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Year : 2005  |  Volume : 53  |  Issue : 4  |  Page : 261-265

Fulminate retinopathy of prematurity - Clinical characteristics and laser outcome

Vitreo-Retinal Services, Aravind Eye Hospital & Postgraduate Institute of Ophthalmology, Coimbatore, Tamil Nadu, India

Correspondence Address:
Parag K Shah
Department of Vitreous & Retina, Aravind Eye Hospital, Avinashi Road, Coimbatore- 641 014, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0301-4738.18908

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Purpose: To analyse the clinical characteristics and treatment outcome of zone 1 Fulminate type of Retinopathy of Prematurity (ROP) and compare it to Conventional ROP.
Preterm infants from two neonatal intensive care units (NICU) born between July 2002 and November 2003 were screened for ROP. Cases with Conventional ROP were classified according to the International Classification of Retinopathy of Prematurity (ICROP) while that of Fulminate ROP according to Shapiro's classification. Threshold disease was kept the cut off for treatment for Conventional ROP and stage 3A for Fulminate ROP.
Of the 54 cases that had treatable ROP, 36 (66.67%) had Fulminate type. The mean gestational age and birth weight was higher in Fulminate ROP compared to Conventional disease (31.75 weeks and 1554 gms vs 31 weeks 1387 gms) whereas the mean postnatal age at laser was lower (4.62 weeks vs 6.3 weeks). The average number of laser spots given was 3036.6 for Fulminate disease.
Fulminate ROP had an atypical morphology which was difficult to classify according to ICROP classification and we would like to lay stress upon the importance of screening of premature infants from the age of 4 weeks and to start treatment immediately once Fulminate ROP has been diagnosed.

Keywords: Zone 1, Fulminate, retinopathy of prematurity

How to cite this article:
Shah PK, Narendran V, Saravanan V R, Raghuram A, Chattopadhyay A, Kashyap M, Morris RJ, Vijay N, Raghuraman V, Shah V. Fulminate retinopathy of prematurity - Clinical characteristics and laser outcome. Indian J Ophthalmol 2005;53:261-5

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Shah PK, Narendran V, Saravanan V R, Raghuram A, Chattopadhyay A, Kashyap M, Morris RJ, Vijay N, Raghuraman V, Shah V. Fulminate retinopathy of prematurity - Clinical characteristics and laser outcome. Indian J Ophthalmol [serial online] 2005 [cited 2023 Jan 29];53:261-5. Available from: https://www.ijo.in/text.asp?2005/53/4/261/18908

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In 1977 the report of the Japanese retinopathy of prematurity (ROP) group identified a special form of ROP, which occurred in zone 1 or posterior zone 2 which they called Fulminate or type-II ROP.[1],[2] The International classification of retinopathy of prematurity (ICROP)[3] only stages the common cases of ROP (for the purpose of this study we named ROP that can be classified by ICROP as Conventional ROP). However, it does not identify the special findings and morphology seen in Fulminate ROP. Since the ICROP classification only includes the vascular abnormalities associated with demarcation line or ridge, the vascular proliferation seen in cases of Fulminate ROP is often overlooked until late when even the laser treatment is of little benefit and the eye ends up in an unfavourable outcome defined as a posterior retinal fold involving macula, a retinal detachment involving zone 1 or a retrolental mass that obscures the view of the posterior pole.[4]

These infants usually have very short gestational age along with very low birth weight. The natural history of Fulminate ROP is not fully understood and a new classification is needed to define its morphology and appropriate timing of intervention. In this study, we have followed the classification of Fulminate ROP, which has been proposed by Shapiro[5] in 1996. There are three stages. In stage 1 there is no definite opaque demarcation line at the junction of the vascular and avascular retina. There may be a halo at the edge of the vascular junction. In stage 2, the fibrous tissue is transparent and arteriovenous anastomoses are seen in the avascular retina. Stage 3 is divided into 3A, 3B and 3C. In stage 3A new vessels are seen, which appear flat as fronds or tangles in circumferential extent. In stage 3B neovascular frond is clearly above the retinal plane and is seen in isolated regions less than 2 Clock h. In stage 3C the new vessels continue to extend circumferentially, radially and in height.

