depression13.9% Diabetes mellitus13.4% Osteoarthritis12.7% Gastroesophageal reflux disease12.2% Hypothyroidism12.0% Anxiety11.9%aHormone receptor positive but HER2 negative. Citation Format: Li X, Barron R, Tzivelekis S, Li Y, Chandler D, Xu H, Morrow PK, Klippel Z, Nagarajan A, Reiner M, Page JH. A prospective study of patterns of chemotherapy, colony-stimulating factor use, and burden of colony-stimulating factor injections in patients with early-stage breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-10-04.

Patient-reported outcomes of parenteral somatostatin analogue injections in 195 patients with acromegaly.

BackgroundLong-acting somatostatin analogues delivered parenterally are the most widely used medical treatment in acromegaly. This patient-reported outcomes survey was designed to assess the impact of chronic injections on subjects with acromegaly.MethodsThe survey was conducted in nine pituitary centres in Germany, UK and The Netherlands. The questionnaire was developed by endocrinologists and covered aspects of acromegaly symptoms, injection-related manifestations, emotional and daily life impact, treatment satisfaction and unmet medical needs.ResultsIn total, 195 patients participated, of which 112 (57%) were on octreotide (Sandostatin LAR) and 83 (43%) on lanreotide (Somatuline Depot). The majority (>70%) of patients reported acromegaly symptoms despite treatment. A total of 52% of patients reported that their symptoms worsen towards the end of the dosing interval. Administration site pain lasting up to a week following injection was the most frequently reported injection-related symptom (70% of patients). Other injection site reactions included nodules (38%), swelling (28%), bruising (16%), scar tissue (8%) and inflammation (7%). Injection burden was similar between octreotide and lanreotide. Only a minority of patients received injections at home (17%) and 5% were self-injecting. Over a third of patients indicated a feeling of loss of independence due to the injections, and 16% reported repeated work loss days. Despite the physical, emotional and daily life impact of injections, patients were satisfied with their treatment, yet reported that modifications that would offer major improvement over current care would be ‘avoiding injections’ and ‘better symptom control’.ConclusionLifelong injections of long-acting somatostatin analogues have significant burden on the functioning, well-being and daily lives of patients with acromegaly.

POLYPOIDAL CHOROIDAL VASCULOPATHY IN WHITE PATIENTS

To report on a series of white patients in the United States with polypoidal choroidal vasculopathy (PCV). This is a retrospective chart review of 27 patients at a single center with PCV. The mean age was 74.3 with 48% being male. The most common presenting diagnosis was exudative age-related macular degeneration in 59%, and it took 17.5 months to diagnose PCV. During this time, patients received one antivascular endothelial growth factor injection every 1.3 months. The most common reason for suspecting PCV was a large retinal pigment epithelial detachment or a poor response to antivascular endothelial growth factor therapy. Once PCV was diagnosed, most underwent photodynamic therapy. In those who received photodynamic therapy, the fluid and/or age-related macular degeneration decreased in 86%. The vision improved in 41% with 36% maintaining stable vision. Patients received only one additional injection every 3.95 months after photodynamic therapy. This is one of the larger series of PCV in an entirely white population. It emphasizes the importance of diagnosis in whites as PCV can masquerade as recalcitrant exudative age-related macular degeneration. Common findings were a temporal or peripapillary location and the presence of lipid. After photodynamic therapy, the patients still required antivascular endothelial growth factor therapy, but the injection burden was decreased by 67% and vision was found to be improved or maintained in 77% of patients.

REASONS FOR DISCONTINUATION OF INTRAVITREAL VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION

This study was aimed to identify the reasons for discontinuing intravitreal anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration. This study is a retrospective chart review of a single Australian private practice. Analysis included patients who discontinued treatment from March 2006 to June 2012. Of 248 patients who commenced treatment, 105 (42.3%) had discontinued by June 2012. The reasons for discontinuation were available for 102 of the 105 (97.1%) patients. In 9 (3.6%) patients of the entire cohort, the doctor stopped the treatment as the lesion became inactive, whereas further treatment was thought to be futile in 27 (10.9%) patients. Twenty-six (10.5%) patients declined further treatment with 2 (0.8%) because of excessive treatment visits, 2 (0.8%) because of difficulty in attending, 2 (0.8%) because of the expense, 3 (1.2%) because of pain/discomfort, 6 (2.4%) thought that the treatment was not beneficial, and 11 (4.4%) had other medical conditions that were more severe. Treatment was discontinued in 40 (16.1%) patients for other reasons such as moving to another region in 27 (10.9%) and death in 11 (4.4%). These results indicate that the burden of intravitreal anti-vascular endothelial growth factor injections was a reason for treatment discontinuation in only a small minority of patients.