Regression Of Retinopathy Of Prematurity Research Articles

Impact of the Cryotherapy for Retinopathy of Prematurity Randomized Clinical Trial

T HE TRUE IMPACT OF THE CRYOTHERAPY FOR Retinopathy of Prematurity (ROP) randomized trial, or CRYO-ROP trial as it came to be known, cannot be measured apart from the development of the international classification of ROP (ICROP), which served as the backbone of the trial’s organization. The trial served as a necessary and sufficient test of the validity of the classification itself. Both were validated by the exercise. A brief overview of the background of the ICROP is in order to understand how closely entwined the two were and how both were born in response to the upsurge of ROP following a more liberal policy of oxygen use in the decade of the 1960s and the sporadic reports of the beneficial effects of photocoagulation and cryotherapy (coming from Japan and Israel primarily). The need for a new classification became obvious because studies had shown in previous decades that spontaneous regression of ROP indeed occurred. A better way of describing the eyes that truly needed treatment was required to separate a true response to therapy from the natural history of the disease itself. In answer to the need, some 23 members from 11 countries with an interest in ROP assembled in Calgary, Alberta, Canada, in 1981 to map out a rough sketch of a classification system that they agreed to use for a year without publication. The group then reconvened on the campus of the National Institutes of Health, Bethesda, Maryland, to finalize the document, which was published in 1984. The direct results of these efforts were the conception, planning, and implementation of the Cryotherapy for ROP randomized clinical trial of cryotherapy against observation (no treatment). A group of ophthalmologists from the United States intimately involved in the development of knowledge of ROP and its classification, among them Earl Palmer, MD, the study’s principal investigator, David Schafer, MD, Graham Quinn, MD, Dale Phelps, MD, myself, and others, put together the manual of procedure. In this effort, we were joined by Robert Hardy, PhD, professor of epidemiology and biostatistics at the School of Public Health, University of Texas, Houston, who lent design and biostatistical expertise and served as study coordinating center principal investigator during this and subsequent studies. The study manual of procedure outlined in exquisite detail every step in the selection of eligible infants, examining technique, diagnosis of the disease, threshold for treatment, technique of treatment, and follow-up of the infant’s treatedeye.Because thediseasewasmostoftensymmetrical in patients ( 80%), one eye served as the treated eye and the other as its control. The threshold for treatment was greater than 5 clock hours of grade 3 ROP in zone 1 or 2 accompanied by plus disease—defined for the study as dilated and tortuous veins and arteries of the posterior pole vessels. Twenty-three centers were enrolled in the study and their principal investigators were trained in the study protocol, applying ICROP to the disease as they examined premature infants of birth weight less than 1251 gandaccuratelydiagnosingROPand its severity.Aftercareful peer review, the National Eye Institute fully supported the study and subsequent follow-up of the enrolled infants. The study compared treatment with cryotherapy to the avascular retina for threshold ROP vs observation and no treatment for threshold disease in the opposite eye. Subjects were randomized by eye when the level of ROP was equal in both eyes and by patient when one eye was at the threshold but the other was not. Unfavorable outcome was definedasa total retinaldetachmentoraretinal fold through the macula destroying central vision. The results, both anatomical and later functional, were positive for cryotherapy. The finding of an unfavorable outcome in the treated eye was reduced by 50% (to approximately 25%) over its nontreated control (unfavorable outcome in approximately 46%). Some 291 premature infants were entered in the trial. At that point, the trial was stopped as it became clear that even if all future infants needed to attain sample size had failed cryotherapy, the study results would not be reversed. The infants enrolled in the study have been carefully followed up for 15 years. And although the visual results have not been as striking as had been hoped, they have nevertheless maintained a statistically significant edge over the results in the untreated eye. Author Affiliation: Department of Ophthalmology, Harkness Eye Institute, Columbia University, New York, New York. The articles that follow are part of an ongoing series that aims to review collaborative prospective studies supported by the National Eye Institute. The first article, written by investigators, will remind readers of the rationale, goals, methods, findings, and recommendations. The second article, written by an expert who did not participate in the investigations, will offer a constructive critique and attempt to estimate the impact of the study on the practice of ophthalmology.

