Active Retinopathy Of Prematurity Research Articles

USE OF HAND-HELD OPTICAL COHERENCE TOMOGRAPHY DURING RETINOPATHY OF PREMATURITY SCREENING DEMONSTRATES AN INCREASED OUTER RETINA FROM EARLY POSTMENSTRUAL AGE IN PRETERM INFANTS WITH RETINOPATHY OF PREMATURITY.

To identify structural markers of active retinopathy of prematurity (ROP) in foveal and parafoveal retinal layers using hand-held optical coherence tomography. Hand-held optical coherence tomography images (n = 278) were acquired from a prospective mixed cross-sectional longitudinal observational study of 87 participants (23-36 weeks gestational age; n = 30 with ROP, n = 57 without ROP) between 31 and 44 weeks postmenstrual age excluding treated ROP and features of cystoid macular edema. Six retinal layer thicknesses from the fovea to the parafovea were analyzed at five locations up to 1,000 µ m, temporally and nasally. The mean outer retinal thickness during active ROP increased at the fovea and parafovea from postmenstrual age 33 weeks to 39 weeks ( P < 0.001), whereas the parafoveal inner nuclear layer and retinal nerve fiber layer reduced ( P < 0.001). Outer retinal thickness at the fovea from 33 weeks to 39 weeks postmenstrual age was consistently thicker in infants with ROP across all levels of prematurity (gestational age). Increased foveal and parafoveal outer retina measured using hand-held optical coherence tomography shows potential as a marker for ROP screening.

EVALUATION OF RISK FACTORS LEADING TO ROP IN SOUTHERN PUNJAB, A HOSPITAL BASED STUDY

The study aimed to assess the risk factors associated with retinopathy of prematurity (ROP) in premature children. The study was conducted prospectively in the Neonatal Unit of Nishtar Medical Hospital from January 2022 to December 2022 located in southern Punjab. The study included premature children who had a birth weight of less than 1500 g, gestational age of 32 weeks or less, and infants who had low Apgar scores, respiratory distress syndrome, blood transfusion, sepsis, infection, hydrocephaly, microcephaly, and twin pregnancy. Children with ischemic zones and changes in blood vessels had ROP and were treated by ophthalmologists and surgeons. The study found that out of the total 70 premature children included, 4 (5.7%) had active ROP, and 66 (94.2%) showed spontaneous regression of ROP. The patients with active ROP had a mean gestational age of 27.4±1.4 weeks, and there was a significant association between early gestational age and ROP. Patients who developed active ROP had oxygen therapy for 21±3.5 days compared to 12.6±1.2 days in those without ROP (P&lt;0.05). The most common retinal changes were the development of ischemic zones (61.4%), bleeding (24.2%), changes in blood vessels (15.7%), and changes in the optic nerve (1.4%). Of the 70 patients, 4 (5.7%) were in Zone I, 21 (30%) were in Zone II, and 45 (64.2%) were in Zone III. All patients in the zone I had active ROP, suggesting a significant association between zones and the development of ROP (P &lt;.05). In conclusion, the study found that low birth weight, early gestational age, low Apgar score, and longer duration of oxygen therapy significantly increased the risk of ROP.

Современные подходы к оказанию высокотехнологичной офтальмологической помощи детям с ретинопатией недоношенных в Калужском филиале МНТК «Микрохирургия глаза»

Purpose. To present modern approaches to providing high-tech ophthalmic care to children with retinopathy of prematurity (ROP) in Kaluga branch of the S. Fyodorov Eye Microsurgery Federal State Institution. Methods. For the 2003–2022 period screening for detection of active ROP was carried out in 16 000 premature infants. Various stages of the disease were identified in 4129 premature infants (24.9 %). Premature infants with various stages and forms of active ROP have been subjected to multimodal diagnostics of changes in the vascular system of the eye since 2016. Early laser treatment by pattern laser coagulation of the retina using hexagonal patterns was carried out in 226 children (286 eyes) in 2016–2021. Transpupillary laser coagulation of the retina using navigatied laser system was performed in 16 premature babies (26 eyes) in 2021–2023. Primary vitrectomy for severe stage 3 active ROP with the development of extraretinal retinovitreal neovascularization involving the posterior hyaloid membrane was performed in 9 premature infants (12 eyes) in 2021–2023. Results. Based on a comprehensive analysis of the results of multimodal diagnostics, informative prognostic signs of the type of active ROP were established, according to the data of fluorescein angiography of the fundus, spectral optical coherence tomography in the angio mode, and color duplex scanning. These signs provide an accurate definition of the type of course of the disease – a decisive factor in the choice of tactics for managing patients. The developed technologies of pattern hexagonal and navigatied laser coagulation of the retina provide maximal percentage of disease regression. These technologies create the most favorable conditions for further development of visual functions. Primary vitrectomy in all cases made it possible to achieve stable regression of the pathological process. Conclusion. Modern approaches to the provision of high-tech ophthalmic care for children with ROP, implemented in Kaluga branch of S. Fyodorov Eye Microsurgery Federal State Institution, provide high efficiency in the treatment of active ROP with a minimal risk of late complications in the cicatricial period of the disease. Key words: retinopathy of prematurity; multimodal diagnostics; navigated laser coagulation of the retina; primary vitrectomy.

