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The International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), acknowledged that plus-like retinopathy of prematurity (ROP) vascular changes occurs along a spectrum. Historically, clinician-experts demonstrate variable agreement for plus diagnosis. We developed a 9-photograph reference image set for grading plus-like changes and compared intergrader agreement of the set with standard grading with no plus, preplus, and plus disease. Retinal photographic grading and expert consensus opinion. The development set included 34 international ICROP3 committee members. The validation set included 30 ophthalmologists with ROP expertise (15 ICROP3 committee members and 15 non-ICROP3 members) Nine ROP fundus images (P1 through P9) representing increasing degrees of zone I vascular tortuosity and dilation, based on the 34 ICROP3 committee members' gradings and consensus image reviews, were used to establish standard photographs for the plus (P) score. Study participants graded 150 fundus photographs 2 ways, separated by a 1-week washout period: (1) no plus, preplus, or plus disease and (2) choosing the closest P score image. Intergrader agreement measured by intraclass correlation coefficient. Intergrader agreement was higher using the P score (intraclass correlation coefficient, 0.75; 95% confidence interval, 0.71–0.79) than no plus, preplus, or plus disease (intraclass correlation coefficient, 0.67; 95% confidence interval, 0.62–0.72). Mean ± standard deviation P scores for images with mode gradings of no plus, preplus, and plus disease were 2.5 ± 0.7, 4.8 ± 0.8, and 7.4 ± 0.8, respectively. Intergrader agreement of plus-like vascular change in ROP using the P score is high. We now incorporate this 9-image reference set into ICROP3 for use in clinician daily practice alongside zone, stage, and plus assessment. P score is not yet meant to replace plus diagnosis for treatment decisions, but its use at our institutions has permitted better comparison between examinations for progression and regression, communication between examiners, and documentation of vascular change without fundus imaging. P score also could provide more detailed ROP classification for clinical trials, consistent with the spectrum of plus-like change that is now formally part of the International Classification of Retinopathy of Prematurity. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Abstract Background We present a patient with retinopathy of prematurity (ROP) who developed worsening plus disease after complete regression of stage 3 ROP. The use of fundus fluorescein angiography (FFA) aided the visualization of occult neovascularization that caused the disease progression. Case presentation The patient was at high risk for ROP due to low birth weight of 690 g and gestational age of 25 weeks. After the diagnosis of stage 3 ROP in zone I without plus disease, she was treated initially with bilateral intravitreal bevacizumab (IVB) and followed by laser photocoagulation 5 weeks later. Despite the resolution of ROP stage, the plus disease worsened. Neither systemic risk factors nor skip laser areas were observed. Hence, FFA was performed and subsequently identified occult neovascularization with active leakage. Additional IVB and laser treatment in the capillary dropout area inside vascularized retina were added. The plus disease improved but mild arteriolar tortuosity persisted. Conclusions Worsening of plus disease after completion of laser ablation and IVB with complete regression of stage 3 ROP is rare. Systemic risk factors such as continuous oxygen therapy and cardiovascular disease should be ruled out. FFA aided in identifying occult neovascularization and prompted further treatment.

Background: We present a patient with retinopathy of prematurity (ROP) who developed worsening plus disease after complete regression of stage 3 ROP. The use of fundus fluorescein angiography (FFA) aided the visualization of occult neovascularization that caused the disease progression. Case presentation: The patient was at high risk for ROP due to low birth weight of 690 g and gestational age of 25 weeks. After the diagnosis of stage 3 ROP in zone I without plus disease, she was treated initially with bilateral intravitreal bevacizumab (IVB) and followed by laser photocoagulation 5 weeks later. Despite the resolution of ROP stage, the plus disease worsened. Neither systemic risk factors nor skip laser areas were observed. Hence, FFA was performed and subsequently identified occult neovascularization with active leakage. Additional IVB and laser treatment in the capillary dropout area inside vascularized retina were added. The plus disease improved but mild arteriolar tortuosity persisted. Conclusions: Worsening of plus disease after completion of laser ablation and IVB with complete regression of stage 3 ROP is rare. Systemic risk factors such as continuous oxygen therapy and cardiovascular disease should be ruled out. FFA aided in identifying occult neovascularization and prompted further treatment. [ABSTRACT FROM AUTHOR]