Combination of laser photocoagulation and intravitreal bevacizumab (Avastin®) for aggressive zone I retinopathy of prematurity

This report describes the use of combined laser photocoagulation and intravitreal bevacizumab administration for aggressive zone I retinopathy of prematurity (ROP). A male patient, born at 25 weeks gestation with a birth weight of 884 g, received indirect laser photocoagulation and a 0.75 mg intravitreal bevacizumab injection to each eye for aggressive stage 3 zone I ROP. Structural outcomes were evaluated 3 months after treatment. At 3-month follow-up, treatment had resulted in ROP regression, prompt resolution of plus signs and neovascular proliferation in both eyes, and no signs of systemic or ocular adverse events. The combination of indirect laser photocoagulation and intravitreal bevacizumab injection was well tolerated and induced prompt regression of aggressive zone I ROP.

LASER TREATMENT FOR RETINOPATHY OF PREMATURITY

To assess the number of laser burns applied to the peripheral retina to treat retinopathy of prematurity (ROP) in a recent population of patients and to compare that number with historical data. The authors performed a retrospective chart review of all patients treated for ROP within a single practice from 2002-2004. There were 183 eyes from 93 patients. Sufficient data for analysis were available on 112 eyes from 57 patients. Data from these patients were compared to those of patients reported upon in 1991. The average number of laser burns applied to the 112 eyes was 2163. Eyes with zone 1 disease had an average of 3077 spots and those with zone 2 disease had an average of 2072 spots. Greater than three months follow-up was available on 42 eyes from 21 patients. Of those eyes, 90% had complete regression of ROP. In an initial report of laser treatment for ROP by several of the same authors in 1991, the average number of laser burns applied for treatment of ROP was 816. There was a 265% increase in the average number of laser applications from the early study to the present. The data indicate that there has been a trend towards more confluent laser treatment to the avascular zone in ROP.

Fundus Fluorescein Angiography in the Screening for and Management of Retinopathy of Prematurity

Abstract Objectives: To describe the characteristics of fundus fluorescein angiography in retinopathy of prematurity (ROP) and to explore the possible benefits of fundus fluorescein angiography over conventional indirect ophthalmoscopy in the screening for and management of ROP. Patiente and Methods: Beginning in January 2003, 23 consecutive patients were recruited for a nonrandomized, investigational trial. Fifty-one sessions of fundus fluorescein angiography were performed as part of ROP screening. Resulte: Fundus fluorescein angiography caused no adverse effect. Clear angiograms were easily obtained. There was delayed arm-to-eye fluorescein transit. Leakage of fluorescein was observed in all stage 2 and stage 3 ROP The leakage resolved soon after treatment. Arteriovenous tufts were found far posterior to the ROP ridge and were a feature of severe ROP Conclusions: Some vascular pathology observed on angiograms cannot be seen on indirect ophthalmoscopy. There was delayed arm-to-eye transit and fluorescein transit within the eyes. Fundus fluorescein angiography allows more objective assessment of disease stage and zone. Regression of ROP is clearly observed on fundus fluorescein angiography. J Pediatr Ophthalmol Strabismus 2006;43:85-90.

Fundus Fluorescein Angiography in the Screening for and Management of Retinopathy of Prematurity

To describe the characteristics of fundus fluorescein angiography in retinopathy of prematurity (ROP) and to explore the possible benefits of fundus fluorescein angiography over conventional indirect ophthalmoscopy in the screening for and management of ROP. Beginning in January 2003, 23 consecutive patients were recruited for a nonrandomized, investigational trial. Fifty-one sessions of fundus fluorescein angiography were performed as part of ROP screening. Fundus fluorescein angiography caused no adverse effect. Clear angiograms were easily obtained. There was delayed arm-to-eye fluorescein transit. Leakage of fluorescein was observed in all stage 2 and stage 3 ROP. The leakage resolved soon after treatment. Arteriovenous tufts were found far posterior to the ROP ridge and were a feature of severe ROP. Some vascular pathology observed on angiograms cannot be seen on indirect ophthalmoscopy. There was delayed arm-to-eye transit and fluorescein transit within the eyes. Fundus fluorescein angiography allows more objective assessment of disease stage and zone. Regression of ROP is clearly observed on fundus fluorescein angiography.

