Ten-year outcomes after initial management with laser photocoagulation versus intravitreal bevacizumab injection in a pair of identical twins with aggressive posterior retinopathy of prematurity





Abstract


Purpose


To evaluate the long-term clinical outcomes after initial management with retinal laser photocoagulation (RLP) versus intravitreal bevacizumab (IVB) injection in identical twins with zone Ⅰ aggressive posterior retinopathy of prematurity (AP-ROP).


Observations


Identical female twins were born at a gestational age of 28 2/7 weeks, weighing 970 g and 1020 g. The twins were diagnosed with bilateral AP-ROP, referred to a different hospital due to unavilability of a neonatal intensive care unitand received different initial treatments. At a postmenstrual age of 32 6/7 weeks, the first-born infant underwent bilateral IVB (0.313 mg) injection, whereas the second-born infant received bilateral laser photocoagulation on the same day. To treat recurrence, the first-born infant underwent additional bilateral IVB reinjection at 10 weeks post-treatment, while the second-born infant underwent combined bilateral laser photocoagulation and IVB injection at 2 weeks post-treatment.


After 10 years, the first-born infant’s best corrected visual acuities (BCVAs) of the right and left eyes were 20/20 and 20/50, respectively. Both eyes showed complete retinal vascularization of the peripheral retina and an anatomically normal foveal contour on swept-source optical coherence tomography (SS-OCT). However, the second-born infant’s BCVAs of the right and left eyes were 20/50 and 1-m finger-counting, respectively. Both eyes of the second-born infant showed panretinal chorioretinal atrophy due to laser scars, a flattened foveal contour with thin epiretinal membrane in the right eye, and loss of foveal curvature in the left eye on SS-OCT images, 10 years after the initial treatment. Moreover, severe myopia and astigmatism were observed in both eyes of the second-born infant, compared with those of the first-born infant during follow-up.


Conclusion and importance


These cases involving identical twins indicated that the effect of initial IVB injection for AP-ROP was superior to that of initial RLP in terms of functional and anatomical outcomes during a 10-year follow-up.



Introduction


Retinopathy of prematurity (ROP) is a leading cause of visual morbidity worldwide. Although the Early Treatment for Retinopathy of Prematurity Cooperative Group reported that unfavorable clinical outcomes were reduced by performing retinal laser photocoagulation (RLP) at pre-threshold retinopathy, rather than at threshold retinopathy, severe vision loss due to serious complications, including retinal detachment, retinal folds, and retrolental hyperplasia, occurred in about 10% of patients. A severe form of ROP, including Rush-type ROP and type Ⅱ ROP, was classified as aggressive posterior retinopathy of prematurity (AP-ROP) in 2005. AP-ROP usually occurs in premature infants with gestational age (GA) < 28 weeks and low birth weight (<1000 g). Since AP-ROP is located more posteriorly and progresses rapidly, the prognosis of AP-ROP has been poor, despite early intervention. Given that vascular endothelial growth factor (VEGF) dysregulation has been associated with the pathogenesis of ROP, anti-VEGF agents, mostly bevacizumab (Avastin, Genentech, San Francisco, CA, USA), have been used off-label in several studies.


While RLP is associated with ocular complications, such as visual field defects due to photoreceptor damage and development of high myopia, intravitreal bevacizumab (IVB) injection is less invasive and can be performed under topical anesthesia. , , Although the Bevacizumab Eliminates the Angiogenic Threat of Retinopathy (Beat-ROP) study showed significant benefits of IVB, as compared with RLP, several comparative studies of IVB and RLP did not confirm its superiority. ,


Here, we report the 10-year clinical outcomes of identical twins who received different initial treatments, either IVB or RLP.



