Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease that may cause blindness, in which vascular endothelial growth factor (VEGF) plays a key role in the pathogenesis.1–3 Today, laser photocoagulation is still the gold standard in the treatment of ROP; peripheral avascular retina is ablated by laser photocoagulation, reducing the amount of VEGF and inducing the regression of the disease.3,4 Although the development of blindness is prevented by laser photocoagulation, a permanent peripheral visual field loss occurs due to ablation. This may lead to high refractive errors and poor visual outcomes, especially in cases of posterior disease.4–7
In ROP, anti-VEGF drugs (bevacizumab, ranibizumab, and aflibercept) that treat the disease by blocking VEGF in the vitreous have been widely used intravitreally.8–11 Anti-VEGF agents have higher anatomic success and produce less refractive error compared to laser photocoagulation, especially in cases of posterior disease.7 However, the disruption of vascularization by anti-VEGF treatment, late recurrences, and lack of clarity about the systemic side effects suggest that patients to be treated with these agents should be selected carefully.12–14 Our study aimed to compare the efficacy, recurrence rate, and requirement for additional treatment between laser photocoagulation and 1 mg/0.025 mL of intravitreal aflibercept in the treatment of ROP.
Patients and Methods
Before starting the study, the approval of the clinical research ethics committee of Gazi Yasargil Training and Research Hospital was obtained and the study was conducted in accordance with the ethical standards of the Declaration of Helsinki. The study was conducted by retrospectively analyzing the files of infants who were followed up and treated in the ROP Diagnosis and Treatment Center of Gazi Yasargil Training and Research Hospital between January and April 2018. Written consent was obtained from the families of all infants who participated in the study.
Patients who were lost to follow-up, died after treatment, were treated in another center for ROP, or had additional ocular disease were excluded from the study.
For the examination, mydriasis was achieved by administering 0.5% tropicamide (Tropamid; Bilim Ilaç, Istanbul, Turkey) and 2.5% phenylephrine (Mydfirin; Alcon Laboratories, Inc., Fort Worth, TX) to the eyes three times at 10-minute intervals after the discontinuation of oral feeding of the patients. Thirty minutes after the eye drops were instilled, topical anesthesia was administered with 0.5% proparacaine hydrochloride (Alcain; Alcon Laboratories, Inc.). The examinations were performed by an experienced ophthalmologist (DYE) using a 20-diopter (D) lens (Volk Optical Inc., Mentor, OH) with the help of Heine Video Omega 2c binocular indirect ophthalmoscope (Heine Optotechnik, Herrsching, Germany). The retinal images of the patients were recorded in the ArchiMED software (Digital Imaging S.r.l., Turin, Italy). The findings were evaluated according to the International Classification of Retinopathy of Prematurity.15
In eyes with ROP, treatment was administered to those diagnosed as having type 1 ROP or aggressive posterior ROP (APROP) according to the criteria of the Early Treatment for Retinopathy of Prematurity study.4 The treatment was administered within 72 hours after the families were informed about the possible risks of the treatment (laser photocoagulation/intravitreal injection) and signed an informed consent form.
Intravitreal aflibercept (1 mg/0.025 mL) was administered to the patients whose disease was zone I or zone II posterior, in whom adequate dilatation could not be achieved due to rubeosis and laser treatment could not be performed effectively due to vitreous hemorrhage, and whose general condition was not appropriate for laser photocoagulation. Laser photocoagulation was performed on the patients who did not meet these criteria and in whom the disease was in zone II periphery.
Intravitreal aflibercept injection was administered in the operating room under local anesthesia with monitoring by an anesthetist. After the eye was stained with 10% betadine (Poviiodeks; Tip Kim San, Istanbul, Turkey), a sterile eyelid speculum was applied and the eye was washed with 5% povidone-iodine. Using a 30-gauge, 4-mm microneedle, 1 mg/0.025 mL (20% of adult dose) of aflibercept (Eylea; Regeneron Pharmaceuticals Inc., Tarrytown, NY) was administered from the upper temporal area at a distance of 1.5 mm to the limbus. The pulsation of the central retinal artery was evaluated immediately after the injection. Topical antibiotic eye drops were used four times daily for 1 week after the injection. After the injection, the patients were examined at postoperative 1 day, 1 week, and then weekly until the disease completely regressed.