Level of prematurity as a predictor for the activity of retinopathy of prematurity and strabismus.

Objective: To evaluate the prevalence of strabismus in premature children after the screening for retinopathy of prematurity (ROP) and to determine whether the level of prematurity (birth weight and gestation age) can be used as a predictor for both strabismus development and disease activity. Methods: This is a retrospective study, conducted in the Clinic for Eye Disease, section for Pediatric Ophthalmology of the Clinical Centre University of Sarajevo during the period from December 2013 until January 2017. 126 patients were involved. The inclusion criteria were gestational age ≤ 34 weeks, birthweight ≤ 2000 g and performed screening test for ROP. Patients were divided into three groups: patients without ROP, patients with spontaneous regression and patients with active ROP. Results: 52.4% patients were suffering from strabismus (30.2% esotropia, 22.2% exotropia). All the patients with active ROP had esotropia (60.0%). The average birth weight and gestational age were lower in patients with strabismus (1371.3 ± 58.0 g and 29.7 ± 0.4 weeks respectively). Conclusion: Lower gestational age and birth weight of premature children showed the increased probability of strabismus development especially esotropia. Prematurity level was significantly lower in patients with active ROP compared to the rest of the patients. Abbreviations: ROP = Retinopathy of prematurity, ICROP = International Classification of Retinopathy of prematurity, BCVA = best corrected visual acuity.

Features of the Foveal Avascular Zone in Children with Active Retinopathy of Prematurity According to Optical Coherence Tomography in Angio Mode

The purpose — to study the features of the foveal avascular zone (FAZ) in children with active retinopathy of prematurity according to the data of optical coherence tomography in angio-mode.Patients and methods. OCT-A was performed on 37 premature infants (37 eyes) with active ROP: at stages 1–2 — in 14 eyes (8 — with a favorable current type, 6 — with an unfavorable current), at stage 3 — in 16 eyes (6 — with a favorable type, 10 — with unfavorable), with aggressive posterior ROP — in 7 eyes (4 — at the stage of early clinical manifestations, 3 — at the stage of manifestation). Patients with stages 1 and 2 of active ROP were combined into one group due to similar findings. The control was the data of OCT-A performed on 10 premature infants without signs of ROP.Results. At 1–2 stages with a favorable type in children with a somatic state of moderate severity in the FAZ area, statistically significant differences in comparison with the control parameters were not determined. In children with a severe condition, FAZ was significantly expanded, which was accompanied by a significant decrease in the density of capillaries in the fovea. With an unfavorable type, a significant decrease in the size of the FAZ was noted, as well as a slight decrease in the density of the capillaries of the superficial plexus in the fovea. At stage 3 with a favorable type, an expansion of the FAZ, a decrease in the density of capillaries in the fovea in the superficial and deep plexus were recorded, and the values of the density of capillaries in the parafovea were slightly increased. At 3 stages with an unfavorable course in children born at a gestational age of 29–32 weeks, the FAZ was expanded. In children born at a gestational age of 25–28 weeks, a significant decrease in the size of the FAZ was recorded in comparison with children with a long gestation period, as well as those with a favorable course of stage 3. At the stage of early clinical manifestations of the posterior aggressive ROP, the FAZ was absent; vessels grew into it, which formed shunts and zones of intraretinal neovascularization in the form of “tangles”. At the stage of manifestation of the posterior aggressive ROP, a gross violation of the architectonics of the microvasculature was determined. As at the stage of early clinical manifestations, FAZ was absent; shunt vessels grew into it.Conclusion. The OCT method in angio-mode has showed high information content in studying the features of the foveal avascular zone in children with various forms, stages and types of active ROP. The characteristics of FAZ with an unfavorable type of the disease are of the greatest value for clinical practice. Their identification at the early stages of the pathological process will make it possible to timely determine the correct tactics and carry out the necessary treatment.

