Analysis of pathogenic factors of retinopathy of prematurity in Heilongjiang Province (preprint)

Background and purpose Retinopathy of prematurity is a vascular development disorder in immature retinas of premature infants, which is the leading cause of blindness in children worldwide. Because the screening delay may lead to the occurrence of blindness in children, it is particularly important to conduct timely screening for children with high risk factors. Currently, the pathogenesis of ROP may be related to multiple factors such as gestational age and birth weight of premature infants. In this study, the prevalence and risk factors of ROP in Heilongjiang Province were determined through screening for premature infants in the region, aiming to proceed early prevention of the disease. Methods Retrospectively analyzed 714 premature infants admitted to the Ophthalmology Clinic of the Second Affiliated Hospital of Harbin Medical University from January 2016 to February 2022. 12 related factors was recorded including patients’ gender, gestational age, birth weight, oxygen duration, blood transfusions, anemia, neonatal infections, respiratory distress syndrome, maternal feeding way, childbirth way, pregnancy age and parity. The prevalence of ROP and the differences in related factors between ROP patientsand non-ROP patients were found. Results Among 714 premature infants, 188 had ROP of which the incidence is 26.3%，and 61 patients received treatment. There were statistically significance(P<0.05) in gestational age, birth weight, oxygen duration, blood transfusion, anemia, neonatal infection, respiratory distress syndrome and childbirth way between the 188 ROP patients and non-ROP patients in univariate regression analysis. Variables with statistical significance for single factor were selected and conducted by multivariate regression analysis, which showed that gestational age, birth weight, and oxygen duration had remarkable statistical significance(P<0.05) with the occurrence of ROP. Gestational age and birth weight were the protective factors of disease (OR=0.43 and OR=0.8), while oxygen duration was the risk factor of disease (OR=1.02), and the diagnostic value of the model was high (AUC=0.776). five of the 61 patients who received treatment for ROP accepted two treatments, with gestational age < 32 weeks, birth weight < 1500g, and oxygen inhalation time > 20 days. The Kendall grade relative analysis of 188 patients with ROP showed that disease severity was significantly correlated with gestational age, birth weight, oxygen duration, anemia, blood transfusion and respiratory distress syndrome(P<0.05), in which the gestational age, birth weight, anemia, blood transfusion and respiratory distress syndrome were negatively correlated with the severity of the disease, while oxygen duration was positively correlated with severity of the disease. 507 children were screened from 2016 to December 31th in 2019, 138 of which were ROP patients, 36 children were treated (7.1%). Due to the spread of the COVID-19, 207 children were screened after January 1th in 2020, 50 children were ROP patients, and 25 of whom got treatment (12%), 21were treated after 8 weeks of birth or more than 37 weeks of corrected gestational age. Four out of five children who received the second treatment happened after the epidemic, and three of them missed treatment due to the epidemic. Conclusions The gestational age, birth weight and oxygen duration are significantly correlated with the incidence and severity of the disease in premature infants screening of Heilongjiang Province. Premature infants screening and subsequent visit were affected due to the spread of the COVID-19 in the past two years, the proportion of children needed to be cured augmented apparently, therefore, it matters a lot for premature infants to be screened standardly and timely.

The impact of the COVID-19 lockdown on retinopathy of prematurity screening and management in the United States: a multicenter study.

PURPOSE: To study the effect of the pandemic-related lockdown (physical distance measures and movement restrictions) on the characteristics and management of retinopathy of prematurity (ROP). METHODS: In this controlled, multicenter cohort study, the medical records of patients born prematurely and screened for ROP in the neonatal intensive care unit during four time periods were reviewed retrospectively: (1) November 1, 2018, to March 15, 2019; (2) March 16, 2019, to August 2, 2019 (lockdown control period); (3) November 1, 2019, to March 15, 2020; and (4) March 16, 2020-August 2, 2020. RESULTS: A total of 1,645 patients met inclusion criteria. Among the 1,633 patients with complete data, mean gestational age (GA) at birth was 28.2, 28.4, 28.0, and 28.3 weeks across time periods 1 to 4, respectively (P = 0.16). The mean birth weight of all patients was 1079.1 ± 378.60 g, with no significant variation across time periods (P = 0.08). There were fewer patients screened during the lockdown period (n = 411) compared with the period immediately before (n = 491) and the same period in the prior year (n = 533). Significantly more patients were screened using indirect ophthalmoscopy, compared to digital imaging (telemedicine), during the lockdown (P < 0.01). There were 11.7%, 7.7%, 9.0%, and 8.8% of patients requiring treatment in each time period, respectively (P = 0.42), with a median postmenstrual age at initial treatment of 37.2, 36.45, 37.1, and 36.3 weeks, respectively (P = 0.32). CONCLUSIONS: We recorded a decrease in the number of infants meeting criteria for ROP screening during the lockdown. The GA at birth and birth weight did not differ. Significantly more infants were screened with indirect ophthalmoscopy, compared to digital imaging, during the lockdown.