Laser Photocoagulation Technique
Laser photocoagulation was performed in the operating room under general anesthesia with a 810-nm diode laser (Iridex; Oculight Sl, Mountainview, CA) in the near confluent pattern. Topical steroid and antibiotic eye drops were used for 1 week after the procedure. After laser photocoagulation, the follow-up visits were performed at postoperative 1 day, 1 week, and then weekly until the disease completely regressed.
Unresponsiveness to the first treatment was evaluated as the absence of any regression in the stage and the plus disease in the first postoperative week. Recurrence was accepted as the presence of a demarcation line or neovascularization in the retinal vascular termination region during the follow-up visits with or without plus disease after complete regression of the disease. Laser photocoagulation was performed if the patients who developed recurrence met the type 1 ROP criteria.
The presence of any of the following in the study was considered an unfavorable anatomic outcome: dragging of the disc, localized tractional or non-tractional membranes at the posterior pole or in the retinal periphery, and total or partial retinal detachment.
The patients' sex, birth weight (BW) and gestational age (GA), diagnosis of ROP, presence of plus disease, rubeosis and vitreous hemorrhage, regression status of plus disease and ROP in the postoperative follow-up visits, requirement for additional treatment and recurrence status, and anatomic success rate during the postoperative visit were recorded. The success rates were compared in the eyes treated with intravitreal aflibercept or laser photocoagulation.
Mean, standard deviation, median, minimum, maximum, frequency, and rate values were used for the descriptive statistics of the data. The distribution of the variables was measured by the Kolmogorov–Smirnov test. The Mann–Whitney U test was used to analyze the quantitative independent variables. The chi-square test was used to analyze the qualitative independent data, and the Fisher's exact test was used when the conditions for the chi-square test were not met. SPSS software (version 22.0; SPSS, Inc., Chicago, IL) was used in the analyses.
A total of 27 infants (51 eyes) who completed the follow-up period after laser photocoagulation or intravitreal aflibercept treatments were enrolled in the study. There were 27 eyes of 15 infants (55.6%) in the laser photocoagulation group and 24 eyes of 12 infants (44.6%) in the intravitreal aflibercept group. The demographic and clinical characteristics of the study groups are shown in Table 1. In the laser photocoagulation group, stage 3 ROP was detected in 25 eyes (92.6%) and stage 2 ROP in 2 eyes (7.4%). In the intravitreal aflibercept group, stage 3 ROP was detected in 14 eyes (58.3%) and APROP in 10 eyes (41.7%) (P < .05).
Demographic and Clinical Characteristics
No treatment-related ocular or systemic complication was observed in both groups. The regression rates after treatment were 92.6% and 100%, respectively (P > .05). Figures 1–2 show the treatment response to laser photocoagulation and intravitreal aflibercept in ROP. In the laser photocoagulation group, rescue therapy with intravitreal aflibercept was administered to the 2 eyes unresponsive to treatment in the first week after the first treatment and the disease was brought under control. As a result of both treatment modalities, no recurrence was observed in the first group after the disease completely regressed. However, recurrence occurred in 8 eyes (30%) in the intravitreal aflibercept group (P < .05). During the follow-up visits, the disease spontaneously regressed in the 2 eyes that developed recurrence. Progression to stage 3 along with plus disease was detected in 6 eyes (25%); these eyes were treated with laser photocoagulation and the disease completely regressed. The mean PMA for recurrence development was 48.2 weeks and treatment was administered at PMA of 52.4 weeks. Of these eyes, 4 were zone I APROP and 2 were zone I stage 3. In the intravitreal aflibercept group, the mean GA of the patients who underwent laser photocoagulation due to recurrence was 25.6 ± 0.5 weeks (range: 25 to 26 weeks) and the mean BW was 745 ± 54.4 g (range: 650 to 810 g). The GA and BW of the patients who developed recurrence and were treated were significantly lower than those who did not develop recurrence (P < .05).
