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      Wide-field digital imaging based telemedicine for screening for acute retinopathy of prematurity (ROP). Six-year results of a multicentre field study

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          Abstract

          Objective

          To report on a 6-year experience with wide-field digital imaging based telemedicine (WFDI telemedicine) to reduce the risk for blindness from retinopathy of prematurity (ROP).

          Methods

          Wide-angle digital fundus cameras (RetCam 120, Massie Lab, Pleasanton, CA, USA) were installed in five neonatal intensive care units (NICUs) in Germany. All prematures at risk were screened with WFDI, and the local ophthalmologists were asked to continue binocular indirect ophthalmoscopy (BIO) according to the German guidelines. Image data were coded and transferred to the Reading Centre in Regensburg. Image evaluation and additional BIO of infants with suspected treatment-requiring ROP (STR-ROP i.e. threshold ROP zone II, prethreshold ROP zone I (type-1 ROP according to ETROP), and ROP possibly requiring treatment but not reliably classifiable from the images) were performed by paediatric ophthalmologists at the Reading Centre. ROP was classified following ICROP, ETROP, and revised ICROP criteria. Outcome measures were incidence of clinically relevant ROP (CR-ROP, i.e. any ROP up to mid-peripheral zone III, ≤ stage 3+), sensitivity to detect STR-ROP, and positive predictive value to detect treatment-requiring ROP (TR-ROP).

          Results

          In total, 1,222 prematures at risk were screened (mean BW 1395 g, SD ±507 g; mean GA 30 wks, SD ±3 wks). The overall incidence of CR-ROP was 27.6% (71.8% mild = stage 1 to 3 without plus disease, 15.7% prethreshold = type-1 ROP according to ETROP, 12.5% threshold according to ICROP). Zone I disease was present in 3.3%, zone II disease in 76.5%, and zone III disease in 20.2%. According to ETROP, 95 infants were type-1 or type-2 ROP; 67.4% type-1 ROP, and 32.6% type-2 ROP. Of all 1,222 infants, 3.5% received treatment. Following ETROP (not applied in the study), 5.3% would have been treated. The sensitivity for detecting STR-ROP was 100%, and the positive predictive value for TR-ROP 82.4% (28/34) at the time of the first referral (28 infants, ≤ stage 3+ in zone I or II).

          Conclusion

          All TR-ROP was detected in time, showing the potential of our telemedical screening program. The overall incidence of CR-ROP was comparable to ROP incidences reported in other West European countries.

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          Most cited references54

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          Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial.

          To determine whether earlier treatment using ablation of the avascular retina in high-risk prethreshold retinopathy of prematurity (ROP) results in improved grating visual acuity and retinal structural outcomes compared with conventional treatment. Infants with bilateral high-risk prethreshold ROP (n = 317) had one eye randomized to early treatment with the fellow eye managed conventionally (control eye). In asymmetric cases (n = 84), the eye with high-risk prethreshold ROP was randomized to early treatment or conventional management. High risk was determined using a model based on the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity natural history cohort. At a corrected age of 9 months, visual acuity was assessed by masked testers using the Teller acuity card procedure. At corrected ages of 6 and 9 months, eyes were examined for structural outcome. Outcomes for the 2 treatment groups of eyes were compared using chi2 analysis, combining data for bilateral and asymmetric cases. Grating acuity results showed a reduction in unfavorable visual acuity outcomes with earlier treatment, from 19.5% to 14.5% (P =.01). Unfavorable structural outcomes were reduced from 15.6% to 9.1% (P<.001) at 9 months. Further analysis supported retinal ablative therapy for eyes with type 1 ROP, defined as zone I, any stage ROP with plus disease (a degree of dilation and tortuosity of the posterior retinal blood vessels meeting or exceeding that of a standard photograph); zone I, stage 3 ROP without plus disease; or zone II, stage 2 or 3 ROP with plus disease. The analysis supported a wait-and-watch approach to type 2 ROP, defined as zone I, stage 1 or 2 ROP without plus disease or zone II, stage 3 ROP without plus disease. These eyes should be considered for treatment only if they progress to type 1 or threshold ROP. Early treatment of high-risk prethreshold ROP significantly reduced unfavorable outcomes to a clinically important degree. Additional analyses led to modified recommendations for the use of peripheral retinal ablation in eyes with ROP. Long-term follow-up is being conducted to learn whether the benefits noted in the first year after birth will persist into childhood.
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            Retinopathy of prematurity in middle-income countries.

