Despite major advances in the management of retinopathy of prematurity (ROP), ensuing complications and reduced visual acuity remain major causes of childhood blindness or decreased visual acuity.1,2 High variability in outcomes of patients with advanced ROP suggests that screening and model of care play an important role in prevention and treatment.1,3,4 In essence, appropriately timed treatment is paramount to better outcomes, with comprehensive eye examinations for at-risk patients serving as an effective screening tool, particularly in extremely low–birth weight infants receiving advanced antenatal and prenatal care.5,6 For outpatient screening in which parents must cooperate to bring in their child, communicating the importance of timely ROP appointments is essential. Missed examinations can lead to permanent blindness, an unacceptable outcome.7,8
In the United States, official recommendations classify at-risk infants as those with a birth weight of less than 1,500 g or a gestational age of 30 weeks and selected infants with a birth weight between 1,500 and 2,000 g or a gestational age older than 32 weeks with an unstable clinical course.9 For these at-risk infants, retinal screening examinations following pupillary dilation are the standard of care, with one examination sufficient if it unequivocally demonstrates full vascularization in each eye.9
For infants requiring follow-up examination, a standardized management schedule for ROP (Table 1)9 is highly recommended.2 Treatment depends on zone and type of ROP and includes laser photocoagulation10–12 and in some cases intravitreal bevacizumab,13–15 although optimal treatment considerations have not been delineated.14,16 Further, recent studies have suggested early treatment for eyes with type 1 ROP improved visual acuity outcomes at 6 years of age, whereas this association did not hold for eyes with type 2 ROP.17 However, one concern with the American Academy of Pediatrics, American Association for Pediatric Ophthalmology and Strabismus, and American Academy of Ophthalmology joint statement guidelines is that there is no room for error; a physician or screening program employing these guidelines will find that any patients that miss an appointment will be outside of the screening window. While this may be of little consequence for the vast majority of patients being screened, the goal should be zero tolerance for patients that go blind because they fell outside the screening window, because this is the standard screeners are held to in the U.S. medico-legal system.18
Table 1: Management Schedule per Joint Statement Screening Guidelines
The system we have developed aims to ensure that all patients with any ROP are examined on a weekly basis, with the goal that any patient with missed examinations will be seen and re-examined within the time frame stipulated by the joint statement guidelines. For patients missing appointments for various reasons, course of care includes same-day phone calls to the caregiver, referring physician, and social workers until a make-up appointment is scheduled. In the event of inability to contact the caregiver or failure to reschedule an appointment, a report is made with Child Protective Services.
Patients and Methods
This study retrospectively reviewed medical records of prematurely born patients treated at the Byers Eye Institute outpatient ROP clinic at Stanford University School of Medicine (a quaternary referral pediatric clinic including patients previously discharged from neonatal care) from January 2010 to December 2011. This study adhered to the tenets of the Declaration of Helsinki. All at-risk infants visiting for routine acute-phase ROP screening during this 2-year interval were included in the analysis. The institutional review board was consulted and determined that approval was not required for this analysis because it was a practice management evaluation. For each patient, demographic information on birth weight, gestational age, insurance, distance to the eye clinic, and primary language was collected. Additionally, a list of scheduled appointments for each infant was generated and categorized into canceled, no-showed, or completed examinations. All data were securely extracted from patient electronic medical records, de-identified, and entered into a Research Electronic Data Capture (REDCap) database in a HIPAA-compliant manner.
If a patient canceled or failed to show up for at least one appointment, further details on total number of missed visits, diagnosis of ROP, and given reason for not attending the examination were obtained from medical records. We categorized reasons for missed appointments as caregiver-related or caregiver-unrelated. Caregiver-related reasons for missed appointments included rescheduling for any reason, lack of transportation, no reason, illness, conflicting appointment, forgetfulness, financial issues not related to insurance, insurance issues, and family emergency. Caregiver-unrelated issues included physician unavailable, system error, hospitalization, discharged by clinic, and patient deceased. ROP status was determined independently for each eye and expressed in terms of zone, stage, and plus of retinal vascularization. Termination of acute-phase ROP screening was determined using the Joint Statement Screening Guidelines (Table 1). If Child Protective Services was contacted, the use of county intervention procedures for alleged child abuse was also noted.19
All statistical analyses were performed using Microsoft Excel 2010. Appropriate statistical procedures including student’s t-test, Chi-squared analysis, odds ratios, and 95% confidence intervals were selected. For all tests, a P value of less than 0.05 was considered statistically significant.
