【In Press】 The progress of prophylactic treatment in retinopathy of prematurity

Retinopathy of prematurity (ROP) is a retinal vascular disorder frequently found in premature infants. Different therapeutic strategies have been developed to treat ROP. However, there are still many children with ROP suffering by severe limitations in vision or even blindness. Recently, ROP has been suggested to be caused by abnormal development of the retinal vasculature, but not simply resulted by retinal neovascularization which takes about 4-6wk after birth in premature infants. Thus, instead of focusing on how to reduce retinal neovascularization, understanding the pathological changes and mechanisms that occur prior to retinal neovascularization is meaningful, which may lead to identify novel target(s) for the development of novel strategy to promote the healthy growth of retinal blood vessels rather than passively waiting for the appearance of retinal neovascularization and removing it by force. In this review, we discussed recent studies about: 1) the pathogenesis prior to retinal neovascularization in oxygen-induced retinopathy (OIR, a ROP in animal model) and in premature infants with ROP; 2) the preclinical and clinical research on preventive treatment of early OIR and ROP. We will not only highlight the importance of the mechanisms and signalling pathways in regulating early stage of ROP but also will provide guidance for actively exploring novel mechanisms and discovering novel treatments for early phase OIR and ROP prior to retinal neovascularization in the future.     

Time to consider a new treatment protocol for aggressive posterior retinopathy of prematurity?

Purpose: To discuss treatment modalities for aggressive posterior retinopathy of prematurity (AP‐ROP). Methods: The medical charts of all infants with AP‐ROP at Uppsala University Hospital, Sweden, during a 2‐year period (2009 and 2010) were reviewed. Eight infants (16 eyes) with a mean gestational age of 23.8 weeks and a mean birth weight of 592 g were treated with laser and/or intravitreal injections of bevacizumab (0.4 and 0.625 mg). RetCam photography was used to document the retinal appearance before and after treatment. Results: All infants (16 eyes) had AP‐ROP in zone I. Mean time at initial treatment was 34 weeks postmenstrual age. Two eyes (one infant) were only treated with laser, and six eyes (three infants) were treated with laser therapy or cryopexy and, because of lack of regression, with bevacizumab as salvage therapy. Eight eyes (four infants) were treated with a first‐line bevacizumab injection and four of these eyes (two infants) with additional laser ablation for continued disease progression in zone II. Macular dragging occurred in one eye of one infant primarily treated with laser. Conclusions: Given the high complication rate of the extensive laser treatment for zone I ROP, it is worth considering anti‐vascular endothelial growth factor treatment as an alternative therapy. Further knowledge concerning side effects and long‐term ocular and systemic outcome is warranted before this drug becomes general clinical practice.     

Characteristics of severe retinopathy of prematurity patients in China: a repeat of the first epidemic?

AIM: To describe the characteristics of babies treated for severe retinopathy of prematurity (ROP) in a tertiary referral unit in China, to provide information to assist in determining screening criteria. METHODS: Information on consecutive babies referred to one eye department for treatment of stage 3 (prethreshold and threshold disease), and stages 4 and 5 ROP between January 2001 and May 2005 were retrieved from medical records. RESULTS: Data from 114 babies were analysed. The number of babies treated increased from nine in 2001 to 52 in 2004. The numbers of infants in each stage of ROP were as follows: stage 3, 40 babies; stage 4, 19 babies, and stage 5, 55 cases. The mean gestational age (GA) was 29.8 (SD 1.9) weeks (range 26-34 weeks) and the mean birth weight (BW) was 1432 (319) g (range 760-2500 g). 31 babies had BWs more than 1500 g (27.2%). 10 cases (8.8%) had GAs more than 32 weeks, and 82 (71.9%) had GAs more than 28 weeks. Overall, 18 (16.2%) infants exceeded UK screening criteria, and 34 (30.4%) exceeded the criteria used in the United States. The median age at presentation was 5.5 months (range 1-72 months). CONCLUSION: Comprehensive screening programmes for ROP are urgently needed in China. Screening criteria recommended by the American Academy of Pediatric Ophthalmology and Strabismus and the Royal College of Ophthalmologists, United Kingdom, may not be suitable for China where bigger, more mature babies are developing severe disease.     

Should parents be present during screening examinations for retinopathy of prematurity?