Fundus photographs of an infant with zone II stage 3 retinopathy of prematurity (ROP). (A and B) Plus disease and stage 3 ROP are clearly observed. (C and D) The response to treatment is seen 1 week following laser photocoagulation with regression of plus disease and ridge.
Fundus photographs of an infant with zone II posterior retinopathy of prematurity (ROP). (A and B) Plus disease and stage 3 ROP are clearly observed. (C and D) The response to treatment is seen 1 month following laser photocoagulation with regression of plus disease and ridge.
In the intravitreal aflibercept group, prophylactic laser photocoagulation was performed on the 4 eyes (16.6%) with non-progressive vascularization at the corrected sixth month. At the end of the follow-up period, the rate of additional treatment was higher in the intravitreal aflibercept group than in the laser photocoagulation group (P < .05).
A fibrotic band and dragging of the optic disc developed in one eye of a patient who received intravitreal aflibercept with the diagnosis of aggressive posterior ROP and underwent laser photocoagulation due to recurrence (zone II stage 3 ROP, plus disease) during the follow-up visits. No additional fibrotic band–related complication was observed during the follow-up visits.
In the refraction measurements at the corrected sixth month, the spherical equivalent was +1.10 ± 2.30 D in the laser photocoagulation group and +1.50 ± 2.41 D in the intravitreal aflibercept group (P > .05). Myopia of greater than 6.00 D was detected in 1 eye (3.7%) in the laser photocoagulation group and 2 eyes (8.3%) in the intravitreal aflibercept group (P > .05). One patient had esotropia in the laser photocoagulation group, whereas one patient had exotropia and one patient had esotropia in the intravitreal aflibercept group (P > .05).
Laser ablation of the peripheral retina is still the gold standard in the treatment of ROP.4,5,16 Especially in cases of zone I disease and previously failed laser photocoagulation, the disease can be successfully treated with anti-VEGF agents.7,8 In the Bevacizumab Eliminates the Angiogenic Threat of Retinopathy of Prematurity (BEAT-ROP) study, it was reported that intravitreal bevacizumab treatment was more successful than laser photocoagulation in patients with zone 1 ROP and had a lower recurrence rate.8 In addition, it was shown that intravitreal bevacizumab, intravitreal aflibercept, and intravitreal ranibizumab were effective in the treatment of ROP in patients with zone II disease and retinal vascularization continued after the treatment, unlike laser photocoagulation.11,17,18 In our study, the first study comparing the efficacy of intravitreal aflibercept and laser photocoagulation in the treatment of ROP, both treatment modalities were found to have similar efficacy. According to our results, intravitreal aflibercept provides a high rate of anatomical success in patients with zone I ROP. This result demonstrates that intravitreal aflibercept is an alternative treatment modality in such cases where laser photocoagulation is likely to have a poor prognosis.
In cases of zone I ROP, it is known that the disease is detected at a lower PMA and progresses faster than the cases of zone II ROP.19 Moreover, it has been shown that patients with zone I disease have poorer GA, BW, and anatomical and visual outcomes than those with zone II disease.4,5,20–23 In our study, most of the patients in the intravitreal aflibercept group had zone I disease and, although not statistically significant, had lower BW and GA than the laser photocoagulation group. Contrary to the literature data, this result can be explained by the small sample size in both groups.
