CLINICAL FEATURES AND OUTCOMES OF INFANTS WITH RETINOPATHY OF PREMATURITY WHO FAIL ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY

Abstract

Purpose: To describe characteristics and outcomes of patients with retinopathy of prematurity who failed intravitreal antivascular endothelial growth factor.

Methods: A retrospective case series of 211 eyes (112 patients) treated with antivascular endothelial growth factor as initial therapy for retinopathy of prematurity at a single academic institution between 2011 and 2019 and an additional 6 eyes (3 patients) referred to us for management of failed antivascular endothelial growth factor.

Results: Among the 211 eyes receiving initial treatment at our institution, 17 eyes (11%) failed. Of the 23 total eyes managed by us for failure, 3 eyes (13%) failed after 50-week postmenstrual age. Failure manifested as recurrent plus in 14 eyes (58%), recurrent Stage 3 in 13 eyes (54%) and retinal detachment in 5 eyes (21%). Treatment failures were managed with laser (13 eyes), repeat injection (4 eyes), vitrectomy (2 eyes), or a combination of modalities (4 eyes). Follow-up of ≥6 months was available for 18 of the 23 eyes. The retina was fully attached in 17 eyes, and fixation behavior was present in 10 eyes.

Conclusion: The most common manifestations of treatment failure were recurrent plus and Stage 3. The failure rate at our institution was 11.0%. A significant proportion of failures occurred after 50-week postmenstrual age. Most failed eyes had favorable anatomical outcomes and over half demonstrated fixation behavior.

Figure 1:

Plot of time to failure for each eye. The end of blue bar represents PMA at initial anti-VEGF treatment. The end of the orange bar represents the PMA at time of 1^st failure. The end of the gray bar represents the PMA at time of 2^nd failure and the end of yellow bar represents the PMA at time of 3^rd failure. Asterisks (*) denote failures that manifested as retinal detachments.

Figure 2.

A boy born at 25 weeks gestational age. The initial anti-VEGF therapy failed after developing recurrent plus and recurrent stage 3 disease in both eyes at 43 weeks PMA (A: right eye fundus photos and fluorescein angiogram, B: left eye fundus photos and fluorescein angiogram) and were treated with combined bevacizumab and laser. A small area of avascular retina was purposefully left untreated hoping that after repeat IVB vascularization would continue into this area of untreated avascular retina. In both eyes stage 3 never fully regressed and, when stage 3 became more prominent at 64 weeks, both eyes were treated with additional laser (C: right eye fundus photos and fluorescein angiogram, D: left eye fundus photos and fluorescein angiogram). The right eye (E) stabilized but the left eye (F) developed a partial tractional retinal detachment (stage 4A) at 71 weeks and underwent pars plana vitrectomy.

Figure 2.

A boy born at 25 weeks gestational age. The initial anti-VEGF therapy failed after developing recurrent plus and recurrent stage 3 disease in both eyes at 43 weeks PMA (A: right eye fundus photos and fluorescein angiogram, B: left eye fundus photos and fluorescein angiogram) and were treated with combined bevacizumab and laser. A small area of avascular retina was purposefully left untreated hoping that after repeat IVB vascularization would continue into this area of untreated avascular retina. In both eyes stage 3 never fully regressed and, when stage 3 became more prominent at 64 weeks, both eyes were treated with additional laser (C: right eye fundus photos and fluorescein angiogram, D: left eye fundus photos and fluorescein angiogram). The right eye (E) stabilized but the left eye (F) developed a partial tractional retinal detachment (stage 4A) at 71 weeks and underwent pars plana vitrectomy.

Figure 2.

A boy born at 25 weeks gestational age. The initial anti-VEGF therapy failed after developing recurrent plus and recurrent stage 3 disease in both eyes at 43 weeks PMA (A: right eye fundus photos and fluorescein angiogram, B: left eye fundus photos and fluorescein angiogram) and were treated with combined bevacizumab and laser. A small area of avascular retina was purposefully left untreated hoping that after repeat IVB vascularization would continue into this area of untreated avascular retina. In both eyes stage 3 never fully regressed and, when stage 3 became more prominent at 64 weeks, both eyes were treated with additional laser (C: right eye fundus photos and fluorescein angiogram, D: left eye fundus photos and fluorescein angiogram). The right eye (E) stabilized but the left eye (F) developed a partial tractional retinal detachment (stage 4A) at 71 weeks and underwent pars plana vitrectomy.

Figure 2.

A boy born at 25 weeks gestational age. The initial anti-VEGF therapy failed after developing recurrent plus and recurrent stage 3 disease in both eyes at 43 weeks PMA (A: right eye fundus photos and fluorescein angiogram, B: left eye fundus photos and fluorescein angiogram) and were treated with combined bevacizumab and laser. A small area of avascular retina was purposefully left untreated hoping that after repeat IVB vascularization would continue into this area of untreated avascular retina. In both eyes stage 3 never fully regressed and, when stage 3 became more prominent at 64 weeks, both eyes were treated with additional laser (C: right eye fundus photos and fluorescein angiogram, D: left eye fundus photos and fluorescein angiogram). The right eye (E) stabilized but the left eye (F) developed a partial tractional retinal detachment (stage 4A) at 71 weeks and underwent pars plana vitrectomy.

