Regression Of Retinopathy Of Prematurity Research Articles

A Dosing Study of Bevacizumab for Retinopathy of Prematurity: Late Recurrences and Additional Treatments

Intravitreal bevacizumab is increasingly used to treat severe retinopathy of prematurity (ROP), but it enters the bloodstream, and there is concern that it may alter development of other organs. Previously we reported short-term outcomes of 61 infants enrolled in a dose de-escalation study, and we report the late recurrences and additional treatments. Masked, multicenter, dose de-escalation study. A total of 61 premature infants with type 1 ROP. If type 1 ROP was bilateral at enrollment, then the study eye was randomly selected. In the study eye, bevacizumab intravitreal injections were given at de-escalating doses of 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg; if needed, fellow eyes received 1 dose level higher: 0.625 mg, 0.25 mg, 0.125 mg, or 0.063 mg, respectively. After 4 weeks, additional treatment was at the discretion of the investigator. Early and late ROP recurrences, additional treatments, and structural outcomes after 6 months. Of 61 study eyes, 25 (41%; 95% confidence interval [CI], 29%-54%) received additional treatment: 3 (5%; 95% CI, 1%-14%) for early failure (within 4 weeks), 11 (18%; 95% CI, 9%-30%) for late recurrence of ROP (after 4 weeks), and 11 (18%; 95% CI, 9%-30%) for persistent avascular retina. Re-treatment for early failure or late recurrence occurred in 2 of 11 eyes (18%; 95% CI, 2%-52%) treated with 0.25 mg, 4 of 16 eyes (25%; 95% CI, 7%-52%) treated with 0.125 mg, 8 of 24 eyes (33%; 95% CI, 16%-55%) treated with 0.063 mg, and 0 (0%; 95% CI, 0%-31%) of 10 eyes treated with 0.031 mg. By 6 months corrected age, 56 of 61 study eyes had regression of ROP with normal posterior poles, 1 study eye had developed a Stage 5 retinal detachment, and 4 infants had died of preexisting medical conditions. Retinal structural outcomes are very good after low-dose bevacizumab treatment for ROP, although many eyes received additional treatment.

Comparison of Intravitreal Bevacizumab and Laser Photocoagulation in the Treatment of Retinopathy of Prematurity

To compare the outcomes of patients with type I retinopathy of prematurity (ROP) treated with either intravitreal bevacizumab (IVB) or retinal laser photocoagulation (RLP). Retrospective case series. Infants treated for type I ROP with IVB or RLP. Patients who were born between January 2011 and December 2014 and were treated in Farabi Eye Hospital were included. The outcomes were stratified and analyzed, based on the treatment type and ROP zone. Need for retreatment, time to regression, refractive errors, retinal adverse anatomic outcomes, and rate of complications. Five hundred twenty-three patients were treated for type 1 ROP, of whom 493 (986 eyes) met inclusion criteria. Seven hundred twenty-four eyes (73.4%) received IVB, and 262 eyes (26.5%) received RLP. Re-treatment (because of recurrent or persistent retinopathy) occurred in 14.4% (106/724) of eyes initially treated with IVB and in 8.8% (23/262) eyes initially treated with RLP (P= 0.065). Re-treatment was not significantly different between the 2 groups for patients with zone I disease (P= 0.978). Re-treatment rate was considerably higher in patients with zone II disease treated with IVB (69/558 [12.3%]) compared with those treated with RLP (20/251 [7.9%]; P= 0.017). In the IVB group, 82.8% and 53.4% of eyes showed an avascular area in zone III (despite ROP regression) at 1 and 2 years after treatment, respectively. The spherical power and the spherical equivalent were significantly higher in eyes treated with RLP (-1.31±2.83 diopters [D] and-2.84±2.77 D, respectively) than eyes treated with IVB (0.19±3.21 D and-1.26±3.19 D, respectively; P= 0.016 and P= 0.007, respectively). Differences in astigmatic power were not significant. Both IVB and RLP are effective treatments for type 1 ROP. Longer follow-up time is necessary for infants treated with IVB. More patients with zone II disease treated with RLP achieved disease regression after a single treatment than those who received IVB, although outcomes after re-treatment were comparable except for a greater refractive error in patients treated with RLP.