Опыт использования моно и комбинированного лечения ретинопатии недоношенных с применением лазерной коагуляции сетчатки и введения ингибиторов сосудистого эндотелиального фактора роста

Retinopathy of prematurity (ROP) is one of the main causes of blindness and visual impairment in young children. Laser coagulation of the avascular retina is a generally recognized method of treating active progressive ROP. The efficiency of laser coagulation depends on the type of ROP. Combined treatment is used when one of the types of monotherapy is ineffective. Purpose. To evaluate the effectiveness of mono and combined treatment of ROP using laser coagulation and introduction of vascular endothelial growth factor inhibitors. Material and methods. In the period 2020–2022, 403 babies born prematurely were under observation. The diagnosis of ROP was made to 170 (42 %) children. 47 (27 %) patients needed treatment. Mono laser coagulation was performed in 32 (68 %) patients, and 9 (19.1 %) were administered introduction of vascular endothelial growth factor inhibitors. Conclusions. Combined treatment was carried out on 6 (12.7 %). In all cases of PH treatment, a positive result was achieved with the preservation of vision. If we consider the PH of the scar phase of the 3rd degree as an unfavorable outcome, then success is achieved only in 95.6 % of cases. Combined treatment proved to be justified and effective – in our observation in 6.4 % of cases. The results of our study confirm the expediency of monitoring children after the introduction of vascular endothelial growth factor inhibitors until they reach the postconceptual age of 70–80 weeks. Keywords: retinopathy of prematurity, laser photocoagulation of the retina, inhibitors of vascular endothelial growth factor, combined treatment, monotherapy

Smartphone-based fundus imaging for evaluation of Retinopathy of Prematurity in a low-income country: A pilot study.

To evaluate the feasibility of a novel and simple smart phone-based Retinopathy of Prematurity (ROP) screening approach in a resource-constrained setting. This cross-sectional validation study was conducted at the Department of Ophthalmology and Neonatal Intensive Care Unit (NICU) of The Aga Khan University Hospital, Pakistan, from January 2022 to April 2022. A total of 63 images of eyes with active ROP (stage-1, 2, 3, 4 and/or plus or pre-plus disease) were included in this study. The stage of ROP was documented by the principal investigator using an indirect ophthalmoscope and retinal images were obtained using this novel technique. These images were shared with two masked ROP experts who rated the image quality and determined the stage of ROP and presence of plus disease. Their reports were compared with the initial findings reported by principal investigator using indirect ophthalmoscope. We reviewed 63 images for image quality, stage of ROP and presence of plus disease. There was significant agreement between the gold standard and the Rater-1 and 2 for the presence of plus disease (Cohen's kappa was 0.84 and 1.0) and the stage of the disease (Cohen's kappa 0.65 and 1.0). There was significant agreement between the Rater for presence of plus disease and any stage of ROP (Cohen's κ: 0.84 and 0.65 for plus disease and any stage of the ROP, respectively). Rater-1 and 2 rated 96.83% and 98.41% images as excellent / acceptable respectively. High quality retinal images can be captured with a smartphone and 28D lens without using any additional adapter equipment. This approach of ROP screening can form basis of telemedicine for ROP in resource constrained areas.

Predictive Model for the Type of Active Retinopathy of Prematurity Based on Data from Angiological Studies

The purpose — to develop a prognostic model of the type of active retinopathy of prematurity (ROP) based on informative prognostic parameters of optical coherence tomography of the retina in angio-mode (OCT-A) and color duplex scanning (CDS) for a reliable choice of patient management tactics.Patients and methods. 30 premature infants (30 eyes) with favorable and unfavorable types of 1–3 stages of active ROP were performed with optical coherence tomography of the retina in angio-mode. Children were born at a gestational age of 25–34 weeks. The birth weight of children was 680–2030 g. 55 premature infants (55 eyes) with active ROP were performed with CDS in modes of color Doppler mapping and pulsed Doppler sonography. Children were born at a gestational age of 25–32 weeks. The birth weight of children was 680–1760 g. ROC analysis was used to estimate the prognostic information content of the quantitative indicators of OCT-A and CDS in relation to the type of active ROP. The discriminant analysis was used to estimate the contribution of the studied quantitative indicators to the intergroup differences in the type of active ROP. A regression model was built to obtain a prediction of a favorable or unfavorable type of disease. The assessment of the acceptability of the model as a whole was carried out according to the index of determination and the level of significance of the resulting model (p &lt; 0.05).Results. The most informative prognostic indicators of the type of active ROP were determined, according to OCT in angio-mode: the area of the foveal avascular zone — and, according to CDS: maximum systolic and end diastolic blood flow velocity in the ophthalmic artery, maximum systolic blood flow velocity in the posterior short ciliary arteries, minimum velocity blood flow in the central retinal vein. On the basis of informative indicators, a reliable prognostic model of the type of active ROP was built, which has two independent variables: the area of the foveal avascular zone and the end diastolic blood flow velocity in the ophthalmic artery. The dependent variable can take values close to 0, which determine the favorable type of the disease, or close to 1, which determines the unfavorable type of the disease.Conclusion. The introduction of the obtained model into clinical practice will allow to objectively determine the unfavorable course of the pathological process at the earliest stages, as well as to carry out early treatment of active ROP.

