Peripheral retinal ablation in premature infants with threshold retinopathy of prematurity

Cover Sheet

Short title: Peripheral retinal ablation for ROP
Reviewer(s): Andersen CC, Phelps DL

Date of most recent amendment: 25/05/1999
Date of most recent substantive amendment: 10/05/1999
Date next stage expected: 10/05/2000

Contact
Dr Chad Andersen
Department of Pediatrics
Mercy Hospital for Women
Clarendon Street
East Melbourne
AUSTRALIA
3002
E-mail: candersen@mercy.com.au

Sources of support for the review

Acknowledgements
The authors thank Dr. B. Lemyre and Dr. P. Hamr for assistance with the translation of foreign language articles and Scott Shutts and Audra Boyer for extraction, copying and management of the numerous references. This work was supported in part by the NIH, National Eye Institute (DLP).

Potential conflict of interest
None

Abstract

Objective

In premature infants with threshold retinopathy of prematurity (ROP) does peripheral retinal ablation, by any means, reduce the incidence of adverse ophthalmic outcome?

Search strategy

The standard search strategy of the Cochrane Neonatal Review Group was used. This included a search of the Cochrane Neonatal Group Register of Clinical Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts from pediatric and ophthalmologic meetings, letters and expert informants. Search terms included "Retinopathy of Prematurity" [MeSH Terms], "Retrolental Fibroplasia" [All Fields] and "Lightcoagulation" [All Fields] or "Cryosurgery" [All Fields]. In addition, a personal bibliographic database was used as a cross-reference.

Selection criteria

All trials in human premature infants with threshold ROP utilizing random or quasi random allocation to either peripheral retinal ablation of the avascular retina, by any means, or concurrent control group with independent outcome assessment were initially selected for review. Following methodologic review, only studies using random allocation were selected for data extraction.

Data collection & analysis

Relevance and validity were assessed by the two authors and consensus reached. Each author extracted clinical outcomes from valid reports independently. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group.

Main results

Two randomised trials were identified. Data from these studies show that peripheral retinal ablation reduces the risk of (1) early unfavorable retinal structure from 47.9% to 28.1% (absolute risk reduction 19.8% [95% CI 27.9 - 11.8%]), (2) unfavorable retinal structure in early childhood from 44.3% to 26.3% (absolute risk reduction 18% [95% CI 27.0 - 9.1%]) and (3) unfavorable visual acuity in early childhood from 63% to 50.6% (absolute risk reduction 12.2% [95% CI 21.2 - 3.1]). In addition, visual fields in sighted eyes were slightly smaller in the treated (51.3° ± 11.8°) group as compared to the control (58.2°± 14.5°) group.

Conclusions

Peripheral retinal ablation reduces the incidence of adverse ophthalmic outcome in premature infants with threshold ROP. In sighted eyes, peripheral retinal ablation may reduce the size of the visual field. At this stage, long term outcomes remain unknown.

Background

Along with advances in perinatal medicine and the associated increased survival of extremely low birth weight infants has been a rise in the incidence of retinopathy of prematurity (ROP). As a vascular proliferative disorder of the immature retina in premature infants, ROP has both immediate and long-term complications. In the acute stages retinopathy can progress and threaten vision. In the long-term, even after regression, retinopathy can lead to acuity defects, refractive errors (especially high myopia) and gaze abnormalities. As such, it is a life long disorder that has a significant impact on the neurodevelopmental progress of premature infants.

Normally, the nasal and temporal retina are usually completely vascularised, to the ora serrata, by 36 and 40 weeks respectively. However, if damage occurs to the retinal capillaries during vascularisation then delay in vascularisation results. The pathophysiology in understood to start with injury to the developing retinal capillaries. This could potentially occur before or during birth, but is thought to primarily occur in the days following delivery. Once the developing vessels have been damaged, it is hypothesized that the retina responds with the production of vascular growth factors stimulating neovascularization, which is the observable retinopathy. This may result in successful revascularization of the retina (regression of the ROP), or in progression to neovascular membranes in the vitreous and subsequent scarring (cicatrix) and retinal detachment. Recent research suggests that vascular endothelial cell growth factor (VEGF) is one of the most important growth factors involved in this process (Aiello 1996, Provis 1997).