Coats plus in prematurity.

BACKGROUND: Coats plus syndrome or cerebroretinal microangiopathy with calcifications and cysts (CMCC) is an exceedingly rare autosomal recessive disorder that predominantly affects the microvasculature in the retina, brain, bones, and gastrointestinal system. Unlike Coats disease, CMCC is bilateral and affects multiple organ systems. MATERIALS AND METHODS: Case report. RESULTS: We report the case of two brothers with Coats Plus syndrome who presented with variable phenotypic expression. One sibling (Patient 1) was thought to have atypical retinopathy of prematurity and was only diagnosed with Coats plus after his older brother (Patient 2) presented with a seizure and a left upper extremity tremor at 4 years of age. The CTC1 mutation was confirmed in both patients. Aggressive treatment with laser photocoagulation and intravitreal bevacizumab dramatically improved the retinal vascular and exudative changes. CONCLUSION: Coats Plus syndrome can have a variable phenotypic presentation, including retinal vascular findings. This rare genetic disease should be in the differential diagnosis in patients who present with atypical retinal pathology, including Retinopathy of Prematurity, Familial Exudative Vitreoretinopathy, or Coats disease associated with non-specific multiorgan abnormalities.

Effectiveness and future implications of COVID-19-related risk stratification for managing retinopathy of prematurity: The Indian twin cities retinopathy of prematurity study report number 10.

Purpose: To evaluate the effectiveness and future implications of COVID-related risk stratification for managing retinopathy of prematurity (ROP). Methods: A prospective study was conducted at a tertiary eye care center from the beginning of the lockdown in India from 23 March 2020 till the end of the first phase of lockdown on 29 May 2020. We evaluated 200 prematurely born infants (< 34 weeks of gestational age) using the new safety guideline protocols for low-risk babies developed in conjunction with the Indian ROP Society for care during the COVID-19 pandemic. Low risk included babies born at more than 30 weeks of gestational age, post menstrual age 34 weeks or above at presentation, more than 1000 grams of birth weight, and stable systemically with good weight gain. Results: New guidelines were implemented in 106 (53%) infants who were low risk while 94 (47%) infants with high risk were followed up as per the old guidelines. Out of the 106 infants (212 eyes) managed by the new guidelines, good outcome (group 1) was seen in 102 (96.2%) infants. Twenty-seven of the 102 infants had some form of ROP and 5 of these infants needed treatment. None of the low-risk babies with no detachment at presentation managed by new guidelines required surgery later (group 2). Two (1.9%) infants came with retinal detachment at presentation and underwent successful surgery (group 3) and two infants (1.9%) were lost to follow up. Conclusion: New risk stratification during the COVID-19 pandemic was an efficient and safe strategy in managing low-risk ROP babies.

Evaluation of a revised care plan for babies with retinopathy of prematurity during SARS-CoV-2 pandemic in India.

Purpose: To analyze the impact of a revised care plan for retinopathy of prematurity (ROP) during SARS-CoV-2 pandemic in a tertiary eye care facility in eastern India. Methods: In a retrospective study, we analyzed the medical records of babies managed for ROP during the peak of the SARS-CoV-2 pandemic, with particular reference to the challenges, and the revised strategies addressing travel restrictions for five months, from April to August 2020. The strategy included selective referral (babies with higher treatment probability), longer follow-up intervals (babies with non-alarming findings), use of locally available workforce, and teleconsultation whenever feasible. Results: In the given period, 222 babies were examined versus 624 in the preceding year (P = 0.001). The average gestational age, birth weight, and postmenstrual age at presentation were 30.4 weeks, 1.31 kg, and 37.7 weeks, respectively. The first examination was on time in 40.1% of babies but was delayed by a median of 23 days in the remaining babies. In the cohort, 56.7% of babies had any ROP, and 27.9% required treatment (versus 8.8% in the previous year; P < 0.001). The intravitreal anti-vascular growth factor (anti-VEGF) injection was more often used than in the previous year (n = 72 vs 36; P < 0.0001). The treatment outcome was comparable before and after the SARS-CoV-2 lockdown period. There was no report of health issues among the care providers attributable to ROP care. Conclusion: The revised strategy resulted in a smaller pool of babies screened but a larger proportion of babies treated for ROP. This strategy could be used more profitably in future ROP care.

