Therapy For Retinopathy Of Prematurity Research Articles

Treatment success of laser therapy for retinopathy of prematurity in referred and non-referred patients

Comparison of laser therapy (LT) outcomes in patients with retinopathy of prematurity (ROP) followed up in our clinic and referred from other centers. Medical records of 1,856 ROP patients were retrospectively evaluated, and a total of 128 patients who underwent LT were included in the study. The study population was divided into the following two groups: patients who were followed up and treated in our clinic (group 1, N=45) and patients who were referred to our clinic from other centers (group 2, N=83). Data regarding birth weight, sex, gestational age, postnatal treatment time, disease localization, and stage were analyzed and compared between the two groups. Treatment success was defined by anatomic success 6 months after treatment. Patients in the referred group presented with a more advanced disease (p<0.01), a lower treatment success rate (p=0.01), and a longer time interval between diagnosis and LT (p=0.04). The treatment success rate of ROP was significantly lower in referred patients because of the potential delay in LT and more advanced disease at the time of treatment initiation.

Clinical features of infants treated for severe retinopathy of prematurity: 8-yearstudy from a large tertiary neonatal intensive care unit in Turkey.

The aim of this study was to report the gestational age (GA) and birth weight (BW) distribution of premature babies who needed treatment for retinopathy of prematurity (ROP) and to assess the timing of the treatment. The records of 9008 infants who were screened for ROP were examined and 556 infants who underwent laser therapy for ROP were reviewed. Sex, GA, BW, postnatal age, and postmenstrual (PM) age at the time of laser therapy were recorded. The babies were classified as in-born (Group 1) and out-born infants (Group 2). The mean GA was 27.3 weeks (range: 22-33 weeks) and the mean BW was 991.1 g (range: 520-2160 g). Of the treated infants, 7.0% were born later than 32 weeks and 8.3% were born over 1500 g. The mean postnatal age was 9.48 weeks (range: 5-22 weeks) and the mean PM age was 36.72 weeks (range: 29-48 weeks) at the time of treatment. Mean BWs and GAs were significantly higher and the mean postnatal age at the time of laser therapy was significantly earlier in Group 2. Infants with severe ROP had a wider range of BWs and GAs compared to those from developed countries and earlier treatment was needed for out-born infants.

Expression of Total Vascular Endothelial Growth Factor and the Anti-angiogenic VEGF165b Isoform in the Vitreous of Patients with Retinopathy of Prematurity

Background:This study was to examine the expression of total vascular endothelial growth factor (VEGF) and the anti-angiogenic VEGF165b isoform in the vitreous body of retinopathy of prematurity (ROP) patients, and to further study the role of the VEGF splicing in the development of ROP.Methods:This was a prospective clinical laboratory investigation study. All patients enrolled received standard ophthalmic examination with stage 4 ROP that required vitrectomy to collect the vitreous samples. The control samples were from congenital cataract patients. The expression of total VEGF and the anti-angiogenic VEGF165b were measured by enzyme-linked immunosorbent assay. Results were analyzed statistically using nonparametric tests.Results:The total VEGF level was markedly elevated in ROP samples while VEGF165b was markedly decreased compared to control group. The relative protein expression level of VEGF165b isoform was significantly decreased in ROP patients which were correlated with the ischemia-induced neovascularization.Conclusions:There was a switch of VEGF splicing from anti-angiogenic to pro-angiogenic family in ROP patients. A specific inhibitor that more selectively targets VEGF165and controls the VEGF splicing between pro- and anti-angiogenic families might be a more effective therapy for ROP.

One-year clinical outcome after laser treatment for retinopathy of prematurity at a tertiary center in Turkey.

The purpose of the study is to evaluate the clinical outcome of laser photocoagulation (LPC) in the treatment of retinopathy of prematurity (ROP) at a referral hospital in Turkey. In this retrospective study, a chart review of infants who underwent LPC for ROP between June 2011 and June 2013 was done. Clinical and demographic characteristics, laser parameters, anatomic, and refractive outcomes were evaluated. Totally 113 infants (202 eyes) were enrolled in the study. Of the 202 eyes, 29 eyes had threshold ROP, 141 eyes had prethreshold ROP, and 32 eyes had aggressive posterior ROP (APROP) at initial interventions. The mean gestational age (GA) was 28.13 ± 1.99 weeks (range between 24 and 33 weeks), the mean birth weight (BW) was 1,147.77 ± 341.77 g (range between 530 and 2,000 g) and the mean postmenstrual age (PMA) at first laser treatment time was 35.79 ± 1.74 weeks (range between 33 and 39 weeks). The mean number of laser spots (NLS) applied for each eye was 1,358.05 ± 369.91. Eyes with APROP had higher number of NLS than eyes with threshold ROP and prethreshold ROP (P < 0.01). Anatomic outcome was favorable for 171 eyes (84.7 %) at the end of the 1-year follow-up. Refractive data were available for 56 infants (100 eyes). The mean refractive error was 0.00 ± 2.48D SE. The incidence of high myopia (>5D) and strabismus was 2 and 14.3 %, respectively. Laser photocoagulation is an effective therapy for ROP. Early and appropriate laser treatment improves the clinical outcome of the disease.