The state of ocular arterial blood flow in active retinopathy of prematurity

Purpose: to study the state of blood flow in the ocular arteries of patients with various forms, stages and course types of active retinopathy of prematurity (ROP). Material and methods. Colour duplex scanning was performed by colour Doppler mapping and pulsed Doppler sonography for 55 premature babies (55 eyes) with active ROP and 8 premature babies (8 eyes) without ROP signs. The children’s gestation age was 25 to 32 weeks, and the body weight at birth was 680 to1760 g. Blood flow was examined in the ophthalmic artery (OA), the central retinal artery (CRA) and the medial and lateral posterior short ciliary arteries (PSCA). Results. The ophthalmic artery revealed no significant differences between the children with ROP and without ROP, except for a significant increase in the peak systolic velocity (Vsyst) in an unfavorable course of stage III of ROP. The development of aggressive posterior ROP is accompanied by a statistically insignificant decrease in blood flow velocity of OA. Hemodynamic parameters of CRA indicate an increase in peripheral vascular resistance in children with an unfavorable course of ROP. A significant increase of Vsyst in the posterior short ciliary arteries was revealed in children with an unfavorable course of stages I–III of ROP and Vsyst, and Vdiast (diastolic blood flow velocity) in children with aggressive posterior ROP as compared with children without ROP. A pronounced impact of the ROP course (favorable or unfavorable) on the Vsyst, Vdiast, and PI indicators in the posterior short ciliary arteries was revealed. The most informative hemodynamic parameters in predicting the course of active ROP are Vsyst and Vdiast values in the ophthalmic artery and Vsyst in the posterior short ciliary arteries. The least informative were the hemodynamic parameters of the central retinal artery. Conclusion. The assessment of hemodynamic changes in eye arteries may be used as an additional diagnostic criterion in the early diagnosis of ROP.

Effect of Intravitreal Aflibercept vs Laser Photocoagulation on Treatment Success of Retinopathy of Prematurity

Laser photocoagulation, which is the standard treatment for retinopathy of prematurity (ROP), can have adverse events. Studies of anti-vascular endothelial growth factor injections have suggested efficacy in the treatment of ROP, but few studies have directly compared them with laser treatments. To compare intravitreal aflibercept vs laser photocoagulation in infants with ROP requiring treatment. This noninferiority, phase 3, 24-week, randomized clinical trial was conducted in 27 countries (64 hospital sites) throughout Asia, Europe, and South America. Overall, 118 infants (gestational age ≤32 weeks at birth or birth weight ≤1500 g) with ROP severity (zone I stage 1+ [stage 1 plus increased disease activity], zone I stage 2+, zone I stage 3, zone I stage 3+, zone II stage 2+, or zone II stage 3+) requiring treatment or with aggressive posterior ROP in at least 1 eye were enrolled between September 25, 2019, and August 28, 2020 (the last visit occurred on February 12, 2021). Infants were randomized 2:1 to receive a 0.4-mg dose of intravitreal aflibercept (n = 75) or laser photocoagulation (n = 43) at baseline. Additional treatment was allowed as prespecified. The primary outcome was the proportion of infants without active ROP and unfavorable structural outcomes 24 weeks after starting treatment (assessed by investigators). The requirement for rescue treatment was considered treatment failure. Intravitreal aflibercept was deemed noninferior if the lower limit of the 1-sided 95% bayesian credible interval for the treatment difference was greater than -5%. Among 118 infants randomized, 113 were treated (mean gestational age, 26.3 [SD, 1.9] weeks; 53 [46.9%] were female; 16.8% had aggressive posterior ROP, 19.5% had zone I ROP, and 63.7% had zone II ROP) and 104 completed the study. Treatment (intravitreal aflibercept: n = 75; laser photocoagulation: n = 38) was mostly bilateral (92.9%), and 82.2% of eyes in the intravitreal aflibercept group received 1 injection per eye. Treatment success was 85.5% with intravitreal aflibercept vs 82.1% with laser photocoagulation (between-group difference, 3.4% [1-sided 95% credible interval, -8.0% to ∞]). Rescue treatment was required in 4.8% (95% CI, 1.9% to 9.6%) of eyes in the intravitreal aflibercept group vs 11.1% (95% CI, 4.9% to 20.7%) of eyes in the laser photocoagulation group. The serious adverse event rates were 13.3% (ocular) and 24.0% (systemic) in the intravitreal aflibercept group compared with 7.9% and 36.8%, respectively, in the laser photocoagulation group. Three deaths, which occurred 4 to 9 weeks after intravitreal aflibercept treatment, were considered unrelated to aflibercept by the investigators. Among infants with ROP, intravitreal aflibercept compared with laser photocoagulation did not meet criteria for noninferiority with respect to the primary outcome of the proportion of infants achieving treatment success at week 24. Further data would be required for more definitive conclusions regarding the comparative effects of intravitreal aflibercept and laser photocoagulation in this population. ClinicalTrials.gov Identifier: NCT04004208.