Comparing the diagnostic accuracy of telemedicine utilization versus in-person clinical examination for retinopathy of prematurity in premature infants: a systematic review.

PURPOSE: To synthesize the literature assessing the diagnostic accuracy of telemedicine evaluation compared with clinical examination for retinopathy of prematurity (ROP) in premature infants. METHODS: Covidence software was used to conduct a systematic literature search from September 14, 2020, through September 27, 2020, on MEDLINE (Ovid), EMBASE (Ovid), CINAHL, and the gray literature to identify studies relevant to telemedicine utilization for ROP detection. After duplicate removal and two-levels of screening, studies comparing telemedicine evaluation with binocular indirect ophthalmoscopic examination were included. Risk of bias assessment was conducted for the included studies following data extraction. A qualitative review was performed to summarize estimates of accuracy of ROP evaluation by telemedicine. RESULTS: A total of 507 studies were reviewed, of which 323 were found in EMBASE, 115 in MEDLINE, and 79 in CINAHL. Three possibly relevant conference abstracts were found. Following duplicate removal, 410 studies were reviewed based on titles and abstracts. Subsequently, 19 articles were thoroughly examined, and 14 studies (2,655 participants) were included. Most studies found that telemedicine performance for detecting ROP was comparable to ophthalmic examination, especially with regard to identifying treatment-requiring ROP. CONCLUSIONS: Telemedicine evaluation can reliably detect ROP. Incorporation of telemedicine into conventional neonatal care has the potential to improve access to ROP care.

Changes in fetal growth restriction and retinopathy of prematurity during the coronavirus disease 2019 pandemic: A cross-sectional study.

PURPOSE: To investigate changes in the number of preterm infants, low birth weight infants, and infants with fetal growth restriction (FGR) or retinopathy of prematurity (ROP) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In this retrospective cross-sectional study, we reviewed the medical records of infants born and admitted to the neonatal intensive care unit and growth care unit of Shiga University of Medical Science Hospital before the COVID-19 pandemic (April 1, 2019 to September 30, 2019) and during the pandemic (April 1, 2020 to September 30, 2020). Medical records of infants' mothers were also collected. Preterm infants, low birth weight infants, infants with FGR, infant and maternal factors associated with FGR, and infants requiring treatment for ROP were compared between the two periods. RESULTS: There were fewer infants born at < 28 weeks of gestation, infants with birth weight < 1,500 g, and infants with FGR during the pandemic period than the pre-pandemic period (pre-pandemic: n = 4 vs. during pandemic: n = 0, P = 0.048; pre-pandemic: n = 15 vs. during pandemic: n = 6, P = 0.02; and pre-pandemic: n = 31 vs. during pandemic: n = 12, P = 0.0002, respectively). There were no significant differences in any infant or maternal factors associated with FGR. The number of infants requiring treatment for ROP decreased during the pandemic, although this difference was not statistically significant (pre-pandemic: n = 3 vs. during pandemic: n = 0, P = 0.08). CONCLUSIONS: Our findings showed a reduction in the number of infants with FGR during the COVID-19 pandemic. The number of infants born at < 28 weeks of gestation and infants with birth weight < 1,500 g also decreased during the pandemic period. There was a trend toward fewer infants requiring treatment for ROP during the COVID-19 pandemic.