Intravitreal bevacizumab as single drug therapy for retinopathy of prematurity in 12 patients

Intravitreal bevacizumab as single drug therapy for retinopathy of prematurity in 12 patients

Persistent plus Disease after Laser in Retinopathy of Prematurity with Tetralogy of Fallot

We present a patient with retinopathy of prematurity (ROP) who received panretinal photocoagulation (PRP), but in whom plus disease developed, likely secondary to a complicated cardiovascular history, including DiGeorge syndrome and tetralogy of Fallot. Interventional case report with clinical and angiographic correlation. Our patient had been born at 29 weeks and 2 days gestational age with a birthweight of 940 grams, tetralogy of Fallot, DiGeorge syndrome, and major aortopulmonary collaterals. Type 1 Early Treatment for Retinopathy of Prematurity ROP (zone 2, stage 2 with plus) developed, requiring PRP. Worsening plus disease developed and mild further PRP was performed. Despite this, plus disease persisted. We report plus disease even after appropriate PRP therapy for ROP. In this case, it is likely the patient's cardiovascular diseases that caused the persistent plus disease. Vascular tortuosity can be due to a number of different systemic disorders, so it is important to consider an infant's systemic conditions in the evaluation of ROP.

Treatment of retinopathy of prematurity: a review of conventional and promising new therapeutic options.

Retinopathy of prematurity (ROP), a retinal vascular disease of premature infants, continues to be a major cause of preventable childhood blindness all over the world. The incidence of ROP varies among countries, being influenced by the quality of the level of neonatal intensive care. Here, we discuss the potential treatments that are now available or will soon or probably be available for ROP. Although ablation of the avascular retina with laser photocoagulation remains the current gold standard and well established therapy for ROP, some new therapeutic options including angiostatic therapies are being explored based on our knowledge of the pathophysiology of the ROP and complications and efficacy of laser treatment. However, prevention of the development of severe ROP and screening for ROP seem to be the best strategy in avoiding visual impairment caused by ROP in premature infants. New therapeutic interventions including vascular endothelial growth factor antibody administration, gene therapy and supplemental therapies should be supported with evidence-based data for the treatment of ROP.

Comparison of fentanyl and morphine in laser surgery for retinopathy of prematurity

To compare complication rates of the analgesics fentanyl and morphine in preterm infants undergoing laser therapy for retinopathy of prematurity (ROP). In this observational study, the medical records of consecutive preterm neonates undergoing laser treatment of ROP from June 2007 through September 2010 were retrospectively reviewed. Because a fentanyl-based infusion protocol was initiated in November 2009, there was approximately the same number of treatment sessions with morphine and with fentanyl. In both groups, midazolam was used additionally on a case-by-case basis. Analgesia type, complications, and vital signs were documented at 5-minute intervals for all surgeries. The primary outcome was change in ventilation status. Secondary complications included change in temperature and incidence of apneic, bradycardic, and desaturation events. A total of 35 patients were included, with 17 in the morphine group (mean gestational age, 24.8 weeks; mean birth weight, 661 g) and 18 in the fentanyl group (mean gestational age, 24.4 weeks; mean birth weight, 681 g). Overall worsening of ventilation status was noted in 29% of patients in the morphine group and 6% of patients in the fentanyl group (P = 0.08; 95% confidence interval, -2% to 48%). Temperature instability (outside of 36.5° to 37.4°C range) was noted in 6% of patients in the morphine group and no patients in the fentanyl group. Apneic events were 3.2 times more common and bradycardic events 1.5 times more common in the morphine group. We found no difference in safety parameters for fentanyl infusion or morphine for analgesia in preterm infants undergoing ROP laser therapy in the neonatal intensive care unit setting. Although estimates of complication rates suggest that fentanyl may be safer, further study is needed to confirm this premise.

Stem Cell Therapy for Retinopathy of Prematurity

Retinopathy of Prematurity (ROP) is a leading cause of childhood blindness that severely affecting the quality of life of these children. Few treatment options are available but without favorable outcomes. Stem cell therapy, through its proven potential in tissue regeneration, provides an attractive therapeutic approach in treating ROP and thereby restoring vision.