Changes in the microvasculature with active retinopathy of prematurity as evidenced by OCT angiography

Purpose: to evaluate the degree of structural lesions of the microvasculature, depending on the stage and type of active ROP with optical coherence tomography (OCT) in angio-mode (OCTA). Material and methods. 63 premature infants (63 eyes) with active ROP were tested by OCT of the retina, of which 30 were tested by OCTA. Additionally, 10 premature infants (10 eyes) without signs of ROP were tested by OCTA. We assessed the area and perimeter of the foveal avascular zone (FAZ), the thickness of the retina in the fovea, the density of the superficialand deep plexuses in the fovea and parafovea, the presence or absence of intraretinal, epiretinal and retinovitreal neovascular complexes. Results. We revealed gross structural and microvascular retinal pathology in children with ROP, which was more pronounced in children with an unfavorable course of the disease. Of these, the most affected were children with a shorter gestational period, i. e , more immature. In children with a favorable type of ROP course, a severe general condition has a serious impact on the child’s microvasculature state. The analysis of the correlation dependences of OCTA on the gestational age, stage and type of active ROP, showed a strong direct correlation between the retinal thickness in the fovea, the density of superficial plexus vessels in the fovea, the area and perimeter of the FAZ, on the one hand, and the course of the disease, which is crucial for the correct choice of management and treatment tactics. Conclusion. The OCTA data allow an objective assessment of the severity of the changes in the retinal vasculature, including its microcirculatory component. The data effectively supplement the clinical picture and help identifying the progressive course o f active ROP at the earliest stages of the pathological process, thereby contributing to timely treatment and good clinical and functional results.

Первый опыт навигационной лазерной коагуляции сетчатки в лечении активной ретинопатии недоношенных

Purpose is to demonstrate the first experience of the automated navigation system “Navilas” using in the treatment of active stages of retinopathy of prematurity (ROP) in the Kaluga branch of “Eye Microsurgery” complex. Material and methods. Transpupillary retinal laser coagulation (RLC) using the “Navilas 577s” navigation system (OD-OS, Germany) was performed in 5 premature infants with an unfavorable type of stages 2nd and 3rd of active ROP. The postconceptual age (PCA) at the time of treatment was 34–37 weeks. Body weight at birth – from 900 to 1900 g, gestation age – 27–33 weeks. Results. The “Eye tracking” function ensured the absolute accuracy of the laser spots, as well as the uniformity and safety of their application during the automated navigation RLC. After 1 month, the formation of chorioretinal atrophy zone with heterogeneous pigmentation was noted in all patients at the site of the RLC. The growth of retinal vessels into the avascular retina in the direction of ora serrata was observed. Conclusion. The first experience has shown that RLC of the avascular retina on the automated navigation system “Navilas” is safe, precision, metered, topographically oriented, which in the future will allow to standardize the technique of laser treatment for patients with ROP active stages. Keywords: retinopathy of prematurity, unfavorable type, navigation retinal laser coagulation.

