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 Table of Contents  
Year : 2021  |  Volume : 59  |  Issue : 1  |  Page : 74-76

Aggressive posterior retinopathy of prematurity in baby showing features of cardiofacial syndrome overlapping with pearl syndrome

Department of Retina and Vitreous, Aravind Eye Hospital, Tirunelveli, Tamil Nadu, India

Date of Submission21-Sep-2020
Date of Acceptance30-Jan-2021
Date of Web Publication27-Mar-2021

Correspondence Address:
Dr. Vinit Jayendra Shah
Aravind Eye Hospital, Tirunelveli, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tjosr.tjosr_138_20

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We report the case of a preterm infant referred to us for retinopathy of prematurity (ROP) screening at postmenstrual age of 35 weeks who presented with right-sided congenital lower motor neuron type facial nerve palsy, lagophthalmos, normal anterior segment findings, and aggressive posterior ROP on the fundus examination in both eyes. Right-sided microtia, normal left ear, and asymmetric crying facies were noted. The baby received intravitreal bevacizumab 0.625 mg in both eyes after systemic workup which revealed a ventricular septal defect with patent ductus arteriosus and normal brain magnetic resonance imaging. At 2 months postinjection, the plus disease decreased significantly with vessels developing up to zone 3 with no ROP in both the eyes.

Keywords: Aggressive posterior retinopathy of prematurity, cardiofacial syndrome, congenital facial palsy, intravitreal bevacizumab, microtia, pearl syndrome

How to cite this article:
Shah VJ, Khadar SM, Adeel SS, Nair S. Aggressive posterior retinopathy of prematurity in baby showing features of cardiofacial syndrome overlapping with pearl syndrome. TNOA J Ophthalmic Sci Res 2021;59:74-6

How to cite this URL:
Shah VJ, Khadar SM, Adeel SS, Nair S. Aggressive posterior retinopathy of prematurity in baby showing features of cardiofacial syndrome overlapping with pearl syndrome. TNOA J Ophthalmic Sci Res [serial online] 2021 [cited 2021 Oct 20];59:74-6. Available from: https://www.tnoajosr.com/text.asp?2021/59/1/74/312291

  Introduction Top

Aggressive posterior retinopathy of prematurity (APROP) is a fulminant form of retinopathy of prematurity (ROP) which can rapidly progress to stage 4 ROP with retinal detachment if left untreated. It shows severe-plus disease in Zone 1 or posterior Zone 2, with flat neovascularization at the edge of the vascular retina and can also have retinal hemorrhages with intraretinal arteriovenous shunts.[1] Pearl first described a triad of unilateral congenital facial palsy, unilateral anotia, and congenital heart disease.[2] There are only a handful of cases reported in literature with these congenital anomalies, and we report the first case of APROP in baby showing features of cardiofacial syndrome overlapping with Pearl Syndrome.

  Case Report Top

A 28-day-old male born out of nonconsanguineous marriage, 31-week preterm with cesarean delivery, 1300 g birth weight, who cried immediately after birth with facial asymmetry, and abnormal right ear was referred for ROP screening. He had respiratory distress at birth which was managed with surfactant and supplemental oxygen. Antenatal period was uneventful with no history of drug intake or any intrauterine infection. Family history was insignificant.

On facial examination, he had right microtia with a postauricular tag [Figure 1]a, a normal left external ear [Figure 1]b, and microcephaly. Right lower motor neuron type facial palsy was evident by inability to close the right eye with reduced blink rate, absent forehead creases, and nasolabial folds [Figure 1]c. On crying, right lower lip was pulling down indicating weakness of left depressor anguli oris giving rise to asymmetric crying facies [Figure 1]d. No other congenital anomalies of the eyes or limbs were present.
Figure 1: Color photograph of the right ear showing microtia with postauricular tag (a), left normal external ear (b), congenital lower motor neuron type right facial nerve palsy showing absent forehead creases, lagophthalmos without corneal exposure and absent nasolabial folds at presentation (c), asymmetry of eye closure, nasolabial folds, and angle of mouth on crying taken at last visit (d)

