Atypical case of retinopathy of prematurity with candle wax-like preretinal deposits and its surprising response to intravitreal antivascular endothelial growth factor

Abstract

Presented here is a case of hybrid retinopathy of prematurity (ROP) with features of both aggressive posterior ROP and ridge-like staged ROP with extensive candle wax-like preretinal deposits plastered on the surface of the retina from optic disc to vascular–avascular junction at a postmenstrual age (PMA) of 34 weeks. The baby was too sick for laser photocoagulation and so underwent intravitreal bevacizumab at half adult doses in both eyes. The deposits melted dramatically within 1–2 weeks of antivascular endothelial growth factor injection without any signs of recurrence till the last visit at 58 weeks of PMA.

Background

Retinopathy of prematurity (ROP) affects babies born too early and/or underweight at birth with or without systemic risk factors. ROP classically progresses from stages 1 to 5 except for aggressive posterior form of ROP (APROP) which can skip stages and progresses rapidly. At times we see cases with features suggestive of APROP as well as staged ROP co-existing in the same eye described as Hybrid ROP by Sanghi et al.¹ Three patterns of hybrid ROP have been described: I Ridge at the junction of the vascular and avascular retina; II Ridge in the vascularised retina; III Poorly-defined ridge close to the optic disc with mat-like fibrous proliferation into the vitreous.¹

We describe an atypical ROP in posterior Zone I with features of hybrid ROP and unusual extensive candle wax like pre retinal deposits, not only at vascular avascular junction but also within the vascularised area up to the optic disc. These deposits melted dramatically within 1–2 weeks of anti-vascular endothelial growth factor (anti-VEGF) injection. Postinjection the retina continued to vascularise and the disease showed no signs of recurrence till the last visit.

Case presentation

A prematurely born baby hailing from a special newborn care unit (SNCU) was referred for ROP screening at 34 weeks of postmenstrual age (PMA). This baby was born out of a twin pregnancy (the other twin expired after birth) at 30 weeks of gestational age with a birth weight of 1500 g. There was respiratory distress and frequent apnoea for which he was on 100% O2 supplementation via hood (3 weeks) and nasal prongs (1 week) along with systemic antibiotics for suspected sepsis. Instead of weight gain, there was continued weight loss (weight at examination: 1250 g). The baby was on 100% oxygen via hood for 3 weeks followed by nasal prongs for a week. The oxygen saturation was 89%–94%.

Both the eyes had good mydriasis, clear media, pre retinal deposits, arterio-venous loops and a ridge. The baby was too sick, and fundus imaging was deferred. A week later (35 weeks of PMA), there was further worsening and the pupillary dilatation was moderate. Fundus as imaged with RetCam (Clarity Medical Pleasanton, California) showed tortuous retinal vessels within posterior zone I. The arteries and veins were looking alike with arteriovenous shunts at multiple levels. There were extensive preretinal candle wax-like preretinal deposits extending from the disc up to the vascular–avascular junction(figure 1A, B). The deposits were confluent and more extensive nasally then temporally. There was preretinal haemorrhage superotemporal to the optic disc in the right eye (figure 1A). A ridge was seen superonasally in the right and inferiorly and superotemporally in the left eye.

Figure 1.

RetCam fundus image of the right (A) and left eye (B) at 35 weeks of postmenstrual age shows retinal vascular tortuosity, retinal arteriovenous shunts at multiple levels within posterior zone I (arrow heads). There was extensive candle wax preretinal deposits extending from vascular avascular junction up to optic disc in both eyes (arrows). They were discrete near the optic disc but tend to be confluent and more extensive in the nasal periphery. Right eye (A) showed pre-retinal haemorrhage superotemporal to the disc while ridge was seen nasally in both eyes.

Treatment

The baby was sick, so laser was deferred and intravitreal anti-VEGF (Bevacizumab half adult dose) was given in both the eyes on the same day at the bedside after parental consent on the off-label use of Bevacizumab for ROP, need for bedside injection as the baby was non-transferrable and possible ocular and systemic alerts. Need for long and frequent follow-up, possibility of disease recurrence and need for additional treatment in that event were explained to the parents.