            In the 1940s and 1950s retinopathy of prematurity (ROP) was the single commonest cause of blindness in children in many industrialised countries; it now accounts for only 6-18% of blindness registrations. It is not known what proportion of blindness is due to ROP in countries that do not have blindness registers. Information on blindness in children in these countries can be obtained by examining children in schools for the blind. Between 1991 and 1996, 4121 children in 23 countries with a visual acuity in the better eye of less than 6/60 were examined with a standard method. The proportion of severe visual impairment or blindness due to ROP ranged from 0% in most African countries to 38.6% in Cuba. These data suggest that ROP is becoming a major cause of potentially preventable blindness among children in middle-income countries that have introduced neonatal intensive-care services for preterm and low-birthweight babies.
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              Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: direct correlation with clinical retinopathy of prematurity.

              Retinopathy of prematurity is a blinding disease, initiated by lack of retinal vascular growth after premature birth. We show that lack of insulin-like growth factor I (IGF-I) in knockout mice prevents normal retinal vascular growth, despite the presence of vascular endothelial growth factor, important to vessel development. In vitro, low levels of IGF-I prevent vascular endothelial growth factor-induced activation of protein kinase B (Akt), a kinase critical for endothelial cell survival. Our results from studies in premature infants suggest that if the IGF-I level is sufficient after birth, normal vessel development occurs and retinopathy of prematurity does not develop. When IGF-I is persistently low, vessels cease to grow, maturing avascular retina becomes hypoxic and vascular endothelial growth factor accumulates in the vitreous. As IGF-I increases to a critical level, retinal neovascularization is triggered. These data indicate that serum IGF-I levels in premature infants can predict which infants will develop retinopathy of prematurity and further suggests that early restoration of IGF-I in premature infants to normal levels could prevent this disease.
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                Author and article information

                Contributors
                +49-641-9943801 , +49-641-9943809 , birgit.lorenz@uniklinikum-giessen.de
                Journal
                Graefes Arch Clin Exp Ophthalmol
                Graefe's Archive for Clinical and Experimental Ophthalmology
                Springer-Verlag (Berlin/Heidelberg )
                0721-832X
                1435-702X
                22 May 2009
                September 2009
                : 247
                : 9
                : 1251-1262
                Affiliations
                [1 ]Department of Ophthalmology, Justus-Liebig-University Giessen, Universitaetsklinikum Giessen and Marburg GmbH Giessen Campus, Friedrichstrasse 18, 35385 Giessen, Germany
                [2 ]Department of Paediatric Ophthalmology, Strabismology and Ophthalmogenetics, Regensburg University Medical Centre, University of Regensburg, Regensburg, Germany
                [3 ]Department of Ophthalmology, Regensburg University Medical Centre, University of Regensburg, Regensburg, Germany
                [4 ]Department of Ophthalmology, Johannes Gutenberg-Universitaet, Mainz, Germany
                Article
                1077
                10.1007/s00417-009-1077-7
                2720584
                19462177
                2551a06e-fe14-4c61-bca5-6ede0825a544
                © The Author(s) 2009
                History
                : 3 August 2008
                : 17 March 2009
                : 24 March 2009
                Categories
                Pediatrics
                Custom metadata
                © Springer-Verlag 2009

                Ophthalmology & Optometry
                telemedicine,retcam 120,wide-field digital imaging (wfdi),sensitivity,positive predictive value,retinopathy of prematurity (rop)

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