Evolution of Retinal Detachment in Posterior Retinopathy of Prematurity: Impact on Treatment Approach

doi:10.1016/j.ajo.2007.10.027

American Journal of Ophthalmology

Volume 145, Issue 3, March 2008, Pages 548-555.e2

https://doi.org/10.1016/j.ajo.2007.10.027 Get rights and content

Purpose

To provide insight into the course of retinal detachment in eyes with aggressive posterior retinopathy of prematurity (APROP).

Design

Prospective, multicenter, masked clinical trial.

Methods

Multicenter trial based on serial digital photographic imaging detailing five infants (in the Photographic Screening for Retinopathy of Prematurity [PHOTO-ROP] Study) in whom bilateral retinal detachment developed during the course of the study.

Results

Retinal detachment developed in both eyes (n = 10) of all five infants despite peripheral retinal laser ablation. The mean birth weight was 651.4 ± 45.30 g (range, 601 to 718 g), and the mean gestation was 26.75 ± 0.96 weeks (range, 24 to 26 weeks). APROP (flat neovascularization) was present in all eyes at the time of treatment. Laser treatment was performed at a mean postconceptual age of 37.25 ± 1.8 weeks (range, 35 to 39.57 weeks). Plus disease resolved initially and then recurred (mean, 9.5 days) with progression to retinal detachment; the mean postconceptual age at the time of retinal detachment was 41.42 ± 3.6 weeks (range, 36 to 47.29 weeks). Untreated avascular retina became visible with regression of flat preretinal neovascularization. All 10 eyes showed preretinal vitreous organization (most prominent nasally) along the retinal surface without significant transvitreal components.

Conclusions

Eyes with APROP may follow an atypical course after laser ablation. Such eyes may still fare poorly, even when plus disease wanes. Additional laser to avascular retina may be necessary after the overlying flat stage 3 neovascularization regresses. The absence of obvious fibrosis at the time of laser should provide no reassurance as to reduced probability of progression to retinal detachment.

Section snippets

Methods

The data is derived from the PHOTO-ROP Study material. The design⁹ and results¹⁰ of this prospective, multicenter, masked, internet-based clinical trial were reported earlier. The study protocol and informed consent were approved by individual institutional review boards at each participating center. One of the secondary aims of the study was to document the evolution of posterior ROP-related retinal detachments.

Briefly, eyes were examined using the PHOTO-ROP standard imaging protocol.⁹ Digital

Results

All eyes showed initial reduction of plus disease after treatment. After a mean of 9.5 days (range, seven to 14 days) all 10 eyes showed a recurrence of plus disease and retinal detachment. Retinal detachments predominantly were located nasally. The mean postconceptual age at which retinal detachment was first noted was 41.42 ± 3.6 weeks (range, 36 to 47.29 weeks). Flat preretinal vitreous organization was apparent in all 10 eyes, without significant transvitreal components. FIGURE 1, FIGURE 2,

Discussion

Eyes with zone 1 ROP often fare poorly.1, 2, 3, 4, 5, 6, 7, 8 Aggressive posterior ROP is characterized by a broad, flat, neovascular syncytium in zone 1.² This is opposed to the typical elevated extraretinal neovascular proliferation arising at 90 degrees to the retina posterior to the ROP ridge, typical of stage 3 ROP in zones 2 and 3.

The explanations for why such flat neovascular changes occur currently are speculative. Recently, a distinct vasculogenic stage of development has been

Anand Vinekar, MS, DNB, FRCS, completed his Ophthalmology residency and fellowship in surgical Vitreo-Retina at Postgraduate Institute of Medical Education & Research, Chandigarh, India. He has received the “Best Postgraduate Medal” awarded by the Prime Minister & the “Young Researcher Award” in 2005. After completing his International Fellowship in Pediatric Retina at the William Beaumont Hospital, Royal Oak, Dr Vinekar returned to Bangalore, India. His primary research interests include

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Cited by (56)