Outcome and follow-up

The preretinal deposits melted dramatically within a week (PMA-37 weeks), with a reduction in the plus component. There was no trace of these preretinal deposits at 39 weeks of PMA (figure 2A, B). At 43 weeks of PMA, the baby was stable and discharged from the SNCU and showed stage I zone II ROP with no plus component in both the eyes. The vascular outgrowth was very slow, thereafter, with regression of retinopathy and vascularisation up to zone III (figure 3A, B). There was no return of the disease activity till the last follow-up at 58 weeks of PMA.

Figure 2.

Composite fundus picture of the right (A) and left eyes (B) imaged with RetCam at 39 weeks of postmenstrual age (4 weeks postinjection), showing complete resolution of pre-retinal deposits along with reduction in plus component.

Figure 3.

Composite fundus images of the right (A) and the left eye (B) at 51 weeks of postmenstrual age shows retinal blood vessels of normal calibre without any tortuosity extending up to zone III in both eyes. There was a demarcation line (stage 1) in zone III (not clear here) in both eyes.

Discussion

The ROP case presented here had an atypical phenotype that one needs to be aware of to avoid delay in the diagnosis and management. The baby was quite big to have features of aggressive ROP, which is not unusual in India.^2–6 The candle wax-like pre retinal deposits were quite interesting and we had the following differentials in mind with respect to its composition and pathogenesis.

Popcorn lesions (intraretinal new vessels) especially when fused can grow posteriorly from the ridge.^{7 8} The exudates were too extensive and were extending up to the optic disc, which usually is not seen with the popcorns.^{2 3} Sometimes, popcorn or popcorn-like deposits disappear with laser but not so rapidly that is seen here. Endogenous endophthalmitis can sometimes present with these exudates but was ruled out as the eye was quiet, vitreous was clear and had a good therapeutic response with anti-VEGF monotherapy. Organised preretinal haemorrhage especially when longstanding and altered can have a similar appearance but usually has some fresh and red colour blood to variable extent. Fibrovascular proliferation, where fibrosis dominates over the vascular component, can, at times, give a similar appearance, but usually, they tend to be located at the posterior border of the ridge and show some vascularity (unlike the present case where the deposits did not have any blood vessels clinically). Extensive vitreous condensation overlying the vascularised retina is another possibility, but the deposits noted in the present cases were noted to be lying on the retinal surface rather than vitreous cavity. Mat-like opaque fibrous membranes in cases of pattern III hybrid ROP as described by Sanghi et al¹ or in canine model of oxygen-induced retinopathy had a resemblance with the morphology described here.³ We believed that poorly formed retinal vessels and blood retinal barrier secondary to oxygen toxicity could have resulted in abnormal exudation or fibrin within the vascularised retina in the present case. Fundus fluorescein angiogram could have given a better insight into the underlying pathogenesis. Unfortunately, we did not have access to bedside fundus fluorescein angiogram (FFA) in neonates. Dramatic resolution of the exudates with anti-VEGF injection hints at a possible VEGF-dependent pathogenesis. Poor systemic status like sepsis, apnoea, poor weight gain could have contributed to the pathogenesis of these changes further. Documentation and analysis of similar cases in the future would give a better insight into the nature of these exudates.

Patient’s perspective.

We were extremely worried about our baby’s eyes. Multiple counselling regarding the nature of the disease, bed side intravitreal injection and subsequent disease resolution gave us great relief.

Learning points.

• Retinopathy of prematurity at times can have atypical features such as extensive candle wax-like preretinal deposits as seen in this case.

• Knowing this entity could avoid one for any unnecessary investigation and help in prompt management.

• The dramatic resolution of the deposits with antivascular endothelial growth factor (anti-VEGF) could hint at a VEGF-dependent mechanism responsible in the pathogenesis of such lesions.

Ethics statements

Patient consent for publication

Consent obtained from parent(s)/guardian(s)