Retinopathy of Prematurity is a leading cause of visual impairment in preterm infants and is characterized by dilation and tortuosity of the retinal blood vessels in the plus disease stage. However, the diagnosis of plus disease is subjective and qualitative; hence, quantitative methods and computer-based image analysis are required to improve the objectivity of the diagnosis. In this study, we proposed a computer-based image analysis method aimed at segmenting blood vessels and the optic disc in retinal images and providing quantitative features of the vessels to assist doctors in diagnosing plus disease. This method comprises two main stages. In the first stage, we used fundus images of a preterm infant with manually annotated vessel segmentation labels to train U-Net3 network, which is a U-Net network with the dual attention modules. Simultaneously, we used images with optic disc segmentation labels to train U-Net1 network, which is a U-Net network with half of the channels. The F1 score of the vessel segmentation network was 0.8116, and the sensitivity was 0.8273. The F1 score of the optic disc segmentation network was 0.9346, with a sensitivity of 0.9395. In the second stage, we calculated the vessel tortuosity in different retinal regions of the vessel segmentation images using least-squares linear regression. In addition, we computed the vessel density and width within the optimal region of interest, which is defined as a radius four times the diameter of the optic disc. The quantitative results revealed that the vessel tortuosity, density, and width obtained in this study can be used as diagnostic features.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness affecting the retina of low birth weight preterm infants. Plus disease in ROP characterised by abnormal tortuosity and dilation of posterior retinal blood vessels, is a benchmark that identifies treatment-requiring ROP cases. A Plus disease classifier with zero false negatives is a major requirement of an ROP screening system. In this paper, an efficient Artificial Neural Network (ANN) architecture with an optimal feature set is proposed which meets the above requirement. A total of 178 images with 81(45%) Plus and 97 (55%) No Plus are used for the analysis. A feature set derived from transform domain representation of retinal funds images is used along with the existing vascular features in the proposed work. Wavelet and Curvelet transforms are considered for deriving the additional feature set in the experimental analysis. The feature set containing Curvelet transform energy coefficient along with the vascular features gave an Accuracy of 96% and Specificity of 93% with 100% Sensitivity. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity (ROP), sometimes known as Terry syndrome, is an ophthalmic condition that affects premature babies. It is the main cause of childhood blindness and morbidity of vision throughout life. ROP frequently coexists with a disease stage known as Plus disease, which is marked by severe tortuosity and dilated retinal blood vessels. The goal of this research is to create a diagnostic technique that can discriminate between infants with Plus disease from healthy subjects. Blood vascular tortuosity is used as a prognostic indicator for the diagnosis. We examine the quantification of retinal blood vessel tortuosity and propose a computer-aided diagnosis system that can be used as a tool for ROP identification. Deep neural networks are used in the proposed approach to segment retinal blood vessels, which is followed by the prediction of tortuous vessel pixels in the segmented vessel map. Digital fundus images obtained from Retcam3 TM is used for screening. We use a proprietary data set of 289 infant retinal images (89 with Plus disease and 200 healthy) from Narayana Nethralaya in Bangalore, India, to illustrate the efficacy of our methodology. The findings of this study demonstrate the reliability of the proposed method as a computer-aided diagnostic tool that can help medical professionals make an early diagnosis of ROP. [ABSTRACT FROM AUTHOR]

