MHANet: A hybrid attention mechanism for retinal diseases classification.

With the increase of patients with retinopathy, retinopathy recognition has become a research hotspot. In this article, we describe the etiology and symptoms of three kinds of retinal diseases, including drusen(DRUSEN), choroidal neovascularization(CNV) and diabetic macular edema(DME). In addition, we also propose a hybrid attention mechanism to classify and recognize different types of retinopathy images. In particular, the hybrid attention mechanism proposed in this paper includes parallel spatial attention mechanism and channel attention mechanism. It can extract the key features in the channel dimension and spatial dimension of retinopathy images, and reduce the negative impact of background information on classification results. The experimental results show that the hybrid attention mechanism proposed in this paper can better assist the network to focus on extracting thr fetures of the retinopathy area and enhance the adaptability to the differences of different data sets. Finally, the hybrid attention mechanism achieved 96.5% and 99.76% classification accuracy on two public OCT data sets of retinopathy, respectively.

Surgery for stage 5 retinopathy of prematurity.

PURPOSE OF REVIEW: Our understanding of the pathogenesis and surgical management of stage 5 retinopathy of prematurity has come a long way. Despite of new technologies in retinal surgical devices, the dissection of thick membranes is still a challenge. We use a capsulotomy 'plug on tip' 0.05 mm designed for capsular fimosis. This diathermy instrument is used to cut the lens capsule by low power waves transmitted from the tip of an active incising electrode and make incisions in the tissue. We tested this technique with 226 infants of which all 226 eyes retrolental membrane were removed. In 6-46 months follow-up, light perception or better visual function was achieved in 92%. RECENT FINDINGS: Despite of new technologies in retinal surgical devices, the dissection of thick membranes is still a challenge. Sometimes, we need to use tools that were made for another purpose and adapt it to our current techniques. SUMMARY: Achieving at least a vision of light perception in eyes that were considered untreatable is a good outcome as light perception maintains the circadian circle and helps in the brain development. VIDEO ABSTRACT: http://links.lww.com/COOP/A47.

International Classification of Retinopathy of Prematurity, Third Edition.

PURPOSE: The International Classification of Retinopathy of Prematurity is a consensus statement that creates a standard nomenclature for classification of retinopathy of prematurity (ROP). It was initially published in 1984, expanded in 1987, and revisited in 2005. This article presents a third revision, the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), which is now required because of challenges such as: (1) concerns about subjectivity in critical elements of disease classification; (2) innovations in ophthalmic imaging; (3) novel pharmacologic therapies (e.g., anti-vascular endothelial growth factor agents) with unique regression and reactivation features after treatment compared with ablative therapies; and (4) recognition that patterns of ROP in some regions of the world do not fit neatly into the current classification system. DESIGN: Review of evidence-based literature, along with expert consensus opinion. PARTICIPANTS: International ROP expert committee assembled in March 2019 representing 17 countries and comprising 14 pediatric ophthalmologists and 20 retinal specialists, as well as 12 women and 22 men. METHODS: The committee was initially divided into 3 subcommittees-acute phase, regression or reactivation, and imaging-each of which used iterative videoconferences and an online message board to identify key challenges and approaches. Subsequently, the entire committee used iterative videoconferences, 2 in-person multiday meetings, and an online message board to develop consensus on classification. MAIN OUTCOME MEASURES: Consensus statement. RESULTS: The ICROP3 retains current definitions such as zone (location of disease), stage (appearance of disease at the avascular-vascular junction), and circumferential extent of disease. Major updates in the ICROP3 include refined classification metrics (e.g., posterior zone II, notch, subcategorization of stage 5, and recognition that a continuous spectrum of vascular abnormality exists from normal to plus disease). Updates also include the definition of aggressive ROP to replace aggressive-posterior ROP because of increasing recognition that aggressive disease may occur in larger preterm infants and beyond the posterior retina, particularly in regions of the world with limited resources. ROP regression and reactivation are described in detail, with additional description of long-term sequelae. CONCLUSIONS: These principles may improve the quality and standardization of ROP care worldwide and may provide a foundation to improve research and clinical care.

Deep Learning for the Diagnosis of Stage in Retinopathy of Prematurity: Accuracy and Generalizability across Populations and Cameras.