It is clear that the incidence and severity of retinopathy is inversely related to gestational age. Whilst the majority of infants less than 30 weeks gestational age will develop some form of retinopathy, in most cases it will regress spontaneously. Some infants, however, will develop progressive retinopathy which threatens vision.

Following a series of consensus meetings in 1984, ROP was newly classified according to the location (zone), extent (clock hours of disease), severity (stage) and presence or absence of plus disease, which represents vascular decompensation manifest as vessel dilatation and tortuosity (ICCROP 1984). This included the description of 'threshold' ROP, a prognostically relevant level of disease severity at which the risk of blindness in untreated eyes is greater than 47% (CRYO- ROP 1988).

Treatment of established 'threshold' ROP was introduced in order to prevent the high risk of blindness in affected eyes. This involves ablation of the peripheral avascular retina, thus preserving central macula vision. Initially transscleral cryoablation was used, as it was technically easier in infants with hazy vitreous. Subsequently, both photocoagulation and cryoablation have been used to destroy the avascular immature retina thought to be responsible for the angiogenic growth factors that drive the neovascularisation of the ROP.

The purpose of this review is to systematically evaluate the effect of peripheral avascular retinal ablation, by any means, on the incidence of adverse ophthalmic outcome in premature infants with threshold ROP.

Objectives

The objective of this review is to answer the question "In premature infants with threshold ROP does peripheral retinal ablation, by any means, reduce the incidence of adverse ophthalmic outcomes?"

Materials and Methods

Criteria for considering studies for this review

Types of studies
Relevant:
Human, premature infants with threshold ROP.
Peripheral retinal ablation of the avascular retina by any means.
Concurrent control group.
Outcomes identified and recorded systematically

Valid: In addition to relevant:
Randomised assignment
Concealment of group assignment prior to randomisation
Independent outcome assessment with masking of treatment allocation where possible.
Follow up rate > 80%.

Types of participants
Human preterm infants with "Threshold ROP".

Types of intervention
Ablation of the peripheral avascular retina by any means including cryotherapy, laser diode, laser argon, xenon arc photocoagulation. Reports using treatment to the proliferating ridge were not included.

Types of outcome measures

1. Early unfavorable retinal structure, assessed at less than 12 months, defined as:
(1) a posterior retinal fold (usually involving the macula) or
(2) a retinal detachment involving zone 1 of the posterior pole or
(3) retrolental tissue or mass obscuring the view of the posterior pole.

2. Early childhood unfavorable retinal structure, assessed at 4 to 6 years, defined as:
(1) ROP stage 4B or greater,
(2) obstructed view of macula from
(a) partial or complete cataract,
(b) partial retrolental membrane or
(c) partial or complete corneal opacity (owing to ROP),
(3) enucleation from all causes.

3. Early childhood unfavorable visual acuity, assessed at 4 to 6 years, defined as absence of vision or Snellen visual acuity of 20/200 or worse.

Search strategy for identification of studies

Multiple sources were searched with the following used as MeSH headings and/or keywords: [Retinopathy of Prematurity], [Retrolental Fibroplasia] and [Lightcoagulation] or [Cryosurgery].

Databases searched included the Cochrane Neonatal Review Group Register of Clinical Trials, MEDLINE, EMBASE and the Oxford Database of Perinatal Trials. In addition to the databases, review articles, abstracts from pediatric and ophthalmologic meetings through 1998, letters and expert informants were used.

Methods of the review

The standard methods of the Cochrane Collaboration for conducting a systematic review were used (Cochrane Handbook).

The initial comprehensive search yielded approximately 500 articles. These articles were screened independently by both authors by title and abstract into two groups, not relevant (by selection criteria) and possibly relevant (112). There was very strong agreement between the authors.
Photocopies of the possibly relevant articles were provided to two independent reviewers in order to determine the true relevance of the article and the methodology used in the study. Fifteen articles were considered relevant; twenty-six others were editorials, letters (without data), retrospective reviews and case series without controls; sixty were not relevant and six required further assessment (foreign language).
Four relevant studies contained in twenty citations were identified. Photocopies of the citations were provided to both reviewers who independently determined the methods used in the study. Methods were evaluated for concealment of randomisation and intervention, masking of outcome assessment where possible and completeness of follow up. Two studies were excluded; one did not use random allocation and the other used ablation to the peripheral avascular retina as well as the demarcation line, which is no longer recommended therapy (Harris 1976).
For the two remaining randomised studies, both reviewers independently extracted the data. As the unit of randomisation is the eye and not the infant, data extraction was based on results in eyes rather than in infants.