The cryotherapy for retinopathy of prematurity (CRYO-ROP) study has established the effectiveness of peripheral retinal cryotherapy for infants with threshold ROP.[4] Recently, the early treatment for retinopathy of prematurity (ETROP) study has shown to significantly reduce the unfavourable outcomes to a clinically important degree in early treatment of high risk prethreshold ROP.[6] Laser treatment has become the treatment of choice in zone 1 ROP because of its better outcome.[7] But these results still lag far behind compared to Conventional ROP. We analysed our cases of Fulminate ROP and assessed their clinical characteristics and treatment outcome.

  Material and Methods Top

All preterm infants born between July 2002 and November 2003 were screened for ROP from two neonatal intensive care units (NICU). All preterm infants were screened and there was no cut-off criteria as in past we have seen infants with birth weight >2000 g and gestational age >32 weeks going for unfavourable outcome. The neonatal nurse administered dilating drops 45 min before examination. The drops used were a combination of 0.5% cyclopentolate and 2.5% phenylephrine, one drop repeated every 15 min. The first examination was done at the NICU before discharge and subsequent examinations were done at the base hospital. Follow-up visits were timed according to the severity of the disease. If immediate treatment was warranted then laser was done at the NICU within 72 h of diagnosis using a portable green laser.

Clinical examination was performed by one of the authors with an indirect ophthalmoscope using a 20 D lens, lid speculum and scleral depressor. A drop of 0.5% proparacaine was used for topical anaesthesia. RetCam 120 (Massie laboratories, CA, USA)[8] was used to photograph the posterior pole and as much as possible of the periphery for all the cases examined at the base hospital after the clinical examination. We classified all patients as having either zone 1, zone 2 or zone 3 disease. If it spanned more than a single zone then it was classified in the more posterior zone. Cases with conventional ROP were classified according to the ICROP classification[3] while that of Fulminate ROP were classified according to the classification proposed by Shapiro.[5] Laser was given at threshold disease[4] for conventional ROP and stage 3A[5] for Fulminate ROP. Treated eyes received photocoagulation of the entire avascular retina with near confluent burns. Diode green laser (Oculight GL, Iridex Co., CA, USA) was used when performed in the NICU and double frequency Yttrium aluminum garnet (YAG) laser (Zeiss Visulas 532) when done at base hospital. All lasers were done under topical anaesthesia with neonatologist standby. An unfavourable outcome was defined in the same manner as in the CRYO-ROP study.[4]

  Results Top

We screened 166 infants from two NICU's. Of these 54 (32.53%) cases had treatable ROP, of which 36 (66.67%) had Fulminate ROP. All the fulminate cases were bilateral symmetrical and were of stage 3A. In cases of uncertainty between stages 2 and 3A, we preferred to upgrade the stage and treat early rather than late. The mean gestational age was 31.75 weeks (range 28-34 weeks) and the mean birth weight was 1554 g (range 850-2290 g). Five were lost to follow up and in one case the consent for laser was not given by the parents. This baby later presented with stage 5 ROP in both eyes. The mean postconceptional age at treatment of the remaining 30 cases was 36.56 weeks (range 31.5-41 weeks) and mean postnatal age at laser was 4.62 weeks (range 1.5-8 weeks). The average number of laser spots given was 3036.6 (range 920-7000) and the average number of sittings was 1.86 (range 1-4). Thirteen eyes (18%) of seven cases had an unfavourable outcome postlaser. Six had stage 5 ROP, six had stage 4A and one had stage 4B. One eye developed disc drag as the baby presented 1 week late for laser.

