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.

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.

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.

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.

Erratum: Methods for real-time feature-guided image fusion of intrasurgical volumetric optical coherence tomography with digital microscopy: publisher's note.

[This corrects the article on p. 3308 in vol. 14, PMID: 37497493.].

A Deep-Learning Algorithm to Predict Short-Term Progression to Geographic Atrophy on Spectral-Domain Optical Coherence Tomography.

Importance: The identification of patients at risk of progressing from intermediate age-related macular degeneration (iAMD) to geographic atrophy (GA) is essential for clinical trials aimed at preventing disease progression. DeepGAze is a fully automated and accurate convolutional neural network-based deep learning algorithm for predicting progression from iAMD to GA within 1 year from spectral-domain optical coherence tomography (SD-OCT) scans. Objective: To develop a deep-learning algorithm based on volumetric SD-OCT scans to predict the progression from iAMD to GA during the year following the scan. Design, Setting, and Participants: This retrospective cohort study included participants with iAMD at baseline and who either progressed or did not progress to GA within the subsequent 13 months. Participants were included from centers in 4 US states. Data set 1 included patients from the Age-Related Eye Disease Study 2 AREDS2 (Ancillary Spectral-Domain Optical Coherence Tomography) A2A study (July 2008 to August 2015). Data sets 2 and 3 included patients with imaging taken in routine clinical care at a tertiary referral center and associated satellites between January 2013 and January 2023. The stored imaging data were retrieved for the purpose of this study from July 1, 2022, to February 1, 2023. Data were analyzed from May 2021 to July 2023. Exposure: A position-aware convolutional neural network with proactive pseudointervention was trained and cross-validated on Bioptigen SD-OCT volumes (data set 1) and validated on 2 external data sets comprising Heidelberg Spectralis SD-OCT scans (data sets 2 and 3). Main Outcomes and Measures: Prediction of progression to GA within 13 months was evaluated with area under the receiver-operator characteristic curves (AUROC) as well as area under the precision-recall curve (AUPRC), sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. Results: The study included a total of 417 patients: 316 in data set 1 (mean [SD] age, 74 [8]; 185 [59%] female), 53 in data set 2, (mean [SD] age, 83 [8]; 32 [60%] female), and 48 in data set 3 (mean [SD] age, 81 [8]; 32 [67%] female). The AUROC for prediction of progression from iAMD to GA within 1 year was 0.94 (95% CI, 0.92-0.95; AUPRC, 0.90 [95% CI, 0.85-0.95]; sensitivity, 0.88 [95% CI, 0.84-0.92]; specificity, 0.90 [95% CI, 0.87-0.92]) for data set 1. The addition of expert-annotated SD-OCT features to the model resulted in no improvement compared to the fully autonomous model (AUROC, 0.95; 95% CI, 0.92-0.95; P = .19). On an independent validation data set (data set 2), the model predicted progression to GA with an AUROC of 0.94 (95% CI, 0.91-0.96; AUPRC, 0.92 [0.89-0.94]; sensitivity, 0.91 [95% CI, 0.74-0.98]; specificity, 0.80 [95% CI, 0.63-0.91]). At a high-specificity operating point, simulated clinical trial recruitment was enriched for patients progressing to GA within 1 year by 8.3- to 20.7-fold (data sets 2 and 3). Conclusions and Relevance: The fully automated, position-aware deep-learning algorithm assessed in this study successfully predicted progression from iAMD to GA over a clinically meaningful time frame. The ability to predict imminent GA progression could facilitate clinical trials aimed at preventing the condition and could guide clinical decision-making regarding screening frequency or treatment initiation.

Computer versus human-expert ranking of posterior pole vascular tortuosity and dilation using retinal vessel maps generated from bedside optical coherence tomography: a proof-of-concept study.

Semiautomated computer software (ie, ROPtool) can trace and analyze optical coherence tomography (OCT)-generated retinal vessel maps for plus/pre-plus disease with high reliability and accuracy. This proof-of-concept study found that ROPtool can reliably rank OCT-generated vessel maps for tortuosity and combined tortuosity/dilation, which correlated well with human-expert rankings and clinical examination.

Preterm infant retinal OCT markers of perinatal health and retinopathy of prematurity.