Relative risk and absolute risk reduction were examined for each study and for pooled data.

Description of studies

1. Multicenter Trial of Cryotherapy for Retinopathy of Prematurity 1988: Included
In this study, 291 infants with threshold ROP (defined as at least five contiguous or eight cumulative 30° sectors (clock hours) of stage 3+ ROP in zone 1 or zone 2) were enrolled at 23 centres. Eyes with 'threshold' ROP were randomised to either treatment with cryotherapy or control (no therapy). Random assignment was centralised with a telephone call to the coordinating centre. If the disease was bilateral, one eye was randomised and the fellow eye received the alternate therapy. If the disease was unilateral, only that eye was randomised. For the eyes allocated to treatment, cryotherapy was undertaken within 72 hours of randomisation. The results from this large study have been reported in multiple publications at various intervals of follow up from 3 months to 5½ years (see multiple citations in reference list). The current analysis was restricted to results at 3 months (Arch Ophthalmol 1990;108:195-204) and 5½ years (Arch Ophthalmol 1996;114:417-424) for simplicity. The results at 3½ years (Arch Ophthalmol 1993) were similar. At 3 and 12 months after randomisation, fundus examination was performed independently by two ophthalmologists and stereoscopic photographs of the retina were taken. Retinal scars from cryotherapy were obscured on the photographs before assessment at the central reading centre. 234 infants were available for follow up at 5½ years (36 died and 21 lost to follow up). Structural outcome was assessed by a "study certified ophthalmologist" and functional outcome was determined using Snellen visual acuity scores.

2. Tasman, et al 1985: Included
In this study, 28 infants with bilateral threshold ROP (stage III ROP and plus disease) were randomised to cryotherapy or control (no therapy). One eye was randomised to treatment or control and the fellow eye received the alternate therapy. Treatment occurred within 48 hours of randomisation. Infants with unilateral disease were excluded. Outcome assessment was determined within 14 days of therapy as satisfactory or unsatisfactory defined as persistence of plus disease and continued development of extraretinal fibrovascular proliferation leading to Stage 4 ROP. It is not clear if treatment allocation was masked or if outcome assessment was independent.

3. Harris, 1976: Excluded from analysis
In this study 10 premature infants with bilateral ROP were randomised to either retinal ablation or control. One eye was randomised using a coin toss and the fellow eye received the alternate therapy. Treatment consisted of either "direct xenon photocoagulation to the advancing fibrovascular margin, transscleral cryocoagulation of this margin, transscleral cryocoagulation of the margin plus cryocoagulation of the anterior avascular retina or delimiting photocoagulation of the normal retina immediately behind the vascularised ridge". Outcomes were not individually reported for the twenty eyes as the authors intended to report only long term outcomes many years later. The report concluded that treatment of the fibrovascular margin often resulted in haemorrhage, and for this reason, it is no longer recommended practice.

4. Mousel et al 1985: Excluded from analysis
Six eyes of six infants with bilateral ROP were treated with cryotherapy at two centres. One eye was assigned to cryoablation and the fellow eye received no therapy. In five of the six cases, treatment allocation was non-random. The authors performed all the eye examinations and outcome assessments.

Methodological quality of included studies

CRYO-ROP 1988
Concealment of randomisation - yes
Masked intervention - not possible
Complete follow-up - all randomised accounted for, 7% lost at 5½ years.
Masked outcome assessment - yes

Tasman et al 1985
Concealment of randomisation - cannot tell, probably not
Masked intervention - not possible
Complete follow up - yes (although excluded infants not described)
Masked outcome assessment - cannot tell, probably not

Results

Two randomised cohorts were combined and analysed with the CRYO-ROP study contributing the majority of the data (87%). Both studies used cryoablation. In eyes (265 total) with threshold ROP, cryotherapy reduced the incidence of unfavorable retinal structure at less than 12 months after randomisation from 47.9% to 28.1% (absolute risk reduction of 19.8% [95% CI 27.9 - 11.8%]), RRR of 41%. Therefore the number of eyes with threshold ROP needed to treat (NNT) to avoid one unfavorable outcome is five.