Лазерные методы лечения активной ретинопатии недоношенных: от режима одиночного импульса до навигации

Purposе. Тo present the stages of development of laser technologies for the treatment of active retinopathy of prematurity at the S. Fyodorov Eye Microsurgery Federal State Institution, the Kaluga Branch. Material and methods. Transpupillary laser photocoagulation of the retina was performed in 1546 children (2523 eyes) with active ROP from 2004 to 2021. Laser coagulation of the retina was carried out on various stationary laser ophthalmocoagulators acting in green and yellow spectra with a wavelength of 532 nm, 561 nm and 577 nm. Indications for laser treatment were the 2 nd and the 3 rd stage of the disease with an unfavorable course, the stage of early clinical manifestations, and the stage of manifestation of aggressive posterior ROP. Results. As the technology of retinal laser photocoagulation improved in patients with active ROP, the efficiency naturally increased and the duration of laser treatment decreased. Currently, the effectiveness of transpupillary laser coagulation of the retina using a hexagonal pattern has made it possible to achieve regression of the disease at the 2 nd stage with an unfavorable course in 100 % of cases, at the 3 rd stage with an unfavorable course type – in 97 %. The time for laser coagulation of the retina for the 2 nd stage was 6 ± 2 minutes, for the 3 rd stage it was 8 ± 3 minutes. Navigation assisted laser coagulation of the retina is the latest trend in laser treatment of active ROP. Conclusion. Permanent improvement of laser ophthalmocoagulators and the introduction of new methods of laser coagulation into clinical practice determine their continuous progress in achieving the maximum percentage of regression of active ROP with a minimum duration of the treatment session. Keywords: retinal laser photocoagulation, retinopathy of prematurity, ophthalmocoagulator.

Спектральная оптическая когерентная томография с функцией ангиографии в оценке структурных и микроциркуляторных нарушений сетчатки при задней агрессивной ретинопатии недоношенных

Purpose. To identify the structural and microvascular changes in the retina in children with aggressive posterior retinopathy of prematurity (ROP) with early and pronounced clinical features using spectral optical coherence tomography (SOCT) with angiography function. Material and methods. SOCT was performed in 40 premature infants (40 eyes) with aggressive posterior ROP, born at 25–28 weeks gestation, with a birth weight of 680–1350 g. 15 infants had early clinical features, optical coherence tomography with angiography function (OCT-A) was performed in 4. 25 infants had pronounced clinical features, OCT-A was performed in 3. The comparison group included 10 premature infants (10 eyes) without signs of ROP, as well as 23 children (23 eyes) with an unfavorable type of stage 3 of classical active ROP. Results. Early clinical features of aggressive posterior ROP were characterized by the absence of an avascular zone in fovea, vasodilation of the superficial and deep retinal plexus, the presence of intraretinal neovascularization in the perifovea, and multiple arteriolo-venular shunts. The severity of the pathological process in children with pronounced clinical features of aggressive posterior ROP reflected the development of massive neovascularization affecting all structures of the vitreoretinal interface, as well as the presence of areas of retinoschisis, indicating a high risk of the retinal detachment. Conclusion. The studies revealed gross structural and microvascular retinal pathology in children with aggressive posterior ROP at an early stage already, which indicates the indisputable importance of the earliest diagnosis, and, consequently, earlier treatment, which plays a key role in creating favorable conditions for the visual functions development. Key words: spectral optical coherence tomography-angiography, aggressive posterior retinopathy of prematurity

Decoupling Oxygen Tension From Retinal Vascularization as a New Perspective for Management of Retinopathy of Prematurity. New Opportunities From β-adrenoceptors.

Retinopathy of prematurity (ROP) is an evolutive and potentially blinding eye disease that affects preterm newborns. Unfortunately, until now no conservative therapy of active ROP with proven efficacy is available. Although ROP is a multifactorial disease, premature exposition to oxygen concentrations higher than those intrauterine, represents the initial pathogenetic trigger. The increase of oxygenation in a retina still incompletely vascularized promotes the downregulation of proangiogenic factors and finally the interruption of vascularization (ischemic phase). However, the increasing metabolic requirement of the ischemic retina induces, over the following weeks, a progressive hypoxia that specularly increases the levels of proangiogenic factors finally leading to proliferative retinopathy (proliferative phase). Considering non-modifiable the coupling between oxygen levels and vascularization, so far, neonatologists and ophthalmologists have “played defense”, meticulously searching the minimum necessary concentration of oxygen for individual newborns, refining their diagnostic ability, adopting a careful monitoring policy, ready to decisively intervene only in a very advanced stage of disease progression. However, recent advances have demonstrated the possibility to pharmacologically modulate the relationship between oxygen and vascularization, opening thus the perspective for new therapeutic or preventive opportunities. The perspective of a shift from a defensive towards an attack strategy is now at hand.