PURPOSE: Stage is an important feature to identify in retinal images of infants at risk of retinopathy of prematurity (ROP). The purpose of this study was to implement a convolutional neural network (CNN) for binary detection of stages 1, 2, and 3 in ROP and to evaluate its generalizability across different populations and camera systems. DESIGN: Diagnostic validation study of CNN for stage detection. PARTICIPANTS: Retinal fundus images obtained from preterm infants during routine ROP screenings. METHODS: Two datasets were used: 5943 fundus images obtained by RetCam camera (Natus Medical, Pleasanton, CA) from 9 North American institutions and 5049 images obtained by 3nethra camera (Forus Health Incorporated, Bengaluru, India) from 4 hospitals in Nepal. Images were labeled based on the presence of stage by 1 to 3 expert graders. Three CNN models were trained using 5-fold cross-validation on datasets from North America alone, Nepal alone, and a combined dataset and were evaluated on 2 held-out test sets consisting of 708 and 247 images from the Nepali and North American datasets, respectively. MAIN OUTCOME MEASURES: Convolutional neural network performance was evaluated using area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), sensitivity, and specificity. RESULTS: Both the North American- and Nepali-trained models demonstrated high performance on a test set from the same population: AUROC, 0.99; AUPRC, 0.98; sensitivity, 94%; and AUROC, 0.97; AUPRC, 0.91; and sensitivity, 73%; respectively. However, the performance of each model decreased to AUROC of 0.96 and AUPRC of 0.88 (sensitivity, 52%) and AUROC of 0.62 and AUPRC of 0.36 (sensitivity, 44%) when evaluated on a test set from the other population. Compared with the models trained on individual datasets, the model trained on a combined dataset achieved improved performance on each respective test set: sensitivity improved from 94% to 98% on the North American test set and from 73% to 82% on the Nepali test set. CONCLUSIONS: A CNN can identify accurately the presence of ROP stage in retinal images, but performance depends on the similarity between training and testing populations. We demonstrated that internal and external performance can be improved by increasing the heterogeneity of the training dataset features of the training dataset, in this case by combining images from different populations and cameras.

PREOPERATIVE ANATOMICAL FEATURES ASSOCIATED WITH IMPROVED SURGICAL OUTCOMES FOR STAGE 5 RETINOPATHY OF PREMATURITY.

PURPOSE: To describe preoperative anatomical features of Stage 5 retinopathy of prematurity with results of surgery and patient-related and surgery-related factors affecting postoperative success. METHODS: Forty eyes of 33 infants who underwent vitrectomy with lensectomy or lens-sparing vitrectomy for Stage 5 retinopathy of prematurity were enrolled. Stage 5 cases were divided into different groups according to their preoperative anatomical features as follows: A: for eyes with ophthalmoscopically observable total retinal detachment; B: for eyes with total leucocoria associated with funnel retinal detachment; and C: for eyes with very shallow anterior chamber and corneal opacity. Only A and B eyes underwent surgery. The effect of the presence of vascular dilation and tortuosity, preoperative treatment status, surgically induced posterior hyaloid detachment, and sparing the lens on anatomical and functional results was evaluated. RESULTS: Thirty-five percentage of the eyes were in Group A and 65% were in Group B. The mean follow-up was 30.6 months (12-68). Anatomical success was 55.5% for Group A and 15.4% for Group B (P: 0.047), and functional success was 33.3% for Group A and 7.7% for Group B at the third year (P: 0.125). The presence of vascular dilation and tortuosity and postoperative vitreous hemorrhage were found to have negative effects; preoperative treatment and surgical induction of posterior hyaloid detachment were found to have positive effects on anatomical and functional results. CONCLUSION: Surgery for ophthalmoscopically observable retinopathy of prematurity-associated retinal detachment resulted in better anatomical and functional outcomes, and the results are even better in eyes with preoperative treatment, lens-sparing vitrectomy, and surgically induced posterior hyaloid detachment.

Automated detection of early-stage ROP using a deep convolutional neural network.

BACKGROUND/AIM: To automatically detect and classify the early stages of retinopathy of prematurity (ROP) using a deep convolutional neural network (CNN). METHODS: This retrospective cross-sectional study was conducted in a referral medical centre in Taiwan. Only premature infants with no ROP, stage 1 ROP or stage 2 ROP were enrolled. Overall, 11 372 retinal fundus images were compiled and split into 10 235 images (90%) for training, 1137 (10%) for validation and 244 for testing. A deep CNN was implemented to classify images according to the ROP stage. Data were collected from December 17, 2013 to May 24, 2019 and analysed from December 2018 to January 2020. The metrics of sensitivity, specificity and area under the receiver operating characteristic curve were adopted to evaluate the performance of the algorithm relative to the reference standard diagnosis. RESULTS: The model was trained using fivefold cross-validation, yielding an average accuracy of 99.93%±0.03 during training and 92.23%±1.39 during testing. The sensitivity and specificity scores of the model were 96.14%±0.87 and 95.95%±0.48, 91.82%±2.03 and 94.50%±0.71, and 89.81%±1.82 and 98.99%±0.40 when predicting no ROP versus ROP, stage 1 ROP versus no ROP and stage 2 ROP, and stage 2 ROP versus no ROP and stage 1 ROP, respectively. CONCLUSIONS: The proposed system can accurately differentiate among ROP early stages and has the potential to help ophthalmologists classify ROP at an early stage.