For outcomes in early childhood (5½ years) only data from the CRYO-ROP study were used. At 5½ years, cryotherapy reduced the incidence of unfavorable retinal structure from 44.3% to 26.3% (absolute risk reduction 18% [95% CI 27.0 - 9.1%]), RRR of 41%, and unfavorable visual acuity from 63% to 50.6% (absolute risk reduction of 12.2% [95% CI 21.2 - 3.1]), RRR of 19%. Therefore the number of eyes with threshold ROP needed to treat to prevent one early childhood unfavorable retinal structural event (NNT) is 5.5 . Similarly, the number needed to treat to prevent one unfavorable visual acuity event (NNT) in early childhood is 8. Visual field data from 78 infants at 5 of the 23 centres in the CRYO-ROP cohort and from 14 of 28 infants in Tasman's study was combined to provide information on visual field outcome in premature infants with ROP treated with cryotherapy. In the CRYO-ROP cohort the white sphere used for testing fields was 6 degrees in diameter whereas the Goldmann stimulus used in Tasman's cohort was approximately 3 degrees (25mm2 ). Analysis of the combined data show that cryotherapy reduced the visual field in sighted eyes from 58.2°± 14.5° in controls with ROP to 51.3° ± 11.8° in the treated group with ROP.

Discussion

Data from published randomised studies provides strong evidence that peripheral retinal ablation reduces the incidence of adverse visual outcome in premature infants with threshold ROP. Specifically, peripheral retinal ablation reduces the risk of adverse structural outcome at 12 months and at 5½ years. Further, this reduction in adverse structural outcome is reflected in a corresponding reduction in adverse acuity in the same infants. The advantage of retinal ablation in these eyes outweighs short term morbidity associated with the therapy. This includes an increase incidence of apnoea and bradycardia both during the procedure and in the following 1 to 3 days.

Interpretation of the data on visual fields is a little more complex. Although the studies tested visual fields differently, both are kinetic perimetry procedures and as such they are similar in methodology. In addition, although only a quarter of the inception cohort from the CRYO-ROP randomised study are reported, the cohort includes infants from five of twenty-three participating centres. Clearly, it is difficult to make generalisations from these data particularly as they do not include all of the original cohort. However, these data were included in the review to provide an insight into a possible adverse risk in the sighted eyes of infants treated with cryotherapy for threshold ROP. Further data from the whole cohort will be required before the significance of visual field reduction after peripheral retinal ablation is known. It is important to note that, compared to normal, eyes with ROP that spontaneously recovered also had a reduction in visual field.

Conclusions

Implications for practice

There is good evidence that peripheral retinal ablation reduces the incidence of adverse ophthalmic outcomes, both structural and functional, in premature infants with threshold retinopathy of prematurity.

Implications for research

Further research is needed before the significance of visual field defects in premature infants with ROP is known and whether the advantage conferred by peripheral ablation will persist into adult life.

Characteristics of Included Studies

Study: CRYO-ROP 1988
Method: Randomized controlled trial of peripheral ablation of avascular retina with cryotherapy
Participants: 291 infants with birth weight <1251grams, confirmed defined severity of ROP ("threshold") by certified examiners. Infants with congenital anomalies, or retinal detachment in one eye were not eligible for enrollment.
Interventions: Cryotherapy to avascular retina in one randomly selected eye if bilateral. Random assignment to treatment or control if only one eye. No infant received cryotherapy to both eyes.
Outcomes: Early: (up to one year) Retinal detachment, retinal folds involving the macula, or retrolental tissue or mass were unfavorable outcomes. Later outcomes included visual acuity, color vision, peripheral fields, myopia, and other visual outcomes.
Notes: Multiple manuscripts over several years of accumulating data

Study: Tasman 1985
Method: Controlled trial of treatment to one eye, allocation uncertain
Participants: 28 infants with bilateral stage 3 ROP with plus disease in Zone I or II.
Interventions: Cryotherapy to the avascular retina in one eye.
Outcomes: Regression of ROP vs retinal detachment.
Notes: Allocation of eyes was apparently not random. However, treatment was not clearly based on the relative severity of the ROP.