Eighteen (33.33%) cases had conventional ROP threshold stage. The mean gestational age was 31 weeks (range 28-34 weeks) and mean birth weight was 1387 g (range 1000-1880 g). Five eyes of five cases regressed without laser. Of the remaining 31 eyes the mean postconceptional age at treatment was 37.15 weeks (range 33.3-40.6 weeks) and the mean postnatal age at treatment was 6.3 weeks (range 4-8.6 weeks). The average number of laser spots given was 1356.13 (range 175-5605) and the average number of sittings was 1.58 (range 1-4). Three eyes (8.33%) of two cases had unfavourable outcome, each eye having stages 4A, B and 5, respectively.

  Discussion Top

All the cases of Fulminate ROP showed an atypical morphology that was difficult to analyse according to the ICROP criteria. Instead of a demarcation line between vascular and avascular retina, a demarcation vessel was observed which had a direction perpendicular to the retinal blood vessels [Figure - 1]. The disease usually occurs inside a definite zone, which on the nasal side extends 2-3 disc diameters from the disc margins and on the temporal side reached up to the lateral edge of the macula [Figure - 2]. When proliferation ensues, it arises from the arteriovenous arcades in flat nets that become thicker and more elevated with time, forming a brush-like neovascular network [Figure - 3]. Characteristic stage 2 may be absent, and stage 1 quickly progresses to a network of neovascularisation that may extend for many clock hours. Classic stage 3 was not always observed despite plus disease. In many instances the neovascular proliferation associated with plus disease took the form of a flat network of vessels either at the level of the demarcation or slightly more posterior. We have found that in Fulminate cases the shunting does not occur across the ridge characteristic of stage 3 but in a peripheral arteriovenous arcade as described by Shapiro et al.[9] [Figure - 4]. There may be a halo seen at the edge of the vascular junction and also around the arteriovenous anastomotic vessel. These vessels may go beyond the junction in the avascular retina, so finding the exact junction between the vascular and avascular retina might be difficult and while treating these cases we have given laser spots even inside the vascular loops formed by the arteriovenous shunt. Fundus fluorescein angiography (FFA) is a tool that could have highlighted the exact junction between the avascular and vascular retina. All these vascular changes are often overlooked and the eye rapidly ends up in retinal detachment and blindness.

Although, no infant reached threshold disease before age 5 weeks in the CRYO ROP study, in our study Fulminate ROP was treated at an average age of 4.62 weeks (1.5-8 weeks). Thus we think that Fulminate ROP develops earlier and progresses faster than conventional ROP, a fact that has been proved in the literature.[2],[10],[11],[12] Except for the study by Nissenkorn et al.,[10] the mean postnatal age at treatment is much lesser in our series. Thus a screening program that begins at 4 weeks of postnatal age[13],[14] is recommended. This will lead to earlier identification of Fulminate ROP, which can alert the screening ophthalmologist to the need for a closer follow up. The Fulminate cases were observed with a high degree of symmetry between the two eyes, also reported in literature.[11] This is not always the case in conventional ROP.

Fulminate ROP is known to occur in infants with very low gestational age and birth weight. The mean gestational age and mean birth weight is much higher in our study compared to earlier Western studies [Table - 1], but is comparable to some studies from India.[12],[15],[16],[17] So, we conclude that zone 1 ROP occurs in babies with higher birth weight and gestational age in Indian compared to Western population.

Three hundred and thirty-six was the average number of laser burns per eye reported by Despande et al.[18] and they had an unfavourable outcome in all the cases of zone 1 ROP. The average number of laser spots given was 3036.6 in our study with a near confluent configuration [Figure - 5] and a good outcome, which is comparable to our previous report.[12] Circumferential ablation of the avascular peripheral retina while getting as close as possible to the edge of the vascularisation has been shown to achieve retinal quiescence within hours.[19] Thus we recommend a very aggressive laser when it comes to zone 1 disease. [Figure - 6][Figure - 7][Figure - 8][Figure - 9] show pre and postlaser regressed Fulminate ROP.