In our study, patients who received intravitreal aflibercept were treated at an earlier PMA compared to those who underwent laser photocoagulation. The requirement for treatment at an earlier PMA in the intravitreal aflibercept group, the detection of rubeosis in the majority of eyes at the time of diagnosis, and retinal vascularization in zone 1 in almost all patients demonstrate that the disease was more severe in this group compared to the other group. Treatment of all eyes in the laser photocoagulation group with a 100% success rate using the intravitreal aflibercept mono-therapy demonstrates that aflibercept is an anti-VEGF agent that can be used as an alternative to intravitreal bevacizumab and laser photocoagulation.7–9,12
Laser photocoagulation may cause a progression in ROP leading to a temporary increase in VEGF levels in the vitreous.24 It is known that intravitreal bevacizumab is successfully used as a rescue therapy in patients who fail with laser photocoagulation.25,26 In our study, response to treatment could not be obtained in 2 eyes of 1 patient as a result of laser photocoagulation applied without leaving avascular space. In the postoperative first week, intravitreal aflibercept was administered to the 2 eyes of the patient and the disease completely regressed. The successful outcome of rescue therapy with intravitreal aflibercept was reported for the first time in the literature and demonstrated that intravitreal aflibercept can be used safely after failed laser photocoagulation treatment such as intravitreal bevacizumab.
It is known that patients who receive anti-VEGF agents due to ROP develop recurrence in the late period and blindness may develop due to these recurrences.8,12,14,17,27 Recurrence after treatment with anti-VEGF agents is more common in infants who are treated for APROP, hospitalized for a long time, and have a low BW and GA.14 In addition, eyes with slow progression of retinal vascularization are considered at risk in terms of recurrence.14 It is emphasized that patients with these risk factors should be followed up at more frequent intervals and for a longer period of time. Especially for patients treated with intravitreal bevacizumab, a PMA between 45 and 55 weeks is considered a window in terms of recurrence and it is recommended to increase the frequency of follow-up visits in this period.14
In addition to these risk factors, an anti-VEGF agent administered was also found to be effective in recurrence. In a study comparing intravitreal bevacizumab and intravitreal ranibizumab, eyes treated with intravitreal ranibizumab developed recurrence more frequently. This was attributed to the fact that the half-life of ranibizumab was shorter than that of bevacizumab.12 In a study comparing intravitreal ranibizumab and intravitreal aflibercept, eyes treated with intravitreal ranibizumab again developed recurrence more frequently and at an earlier period.28 In the same study, the recurrence rate was 13.9% in the intravitreal aflibercept group. In another study evaluating the efficacy of intravitreal aflibercept, the recurrence rate was 7.7% and the eyes that developed recurrence were treated with a second dose of intravitreal aflibercept.
In our study, the recurrence rate was 30% in the intravitreal aflibercept group throughout the follow-up and 25% of all eyes were treated for recurrence. We found that the BW and GA of the patients who developed recurrence were lower than those who did not develop recurrence, supporting the view that very low BW and GA are risk factors for recurrence. However, because the other two studies conducted with intravitreal aflibercept did not evaluate BW and GA of the patients who developed recurrence, it could not be clarified whether these two factors had an effect on our high recurrence rate compared to the others. PMA at which the second treatment was administered for recurrence was similar in all three studies. Our higher recurrence rate compared to the other two studies may be due to the initial disease being zone I in almost all of our patients in contrast to the other two studies.
The disruption of vascular development after intravitreal bevacizumab, intravitreal aflibercept, and intravitreal ranibizumab treatments has been ophthalmoscopically and angiographically demonstrated.11,13,28,29 Prophylactic laser photocoagulation is recommended to prevent recurrence-related blindness in cases of avascular areas detected by fundus fluorescein angiography during the follow-up of patients receiving VEGF monotherapy.29,30 Considering that we were unable to evaluate patients using fundus fluorescein angiography in our clinic and that our patients had risk factors in terms of recurrence, prophylactic laser photocoagulation was performed on 4 eyes (16.6%) with ophthalmoscopically residual avascular areas at the corrected sixth month.