The increasing survival of preterm infants has led to the importance of improving long-term outcomes associated with preterm birth. Antenatal and perinatal insults not only impact mortality, but also long-term disability. While in the intensive care nursery, preterm infants are also exposed to various stressors that lead to long-term cognitive deficits. It is therefore critical to identify early, low-stress, non-invasive biomarkers for preterm infant health. Optical coherence tomography (OCT) is a powerful imaging modality that has recently been adapted to the infant population and provides noninvasive, high-resolution, cross-sectional imaging of the infant eye at the bedside with low stress relative to conventional examination. In this review we delve into discussing the associations between preterm systemic health factors and OCT-based retinal findings and their potential contribution to the development of non-invasive biomarkers for infant health and for retinopathy of prematurity (ROP).

MACULAR NEUROVASCULAR ABNORMALITIES IN A CHILD WITH INCONTINENTIA PIGMENTI ON HANDHELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To report macular neurovascular abnormalities in a child with incontinentia pigmenti using handheld optical coherence tomography (OCT) and OCT angiography (OCT-A). METHODS: An eye of a child with incontinentia pigmenti enrolled in BabySTEPS was imaged using an investigational noncontact, handheld swept-source OCT device during examination under anesthesia. Custom MATLAB scripts were used to generate depth-resolved vascular slabs, B-scans with flow overlay, and retinal thickness maps. RESULTS: Depth-resolved OCT and OCT-A imaging demonstrated focal areas of decreased capillary flow that corresponded to areas of both inner retinal and outer retinal thinning on retinal thickness maps. Atypical diving of superficial retinal vessels occurred as they traversed from thin retina to normal-thickness retina. CONCLUSION: Depth-resolved OCT and OCT-A identified retinal vascular abnormalities that were not evident on fundus photography or fluorescein angiography. This case depicted concurrent, localized abnormalities in retinal thickness and microvasculature in an eye with incontinentia pigmenti.

Ocular Pigmentation Impact on Retinal Versus Choroidal Optical Coherence Tomography Imaging in Preterm Infants.

Purpose: To evaluate the association of fundus pigmentation with the visibility of retinal versus choroidal layers on optical coherence tomography (OCT) in preterm infants. Methods: For infants enrolled in BabySTEPS, ophthalmologists recorded fundus pigmentation (blond, medium, or dark) at the first retinopathy of prematurity (ROP) examination. Bedside OCT imaging was performed at each examination, and a masked grader evaluated all OCT scans from both eyes of each infant for visibility (yes/no) of all retinal layers and of the chorio-scleral junction (CSJ). Multivariable logistic regression was used to assess associations between fundus pigmentation and visibility of all retinal layers and CSJ, controlling for potential confounders (i.e., birth weight, gestational age, sex, OCT system, pupil size, and postmenstrual age at imaging). Results: Among 114 infants (mean birth weight, 943 grams; mean gestational age, 27.6 weeks), 43 infants (38%) had blond, 56 infants (49%) had medium, and 15 infants (13%) had dark fundus pigmentation. Of 1042 scans, all retinal layers were visible in 977 (94%) and CSJ in 895 (86%). Pigmentation was not associated with retinal layer visibility (P = 0.49), but medium and dark pigmentation were associated with decreased CSJ visibility (medium: odds ratio [OR] = 0.34, P = 0.001; dark: OR = 0.24, P = 0.009). For infants with dark pigmentation, retinal layer visibility increased (OR = 1.87 per week; P ≤ 0.001) and CSJ visibility decreased (OR = 0.78 per week; P = 0.01) with increasing age. Conclusions: Although fundus pigmentation was not associated with the visibility of all retinal layers on OCT, darker pigmentation decreased CSJ visibility, and this effect increased with age. Translational Relevance: The ability of bedside OCT to capture retinal layer microanatomy in preterm infants, regardless of fundus pigmentation, may represent an advantage over fundus photography for ROP telemedicine.

Methods for real-time feature-guided image fusion of intrasurgical volumetric optical coherence tomography with digital microscopy.

4D-microscope-integrated optical coherence tomography (4D-MIOCT) is an emergent multimodal imaging technology in which live volumetric OCT (4D-OCT) is implemented in tandem with standard stereo color microscopy. 4D-OCT provides ophthalmic surgeons with many useful visual cues not available in standard microscopy; however it is challenging for the surgeon to effectively integrate cues from simultaneous-but-separate imaging in real-time. In this work, we demonstrate progress towards solving this challenge via the fusion of data from each modality guided by segmented 3D features. In this way, a more readily interpretable visualization that combines and registers important cues from both modalities is presented to the surgeon.

Visualization of surgical maneuvers using intraoperative real-time volumetric optical coherence tomography.