Figure 2.

A boy born at 25 weeks gestational age. The initial anti-VEGF therapy failed after developing recurrent plus and recurrent stage 3 disease in both eyes at 43 weeks PMA (A: right eye fundus photos and fluorescein angiogram, B: left eye fundus photos and fluorescein angiogram) and were treated with combined bevacizumab and laser. A small area of avascular retina was purposefully left untreated hoping that after repeat IVB vascularization would continue into this area of untreated avascular retina. In both eyes stage 3 never fully regressed and, when stage 3 became more prominent at 64 weeks, both eyes were treated with additional laser (C: right eye fundus photos and fluorescein angiogram, D: left eye fundus photos and fluorescein angiogram). The right eye (E) stabilized but the left eye (F) developed a partial tractional retinal detachment (stage 4A) at 71 weeks and underwent pars plana vitrectomy.

Figure 3.

A girl born at 22 5/7 weeks developed zone I, stage 3, plus disease in both eyes (A: right eye, B: left eye). She was treated with IVB at PMA 33 weeks in the left eye and 35 weeks in the right eye. She developed recurrent plus and recurrent stage 3 disease at PMA 49 weeks in both eyes (C: right eye fundus photos and fluorescein angiogram, D: left eye fundus photos and fluorescein angiogram) which were treated with laser. At PMA 51 weeks, both eyes (E: right eye, F: left eye) developed stage 4A detachments which were treated with concurrent IVB and PPV. Both eyes responded well with resolution of retinal detachment.

Figure 3.

A girl born at 22 5/7 weeks developed zone I, stage 3, plus disease in both eyes (A: right eye, B: left eye). She was treated with IVB at PMA 33 weeks in the left eye and 35 weeks in the right eye. She developed recurrent plus and recurrent stage 3 disease at PMA 49 weeks in both eyes (C: right eye fundus photos and fluorescein angiogram, D: left eye fundus photos and fluorescein angiogram) which were treated with laser. At PMA 51 weeks, both eyes (E: right eye, F: left eye) developed stage 4A detachments which were treated with concurrent IVB and PPV. Both eyes responded well with resolution of retinal detachment.

Figure 3.

A girl born at 22 5/7 weeks developed zone I, stage 3, plus disease in both eyes (A: right eye, B: left eye). She was treated with IVB at PMA 33 weeks in the left eye and 35 weeks in the right eye. She developed recurrent plus and recurrent stage 3 disease at PMA 49 weeks in both eyes (C: right eye fundus photos and fluorescein angiogram, D: left eye fundus photos and fluorescein angiogram) which were treated with laser. At PMA 51 weeks, both eyes (E: right eye, F: left eye) developed stage 4A detachments which were treated with concurrent IVB and PPV. Both eyes responded well with resolution of retinal detachment.

Figure 3.

A girl born at 22 5/7 weeks developed zone I, stage 3, plus disease in both eyes (A: right eye, B: left eye). She was treated with IVB at PMA 33 weeks in the left eye and 35 weeks in the right eye. She developed recurrent plus and recurrent stage 3 disease at PMA 49 weeks in both eyes (C: right eye fundus photos and fluorescein angiogram, D: left eye fundus photos and fluorescein angiogram) which were treated with laser. At PMA 51 weeks, both eyes (E: right eye, F: left eye) developed stage 4A detachments which were treated with concurrent IVB and PPV. Both eyes responded well with resolution of retinal detachment.

Figure 4.

A boy born at 23 weeks gestational age transferred to our facility for stage 4a traction retinal detachments in both eyes at 42 weeks. The right eye (A) was treated with intravitreal bevacizumab and concurrent PPV at that time. The left eye (B) had only a small nasal 4A TRD with circumferential fibrosis that appeared deceivingly inactive. This eye was initially observed. Later, the left eye had laser ablation of peripheral avascular retina with the outside provider and the TRD in that eye worsened shortly thereafter. When he came back to us at 47 weeks, the right eye was doing well (C) but the left eye (D) developed a retinolenticular adhesion superonasally with associated TRD.

Figure 4.

A boy born at 23 weeks gestational age transferred to our facility for stage 4a traction retinal detachments in both eyes at 42 weeks. The right eye (A) was treated with intravitreal bevacizumab and concurrent PPV at that time. The left eye (B) had only a small nasal 4A TRD with circumferential fibrosis that appeared deceivingly inactive. This eye was initially observed. Later, the left eye had laser ablation of peripheral avascular retina with the outside provider and the TRD in that eye worsened shortly thereafter. When he came back to us at 47 weeks, the right eye was doing well (C) but the left eye (D) developed a retinolenticular adhesion superonasally with associated TRD.