Ihab Abdel Aziz,1 Mohamed Fawzy Alsoda,2 Tarek Mohamed Elmenofy,1 Mohamed Medhat Sakhsoukh,1 Noha Mohamed Abd el Azim,1 Amr Mahmoud Ahmed,1 Sohaila Ali Abd El-Halim,3 Sherine Salaheldin Hassan Baris,3 Yousef Ahmed Fouad,4 Ayman Mohyieldin Elghonemy,1 Heba Metwally,1 Wael Mohamed El Gendy,1 Raghdaa Ali,2 Yehia Mahmoud Basha,5 Eman Abo ElMaaty Mohamed,6 Wafaa Mohamed Amin,6 Maged Adly Naguib,1 Hazem Abdallah Elnashar1 1Department of Ophthalmology, The Memorial Institute for Ophthalmic Research, Giza, Egypt; 2Department of Pediatrics and Neonatology, Ahmed Maher Teaching Hospital, Cairo, Egypt; 3Department of Pediatrics and Neonatology, Mataria Teaching Hospital, Cairo, Egypt; 4Department of Ophthalmology, Ain Shams University Hospitals, Cairo, Egypt; 5Department of Pediatrics and Neonatology, Damanhour Teaching Hospital, Beheira, Egypt; 6Department of Pediatrics and Neonatology, El-Galaa Teaching Hospital, Cairo, EgyptCorrespondence: Hazem Abdallah Elnashar, Department of Ophthalmology, The Memorial Institute for Ophthalmic Research, Giza, 23314, Egypt, Tel +201227011043, Email Dr.hazemelnashar@gmail.comBackground: Retinopathy of prematurity (ROP) is increasing in incidence in developing nations, including Egypt. Secondary prevention requires timely detection through the development of regional screening guidelines, which should be preceded by large-scale studies to characterize the population at risk.Methods: A prospective, multicentric exploratory study that included five large tertiary institutions in an urban Egyptian setting. All infants born with gestational age (GA) < 37 weeks and/or birth weight (BW) ≤ 2000 grams were screened. More mature and heavier infants with unstable clinical course were also included. The primary outcome measure was the rate of ROP and high-risk disease occurrence in relation to underlying risk factors.Results: Of the 768 eyes (384 screened infants), 347 eyes (45.2%) had stage 1 or higher disease, and 43 eyes (5.6%) had high-risk disease. Eyes with stage 1 or higher ROP and treatment-requiring ROP had a mean (± SD) GA of 33.4 (± 2.6) weeks and 32.8 (± 3.2) weeks, and BW of 1842.3 (± 570.1) grams and 1747.6 ± (676.2) grams, respectively. Treatment-requiring eyes belonged to infants that had significantly lower GA and significantly higher prevalence of co-morbidities than non-treatment-requiring eyes.Conclusion: The incidence of ROP and high-risk disease in an urban Egyptian setting are similar to those in comparable settings elsewhere and locally. This exploratory study supports tailoring local screening criteria for ROP, and may aid the future development of national guidelines.Keywords: retinopathy of prematurity, ROP, screening, plus disease, preterm

Objectives: To evaluate the feasibility of a novel and simple smart phone-based Retinopathy of Prematurity (ROP) screening approach in a resource-constrained setting. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

BackgroundInadequate screening of treatment-warranted retinopathy of prematurity (ROP) can lead to devastating visual outcomes. Especially in resource-poor communities, the use of an affordable, portable, and easy to use smartphone-based non-contact fundus photography device may prove useful for screening for high-risk ROP. This study evaluates the feasibility of screening for high-risk ROP using a novel smartphone-based fundus photography device, RetinaScope.MethodsRetinal images were obtained using RetinaScope on a cohort of prematurely born infants during routine examinations for ROP. Images were reviewed by two masked graders who determined the image quality, the presence or absence of plus disease, and whether there was retinopathy that met predefined criteria for referral. The agreement between image-based assessments was compared to the gold standard indirect ophthalmoscopic assessment.ResultsFifty-four eyes of 27 infants were included. A wide-field fundus photograph was obtained using RetinaScope. Image quality was acceptable or excellent in 98% and 95% of cases. There was substantial agreement between the gold standard and photographic assessment of presence or absence of plus disease (Cohen's κ = 0.85). Intergrader agreement on the presence of any retinopathy in photographs was also high (κ = 0.92).ConclusionsRetinaScope can capture digital retinal photographs of prematurely born infants with good image quality for grading of plus disease.

Inter-clinician variation could cause uncertainty in disease management. This is reported to be high in Retinopathy of Prematurity (ROP), a potentially blinding retinal disease affecting premature infants. Machine learning has the potential to quantify the differences in decision-making between ROP specialists and trainees and may improve the accuracy of diagnosis. An anonymized survey of ROP images was administered to the expert(s) and the trainee(s) using a study-designed user interface. The results were analyzed for repeatability as well as to identify the level of agreement in the classification. "Ground truth" was prepared for each individual and a unique classifier was built for each individual using the same. The classifier allowed the identification of the most important features used by each individual. Correlation and disagreement between the expert and the trainees were visualized using the Dipstick™ diagram. Intra-clinician repeatability and reclassification statistics were assessed for all. The repeatability was 88.4% and 86.2% for two trainees and 92.1% for the expert, respectively. Commonly used features differed for the expert and the trainees and accounted for the variability. This novel, automated algorithm quantifies the differences using machine learning techniques. This will help audit the training process by objectively measuring differences between experts and trainees. Training for image-based ROP diagnosis can be more objectively performed using this novel, machine learning-based automated image analyzer and classifier. [ABSTRACT FROM AUTHOR]