In the BEAT-ROP study, the rate of recurrence after laser photocoagulation was higher in patients with zone 1 compared to those treated with intravitreal bevacizumab and similar in zone 2 posterior cases.8 Moreover, the rate of anatomic success was lower in patients treated with laser photocoagulation than in those treated with intravitreal bevacizumab in the zone 1 group. In our study, no recurrence was observed in the eyes treated with laser photocoagulation after the disease completely regressed. The anatomic success rate during the last visit was similar in both groups. This difference between the two studies in terms of recurrence and anatomical success may be due to the fact that we preferred intravitreal aflibercept instead of laser photocoagulation for patients with zone 2 posterior ROP and left avascular areas that might cause VEGF production by applying laser spots in the near-confluent pattern.
When the effects of intravitreal bevacizumab and laser photocoagulation on refraction were evaluated, it was found that the eyes with zone 1 disease developed less myopia in the intravitreal bevacizumab group than in the laser group.8 In a study in which zone 1 and zone 2 distribution was more equal, myopia and mean spherical equivalent were similar in patients treated with intravitreal bevacizumab and laser photocoagulation.31 In the refraction tests of the patients treated with intravitreal aflibercept at the age of 1 year, myopia of greater than 5.00 D was detected only in 1 patient (3.8%); the disease located in zone 1 and a low PMA at which the treatment was administered were determined to be risk factors for the development of high myopia. Posterior location of the disease and low BW and GA, especially in the eyes treated with laser photocoagulation, are risk factors for myopia development.17 In our study, there was no difference between the groups in terms of spherical equivalent. Lower refractive error compared to the other studies, especially in the laser photocoagulation group, may be due to the preference for intravitreal aflibercept instead of laser photocoagulation in patients with zone 1 ROP.
Intravitreal aflibercept treatment provides successful anatomical and refractive outcomes in cases of posterior disease and allows the retinal vascularization to progress. However, the recurrence rate and requirement for additional treatment compared to laser photocoagulation suggest that patients receiving this treatment should be followed up more frequently.
- Kandasamy Y, Hartley L, Rudd D, Smith R. The association between systemic vascular endothelial growth factor and retinopathy of prematurity in premature infants: a systematic review. Br J Ophthalmol. 2017;101(1):21–24. doi:10.1136/bjophthalmol-2016-308828 [CrossRef]
- Hartnett ME. Pathophysiology and mechanisms of severe retinopathy of prematurity. Ophthalmology. 2015;122(1):200–210. doi:10.1016/j.ophtha.2014.07.050 [CrossRef]
- Ng EYJ, Connolly BP, McNamara JA, Regillo CD, Vander JF, Tasman W. A comparison of laser photocoagulation with cryotherapy for threshold retinopathy of prematurity at 10 years: part 1. Visual function and structural outcome. Ophthalmology. 2002;109(5):928–934. doi:10.1016/S0161-6420(01)01017-X [CrossRef]
- Early Treatment for Retinopathy of Prematurity Cooperative Group. 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. doi:10.1001/archopht.121.12.1684 [CrossRef]
- Good WV, Hardy RJ, Dobson V, et al. Early Treatment for Retinopathy of Prematurity Cooperative Group. 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]
- Lok JYC, Yip WWK, Luk ASW, Chin JKY, Lau HHW, Young AL. Visual outcome and refractive status in first 3 years of age in preterm infants suffered from laser-treated Type 1 retinopathy of prematurity (ROP): a 6-year retrospective review in a tertiary centre in Hong Kong. Int Ophthalmol. 2018;38(1):163–169.
- Mueller B, Salchow DJ, Waffenschmidt E, et al. Treatment of type I ROP with intravitreal bevacizumab or laser photocoagulation according to retinal zone. Br J Ophthalmol. 2017;101(3):365–370.