The CRYO ROP study demonstrated that cryo therapy resulted in a significant decrease in the rate of unfavourable outcome when compared with untreated eyes.[4] However, in zone 1 eyes, it demonstrated that the rate of unfavourable outcome was reduced by only 17% (from 92% unfavourable outcome in control eyes vs 75% of unfavourable outcome in treated eyes) as compared to overall reduction of 39.5% in all the eyes. Much better results have been reported with laser treatment. In the ETROP study the greatest benefit of treatment was seen in eyes with zone 1 stage 3 ROP with or without plus disease (30.8% unfavourable outcome in early treatment eyes vs 53.8% unfavourable outcome in conventionally treated eyes).[6] In 1992, Fleming et al.[20] reported a 100% success rate by using indirect laser treatment. However, they performed treatment much earlier than threshold stage. In 1993, Capone et al.[7] reported a 17% unfavourable outcome. They performed treatment at threshold stage. Shapiro et al.[9] reported a 36% unfavourable outcome rate in zone 1 eyes. Vander et al.[11] reported a 16% unfavourable outcome in zone 1 eyes treated earlier than threshold and an 18% unfavourable outcome for control eyes treated at threshold. Katx et al.[21] reported 40% unfavourable outcome for zone 1 cases, but in this study there was a mixture of cases treated at varying stages of the disease, some of them having passed even the threshold stage. Zone 2 eyes showed a 9.8% unfavourable outcome in the same study. Despande et al.[18] reported unfavourable outcome in both the cases of zone 1 ROP they diagnosed. In our study 18% of Fulminate ROP had unfavourable outcome [Table - 2]. For conventional ROP it was 8.33%.

Fulminate ROP is less common than conventional ROP. The natural history of this type has not been clearly documented. A number of series[2],[4],[7] have reported that zone 1 eyes comprise between 1 and 9% of the total number of treated patients. The ETROP study[6] showed that zone 1 disease accounted for approximately 40%. In our study, it was found to be 66.67%. The higher number of Fulminate cases in our study is unusual. Of the 36 cases, 34 were from a single NICU. This NICU was observed to give unmonitored 100% Oxygen (O2) to the babies via a plastic funnel which was tied tightly to the infants face fully covering the mouth and nose, while the other NICU gave monitored O2 in the form of hood. STOP ROP study[22] has already ruled out the role of O2 in the progression of prethreshold to threshold ROP. But O2 being a cause of this high incidence of Fulminate ROP in present study cannot be substantiated as it is a retrospective one and only a prospective randomised study can prove it.

Thus in conclusion, Fulminate ROP, which is known to occur only in children with very low birth weight and gestational age, can still be present in bigger babies in developing countries like India where good NICU management is still lacking in many centres. Thus, we recommend screening of all infants at 4 weeks of age with early aggressive treatment as soon as Fulminate ROP is diagnosed for a better outcome[23].