Characteristics of Excluded Studies

Study Identifier: Ben-Sira 1986
Reason for exclusion: Case matched controls, not concurrent.

Study Identifier: Bert 1981
Reason for exclusion: Case series, no controls.

Study Identifier: Davis 1990
Reason for exclusion: Narrative review.

Study Identifier: Fritch 1983
Reason for exclusion: Case series, no controls.

Study Identifier: Gerhard 1986
Reason for exclusion: Narrative review.

Study Identifier: Goggin 1993
Reason for exclusion: Laser compared to cryotherapy, no untreated controls.

Study Identifier: Guilbert 1986
Reason for exclusion: Observational study, no control group.

Study Identifier: Harris 1976
Reason for exclusion: Treatment was not limited to the avascular retina. Unable to assess outcomes from report.

Study Identifier: Hindle 1990
Reason for exclusion: Letter, no new data reported.

Study Identifier: Holmstrom 1993
Reason for exclusion: Narrative review.

Study Identifier: Iverson 1991
Reason for exclusion: Laser vs cryotherapy, no untreated controls.

Study Identifier: Kalina 1990
Reason for exclusion: Commentary, no data.

Study Identifier: Keith 1989
Reason for exclusion: Letter, contains case series data, no controls.

Study Identifier: L'Esperance 1969
Reason for exclusion: Review of techniques, single case described, no controls.

Study Identifier: Landers 1990
Reason for exclusion: Case series, no controls.

Study Identifier: Laser Group 1994
Reason for exclusion: No control group. Meta-analysis of laser vs cryotherapy with original data.

Study Identifier: Mousel 1985
Reason for exclusion: Six infants with bilateral ROP. One eye treated with cryotherapy; however, selection was based on severity. Treatment was applied to both the avascular retina and the line of demarcation. Ablation of the vessels at the transition is no longer recommended.

Study Identifier: Nagata 1988
Reason for exclusion: Natural history study, all severe ROP treated with photocoagulation or cyrotherapy. No controls.

Study Identifier: NH Cryo 1986
Reason for exclusion: No randomized subjects, no control group.

Study Identifier: Nissenkorn 1984
Reason for exclusion: Case report, no controls.

Study Identifier: Patz 1971
Reason for exclusion: Narrative review.

Study Identifier: Schechter 1993
Reason for exclusion: Letter, no data.

Study Identifier: Silverman 1986
Reason for exclusion: Narrative review.

Study Identifier: Stefansson 1983
Reason for exclusion: Narrative review

Study Identifier: Topilow 1990
Reason for exclusion: No control group.

References to Studies

Section 1. References to studies included in this review

Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity: preliminary results. Pediatrics 1988;81:697-706.

Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity. Preliminary results. Arch Ophthalmol 1988;106:471-479.

Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity. Three-month outcome. Arch Ophthalmol 1990;108:195-204.

Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity. One-year outcome--structure and function. Arch Ophthalmol 1990;108:1408-1416.

Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity. 3 1/2-year outcome--structure and function. Arch Ophthalmol 1993;111:339-344.

Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity. Snellen visual acuity and structural outcome at 5 1/2 years after randomization. Arch Ophthalmol 1996;114:417-424.

Dobson V, Quinn GE, Abramov I, Hardy RJ, Tung B, Siatkowski RM, Phelps DL. Color vision measured with pseudoisochromatic plates at five-and-a-half years in eyes of children from the CRYO-ROP study. Investigative Ophthalmology & Visual Science 1996;37:2467-2474.

Gilbert WS, Quinn GE, Dobson V, Reynolds J, Hardy RJ, Palmer EA. Multicenter Trial of Cryotherapy for Retinopathy of Prematurity Cooperative Group. Partial retinal detachment at 3 months after threshold retinopathy of prematurity. Long-term structural and functional outcome. Arch Ophthalmol 1996;114:1085-1091.

Palmer EA. Results of U.S. randomized clinical trial of cryotherapy for ROP (CRYO-ROP). Documenta Ophthalmologica 1990;74:245-251.