Ophthalmic microsurgery is traditionally performed using stereomicroscopes and requires visualization and manipulation of sub-millimeter tissue structures with limited contrast. Optical coherence tomography (OCT) is a non-invasive imaging modality that can provide high-resolution, depth-resolved cross sections, and has become a valuable tool in clinical practice in ophthalmology. While there has been substantial progress in both research and commercialization efforts to bring OCT imaging into live surgery, its use is still somewhat limited due to factors such as low imaging speed, limited scan configurations, and suboptimal data visualization. In this paper we describe, to the best of our knowledge, the translation of the fastest swept-source intraoperative OCT system with real-time volumetric imaging with stereoscopic data visualization provided via a heads-up display into the operating room. Results from a sampling of human anterior segment and retinal surgeries chosen from 93 human surgeries using the system are shown and the benefits that this mode of intrasurgical OCT imaging provides are discussed.

NOVEL METHOD FOR VISUALIZING PERIPHERAL RETINAL STRUCTURES WITH MICROSCOPE-INTEGRATED OPTICAL COHERENCE TOMOGRAPHY.

BACKGROUND/PURPOSE: Visualization of peripheral retinal structures with optical coherence tomography (OCT) can be challenging but can offer valuable clinical information. We describe a method for intraoperative OCT of the peripheral retina. METHODS: An investigational microscope-integrated OCT system with real-time 4D volumetric imaging was used in conjunction with a Goldmann style mirrored contact lens intraoperatively to capture peripheral images in three patients. RESULTS: We identified retinoschisis, a retinal break, and areas of focal retinal detachment using our peripheral OCT method. CONCLUSION: Use of a Goldmann lens in conjunction with intraoperative OCT offers surgeons the ability to resolve peripheral pathology that cannot be easily evaluated with OCT otherwise.

Low-Dose Intravitreal Methotrexate for Proliferative Vitreoretinopathy.

BACKGROUND AND OBJECTIVE: Proliferative vitreoretinopathy (PVR) has been mitigated by intravitreal methotrexate (MTX) 400 µg/0.1 mL in several studies. Here, we evaluate the results from a lower dose of MTX, 200 µg/0.05 mL. MATERIALS AND METHODS: We identified and reviewed records of patients with grade ≥C1 PVR who were treated with 200 µg/0.05 mL MTX injections: during PVR surgery and every 2 weeks thereafter. RESULTS: Twenty-four eyes met inclusion criteria with a mean of 5.6 injections and follow-up ranging 6 to 56 months. The retina was reattached in 19 of 24 eyes (79%) after a single surgery and in 5 of 24 eyes (21%) after one additional PVR surgery. Visual acuity improved from baseline logMAR 1.63 to 0.97 at 12 months (P < .001), with 5 of 20 achieving 20/60 or better and 16 of 20 achieving 20/200 or better. One eye developed a transient corneal abrasion that resolved within 1 week. CONCLUSION: Low-dose MTX (200 µg/0.05 mL) during and after PVR surgery resulted in good rates of retinal reattachment and visual acuity recovery. [Ophthalmic Surg Lasers Imaging Retina 2023;54(3):139-146.].

A differential proteomics study of cerebrospinal fluid from individuals with Niemann-Pick disease, Type C1.

Niemann-Pick, type C1 (NPC1) is a fatal, neurodegenerative disease, which belongs to the family of lysosomal diseases. In NPC1, endo/lysosomal accumulation of unesterified cholesterol and sphingolipids arise from improper intracellular trafficking resulting in multi-organ dysfunction. With the proximity between the brain and cerebrospinal fluid (CSF), performing differential proteomics provides a means to shed light to changes occurring in the brain. In this study, CSF samples obtained from NPC1 individuals and unaffected controls were used for protein biomarker identification. A subset of these individuals with NPC1 are being treated with miglustat, a glycosphingolipid synthesis inhibitor. Of the 300 identified proteins, 71 proteins were altered in individuals with NPC1 compared to controls including cathepsin D, and members of the complement family. Included are a report of 10 potential markers for monitoring therapeutic treatment. We observed that pro-neuropeptide Y (NPY) was significantly increased in NPC1 individuals relative to healthy controls; however, individuals treated with miglustat displayed levels comparable to healthy controls. In further investigation, NPY levels in a NPC1 mouse model corroborated our findings. We posit that NPY could be a potential therapeutic target for NPC1 due to its multiple roles in the central nervous system such as attenuating neuroinflammation and reducing excitotoxicity.

Quantitative measurements of intraocular structures and microinjection bleb volumes using intraoperative optical coherence tomography.