A total of 1,823 ROP-related visits were scheduled, of which 327 (17.9%) resulted in cancellations and 90 (4.9%) resulted in no-shows. Of these 417 (22.9%) total missed appointments, 238 (57.1%, or 13.1% of the total ROP-related visits) were due to caregiver-related reasons (Table 2). Of the 399 total patients with ROP represented in this study, 205 (51.4%) canceled or failed to show up for at least one appointment, of which 142 (35.6%) were due to caregiver-related reasons. The most common of these reasons were a need to reschedule (36.1%), lack of transportation (12.2%), conflicting appointment (7.56%), and illness (4.62%). Of the 1,823 ROP-related visits, 179 (9.8%) missed appointments were the result of caregiver-unrelated reasons. From the total patients with ROP, 63 (15.8%) canceled or failed to show up for a visit because of caregiver-unrelated reasons only. The most common caregiver-unrelated reasons were physician unavailable (50.8%), system error (24.6%), hospitalization (20.1%), and discharged by clinic (3.9%). Physician unavailable was defined as an appointment scheduled at a time when the physician was not in clinic. System error was defined as an incorrectly selected appointment time by the clinic staff. We observed variability in the frequency with which patient appointments resulted in cancellation or no-shows, with a low miss frequency (only one caregiver-related missed appointments) for 88 patients, medium (two to three caregiver-related missed appointments) for 44 patients, and high (four or more caregiver-related missed appointments) for 10 patients (Table 3). In line with our protocol for patients not receiving care despite repeated attempts to contact and reschedule we called Child Protective Services regarding nine patients (4.4%).
Table 2: Missed Appointments Types, Reasons
Table 3: Comparing Demographic Factors of Screening Patients by Frequency of Missed Appointments
The scheduled follow-up for zone II, stage 1 ROP (n = 8) was 8.80 days (range: 2 to 20 days, 95% CI: 4.23–13.37), and actual follow-up was 12.87 days (range: 5 to 33 days, 95% CI: 5.19–20.54). For zone III, stage 1 ROP (n = 10), scheduled follow-up was 12.06 days (range: 1 to 35 days, 95% CI: 4.33–19.78), and actual follow-up was 20.47 days (range: 7 to 42 days, 95% CI: 7.03–33.91). Similarly for zone II, stage 2 ROP (n = 1), the scheduled follow-up was 21.00 days (range: 10 to 31 days, 95% CI: 11.46–30.54) and actual follow-up was 34 days (range: 34, 95% CI: 34). This follow-up duration was largely due to transportation difficulties for the patient, with shorter follow-up time desirable. Finally, for patients with zone III, stage 2 ROP (n = 3), the scheduled follow-up was 6.83 days (range: 6 to 8 days, 95% CI: 6.08–7.59), and actual follow-up was 13.17 days (range: 8 to 19 days, 95% CI: 8.50–17.83). We found that for zone III, stage 1 patients, three of 10 (30%) exceeded the recommended follow-up duration of 21 days. For zone II, stage 1 patients, only two of eight (25%) exceeded the recommended 14 days. None of the zone III, stage 2 patients exceeded 21 days for follow-up.
Those patients requiring Child Protective Services intervention took much longer on average from missed appointment to date examined (17.6 days compared to 8.9 days for no Child Protective Services intervention) (P = .080). Those with a higher miss frequency were also more likely to skip more days per missed visit (17.9 days for high, 7.34 for medium, 5.93 for low) (P = .00073 for high vs low, P = .0042 for high vs medium). Duration from date of missed appointment to date seen for all patients ranged from 0 to 114 days (Figure).
Figure. Intended and actual follow-up durations among study population.
Insurance type was also shown to correlate with caregiver-related missed appointments. Patients with government-funded insurance (eg, Medi-Cal or HP San Mateo) missed more appointments than those with private insurance (P = .0019 for high vs non-missed; P = .0017 for all missed vs non-missed). Average duration in days from date of missed appointments to date seen was lower for private insurance (5.27) compared to government insurance (9.59) (P = .01). There was no difference between English and non-English speakers in terms of missed appointments (P = .34 for all missed vs non-missed) (Table 3).