Quinn GE, Dobson V, Hardy RJ, Tung B, Phelps DL, Palmer EA. Visual fields measured with double-arc perimetry in eyes with threshold retinopathy of prematurity from the cryotherapy for retinopathy of prematurity trial. Ophthalmology 1996;103:1432-1437.

Quinn GE, Miller DL, Evans JA, Tasman WE, McNamara JA, Schaffer DB. Measurement of Goldmann visual fields in older children who received cryotherapy as infants for threshold retinopathy of prematurity. Arch Ophthalmol 1996;114:425-428.

Tasman W, Benson WE, Brown GC, Diamond G, Naidoff M, Quinn GE, Schaffer DB. Cryotherapy in active retinopathy of prematurity. International Ophthalmology 1987;10:107.

Tasman W, Brown GC, Naidoff M, Schaffer DB, Benson W, Quinn GE, Diamond G. Cryotherapy for active retinopathy of prematurity. Graefes Archive for Clinical & Experimental Ophthalmology 1987;225:3-4.

Tasman W, Brown GC, Schaffer DB, Quinn GE, Naidoff M, Benson WE, Diamond G. Cryotherapy for active retinopathy of prematurity. Ophthalmology 1986;93:580-585.

Tasman W. A pilot study on cryotherapy and active retinopathy of prematurity. Graefes Archive for Clinical & Experimental Ophthalmology 1986;224:201-202.

Tasman W. Management of retinopathy of prematurity. Ophthalmology 1985;92:995-999.

Section 2. References to studies excluded from this review

Ben-Sira I, Nissenkorn I, Weinberger D, Shohat M, Kremer I, Krikler R, Reisner SH. Long-term results of cryotherapy for active stages of retinopathy of prematurity. Ophthalmology 1986;93:1423-1428.

Bert MD, Friedman MW, Ballard R. Combined cryosurgery and scleral buckling in acute proliferative retrolental fibroplasia. Journal of Pediatric Ophthalmology & Strabismus 1981;18:9-12.

Davies PA. Retinopathy of prematurity [editorial]. Developmental Medicine & Child Neurology 1990;32:377-378.

Fritch CD. Early management of retinal problems associated with prematurity: cryotherapy treatment. Annals of Ophthalmology 1983;15:565-566.

Gerhard JP. [Prevention of retinopathy of prematurity]. [Review] [French]. Journal Francais d Ophtalmologie 1986;9:583-596.

Goggin M, O'Keefe M. Diode laser for retinopathy of prematurity--early outcome. Br J Ophthalmol 1993;77:559-562.

O'Keefe M, Goggin M, Algawi K. Laser therapy for retinopathy of prematurity [letter; comment]. Arch Ophthalmol 113:137;1995.

Guilbert F, Castier P, Madelain F, Amber A, and Leguern P. [Current status of retinopathy of premature infants in northern France]. [French]. Bulletin des Societes d Ophtalmologie de France 1986;86:869-873.

Harris GS, McCormick AQ. The prophylactic treatment of retrolental fibroplasia. Modern Problems in Ophthalmology 1977;18:364-367.

Harris GS. Retinopathy of prematurity and retinal detachment. Canadian Journal of Ophthalmology 11:21-25, 1976.

Hindle NW. Cryotherapy for retinopathy of prematurity: none, one, or both eyes [letter; comment]. Arch Ophthalmol 1990;108:1375-1376.

Hindle NW. Cryotherapy in infants with retinopathy of prematurity [letter; comment]. JAMA 1990;263:2052.

Holmstrom G. Retinopathy of prematurity [editorial] [see comments]. BMJ 1993;307:694-695.

Iverson DA, Trese MT, Orgel IK, Williams GA. Laser photocoagulation for threshold retinopathy of prematurity [letter]. Arch Ophthalmol 1991;109:1342-1343.

Kalina RE. Update on retinopathy of prematurity. Western Med 1990;153:188-189.

Keith CG, Doyle LW, Kitchen WH. Cryotherapy for retinopathy of prematurity [letter]. Arch Ophthalmol 107:1989;315-316.

L'Esperance FAJ. The treatment of ophthalmic vascular disease by argon laser photocoagulation. Transactions - American Academy of Ophthalmology & Otolaryngology 1969;73:1077-1096.

