Significance of isolated neovascular tufts (“Popcorn”) in retinopathy of prematurity

Wallace, David K.; Kylstra, Jan A.; Greenman, David B.; Freedman, Sharon F.

doi:10.1016/s1091-8531(98)90111-2

Cited by 20 publications

(14 citation statements)

References 9 publications

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“…We believe that these preretinal structures are fibrovascular and likely similar to neovascular tufts that have been found to be associated with disease progression in cases of zone II ROP. 23 …”

Section: Discussionmentioning

confidence: 99%

Insights into Advanced Retinopathy of Prematurity Using Handheld Spectral Domain Optical Coherence Tomography Imaging

et al. 2009

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Purpose To elucidate the subclinical anatomy of retinopathy of prematurity (ROP) using spectral domain optical coherence tomography (SD OCT). Design Prospective, observational case series. Participants Three low-birth-weight, severely premature infants. Methods Clinical examination was performed using a portable slit lamp and indirect ophthalmoscope. Imaging was performed by using a handheld SD OCT device and Retcam (Clarity Medical Systems, Pleasanton, CA) or video-indirect recording. Spectral domain optical coherence tomography imaging was conducted without sedation at the bedside in the neonatal intensive care unit on 1 patient. The other 2 patients had an examination under anesthesia with SD OCT imaging in the operating room. Main Outcome Measures In vivo determination of vitreoretinal morphology, anatomy, and pathology by clinical examination, imaging, and SD OCT. Results Linear and volumetric imaging was achieved with the handheld system in infant eyes despite tunica vasculosa lentis and vitreous bands. Imaging was not possible in eyes with notable vitreous hemorrhage. Analysis of SD OCT images revealed preretinal structures (ranging from 409 to 2700 μm in width and 212 to 440 μm in height), retinoschisis, and retinal detachment in the posterior pole of patients with advanced ROP. Both the retinoschisis and the preretinal structures were not identified on conventional examination or imaging by expert pediatric ophthalmologists. The preretinal structures varied in location and size, and may represent preretinal fibrovascular proliferation. Some were found in close proximity to blood vessels, whereas others were near the optic nerve. Conclusions Handheld SD OCT imaging can be performed on the sedated or nonsedated neonate and provides valuable subclinical anatomic information. This novel imaging modality can reveal the location and extent of posterior ROP pathology not evident on standard examination. This could affect future clinical decision-making if studies validate a management strategy based on findings from this imaging technique.

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Section: Discussionmentioning

confidence: 99%

Insights into Advanced Retinopathy of Prematurity Using Handheld Spectral Domain Optical Coherence Tomography Imaging

et al. 2009

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“…In the most commonly used rodent models, experimental alteration of the ambient oxygen level in early postnatal life disrupts retinal vascular development, resulting in the growth of neovessels onto the retinal surface, where blood vessels are never found under physiological conditions. The clinical relevance of these models is supported by the similarity of their preretinal neovascular complexes with those observed in infants with retinopathy of prematurity (ROP) (8). Of practical importance, the preretinal location of pathological neovascular complexes makes them relatively easy targets for electrophysiological recording.…”

