P Score: A Reference Image-Based Clinical Grading Scale for Vascular Change in Retinopathy of Prematurity.

PURPOSE: 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. DESIGN: Retinal photographic grading and expert consensus opinion. PARTICIPANTS: 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) METHODS: 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. MAIN OUTCOME MEASURES: Intergrader agreement measured by intraclass correlation coefficient. RESULTS: 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. CONCLUSIONS: 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. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Early Single-Examination Optical Coherence Tomography Biomarkers for Treatment-Requiring Retinopathy of Prematurity.

Purpose: Optical coherence tomography (OCT) is an emerging adjunct imaging modality to evaluate retinopathy of prematurity (ROP). From an 11-year research database, we identify early OCT biomarkers that predict treatment-requiring ROP (TR-ROP). Methods: For preterm infants with acceptable OCT images at 32 ± 1 weeks postmenstrual age (PMA), we extracted the following measures: total retina, inner retinal layer (IRL), and outer retinal layer (ORL) thicknesses at the fovea and the parafovea, inner nuclear layer (INL) and choroidal thickness, parafovea/fovea (P/F) ratio, and presence of macular edema. Using univariable and multivariable logistic regression models, we evaluated the association between retinal and choroidal OCT measurements at 32 ± 1 weeks PMA and development of TR-ROP. Results: Of 277 eyes (145 infants) with usable OCT images, 67 eyes had TR-ROP. Lower P/F ratio (P < 0.0001), thicker foveal IRL (P = 0.0001), and thinner choroid (P = 0.03) were associated with TR-ROP in univariable analysis, but lost significance of association when adjusted for gestational age and race. Absence of macular edema was associated with TR-ROP when adjusted for gestational age and race (P = 0.01). In 185 eyes without macular edema, P/F ratio was associated with TR-ROP in both univariable analysis (P < 0.0001) and multivariable analysis (P = 0.02) with adjustment for gestational age and race. Conclusions: Presence of macular edema at 32 ± 1 weeks PMA in infants with lower gestational age may be protective against TR-ROP. In infants without macular edema, P/F ratio may be an early OCT biomarker for development of TR-ROP. Incorporation of early OCT biomarkers may be useful in prediction of TR-ROP.

Longitudinal Choroidal Development in Preterm Infants.

Purpose: To characterize changes in subfoveal choroidal thickness in preterm infants from 30 to 60 weeks' postmenstrual age (PMA). Design: The prospective, observational Study of Eye Imaging in Preterm infantS (BabySTEPS) enrolled infants eligible for retinopathy of prematurity screening per the American Association of Pediatrics guidelines. Subjects: Infants imaged with an investigational, handheld OCT at ≥ 4 distinct imaging sessions between 30 to 60 weeks' PMA as part of BabySTEPS. Methods: Average choroidal thickness across the central subfoveal 1 mm in each eye at each time point was measured using custom segmentation software, and errors were manually corrected by a trained grader. We prospectively collected birth history data. A segmented mixed model was used to analyze the change in choroidal thickness as a function of PMA, birth weight, and gestational age (GA). Main Outcome Measures: Characterization of normative subfoveal choroidal thickness values and choroidal growth rate between 30 to 60 weeks' PMA. Results: We included 592 imaging sessions of 79 preterm infants (152 eyes). Mean (± standard deviation) GA was 27.5 ± 2.5 weeks. Mean choroidal thickness was 141.4 ± 34.5 µm at 30 weeks, 272.2 ± 83.9 µm at 38 weeks, and 306.2 ± 77.4 µm between 56 and 60 weeks. Between 30 and 60 weeks' PMA, choroidal growth followed a biphasic model, with a linear growth rate of 14.8 µm per week (95% confidence interval [CI], 13.6-16.0) from 30 until 38.4 weeks, then cessation of growth, with a growth rate of 0.3 µm per week (95% CI, -1.1 to 1.6) from 38.4 to 60 weeks. Infants with extremely low birth weight (ELBW; < 1000 g) and extremely preterm (GA < 28 weeks) infants had significantly slower initial growth rates compared with very low and low birth weight and very preterm and preterm infants (ELBW 13.0 vs. 21.0 µm per week; P < 0.0001 and extremely preterm 13.2 vs. 18.0 µm per week; P = 0.003). Conclusions: Preterm infant choroidal thickness experiences rapid linear growth from 30 to 38 weeks' PMA, at which time growth nearly stops. These foundational measurements and identification of the impact of extremes of low birth weight and prematurity on choroidal development will be essential as researchers begin to understand the role of choroidal development in ocular and retinal health in human infants. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A pilot optical coherence tomography angiography classification of retinal neovascularization in retinopathy of prematurity.

Extraretinal neovascularization is a hallmark of treatment-requiring retinopathy of prematurity (ROP). Optical coherence tomography angiography (OCTA) offers vascular flow and depth information not available from indirect ophthalmoscopy and structural OCT, but OCTA is only commercially available as a tabletop device. In this study, we used an investigational handheld OCTA device to study the vascular flow in and around retinal neovascularization in seven preterm infants with treatment-requiring ROP and contrasted them to images of vascular flow in six infants of similar age without neovascular ROP. We showed stages of retinal neovascularization visible in preterm infants from 32 to 47 weeks postmenstrual age: Intraretinal neovascularization did not break through the internal limiting membrane; Subclinical neovascular buds arose from retinal vasculature with active flow through the internal limiting membrane; Flat neovascularization in aggressive ROP assumed a low-lying configuration compared to elevated extraretinal neovascular plaques; Regressed neovascularization following treatment exhibited decreased vascular flow within the preretinal tissue, but flow persisted in segments of retinal vessels elevated from their original intraretinal location. These findings enable a pilot classification of retinal neovascularization in eyes with ROP using OCTA, and may be helpful in detailed monitoring of disease progression, treatment response and predicting reactivation.

Artificial Intelligence, Digital Imaging, and Robotics Technologies for Surgical Vitreoretinal Diseases.

OBJECTIVE: To review recent technological advancement in imaging, surgical visualization, robotics technology, and the use of artificial intelligence in surgical vitreoretinal (VR) diseases. BACKGROUND: Technological advancements in imaging enhance both preoperative and intraoperative management of surgical VR diseases. Widefield imaging in fundal photography and OCT can improve assessment of peripheral retinal disorders such as retinal detachments, degeneration, and tumors. OCT angiography provides a rapid and noninvasive imaging of the retinal and choroidal vasculature. Surgical visualization has also improved with intraoperative OCT providing a detailed real-time assessment of retinal layers to guide surgical decisions. Heads-up display and head-mounted display utilize 3-dimensional technology to provide surgeons with enhanced visual guidance and improved ergonomics during surgery. Intraocular robotics technology allows for greater surgical precision and is shown to be useful in retinal vein cannulation and subretinal drug delivery. In addition, deep learning techniques leverage on diverse data including widefield retinal photography and OCT for better predictive accuracy in classification, segmentation, and prognostication of many surgical VR diseases. CONCLUSION: This review article summarized the latest updates in these areas and highlights the importance of continuous innovation and improvement in technology within the field. These advancements have the potential to reshape management of surgical VR diseases in the very near future and to ultimately improve patient care. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.