Background: Retinopathy of prematurity (ROP) is increasing in incidence in developing nations, including Egypt. Secondary prevention requires timely detection through the development of regional screening guidelines, which should be preceded by large-scale studies to characterize the population at risk. Methods: A prospective, multicentric exploratory study that included five large tertiary institutions in an urban Egyptian setting. All infants born with gestational age (GA) < 37 weeks and/or birth weight (BW) ≤ 2000 grams were screened. More mature and heavier infants with unstable clinical course were also included. The primary outcome measure was the rate of ROP and high-risk disease occurrence in relation to underlying risk factors. Results: Of the 768 eyes (384 screened infants), 347 eyes (45.2%) had stage 1 or higher disease, and 43 eyes (5.6%) had high-risk disease. Eyes with stage 1 or higher ROP and treatment-requiring ROP had a mean (± SD) GA of 33.4 (± 2.6) weeks and 32.8 (± 3.2) weeks, and BW of 1842.3 (± 570.1) grams and 1747.6 ± (676.2) grams, respectively. Treatment-requiring eyes belonged to infants that had significantly lower GA and significantly higher prevalence of co-morbidities than non-treatment-requiring eyes. Conclusion: The incidence of ROP and high-risk disease in an urban Egyptian setting are similar to those in comparable settings elsewhere and locally. This exploratory study supports tailoring local screening criteria for ROP, and may aid the future development of national guidelines. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the relationship between the severity of type 1 retinopathy of prematurity (ROP) and the level of vascular endothelial growth factor (VEGF) in aqueous fluid. Methods: The aqueous VEGF levels of 49 patients (88 eyes) with type 1 ROP were retrospectively analyzed. These eyes were categorized into three groups according to the severity of disease: aggressive retinopathy of prematurity (A-ROP), threshold of ROP (T-ROP), and type 1 pre-threshold ROP (P-T-1). The differences in aqueous VEGF levels among these three groups were compared. The relationship between the aqueous VEGF level and the retinal changes of ROP, including the vessel tortuosity in zone I, and the location and stage of the ROP lesions, were also analyzed. Results: The aqueous VEGF level of the A-ROP group was the highest among the three groups, followed by those of the T-ROP and P-T-1 groups. The aqueous VEGF level was negatively correlated with the zone and the stage of the ROP diseases, while it was positively correlated with the venous tortuosity in zone I and had no relevance with the artery tortuosity in zone I. Conclusions: The aqueous VEGF level in A-ROP was the highest in type I ROP. The location of the ROP lesions and the venous tortuosity in zone I correlated with the aqueous VEGF level and could indicate the severity of ROP. [ABSTRACT FROM AUTHOR]

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.

Insufficient effectiveness of laser coagulation of the avascular retinal areas in retinopathy of prematurity (ROP) plus-disease in zone I and aggressive posterior retinopathy of prematurity (APROP) requires new treatment approaches, based on the regulation of retinal angiogenesis and anti-VEGF drugs use. The BEAT-RAP study, which was the first major randomized study of anti-VEGF therapy in ROP, revealed a higher effectiveness of bevacizumab compared to retinal laser coagulation in stage 3 plus-disease of zone I. A prospective randomized trial, RAINBOW, demonstrated the effectiveness of ranibizumab in plus-disease stages 1, 2 and 3 in zone I and stage 3 in zone II and in APROP, so that the drug may be recommended for use in children with ROP. The demonstrated high effect of anti-VEGF therapy in ROP is consistent with our own data. Anti-VEGF therapy opens up new possibilities in the treatment of a particular class of ROP forms. The advantages of anti-VEGF therapy include higher clinical effectiveness of treatment of ROP type I with localization in the posterior pole (I and posterior II zone), absence of "blockage" of the peripheral retina, lower frequency of myopia development and degree, relative fastness of the procedure, the acceptability for patients whose fundus is difficult to visualize, and somatically burdened patients who are contraindicated for prolonged anesthesia used for retinal laser coagulation. When using anti-VEGF drugs in the post-threshold stages of the disease, one should take account of an increased risk of proliferation progression and retinal detachment development. Premature infants with retinopathy regression after anti-VEGF therapy require a longer duration of regular and frequent follow-up (up to 70 weeks of postmenstrual age) due to the risk of relapse and extraretinal proliferation in future.

