Successful Surgical Management of Retinopathy of Prematurity Showing Rapid Progression despite Extensive Retinal Photocoagulation.

The management of retinopathy of prematurity (ROP) can be challenging in preterm babies with a gestational age <30 weeks, those with very low birth weight and multiple risk factors (eg., oxygen therapy for respiratory distress, sepsis, neonatal jaundice). A premature infant presented with "hybrid" zone 1 disease in the right eye and aggressive posterior ROP in the left eye. Both eyes were adequately treated with laser photocoagulation; however, the eyes deteriorated and progressed to stage 4 ROP. Both eyes eventually underwent intravitreal bevacizumab followed by lens sparing vitrectomy with good anatomical and visual outcome. Anticipation of progression despite laser photocoagulation in certain clinical scenarios, frequent follow-up and timely surgical intervention is paramount.

INTRODUCTION

Infants with aggressive posterior retinopathy of prematurity (APROP) and specific clinical profiles are likely to progress despite laser treatment.1 In these patients, frequent follow-up (every 3–4 days) after laser photocoagulation (LP) is imperative. Additionally, timely vitreous surgery on the development of a retinal detachment is essential. Acceptable visual outcomes can be achieved if the above protocol is followed. This case report presents the progression and management of a premature infant with APROP with a protracted clinical course.

CASE REPORT

An female infant was referred to our tertiary care ophthalmology center, 9 weeks after birth on detection of retinopathy of prematurity (ROP) by the local ophthalmologist. The birth weight was 700 g and gestational age was 26–28 weeks. The infant had been admitted to a neonatal intensive care unit (NICU) due to multiple risk factors including respiratory distress syndrome, sepsis and neonatal jaundice. At presentation, she weighed 1400 g. The anterior segment showed neovascularization of the iris, poorly dilating pupils and significant tunica vasculosa lentis. The posterior segment was evaluated using the binocular indirect ophthalmoscope and documented with the RetCam imaging system (Clarity Medical Systems, USA). The patient had bilateral APROP with a few preretinal hemorrhages with plus disease.2 The presence of a ridge with new vessels elsewhere (NVE) that had bled in the right eye qualified this as “hybrid” zone 1 disease [Figure 1].3 Parents were exhaustively counseled and consent obtained for LP. The patient underwent LP the same day.

Figure 1

RetCam images at presentation showing Hybrid form of retinopathy of prematurity, zone 1 disease in the right eye, aggressive posterior retinopathy of prematurity in the left eye. Arrows show flat neovascularization

Laser photocoagulation was performed with the double frequency yttrium-aluminum-garnet laser of wavelength 532 nm with an indirect ophthalmoscope delivery system with a spot size of 500 microns (Iridex Oculight Tx; Iridex Corporation, USA). The laser parameters were as follows right eye 2981 shots and left eye 2611 shots with energy of 90–110 mW, each shot duration being 100 ms. Pigmented eyes of Indian infants have a higher uptake of laser energy.4 The extensive LP bilaterally was punctuated by spells of bradycardia. The bradycardia, poorly dilating pupils and tunica vasculosa lentis may interfere with complete treatment. An improvement in the plus disease was observed 6 days after laser treatment. Ten days after the initial LP, additional LP was performed to cover the areas inside the vascular loops (right 846 shots/left 346 shots). No skip areas were noted. Few elevated fibrovascular proliferative bands were seen though the NVEs were regressing [Figure 2]. The patient was followed-up every 4 days.

Figure 2

After first retinal laser photocoagulation. Image quality affected in left eye due to tunica vasculosa lentis

Eleven days after the additional laser, deterioration of both eyes was noted. The APROP had progressed to stage 4 ROP showing the tractional retinal detachment, vitreous bleed and recurrence of the plus disease [Figure 3].2 The patient underwent surgery and had to be given packed red blood cells as the hemoglobin was only 7 g/dL. The patient received intravitreal bevacizumab (IVB) (0.625 mg i.e. 0.025 ml) in the right eye followed 4 days later by lens sparing vitrectomy (LSV). Intravitreal bevacizumab was injected in the left eye at the end surgery in the right eye. This was followed by left eye LSV, a few days later as depicted in Table 1. Three port pars plana vitrectomy was performed by standard technique described by Trese et al.5

Figure 3

Progression of aggressive posterior retinopathy of prematurity with vitreous bleed, stage 4A (right eye 3, right eye 3) and nasal tractional retinal detachment (left eye3)

Table 1

Time frame of treatment

Postoperatively, the patient was meticulously followed-up for over 10 months after the 2nd surgery that included assessment for visual acuity and retinal status. Total regression of the retinopathy was noted postoperatively with complete resolution of vitreoretinal traction bilaterally [Figure 4]. At 46 weeks follow-up at a postmenstrual age of 300 days, the baby had central, steady and maintain fixation in both eyes with a visual acuity of 4.7 cpd (cycles per degree) @ 55 cm in each eye and 9.6 cpd @ 55 cm binocularly. No resistance to unilateral occlusion was noted. The patient had 6 D of myopia bilaterally.

Figure 4

8 months after lens sparing vitrectomy showing an attached retina

DISCUSSION

In this case, the right eye showed the hybrid form of ROP demonstrating both ridge tissue (simulating staged ROP) and flat neovascularization simulating APROP in the same eye.3 infants <1000 g should be screened within 20 after birth. This is a cardinal rule that was not followed by the referring NICU in this case.6 Preterm, very low birth weight infants with multiple risk factors can be challenging to manage.1 Progression of retinopathy can occur despite adequate LP.17 In fact, APROP is known to progress directly to retinal detachment.2 In patients with APROP, recognizing the unique high risk characteristics such as gestational age <29.5 weeks, zone 1 disease, presence of preretinal hemorrhages prior to laser therapy, and appearance of de novo fibrovascular proliferation after laser is as essential as is strict daily follow-up and aggressive surgical intervention to ensure good visual outcomes.1

Studies have reported extremely high levels of vascular endothelial growth factor (VEGF) in ROP as compared to other retinal vascular diseases.8 LP does not neutralize the VEGF that is already produced but prevents further production of VEGF. This effect occurs over a week the ablative effect of LP is established. However, a is a relatively long interval in the natural course of ROP.7 The patient received bevacizumab a few days prior to surgery to neutralize the VEGF and decrease the chances of intra- and postoperative bleeding. A few centers advocate use of bevacizumab as initial therapy for APROP.9 We treat APROP with LP, with remains the gold standard, due unaddressed long-term safety concerns associated with IVB treatment. At our center, IVB is reserved as a rescue therapy for cases with small pupils, rubeosis (where laser is impossible, as primary treatment) or for ablated nonregressing APROP as a secondary treatment.

In this case, strict and frequent follow-up and aggressive intervention were important to the outcome. Marked deterioration of similar cases is known to occur within a couple of days.1 Without frequent follow-up, the progression (despite treatment) of the disease would have been missed. If follow-up is every 2–3 months cases often return with stage 5 ROP despite adequate laser treatment. The role of LSV to relieve vitreoretinal traction in such cases cannot be overemphasized.510 The surgical intervention prior to detachment of the macula was a significant prognostic factor for visual recovery.510

Our case illustrates that infants with APROP and with similar (specific) clinical profiles are likely to progress despite laser treatment.1 Frequent follow-up, every 3–4 days, is warranted for these cases. Decisive and timely vitreous surgery on the development of a retinal detachment is the key to good anatomical and visual outcomes. In high-risk infants similar to this case, there is no room for complacency even after adequate photocoagulation.