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ORIGINAL ARTICLE
Year : 2014  |  Volume : 62  |  Issue : 5  |  Page : 610-614

Impact of the day-30 screening strategy on the disease presentation and outcome of retinopathy of prematurity. The Indian twin cities retinopathy of prematurity report number 3


Srimati Kanuri Santhamma Centre for Vitreoretinal Diseases, Kallam Anji Reddy Campus, L V Prasad Eye Institute, Hyderabad, India

Date of Submission27-Mar-2012
Date of Acceptance12-Oct-2012
Date of Web Publication30-May-2014

Correspondence Address:
Subhadra Jalali
Srimati Kanuri Santhamma Centre For Vitreoretinal Diseases, Kallam Anji Redy Campus, L V Prasad Eye Institute, L V Prasad Marg, Banjara Hills, Hyderabad, Andhra Pradesh -500 034
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0301-4738.118449

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  Abstract 

Context: Outcomes of various screening strategies in retinopathy of prematurity are not well reported. Aim: To assess the impact of a city-wide, ROP screening strategy, on the disease presentation and treatment outcome. Materials and Methods: A retrospective case-control study from a prospectively collected ROP data-base was analyzed. Cases (group 1a) included ROP babies that were screened directly in neonatal intensive care units, and controls (group 1b) were babies referred directly to the institute from other neonatal centers during the same period. Historical controls (group 2) were ROP cases seen in the years preceding establishment of this ROP program and database. Primary outcome measure was the risk of eyes presenting with stage 4 or worse ROP, and main secondary outcome measure was the final anatomic outcome. Results: Of the 643 cases screened, 322 eyes of 161 babies had ROP. The median age of 7.19 months at presentation for the 46 patients (92 eyes) in group 2 was higher than the median age of 1.29 months for the 115 patients (230 eyes) in group 1. Within the group 1, group 1a had lower median age at presentation than group 1b (0.91 months versus 2.30 months). The relative risk of an eye presenting in the stage 4 and 5 in group 2 was 4.7 times higher (95% confidence interval 3.07 -7.32) than in group 1. Eyes that could be given treatment in group 2 were significantly less (P < 0.0005) than in group 1. The relative risk of poor outcome in group 2 was 3.83 times higher (95% confidence interval 2.75 -5.34) than in group 1. Group 1a eyes had the best outcomes. Conclusion: Early screening before one month of age in neonatal centers detects the disease early where prompt treatment can lead to favorable outcomes. The study provides early results of a model strategy for ROP screening.

Keywords: Childhood blindness, developing countries, neonatal intensive care unit, retinopathy of prematurity, screening strategy


How to cite this article:
Jalali S, Anand R, Rani PK, Balakrishnan D. Impact of the day-30 screening strategy on the disease presentation and outcome of retinopathy of prematurity. The Indian twin cities retinopathy of prematurity report number 3. Indian J Ophthalmol 2014;62:610-4

How to cite this URL:
Jalali S, Anand R, Rani PK, Balakrishnan D. Impact of the day-30 screening strategy on the disease presentation and outcome of retinopathy of prematurity. The Indian twin cities retinopathy of prematurity report number 3. Indian J Ophthalmol [serial online] 2014 [cited 2022 Dec 1];62:610-4. Available from: https://www.ijo.in/text.asp?2014/62/5/610/118449

Retinopathy of prematurity (ROP) is recognized by the World Health Organization within its VISION 2020: Right to Sight, program initiative as an important, potentially avoidable cause of blindness in children. ROP is not present at birth, and the eye has the potential for good vision. In a preterm infant, retinal vascularization is immature that continues to develop after birth. If this development becomes aberrant, it manifests as ROP. Although it has been more than 3 decades since the establishment of safe and effective prophylaxis against ROP-blindness using laser photocoagulation or cryotherapy, [1],[2],[3] there is still a lack of uniform agreement and implementation of updated NICU-based effective and timely ROP screening programs in some service areas. Especially in developing countries, there are many areas and neonatal centers where there are less or none established protocols of ophthalmic care of newborns and premature babies. [4]

The guidelines and reports regarding criteria and timing of first screening are different in different countries and could reflect the magnitude of problem and different characteristics of babies in different economic regions. [4] Based on multicentric trials, Indian studies and our initial experience with fulminant ROP, screening for ROP was suggested to be done within 3-4 weeks of birth. [3],[4],[5],[6],[7] Successful treatment depends on robust screening programs that identify and promptly treat premature babies who are likely to develop severe vision-threatening ROP. [1],[2],[3],[4],[5],[6],[7] Late disease presentation is indeed the most common cause of failed treatment and ROP blindness. For any strategy aimed at reducing ROP blindness, the most important challenge is to identify and treat the 'at-risk babies' on time. Treatment has to be carried out within 48-72 hours of detection of the condition. Since most of the premature babies at this stage are in critical condition and often in the neonatal intensive care units (NICU) or recently discharged from NICU, ROP screening and treatment must be suitably geared to address this situation.