Distance to center of care had an impact, with patients missing more caregiver-related appointments living farther away on average (average distance of 63.3 miles for high, 53.4 for medium miss frequency, 47.4 for low, 40.33 for non-missed; P = .0046 for all missed vs non-missed) (Table 3).
Higher stage ROP was shown to correlate with a greater number of caregiver-related appointments missed (P = .003321) (Table 4). However, higher stage was also shown to correlate with shorter intervals from missed appointment to date seen (P = .02593) and birth weight (P = .03426) (Table 5).
Table 4: Comparing Demographics of ROP Screening Cases by Stage of Disease
Table 5: Comparing Scheduling of ROP Cases by Zone and Stage of Disease
In the present study, 110 of 142 patients (77.5% of infants) who missed appointments had zone III ROP, immature without plus or pre-plus in both eyes, and would not have traditionally required additional screening per the joint statement guidelines.9 Furthermore, 10 (7.0%) of the 142 patients had ROP rated zone II, immature without plus or pre-plus in at least one eye and were on average seen within the recommended screening period. Of the remaining 22 infants, 81.8% (n = 18) had stage 1 and 18.2% (n = 4) had stage 2 ROP (Table 5). On average, patients with zone II or III with stage 1 ROP or zone II with stage 2 ROP were seen within the recommended time period9 (Tables 1, 5). Only for patients with zone II, stage 2 ROP was the interval between appointments longer than the recommended screening frequency, affecting one patient without adverse outcome. This is most likely attributed to more intensive care of higher-stage patients, with less tolerance given for misses on the part of clinic staff.
The true risk of delay in screening in the quaternary clinic ROP outpatient setting is difficult to assess because all infants that met treatment criteria did so prior to discharge from the hospital. In such a situation, screening is directed towards the infants at lower risk who are unlikely to require treatment or towards infants who have already received treatment to observe for treatment failure. Despite this conundrum, using the current screening paradigm, no infant was noted to progress to retinal detachment after previous therapy or to need for treatment having not had prior treatment.
Interestingly, we found that 75.42% of caregiver-unrelated missed appointments were due to scheduling errors on the clinic side; either patients were scheduled for an appointment when the physician was not in clinic or there was another system error (Table 2). We have corrected such scheduling errors by assigning one ROP coordinator to look after only infants with ROP on the clinical schedule. Like many large academic medical centers, Stanford uses the EpicCare electronic health records and scheduling system (Epic Systems, Verona, WI) in conjunction with a centralized call center for scheduling appointments into all clinics. Despite having a dedicated ophthalmic technician and new patient coordinator within the department who are in charge of patients with ROP, these data suggest that the current electronic medical record system itself is inadequate to schedule patients into the clinic, resulting in 135 of the 179 (75.42%) caregiver-unrelated missed appointments, 32.3% of all missed appointments, and 7.4% of all appointments. This type of centralized schedule system, with physician screening available 4 days each week and inadequacies in the scheduling system resulting in rescheduling, may have the unintended effect of reinforcing that the eye examination for ROP is not important, particularly if it is routinely rescheduled by the clinic for physician unavailability or system errors. Fortunately, we noted that patients who experienced caregiver-unrelated missed appointments were not more likely to experience caregiver-related missed appointments, and we are currently undergoing analysis of ways to improve the system.
Recently, algorithms using postnatal weight measurements have been proposed and implemented in several Swedish neonatal intensive care units to reduce the frequency and associated costs of ROP screening.18 However, such algorithm-based recommendations may not be favorable in the U.S. due to the medico-legal environment of zero tolerance for blindness from lack of proper medical examination.19 By screening every infant with ROP on a weekly basis and evaluating immature retina cases (zone II or III) on a biweekly basis, we were able to capture the missed appointments that might occur within the recommended timeline as put forth by the joint statement guidelines. This aggressive screening method ensured that no infants in our care were permanently lost to follow-up, nor did any go blind or develop adverse anatomic outcome. Additionally, in none of the 399 total patients with ROP examined in this study did stage 3 or worse condition develop.
In keeping with our goal of preventing blindness, we have found that in order to achieve maximal compliance with the joint statement guidelines on screening for ROP, it is necessary to schedule patients for examination earlier than recommended to ensure that infants at risk are screened within the recommended time frame.