Treatment of retinopathy of prematurity (ROP) outside International Classification of ROP (ICROP) guidelines.

AIM: To evaluate the incidence and clinical indications for which eyes were treated for retinopathy of prematurity (ROP) outside the guidelines set by International Classification of ROP (ICROP). METHODS: Medical records of the patients treated at a single tertiary care ophthalmology hospital for ROP from January 2016 to December 2019 were retrospectively analysed to evaluate the indications for which they were treated. RESULTS: Out of 241 eyes, 33 eyes (13.7%) were treated outside the guidelines. The reasons for the treatment outside the guidelines were structural changes (n = 24, 72.7%), persistent stage 3 ROP that did not show any sign of regression for 6 weeks (n = 7, 21.2%) and active ROP with fellow eye being treated (n = 2, 6.1%). The recorded specific structural changes were tangential traction with temporal vessel straightening concerning for macular distortion and ectopia (n = 5, 15.2%), and stage 3 neovascularisation or ridge with anteroposterior traction with risk of progression to stage 4 disease (n = 19, 57.6%). Pre-plus disease was present in 11 eyes (33.3%).After the treatment, ROP stages regressed and retinal vessels grew either until the ora or at least into zone III in all the treated eyes. None of the eyes showed worsening of structural changes after treatment. The mean follow-up of the patients was 12.4 ± 11.7 months. CONCLUSION: Experts occasionally recommend treatment in eyes with disease milder than type 1 ROP. This study may help paediatric retinal practitioners in decision-making in borderline cases.

Differentiating Retinal Detachment and Retinoschisis Using Handheld Optical Coherence Tomography in Stage 4 Retinopathy of Prematurity.

Importance: Progression of retinopathy of prematurity (ROP) to stage 4 may require surgical intervention. The partial retinal detachment of stage 4 ROP may involve the fovea (stage 4B ROP) or may not (stage 4A ROP). This determination has heretofore been based on indirect ophthalmoscopy and documented with color fundus photography. Objective: To investigate optical coherence tomography (OCT) features of eyes with stage 4 ROP and compare them with indirect ophthalmoscopy findings and grading of photographs. Design, Setting, and Participants: In this study, research and clinical medical records of 15 infants with clinically diagnosed stage 4 ROP were retrospectively reviewed. Infants were treated at an academic center from May 2011 to January 2018. Main Outcomes and Measures: Review of OCT images for the presence and foveal involvement of retinoschisis, retinal detachment, and/or vitreomacular traction masked to indirect ophthalmoscopy findings. Results: Of the 15 included infants, 9 (60%) were male, the mean (SD) gestational age at birth was 23.9 (1.1) weeks, and the mean (SD) postmenstrual age at surgery was 42.4 (4.9) weeks. A total of 21 eyes were analyzed, of which 19 had adequate OCT imaging. Optical coherence tomography imaging extended to the retinal midperiphery but did not cover the entire region of possible detachment in each eye. Among these eyes, 7 eyes had peripheral retinoschisis without retinal detachment or foveal involvement, 5 eyes had peripheral retinoschisis and retinal detachment without foveal involvement, 7 eyes had either retinoschisis or retinal detachment involving the fovea, and 2 eyes had poor OCT signal owing to high retinal detachment. Conclusions and Relevance: Handheld OCT imaging is useful in clinical evaluation of stage 4 ROP to determine foveal involvement and differentiate retinal detachment and retinoschisis. Many infants diagnosed as having stage 4A ROP had retinoschisis without OCT evidence of retinal detachment. This group of infants may represent a substage of stage 4A ROP, ie, stage 4A-schisis by OCT. These findings suggest handheld OCT imaging may be useful in the clinical evaluation of stage 4 ROP. Further investigations are needed to determine if this subgroup portends a different prognosis and if this observation should alter future clinical practice.