A Model ROP screening program was planned in our center. An ROP project in-charge was trained at William Beaumont Hospital, USA, (which was one of the CRYO-ROP study centers) [1] between May and July 1999. A prospective twin-cities data collection of premature babies was set up by us in October 1999. A rough estimate showed that the twin cities had 4 advanced in-vitro fertilization centers and about 80 NICU-beds taking care of premature babies in 12 centers/practitioners (appendix, data obtained from the company providing the incubators/warmers to NICUs) at that time. None of these was covered by any ROP screening program or protocols. To assess the impact of this twin city-wide, NICU screening strategy for ROP on the disease presentation and treatment outcome in a tertiary level eye hospital, an ongoing computerized prospective database was maintained.


  Materials and Methods Top


All major NICU and individual neonatology practitioners were contacted (appendix 1). [Additional file 1] Hand-outs in the local languages were provided to all with a simple description regarding screening criteria that could be understood even by casual observers. Every week at a prefixed schedule, an ROP-trained retinal specialist (SJ) visited each participating NICU for ROP screening. Screening and treatment protocols were standardized, and a portable diode laser with indirect ophthalmoscope delivery was used. [1],[2],[4] After each evaluation, all the data of preterm babies recorded prospectively on standard forms and was entered into a computerized database for analysis. All preterm babies who came from other NICU's/practitioners to the institute retina services directly with any stage ROP were also included prospectively in our database.

The timing of First Screening Strategy, called as 'The day-20, day-30 strategy,' was modified to suit local needs. The timing of first examination had been recommended at that time as 3-6 weeks after birth or 31 weeks post-conceptional age, whichever was earlier. [1],[4] This was to be calculated based primarily on the gestational age (depending on the post-menstrual age) plus the chronological age. We realized that this approach had its problems for strict implementation and comprehension by various service providers. Gestational age in weeks was difficult to calculate readily and was cumbersome as many mothers could not accurately recall the date of their last menstrual period (LMP), and antenatal data was often missing. To have a benchmark and to avoid inconsistencies, ambiguity, and confusion, our strategy recommendation was to 'Complete one ROP screening session definitely before 'Day 30' of life and in smaller babies (possibly less than 30 weeks and/or birth weight less than 1200 gms), by day 20 of life.' The date of birth was reliably known to all and so, the criteria of day 30 and day 20 of life was found to be easy to comprehend and follow by all involved in the care of the preterm child. Where gestational age was unknown, then a preterm baby should have one screening irrespective of the weight recorded or estimated gestational age. [7]

In order to analyze and audit our work, and to plan further screening strategies, we decided to evaluate the impact of our screening strategy to control the ROP blindness in our community after 2 years of the program onset. The institutional review board gave consent for maintaining and analyzing the prospective ROP database. All treatments were done with informed consent of one of the parents.

This report 3 of the Indian twin cities ROP study (ITCROPS) is an unmasked, retrospective, case- control study of records from the prospectively collected ITCROP database. We included for cases those ROP babies that were screened directly in NICU where we went regularly, and controls as those ROP babies who were referred to the institute's retinal services from other NICU/practitioners in our city or surrounding areas/other states during the same time period. Historical controls included ROP cases seen in the institute in the years preceding the start of ITCROPS. Premature babies with no ROP were excluded from the current analysis. Our hypothesis for the study was that an NICU- based screening program would enhance timely screening, detection, and treatment of retinopathy of prematurity and improve treatment outcomes.

The ROP patients were first grouped into a prospective, post-screening program ITCROPS database (Group 1; after 1 st Dec 1999 to Dec 2001). This post-screening group of patients was further sub-divided into NICU-screened patient (Group 1a, child from a center that was part of our program-cases) and non-NICU-screened patient (Group 1b, child from an NICU center, not part of our program, but seen during the same period when directly referred to the institute's retinal services-controls). For the historical control group (group 2), records of consecutive babies with diagnostic ICD (International classification of diseases) coding of ROP were retrieved retrospectively from the institute computerized medical records from June 1987 (when the institute started) to 30 th November 1999. The data sheets of all participants were analyzed for gestational age, birth weight, age at presentation, stage and severity of the disease at time of presentation. The treatment modality used, and final structural outcome was analyzed.