- Gilbert C, Fielder A, Gordillo L, et al. Characteristics of infants with severe retinopathy of prematurity in countries with low, moderate, and high levels of development: implications for screening programs. Pediatrics. 2005;115(5):e518–525. doi:10.1542/peds.2004-1180 [CrossRef]
- Chen J, Stahl A, Hellstrom A, Smith LE. Current update on retinopathy of prematurity: screening and treatment. Curr Opin Pediatr. Apr2011;23(2):173–178. doi:10.1097/MOP.0b013e3283423f35 [CrossRef]
- Gilbert C, Rahi J, Eckstein M, O’Sullivan J, Foster A. Retinopathy of prematurity in middle-income countries. Lancet. 1997;350(9070):12–14. doi:10.1016/S0140-6736(97)01107-0 [CrossRef]
- Chow LC, Wright KW, Sola A. Can changes in clinical practice decrease the incidence of severe retinopathy of prematurity in very low birth weight infants?Pediatrics. 2003;111(2):339–345. doi:10.1542/peds.111.2.339 [CrossRef]
- Karna P, Muttineni J, Angell L, Karmaus W. Retinopathy of prematurity and risk factors: a prospective cohort study. BMC Pediatr. 2005;5(1):18. doi:10.1186/1471-2431-5-18 [CrossRef]
- Kemper AR, Freedman SF, Wallace DK. Retinopathy of prematurity care: patterns of care and workforce analysis. J AAPOS. 2008;12(4):344–348. doi:10.1016/j.jaapos.2008.02.012 [CrossRef]
- Reynolds J. Malpractice and the quality of care in retinopathy of prematurity (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2007;105:461–480.
- Day S, Menke A, Abbott R. Retinopathy of prematurity malpractice claims: the Ophthalmic Mutual Insurance Company experience. Arch Ophthalmol. 2009;127(6):794–798. doi:10.1001/archophthalmol.2009.97 [CrossRef]
- [No authors listed.] Screening examination of premature infants for retinopathy of prematurity. Pediatrics. 2006;117(2):572–576.
- Group ETFROPC. Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial. Arch Ophthalmol. 2003;121(12):1684–1694.
- Simpson JL, Melia M, Yang MB, Buffenn AN, Chiang MF, Lambert SR. Current role of cryotherapy in retinopathy of prematurity: a report by the American Academy of Ophthalmology. Ophthalmology. 2012;119(4):873–877. doi:10.1016/j.ophtha.2012.01.003 [CrossRef]
- Connolly BP, McNamara JA, Sharma S, Regillo CD, Tasman W. A comparison of laser photocoagulation with trans-scleral cryotherapy in the treatment of threshold retinopathy of prematurity. Ophthalmology. 1998;105(9):1628–1631. doi:10.1016/S0161-6420(98)99029-7 [CrossRef]
- Mintz-Hittner H, Kennedy K, Chuang A. Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity. N Engl J Med. 2011;364(7):603–615. doi:10.1056/NEJMoa1007374 [CrossRef]
- Chung EJ, Kim JH, Ahn HS, Koh HJ. Combination of laser photocoagulation and intravitreal bevacizumab (Avastin) for aggressive zone I retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol. 2007;245(11):1727–1730. doi:10.1007/s00417-007-0661-y [CrossRef]
- Shah V, Yeo C, Ling Y, Ho L. Incidence, Risk Factors of Retinopathy of Prematurity Among Very Low Birth Weight Infants in Singapore. Ann Acad Med Singapore. 2005;34:169–178.
- Moshfeghi DM, Berrocal AM. Retinopathy of prematurity in the time of bevacizumab: incorporating the BEAT-ROP results into clinical practice. Ophthalmology. 2011;118(7):1227–1228.
- Good WV, Hardy Rj, Dobson V, Palmer EA, Phelps DL, Tung B, et al. Final Visual Acuity Results in the Early Treatment for Retinopathy of Prematurity Study. Arch Ophthalmol. 2010;128(6):663–671. doi:10.1001/archophthalmol.2010.72 [CrossRef]
- Wu C, Lofgvist C, Smith LE, VanderVeen DK, Hellstrom AWINROP. Importance of early postnatal weight gain for normal retinal angiogenesis in very preterm infants: a multicenter study analyzing weight velocity deviations for the prediction of retinopathy of prematurity. Arch Ophthalmol. 2012;130(8): 992–999. doi:10.1001/archophthalmol.2012.243 [CrossRef]
- Reynolds J. Retinopathy of prematurity (ROP). In: Reynolds J, Olitsky S, eds. Pediatric Retina. Heidelberg: Springer; 2011:110–112.