Potentially life-threatening intravenous acetaminophen overdose in a 3-month-old (40 weeks’ post-menstrual age), 2.3 kg baby girl

A case is presented of a serious, potentially life-threatening intravenous acetaminophen overdose in a 3-month-old (40 weeks’ post menstrual age),2.3 kgbaby girl. The neonate was scheduled for urgent laser therapy for retinopathy of prematurity. Instead of an intended intravenous Hartmann’s solution bolus of 10 ml·kgˉ1, the neonate received a 17 ml bolus of correctly labelled intravenous 1% acetaminophen. The National Poisons Bureau was immediately contacted for advice and in the absence of data suggested a treatment with N-acetylcysteine for a 24-hour period. Baseline blood samples for clotting, liver function, urea and electrolytes, full blood count and plasma acetaminophen concentration were taken 30 min, 8.25 h, 12.5 h, 18.5 h and 120 h after the overdose. Acetaminophen concentration was 78 mg·Lˉ1 at 30 min, but it was undetectable at any other time. Using a recent and complete PK-PD dataset we are able to show that the measured plasma acetaminophen concentration fits well on PK estimates for acetaminophen in this neonate. The non-detectable (low) plasma acetaminophen concentration at >8 h is also consistent with this model, especially if clearance is slightly increased in the premature nursery graduate. Medical errors are rarely the fault of an individual and they are often due to a combination of factors. Contributing factors, in this case, are described under the following headings: Catalyst event, system fault, loss of situational awareness, and human error.

Pathogenese der Frühgeborenenretinopathie

Retinopathy of prematurity (ROP) is a complex disease with a multifactorial pathogenetic cascade that is still only partially understood. Important pathogenetic factors are gestational age at birth and birth weight. Potent postnatal factors are exposure to supplemental oxygen, slow weight gain and expression of angiogenic growth factors. Some of these crucial aspects of ROP pathogenesis will be discussed in this article and put into clinical context. With the introduction of intravitreal anti-VEGF (vascular endothelial growth factor) treatment into ROP therapy, the pathomechanistic role of VEGF in ROP deserves a special focus. Apart from VEGF, other factors will be discussed that may precede VEGF upregulation and thus may represent targets for an earlier and potentially protective intervention. Among these insulin-like growth factor 1 (IGF-1) appears to be most prominent. Finally, factors such as postnatal weight gain will be discussed in light of their potential role as screening parameters and their ability to predict ROP severity.

168 Serum Veg F Levels in Preterm Infants: Effects of Gestation and Laser or Bevacizumab Therapy for Retinopathy of Prematurity

BackgroundBevacizumab, a monoclonal antibody to the vascular endothelial growth factor Veg F appears to offer successful treatment of severe retinopathy of prematurity (ROP), but there are no human data addressing...

Frühgeborenenretinopathie - Pathophysiologische Grundlagen und aktuelle Behandlungsoptionen

Retinopathy of prematurity (ROP), like other angioproliferative retinal disorders, has witnessed the advent of anti-VEGF therapy in clinical practice. The first report from the BEAT-ROP study published in 2011 represents the first comparison of anti-VEGF therapy versus conventional laser treatment in a randomised controlled trial. This review article investigates these novel aspects of ROP therapy from a pathophysiological angle and delineates the stages of ROP in which anti-VEGF treatment appears as a reasonable option. Furthermore, the novel chances of anti-VEGF therapy are being weighed against some still unanswered questions and novel study concepts are being presented.

Intravitreal pegaptanib as adjunctive treatment for stage 3+ ROP shown to be effective in a prospective, randomized, controlled multicenter clinical trial

Both intravitreal pegaptanib with laser therapy and intravitreal bevacizumab monotherapy have been found to be more efficacious than laser therapy alone in prospective, randomized, controlled clinical trials. The use of pegaptanib with laser therapy was efficacious in 91.2% compared with 69.0% in controls. The use of bevacizumab monotherapy was efficacious in 95.7% compared with 78.1% in controls. The use of anti-vascular endothelial growth factor therapy for retinopathy of prematurity has been shown to be efficacious, without toxicity reported to date; however, the best drug and dose which allows greatest efficacy with fewest recurrences and without toxicity must be determined.

Pain assessment in premature infants treated with intravitreal antiangiogenic therapy for retinopathy of prematurity under topical anesthesia

To evaluate the physiological and behavioral pain response in premature infants receiving intravitreal bevacizumab injection (IVB) for retinopathy of prematurity (ROP) under topical anesthesia. A prospective interventional non-comparative case series. Premature infants with high-risk prethreshold or threshold ROP received IVB using topical anesthesia with tetracaine eye drops. A Premature Infant Pain Profile was used to assess the pain response during the procedure. Nine premature infants requiring bilateral IVB therapy were included in the study. Mean gestational age was 28.7 ± 1.3 weeks, and birth weight was 1,200 ± 194 grams. The mean total pain score was found to be 8.7 ± 2.4 (range 5-14), indicating generally mild pain during the procedure. Eye squeeze was the most prominent indicator of pain. Most changes occurred at the beginning, with the insertion of the lid speculum and were hardly noted during the rest of the procedure including the injection itself. Topical anesthesia with tetracaine is an effective method for the relief of pain associated with intravitreal injections in premature infants with ROP.