Первая доклиническая ангиоспастическая фаза ретинопатии недоношенных

Purpose. To evaluate the role of the first preclinical phase in the pathogenesis of retinopathy of prematurity (ROP). Material and methods. 642 premature babies were examined. The gestational age at the time of birth was up to 30 weeks and the weight was up to 1500 g. Ophthalmological monitoring was carried out from 28–30 weeks of postconceptional gestational age. Indirect ophthalmoscopy, digital calibration of retinal vessels, and studies on a wide-field retinal pediatric camera were performed. Dopplerography data of the blood flow in the brain vessels and in the ocular artery were analyzed in 28 children (56 eyes). The partial pressure of oxygen (pO2) and carbon dioxide (pCO2) in capillary blood was studied using Radiometer ABL800 FLEX gas analyzer (normal levels of pO2 are 40–60 mmHg, pCO2 is 35–45 mmHg). Results. It was revealed that the lower the degree of maturity of the child’s body was, the more often retinal arteriospasm was detected. In children with a postconceptional age of 25–27 weeks, arteriospasm was detected in 82% of cases, at 28 – 29 weeks – in 67%, 30 – 32 weeks – in 54% of cases. The degree of angiospasm correlates with a high index of blood flow resistance in the brain vessels and the ocular artery. The predominance of a high index of blood flow resistance in more premature infants with low body weight was revealed.The index of resistance of brain vessels 0.8 and higher, according to dopplerography, is a critical indicator of the threat of ROP development in a premature baby. Conclusion. During retinopathy of prematurity, it is important to detect the first preclinical, antispasmodic phase of ROP development, which lasts about one month and until now practically does not attract the attention of ophthalmologists. In this phase, the pathogenesis of pathological angiogenesis is formed. Further study of the preclinical phase will radically revise the strategy and tactics of diagnosis and treatment of RP. Key words: retinopathy of prematurity, first preclinical angiospastic ROP phase, active ROP phase, scarring ROP phase, autoregulation of retinal vessels, hypoxic and hypercapnic drives.

Time of vitreal surgery for active retinopathy of prematurity

Background. The anatomical and functional results of surgery for retinopathy of prematurity (ROP) are determined not only by the stage of the pathological process, but also depend on the timing of its implementation.The aim: to estimate the effectiveness of vitrectomy for severe active retinopathy of prematurity, depending on the timing of surgical treatment.Methods. Vitreoretinal surgery was performed in 138 children (198 eyes) with severe stages of ROP. All patients were divided into three groups depending on the timing of surgical treatment: group 1 – 42–48 weeks of postconceptual age (PCA), with the progression of ROP after laser coagulation of the retina (LCS), group 2 – 39–41 weeks of PCA, with the progression of ROP after LCS, group 3 – 36–39 weeks of PCA, without previous LCS. A 3-port transscleral 27-G vitrectomy was performed by all patients. At the postoperative period, the results of vitrectomy were estimated by the anatomical attachment of the retina. The follow-up period was 12 months. Results. In group 1, in 31 cases (73.8 %), the surgical intervention was completed with silicone tamponade. By the end of the follow-up period, anatomical retinal attachment was achieved in 17 eyes (40.5 %).In group 2, surgical intervention was completed with silicone tamponade in 29 eyes (42 %). By the end of the follow-up period, anatomical retinal attachment was achieved in 52 eyes (75 %).In group 3, surgical intervention was completed with silicone tamponade in 11 of 87 eyes (12.6 %). Anatomical retinal attachment was achieved in 80 eyes (92 %).Conclusion. Untimely vitrectomy (42–48 weeks of PCA) in cases of ROP progression after LCR led to a worse result. If progress of ROP after laser treatment happens, early vitrectomy (39–41 weeks of PCA) should be performed. Primary vitrectomy should be performed in case of the optimal timing of laser treatment has been missed (after 36 weeks of PCV).