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Management Schedule per Joint Statement Screening Guidelines
|Stage 1 or 2 ROP: zone 1||1 week or less|
|Stage 3 ROP: zone 2||1 week or less|
|Immature vascularization: zone 1, no ROP||1 to 2 weeks|
|Stage 2 ROP: zone 2||1 to 2 weeks|
|Regressing ROP||1 to 2 weeks|
|Stage I ROP: zone 2||2 weeks|
|Regressing ROP: zone 2||2 weeks|
|Immature vascularization: zone 2, no ROP||2 to 3 weeks|
|Stage 1 or 2 ROP: zone 3||2 to 3 weeks|
|Regressing ROP: zone 3||2 to 3 weeks|
Missed Appointments Types, Reasons
|Total caregiver-related missed appointments||238||100|
| New patient visit||36||15.13|
| Return patient visit||202||84.87|
| Canceled by patient||152||63.87|
|Most common caregiver-related reasons|
| Patient rescheduled||86||36.13|
| No transportation||29||12.18|
| Conflicting appointment||18||7.56|
| Family emergency||6||2.52|
| Out of town||4||1.68|
| Insurance issue||4||1.68|
| Financial issue||1||0.42|
|Total caregiver-unrelated missed appointments||179||100|
| New patient visit||33||18.44|
| Return patient visit||146||81.56|
|Most common caregiver-unrelated reasons|
| Physician unavailable*||91||50.84|
| System error||44||24.58|
| Discharged by clinic||7||3.91|
| Patient deceased||1||0.56|
Comparing Demographic Factors of Screening Patients by Frequency of Missed Appointments
|Frequency of Caregiver-Related Missed Appointments||High (n = 10)||Medium (n = 44)||Low (n = 88)||PValue for High vs. Low*|
|Mean birth weight in grams (95% CI)||1,115 (979–1,251)||1,192 (1,089–1,295)||1,357 (1,263–1,451)||.0482|
|Mean distance from eye clinic in miles (95% CI)||63.3 (24.9–101.7)||53.4 (42.0–64.8)||47.4 (39.8–55.0)||.1163|
|Mean duration in days from missed appointment to date seen (95% CI)||17.9 (6.5–29.3)||7.34 (5.3–9.3)||5.93 (4.1–7.7)||< .001|
|No. with government-funded insurance (%)||10 (100)||21 (47.7)||35 (39.7)||< .0001|
|No. not fluent in English (%)||3 (30.0)||6 (13.6)||9 (10.2)||.2079|
|No. contacted by Child Protective Services (%)||5 (50.0)||1 (2.3)||3 (3.4)||<.0001|
|No. cases of ROP||3 (30.0)||11 (25.0)||8 (9.1)||.0214|
Comparing Demographics of ROP Screening Cases by Stage of Disease
|Mean Variable (95% CI)||Non-ROP (n = 120)||Stage 1 ROP (n = 18)||Stage 2 ROP (n = 4)||P Value for ROP vs. Non-ROP*|
|Birth weight in grams||1,261 (1,188–1,333)||1,089 (874–1,304)||1,067 (779–1,355)||.0343|
|Distance from eye clinic in miles||51.5 (44.3–58.6)||51.7 (35.9–67.4)||13.3 (7.1–19.5)||.2066|
|Number of caregiver-related missed appointments||1.56 (1.37–1.74)||2.05 (1.45–2.66)||3.50 (2.23–4.77)||.0033|
Comparing Scheduling of ROP Cases by Zone and Stage of Disease
|Mean Variable (Range)||Zone III Immature (n = 110)||Zone II Immature (n = 10)||Stage 1 ROP Zone III (n = 10)||Stage 1 ROP Zone II (n = 8)||Stage 2 ROP Zone III (n = 3)||Stage 2 ROP Zone II (n = 1)|
|Intended follow-up duration in days||19.90 (0–151)||17.00 (1–82)||12.06 (1–35)||8.80 (2–20)||6.83 (6–8)||21.00 (10–31)|
|Duration in days from missed appointment to date seen||10.01 (0–114)||2.77 (0–13)||8.41 (0–35)||4.07 (0–17)||6.33 (1–12)||13.00 (3–24)|
|Actual follow-up duration in days due to missed appointment||31.46 (6–152)||19.77 (8–89)||20.47 (7–42)||12.87 (5–33)||13.17 (8–19)||34.00 (34–34)|