Evidence based management of retinopathy of prematurity: More than meets the eye
2024, Clinical Epidemiology and Global Health
Retinopathy of prematurity (ROP) is a potentially blinding disorder of infants born preterm. With increased survival of preterm infants, ROP is on the rise especially in the developing world. An international classification is used to classify ROP. Based on a randomized control trial, well defined guidelines for laser treatment exist. Although randomized trials for new age anti-vascular endothelial growth factor (anti-VEGF) drugs in ROP exist, their role is less well defined.
The current review includes studies that report the newer variations in disease presentation, treatment indications outside current guidelines and the unanswered controversies surrounding the use of anti -VEGF agents in ROP. Evidence and flaws from major randomized trials and meta-analysis is presented.
Data from randomized trials, real world studies and perspective from practicing ROP physicians is collated.
Disease classification needs to expand to include certain subtypes like posterior zone 1 ROP and hybrid ROP. Objective criterion need to be defined for plus disease.Treatment indications need to be revisited for gray areas like persistent non resolving ROP or Stage 3 ROP in zone 2 without plus disease, which constitute a fair number of eyes being treated outside treatment criteria. Practical guidelines need to be developed for indications and rational use of anti-VEGF drugs in ROP. These also need to address management of disease reactivation and persistent avascular retina (PAR), after anti-VEGF treatment.
Further evidence based studies and guidelines are required to address real world dilemmas in managing ROP.
Posterior zone I retinopathy of prematurity: spectrum of disease and outcome after laser treatment
2019, Canadian Journal of Ophthalmology
To report the morphological spectrum and outcome after laser treatment in posterior zone I retinopathy of prematurity.
Retrospective, consecutive, interventional case series.
Review of charts and RetCam images of preterm infants with posterior zone I retinopathy of prematurity (defined as area within a circle, the radius of which extends from the center of the optic disc to the center of the macula) treated with confluent laser at a tertiary care referral institute between January 2006 and December 2015. Data was analyzed and tabulated using frequency and descriptive statistics to describe the demography, morphology, and outcome after laser treatment.
Fifty-six eyes (28 infants) with a mean gestational age of 28.65 ± 2.18 weeks and birth weight of 1153.04 ± 251.51 g were analyzed. Forty-two (75%) eyes had persistent tunica vasculosa lentis and 25 (44.6%) had preretinal hemorrhages. All eyes had circumferential ROP and a poorly developed foveal vasculature. Four distinct morphological patterns were encountered: I − typical aggressive posterior retinopathy was seen in 36 (64.3%) eyes; II − atypical aggressive posterior retinopathy (14 eyes; 25%) had raised fibrovascular proliferation always on the nasal retina close to the optic disc; III − hybrid retinopathy of prematurity (4 eyes; 8.7%) had a mat-like fibrous proliferation on vascularized posterior retina; and IV − threshold retinopathy of prematurity seen in 2 (4.4%) eyes. An unfavourable outcome was seen in 44 (78.6%) eyes.
Retinopathy of prematurity in posterior zone I presents with atypical morphology and poor outcomes despite confluent laser photocoagulation.
Présenter le spectre morphologique de la rétinopathie du prématuré (RDP) postérieure de zone I de même que les résultats du traitement au laser.
Étude rétrospective d’intervention d’une série de cas cliniques consécutifs.
Examen des dossiers médicaux et des images obtenues à la RetCam de nourrissons prématurés présentant une RDP postérieure de zone I (qui se définissait comme une zone à l’intérieur d’un cercle dont le rayon s’étale du centre du disque optique au centre de la macula) qui ont été traités par laser (photocoagulation confluente) après avoir été adressés à un centre de soins tertiaires entre janvier 2006 et décembre 2015. Les données ont été analysées et compilées à l’aide de statistiques de fréquence et de statistiques descriptives afin de codifier la démographie, la morphologie et les résultats du traitement au laser.
Cinquante-six yeux de 28 nourrissons dont l’âge gestationnel moyen était de 28,65 ± 2,18 semaines et dont le poids de naissance s’élevait à 1153,04 ± 251,51 g ont ainsi été analysés. Dans 42 yeux (75 %), on notait la persistance de la tunique vasculaire du cristallin, tandis que 25 yeux (44,6 %) présentaient des hémorragies prérétiniennes. Tous les yeux avaient une RDP circonférentielle de même qu’une vascularisation fovéale sous-développée. On a cerné 4 morphologies distinctes: I − rétinopathie postérieure agressive typique dans 36 yeux (64,3 %); II − rétinopathie postérieure agressive atypique dans 14 yeux (25 %) caractérisée par une augmentation de la prolifération fibrovasculaire, toujours du côté nasal de la rétine près du disque optique; III − RDP hybride dans 4 yeux (8,7 %) caractérisée par une prolifération fibreuse qui forme une sorte de tapis sur la rétine postérieure vascularisée; et IV − RDP seuil dans 2 yeux (4,4 %). Des résultats négatifs ont été observés dans 44 yeux (78,6 %).
La morphologie de la RDP postérieure de zone I est atypique, et le pronostic visuel des patients est peu encourageant en dépit du recours à la photocoagulation confluente.
Pathophysiology, screening and treatment of ROP: A multi-disciplinary perspective
2018, Progress in Retinal and Eye Research
Citation Excerpt :
Early vitreous surgery has been advocated but the results remain poor especially if fibrovascular growth has already reached the vitreous base when surgery is performed (Azuma et al., 2013). After laser for AP-ROP, there may be early decrease in posterior vascular abnormality, but the retinopathy can reappear and progress rapidly to intractable retinal detachment (Vinekar et al., 2008). A second session of laser to fill in areas of regression of flat neovascularization produced by a first session will produce fewer haemorrhages and less fibrosis post treatment than a single session of heavier laser (Vinekar et al., 2015a).