Retinopatia da prematuridade: análise de uma tentativa de redução de danos / Retinopathy of prematurity: analysis of a damage reduction attempt

Resumo Objetivo: Avaliar a eficácia de um protocolo de redução da saturação do oxigênio utilizado na suplementação dos recém-nascidos pré-termos (RNPT) internados em uma UTI neonatal para prevenir o aparecimento da Retinopatia da prematuridade (ROP). Métodos: Trata-se de estudo de coorte realizado em única UTI Neonatal. O primeiro grupo (pré-protocolo, n=30) fez uso de oxigênio com saturação de hemoglobina >95%. A partir da instituição de um novo protocolo de oxigenioterapia que manteve a saturação de hemoglobina entre 90% e 95% obteve-se o segundo grupo (pós-protocolo n=28). Todos os RNPT incluídos tinham idade gestacional de menor ou igual 32 semanas e/ou com peso de nascimento igual ou abaixo de 1500g, fizeram mapeamentos de retina a partir de 28 dias de vida e seguimento por até 45 semanas de idade gestacional corrigida. Resultados: Dos 58 casos estudados, excluindo-se os que foram a óbito (15/58; 26,8%) dos casos, ROP foi diagnosticado em 15/43 (34,9%) pacientes. A menor idade gestacional influenciou significativamente no aparecimento da ROP (p=0,002). Em relação ao número de casos de ROP e de óbitos não se observou diferença estatisticamente significativa entre os grupos. O tempo de oxigenioterapia foi significativamente associado com a presença de ROP em ambos grupos. Meninos foram seis vezes mais acometidos por ROP que as meninas. Conclusão: A redução da saturação de oxigênio não se mostrou eficaz para redução de número de casos de ROP.

Abstract Objective: To evaluate the efficacy of an oxygen saturation reduction protocol used to supplement preterm newborns (PTNB) hospitalized in a neonatal ICU to prevent the onset of retinopathy of prematurity (ROP). Methods: This is a cohort study performed in a single Neonatal ICU. The first group (pre-protocol, n = 30) used oxygen with hemoglobin saturation > 95%. Since the institution of a new oxygen therapy protocol that maintained hemoglobin saturation between 90% and 95%, the second group was obtained (post-protocol n = 28). All included preterm infants had a gestational age of less than or equal to 32 weeks and / or birth weight of 1500 g or less, retinal mappings from 28 days of life and follow up for up to 45 weeks of corrected gestational age. Results: 58 cases were studied, excluding those who died (15/58; 26.8%), ROP was diagnosed in 15/43 patients (34.9%). The lower gestational age significantly influenced the appearance of ROP (p = 0.002). Regarding the number of ROP cases and deaths, no statistically significant difference was observed between groups. Oxygen therapy time was significantly associated with the presence of ROP in both groups. Boys were six times more affected by ROP than girls. Conclusion: Reduction of oxygen saturation was not effective in reducing the number of cases of ROP.

Parameters affecting postoperative success of surgery for stage 4A/4B ROP.

PURPOSE: To describe the long-term anatomical and functional results of surgery for retinal detachment (RD) associated with stage 4 retinopathy of prematurity (ROP) and patient and surgery-related factors affecting postoperative success. DESIGN: Retrospective case series at a single tertiary referral paediatric vitreoretinal practice. METHODS: One hundred and twenty-one eyes of 82 infants (40 female/42 male) who underwent lens-sparing vitrectomy (LSV) or lensectomy with vitrectomy surgery for stage 4A and 4B ROP at Gazi University Department of Ophthalmology between 2011 and 2016 were enrolled in this study. Patient characteristics including gestational age, birth weight, gender, stage of ROP at presentation, preoperative treatment (laser, anti-vascular endothelial growth factor (VEGF) or combined), anatomical and functional outcome and complications were recorded. The effect of birth weight, gestational age, presence of plus disease, preoperative treatment status, surgically induced posterior hyaloid detachment, postoperative vitreous haemorrhage and iatrogenic retinal tear formation on anatomical and functional results was evaluated. RESULTS: 61.2% of the eyes were stage 4A and 38.8% were stage 4B ROP. The mean follow-up was 24.5 months. 18.2% of the eyes had no preoperative treatment. Anatomical success was 86.5% for stage 4A and 68.1% for stage 4B at the first year, 91.7% for stage 4A and 69.4% for stage 4B at the second year, and 95.8% for stage 4A and 57.9% for stage 4B at the third year. Functional success was 85.1% for stage 4A and 65.9% for stage 4B at the first year, 89.6% for stage 4A and 61.1% for stage 4B at the second year, and 87.5% for stage 4A and 57.8% for stage 4B at the third year. The mean visual acuity was 1.12±0.34 logarithm of the minimum angle of resolution (logMAR) for stage 4A and 1.34±0.32 logMAR at the 3-year follow-up duration (p>0.05). There was preoperative plus disease in 59.5% of the eyes. Subsequent retinal surgeries were required in 17.4% of the eyes. Presence of plus disease and absence of preoperative treatment, iatrogenic retinal tear formation and postoperative vitreous haemorrhage were found to have significant negative effects, while surgical induction of posterior hyaloid detachment and sparing the lens intraoperatively affected the anatomical and functional results positively. CONCLUSIONS: Surgery for stage 4 ROP-associated RD resulted in encouraging anatomical and functional outcomes and the results are even better in eyes with preoperative (laser/anti-VEGF) treatment, LSV and surgically induced posterior hyaloid detachment.