Landers MB, Semple HC, Ruben JB, Serdahl C. Argon laser photocoagulation for advanced retinopathy of prematurity. Am J Ophthalmol 1990;110:429-431.

Clarkson JG, Capone JA, Sternberg JP, Repka MX, Gilbert W, Chase C, Trese M, Palmer EA, Brown GC, McNamara JA, Quinn GE, Schaffer DB, Tasman W, Vander JF, Landers III MB, Spencer R, Hardy RJ. Laser therapy for retinopathy of prematurity. Arch Ophthalmol 1994;112:154-156.

Mousel DK, Hoyt CS. Cryotherapy for retinopathy of prematurity. Ophthalmology 1980;87:1121-1127.

Mousel DK. Cryotherapy for retinopathy of prematurity. A personal retrospective. Ophthalmology 92:375-378, 1985.

Nagata M, Terauchi H, Takeuchi A, Eguchi K, Tada K, Fujioka K, Oshima T, Majima A, Kato T, Ichikawa K, et al. [Multicenter prospective studies of retinopathy of prematurity. I. Incidence and results of treatment]. [Japanese]. Nippon Ganka Gakkai Zasshi - Acta Societatis Ophthalmologicae Japonicae 1988;92:646-657.

Palmer EA, Phelps DL. Multicenter trial of cryotherapy for retinopathy of prematurity. Pediatrics 1986;77:428-429.

Nissenkorn I, Kremer I, Ben-Sira I, Cohen S, Garner A. A clinicopathological case of retinopathy of prematurity (ROP) treated by peripheral cryopexy. Br J Ophthalmol 1984;68:36-41.

Nissenkorn I, Kremer I, Cohen S, Garner A, Ben-Sira I. Cryotreatment of retinopathy of prematurity [letter]. Br J Ophthalmol 68:686-687, 1984.

Patz A, Maumenee AE, Ryan SJ. Argon laser photocoagulation. Advantages and limitations. Transactions - American Academy of Ophthalmology & Otolaryngology 1971;75:569-579.

Schechter RJ. Laser treatment of retinopathy of prematurity [letter; comment]. Arch Ophthalmol 1993;111:730-731.

Silverman WA. Epoche in retinopathy of prematurity. Arch Dis Child 1986;61:522-525.

Stefansson E, Landers MB, Wolbarsht ML. Oxygenation and vasodilatation in relation to diabetic and other proliferate retinopathies. Ophthal Surg 1983;14:209-226.

Topilow HW, Ackerman AL. Cryotherapy for stage 3+ retinopathy of prematurity [letter; comment]. Arch Ophthalmol 1990;108:15-16.

Section 3. References to studies awaiting assessment

Al'banskii VG, Medvedev AN. [Retrolental fibroplasia]. [Review] [RUSSIAN]. Vestnik Oftalmologii 1983;65-69.

Helm W, Matzen C. [Symptomatic treatment of retinopathy in premature infants by photocoagulation]. [Polish]. Klinika Oczna 1982;84:303-304.

Majima A, Takahashi M, Hibino Y. Clinical observations of photocoagulation on retinopathy of prematurity. Japanese Journal of Clinical Ophthalmology 1976;30:93-97.

Prost M. [Present therapeutic possibilities in retrolental fibroplasia]. [Polish]. Klinika Oczna 1984;86:309-311.

Other References

Section 5. Additional references

Aiello LP. Vascular endothelial growth factor and the eye - past, present, and future. Arch Ophthalmol 1996;114:1252-1254.

International Committee for the Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity. Pediatrics 1984;74:127-133.

Provis JM, Leech, J, Diaz CM, Penfold PL, Stone J, and Keshet E. Development of the human retinal vasculature - cellular relations and VEGF expression. Experimental Eye Research 1997;65:555-568.

Table of Comparisons

01.00.00 Peripheral retinal ablation vs control

01.01.00 Early unfavorable retinal structure (<12 mo) (RR)

01.01.00 Early unfavorable retinal structure (<12 mo) (RD)

01.02.00 Early childhood retinal outcomes (5.5 yr) (RR)

01.02.00 Early childhood retinal outcomes (5.5 yr) (RD)

01.02.01 Unfavorable retinal structure

01.02.02 Unfavorable visual acuity

01.03.00 Extent of visual fields (degrees)