Analysis of the Recurrence of Plus Disease after Intravitreal Ranibizumab as a Primary Monotherapy for Severe Retinopathy of Prematurity

To assess the outcomes of severe retinopathy of prematurity (ROP) in zone I or posterior zone II, and of aggressive posterior ROP treated with a single dose of intravitreal ranibizumab (IVR) as monotherapy. Retrospective study. The study included premature babies diagnosed with aggressive posterior ROP or ROP 3+ in zone I or posterior zone II. Intravitreal injection of 0.25 mg (0.025 mL) ranibizumab was performed in the operating room. A disposable 1-mL syringe with a 30-gauge needle was used. Favorable outcome was considered regression of ROP after treatment (meaning regression of the retinal neovascularization and plus disease). Unfavorable outcome was progression to stages 4 and 5 of ROP. The study included 43 infants (85 eyes). The mean birth weight and gestational age were 1276±302 g and 29.7±2.0 weeks, respectively. The mean postmenstrual age at ROP diagnosis was 36±2.7 weeks and at treatment was 37.2±2.2 weeks. All 85 eyes demonstrated total regression of plus disease after a single dose of IVR. Twelve infants (29.2%) developed full vascularization of the peripheral retina in both eyes. Twenty-two infants (43 eyes [53.6%]) developed ROP reactivation at a mean interval of 7.1±3 weeks (range, 3-15 weeks) after IVR and needed rescue laser treatment of the peripheral avascular retina. The mean postmenstrual age at rescue laser was 43±3.2 weeks (range, 35.5-54.5 weeks). Six patients (11.6%) had persistent peripheral avascular retina in zone II for >6 months (or 24 weeks) after IVR treatment. Although there was complete regression of plus disease in all treated eyes, only 29.2% of the patients reached complete peripheral retinal vascularization. There was a disease reactivation in 53.6% of the patients and they needed additional laser therapy. The results of IVR treatment in severe ROP, even when initial control of the disease was achieved, did not eliminate the risk of late reactivation of the disease by retinal neovascularization. Some of the treated patients may achieve a permanent interruption in the development of the peripheral retinal vascularization.

Effect of Intravitreal Aflibercept on Central Retinal Arterial Blood Flow in Type 1 Retinopathy of Prematurity.

To evaluate the blood flow changes of the central retinal artery measured with color Doppler imaging (CDI) in infants receiving intravitreal aflibercept (IVA) for treatment of type 1 retinopathy of prematurity (ROP). Patients with type 1 ROP were assessed prospectively by CDI following IVA. Color Doppler imaging was used to measure the peak systolic velocity, end diastolic velocity (EDV), pulsatility index (PI), and resistivity index (RI) of the central retinal artery (CRA) before IVA injection and 1 hour, 1 week, and 1 month after injection. A total of 29 eyes of 15 infants were included in this study. The mean gestational age at birth was 28.62 ± 2.48 weeks and the mean birthweight was 1,198.62 ± 348.99 g. All treated eyes showed complete regression of ROP and peripheral retinal vascularization continued. Measurements of EDV-CRA, RI-CRA, and PI-CRA showed significant changes after IVA treatment. This study showed that IVA is an effective treatment for type 1 ROP. After IVA treatment, vascular resistance increases, ocular blood flow decreases, and changes in hemodynamic parameters of CRA may remain for a month. Further studies are needed to evaluate the effect of anti-vascular endothelial growth factor agents on ocular hemodynamics in infants with ROP.