The population of infants at risk for retinopathy of prematurity (ROP) varies by world region; in countries with well developed neonatal intensive care services, the highest risk infants are those born at less than 28 weeks gestational age (GA) and less than 1 kg at birth, while, in regions where many aspects of neonatal intensive and ophthalmological care are not routinely available, more mature infants up to 2000 g at birth and 37 weeks GA are also at risk for severe ROP. Treatment options for both groups of patients include standard retinal laser photocoagulation or, more recently, intravitreal anti-VEGF drugs. In addition to detection and treatment of ROP, this review highlights new opportunities created by telemedicine, where screening and diagnosis of ROP in remote locations can be undertaken by non-ophthalmologists using digital fundus cameras. The ophthalmological care of the ROP infant is undertaken in the wider context of neonatal care and general wellbeing of the infant. Because of this context, this review takes a multi-disciplinary perspective with contributions from retinal vascular biologists, pediatric ophthalmologists, an epidemiologist and a neonatologist. This review highlights the latest insights regarding cellular and molecular mechanisms in the formation of the retinal vasculature in the human infant, pathogenesis of ROP, detection and treatment of severe ROP, the risks and benefits of anti-VEGF therapy, the identification of new therapies over the horizon, and the optimal neonatal care regimen for best ROP outcomes, and the benefits and pitfalls of telemedicine in the remote screening and diagnosis of ROP, all of which have the potential to improve ROP outcomes.
Monitoring neovascularization in aggressive posterior retinopathy of prematurity using optical coherence tomography angiography
2016, Journal of AAPOS
We describe the use of optical coherence tomography angiography (OCTA) in detecting and monitoring regression of the neovascular complex (NVC) in a case of aggressive posterior retinopathy of prematurity (AP-ROP). A premature Asian Indian girl with AP-ROP underwent laser photoablation at 26 days of life. Persistent NVC at the posterior border of the lasered retinal bed was detected clinically. On en face spectral domain optical coherence tomography (SD-OCT) and OCTA, the NVC appeared as an arborizing vascular net in the superficial capillary plexus. The deep capillary plexus and outer retinal layers showed corresponding flow outlines that suggested deeper extensions of the lesion. Supplemental laser treatment of the NVC was performed. Ten days later repeat en face SD-OCT and OCTA of the identical retinal location revealed that the vascular tortuosity and dilatation had reduced and that the flow lesions in the deeper layers were undetectable. Our findings in this case suggest that the NVC in AP-ROP extends beyond the superficial retina.
Off-label use of intravitreal bevacizumab for severe retinopathy of prematurity
2015, Archivos de la Sociedad Espanola de Oftalmologia
Examinar la calidad de la evidencia y variabilidad en el uso off-label de bevacizumab intravítreo en retinopatía del prematuro (ROP).
Se realizó una revisión amplia en Pubmed, Cochrane, Medline, utilizando las palabras factor de crecimiento vascular endotelial (VEGF), retinopatía del prematuro, tratamiento y bevacizumab.
Se encontraron publicados casos y series de casos, revisiones, una revisión sistemática y un ensayo clínico controlado y aleatorizado sobre uso de bevacizumab intravítreo en ROP severa, como monoterapia o combinado con láser o vitrectomía.
Aunque los resultados de la revisión han mostrado que la inyección intravítrea de bevacizumab es promisoria para el tratamiento de la ROP estadio 3+ en zona I o la ROP agresiva posterior, aún permanecen inciertas algunas cuestiones fundamentales como dosis máxima aceptada para prematuros, riesgo de efectos colaterales sistémicos y oculares a largo plazo, eficacia y bioactividad en un niño en desarrollo. En los reportes no hubo diferencias significativas en la tasa de recurrencia entre el tratamiento con bevacizumab intravítreo como monoterapia y tratamiento láser para el estadio 3 en zona II; este último es la mejor opción por seguridad y efectividad a largo plazo. En los estadios 1 y 2 de ROP no está indicado el tratamiento con bevacizumab intravítreo porque el riesgo de pérdida visual severa es bajo y el VEFG es necesario para el desarrollo de los vasos normales de la retina. Por otra parte, en estadios 4 y 5 debería ser contraindicado el uso de bevacizumab intravítreo porque acelera el desprendimiento de retina traccional.
To examine the quality of evidence and the variability in the off-label use of intravitreal bevacizumab for retinopathy of prematurity (ROP).
A wide review of the literature was performed using Pubmed, Medline, and Cochrane database, using the words vascular endothelial growth factor (VEGF), retinopathy of prematurity, treatment and bevacizumab.
Case reports, case series, reviews, one sistematic review and one randomized controlled trial were found on the use of intravitreal bevacizumab in severe ROP, as monotherapy or combined with láser and/or vitrectomy.
The results shown on the use of intravitreal bevacizumab in ROP stage 3+ in zone I or in aggressive posterior ROP are promising. However, uncertainty remains regarding its maximum tolerable dose in the neonatal group, its ocular and systemic safety profile, or its efficacy and bioactivity in a developing child. This report found no significant differences in the recurrence rates of ROP stage 3+ in zone II in patients treated with intravitreal bevacizumab monotherapy in comparison to láser, although the latter is the best option due to long-term safety and efficacy. The use of intravitreal bevacizumab is not indicated in stages 1 and 2 of ROP as the risk of severe visual loss is low and VEFG is necessary for normal retinal vessel development. On the other hand, the use of intravitreal bevacizumab would be contraindicated in stages 4 and 5 because the retinal detachment is accelerated.
A pilot optical coherence tomography angiography classification of retinal neovascularization in retinopathy of prematurity
2024, Scientific Reports