Clinical relevance: Retinopathy of prematurity is a preventable blinding disorder worldwide. Laser photocoagulation is said to be the gold standard care of treatment. However, various factors are known to affect the outcome.Background: The purpose of this study was to analyse the risk factors in patients with laser treatment requiring retinopathy of prematurity (ROP) and the outcome of 532 nm Nd:YAG laser photocoagulation (LP).Methods: Patients who underwent LP for ROP at a tertiary referral centre between January 2012 and January 2019 were enrolled. Those who were born and followed-up at the institution of the authors were in Group 1 and those who were born and followed-up elsewhere and referred to the authors for treatment were in Group 2. The clinical features, gestational ages, birth weights, and data regarding the treatment were retrospectively reviewed. The need for pars plana vitrectomy was taken as a poor outcome.Results: The mean gestational age and birth rate was 26.7 ± 1.9 weeks and 927.2 ± 263.5 grams, respectively, in Group 1 (57 infants, 111 eyes); and 28.5 ± 2.5 weeks and 1174.8 ± 385 grams, respectively, in Group 2 (66 infants, 131eyes) (p < 0.001 for both). The extent of the disease (p < 0.001), the zone of the disease (p = 0.002), and the timing of LP (p < 0.001) were significantly different between groups. In the whole cohort, the zone (p = 0.006) and stage (p < 0.001) of the disease, aggressive posterior disease (p = 0,009), and tunica vasculosa lentis were found to significantly interfere with the outcome.Conclusion: Eyes with more severe disease undergoing timely treatment and eyes with less severe disease undergoing delayed management had similar prognosis. A favourable outcome was obtained with 532 nm green laser in ROP. [ABSTRACT FROM AUTHOR]

Purpose: To compare objectively measured changes in plus disease after bevacizumab and laser for Type 1 retinopathy of prematurity. Methods: ROPtool (a computer program) analyzed fundus images at baseline, 1 week, and subsequent examinations. Results: Six infants (9 eyes) were treated with bevacizumab and 7 (12 eyes) with laser. One week after treatment, bevacizumab compared with laser resulted in a greater median percent change from pretreatment in tortuosity (-53.8 vs. -0.2%, P, 0.001) and overall plus disease (-20.1 vs. -3.1%, P, 0.001). Change in dilation did not differ (-3.5 vs. -5.5%, P = 0.48). After week 1, all median ROPtool parameters continued to decrease for both groups. At last follow-up (median 3, range: 2-10 weeks), both bevacizumab and laser significantly decreased tortuosity (-54.3 and -23.8%), dilation (-8.7 and -7.5%), and overall plus disease (-27.3 and -10.3%). Conclusion: Improvement in plus disease, in particular tortuosity, likely occurs more quickly after bevacizumab compared with laser, particularly at 1 week after treatment. These results guide clinical expectations for plus disease resolution after both treatment modalities. [ABSTRACT FROM AUTHOR]

Background: Color Doppler imaging (CDI) is a non-aggressive and safe technique for the clinical management of retinal diseases. Recently, the number of infants with retinopathy of prematurity (ROP) has increased due to the incidence of premature births. Objectives: This study aimed to compare the CDI criteria for the ophthalmic artery (OA) and central retinal artery (CRA) in ROP infants with and without plus disease. Patients and Methods: In this case-control study, 42 premature infants (21 infants with plus disease and 21 infants without plus disease) underwent CDI. The arterial CDI parameters, including end-diastolic velocity (EDV), pulsatility index (PI), resistance index (RI), and peak systolic velocity (PSV), were measured in these patients. After collecting the data, t-test and chi-square tests were used for data analysis. P < 0.05 was considered to be statistically significant. Results: The mean EDV of CRA in patients with and without plus disease was 4.35 ± 1.00 and 5.27 ± 1.02 cm/sec, respectively (P = 0.005). The mean PSV of CRA in patients with and without plus disease was 15.65 ± 3.35 and 18.39 ± 4.39 cm/sec, respectively (P = 0.029). However, no significant difference was found between the two groups in terms of PSV or EDV of OA (P > 0.05). Also, no significant difference was observed between the two groups considering the RI and PI of CRA and OA(P> 0.05). Conclusion: According to the findings of this study, CDI criteria, such as EDV and PSV of CRA, were significantly lower in infants with plus disease as compared to those without plus disease. Since detecting the early stages of plus disease is a challenge for ophthalmologists, assessment of these criteria can be helpful for differentiation of these two subgroups of patients. However, further studies with a larger sample size are needed to determine the cutoff value. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity (ROP) is an eye disorder that mainly affects fundus vasculature of immature infants. The effect of this disease can be mild with no observable impairments or may become severe with neovascularization, leading to retinal detachment and possibly childhood blindness. A vital sign for initiating treatment for ROP is the detection of Plus disease, which is clinically diagnosed by identifying certain morphological changes to the blood vessels present in the retina of preterm infants. The main goal of this study is to develop a diagnostic method that can distinguish between Plus-diseased and healthy infant retinal images. This work utilizes a fully convolutional deep learning architecture for achieving the desired objective. We use a semi-supervised learning technique for training the network. The proposed technique accurately predicts bounding boxes over the tortuous vessel segments present in an infant retinal image. The count of bounding boxes serve as a measure to quantify tortuosity. We also compare the proposed technique with a recently introduced ROP diagnostic method employing U-COSFIRE filters. We show the efficacy of the proposed methodology on a proprietary data set of 289 infant retinal images (89 with ROP, and 200 healthy), obtained from KIDROP Bangalore, India. We obtain sensitivity (true positive rate) and specificity (true negative rate) equal to 0.99 and 0.98, respectively in the experimented data set. The results obtained in this study show the robustness of the proposed pipeline, as a computer aided diagnostic tool, that can augment medical experts in the early diagnosis of ROP. [ABSTRACT FROM AUTHOR]

