Retinopathy of prematurity (ROP), one of the leading causes of blindness in children, affects retinal vascular development and may lead to extraretinal fibrovascular proliferation (EFP), macular dragging, and, in severe cases, tractional retinal detachment (TRD).1 Early identification, appropriate treatment, and close monitoring are necessary to prevent blindness. Laser ablation and more recently intravitreal anti-vascular endothelial growth factor (VEGF) injections were shown to be effective treatment options for ROP.2,3 Rare cases of exudative retinal detachments (ERD) decades after acute stages of ROP have been reported in literature as late sequelae of ROP.4–6 This late reactivation is likely due to low-level but persistent secretion of VEGF by avascular retina, similar to many other diseases with nonperfused retina. There is controversy regarding the need to treat persistent peripheral avascular retina in regressed ROP, particularly after anti-VEGF treatment, because traditionally avascular retina has not been treated after spontaneously regressed ROP. Herein, a case of unilateral retinal detachment in a 19-year-old with history of treated ROP in the contralateral eye is reported.
A 19-year-old female was referred with blurred vision and floaters in the right eye. At presentation, visual acuity (VA) was count fingers in the right eye and 20/200 in the left eye, with intraocular pressures of 27 mm Hg and 23 mm Hg, respectively. Anterior segment exam was normal. Dilated fundus exam revealed mild vitreous hemorrhage, macular heterotopia, and exudates with temporally dragged vessels in the right eye. Additionally, peripheral retina was detached in the right eye, with exudates and radial vessels emanating from the area of regressed EFP to a new anterior area of EFP (Figure 1). The left eye had nasal dragging of the fovea with vascular tortuosity and attached retina with 360° peripheral panretinal laser treatment (Figure 2). Fluorescein angiography (FA) showed temporal areas of nonperfusion and microaneurysms, as well as areas of leakage from EFP at the edge of nonperfusion zone in the right eye (Figure 3). The left eye had peripheral laser but otherwise normal perfusion (Figure 4).
Fundus photos of the right eye. (A) Macular heterotopia, exudates, and dilated vessels. (B) Radial vessels emanating from the presumed original area of vascular arrest, peripheral fibrotic neovascularization at the vascular-avascular junction, and peripherally detached retina. (C, D) Inferior and inferonasal exudates and fibrovascular tissue.
Fundus photos of the left eye. (A) Nasal dragging of the fovea with vascular tortuosity. (B–D) Attached retina with 360° peripheral laser treatment.
Fluorescein angiogram of the right eye showing (A) posterior pole; (B) temporal areas of capillary dropout, telangiectasias, microaneurysms; and (C, D) areas of leakage from neovascularization at the edge of the avascular zone.
Fluorescein angiogram of the left eye. (A, B) Mild peripheral leakage at the edge of vascular retina and laser.
The patient underwent scleral buckling to support areas of traction and received intravitreal bevacizumab (Avastin; Genentech, South San Francisco, CA) injection to reduce exudation and vascular activity in the right eye. After improvement in subretinal fluid, laser photocoagulation was performed to the areas of avascular retina and telangiectasias. VA improved to 20/400 on postoperative day 1 and then 20/100 at postoperative month 3. The macula was flat with residual tractional elements supported by the buckle.
In the presented patient, only the eye that did not have peripheral ablation developed the combined tractional and exudative retinal detachment, supporting the suggestion that it was caused by constant production of VEGF by the peripheral avascular retina. We believe that untreated peripheral retina may pose a lifelong risk for severe complications from ROP, including retinal detachment. Despite likely chronic RD in this case, our patient had significant improvement in VA after treatment.
ERD is a rare complication in the second to fourth decades of life in adults with history of ROP without peripheral ablation.4–6 Brown et al. as well as Tasman reported small case series of ROP patients with late sequelae of ERD.4–6 Similar to our case, these patients shared common features, such as avascular peripheral retina, microaneurysms, telangiectasias, macular heterotopia, peripheral traction, and lipid exudates. The radial vessels progressing anteriorly from the circumferential structure of the original ridge location is not seen in Coats disease or familial exudative vitreoretinopathy (FEVR) and is characteristic of regrowth of intraretinal vessels after anti-VEGF treatment in ROP.7 Less likely etiologies of the detachment in this patient could be chronic rhegmatogenous detachment due to a tiny, unseen break, with subsequent ischemia and exudate or combined ROP and FEVR.8,9
ROP is a life-long disease beyond the acute phase. Late complications can include strabismus, amblyopia, glaucoma, cataract, retinoschisis, TRD, lattice-like degeneration, retinal breaks, rhegmatogenous retinal detachment, and ERD.
