Original Article
Anti–Vascular Endothelial Growth Factor Therapy for Diabetic Retinopathy: Consequences of Inadvertent Treatment Interruptions

https://doi.org/10.1016/j.ajo.2019.03.005Get rights and content

Purpose

To illustrate that patients with diabetic retinopathy who are treated exclusively with anti–vascular endothelial growth factor (VEGF) therapy and have an interruption in treatment may experience marked progression of disease with potentially devastating visual consequences.

Design

Retrospective, multicenter, case series.

Methods

Retrospective review of patients treated exclusively with anti-VEGF therapy for proliferative diabetic retinopathy (PDR) or nonproliferative diabetic retinopathy (NPDR), with or without diabetic macular edema (DME), and temporarily lost to follow-up. Baseline disease characteristics, cause and duration of the treatment interruption, and resulting disease progression, complications, and outcomes were assessed.

Results

Thirteen eyes of 12 patients with type 2 diabetes were identified. The mean age was 57 ± 10 years, and 50% were women. Anti-VEGF therapy was indicated for PDR with DME in 7 (54%) eyes, PDR without DME in 3 (23%) eyes, and moderate to severe NPDR with DME in 3 (23%) eyes. Eight eyes had visual acuity (VA) of 20/80 or better before treatment interruption. The median duration of treatment hiatus was 12 months. Reasons for treatment interruption included intercurrent illness (31%), noncompliance (31%), and financial issues (15%). Complications upon follow-up included vitreous hemorrhage (9 eyes), neovascular glaucoma (5 eyes), and traction retinal detachment (4 eyes). Despite treatment of these complications, 77% of eyes lost ≥3 lines of VA, with 46% of eyes having a final VA of hand motion or worse.

Conclusions

Diabetic patients are subject to significant lapses in follow-up because of illness, financial hardship, or noncompliance. In patients with diabetic retinopathy, especially PDR, who are managed with anti-VEGF therapy alone, unintentional treatment interruptions can result in irreversible blindness.

Section snippets

Methods

This is a retrospective, multicenter, case series of patients treated exclusively with anti-VEGF therapy for PDR or nonproliferative diabetic retinopathy (NPDR), with or without diabetic macular edema (DME), and who were temporarily lost to follow-up. Patients were identified between April 10, 2017 and April 10, 2018 by recollection of the investigators. The institutional review board of the University of Michigan Medical School, Ann Arbor, Michigan waived oversight because the study involved

Results

Investigators at 6 centers identified 12 patients (13 eyes) that were treated solely with anti-VEGF therapy for DR and were subsequently lost to follow-up for a period of time. The average age of these patients was 56.6 ± 10.4 years and half were women (Table 1). All of the patients had type II diabetes mellitus, with a median disease duration of 19 years and a mean hemoglobin A1c of 9.5% ± 2.5%. Ten of the 13 eyes (77%) in this series were treated exclusively with anti-VEGF therapy for some

Discussion

This case series shows the potentially devastating visual consequences that may occur in a real-world setting when patients with DR are treated exclusively with anti-VEGF therapy and have an unanticipated interruption in treatment. Anti-VEGF therapy has proven to be noninferior to PRP in the treatment of PDR and has shown potential benefit for preventing DR progression or even causing its regression in the tightly controlled setting of a clinical trial where patients follow-up regularly.3, 9, 10

References (27)

Cited by (54)

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  • A Caveat About Financial Incentives for Anti-Vascular Endothelial Growth Factor Therapy for Diabetic Retinopathy

    2022, American Journal of Ophthalmology
    Citation Excerpt :

    Prophylactic treatment of a large cohort of patients will undoubtedly increase the incidence of post-injection endophthalmitis, with its potential for severe and irreversible vision loss; 3 of 160 patients in Protocol W suffered this complication,3,25 which is a catastrophic consequence considering that eyes in this cohort had a median initial BCVA of 20/20. Given these risks associated with an anti-VEGF injection-only treatment strategy, an objective analysis of cost, benefit, and risk concludes that PRP should be the preferred first-line treatment for PDR in most patients.17,26,27 It is possible that data from the 4-year extension of Protocol W and PANORAMA could change the calculus of risk versus benefit.

  • Outcomes of Eyes With Diabetic Macular Edema That Are Lost to Follow-up After Anti–Vascular Endothelial Growth Factor Therapy

    2022, American Journal of Ophthalmology
    Citation Excerpt :

    Patients with more therapy break-offs had significantly greater declines in VA.10 In our study, a modest but significant decline in VA was observed after being LTFU with mean VA declining from about 20/50 at the visit before LTFU to about 20/70 at the first return visit. Significant declines in vision have also been found after anti-VEGF treatment breaks in PDR and nAMD.11,17-19 In contrast, a recent study by Yalamanchili and associates20 of 82 patients with DME who were LTFU for ≥3 months showed no significant difference in VA upon return to care when compared with matched control subjects who were not LTFU.

  • Intravitreal anti-vascular endothelial growth factor versus panretinal LASER photocoagulation for proliferative diabetic retinopathy: a systematic review and meta-analysis

    2021, Canadian Journal of Ophthalmology
    Citation Excerpt :

    The treatment burden associated with anti-VEGF injections can be significant, and maintenance of efficacy requires ongoing assessment and intervention. Wubben et al. highlighted in a retrospective case series that patients with diabetes treated exclusively with anti-VEGF can have disruptions to treatment, which can in turn result in irreversible blindness through complications including neovascular glaucoma and tractional retinal detachment.37 The risk of vitreous hemorrhage, tractional retinal detachment, and permanent visual disability is well-known in patients with untreated PDR.2

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