The safety and feasibility of the screening for retinopathy of prematurity assisted by telemedicine network during COVID-19 pandemic in Wuhan, China.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) epidemic, due to the traffic blockade and the shortage of medical resources, more and more premature infants could not receive timely and effective ROP screening, which delayed treatment and even caused children blindness. Therefore, how to carry out ROP screening safely and effectively during the epidemic was very important and urgent. This study aimed to evaluate the safety and feasibility of ROP screening assisted by telemedicine network during COVID-19 outbreak. METHODS: This retrospective study was conducted at Wuhan Children's hospital in Wuhan, China, from January to October, 2020. The measures which were performed to make the ROP screening more safe and effective were summarized and the comparison between ROP screening assisted by telemedicine network in 2020 and usual screening in 2019 were analyzed. RESULTS: A total of 267 outpatient infants completed ROP screening. The median gestational age was 32 weeks (30w to 34w) and the median birth weight was 1780 g (1460 g to 2100 g). Meanwhile, 149 (55.8%) out of 267 infants were males. During January to May in 2020, 86 screening appointments were received, among which 67 (77.9%) were from telemedicine platform online. The completing percentage of total online ROP appointments was higher than that of total face-to-face appointments (58.1% VS 22. 1%, P = 0.018). As for the number of infants screened between 2020 and 2019 from Februaryto October, 54 infants completed ROP screening in 2020, which was higher than that (51participants) in 2019 on September. Furthermore, compared with the usual screening in 2019, ROP screening assisted by telemedicine network in 2020 had smaller gestational age (32w VS 33w, p<0.001) and lower birth weight (1780 g VS 1900 g, p = 0.001). However, of the 267 infants screened, 18(6.7%) had ROP while the percentage of ROP screened in 2019 was the same (44[6.7%]). During follow-up, none of medical staffs was infected and no adverse reaction was reported. CONCLUSIONS: The screening for retinopathy of prematurity assisted by telemedicine network was safe and feasible during the COVID-19 pandemic. Preventive measures before and after screening were very necessary, which could effectively avoid cross infection.

Retinopathy of prematurity screening and risk mitigation during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has significantly disrupted the delivery of healthcare. Although most nonurgent ophthalmology visits at Boston Children's Hospital were canceled, premature infants at risk for retinopathy of prematurity (ROP) still required timely, in-person care during the initial 3-month period of the infection surge in Massachusetts. The purpose of the current study was to report our protocols for mitigating risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between infants and eye care providers and to compare examination rates and results with the same 3-month period in 2019. METHODS: During the infection surge, we added new infection control measures and strengthened existing ones. Additional personal protective equipment was used, and the number of ophthalmologists rotating in the three high-capacity NICUs we service was limited. RESULTS: More infants required ROP examinations during the study period in 2020 than in the same period in 2019, but fewer examinations were performed. There were no cases of missed progression to severe ROP during this time and no known transmission of SARS-CoV-2 between ROP patients and ophthalmology staff. CONCLUSIONS: Overall, effective ROP care was safely provided during the COVID-19 pandemic, and contact with this vulnerable population was minimized.

Aerosol containment box for laser treatment of retinopathy of prematurity in COVID-19 pandemic.

Type 1 retinopathy of prematurity (ROP) requires emergency intervention and laser is an established modality of treatment. Laser treatment for ROP under topical anesthesia can be considered as an aerosol-generating procedure due to crying that puts health care workers at high risk of COVID-19 transmission. Aerosol containment box (ACB) is known to minimize aerosol transmission and there are reports of ROP laser done through incubator. Combining these two ideas, we describe a new application of ACB with suction for laser treatment of ROP thereby, reducing risk to health care team without compromising timely effective, and safe treatment for ROP.

Virus containment box for retinopathy of prematurity screening and laser.

PURPOSE: Health care workers are susceptible to contracting infection with COVID-19 by aerosol transmission. This is a risk while examining and/or treating an un-sedated neonate in retinopathy of prematurity (ROP) screening and treatment. But screening for neonates for ROP and treating with laser, when required, should not be delayed to avoid the blindness. We describe a cost-effective method of containing aerosols generated during such a procedure in an un-sedated baby. METHODS: An acrylic transparent containment box was prepared to accommodate an average-sized infant. The box had four walls and a roof. The floor was open to place the container box over the baby. The walls have two types of openings, large ones to allow passage of hands to examine the baby, small ones to enable passage of oxygen tubing when required. A simulation was created to examine the impact of aerosol spray on examining healthcare personnel. RESULTS: The cost of the acrylic box was negligible. It could be assembled locally with available acrylic sheets and craftsmen. It was not difficult to examine the baby inside the box, and the simulation demonstrated that it protected the health personnel from the aerosol contamination. CONCLUSION: The described method is likely to increase healthcare personnel's confidence not to delay or deny ROP screening and laser treatment and save the babies from blindness.