Laser photocoagulation for retinopathy of prematurity: structural and functional outcome

To report the structural and refractive outcome after laser photocoagulation for retinopathy of prematurity (ROP). Nineteen consecutive patients who had undergone photocoagulation for ROP between 1997 and 2002 at our clinic were examined for this non-comparative, consecutive, interventional, retrospective case series. A total of 37 eyes received either transscleral or transpupillary laser treatment. Data consisted of grade of ROP pre- and postoperatively, birth weight, perioperative and postoperative complications and refraction. Based on indirect ophthalmoscopy, independent observers graded the extent of ROP and determined the postoperative refraction by retinoscopy. A total of 97% of all eyes responded to laser treatment with regression of ROP. Only one eye out of 37 progressed to stage IV B despite photocoagulation and therefore an encircling procedure was performed. After further progression a vitrectomy was carried out. Perioperative complications included haemorrhages in 22% that resorbed spontaneously and cataract formation in one eye (3%). Postoperative refractive errors at mean ages of 23 +/- 12 months and 45 +/- 14 months were evaluated in 15/19 patients (79%). The spherical equivalents ranged between -8 D and +6 D at the first examination and between -12 D and +7 D at the second examination. In all only 14% of the refracted eyes were myopic. Photocoagulation for ROP in our patients resulted in regression of threshold ROP. In addition, the analyses of the refractive outcomes demonstrated a predominance of hypermetropia in our patients.

Management outcome in prethreshold retinopathy of prematurity.

To evaluate the success of and timing for intervention in retinopathy of prematurity (ROP). Eighty-two eyes of 50 children with stage 3 ROP were divided into two groups based on severity. Cryotherapy or laser therapy was performed soon after the detection of threshold stage in the first group of 40 eyes and at a prethreshold stage in the second group of 42 eyes. The patients were observed from 4 months to 2 years and regression or progression was noted. Unfavorable outcomes including macular and disc drag and the progression of ROP to stages 4 and 5 were correlated with birth weight, gestational age, age at threshold, and age at intervention. Regression of ROP occurred in 75 (91.46%) of the eyes. An overall unfavorable outcome occurred in 14 (17.07%) of the eyes, 11 of which reached threshold during the critical period of 37 to 39 postconceptional weeks of age. Of the cases (n = 14) with an unfavorable outcome, 9 eyes (22.5%) were in the group treated in the threshold stage (n = 40) and 5 eyes (11.9%) were in the group treated at a prethreshold stage (n = 42). The mean birth weight, gestational age, age at threshold, and age at intervention in the favorable and unfavorable outcome groups were 953.2 +/- 2.19 g and 1,059.57 +/- 2.62 g, 28.63 +/- 2.03 weeks and 28.36 +/- 1.98 weeks, 38.04 +/- 2.13 weeks and 37.71 +/- 1.13 weeks, and 38.32 +/- 2.34 weeks and 38.25 +/- 1.05 weeks, respectively. Early intervention at a prethreshold stage of ROP or at a younger postconceptional age (ie, younger than 37 weeks) may decrease the incidence of an unfavorable outcome.

Transscleral diode laser in the treatment of retinopathy of prematurity.

