Pigment epithelial detachment (PED) is well-documented in adult retinal diseases but is rarely reported in neonates. This case describes a preterm infant, born at 31 weeks, who developed PED with thickened choroid at term-equivalent age, detected using handheld OCT. The PED emerged at 39 weeks postmenstrual age, coinciding with inhaled steroid treatment for respiratory distress, and resolved by 41 weeks after steroid discontinuation without structural damage. The temporal relationship suggests an association between steroid use and PED with choroidal changes. This case highlights the value of OCT in detecting retinal and choroidal abnormalities in preterm infants and underscores the potential impact of systemic conditions and medications on the choroid.

The introduction of optical coherence tomography (OCT) in the 1990s revolutionized diagnostic ophthalmic imaging. Initially, OCT's role was primarily in the adult ambulatory ophthalmic clinics. Subsequent advances in handheld form factors, integration into surgical microscopes, and robotic assistance have expanded OCT's utility and impact outside of its initial environment in the adult outpatient ophthalmic clinic. In this review, we cover the use of OCT in the neonatal intensive care unit (NICU) environment with a handheld OCT, recent developments in intraoperative OCT for data visualization and measurements, and recent work and demonstration of robotically aligned OCT systems outside of eye clinics. Of note, advances in these areas are a legacy of our colleague, the late Joseph Izatt. OCT has been an important innovation for ocular diagnostics, and these advances have helped it continue to extend in new directions.

Clinical evaluation of the disease activity of retinopathy of prematurity (ROP) is routinely performed via indirect ophthalmoscopy and/or widefield fundus photography. Herein we report an infant with advanced ROP imaged with an investigational handheld 400kHz optical coherence tomography angiography system that visualized microvascular details not seen in fundus exam or photography.

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.

Purpose: To evaluate a recently developed technique using intraoperative optical coherence tomography (OCT) to measure subretinal tissue plasminogen activator (tPA) volumes in patients with submacular hemorrhage secondary to exudative age-related macular degeneration (AMD). Methods: Three patients (72 to 83 years old) had 25-gauge pars plana vitrectomy, subretinal tPA, and a partial gas fill. An investigational intraoperative OCT system with a modified widefield noncontact indirect viewing apparatus was used to image subretinal tPA blebs. Using the recently developed technique, the volume and surface area in the segmented region of interest were determined. Results: In each case, the delivered tPA volume measured from the syringe differed from the intraoperative OCT-measured subretinal tPA volume: Patient 1, 130 mu L from syringe, 118 mu L based on intraoperative OCT, 9% difference; Patient 2, 140 mu L, 50 mu L, 64%; Patient 3, 110 mu L, 122 mu L, 11%. The total bleb surface area was 129 mm2 in Patient 1, 55 mm2 in Patient 2, and 106 mm2 in Patient 3. Conclusions: This was the first human study to implement and evaluate intraoperative OCT image-based methods to obtain volumetric bleb measurements in patients receiving subretinal tPA for exudative AMD. This proof-of-concept study showed that intraoperative OCT-obtained bleb volume differed from intraoperative recordings, which could be explained by tPA delivery into the vitreous, efflux through the retinotomy, or human error. Intraoperative OCT can provide visualization and quantification of subretinal tPA bleb volume and surface area, which has implications for improved safety, efficacy, and analysis of the effects of subretinal drug delivery.

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.

PURPOSE:To evaluate the clinical outcomes and prognostic factors in unilateral Coats disease in the era of anti-VEGF therapy. DESIGN:Global, multicenter, retrospective case series. SUBJECTS:Six hundred fifty-six eyes of 656 subjects with Coats disease were included in this study. Exclusion criteria were Coats disease secondary to retinitis pigmentosa as well as bilateral cases. METHODS:Clinical data from patients with Coats disease were collected from 20 ophthalmic practices around the world. We compared early-stage (stage 1-2) and advanced-stage (stage 3-5) Coats disease in terms of clinical characteristics and treatment modalities. MAIN OUTCOME MEASURES:Functional outcomes include achieving visual acuity (VA) of 0.3 logarithm of the minimum angle of resolution or better and VA improvement or stability. Anatomical failure was defined as the development of phthisis, chronic retinal detachment, massive fibrosis, or the requirement for enucleation. RESULTS:Subjects with early-stage disease were significantly older, with a mean age of 17.4 ± 17.8 years, compared with 7.1 ± 7.1 years in the advanced-stage group (P < 0.001). There was a male predominance in both early and advanced stages (84.7%). Advanced disease was associated with a higher incidence of strabismus (20.2% vs. 6.7%, P < 0.001) and leukocoria (12.3% vs. 3.2%, P < 0.001). More subjects with early-stage disease received laser photocoagulation as monotherapy (44.7% vs. 21.1%, P < 0.001). Additionally, early-stage disease received more sessions of intravitreal anti-VEGF injections as adjunct therapy (4.4 ± 6.2 vs. 2.7 ± 2.1, P = 0.005). Factors associated with poorer functional outcomes included worse presenting VA, advanced disease stage, and the presence of a foveal nodule. Worse presenting VA and advanced disease stage were associated with lower likelihood of anatomical success, whereas combination therapy increased the odds of anatomical success. CONCLUSIONS:Unilateral Coats disease predominantly affects males, regardless of disease stage. Identifying a foveal nodule is crucial for visual prognosis. Laser photocoagulation remains the primary treatment. Although anti-VEGF may prevent enucleation, its role in early-stage disease requires further clarification. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Significance:Imaging deep structures with optical coherence tomography (OCT) is difficult in highly scattering biological tissue, such as the sclera. There is a need to visualize the suprachoroidal space and choroid through the sclera to study suprachoroidal drug delivery. Aim:We aim to develop optical methods to image through the highly scattering sclera with a custom-built OCT system to visualize the suprachoroidal space and drug delivery within. Approach:We developed a custom handheld OCT scanner to image the anterior segment and suprachoroidal space in ex vivo eye models. Tartrazine (Yellow 5) solution, which has been shown to optically clear biological tissue in the visible regime, was tested as a clearing agent to optimize near infrared OCT imaging through the sclera. Results:Tartrazine dramatically increased OCT signal return from the deeper sclera and choroid and thus enabled visualization of the suprachoroidal drug delivery after transscleral injection. Conclusions:We demonstrated successful optical clearing of the thick, porcine sclera with a compact handheld OCT system to image the suprachoroidal space. We believe there is broader potential to use optical clearing with handheld OCT for a variety of previously inaccessible, highly scattering tissue samples.

[This corrects the article DOI: 10.1117/1.JBO.29.12.120501.].

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.

Joseph Izatt’s work advanced the science of imaging in biophotonics and brought optical coherence tomography imaging to the eye care of infants and children and, as live feedback for the surgeon, to ophthalmic microsurgery.

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.

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.

The 2023 Lasker-DeBakey Clinical Medical Research Award recognizes the effect of optical coherence tomography, invented by Drs. Fujimoto, Huang, and Swanson.