Low-dose ranibizumab as primary treatment of posterior type I retinopathy of prematurity

ObjectiveThe aim of this study was to evaluate the visual and structural outcomes of eyes that received ranibizumab as treatment for retinopathy of prematurity (ROP). MethodsThis was a retrospective case series of infants who received a 0.2 mg (0.02 mL) intravitreal injection of ranibizumab as the primary treatment for type 1 ROP. Outcome measures included regression or recurrence of ROP, complications of treatment, and assessment of visual acuity and refractive error. ResultsForty-two eyes of 21 infants (13 male) were included. Mean gestational age and birth weight were 24.6 ± 1.3 weeks and 613 ± 91 g, respectively. Mean age at injection was 37.4 ± 2.2 weeks postmenstrual age, and mean follow-up period was 10.1 ± 7 months. Active neovascularization regressed rapidly, and anatomical outcomes were favourable in all eyes. Twelve eyes of 6 infants received supplemental laser photocoagulation at a mean post-menstrual age (PMA) of 72.0 ± 27.3 weeks when vascularization had not advanced beyond zone II. Visual acuity was measurable in 28 of 42 eyes. Mean visual acuity was 0.94 ± 0.36 logMAR. Mean spherical equivalent was +1.00. There were no ocular or systemic complications in these patients and no cicatricial complications were observed with no progression to stage 4 or 5 disease. ConclusionsA single intravitreal dose of 0.2 mg (0.02 mL) ranibizumab showed favourable anatomical and functional outcomes in eyes with type 1 ROP.

Anti-Vascular Endothelial Growth Factor Therapy for Primary Treatment of Type 1 Retinopathy of Prematurity: A Report by the American Academy of Ophthalmology

To review the available evidence on the ocular safety and efficacy of anti-vascular endothelial growth factor (VEGF) agents for the treatment of retinopathy of prematurity (ROP) compared with laser photocoagulation therapy. A literature search of the PubMed and Cochrane Library databases was conducted last on September 6, 2016, with no date restrictions and limited to articles published in English. This search yielded 311 citations, of which 37 were deemed clinically relevant for full-text review. Thirteen of these were selected for inclusion in this assessment. The panel methodologist assigned ratings to the selected articles according to the level of evidence. Of the 13 citations, 6 articles on 5 randomized clinical trials provided level II evidence supporting the use of anti-VEGF agents, either as monotherapy or in combination with laser therapy. The primary outcome for these articles included recurrence of ROP and the need for retreatment (3 articles), retinal structure (2 articles), and refractive outcome (1 article). Seven articles were comparative case series that provided level III evidence. The primary outcomes included the effects of anti-VEGF treatment on development of peripheral retinal vessels (1article), refractive outcomes (1 article), or both structural and refractive or visual outcomes (5 articles). Current level II and III evidence indicates that intravitreal anti-VEGF therapy is as effective as laser photocoagulation for achieving regression of acute ROP. Although there are distinct ocular advantages to anti-VEGF pharmacotherapy for some cases (such as eyes with zone I disease or aggressive posterior ROP), the disadvantages are that the ROP recurrence rate is higher, and vigilant and extended follow-up is needed because retinal vascularization is usually incomplete. After intravitreal injection, bevacizumab can be detected in serum within 1 day, and serum VEGF levels are suppressed for at least 8 to 12 weeks. The effects of lowering systemic VEGF levels on the developing organ systems of premature infants are unknown, and there are limited long-term data on potential systemic and neurodevelopmental effects after anti-VEGF use for ROP treatment. Anti-VEGF agents should be used judiciously and with awareness of the known and unknown or potential side effects.

Outcome of solid-state 532nm green laser in high-risk retinopathy of prematurity at a tertiary care centre in India.

The purpose of this study was to analyse the outcome of solid-state green laser in high-risk retinopathy of prematurity (ROP) at a tertiary centre in India. Fifty-nine eyes of 30 infants with high-risk ROP were recruited in this prospective, interventional study. High-risk ROP included prethreshold type 1 ROP and APROP. Laser photocoagulation was performed with 532nm solid-state green laser (Novus Spectra, Lumenis, GmbH, Germany). Of the 30 infants, 18 were males (60%) and 12 were females (40%). The mean birth weight was 1102.83±196.27g. The mean gestational age was 29.5±1.47weeks. Zone 1 disease was present in 10 eyes (16.95%) and zone 2 disease in 49 (83.05%) eyes. Out of 57 eyes with prethreshold type 1 ROP, 39 eyes (68.42%) had stage 2 and 18 eyes (31.58%) had stage 3. The postconceptional age at the time of treatment was 36.03±2.32weeks. The infants received mean 2710.24±747.97 laser spots. Fifty (84.8%) eyes underwent laser in a single sitting and 9 eyes (15.2%) required 2 laser sittings. Mean time for regression of ROP was 5.8±3.8weeks (range 3-11weeks). Total ROP regression was seen in 55 eyes (93.22%). Despite laser treatment, 4 (6.78%) eyes of three infants had unfavourable outcome. One infant developed intra-procedural bradycardia. Vitreous haemorrhage was seen in five eyes (8.4%). Solid-state 532nm green laser is a safe and effective treatment for high-risk retinopathy of prematurity.