To assess the outcome of contact transscleral diode laser (TSDL) in the treatment of threshold retinopathy of prematurity (ROP). TSDL was performed in 14 eyes of 8 babies who presented to the paediatric ophthalmic service at King's College Hospital between 1996 and 1997 with threshold ROP (median post-conceptual age 26 + 1 weeks, median birthweight 835 g) by a single surgeon. Follow-up ranged from 9 to 41 weeks (median 21 weeks). In 11 eyes (79%) regression of ROP occurred after a single laser treatment with a good anatomical outcome. In 3 eyes (21%) there was an unfavourable response with the development of traction retinal detachment. These include both eyes of one baby who rapidly progressed to stage IV ROP. One other eye developed a fibrotic band a few months after treatment. No significant complications of laser treatment were observed. These initial results indicate that TSDL photocoagulation is an effective and technically straightforward alternative to cryotherapy in the treatment of ROP.

Diode laser photocoagulation for stage 3+ retinopathy of prematurity.

Laser photocoagulation in retinopathy of prematurity (ROP) appears to have fewer adverse effects than cryotherapy and seems to be at least as effective. To evaluate the efficacy and safety of diode laser photocoagulation, we included 42 eyes with stage 3+ ROP of 24 preterm infants (gestational age 24-29 weeks, mean +/- SD 26.6 +/- 1.3 weeks; birth weight 480-1400 g, 896 +/- 196 g) in a prospective clinical study. Photocoagulation treatment was performed using a diode laser (810 nm) with a laser indirect ophthalmoscope delivery system. Follow-up ranged from 3 to 16 months (8.8 +/- 4.0 months). In 39 (93%) of 42 eyes ROP regressed after a single laser treatment and the outcome was a flat, attached retina. One eye (2%) had a second laser session and another eye (2%) had additional retinal detachment surgery, resulting in the regression of ROP and a flat, attached retina. Thus, the success rate was 41 (98%) out of 42 eyes. In one (2%) of the 42 eyes treatment failed and ROP progressed to stage 5, although additional retinal detachment surgery was performed. No adverse side effects of diode laser treatment were noticed except for a small amount of retinal/preretinal bleeding in the ridge in five eyes (12%) and a small postoperative anterior chamber hemorrhage in one eye (2%) with dense tunica vasculosa lentis. Neither lenticular opacities nor cataract formation were encountered. Diode laser photocoagulation for stage 3+ ROP showed only minor side effects and was at least as effective as cryotherapy treatment.

Results of cryotherapy for retinopathy of prematurity.

Results are presented from a case material of 22 prematurely born infants (43 eyes) who received cryotherapy for retinopathy of prematurity (ROP); 20 eyes were treated at stage 3, 14 at stage 3 plus, and nine at stage 4A. Follow-up examinations at the age of 26 to 52 months (average 38 months) showed regression of ROP in all eyes and visual acuities of 6/60 or better. The timing of cryotherapy is discussed. The present experience indicates treatment earlier than recommended by the US Cryotherapy of Retinopathy of Prematurity Study Group. There are, as yet, no reliable clinical criteria that can predict which eyes will progress from stage 3 to stages 4 or 5 (tractional retinal detachment or retrolental fibroplasia). Hence, infants at risk should be repeatedly examined and a progression towards impending retinal detachment diagnosed.

Laser therapy for retinopathy of prematurity.

Nine patients were treated with indirect ophthalmoscope argon laser photocoagulation for threshold retinopathy of prematurity (ROP). A total of 16 eyes were treated at an average postconceptional age of 36.31 weeks. All eyes demonstrated regression of threshold ROP. Follow up was between 1 and 14 months postoperatively. Laser photocoagulation for ROP may be an effective alternative in treating high risk levels of ROP.

Limiting Applications of Cryotherapy for Severe Retinopathy of Prematurity

In an effort to minimize surgical and visual morbidity of cryotherapy for retinopathy of prematurity (ROP), 18 eyes of 13 patients with 3 to 7 clock hours of stage 3 ROP with "plus" disease were treated by cryotherapy applications limited to the avascular retina adjacent to the areas of stage 3 disease. In 17 of 18 eyes, this limited use of cryotherapy was sufficient to cause regression of ROP without further treatments. After at least 3 months follow-up, ROP outcome showed a normal macular appearance in 16 eyes; two eyes developed macular dragging; no retinal detachments occurred.