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On ophthalmic examination, RE lagophthalmos without corneal exposure was noted. The anterior segment of both eyes was normal. On fundus examination, both eyes showed significantly dilated tortuous vessels in the posterior pole in Zone 1 with plus disease suggestive of APROP [Figure 2]a and [Figure 2]b. He was advised both eyes intravitreal injection of bevacizumab 0.625 mg (0.025 ml) at the earliest. Retcam images were taken for documentation, and the child was referred to the pediatrician for systemic workup and to obtain a fitness for intravitreal injection. Echocardiography revealed patent ductus arteriosus with ventricular septal defect. There was no other cranial nerve palsy, and the remainder of the neurological examination including magnetic resonance imaging was normal.
Figure 2: Retcam photographs from a male infant weighing 1300 g at birth and postmenstrual age of 35 weeks demonstrate aggressive posterior retinopathy of prematurity in Zone 1 and regression following bevacizumab monotherapy. Fundus photographs prior to injection shows dilated tortuous vessels with arteriovenous shunts in Zone 1 (white arrow) and demarcation line Stage1 (arrowhead) in both the eyes (a and b). Fundus photographs 2 months postinjection showed decreased vascular tortuosity with retinal vascular growth up to Zone 3 (white arrow) with no retinopathy of prematurity in both the eyes (c and d)

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The intravitreal injection was given under strict aseptic precautions under topical anesthesia in the neonatal intensive care unit, 1.5 mm away from the limbus in both the eyes. Post injection indirect ophthalmoscopy showed a well-perfused optic disc. He was started on topical antibiotics and eyelid taping of the right eye when he is asleep.

On follow-up visits, the plus disease reduced with decreased tortuosity of vessels, and the retina showed signs of growth. 2 months postinjection, APROP had regressed with fundus showing Zone 3 immature retina with no ROP [Figure 2]c and [Figure 2]d. Corneal exposure keratopathy was absent, and eyelid taping with lubricating drops were continued and kept on fortnightly follow-up.

  Discussion Top

Cardiofacial syndrome is an ill-defined clinical entity showing asymmetric crying facies pointing toward congenital heart disease in association with abnormalities involving the genitourinary tract, central nervous system, cleft lip/palate, gastrointestinal tract, or skeletal system. It is rarely reported to be associated with microtia/anotia and congenital facial palsy without any systemic involvement.[3]

The triad of congenital heart disease, congenital facial paralysis, and anotia described by Pearl in 1984 was previously reported with teratogenic effects of thalidomide or retinoic acid intake during pregnancy or documented as a variant of Goldenhar syndrome.[2],[3] None of these associations were observed in our case. Girisha and Phadke first reported a case of congenital facial palsy with contralateral hypoplasia of depressor anguli oris, suggesting the involvement of common pathway in the development of facial nerve, ear, and depressor anguli oris.[3]

ROP is a leading cause of lifelong visual impairment in premature infants.[4] In recent years, a more virulent form of ROP known as APROP has emerged in very low birth weight preterm babies. The increased survival of extremely premature infants due to modern neonatal care has led to increased occurrence of Zone 1 ROP.[5]

Management of APROP is usually complicated. Even with early laser treatment in APROP, the outcomes were poor as reported in the ETROP study.[6] In babies with Zone 1 ROP treated with laser therapy, permanent damage of the peripheral retina occurs increasing the probability of high refractive errors and visual field loss.[7] Gunn et al. reported good structural outcomes, but poor visual outcomes in APROP managed with laser treatment. Even after laser therapy, complications such as retinal detachment or persistent angiogenic activity can occur, this needs retreatment with additional laser or antivascular endothelial growth factor (VEGF) injections.[8]

The role of VEGF in stimulating neovascularization in ROP is well established, and blockade of this pathway is emerging as a treatment for ROP. Bevacizumab is a recombinant humanized VEGF antibody that prevents VEGF from binding to its receptors, causes an intense but brief reduction in the disease course, and avoids the side effects related to laser.[6]