Asymmetric Outcomes of Type 1 Retinopathy of Prematurity after Bilateral Intravitreal Ranibizumab Treatment.

Purpose. To present cases with retinopathy of prematurity (ROP), who were treated with intravitreal injection of ranibizumab (IVR) and had unpredictable asymmetric outcomes. Methods. A retrospective review was performed in infants with type 1 ROP and had bilateral IVR (0.25 mg/0.025 mL) as initial treatment. Patients were classified into the asymmetric outcome group and the symmetric outcome group. Results. Eighty-four patients (168 eyes) were included. There were 18 eyes of 9 patients (10.7%) in the asymmetric outcome group and 150 eyes of 75 patients (89.3%) in the symmetric outcome group. In the symmetric outcome group, 86 eyes (57.3%) had ROP regression, 60 eyes (40%) had reactivation requiring laser treatment, and 4 eyes (2.7%) progressed to retinal detachment requiring vitrectomy. In the asymmetric outcome group, one of the eyes of the 9 patients had ROP regression with/without reactivation after IVR, while the contralateral eyes had negative response, including remarkable posterior fibrosis, partial or total retinal detachment, and vitreous hemorrhage. There was statistically significant difference between the birth weight of the two groups. Conclusion. Contralateral eyes with ROP can take a different clinical course after ranibizumab treatment. High rate of reactivation after IVR is another concern that ophthalmologists should pay attention to.

RETINAL VASCULAR DEVELOPMENT WITH 0.312 MG INTRAVITREAL BEVACIZUMAB TO TREAT SEVERE POSTERIOR RETINOPATHY OF PREMATURITY: A Longitudinal Fluorescein Angiographic Study.

To report the outcome of intravitreal 0.312 mg bevacizumab (IVB) monotherapy in acute retinopathy of prematurity (ROP) and to describe the vascular development over time. Seventeen prematurely born infants were treated with IVB (0.312 mg in 0.025 mL per eye) because of acute ROP in posterior Zone II or Zone I, including aggressive posterior ROP. Infants were examined by fluorescein angiography (FA) using RetCam II or III (Clarity Medical Systems Inc) before IVB (n = 21 eyes), within 6 weeks (n = 23 eyes), 8 to 13 weeks (n = 22 eyes), and up to 45 months (n = 10 eyes). Acute ROP regressed in 19 out of 27 analyzed eyes (70%), including 100% and 80% of posterior Zone II and Zone I eyes, respectively, but only 25% of aggressive posterior ROP eyes. Early recurrences (11%, all aggressive posterior ROP) and late reactivations (18%) were observed within 1 week and at 9 to 12 weeks, respectively. All eyes showed leakage at the junction of the vascularized zone and capillary malformation on FA before treatment. Vessel branching abnormalities and circumferential vessel formation were typical FA features after treatment. Vascular outgrowth after one IVB became complete in 87.5% of eyes for which FA was available up to at least 9 weeks after IVB. A single dose of 0.312 mg bevacizumab was efficient to induce regression of ROP in posterior Zone II and most of Zone I cases, but not in aggressive posterior ROP. FA describes vascular abnormalities, the importance of which warrants further investigation.

Antivascular endothelial growth factor in the treatment of retinopathy of prematurity.