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confidence: 99%

Bioelectric impact of pathological angiogenesis on vascular function

Puro

Kohmoto

Fujita

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Pathological angiogenesis, as seen in many inflammatory, immune, malignant, and ischemic disorders, remains an immense health burden despite new molecular therapies. It is likely that further therapeutic progress requires a better understanding of neovascular pathophysiology. Surprisingly, even though transmembrane voltage is well known to regulate vascular function, no previous bioelectric analysis of pathological angiogenesis has been reported. Using the perforated-patch technique to measure vascular voltages in human retinal neovascular specimens and rodent models of retinal neovascularization, we discovered that pathological neovessels generate extraordinarily high voltage. Electrophysiological experiments demonstrated that voltage from aberrantly located preretinal neovascular complexes is transmitted into the intraretinal vascular network. With extensive neovascularization, this voltage input is substantial and boosts the membrane potential of intraretinal blood vessels to a suprahyperpolarized level. Coincident with this suprahyperpolarization, the vasomotor response to hypoxia is fundamentally altered. Instead of the compensatory dilation observed in the normal retina, arterioles constrict in response to an oxygen deficiency. This anomalous vasoconstriction, which would potentiate hypoxia, raises the possibility that the bioelectric impact of neovascularization on vascular function is a previously unappreciated pathophysiological mechanism to sustain hypoxia-driven angiogenesis.neovascularization | proliferative retinopathy | retinopathy of prematurity | proliferative diabetic retinopathy | retina T he abnormal growth of blood vessels is a key pathophysiological feature of numerous disorders, including tumorigenesis, arthritis, endometriosis, and retinopathies. Despite substantial progress from studies of patients and animal models, abnormal neovascularization remains a common threat to health and wellbeing. To help address this challenge, we devised a unique experimental approach to better understand neovascular pathophysiology. Because almost nothing is known about the electrogenic profile of neovascular complexes and how these complexes functionally interact with their parent vessels, we focused on the bioelectric features of neovascularization. These gaps in knowledge are surprising, considering that it is well established that the transmembrane voltage of vascular cells (1), as well as electrotonic cell-cell interactions within a vascular network (2-4), play vital roles in regulating blood flow.In this electrophysiological analysis of pathological angiogenesis, we focused on abnormal vasoproliferation in rodent and human retinas. For multiple reasons, the retina is an ideal tissue for this undertaking. First is its clinical importance. Retinal vasoproliferation is the major cause of blindness in prematurely born infants (retinopathy of prematurity) and persons with diabetes (proliferative diabetic retinopathy) and sickle cell disease (sickle cell retinopathy). The hallmark of these disorders is abno...

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“…Wallace et al studied the significance of isolated buds in stage 2 ROP. [26] They hypothesized that these isolated neovascular tufts, described clinically as "popcorn", can occur either early or late during active disease and may be associated with progression or regression of disease. [26] Similar to our observation, Wallace et al found single or multiple of these tufts in one or more quadrants either immediately posterior to the V-AV junction in stage 3 ROP but at a significant distance from the V-AV junction in stage 2 eyes.…”

Section: Discussionmentioning

confidence: 99%

“…[26] They hypothesized that these isolated neovascular tufts, described clinically as "popcorn", can occur either early or late during active disease and may be associated with progression or regression of disease. [26] Similar to our observation, Wallace et al found single or multiple of these tufts in one or more quadrants either immediately posterior to the V-AV junction in stage 3 ROP but at a significant distance from the V-AV junction in stage 2 eyes. From their study, they concluded that there may be two types of popcorn lesions; one associated with increased risk of disease progression, and one occurring later as the advancing ridge leaves behind benign tufts.…”

Section: Discussionmentioning

confidence: 99%

Three-dimensional pattern of extraretinal neovascular development in retinopathy of prematurity

Mangalesh

Bleicher

Chen

et al. 2019

Graefes Arch Clin Exp Ophthalmol

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Background: The application of three-dimensional (3D) visualization techniques to evaluate the earliest visible onset of abnormal retinal vascular development in preterm infants with retinopathy of prematurity (ROP), using bedside non-contact optical coherence tomography (OCT) imaging to characterize morphology and sequential structural changes of abnormal extraretinal neovascularization. Methods: Thirty-one preterm infants undergoing routine ROP screening with written informed consent for research imaging were enrolled in this prospective observational study. We imaged the macula and temporal periphery of preterm infants using a handheld OCT system (Envisu 2300 or handheld swept-source research system). The scans obtained were segmented and using enhanced ray casting were converted to 3D volumes to which color filter were applied. Results: Using colorized 3D visualization, we defined extraretinal neovascular structures as buds, bridging networks and placoid lesions. We could longitudinally follow progression and regression of extraretinal neovascularization in stage 3 ROP after treatment in one infant over 12 weeks and document the appearance of early buds, and formation of florid neovascularization. From stage 2 to 3 ROP, we observed progression from sessile buds to a complex plaque that corresponded to stage 3 ROP on clinical examination. We demonstrated regression of neovascular complexes to small pre-retinal tufts after treatment with anti-VEGF.

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Significance of isolated neovascular tufts (“Popcorn”) in retinopathy of prematurity

Cited by 20 publications

References 9 publications

Insights into Advanced Retinopathy of Prematurity Using Handheld Spectral Domain Optical Coherence Tomography Imaging

Insights into Advanced Retinopathy of Prematurity Using Handheld Spectral Domain Optical Coherence Tomography Imaging

Bioelectric impact of pathological angiogenesis on vascular function

Three-dimensional pattern of extraretinal neovascular development in retinopathy of prematurity

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