AIM: To evaluate the effect of intravitreal ranibizumab injection for retinopathy of prematurity (ROP) in Zone II Stage 3+. METHODS: Data was collected for ROP patients with Zone II Stage 3+ who received intravitreal ranibizumab injections between October 2014 and Janu­ary 2017 at the Department of Ophthalmology in our hospital. No prior laser or other intravitreal treatment was done. Prior to the intervention and at each follow-up visit, fundus examination was performed. Gestational age at birth, sex, birth weight, ROP zone, ROP stage, post menstrual age (PMA) at treatment, and follow-up pe­riod were recorded. The final clinical status of the retina was evaluated for each patient. The primary outcome mea­sures included ROP recurrences requiring re-treatment, complete or incomplete peripheral vascularization. RESULTS: Eighty-six eyes of 46 premature infants with Zone II Stage 3+ ROP were enrolled in the study. The mean gestational age at birth was 28.18±1.67 (range: 25 to 33)wk and the mean birth weight was 1070.57±226.85 (range: 720.00 to 1650.00) g. The mean PMA at treatment was 38.32±2.99 (range: 32.29 to 46.00)wk. Seventy-one eyes (82.56%) were treated success­fully with intravitreal ranibizumab as monotherapy. Fifteen eyes (17.44%) developed recurrent disease. The mean interval between the treatment and retreatment was 5.96±3.22 (range: 1.86 to 11.71)wk. All eyes vascularized into zone III at the end of the study and among them 62 eyes (72.09%) achieved complete vascu­larization. CONCLUSION: Intravitreal ranibizumab injection is an effective treatment in Zone II Stage 3+ ROP patients. More patients with longer follow-up duration are necessary to confirm the safety and efficacy of this treatment.

Background: The purpose of this study was to develop an automated diagnosis and quantitative analysis system for plus disease. The system provides a diagnostic decision but also performs quantitative analysis of the typical pathological features of the disease, which helps the physicians to make the best judgement and communicate the decisions. Methods: The deep learning network provided segmentation of the retinal vessels and the optic disc (OD). Based on the vessel segmentation, plus disease was classified and tortuosity, width, fractal dimension and vessel density were evaluated automatically. Results: The trained network achieved a sensitivity of 95.1% with 97.8% specificity for the diagnosis of plus disease. For detection of preplus or worse, the sensitivity and specificity were 92.4% and 97.4%. The quadratic weighted k was 0.9244. The tortuosities for the normal, preplus and plus groups were 3.61 ± 0.08, 5.95 ± 1.57 and 10.67 ± 0.50 (104 cm−3). The widths of the blood vessels were 63.46 ± 0.39, 67.21 ± 0.70 and 68.89 ± 0.75 μm. The fractal dimensions were 1.18 ± 0.01, 1.22 ± 0.01 and 1.26 ± 0.02. The vessel densities were 1.39 ± 0.03, 1.60 ± 0.01 and 1.64 ± 0.09 (%). All values were statistically different among the groups. After treatment for plus disease with ranibizumab injection, quantitative analysis showed significant changes in the pathological features. Conclusions: Our system achieved high accuracy of diagnosis of plus disease in retinopathy of prematurity. It provided a quantitative analysis of the dynamic features of the disease progression. This automated system can assist physicians by providing a classification decision with auxiliary quantitative evaluation of the typical pathological features of the disease. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity (ROP) is the interruption of the physiological development of retinal vascularization due to preterm delivery and is a proliferative vitreoretinopathy characterized by an evolving pathological process. Many innovations have emerged in the naming, screening, follow-up, and treatment of the disease in the 70 years since then first defined by Terry. This review is an examination of this difficult and dynamic area of modern-day ophthalmology practice in the light of current information.