To review the most recent literature regarding the clinical experience of antivascular endothelial growth factor (anti-VEGF) therapies in the treatment of retinopathy of prematurity (ROP). Anti-VEGF agents in stage 3+ and aggressive posterior ROP have been shown to induce rapid ROP regression. However, significant reoccurrence rates can require repeat injections and thus longer term and more frequent follow-up. Initial studies reflect conflicting evidence regarding significant systemic side effects of these treatments, and outcomes in these patients past the first few years of life are yet to be definitively determined. Although anti-VEGF therapies show promise in the treatment of ROP, frequent reoccurrences and lack of thorough data about long-term side effects of pharmacologic intervention necessitate further research before anti-VEGF agents become the mainstay of ROP management.

Intravitreal Bevacizumab for Zone II Retinopathy of Prematurity.

To evaluate the treatment outcomes of intravitreal bevacizumab injections as monotherapy in type 1 retinopathy of prematurity (ROP). A retrospective chart review was performed for patients with type 1 ROP who had intravitreal bevacizumab injections between November 2013 and January 2015 at La Paz University Hospital in Madrid, Spain. Gestational age at birth, birth weight, sex, ROP zone, ROP stage, mean age at treatment, and follow-up period were recorded. The final clinical status of the retina was noted for each patient. The primary outcome measures included ROP recurrences requiring re-treatment, complete or incomplete peripheral vascularization, mean age at complete vascularization, and refractive errors. From 14 patients enrolled with type 1 ROP, 28 eyes were included. The mean gestational age at birth was 25.9 ± 2.34 weeks (range: 23.6 to 32.4 weeks) and the median birth weight was 694 g (range: 487 to 1,740 g). All eyes showed zone II ROP: 18 eyes (64.3%) had anterior zone II ROP and 10 eyes (35.7%) had posterior zone II ROP. One week after intravitreal bevacizumab injection, 14 eyes (50%) had achieved complete regression of ROP, and a partial regression of ROP was observed in 10 eyes (35.7%). Twenty-two eyes (78.6%) obtained complete vascularization during the follow-up. The median time to complete vascularization was 134 ± 21.45 days. The mean spherical equivalent at last visit was 1.99 diopters. Intravitreal bevacizumab injection used as a monotherapy is an effective treatment approach in patients with zone II ROP. [J Pediatr Ophthalmol Strabismus. 2016;53(6):375-382.].

Comparison of structural outcome between intravitreal bevacizumab and laser treatment for type 1 retinopathy of prematurity after long-term follow-up

Background: To compare the structural outcome of intravitreal bevacizumab (IVB) and laser treatment for type 1 retinopathy of prematurity (ROP). Methods: This is a retrospective comparative study. From December 2002 to April 2009, patients with type 1 ROP according to criteria of Early Treatment of Retinopathy of Prematurity (ETROP) study were treated by peripheral retinal diode laser photocoagulation in nearly confluent pattern. From May 2009 to January 2015, we performed IVB for patients with type 1 ROP. The patients were closely followed until disappearance of retinal neovascularization in the laser group and regression of avascular zone in the bevacizumab group. The demographical data, postmenstrual age (PMA) for treatment, and fundus findings were recorded by chart review. The difference between laser and bevacizumab groups was compared by Student t-test and Fisher exact test. Results: We collected 43 patients (86 eyes) with type 1 ROP, including 30 male and 13 female infants. Their mean gestation age and birth body weight (BBW) were 27.5 weeks and 1,034 gm. Zone I and zone II disease were found in 8 and 35 patients. The mean PMA for treatment was 37.3 weeks. The mean follow-up period was 54.4 months. Laser treatment was administered in 26 patients, and bevacizumab injection for 17 infants. Single session of laser was performed in all patients of laser group without recurrence of retinal neovascularization. Complete regression of ROP was found in 15 infants of bevacizumab group following the first IVB. Four eyes in two patients (2/17, 11.7%) had recurrence of ROP and received additional injections and adjuvant laser treatment. There was no unfavorable anatomical results such as retinal detachment or macular ectopia or complications such as cataract or endophthalmitis in either bevacizumab or laser management. Conclusions: Laser therapy and IVB were both effective treatments for type 1 ROP to cause favorable anatomical outcomes. Single session of laser ablation in nearly confluent pattern was sufficient for complete regression of ROP in laser group. Single IVB was appropriate for managing most of cases with ROP in bevacizumab group, but a small proportion (nearly one tenth) of them had recurrent episodes requiring adjuvant therapies.

