FP786 : Early versus Late Presentation of Aggressive Posterior Retinopathy of Prematurity

Dr. Simar Rajan Singh, S16917, Dr. Mangat
R Dogra, Dr. Deeksha Katoch, Dr. Savleen Kaur

INTRODUCTION: 

The international committee for classification of ROP (ICROP)¹ classified a rapidly progressing, relatively less common but severe ROP as aggressive posterior ROP (APROP). Multiple treatment modalities including laser photocoagulation, vitreous surgery and intra-vitreal anti VEGF injections isolated or in combination have been tried to arrest the progression of disease and achieve optimal outcome. ETROP² study recommended early peripheral retinal ablation in prethreshold ROP. Although no such guideline exists in case of APROP, early laser treatment (if media permits) at presentation is considered as mainstay of management due to very fast progression of the disease. We conducted the present study to look for the structural outcome in APROP eyes in a tertiary referral centre that were treated at a very early age (less than one month of age). We also compared the early treatment outcome with a cohort of infants who were treated relatively late (more than 1 month) .

METHODOLOGY: 

In our retrospective study,we included infants diagnosed and treated for aggressive posterior ROP (APROP) at Postgraduate Institute of Medical Education and Research, Chandigarh, India from December 2005 to June 2014.All infants were examined in details by indirect ophthalmoscopy and findings were documented by meticulous retinal drawings by an experienced retinal surgeon (MRD).Diagnosis was made according to guidelines of revised international classification of retinopathy of prematurity (ICROP)¹. Study population were divided into two groups; Group A:infants treated at or less than 31 days of age and Group B: infants treated after 31 days of age. The above groups were compared for baseline parameters, disease spectrum and structural outcome.Baseline parameters included birth weight, gestational age at birth, place of birth (inborn/out born), single/multiple birth, postnatal age of laser treatment.Classification of APROP was done into one of the following zones: posterior zone 2, anterior zone 1 (vessels confined to zone 1 but developed beyond the fovea), or posterior zone 1 (vessels posterior to the fovea). Spectrum of disease was defined as Classic in eyes with features consistent with ICROP definition of APROP (flat neovascularization, posterior disease with significant plus disease) and Hybrid in eyes with co-existence of classic features and intermittent presence of ridge tissue. Any presence of tunica vasculosa lentis (TVL), retinal haemorrhage or fibro vascular proliferation before treatment was also noted. Retcam (Clarity MSI, leasanton, California, USA) photograph was taken whenever possible. Eyes with retinal detachment at presentation (stage 4A, 4B, and 5) and eyes lost to follow up were excluded. After obtaining informed consent from the parents, laser photocoagulation was performed by retina specialists with either of the two available laser devices a) 810-nm diode laser (IRIS Medical Oculight SL 810-nm infrared laser; Iris Medical Inc, Mountain View, California, USA) and b)532-nm green laser. All treatments were done under monitoring of neonatal intensive care unit (NICU).Laser burns were applied in a near confluent manner (less than a half burn width apart) to the entire avascular retina from the flat revascularization to the ora serrata. Mode of laser (diode/ green) and no of laser spots were noted. Each of the treated infants were followed on weekly basis to see the course of disease(regression/progression), any appearance of new onset retinal haemorrhage, fibro vascular proliferation (limited: less than 3 clock hour; extensive: more than 3 clock hour) or retinal detachment. Repeat laser treatment was done in skip areas (due to retraction of flat neovascular complex) at subsequent follow ups if required. Time for disease regression was noted. Outcome was considered favorable in cases of complete disease regression and unfavorable in cases of progression to stage 4A, 4B, or 5 or falciform fold. All eyes had a minimum 3-month follow-up after laser treatment.

RESULTS:

One hundred ninety five eyes of 100 infants met the inclusion criteria and were included in this study. Of these 100 infants, 87 eyes of 44 infants were treated before 31 days (Group A) and 108 eyes of 56 infants were treated after 31 days of life (Group B).Baseline characteristics were depicted in table A. The mean birth-weight of early treatment group (1518.7 g) was statistically higher with respect to late treatment group (1312.2 g)(p=0.001).Maximum birth-weight recorded was 2600 gms in Group A and 2300 gms in Group B. Mean gestational age was 30.62.2 wks in Group A and 29.52.6wks in Group B (p= .02).Both the groups had male preponderance. The mean postnatal age at laser treatment was 27.2±3.8 days in Group A and 41.9±9.4 days in Group B. Infants as early as 20 days of postnatal age was treated in Group A and as late as 65 days were treated in Group B. However, such late treatment in Group B is due to delayed referral to our centre. Almost all infants (except 1 in Group A and 2 in Group B) were born outside (labeled as out born) and referred to us for ROP treatment. Posterior zone 2 disease was encountered in 60.9% of Group A and 67.6% of Group B eyes (p=0.3). Rest of the eyes had zone 1 disease. However none of Group An eyes had posterior zone 1 disease as against ten eyes(9.3%) in group B. Both the groups comprised of comparable proportions of classic and hybrid APROP (p=0.07). No statistically significant difference with regard to the pre-existing TVL (p= 0.57) and haemorrhage (p=0.89) was noticed between the groups before laser treatment. 13.8% infants in Group B presented with fibro-vascular proliferation before laser treatment as compared to 3.4% in Group B (p=0.03).Mean no of laser spots required was significantly higher in Group B (p=0.001) with mean time interval between primary and supplemental laser treatment significantly less in Group B (p=0.04). Eighty six out of 87 eyes (98.9%) in Group A achieved favorable outcome as compared to 88 out of 108 eyes (81.5%) in Group B which is statistically significant (p=0.001). Mean time for disease regression was statistically higher in Group A(p= 0.001).After laser treatment, incidence of new onset haemorrhage was significantly higher in Group B (p=0.03) although new onsetfibrovascular proliferation was noted comparably in both the groups (p= 0.73).However, new onset fibro vascular proliferation which were extensive (more than 3 clock hours) and located temporally was particularly noticed in group B.

Table 1: Demographics:

	Group A	Group B	p value
Birth weight (gms) (Mean ± SD) Range	1518.7±379.1 700-2600	1312.2±328.4 700-2300	0.001
Gestational age(wks) (Mean±SD) Range	30.6±2.2 27-37	29.5±2.6 26-38	0.02
Sex: Male	34 (77.3%)	42 (75%)	0.79
Multiple birth(%)	8 (18.2%)	16 (28.5%)	0.38
Post-natal age at laser treatment(days)( Mean ± SD) Range	27.2±3.8   20-31	41.9±9.4   32-65	0.001
Inborn	1(2.3%)	2(3.6%)	0.7

Table 2: Pre-treatment disease characteristics:

	Early group (n=87)	Late group (n=108)	P value
Pattern of Disease Classic APROP Hybrid pattern	65(74.7%) 22(25.3%)	71(65.7%) 37(34.3%)	0.07
Zone of disease Post zone P Ant zone I Post zone I	53(60.9%) 34(39.1%) 0(0%)	73(67.6%) 25(23.1%) 10(9.3%)	0.33
TVL	34(39.5%)	47(43.5%)	0.57
Haemorrhage	11(12.6%)	13(12%)	0.89
Pre-existing FVP Limited Extensive(> 3                        clock hour)	3(3.45%) 3(3.45%) 0	15(13.9%) 8(7.4%) 7(6.5%)	0.03

Table 3: Treatment characteristics:

	Early treatment	Late treatment	p value
No of laser spots (Mean±SD)	2554±876	3081±1308	0.001
Need of supplemental laser	10(11.5%)	17(15.7%)	0.41
Average timing of supplemental laser from primary laser (days)	11.5±4.7	8.2±3.3	0.04

Table 4: Disease outcome characteristics:

	Early treatment (n=87)	Late treatment (n=108)	p value
Outcome: Favourable	86(98.9%)	88(81.5%)	0.001
Mean time of disease regression(wks)	5±1.5	3.8±1.2	0.001
New onset haemorrhage	23(26.4%)	37(34.3%)	0.03
New onset fibro vascular proliferation(FVP): Limited nasal FVP Limited temporal FVP Central FVP Extensive nasal FVP Extensive temporal FVP	19(21.7%)   7(8%) 11(12.6%) 0 1(1.1%) 0	27(25%)   3(2.8%) 7(6.5%) 3(2.8%) 5(4.6%) 9(8.3%)	0.73

CONCLUSION:

Early presentation as APROP in heavier and more mature infants is showing an increasing trend in the developing countries. This has implications for early screening guidelines for ROP at places where higher birth weight infants are developing APROP.