Anti-vascular Endothelial Growth Factor Treatment of Retinopathy of Prematurity: Efficacy, Safety, and Anatomical Outcomes.

PURPOSE: To investigate the efficacy, safety, and anatomical outcomes associated with intravitreal anti-vascular endothelial growth factor (VEGF) treatment of retinopathy of prematurity (ROP). METHODS: We performed a retrospective review of intravitreal anti-VEGF (bevacizumab or ranibizumab) treatment of 153 eyes (83 infants) diagnosed with ROP at two tertiary hospitals from June 2011 to January 2017. The primary outcome was the rate of recurrence requiring additional treatment; secondary outcomes included incidence of major complications and final refractive error. RESULTS: A total of 101 eyes were treated with bevacizumab, and 52 with ranibizumab. The bevacizumab and ranibizumab groups were characterized by mean birthweights of 941.8 ± 296.1 and 1,257.7 ± 514.5 g, gestational ages at birth of 26.9 ± 1.9 and 28.1 ± 3.2 weeks, and postmenstrual ages at treatment of 40.4 ± 2.4 and 39.2 ± 2.3 weeks, respectively. The two groups differed significantly in birthweights and gestational ages at birth, but not in postmenstrual ages at treatment. The mean follow-up duration was 30.9 ± 18.4 months for the bevacizumab group, and 13.9 ± 12.5 months for ranibizumab. More cases were classified as zone 1 ROP in the ranibizumab group (44.2% vs. 11.9%, p < 0.001). Major surgical interventions included scleral encircling and vitrectomy (one and two eyes, respectively, both in the bevacizumab group). Retinal detachment was noted in one eye treated with bevacizumab. There was no significant difference in the most recent spherical equivalence for the two groups (+0.10 ± 3.66 and +0.22 ± 3.00 diopters for bevacizumab and ranibizumab, respectively). Univariable analysis revealed that only ROP stage influenced the occurrence of major complications (odds ratio, 9.046; p = 0.012). CONCLUSIONS: Intravitreal anti-VEGF treatment of ROP with both bevacizumab and ranibizumab achieved stable retinal vascularization with a low rate of complications and recurrence. Ranibizumab achieved similar anatomical outcomes as bevacizumab, without additional risk for major complications.

Spontaneous Attachment of Rhegmatogenous Retinal Detachment Following Vitrectomy for Stage 4B Retinopathy of Prematurity and Atypical Retinal Changes Post-Resolution.

A prematurely born baby underwent lens-sparing vitrectomy for Stage 4B retinopathy of prematurity (ROP) in the left eye. This child had a stormy neonatal course, referred late, and was treated with intravitreal anti-vascular endothelial growth factor and laser in both eyes in the past. The surgery was uneventful, and the retina was attached until a month after surgery. Later, there was development of a break that led to the occurrence of rhegmatogenous retinal detachment in the operated eye. The retinal detachment increased with time during the course of 6 weeks. Surprisingly, the hole disappeared with spontaneous attachment of retina in the following weeks, with multiple depigmented spots over the posterior pole. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:544-547.].

A Domain-Specific Terminology for Retinopathy of Prematurity and Its Applications in Clinical Settings.

A terminology (or coding system) is a formal set of controlled vocabulary in a specific domain. With a well-defined terminology, each concept in the target domain is assigned with a unique code, which can be identified and processed across different medical systems in an unambiguous way. Though there are lots of well-known biomedical terminologies, there is currently no domain-specific terminology for ROP (retinopathy of prematurity). Based on a collection of historical ROP patients' data in the electronic medical record system, we extracted the most frequent terms in the domain and organized them into a hierarchical coding system-ROP Minimal Standard Terminology, which contains 62 core concepts in 4 categories. This terminology has been successfully used to provide highly structured and semantic-rich clinical data in several ROP-related applications.