Comparison of Bevacizumab, Ranibizumab, and Laser Photocoagulation in the Treatment of Retinopathy of Prematurity in Turkey

ABSTRACTPurpose: To evaluate the efficacies and treatment outcomes following intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR), and laser photocoagulation (LPC) in retinopathy of prematurity (ROP).Methods: This was a retrospective interventional case series study including the data of 134 infants (264 eyes) who were treated with IVB, IVR, or LPC for ROP. The data were collected from two major ROP treatment centers in Turkey without any randomization or masking. Regression of ROP, recurrence profile, complications after each treatment modality, and indications for retreatment were evaluated. The main outcome measures included the total inactivation of ROP with anatomic and refractive outcomes at 1.5 years of adjusted age.Results: There were 55 infants (41.1%) in the IVB group, 22 infants (16.4%) in the IVR group, and 57 infants (42.5%) in the LPC group. All but 3 infants (5.5%) in the IVB group and 11 infants (50%) in the IVR group showed recurrence to stage 1 and 2 ROP following IVB and IVR (p < 0.001). Retreatment was performed in three infants in both IVB and IVR groups (p = 0.098). At 1.5 years of adjusted age, all infants showed favorable anatomic outcome except one infant in the LPC group. No significant difference of the mean spherical equivalent (SE) was observed between the groups (p = 0.131). In Zone I ROP, laser treated infants had significantly higher rates of myopia and high myopia than IVB and IVR treated infants (p = 0.040 and p = 0.019, respectively).Conclusions: Both IVB and IVR treated infants had significantly better refractive outcomes in Zone I ROP as compared to LPC treated infants at 1.5 years of adjusted age. The higher rate of disease recurrence was associated with IVR. Gestational age (GA) and the zone of ROP were also predictive factors for recurrence of ROP in the study.

Low dose versus conventional dose of intravitreal bevacizumab injection for retinopathy of prematurity: a case series with paired-eye comparison.

To compare the clinical outcomes of intravitreal bevacizumab (IVB) injection, with different dosing (0.25mg/0.01ml versus 0.625mg/0.025ml) in each eye of the same patient with retinopathy of prematurity (ROP). Intravitreal bevacizumab (IVB) was injected into eight patients with stage 3+ in zone I or posterior zone II ROP (16 eyes). Bevacizumab, with different dosing (0.25mg/0.01ml and 0.625mg/0.025ml), was injected into the vitreous cavity of each eye. Among the 16 eyes treated with IVB, six eyes had zone I ROP and 10 eyes had zone II ROP. The mean birthweight was 800±139g (range, 533-955g), and the mean gestational age was 25.9±1.2 gestational weeks (range, 24.4-28.7weeks). The postmenstrual age at initial treatment was 37.2 gestational weeks (range, 33.7-41weeks). The mean follow-up was 312±50days (median, 305days; range, 238-376days). All eyes showed regression of plus sign after IVB injection within 1week and revascularization to the ora serrata at the time of final visit. There was no difference in the time of anatomical achievement between the eyes with different doses. None of the patients received any additional IVB injection or laser photocoagulation. After the regression of ROP, tractional retinal detachment and macular ectopia were not observed in any patients during follow-up. There was no difference in the short-term clinical outcomes of stage 3+ ROP in zone I or II between the eyes with low dose and conventional dose of IVB.

Intravitreal ranibizumab as a primary or a combined treatment for severe retinopathy of prematurity.