This is a case report which highlights the challenges faced in treating Type 1 early treatment of retinopathy of prematurity (ETROP) with corneal haze. We report a case of a preterm boy born at 28 weeks with birth weight of 1000 g who presented with corneal haze along with Type 1 ETROP. Because of inability to complete LASER and increase in posterior plus disease , intravitreal ranibizumab was given as a rescue therapy to buy time. Finally, we could succeed in treating the disease with complete regression and clear cornea on the last follow-up.

Background: Inadequate screening of treatment-warranted retinopathy of prematurity (ROP) can lead to devastating visual outcomes. Especially in resource-poor communities, the use of an affordable, portable, and easy to use smartphone-based non-contact fundus photography device may prove useful for screening for high-risk ROP. This study evaluates the feasibility of screening for high-risk ROP using a novel smartphone-based fundus photography device, RetinaScope. Methods: Retinal images were obtained using RetinaScope on a cohort of prematurely born infants during routine examinations for ROP. Images were reviewed by two masked graders who determined the image quality, the presence or absence of plus disease, and whether there was retinopathy that met predefined criteria for referral. The agreement between image-based assessments was compared to the gold standard indirect ophthalmoscopic assessment. Results: Fifty-four eyes of 27 infants were included. A wide-field fundus photograph was obtained using RetinaScope. Image quality was acceptable or excellent in 98% and 95% of cases. There was substantial agreement between the gold standard and photographic assessment of presence or absence of plus disease (Cohen's κ = 0.85). Intergrader agreement on the presence of any retinopathy in photographs was also high (κ = 0.92). Conclusions: RetinaScope can capture digital retinal photographs of prematurely born infants with good image quality for grading of plus disease. [ABSTRACT FROM AUTHOR]

• Plus disease is a major indicator of treatment-grade retinopathy of prematurity. • The segmentation stage efficiently extracts blood vessels of varying width and length. • Using the features leaf node count and vessel density improves plus disease detection. • The proposed system would be highly useful in a tele-ophthalmology environment. Retinopathy of Prematurity (ROP) is a blinding disease affecting the retina of low birth-weight preterm infants. Accurate diagnosis of ROP is essential to identify treatment-requiring ROP, which would help to prevent childhood blindness. Plus disease, which characterizes abnormal twisting, widening and branching of the blood vessels, is a significant symptom of treatment requiring ROP. In this paper, we have developed and evaluated a computer-based analysis system for objective assessment of plus disease in ROP, which best mimics the clinical method of disease diagnosis by identifying unique vessel based features. The proposed system consists of an initial segmentation stage, which will efficiently extract blood vessels of varying width and length by utilizing structure adaptive filtering, connectivity analysis and image fusion. The paper proposes the usage of additional retinal features namely leaf node count and vessel density, to portray the abnormal growth and branching of the blood vessels and to complement the commonly used features namely tortuosity and width. The test results show a better classification of plus disease in terms of sensitivity (95%) and specificity (93%), emphasizing the superiority of the proposed segmentation algorithm and vessel-based features. An additional advantage of the proposed system is that the process of selection of relevant vessels for feature extraction is fully automated, which makes the system highly useful to the non-physician graders, owing to the unavailability of a sufficient number of ROP specialists. [ABSTRACT FROM AUTHOR]