Гемодинамические показатели в центральной артерии сетчатки при активной ретинопатии недоношенных и их соотношение с центральной веной сетчатки

Purpose. To analyze the main hemodynamic parameters in the central retinal artery, as well as their relationship with hemodynamic indicators in the central retinal vein, depending on the stage and type of active ROP with the use of color duplex scanning. Material and methods. The 63 premature babies with various stages of active ROP and no signs of ROP were included in the study. The 55 children with active ROP included in the study were distributed according to the stages and type of disease course. All children were at the same gestational age at the time of examination – 37–38 weeks of postmenstrual age or at 6–11 weeks of life. For all these children were performed color duplex scanning of the vessels of the eye and orbit in the modes of color Doppler mapping and pulsed Doppler. Results. The study of the hemodynamic features of the central retinal artery in premature infants with active ROP showed that the progression of the disease was accompanied by a significant increase in blood flow velocity (Vsyst and Vdiast) with each subsequent stage of ROP. A higher index of peripheral vascular resistance is recorded in comparison with the non-progressive favorable type for children with an unfavorable course of the disease.The analysis of the ratio of the maximum blood flow velocities in the central retinal artery and central retinal vein made it possible to determine in which of the vessels the hemodynamic changes are most pronounced, depending on the stage and form of active ROP. Conclusion. Thus, there are statistically significant changes in such large vessels of the retinal bed as the central retinal artery and central retinal vein during active ROP. Color duplex scanning, having a significant diagnostic potential in assessing hemodynamic parameters, made it possible to obtain reliable information about the linear blood flow velocity and the state of peripheral resistance in the central retinal artery and their relationship with the central retinal vein. This information opens up prospects for improving the accuracy of predicting the nature of the course of the disease, especially i n the early stages. Keywords: color duplex scanning, active retinopathy of prematurity, hemodynamic parameters, central retinal artery, central retinal vein

Treatment outside the Recommended Guidelines for Retinopathy of Prematurity (ROP): Prevalence, Characteristics, and Issues.

This study aims to assess the prevalence and characteristics of preterm infants with retinopathy of prematurity (ROP) treated outside the recommended guidelines. In this retrospective monocentric cohort, we included all premature children treated in our department for ROP by laser photoablation or anti-VEGF intravitreal injection. The main outcome was treatment of both eyes for ROP less severe than pre-threshold type 1, treated outside ETROP guidelines. A total of 114 children received treatment for ROP in our department, among whom 32 (28.1%) children received treatment for indications outside the ETROP guidelines for both eyes. The indications outside the guidelines were persistent stage 2 or 3 ROP that showed no evidence of regression after 41 weeks of corrected gestational age (11 children; 34.4%), pre-plus stage (11; 34.4%), difficulties in disease staging (7; 21.9%), type 2 ROP with plus disease (2; 6.2%), and treatment due to logistical difficulties (1; 3.1%; hospitalized in neonatal units hundreds of miles away from our department, with no fundus examination possible in the neonatal unit). To resume, in our cohort, 28.1% of children received treatment for ROP less severe than pre-threshold type 1 both eyes. The main indications for off-label treatment were the persistence of active ROP during follow-up and the presence of pre-plus-stage disease. Our data suggest the need to update ROP treatment criteria to reflect real-life practices. Additional studies are required in order to evaluate the long-term benefits and side effects of treatments outside the recommended indications, and to establish revised treatment guidelines.

Clinical Course and Results of Anti-VEGF Therapy of Retinopathy of Prematurity

The clinical course of active retinopathy after anti-VEGF therapy, the possibility and timing of recurrence of the disease, anatomical and functional outcomes of treatment are widely discussed in the press, not fully studied and relevant.Purpose: to study the clinical course of active retinopathy of prematurity after anti-VEGF therapy and clinical and functional outcomes.Patients and Methods. Children with active retinopathy of prematurity, who turned to the Helmgoltz National Medical Research Centre of Eye Diseases after anti-VEGF therapy, examined by indirect binocular ophthalmoscopy and digital retinal camera (RetcamShuttle). Children were monitored from 1.5 to 6 years (average 2.94 ± 1.47). All children underwent routine examination, 4 children older than 3 years underwent optical coherence tomography.Results. In all cases, after anti-VEGF therapy, there was a decrease in vascular activity and continued vascularization of the retina. Recurrence of the disease requiring additional treatment, were detected in 11 (42.3 %) eyes within 6–22 weeks (in average 13.33 ± 5.57) after intravitreal anti-VEGF therapy. Laser coagulation of the retina was carried out in 4 children (7 eyes) and repeated administration of anti-VEGF drug — 2 children (4 eyes), which led to regression of the disease. In the long-term period, all 13 (100 %) children had successful outcomes.Conclusion. Anti-VEGF therapy is effective in plus-zone 1 disease and posterior aggressive retinopathy of prematurity. Its advantages include the ability to treat retinopathy in zone 1 posterior, the absence of “blockade” of the peripheral retina with the possibility of continued growth of blood vessels to the periphery, lower frequency and severity of myopia. The disadvantages include the possibility of recurrence of the disease, which requires long-term regular monitoring.