PurposeThe aim of the study was to assess the outcomes of severe retinopathy of prematurity (ROP) in zone I or posterior zone II treated with intravitreal ranibizumab (IVR) as monotherapy or combined treatment with laser photocoagulation.MethodsThis is a retrospective study analyzing clinical records of the included patients. Patients were divided into two groups: group 1 included patients who received only IVR treatment; and group 2 was subdivided into group 2A – including patients with IVR as initial treatment and complementary laser photocoagulation if retinal neovascularization or plus disease did not regress, and group 2B – including patients with initial laser photocoagulation and IVR as rescue therapy. Favorable outcomes were regression of the retinal neovascularization and plus disease, meaning control of the disease. Unfavorable outcomes were progression to stages 4 and 5 of ROP.ResultsFifty-seven eyes were included in the study. Mean birth weight and gestational age were 1,281±254 g and 29.5±2.1 weeks, respectively. Group 1 comprised of 16 eyes, with favorable outcomes in 14 eyes (87.5%). Group 2 comprised of 41 eyes, with favorable outcomes in 29 eyes (70.7%), in a mean follow-up period of 12.8 months.ConclusionIVR was effective to treat severe cases of ROP as a primary or a combined treatment. Forty-three of the 57 treated eyes (75.4%) achieved regression of ROP and favorable outcomes.

Reactivation of retinopathy of prematurity after ranibizumab treatment.

Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the developing retina and a significant cause of childhood blindness around the world. Vascular endothelial growth factor (VEGF) plays an important role in the neovascular phase of ROP, and treatment with an anti-VEGF agent is justified in select cases. Bevacizumab is the most commonly used anti-VEGF agent in ROP, but ranibizumab has a shorter half-life with the potential for decreased systemic toxicity. The purpose of this study is to report our experience with anti-VEGF agents for the treatment of ROP. A retrospective chart review was performed on consecutive infants screened for ROP. Infants treated with peripheral retinal ablation, bevacizumab 0.625 mg/0.025 mL, or ranibizumab 0.25 mg/0.025 mL were specifically identified for review of their clinical outcomes. All treated infants had at least 6 months of follow-up with the treating team and were examined until total regression of ROP. One hundred and forty-two infants were screened over a two-year period. Six infants received anti-VEGF agents, with a mean gestational age of 23.48 weeks and mean birth weight of 620 g. Ten eyes from the six infants received anti-VEGF treatment. All ten eyes demonstrated initial regression of ROP. However, ROP reactivation occurred in 5/6 (83%) eyes treated with ranibizumab, on average 5.9 weeks after treatment; whereas none of the 4 eyes treated with bevacizumab experienced reactivation (P < 0.05). One infant who received a unilateral injection of ranibizumab demonstrated bilateral regression of ROP. The role of anti-VEGF treatment for ROP is still being evaluated. Although the shorter half-life of ranibizumab makes it an attractive option, reactivation of ROP is possible. Physicians and families should be aware of this to follow infants closely for an extended period of time.

Primary intravitreal ranibizumab for high-risk retinopathy of prematurity.

To evaluate initial treatment of high-risk retinopathy of prematurity (ROP) with low-dose intravitreal ranibizumab. Case series of premature infants with high-risk pre-threshold or threshold posterior ROP receiving primary therapy with 0.2 mg ranibizumab. Pre-treatment and post-injection examination, RetCam (Clarity Medical Systems, Pleasanton, CA) images, fluorescein angiography, resolution of ROP and plus disease, and stability of examinations were assessed. Eight eyes of four infants received primary ranibizumab treatment. Plus disease resolved within 48 hours of unilateral injection, and there was no change in ROP appearance in the contralateral eye. Complete resolution of stage 3 ROP occurred 1 week after injection. Recurrent progressive stage 2 or 3 ROP in mid to anterior zone 2 was noted 8 to 11 weeks after ranibizumab in all eyes. Treatment of recurrent ROP with peripheral laser led to complete ROP regression. Comparison of images before ranibizumab injection to images after ROP recurred demonstrated anterior retinal growth. Retina examinations remained stable without ROP recurrence or detachment at follow-up 8 to 18 months after ranibizumab injection. Intravitreal ranibizumab induces rapid, complete regression of high-risk posterior ROP with continued retina growth peripherally. The potential for recurrent ROP after a single 0.2 mg ranibizumab injection for posterior ROP requires vigilant monitoring. Subsequent peripheral laser for ROP recurrences may spare the posterior retina from photocoagulation effects.