- Mintz-Hittner HA, Kennedy KA, Chuang AZBEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011;364(7):603–615. doi:10.1056/NEJMoa1007374 [CrossRef]
- Baumal CR, Goldberg RA, Fein JG. Primary intravitreal ranibizumab for high-risk retinopathy of prematurity. Ophthalmic Surg Lasers Imaging Retina. 2015;46(4):432–438. doi:10.3928/23258160-20150422-05 [CrossRef]
- Salman AG, Said AM. Structural, visual and refractive outcomes of intravitreal aflibercept injection in high-risk prethreshold type 1 retinopathy of prematurity. Ophthalmic Res. 2015;53(1):15–20. doi:10.1159/000364809 [CrossRef]
- Vural A, Perente I, Onur IU, et al. Efficacy of intravitreal aflibercept monotherapy in retinopathy of prematurity evaluated by periodic fluorescence angiography and optical coherence tomography. Int Ophthalmol. 2019;39(10):2161–2169. doi:10.1007/s10792-018-1040-x [CrossRef]
- Gunay M, Sukgen EA, Celik G, Kocluk Y. Comparison of bevacizumab, ranibizumab, and laser photocoagulation in the treatment of retinopathy of prematurity in Turkey. Curr Eye Res. 2017;42(3):462–469. doi:10.1080/02713683.2016.1196709 [CrossRef]
- Lorenz B, Stieger K, Jager M, Mais C, Stieger S, Andrassi-Darida M. Retinal vascular development with 0.312 mg intravitreal bevacizumab to treat severe posterior retinopathy of prematurity: a longitudinal fluorescein angiographic study. Retina. 2017;37(1):97–111.
- Mintz-Hittner HA, Geloneck MM, Chuang AZ. Clinical management of recurrent retinopathy of prematurity after intravitreal bevacizumab monotherapy. Ophthalmology. 2016;123(9):1845–1855. doi:10.1016/j.ophtha.2016.04.028 [CrossRef]
- International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. 2005;123(7):991–999. doi:10.1001/archopht.123.7.991 [CrossRef]
- Uparkar M, Sen P, Rawal A, Agarwal S, Khan B, Gopal L. Laser photocoagulation (810 nm diode) for threshold retinopathy of prematurity: a prospective randomized pilot study of treatment to ridge and avascular retina versus avascular retina alone. Int Ophthalmol. 2011;31(1):3–8. doi:10.1007/s10792-010-9411-y [CrossRef]
- Yetik H, Gunay M, Sirop S, Salihoglu Z. Intravitreal bevacizumab monotherapy for type-1 prethreshold, threshold, and aggressive posterior retinopathy of prematurity: 27 month follow-up results from Turkey. Graefes Arch Clin Exp Ophthalmol. 2015;253(10):1677–1683. doi:10.1007/s00417-014-2867-0 [CrossRef]
- Menke MN, Framme C, Nelle M, Berger MR, Sturm V, Wolf S. Intravitreal ranibizumab monotherapy to treat retinopathy of prematurity zone II, stage 3 with plus disease. BMC Ophthalmol. 2015;15(1):20. doi:10.1186/s12886-015-0001-7 [CrossRef]
- Shin DH, Kong M, Kim SJ, et al. Risk factors and rate of progression for zone I versus zone II type 1 retinopathy of prematurity. J AAPOS. 2014;18(2):124–128. doi:10.1016/j.jaapos.2013.12.003 [CrossRef]
- Soh Y, Fujino T, Hatsukawa Y. Progression and timing of treatment of zone I retinopathy of prematurity. Am J Ophthalmol. 2008;146(3):369–374. doi:10.1016/j.ajo.2008.05.010 [CrossRef]
- Kong M, Shin DH, Kim SJ, et al. Retinopathy of prematurity in infants born before 25 weeks gestation in a Korean single neonatal intensive care unit: incidence, natural history and risk factors. J Korean Med Sci. 2012;27(12):1556–1562. doi:10.3346/jkms.2012.27.12.1556 [CrossRef]