BEAT-ROP trial for treatment in Zone 1 Stage 3 plus ROP described substantial treatment advantage with bevacizumab over conventional laser.[9] Isaac et al. reported that 18% of eyes showed full vascularization of the retina at 3 months; all eyes regressed to no ROP and none of the eyes required repeat treatment till the last follow-up. He emphasized the need for careful follow-up to look for peripheral vascularization in all babies with bevacizumab monotherapy.[10] Geloneck et al. in their study found that high myopia was seen in eyes after laser treatment compared to eyes receiving intravitreal bevacizumab. A plausible explanation could be related to anterior segment development that happens with intravitreal bevacizumab but is nominal or absent after laser treatment.[11]

The initial interest in bevacizumab monotherapy for Zone 1 ROP has been mitigated by the possible risk of its impact on angiogenesis, late recurrences, need for frequent follow-ups, and systemic side effects on developing organs such as the brain, kidneys, and lungs.[7]

In our case, the APROP regressed well after bevacizumab monotherapy, the radial vasculature growth was seen up to Zone 3 in both the eyes with no evidence of ROP and was advised regular follow-up till complete vascularization. To the best of our knowledge, it is the first case report of APROP and its management in a baby showing features of cardiofacial syndrome overlapping with those of Pearl syndrome. Our report emphasizes the need for a multidisciplinary approach in preterm babies, the beneficial role of bevacizumab in APROP, and essential long-term follow-up.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.


The authors thank the ROP team and retina department staff of our hospital for their hard work and commitment toward ROP screening.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

International Committee for the Classification of Retinopathy of Prematurity. The international classification of retinopathy of prematurity revisited. Arch Ophthalmol 2005;123:991-9.  Back to cited text no. 1
Pearl W. Syndrome of anotia, facial paralysis, and congenital heart disease. J Pediatr 1984;105:441-2.  Back to cited text no. 2
Girisha KM, Phadke SR. Anotia and facial palsy: Unusual features of cardiofacial syndrome. Indian J Pediatr 2005;72:525-6.  Back to cited text no. 3
Steinkuller PG, Du L, Gilbert C, Foster A, Collins ML, Coats DK. Childhood blindness. J AAPOS 1999;3:26-32.  Back to cited text no. 4
Ahn YJ, Hong KE, Yum HR, Lee JH, Kim KS, Youn YA, et al. Characteristic clinical features associated with aggressive posterior retinopathy of prematurity. Eye (Lond) 2017;31:924-30.  Back to cited text no. 5
Early Treatment for Retinopathy of Prematurity Cooperative Group, Good WV, Hardy RJ, Dobson V, Palmer EA, Phelps DL, et al. Final visual acuity results in the early treatment for retinopathy of prematurity study. Arch Ophthalmol 2010;128:663-71.  Back to cited text no. 6
Padhi TR, Das T, Rath S, Pradhan L, Sutar S, Panda KG, et al. Serial evaluation of retinal vascular changes in infants treated with intravitreal bevacizumab for aggressive posterior retinopathy of prematurity in zone I. Eye (Lond) 2016;30:392-9.  Back to cited text no. 7
Gunn DJ, Cartwright DW, Gole GA. Prevalence and outcomes of laser treatment of aggressive posterior retinopathy of prematurity. Clin Exp Ophthalmol 2014;42:459-65.  Back to cited text no. 8
Darlow BA, Ells AL, Gilbert CE, Gole GA, Quinn GE. Are we there yet? Bevacizumab therapy for retinopathy of prematurity. Arch Dis Child Fetal Neonatal Ed 2013;98:F170-4.  Back to cited text no. 9
Isaac M, Tehrani N, Mireskandari K, Medscape. Involution patterns of retinopathy of prematurity after treatment with intravitreal bevacizumab: Implications for follow-up. Eye (Lond) 2016;30:333-41.  Back to cited text no. 10
Geloneck MM, Chuang AZ, Clark WL, Hunt MG, Norman AA, Packwood EA, et al. Refractive outcomes following bevacizumab monotherapy compared with conventional laser treatment: A randomized clinical trial. JAMA Ophthalmol 2014;132:1327-33.  Back to cited text no. 11


  [Figure 1], [Figure 2]


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