Outcomes and Prognostic Factors of Intravitreal Bevacizumab Monotherapy in Zone I Stage 3+ and Aggressive Posterior Retinopathy of Prematurity.

Purpose. This study aims to evaluate the regression of retinopathy of prematurity (ROP) after one intravitreal injection of bevacizumab and the factors that influenced it. Methods. This retrospective case series was carried out at the “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania. It includes all the consecutive infants treated for ROP with one intravitreal bevacizumab injection, from January 1, 2009, throughout July 31, 2013. The follow-up continued for 60 weeks after injection. We recorded ROP classification, regression, gender, gestational age, birth weight, postnatal age and postmenstrual age at treatment, and pregnancy type. Regression was analyzed according to each of the abovementioned factors, with the program IBM SPSS 20 (Chicago, Illinois, USA). Results. This study includes 74 eyes of 37 infants of which 52 had aggressive posterior ROP (70.27%) and 22 had zone I stage 3+ ROP (29.72%). One week after the bevacizumab injection, ROP regressed in 63 eyes (85.13%), with a statistically significant higher rate in zone I stage 3+ ROP (100%), as compared with aggressive posterior ROP (78.84%) (P = 0.03). We recorded no complications subsequent to the intravitreal injections of bevacizumab. We identified no late retinal detachment. Conclusion. ROP regression rate after one intravitreal bevacizumab injection was 85.13%. This trial is registered with trial registration number IRCT2014101618966N2.

Influence of the blood glucose level on the development of retinopathy of prematurity in extremely premature children.

To investigate the influence of the blood glucose level on the development of retinopathy of prematurity (ROP) in extremely premature infants. Sixty-four premature infants with a gestational age of less than 30 weeks and a birth weight of less than 1500 g were included in the study. Children without ROP were allocated to Group 1 (n=14, gestational age 28.6 ± 1.4 weeks, birth weight 1162 ± 322 g), and children with spontaneous regression of ROP were allocated to Group 2 (n=32, gestational age 26.5 ± 1.2 weeks, birth weight 905 ± 224 g). Children with progressive ROP who underwent laser treatment were included in Group 3 (n=18, gestational age 25.4 ± 0.7 weeks, birth weight 763 ± 138 g). The glucose level in the capillary blood of the premature infants was monitored daily during the first 3 weeks of life. A complete ophthalmological screening was performed from the age of 1 month. The nonparametric signed-rank Wilcoxon-Mann-Whitney test was used for statistical analysis. The mean blood glucose level was 7.43 ± 2.6 mmol/L in Group 1, 7.8 ± 2.7 mmol/L in Group 2, and 6.7 ± 2.6 mmol/L in Group 3. There were no significant differences in the blood glucose levels between children with and without ROP, and also between children with spontaneously regressing ROP and progressive ROP (p>0.05). Additionally, there were no significant differences in the blood glucose levels measured at the first, second, and third weeks of life (p>0.05). The blood glucose level is not related to the development of ROP nor with its progression or regression. The glycemic level cannot be considered as a risk factor for ROP, but reflects the severity of newborns' somatic condition and morphofunctional immaturity.

Diode Laser Photocoagulation for Retinopathy of Prematurity: Outcomes After 7 Years of Treatment

This study aimed to evaluate the outcome of transpupillary diode laser photocoagulation for retinopathy of prematurity (ROP) at one institution in Romania. This retrospective case series included all infants who received indirect diode laser photocoagulation for ROP between January 1, 2006, and December 31, 2012. The 160 eyes of 83 infants were classified into two categories: 136 eyes (85%) with classic disease (stage III ROP in zones 1 or 2) and 24 eyes (15%) with aggressive posterior ROP (AP-ROP). ROP regressed in 141 eyes (88.12%). The success rate was significantly better in the classic ROP group (94.11%) compared to the AP-ROP group (54.16%) (P < .001). The ROP regression rate after the laser treatment was 88% in this series.