Purpose:To investigate whether parents should be present during screening examinations for retinopathy of prematurity (ROP) by investigating the anxiety levels of parents using two different approaches.Methods:This cross-sectional and two-center study was carried out with the parents at the time of the first ROP screening examination of their premature infants. At one center, the parents accompanied the infants during the ROP examination (Group 1), and in the other center, they did not (Group 2). Anxiety levels were assessed with the State-Trait Anxiety Inventory (STAI), which consists of the State Anxiety (STAI-S) and Trait Anxiety (STAI-T) subscales and a visual analog scale (VAS).Results:A total of 147 parents of 127 infants were included in the study. STAI-T and -S levels were 40.5 ± 8 and 37.9 ± 7.5, respectively, in Group 1 and 39.6 ± 8.1 and 39.4 ± 9.1 in Group 2 before the examination. There were no statistically significant differences in terms of these values between the two groups (P > 0.05). The state anxiety levels increased by an average of 1.7 ± 8 in Group 1 and reached 39.6 ± 10.1 after the examination. In Group 2, these levels decreased by an average of − 2.7 ± 7.5 points to a score of 36.4 ± 10.3. This difference was found to be statistically significant (P = 0.001). A similar pattern was observed in the evaluation of the VAS data.Conclusion:As a preliminary opinion, it may be more appropriate for parents to not participate in screening examinations, but single-center controlled studies are required to confirm the results.     

Does observer bias contribute to variations in the rate of retinopathy of prematurity between centres?

Purpose: We aimed to indirectly assess the contribution from observer bias to between centre variability in the incidence of acute retinopathy of prematurity (ROP). Methods: The Australian and New Zealand Neonatal Network (ANZNN) collected data on the highest stage of acute ROP in either eye in 2286 infants born at less than 29 weeks in 1998–1999 and cared for in one of 25 neonatal intensive care units (NICUs). Chi‐squared analysis was used to detect differences in the proportion of stages of ROP for each neonatal intensive care unit. These proportions were compared with those reported in two large studies of treatment for ROP. Results: The incidence of acute ROP in the ANZNN cohort was 42% and the ratio of stage 1:2:3 ROP was 1.5:1.9:1. There was considerable variation in both the incidence of acute ROP and the proportions with stage 1:2:3 ROP between centres. A chi‐squared test determined that the assignment of stages 1, 2 and 3/4 ROP was not independent of centre (χ²₄₈ = 165.2; P < 0.0001). Treatment of stage 3 ROP varied between 15% and 120%, indicating some eyes were treated at less than stage 3. Conclusion: The data are highly suggestive of observer bias contributing to the observed between centre variation in the incidence of acute ROP. In neonatal intervention studies where acute ROP is an outcome it would seem important to have an accreditation process for examining ophthalmologists, and there are similar arguments for neonatal networks which collect these data.     

Does cryotherapy affect refractive error? Results from treated versus control eyes in the cryotherapy for retinopathy of prematurity trial

PURPOSE: To evaluate the effect of cryotherapy on refractive error status between ages 3 months and 10 years in children with birth weights of less than 1251 g in whom severe retinopathy of prematurity (ROP) developed in one or both eyes during the neonatal period. DESIGN: Randomized clinical trial. PARTICIPANTS: Two hundred ninety-one children in whom severe ROP developed during the neonatal period. INTERVENTION: Cryotherapy for ROP. MAIN OUTCOME MEASURES: Cycloplegic Refraction METHODS: The children underwent repeated follow-up eye examinations, including cycloplegic retinoscopy, between 3 months and 10 years after term due date. Refractive error data from all eyes that were randomized to cryotherapy were compared with data from all eyes that were randomized to serve as controls. Refractive error data were also compared for a subset of children who had both a treated and a control eye that could be refracted. RESULTS: At all ages, the proportion of treated eyes that were unable to be refracted because of retinal detachment, media opacity, or pupillary miosis was approximately half the proportion of the control eyes that were unable to be refracted. When data from all eyes that could be refracted were considered, the distribution of refractive errors between fewer than 8 diopters (D) of myopia and more than 8 D of hyperopia was similar for treated and control eyes at all ages. The proportion of eyes with 8 D or more of myopia was much higher in treated than in control eyes at all ages after 3 months. In the subset of children who had a treated eye and a control eye that could be refracted, distributions of refractive errors in treated versus control eyes were similar at most ages. CONCLUSIONS: In both treated and control eyes, there was an increase in the prevalence of high myopia between 3 and 12 months of age. Between 12 months and 10 years of age, there was little change in distribution of refractive error in treated or control eyes. The higher prevalence of myopia of 8 D or more in treated eyes, as compared with control eyes, may be the result of cryotherapy's preservation of retinal structure in eyes that, in the absence of cryotherapy, would have progressed to retinal detachment.     