Intraoperative optical coherence tomography (OCT) systems provide high-resolution, real-time visualization and/or guidance of microsurgical procedures. While the use of intraoperative OCT in ophthalmology has significantly improved qualitative visualization of surgical procedures inside the eye, new surgical techniques to deliver therapeutics have highlighted the lack of quantitative information available with current-generation intraoperative systems. Indirect viewing systems used for retinal surgeries introduce distortions into the resulting OCT images, making it particularly challenging to make calibrated quantitative measurements. Using an intraoperative OCT system based in part on the Leica Enfocus surgical microscope interface, we have devised novel measurement procedures, which allowed us to build optical and mathematical models to perform validation of quantitative measurements of intraocular structures for intraoperative OCT. These procedures optimize a complete optical model of the sample arm including the OCT scanner, viewing attachments, and the patient's eye, thus obtaining the voxel pitch throughout an OCT volume and performing quantitative measurements of the dimensions of imaged objects within the operative field. We performed initial validation by measuring objects of known size in a controlled eye phantom as well as ex vivo porcine eyes. The technique was then extended to measure other objects and structures in ex vivo porcine eyes and in vivo human eyes.

Associations between systemic health and retinal nerve fibre layer thickness in preterm infants at 36 weeks postmenstrual age.

BACKGROUND/AIMS: Neonatal insults from systemic diseases have been implicated in the pathway of impaired neurodevelopment in preterm infants. We aimed to investigate the associations between systemic health factors and retinal nerve fibre layer (RNFL) thickness in preterm infants. METHODS: We prospectively enrolled infants and imaged both eyes at 36±1 weeks postmenstrual age (PMA) using a hand-held optical coherence tomography system at the bedside in the Duke intensive care nurseries. We evaluated associations between RNFL thickness and 29 systemic health factors using univariable and multivariable regression models. RESULTS: 83 infants with RNFL thickness measures were included in this study. Based on the multivariable model, RNFL thickness was positively associated with infant weight at imaging and was negatively associated with sepsis/necrotising enterocolitis (NEC). RNFL thickness was 10.4 µm (95% CI -15.9 to -4.9) lower in infants with than without sepsis/NEC in the univariable analysis (p<0.001). This difference remained statistically significant after adjustment for confounding variables in various combinations (birth weight, birthweight percentile, gestational age, infant weight at imaging and growth velocity). A 250 g increase in infant weight at imaging was associated with a 3.1 µm (95% CI 2.1 to 4.2) increase in RNFL thickness in the univariable analysis (p<0.001). CONCLUSIONS: Low infant weight and sepsis/NEC were independently associated with thinner RNFL in preterm infants at 36 weeks PMA. To our knowledge, this study is the first to suggest that sepsis/NEC may affect retinal neurodevelopment. Future longitudinal studies are needed to investigate this relationship further.

Biphasic change in retinal nerve fibre layer thickness from 30 to 60 weeks postmenstrual age in preterm infants.

BACKGROUND/AIMS: The optic nerve development during the critical postnatal weeks of preterm infants is unclear. We aimed to investigate the change of retinal nerve fibre layer (RNFL) in preterm infants. METHODS: We used an investigational handheld optical coherence tomography (OCT) system to serially image awake preterm infants between 30 and 60 weeks postmenstrual age (PMA) at the bedside. We assessed RNFL thickness in the papillomacular bundle and nasal macular ganglion cell layer+inner plexiform layer (GCL+IPL) thickness. We applied a segmented mixed model to analyse the change in the thickness of RNFL and GCL+IPL as a function of PMA. RESULTS: From 631 OCT imaging sessions of 101 infants (201 eyes), RNFL thickness followed a biphasic model between 30 and 60 weeks, with an estimated transition at 37.8 weeks PMA (95% CI: 37.0 to 38.6). RNFL thickness increased at 1.8 µm/week (95% CI: 1.6 to 2.1) before 37.8 weeks and decreased at -0.3 µm/week (95% CI: -0.5 to -0.2) afterwards. GCL+IPL thickness followed a similar biphasic model, in which the thickness increased at 2.9 µm/week (95% CI: 2.5 to 3.2) before 39.5 weeks PMA (95% CI: 38.8 to 40.1) and then decreased at -0.8 µm/week (95% CI: -0.9 to -0.6). CONCLUSION: We demonstrate the feasibility of monitoring RNFL and GCL+IPL thickness from OCT during the postnatal weeks of preterm infants. Thicknesses follow a biphasic model with a transition age at 37.8 and 39.5 weeks PMA, respectively. These findings may shed light on optic nerve development in preterm infants and assist future study designs.