Primary outcome measure was the stage of disease at first presentation as better or as worse than stage 4 ROP. Secondary outcomes were age at presentation, proportion of babies that could be treated, and the final treatment outcomes.

The final outcome was defined as good, fair, or poor depending on the status of retina in the last follow-up, at least 4 months or more after birth, when acute stage ROP is generally stable. Good outcome included fully regressed ROP with no vision-affecting sequelae, completely attached macular area, and clear media. Outcome was classified as fair for regressed ROP with clear media but sequelae that could potentially affect vision such as macular fold, macular heterotropia, macular pigmentary change, or squint. Poor outcome was defined as total retinal detachment or media haze with no or minimal visual potential. Visual loss from non-ROP causes was not included in poor outcome if the retinal anatomy was normal. All statistical analyzes were performed using SPSS 11.0 software for Windows (SPSS Inc. Chicago, IL, USA). Categorical data were compared using Fisher's exact test, and between-group differences in means were compared using independent sample t-test.


  Results Top


Of the 643 cases screened during the study period, 161 had ROP. Amongst patients with ROP, various parameters were compared between NICU-based ROP patients (group 1 a) and the directly referred patients (group 1b) as shown in [Table 1]. We also compared the pre-screening program group (group 2) and post-screening program group (group 1) as shown in [Table 2].
Table 1: Comparison of NICU-screened vs. non-NICUscreened ROP cases in post-screening program period (group 1)

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Table 2: Comparison of ROP cases in pre-screened and post-screening program period

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The median age of presentation in the group 2 was much higher than in group 1. The range of age was, however, quite large due to outliers who missed timely screening and presented only when child was symptomatic. The number of eyes presenting in the stage 4 and 5 was also significantly high (P < 0.0001) in group 2 compared to group 1. The relative risk of an eye presenting in the stage 4 and 5 in group 2 was 4.7 times higher (95% confidence interval 3.07 - 7.32) than in group 1. The number of eyes that could be provided treatment in the group 2 was significantly less (P < 0.0005) than in the group 1. The final outcome in group 2 was significantly poor (P < 0.0001) than in group 1. The relative risk of poor outcome in group 2 was 3.83 times higher (95% confidence interval 2.75 - 5.34) than in group 1.

Patients in group 1a were seen earlier than those in group 1b and showed good compliance to our day-30 strategy though here too few babies were non-compliant and presented in late stages. The relative risk of an eye presenting in the stage 4 and 5 in group 1b was 1.92 times higher (95% confidence interval 1.4 - 2.6) than in group 1a. Significantly higher number of patients (P < 0.0005) in group 1a received treatment with statistically better outcomes than those in group 1b. The relative risk of having poor outcome in group 1b was 2.21 times (95% confidence interval 1.31 - 3.71) higher than group 1a. This risk was lower than for group 2 patients.


  Discussion Top


The natural course of ROP offers a narrow window of opportunity for the treatment, which is recommended for high-risk pre-threshold and threshold ROP stages. If ROP can be diagnosed and treated in this period, results are quite encouraging. Group 2 shows the natural history of the disease when no ROP program existed, and the disease was just emerging in our city, and we were mainly seeing advanced untreatable blindness with children presenting universally late when leucocoria/squint or vision loss was detected by the caregivers. The problem is to identify in time those infants who need treatment. Our study data shows that the best outcomes were seen in cases from participating centers where cases were screened in the NICU itself and consequently diagnosed and treated earlier. We believe that still better strategies need to be devised to further reduce failure rates due to late presentation and delayed treatment, as even in group 1a, we had some babies who came late [Table 1]. A few isolated, hospital-based screening programs exist in India, [5],[6],[8] but there was lack of a city-based NICU screening strategy that would ensure universal coverage. Similar city-wide strategies improved compliance from 47% to 73% in a geographical area in UK. [9] Periodic screening guidelines and audits such as those presented here and earlier [10],[11] are essential to refine the screening strategies. The goal is to ensure timely and effective ROP screening of all eligible babies without wasting resources in evaluating low-risk infants.