Implementation of a Clinical Prediction Model Using Daily Postnatal Weight Gain, Birth Weight, and Gestational Age to Risk Stratify ROP.

PURPOSE: To develop a simple prognostic model using postnatal weight gain, birth weight, and gestational age to identify infants at risk for developing severe retinopathy of prematurity (ROP). METHODS: Medical records from two tertiary referral centers with the diagnosis code "Retinopathy of Prematurity" were evaluated. Those with a birth weight of 1,500 g or less, gestational age of 30 weeks or younger, and unstable clinical courses were included. Multivariate regression analysis was applied to transform three independent variables into a growth rate algorithm. RESULTS: Seventeen of 191 neonates had severe ROP. Weight gain of at least 23 g/d was determined as a protective cut-off value against development of severe ROP. This value maintained 100% sensitivity with 62% specificity to ensure all neonates who require treatment would be captured. Overall, the Omaha (OMA)-ROP model calculated a 58% reduction in eye examinations within the cohort. CONCLUSIONS: Inclusion of postnatal growth rate in risk stratification will minimize the number of eye examinations performed without increasing adverse visual outcomes. The OMA-ROP model predicts neonates who gain less than 23 g/d are at higher risk for developing severe ROP. Although promising, larger cohort studies may be necessary to validate and implement new screening practices among preterm infants. [J Pediatr Ophthalmol Strabismus. 2018;55(5):326-334.].

Plus Disease in Retinopathy of Prematurity: More Than Meets the ICROP?

Retinopathy of prematurity (ROP), a vasoproliferative retinal disease affecting premature infants, is a leading cause of childhood blindness throughout the world. Plus disease, defined as venous dilatation and arteriolar tortuosity within the posterior retinal vessels greater than or equal to that of a standard published photograph, is the most critical finding in identifying treatment-requiring ROP. Despite an internationally accepted definition of plus disease, there is significant variability in diagnostic process and outcome, producing variable levels of reported intra- and interexpert agreement. Several potential explanations for poor agreement have been proposed, including attention to undefined vascular features such as venous tortuosity, focus on narrower or wider field of view, unfamiliarity with digital images, the magnification and apparent severity of the standard photograph, and cut-off point differences among experts as to the level of tortuosity and dilation sufficient for "plus disease" along a continuum. Moreover, differences in diagnostic consistency among groups of experts separated both geographically and chronologically have been reported. These findings have implications for clinical care, research, and education, and highlight the need for a more precise definition of plus disease and objective diagnostic methods for ROP.

Detection of Potentially Severe Retinopathy of Prematurity by Remote Image Grading.

Importance: Telemedicine in retinopathy of prematurity (ROP) has the potential for delivering timely care to premature infants at risk for serious ROP. Objective: To describe the characteristics of eyes at risk for ROP to provide insights into what types of ROP are most easily detected early by image grading. Design, Setting, and Participants: Secondary analysis of eyes with referral-warranted (RW) ROP (stage 3 ROP, zone I ROP, plus disease) on diagnostic examination from the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) study was conducted from May 1, 2011, to October 31, 2013, in 1257 premature infants with birth weights less than 1251 g in 13 neonatal units in North America. Data analysis was performed between February 1, 2016, and June 5, 2017. Interventions: Serial imaging sessions with concurrent diagnostic examinations for ROP. Main Outcomes and Measures: Time of detecting RW-ROP on image evaluation compared with clinical examination. Results: In the e-ROP study, 246 infants (492 eyes) were included in the analysis; 138 (56.1%) were male. A total of 447 eyes had RW-ROP on diagnostic examination. Image grading in 123 infants (mean [SD] gestational age, 24.8 [1.4] weeks) detected RW-ROP earlier than diagnostic examination (early) in 191 (42.7%) eyes by about 15 days and detected RW-ROP in 123 infants (mean [SD] gestational age, 24.6 [1.5] weeks) at the same time (same) in 200 (44.7%) eyes. Most of the early eyes (153 [80.1%]) interpreted as being RW-ROP positive on imaging evaluation agreed with examination findings when the examination subsequently documented RW-ROP. At the sessions in which RW-ROP was first found by examination, stage 3 or more in 123 infants (mean [SD] gestational age, 24.8 [1.4] weeks) ROP was noted earlier on image evaluation in 151 of 191 early eyes (79.1%) and in 172 of 200 of same eyes (86.0%) (P = .08); the presence of zone I ROP was detected in 57 of 191 (29.8%) early eyes vs 64 of 200 (32.0%) same eyes (P = .90); and plus disease was noted in 30 of 191 (15.7%) early eyes and 45 of 200 (22.5%) same eyes (P = .08). Conclusions and Relevance: In both early and same eyes, zone I and/or stage 3 ROP determined a significant proportion of RW-ROP; plus disease played a relatively minor role. In most early RW-ROP eyes, the findings were consistent with clinical examination and/or image grading at the next session. Because ROP telemedicine is used more widely, development of standard approaches and protocols is essential.