Are we there yet? Bevacizumab therapy for retinopathy of prematurity

The publication of the BEAT-ROP study of bevacizumab (Avastin) treatment for Zone I and II retinopathy of prematurity (ROP) has raised hopes that there might now be a simpler, cheaper...

Continuous intravenous infusion of fentanyl suggests improved safety over morphine in preterm infants undergoing laser therapy in retinopathy of prematurity

Introduction: Currently, there is no consensus regarding the optimal mode of anesthesia for retinopathy of prematurity (ROP) laser treatment. Studies have established that general anesthesia with intubation confers significant risk in preterm neonates, and that opioid analgesia with benzodiazepine sedation is ideal when the NICU is equipped for such surgical procedures. While small retrospective studies have looked at the safety and efficacy of morphine (n = 130), ketamine (n = 11), and remifentanil (n = 6), no studies have looked at fentanyl for ROP laser surgery.

VEGF-Antikörper in der Therapie der Frühgeborenenretinopathie

Retinopathy of prematurity (ROP) is one of the three leading causes of legal blindness in childhood in the developed countries. Improved neonatal care has resulted in the increased survival of extremely immature infants at high risk to develop ROP. Current treatment for ROP with laser may prevent blindness by causing involution of pathological vessels and thus inhibit the development of retinal detachment. But this coagulation of the avascular retina is a destructive therapy and does not otherwise ameliorate retinal development. Recent reports have described vascular endothelial growth factor antibodies as therapy for ROP. This article reports our own experience with this new therapy and gives an overview of the recent literature.

Effects of intravitreal bevacizumab and laser in retinopathy of prematurity therapy on the development of peripheral retinal vessels

To investigate laser photocoagulation and intravitreal bevacizumab efficacy and safety in patients with moderate-to-severe stage 3 retinopathy of prematurity (ROP), and to evaluate the effects of treatment on the development of peripheral retinal vessels. A retrospective chart review of 15 premature babies, all of whom were diagnosed with stage 3 ROP, was conducted. Patients with moderate-to-severe stage 3 ROP, thus with a vascular-active ROP, received intravitreal injections of bevacizumab (0.5 mg/0.02 ml) and laser photocoagulation, whereas those with relatively inactive ROP received laser photocoagulation only. Patients were examined 1, 2, 4, and 8 weeks after treatment, or until peripheral retinal vessel growth over the laser scar was noted. Both eyes of 15 patients diagnosed with moderate-to-severe stage 3 ROP were evaluated. Eight patients (n=16 eyes) received intravitreal bevacizumab injection and laser photocoagulation, and seven patients (n=14 eyes) received laser photocoagulation only. During the follow-up period, regression of plus disease and peripheral retinal vessel development appeared significantly more rapidly in patients who received both intravitreal bevacizumab injection and laser photocoagulation. Peripheral retinal vessel development over the laser scar was identified 1-2 weeks after treatment. No systemic or significant ocular complications, such as vitreous hemorrhage, retinal detachment, or endophthalmitis, were noted during follow-up after treatment. A combination of laser photocoagulation and intravitreal bevacizumab injection seems to be a safe and effective therapy in patients with moderate-to-severe stage 3 ROP, promulgating rapid development of peripheral retinal vessels.

Pharmacological treatment of retinopathy of prematurity: antiangiogenic or proangiogenic?

Evaluation of: Micieli JA, Surkont M, Smith AF. A systematic analysis of the off-label use of bevacizumab for severe retinopathy of prematurity. Am. J. Ophthalmol. 148 (4), 536–543 (2009).In retinopathy of prematurity (ROP), deregulated angiogenesis following the obliteration of developing retinal vessels leads to fibrovascular proliferation and tractional retinal detachment. To date, laser ablation and surgical interventions have largely contributed to rescuing infants with severe ROP from blindness. However, alternative modalities are desired to obviate these destructive treatments. Given the potency of pharmacological agents targeting VEGF in ocular angiogenic diseases, the administration of anti-VEGF drugs is being evaluated in the treatment of ROP. The paper under evaluation systematically analyzed the previous literature studying clinical outcomes of anti-VEGF therapy in ROP. This paper demonstrates that bevacizumab therapy has the potential to halt or improve the disease in patients with severe ROP, although further randomized control trials are required to determine the optimal timing, frequency and dose of the drug, as well as its long-term local and systemic effects.