Case report


Identical female twins with a GA of 28 2/7 weeks at birth were born at a local general hospital. The body weight of the first-born and second-born infants were 970 g and 1002 g, respectively. The first-born infant’s Apgar scores were 5 at 1 minute and 6 at 5 minutes, and the second-born infant’s Apgar scores were 5 at 1 minute and 7 at 5 minutes. Both twins were diagnosed with bronchopulmonary dysplasia and received synchronized intermittent mandatory ventilation treatment for 30 days. On ROP screening at the postmenstrual age (PMA) of 32 3/7 weeks, both eyes of both twins were diagnosed with “plus disease,” with dilatation and tortuosity of the major posterior vessels. A ridge with extraretinal fibrovascular proliferation with a circle in zone Ⅰ without involving the fovea and scattered retinal hemorrhages were observed in both eyes. As the fundus features of stage 3 ROP in zone Ⅰ were very similar between both twins, AP-ROP in both eyes of both twins was confirmed by a retinal specialist at the local hospital. For emergency treatment, the first-born infant was admitted to our hospital, whereas the second-born infant was transferred to another hospital because of the unavailability of a neonatal intensive care unit.


At PMA 32 6/7 weeks, the first-born infant received bilateral IVB with a dose of 0.313 mg/0.015 mL. IVB injection was performed under topical anesthesia with 5% proparacaine in the operating room. Written informed consent for off-label use of IVB was obtained from the patient’s legal guardian. A sterile 30-gauge needle was inserted at 1-mm posterior to the limbus, after povidone-iodine sterilization. Topical moxifloxacin was administered over a period of 7 days. The vascular tortuosity and extraretinal fibrovascular proliferation regressed markedly and retinal vessels grew up to zone Ⅱ at 3-weeks post-treatment. Since both the fundi of the first-born infant showed recurrence, such as increased vascular tortuosity and newly developed focal retinal hemorrhages, bilateral IVB (0.313 mg) reinjection was performed 10 weeks after the initial treatment. The ROP gradually regressed after second IVB injection. Complete retinal vascularization was observed 6 months after the initial IVB, after which the infant was followed up every 6 months. Ten years after the initial IVB in the first-born infant, the best corrected visual acuity (BCVA) of the right and left eye was 20/20 and 20/50, respectively. The spherical equivalent refractive errors of the right eye and left eye were +2.75 D and −5.625 D, respectively. The amblyopia and astigmatism of the left eye was treated with eye patch for 4 years and wore glasses during last 6 years. The axial lengths of the right and left eyes were 19.93 mm and 22.69 mm, respectively, at the 10-year follow-up. Additionally, wide-field fundus photos of both eyes showed complete retinal vascularization of the peripheral retina and swept-source optical coherence tomography (SS-OCT) image revealed a normal foveal contour ( Fig. 1 ). The internal anterior chamber depths of the right and left eyes were 2.90 mm and 3.01 mm, respectively. The flat/steep corneal dioptric values of the right and left eyes were 44.4/46.8 D and 43.6/47.3 D, respectively, as assessed using a Scheimpflug rotating camera (Pentacam HR, Oculus; Wetzlar, Germany) ( Fig. 2 ).




Fig. 1


The first-born infant was treated with bilateral Intravitreal bevacizumab (IVB) injections twice. (A) Wide-field fundus photography of the right eye at 10 years after the initial IVB treatment shows complete retinal vascularization of the peripheral retina. (B) Fundus photography of the left eye shows complete vascularization with a tigroid fundus. (C) Swept-source optical coherence tomography (SS-OCT) image of the right eye shows a normal foveal contour at 10 years. (D) The SS-OCT image of the left eye shows a normal foveal curvature with an ellipsoid zone.



Fig. 2


Axial/sagittal curvature map (top) and internal anterior chamber depth (ACD) map (bottom) at post-treatment 10 years. ( A) The flat/steep corneal dioptric values were 44.4/46.8 D, and the internal ACD was 2.90 mm in the right eye of the first-born infant. (B) The flat/steep corneal dioptric values were 43.6/47.3 D and the internal ACD was 3.01 mm in the left eye of the first-born infant. (C) The flat/steep corneal dioptric values were 43.9/48.3 D and the internal ACD was 2.13 mm in the right eye of the-second-born infant. (D) The flat/steep corneal dioptric values were 44.2/49.0 D and the internal ACD was 2.08 mm in the left eye of the second-born infant.

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Jul 10, 2021 | Posted by in OPHTHALMOLOGY | Comments Off on Ten-year outcomes after initial management with laser photocoagulation versus intravitreal bevacizumab injection in a pair of identical twins with aggressive posterior retinopathy of prematurity
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