The relationship of the subtypes of preterm birth with retinopathy of prematurity.

BACKGROUND: Retinopathy of prematurity is an adverse outcome of preterm birth and is a leading cause of childhood blindness. The relationship between the subtypes of preterm birth with retinopathy of prematurity is understudied. OBJECTIVE: To investigate whether there is a difference in the incidence of type 1 or type 2 retinopathy of prematurity in infants with preterm birth resulting from spontaneous preterm labor, a medical indication of preterm birth, or preterm premature rupture of the membranes. STUDY DESIGN: A retrospective cohort study was conducted of 827 infants screened for retinopathy of prematurity who were delivered at a single tertiary care center in Colorado. All infants fulfilled the American Academy of Pediatrics 2013 screening criteria for retinopathy of prematurity defined as "infants with a birth weight of ≤1500 g or gestational age of 30 weeks or less (as defined by the attending neonatologist) and selected infants with a birth weight between 1500 and 2000 g or gestational age of >30 weeks with an unstable clinical course, including those requiring cardiorespiratory support and who are believed by their attending pediatrician or neonatologist to be at high risk for retinopathy of prematurity." Two independent reviewers masked to retinopathy of prematurity outcomes determined whether preterm birth resulted from spontaneous preterm labor, medical indication of preterm birth, or preterm premature rupture of the membranes. Discrepancies were resolved by a third reviewer. Data were analyzed with univariate and multivariable logistic regression. RESULTS: In our cohort, the frequency of preterm birth resulting from spontaneous preterm labor, medical indication of preterm birth, or preterm premature rupture of the membranes was 34%, 40%, and 26%, respectively. The mean gestational age (weeks, days) ± SD (range) in the cohort and across the preterm birth subtypes was as follows: entire cohort, 28 weeks, 6 days ± 2 weeks, 3 days (23 weeks, 3 days - 36 weeks, 4 days); spontaneous preterm labor, 28 weeks 1 day ± 2 weeks, 3 days (23 weeks, 3 days - 33 weeks, 4 days); medical indication of preterm birth, 29 weeks, 1 day ± 2 weeks, 2 days (24-36 weeks, 4 days); preterm premature rupture of the membranes, 28 weeks, 4 days ± 2 weeks, 1 day (24-33 weeks, 1 day). Among infants with type 1, type 2, or no retinopathy of prematurity, the incidence of type 1 or type 2 retinopathy of prematurity in births from spontaneous preterm labor, medical indication of preterm birth, and preterm premature rupture of the membranes was 37 of 218 (17%), 27 of 272 (10%), and 10 of 164 (6%), respectively. Adjusted for gestational age, birth weight, and multiparity and compared with the preterm premature rupture of the membranes group, the odds ratios of spontaneous preterm labor and medical indication of preterm birth for type 1 or type 2 retinopathy of prematurity were 6.1 (95% confidence interval, 1.8 to 20, P = .003) and 5.5 (95% confidence interval, 1.4 to 21, P = .01), respectively. Among neonates born after preterm premature rupture of the membranes, the probability of developing type 1 or type 2 retinopathy of prematurity was greatest in infants with rupture of membrane duration of up to 24 hours. After 24 hours, the probability of developing type 1 or type 2 retinopathy of prematurity declined. The odds of developing type 1 or type 2 retinopathy of prematurity was 9.0 (95% confidence interval 2.3 to 34, P = .002) in infants who had preterm premature rupture of the membranes ≤ 24 hours compared with infants who had preterm premature rupture of the membranes > 24 hours. CONCLUSION: Type 1 or type 2 retinopathy of prematurity are adverse ocular outcomes linked with not only lower gestational age and birth weight at delivery but also with events in the intrauterine environment that trigger a preterm birth. The reduced incidence of type 1 or type 2 retinopathy of prematurity in the preterm premature rupture of the membranes group compared with other causes of preterm birth may be related to the perinatal therapies associated with preterm premature rupture of the membranes (such as corticosteroids, antibiotics, maternal-fetal surveillance), which may have an inhibitory effect on the development of retinopathy of prematurity. We suggest that the physiologic events that predispose infants to type 1 or type 2 retinopathy of prematurity begin before delivery.

Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) is a vasoproliferative retinal disorder unique to premature infants. As premature births increase in many areas of the world, ROP has become a leading cause of childhood blindness. A better understanding of the pathogenesis of ROP, adherence to strict screening guidelines, and evolution of treatment options have reduced the number of sight-threatening complications from ROP.

Ranibizumab Injection as Primary Treatment in Patients with Retinopathy of Prematurity: Anatomic Outcomes and Influencing Factors.

PURPOSE: To investigate the anatomic outcomes and influencing factors of ranibizumab in the treatment of retinopathy of prematurity (ROP). DESIGN: Retrospective case series. PARTICIPANTS: A total of 283 eyes of 145 patients with type 1 ROP treated with intravitreal injection of ranibizumab (IVR) as primary treatment. METHODS: Retrospective review of infants who were diagnosed with type 1 ROP and accepted IVR (0.25 mg/0.025 ml) as primary treatment from January 2012 to August 2015. The anatomic outcomes and the influencing factors were analyzed. MAIN OUTCOME MEASURES: Anatomic outcomes of ROP eyes after IVR and the influencing factors. RESULTS: A total of 283 eyes of 145 patients were included in this study. There were a total of 266 eyes (94.0%) in the positive response group and 17 eyes (6.0%) in the negative/no response group after IVR. Within the positive response group, 139 eyes (48.6%) were in the regression without reactivation subgroup, and 127 eyes (44.9%) were in the regression with reactivation subgroup. A total of 152 eyes received additional laser or surgical treatment. At the last visit, 278 eyes (98.2%) had attached retinas, and 5 eyes (1.8%) had retinal detachment. A classification tree model showed that for patients with gestational age (GA) ≤29.5 weeks, the possibility of experiencing reactivation after IVR is higher than that of those with GA >29.5 weeks (61.6% vs. 29.6%). Moreover, for patients with GA ≤29.5 weeks, those diagnosed with zone II stage 2+ ROP have a lower possibility of experiencing reactivation than other patients (37.9% vs. 80%). CONCLUSIONS: Intravitreal injection of ranibizumab seemed to be effective in treating patients with ROP. After treatment, there were primarily 3 different outcomes. Our predictive tree model is helpful for ophthalmologists to evaluate the risk of reactivation.

Intraocular Hemorrhages and Retinopathy of Prematurity in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study.

PURPOSE: To describe the clinical characteristics of intraocular hemorrhages (IOHs) in infants in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study and to evaluate their potential use for prediction of disease severity. DESIGN: Secondary data analysis from a prospective study. PARTICIPANTS: Preterm infants with birth weight (BW) ≤1250 g. METHODS: Infants underwent serial digital retinal imaging in both eyes starting at 32 weeks' postmenstrual age. Nonphysician trained readers (TRs) evaluated all image sets from eyes that ever had IOHs documented on image evaluation or eye examination for the presence, location, type, area, and relation of the IOH to the junction between vascularized and avascular retina. Associations of IOH with demographic and neonatal factors, and with the presence and severity of retinopathy of prematurity (ROP) were investigated by univariate and multivariate analyses. Sensitivity and specificity of the telemedicine system for detecting referral-warranted ROP (RW-ROP) were calculated with and without incorporating hemorrhage into the standardized grading protocol. MAIN OUTCOME MEASURES: Retinal and vitreous hemorrhage. RESULTS: Among 1239 infants (mean [standard deviation] BW = 864 [212] g; gestational age [GA] = 27 [2.2] weeks) who underwent an average of 3.2 imaging sessions, 22% had an IOH in an eye on at least 1 of the e-ROP visits. Classification of IOH was preretinal (57%), blot (57%), dot (38%), flame-shaped (16%), and vitreous (8%); most IOHs were unilateral (70%). The IOH resolved in 35% of eyes by the next imaging session and in the majority (76%) of cases by 8 weeks after initial detection. Presence of IOH was inversely associated with BW and GA and significantly associated (P < 0.0001) with the presence and severity of ROP (BW and GA adjusted odds ratios [ORs] of 2.46 for any ROP, 2.88 for stage 3, and 3.19 for RW-ROP). Incorporating IOH into the grading protocol minimally altered the sensitivity of the system (94% vs. 95%). CONCLUSIONS: Approximately 1 in 5 preterm infants examined had IOHs, generally unilateral. The presence of hemorrhage was directly correlated with both presence and severity of ROP and inversely correlated with BW and GA, although including hemorrhage in the grading algorithm only minimally improved the sensitivity of the telemedicine system to detect RW-ROP.