- Kychenthal A, Dorta P, Katz X. Zone I retinopathy of prematurity: clinical characteristics and treatment outcomes. Retina. 2006;26(7) (suppl):S11–S15. doi:10.1097/01.iae.0000244285.79004.e6 [CrossRef]
- Good WV, Hardy RJ, Dobson V, et al. Early Treatment for Retinopathy of Prematurity Cooperative Group. The incidence and course of retinopathy of prematurity: findings from the early treatment for retinopathy of prematurity study. Pediatrics. 2005;116(1):15–23. doi:10.1542/peds.2004-1413 [CrossRef]
- Mintz-Hittner HA, Kuffel RR Jr, . Intravitreal injection of bevacizumab (avastin) for treatment of stage 3 retinopathy of prematurity in zone I or posterior zone II. Retina. 2008;28(6):831–838. doi:10.1097/IAE.0b013e318177f934 [CrossRef]
- Kara C, Hekimoglu E, Petriçli IS, Akil H. Intravitreal bevacizumab as rescue therapy following treatment failure with laser photocoagulation in retinopathy of prematurity. J Curr Ophthalmol. 2017;30(1):80–84. doi:10.1016/j.joco.2017.08.007 [CrossRef]
- Dani C, Frosini S, Fortunato P, et al. Intravitreal bevacizumab for retinopathy of prematurity as first line or rescue therapy with focal laser treatment: a case series. J Matern Fetal Neonatal Med. 2012;25(11):2194–2197. doi:10.3109/14767058.2012.684109 [CrossRef]
- Wallace DK, Dean TW, Hartnett ME, et al. Pediatric Eye Disease Investigator Group. A dosing study of bevacizumab for retinopathy of prematurity: late recurrences and additional treatments. Ophthalmology. 2018;125(12):1961–1966. doi:10.1016/j.ophtha.2018.05.001 [CrossRef]
- Sukgen EA, Koçluk Y. Comparison of clinical outcomes of intravitreal ranibizumab and aflibercept treatment for retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol. 2019;257(1):49–55. doi:10.1007/s00417-018-4168-5 [CrossRef]
- Ekinci DY, Vural AD, Bayramoglu SE, Onur IU, Hergunsel GO. Assessment of vascular leakage and its development with FFA among patients treated with intravitreal anti-VEGF due to aggressive posterior ROP. Int Ophthalmol. 2019.;39(12):2697–2705. doi:10.1007/s10792-019-01088-7 [CrossRef]
- Garcia Gonzalez JM, Snyder L, Blair M, Rohr A, Shapiro M, Greenwald M. Prophylactic peripheral laser and fluorescein angiography after bevacizumab for retinopathy of prematurity. Retina. 2018;38(4):764–772. doi:10.1097/IAE.0000000000001581 [CrossRef]
- Isaac M, Mireskandari K, Tehrani N. Treatment of type 1 retinopathy of prematurity with bevacizumab versus laser. J AAPOS. 2015;19(2):140–144. doi:10.1016/j.jaapos.2015.01.009 [CrossRef]
Demographic and Clinical Characteristics
|Characteristic||LPC Group||IVA Group||P|
|Sex (M/F) (no., %)||9 (33, 3%)/18 (66, 7%)||10 (41, 7%)/14 (58, 3%)||.539a|
|GA, mean ± SD (95% CI), weeks||28.7 ± 3.0||27.3 ± 2.8||.068b|
|BW, mean ± SD (95% CI), g||1,281 ± 438||1,095 ± 442||.12b|
|Treatment (PMA), mean ± SD (95% CI), weeks||37.6 ± 2.5||34.2 ± 2.4||.000b|
|Follow-up, mean ± SD (95% CI), weeks||47.0 ± 10.1||45.2 ± 11.1||.636b|
|Zone I/zone II (no., %)||0 (0%)/27 (100%)||22 (91, 7%)/2 (8, 3%)||.05a|
|Rubeosis iridis (−)/(+)||27 (100, 0%)/0 (0, 0%)||6 (25, 0%)/18 (75, 0%)||.05a|