Purpose: Retinopathy of prematurity (ROP) is a retinal vascular disease affecting premature infants that can culminate in blindness within days if not monitored and treated. A disease stage for scrutiny and administration of treatment within ROP is "plus disease" characterized by increased tortuosity and dilation of posterior retinal blood vessels. The monitoring of ROP occurs via routine imaging, typically using expensive instruments ($50 to $140 K) that are unavailable in low-resource settings at the point of care., Approach: As part of the smartphone-ROP program to enable referrals to expert physicians, fundus images are acquired using smartphone cameras and inexpensive lenses. We developed methods for artificial intelligence determination of plus disease, consisting of a preprocessing pipeline to enhance vessels and harmonize images followed by deep learning classification. A deep learning binary classifier (plus disease versus no plus disease) was developed using GoogLeNet., Results: Vessel contrast was enhanced by 90% after preprocessing as assessed by the contrast improvement index. In an image quality evaluation, preprocessed and original images were evaluated by pediatric ophthalmologists from the US and South America with years of experience diagnosing ROP and plus disease. All participating ophthalmologists agreed or strongly agreed that vessel visibility was improved with preprocessing. Using images from various smartphones, harmonized via preprocessing (e.g., vessel enhancement and size normalization) and augmented in physically reasonable ways (e.g., image rotation), we achieved an area under the ROC curve of 0.9754 for plus disease on a limited dataset., Conclusions: Promising results indicate the potential for developing algorithms and software to facilitate the usage of cell phone images for staging of plus disease., (© 2023 The Authors.)

Retinopathy of prematurity (ROP) is caused by abnormal retinal vascularization in premature infants that has the potential for severe long-term vision impairment. Recent advancements in handheld optical coherence tomography (OCT) have enabled noninvasive, high-resolution, cross-sectional imaging of the infant eye at the bedside. The use of handheld OCT devices in the diagnosis of ROP in premature infants has furthered our understanding of disease state and progression. This review discusses the known and novel biomarkers of ROP severity in premature infants identified through handheld OCT and potential for future directions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Kubsad, Ohan, Wu and Cabrera.)

Purpose To review the incidence and risk factors for retinopathy of prematurity (ROP) King Faisal Specialist Hospital and King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Material and methods In this prospective cohort study, preterm infants who were admitted to a neonatal intensive care unit from 2012 to 2013 were evaluated for ROP. Inclusion criteria were, preterm infants with gestational age <32 weeks and/or birth weight <1500 g. The risk factors that were assessed were intraventricular hemorrhage, patent ductus arteriosus (PDA), sepsis and hydrocephalus. The relative risk was used to measure the risk and logistic regression was used to adjust for confounding factors. Statistical significance was indicated by p < 0.05. Results Thirty-one of 92 (33.7%) preterm infants had unilateral or bilateral ROP. The mean gestational age was 26.7 weeks (range, 24–29 weeks) and mean birth weight was 0.843 kg (range, 0.606–1.450 kg). There were 7 infants with stage 1 ROP, 10 infants with stage 2, 14 infants with stage 3 and no cases of stage 4 or 5. Twelve (13%) infants had plus disease and received laser therapy within 72 h of diagnosis. Statistically significant risk factors for ROP were PDA ( p = 0.0005) and intraventricular hemorrhage ( p = 0.0005). Conclusion The incidence of ROP was 33.7% and risk factors were PDA and intraventricular hemorrhage. Laser therapy was very effective for the treatment of plus disease and preventing progression of ROP. Clinicians should assess for potential risk factors when monitoring premature infants. [ABSTRACT FROM AUTHOR]

Retinal arterial tortuosity and venous dilation are hallmarks of plus disease, which is a severe form of retinopathy of prematurity (ROP). In this study, we examined whether short-term interruption of vascular endothelial growth factor (VEGF) signals leads to the formation of severe ROP-like abnormal retinal blood vessels. Neonatal rats were treated subcutaneously with the VEGF receptor (VEGFR) tyrosine kinase inhibitors, KRN633 (1, 5, or 10 mg/kg) or axitinib (10 mg/kg), on postnatal day (P) 7 and P8. The retinal vasculatures were examined on P9, P14, or P21 in retinal whole-mounts stained with an endothelial cell marker. Prevention of vascular growth and regression of some preformed capillaries were observed on P9 in retinas of rats treated with KRN633. However, on P14 and P21, density of capillaries, tortuosity index of arterioles, and diameter of veins significantly increased in KRN633-treated rats, compared to vehicle (0.5% methylcellulose)-treated animals. Similar observations were made with axitinib-treated rats. Expressions of VEGF and VEGFR-2 were enhanced on P14 in KRN633-treated rat retinas. The second round of KRN633 treatment on P11 and P12 completely blocked abnormal retinal vascular growth on P14, but thereafter induced ROP-like abnormal retinal blood vessels by P21. These results suggest that an interruption of normal retinal vascular development in neonatal rats as a result of short-term VEGFR inhibition causes severe ROP-like abnormal retinal vascular growth in a VEGF-dependent manner. Rats treated postnatally with VEGFR inhibitors could serve as an animal model for studying the mechanisms underlying the development of plus disease. [ABSTRACT FROM AUTHOR]