  References Top

Uemura, Y. Current status of Retrolental Fibroplasia. Report of the joint committee for the study of Retrolental Fibroplasia in Japan. Japan J Ophthalmol 1977:21:366-78.  Back to cited text no. 1
Majima, A. studies on retinopathy of prematurity: statistical analysis of factors related to occurrence and progression in active phase. Japan J Ophthalmol 1977:21:404-20.  Back to cited text no. 2
The Committee for the Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity. Arch Ophthalmol 1984;102:1130-4.  Back to cited text no. 3
Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicentre for trial for cryotherapy of retinopathy of prematurity: three month outcome. Arch Ophthalmol 1990;108:195-204.  Back to cited text no. 4
Shapiro MJ. Type 2 or Fulminate ROP. In: Kumar H, Shapiro MJ, Azad RV, editors. A Practical Approach to Retinopathy of Prematurity Screening and Management. New Delhi: Malhotra Enterprises; 2001. p. 23-33.  Back to cited text no. 5
Early Treatment of Retinopathy of Prematurity Cooperative Group. Revised indications for the treatment of retinopathy of prematurity. Arch Ophthalmol 2003;121:1684-96.  Back to cited text no. 6
Capone A, Diaz RR, Sternberg P, Mandell B, Lambert M, Lopez P. Diode laser photocoagulation for zone 1 threshold retinopathy of prematurity. Am J Ophthalmol 1993;116:444-50.  Back to cited text no. 7
Roth DB, Morales D, Feuer WJ, Hess D, Johnson RN, Flynn JT. Screening for retinopathy of prematurity employing the RetCam 120. Arch ophthalmol 2001;119:268-72.  Back to cited text no. 8
Shapiro MJ, Gieser JP, Warren KA, Resnick KI, Blair NP. Zone 1 retinopathy of prematurity. In : Shapiro MJ, editor. Retinopathy of Prematurity: proceedings of the international conference on retinopathy of prematurity. New York: Kugler Publications; 1995. p. 49-155.  Back to cited text no. 9
Nissenkorn I, Kremer I, Gilad E, Cohen S, Ben-Sira I. 'Rush' type retinopathy of prematurity: report of three cases. Br J Ophthalmol 1987; 71:559-62.  Back to cited text no. 10
Vander JF, Handa J, McNaara A, Treese M, Srencer R, Repka MX, et al . Early treatment of posterior retinopathy of prematurity, a controlled trial. Ophthalmology 1997;104:1731-6.  Back to cited text no. 11
Shah PK, Narendran V, Saravanan VR, Raghuram A, Chattopadhyay A, Kashyap M, Devraj S. Fulminate type of Retinopathy of Prematurity. Indian J Ophthalmol, 2004,52:319-20.  Back to cited text no. 12
Jalali S, Anand R, Kumar H, Dogra MR, Azad R, Gopal L. Programme planning and screening strategies in Retinopathy of Prematurity. Indian J Ophthalmol 2003;51:89-99.  Back to cited text no. 13
Reynolds JD, Dobson V, Quine GC, Fielder AR, Palmer EA, Saunders RA, et al. CRYO-ROP and LIGHT-ROP cooperative groups. Evidence based screening criteria for ROP. Natural history data from the CRYO-ROP and LIGHT-ROP studies. Arch Ophthal 2002;120:1470-6.  Back to cited text no. 14
Gopal L, Sharma T, Ramachandran S, Shanmugasundaram R, Asha V. Retinopathy of prematurity. A study. Indian J Ophthalmol 1995;43:59-61.  Back to cited text no. 15
Charan R, Dogra MR, Gupta A, Narang A. The incidence of retinopathy of prematurity in a neonatal care unit. Indian J Ophthalmol 1995;43:123-6.  Back to cited text no. 16
Gopal L, Sharma T, Shanmugam M, Badrinath SS, Sharma A, Agar HS, et al . Surgery for stage 5 retinopathy of prematurity. The learning curve and evolving technique. Indian J Ophthalmol 2000;48:101-6.  Back to cited text no. 17
Despande DA, Chaturvedi M, Gopal L, Ramachandran S, Shanmugasundaram R. Treatment of threshold retinopathy of prematurity. Indian J Ophthalmol 1998;46:15-9.  Back to cited text no. 18
Ben-Sira I, Nissenkorn I, Grunwald E, Yassur Y. Treatment of acute retrolental fibroplasias by cryopexy. Br J Ophthalmol 1980;64:758-62.  Back to cited text no. 19
Fleming TH, Runge PE, Charles ST. Diode laser photocoagulation for prethreshold posterior retinopathy of prematurity. Am J Ophthalmol 1992;114:589-92.  Back to cited text no. 20
Katx X, Kychenthal A, Dorta P. Zone 1 retinopathy of prematurity. JAAPOS 2000;4:373-6.  Back to cited text no. 21
The STOP-ROP Multicenter Study Group. Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP), a randomized controlled trial: Primary Outcomes. Pediatrics 2000;105: 295-310.  Back to cited text no. 22
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  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8], [Figure - 9]

  [Table - 1], [Table - 2]

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