Guidelines for the application of artificial intelligence in the auxiliary diagnosis of retinopathy of prematurity (2023)北大核心

As society develops, a growing number of premature infants have received effective treatment, which, however, increases the incidence of retinopathy of prematurity (ROP). ROP is characterized by acute onset, rapid progression, and short therapeutic windows, so early screening and diagnosis are crucial for the effective treatment of ROP. Artificial intelligence (AI) has made the healthcare system more intelligent. As machine learning and deep learning improve constantly, AI has been widely used in the diagnosis of fundus diseases. There have been a lot of studies on AI in the auxiliary diagnosis of ROP, achieving good results. This article is aimed at forming guidelines on the application of AI in the auxiliary diagnosis of ROP, to provide references for further research on and application of AI in this field. © The Author(s) 2023.     

Is the partial pressure of carbon dioxide in the blood related to the development of retinopathy of prematurity?

AIMS: To determine the role of carbon dioxide in the development of retinopathy of prematurity (ROP). METHODS: This was a retrospective cohort study of 25 consecutive infants admitted to the neonatal unit with continuously recorded physiological data. The daily mean and standard deviation (SD) of transcutaneous carbon dioxide partial pressure (tcPCO(2)) was compared between infants who had stage 1 or 2 ROP and stage 3 ROP. The time spent hypocarbic (<3 kPa) and/or hypercarbic (>10 kPa and >12 kPa) was also compared between these groups. Intermittent arterial carbon dioxide tension was also measured and compared with the simultaneous tcPCO(2) data. RESULTS: There were no significant differences in carbon dioxide variability or time spent hypocarbic and/or hypercarbic between the ROP groups on any day. 86% of transcutaneous values were within 1.5 kPa of the simultaneous arterial value. CONCLUSION: TcPCO(2) measurement can be a very useful management technique. However, in this cohort neither variable blood carbon dioxide tension nor duration of hypercarbia or hypocarbia in the first 2 weeks of life was associated with the development or severity of ROP.     

Do current retinopathy of prematurity screening guidelines miss the early development of pre-threshold type 1 ROP in small for gestational age neonates?

PURPOSE: To investigate whether current UK retinopathy of prematurity (ROP) screening guidelines miss the early development of pre-threshold type 1 ROP in some neonates born small for gestational age (SGA) and consider if the guidelines should be changed. Methods: Data were collected on neonates of < or =31 completed weeks gestation and/or birth weight (BW) < or =1500 g born over a 37-month period. Babies who did not complete the screening programme in Cambridge and those with other ocular abnormalities were excluded. We compared the time course of ROP progression and the development of the early treatment for ROP pre-threshold ROP in relation to the gestational age and the BW of the babies. RESULTS: A total of 105 neonates were included, 11 (10.5%) were born SGA (less than 9th centile of predicted BW). Of these 11, 2 (18.2%) had pre-threshold ROP at their first screen (median post-natal age (PNA) 6.5 weeks, median postmenstrual age (PMA) 33.5 weeks). No other neonate in this group developed pre-threshold ROP.Of the 94 other neonates, none had pre-threshold ROP at first screen (median PNA 7.1 weeks). Pre-threshold ROP developed in 12 (12.8%) of these babies between 8 and 12 (median 11.5) post-natal weeks, at a PMA of 33-38 (median 35.5) weeks. CONCLUSION: Current UK ROP screening guidelines recommend first screening at 6-7 post-natal weeks. Our study suggests that pre-threshold type 1 ROP can develop before this especially in SGA babies. We suggest that screening should either start at 4 post-natal weeks in such babies, or be based on PMA rather than PNA, to allow timely laser therapy.     

Ophthalmological follow-up at 2 years of age of all children previously screened for retinopathy of prematurity: is it worthwhile?

PURPOSE: To evaluate the extent to which ophthalmological follow-up at 2 years of age of children born before 32 weeks gestation identifies obvious visual problems, strabismus and significant ametropia (target conditions). METHODS: Of 172 children born during a period of 2.5 years from January 2000, 142 underwent an ophthalmological examination at a median age of 2.33 years. This included evaluation of visual behaviour, cover testing and autorefractometry in cycloplegia. For children with the target conditions, we investigated whether the child had been followed in the eye clinic or referred before 2 years of age, or whether the abnormality was detected as a result of the follow-up examination. RESULTS: None of the target conditions were found in 117 children. None of four children with obviously abnormal visual behaviour, two of 10 children with strabismus and four of 11 with large refractive errors were detected in the follow-up examination. Thus the target conditions were detected at the follow-up examination in only six of 142 children (4.2%). CONCLUSIONS: Although ophthalmic abnormalities are common in children born prematurely, most of them are identified because high-risk children are followed regularly in eye clinics and because parents and primary health care personnel detect strabismus. Ophthalmological follow-up of all children born before 32 weeks appears not to be worthwhile and is therefore only recommended for high-risk children.