Timely detection and treatment of these complications requires strategies for long-term follow-up during the toddler stage, childhood, and throughout adult life.
With increase in use of bevacizumab for treatment of ROP, late retinal detachment from ROP may occur more frequently and earlier in life. Peripheral avascular retina is frequently present in patients treated with bevacizumab,10–16 and thus those eyes that do not undergo subsequent laser photoablation will continue to produce VEGF and may lead to reactivation of ROP.11–15 Eyes that require treatment for Type 1 ROP and regress after treatment are fundamentally different from those that have regressed spontaneously. We have previously reported several cases of severe ERD in ROP patients 1 to 3 years after intravitreal bevacizumab treatment.14–16 These patients had significant areas of avascular peripheral retina, which likely led to build-up of VEGF. Persistent avascular retina has been found after ranibizumab (Lucentis; Genentech, South San Francisco, CA) treatment for ROP, as well.17 Unfortunately, this peripheral avascular retina, where early disease reactivation is likely to occur, becomes more challenging to evaluate as infants grow and resist examination. Therefore, patients with ROP treated with bevacizumab should have close and long-term follow-up. Peripheral ablation of avascular retina should be strongly considered to prevent VEGF accumulation and its sequelae during the next years to even decades. Further studies are needed to evaluate long-term effects of peripheral ablation in ROP patients treated with intravitreal anti-VEGF injections.
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- Good WV. Final results of the early treatment for retinopathy of prematurity (ETROP) randomized trial. Trans Am Ophthalmol Soc. 2004;102:233–248; discussion 248–250.
- Mintz-Hittner HA, Kennedy KA, Chuang AZBEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011;364(7):603–615. doi:10.1056/NEJMoa1007374 [CrossRef]
- Brown MM, Brown GC, Duker JS, Tasman WS, Augsburger JJ. Exudative retinopathy of adults: A late sequela of retinopathy of prematurity. Int Ophthalmol. 1994–1995;18(5):281–285.
- Tasman W. Late complications of retrolental fibroplasias. Ophthalmology. 1979;86(10):1724–1740. doi:10.1016/S0161-6420(79)35346-5 [CrossRef]
- Tasman W. Exudative retinal detachment in retrolental fibroplasias. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol. 1977;83(3 Pt 1):535–540.
- Hoang QV, Keirnan DF, Chau FY, Shapiro MJ, Blair MP. Fluorescein angiography of recurrent retinopathy of prematurity after initial intravitreous bevacizumab treatment. Arch Ophthalmol. 2010;128(8):1080–1081. doi:10.1001/archophthalmol.2010.145 [CrossRef]
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- Toy BC, Schachar IH, Tan GS, Moshfeghi DM. Chronic vascular arrest as a predictor of bevacizumab treatment failure in retinopathy of prematurity. Ophthalmology. 2016;123(10):2166–2175. doi:10.1016/j.ophtha.2016.06.055 [CrossRef]
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- Garcia-Gonzalez JM, Snyder L, Blair M, Rohr A, Shapiro M, Greenwald M. Prophylactic peripheral laser and fluorescein angiography after bevacizumab for retinopathy of prematurity. Retina. 2018;38(4):764–772.
- Snyder LL, Garcia-Gonzalez JM, Shapiro MJ, Blair MP. Very late reactivation of retinopathy of prematurity after monotherapy with intravitreal bevacizumab. Ophthalmic Surg Lasers Imaging Retina. 2016;47(3):280–283. doi:10.3928/23258160-20160229-12 [CrossRef]
- Hajrasouliha AR, Garcia-Gonzales JM, Shapiro MJ, Yoon H, Blair MP. Reactivation of retinopathy of prematurity three years after treatment with bevacizumab. Ophthalmic Surg Lasers Imaging Retina. 2017;48(3):255–259. doi:10.3928/23258160-20170301-10 [CrossRef]
- Ittiara S, Blair MP, Shapiro MJ, Lichtenstein SJ. Exudative retinopathy and detachment: A late reactivation of retinopathy of prematurity after intravitreal bevacizumab. J AAPOS. 2013;17(3):323–5. doi:10.1016/j.jaapos.2013.01.004 [CrossRef]
- Day S, Rainey AM, Harper CA 3rd, . Incomplete retinal vascularization after ranibizumab treatment of retinopathy of prematurity. Ophthalmic Surg Lasers Imaging Retina. 2017;48(1):75–78. doi:10.3928/23258160-20161219-11 [CrossRef]