We thank Azad et al. for showing interest in our article.1 As this child needed immediate intervention to save the eye and prevent phthisis bulbi, a formal institutional review board approval was not possible as it would have taken at least a few months. The principal concern was potential altered vasculogenesis in the treated eye and other organs. But as the avascular retina was well ablated, we believe it safer to inject bevacizumab (Avastin) in this situation rather than as primary therapy in an eye with viable peripheral retina. With this background in the face of an eye that was rapidly deteriorating to cyclitic membrane formation and phthisis the authors considered the potential benefits and harmful side effects of intravitreal bevacizumab. The parents received extensive councelling regarding potential complications of bevacizumab including possible retarded growth or maldevelopment of other organs
Aggressive posterior retinopathy of prematurity (ROP) is now a distinct category of ROP which has been published2 and does not need further elaboration. The disease was symmetrical in both the eyes. There was no tunica vasculosa lentis seen prior to laser and iris neovascularization, hypotony, cataract and corneal clouding appeared after the ablative procedure. Given these features, anterior segment ischemia was the most likely diagnosis. Without prompt intervention, the eye would have likely progressed quickly to irreversible phthisis. Ocular hypotony due to scleral indentation is a consideration but typically this will be a transient phenomenon that typically would resolve with anti-inflammatory and cycloplegics therapy. It would typically occur within a day or two of laser rather than at one week's time. Our post-operative examination revealed no obvious choroidal effusion.
With a dramatically worsening clinical course after three days of topical steroids and cycloplegics, we believed that systemic steroids would not help much and could add to the complications. Moreover, use of high dose systemic steroids is ill advised in neonates because of potential growth retardation, adrenal suppression and hypertension. We have used systemic steroids on a series of patients with aggressive ROP and noted minimal ocular benefit. Most authorities in pediatric rheumatology recommend keeping the dose of steroids below 1 mg per kg body weight. In these children that dose is not enough to impact the severe proliferative and inflammatory response. To avoid complications like anterior segment ischemia, previous studies3 have suggested to perform scatter laser in the horizontal meridians, to do laser in multiple sittings (but both these would increase the risk of retinal detachment), to use less power while treating these meridians and to use cryo instead of laser as freezing causes less damage to the ocular vessels. But this should not discourage the treating surgeon from being aggressive in the treatment of ROP. We have shown improved visual and anatomic outcomes with early and thorough treatment.4
Anterior neovascularization, anterior fibrovascular proliferation and hypotony prompted us to the diagnosis of anterior segment ischemia. Iris atrophy and cataract were also seen to develop later, which also are consistent with anterior segment ischemia. There was likely an element of inflammation also but we felt ischemia was the predominant mechanism.
We too have a lot of reservations about injecting a drug like bevacizumab, in a premature child, and recommend that it only be used in carefully monitored trials or as a lat resort in advanced cases. In this precious neonate who was certainly going to lose an eye, we believe that there was no better alternative available and all standard treatments were exhausted. The parents gave a detailed informed consent for this intervention with the understanding of potential risks, and the outcome was favorable.
1. Shah PK, Narendran V, Tawansy KA, Raghuram A, Narendran K. Intravitreal bevacizumab (Avastin) for post laser anterior segment ischemia in aggressive posterior retinopathy of prematurity Indian J Ophthalmol. 2007;55:75–6
2. An international committee for the classification of retinopathy of prematurity. . The international classification of retinopathy of prematurity revisited Arch Ophthalmol. 2005;123:991–9
3. Lambert SR, Capone A Jr, Cingle KA, Drack AV. Cataract and phthsis bulbi after laser photoablation for threshold retinopathy of prematurity Am J Ophthalmol. 2000;129:585–91
4. Ingram A, Tawansy K, Ells A, Shah P. Aggressive Diagnosis and Management of Aggressive Posterior Retinopathy of Prematurity (ROP) Invest Ophthalmol Vis Sci. 2006;47:E–Abstract 5317