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Antonio Capone, Jr, MD, joined the Emory faculty at the conclusion of his Fellowship in Vitreoretinal Surgery and Diseases at Emory University in 1991. He joined Associated Retina Consultants (ARC) PC, in Royal Oak, Michigan in 2000. Dr Capone is a Clinical Associate Professor of Medical Sciences at Oakland University, Director of the ARC Vitreoretinal Fellowship Training Program. His special interests include pediatric retina and macular disease.

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Original articleEvolution of Retinal Detachment in Posterior Retinopathy of Prematurity: Impact on Treatment Approach

Purpose

Design

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

J AAPOS

J AAPOS

Am J Ophthalmol

The International Classification of Retinopathy of Prematurity Revisited

Arch Ophthalmol

Inadvertent skip areas in treatment of zone 1 Retinopathy of Prematurity

Retina

Zone I retinopathy of prematurity: clinical characteristics and treatment outcomes

Retina

15-year outcomes following threshold retinopathy of prematurity: final results from the multicenter trial of cryotherapy for retinopathy of prematurity

Arch Ophthalmol

Supplemental therapeutic oxygen for pre-threshold retinopathy of prematurity (STOP ROP), a randomized clinical trial: primary outcomes

Pediatrics

Original article
Evolution of Retinal Detachment in Posterior Retinopathy of Prematurity: Impact on Treatment Approach