The timing of the first ROP screening had been initially established in the literature based on ROP data and the understanding of the disease before the CRYO-ROP studies. At that time, Zone 1 disease was poorly recognized, and extremely premature babies less than 27 weeks were uncommonly seen. So, the recommendations were based on the natural course of Zone II disease and in babies more than 27 weeks gestational age, as these were represented more in the study groups. Zone 1 disease and aggressive-posterior ROP (APROP) is now being increasingly recognized as a distinct manifestation of a severe and early onset ROP with the highest chance of progression to threshold ROP. It also has a higher chance of treatment failures. [3],[7],[12] The treatment guidelines for ROP have also changed considerably with treatment now recommended in pre-threshold eyes that are at risk. [3] However, in our center, and in many other centers in Asia, progressive pre-threshold ROP, especially in Zone I, have been treated much before the new early ROP treatment guidelines. [7],[12] To detect the disease in this treatable form and to improve outcomes in Zone 1 disease that usually progresses rapidly, newer guidelines are needed as regards timing of first screening. Our data showed that possibly earlier screening has better outcomes as seen between group 1a and 1b. Screening at a median age of less than 1 month of birth had a substantially better impact on stage at presentation being less than 4, ability to offer treatment and good to fair final anatomical outcomes with minimal of poor outcomes. This day 20-day 30 strategy would need further verification in future studies in different geographic areas. We believe that the simplicity and accuracy of this strategy allows improved and measurable compliance as to the timing of the first screening besides being readily understood by all caregivers of the preterm baby.

In our country and maybe in other middle-income countries, where antenatal and cultural/socio-economic circumstances are different from many western countries, ascertainment of gestational age and post-conceptional age is not always accurate. Antenatal records are not universally available, and mothers are often not able to communicate the LMP. Birth weight may or may not be recorded due to home deliveries and lack of infrastructure; accuracy of weighing machines in different centers may not be the same, and the weighing methodology may be different (with or without clothes). Some babies are large for GA as those with fluid retention (hydrocephalus/intestinal obstruction/congenital renal dysfunction/diabetic mothers etc.) and can be overlooked if gestational age is not precisely known. To avoid missing such babies, our screening criteria include that any baby whose exact gestational age is not known and is labeled as preterm by a pediatrician, should have one ROP screening irrespective of birth weight. [7],[12],[13] The day- 20 and day- 30 strategy helped to maintain uniformity and compliance in terms of timing of screening because date of birth was well-known to all, and this was the terminology used in case notes by the pediatricians and other care givers and can be used in epidemiological surveillance. [13] Our treatment and outcome results were better in the NICU-screened group with screening done at a median of less than a month (group 1a) than at a median of 2.3 months (group 1b) during the same study period.

One limitation of our study is that babies in the different groups could have differences in the post-natal events and type of NICU-care that they received before presenting to us. However, some of these differences may be balanced across the groups because of similar mean gestational age in all groups. We have not included that data in the current study because firstly, the risk factors for ROP are already well-known and since these babies have already developed ROP, this report is not looking into the risk factors. Secondly, the emphasis of this report is to document how the disease presentation and outcomes change towards the better if the screening strategy is implemented in the NICU itself (group 1a) and on a city-wide scale rather than no screening (Group 2) or screening at the ophthalmologists' office only (group 1b).

Additionally, our NICU screening involves equal numbers of NICU of tertiary, secondary, and primary level since we screen across the whole of twin cities including government, charitable, and private hospitals. Further database analysis is already underway to present ROP data based on type of NICU versus disease presentation and outcomes.


  Conclusions Top


The current study evaluated a group of ROP children identified through different strategies and evaluated their ROP presentation and anatomical outcome as a measure of success of the program. Our data highlights the positive impact of our NICU-based citywide screening program and the efficacy of the unique strategies developed by us in reducing blindness due to ROP. It provides a model that brings the science and technological know-how from the research literature in journals to the bedside of high-risk infants in the community. Early screening within a month of birth in NICUs and prompt treatment resulted in marked reduction of ROP-related ocular morbidity. The National Neonatology Forum (NNF) of India has recently endorsed some of these strategies in their ROP national guidelines. As in most developed countries, these need further endorsement followed by monitoring and punitive actions for defaulters, by our national pediatric and ophthalmology societies to ensure wider and uniformly effective implementation.

 
  References Top

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Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity. Ophthalmological outcomes at 10 years. Arch Ophthalmol 2001;119:1110-18.  Back to cited text no. 1
    
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    Tables

  [Table 1], [Table 2]


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