Clinical and Experimental Ophthalmology

2005;

33

: 339–340

Blackwell Science, LtdOxford, UKCEOClinical and Experimental Ophthalmology1442-64042005 The Royal Australian and New Zealand College of OphthalmologistsAugust 2005334339340Editorial

EditorialEditorial

Editorial

Retinopathy of prematurity: gone today, here tomorrow?

up in other studies. Single-centre studies may be prone toissues described above: differing entry criteria and small sam-ple size.

This report illustrates another very important phenome-non: individual centres may not see many infants withadvanced ROP, at least on a year-to-year basis. Conversely,individual centres could see many cases of advanced diseasein a short time period. When centres do see a few cases, itwill be tempting to ascribe these changes to coincidental (ornot) changes in neonatal or ophthalmic care. To their credit,the authors have carefully avoided this trap. Also, given thelow adverse structural outcome rates, clinicians could belulled into a state of complacency about this disease. Prob-lems in ascertainment of acuity outcomes in infants andyoung children also contribute to the potential illusion thatinfants’ acuity outcomes after treatment for ROP areimproved compared with 10 and 15 years ago.

It should be clear from the above discussion that the fieldof research dedicated to preserving or reversing eye diseaseprocesses in children needs enhanced measures of acuity, orsurrogate measures of acuity and acuity potential, and needsthese measures earlier in the child’s life. Electrophysiologyand behavioural measures are available to study vision inpreverbal children, each with its advantages and disadvan-tages. Acuity measured at 1 year of age will not necessarilyreflect future optotype acuity. Additionally, there are manyother aspects to visual functioning, including visual fields,contrast sensitivity and colour vision, which cannot be easilymeasured in preverbal children.

We suggest that another diagnostic tool may play animportant role in the evaluation of infant vision or visionpotential. Some of the more state-of-the-art methodologiesof analysis of gene expression may aid our understanding ofthe pathobiology of ROP. Proteomics, or the dynamic studyof protein distribution and expression, may offer a morecomprehensive approach to capturing and understandingROP-related changes in terms of both the ROP disease pro-cess and its possible array of molecular consequences. Bystudying the specific distribution of proteins during theactive phase of ROP, it may be possible to learn which ofthese are expressed, and when, in association with structuraland functional outcomes. This process may also help definechanges in groups of proteins and protein networks thatmight have an impact on the immediate pathobiology ofROP.

Already, proteomics studies are being used to detect smallquantities of protein expression in various tumours.

6

By usingadvanced techniques and bioinfomatics assessments, it will

In many parts of the world, retinopathy of prematurity(ROP) is a leading cause of vision impairment and blindnessin children.

1

Estimates from the USA indicate that ROPranks as the second leading cause of childhood blindness,with cortical visual impairment the leading cause.

2

Both dis-eases occur in premature infants. In middle-income nations,ROP may occur more frequently as neonatal care is providedin a fashion that could contribute to an increased incidenceof the disease. No wonder that considerable attention andresearch is aimed at this disease.

The study reported by Essex

et al

. in this issue of

Clinicaland Experimental Ophthalmology

offers further evidence that ret-inal ablation by laser is effective in preventing retinal detach-ments from ROP.

3

Results in this study show responses totreatment similar to that found in the Early Treatment forRetinopathy of Prematurity Study.

4

The authors note thatcomparisons with other large-scale clinical trials are difficult,in part due to screening and entry criteria for these variousstudies, and in part due to the smaller ‘sample size’ availableto one or even a handful of centres. In the Early Treatmentfor Retinopathy of Prematurity Study, for example, infants’eyes were randomized to early treatment or conventionalmanagement on the basis of risk status; that is, to qualify forrandomization, infants required prethreshold ROP

and

acumulative risk score for blindness of 15% or higher. Thus,an eye or eyes could have reached the threshold for treat-ment as used in the Cryotherapy for Retinopathy of Prema-turity Study, but not been randomized.

Given findings after 15 years of follow-up from the Cryo-therapy for Retinopathy of Prematurity Study, there is causefor concern that visual acuity outcomes after retinal ablationare not as good as initially hoped.

5

Does the research byEssex

et al

. dispel this concern, knowing that laser has largelyreplaced cryotherapy for management of severe ROP? Isthere evidence that laser ablation spares acuity and preventsmyopia? The authors herein report relatively low rates ofmyopia, and they report good acuity outcomes. Unfortu-nately, it is too early to know the extent to which lasertreatment will significantly reduce these additional problems.For example, favourable acuity defined in Essex

et al

.’s studyincluded central steady and maintained vision, and/or morethan one cycle per degree grating acuity. These generousdefinitions could result in an underestimation of acuity lossin this cohort of children. To be sure, eliminating retinaldetachment outcomes is enormously beneficial to children.It is far better to have 6/18 visual acuity than to be blind.However, many children with threshold ROP have signifi-cantly reduced acuity when measured with long-term follow-

340 Editorial

be possible in the future to identify protein ‘fingerprints’ ofdiseases. The concern that proteomics studies are simplyfishing expeditions, hoping to find culpable proteins, is over-stated. Proteomics experiments can be targeted to specificproteins, but also offer the opportunity to identify proteinsthat are expressed in a disease state, compared with controlstate. Perhaps a better metaphor for proteomics studieswould be fishing at a fish farm. The line is dropped in thepool with the virtual certainty that a fish will be hooked.Only the exact fish to be caught is unknown.

The authors are to be congratulated on their thoughtfulpaper. We can hope that their results reflect the possibilitythat ROP has been largely abrogated. But the disease hasbeen resistant in the past, declared cured only to rematerial-ize. Until follow-up studies show the problem resolved, withacuities spared, those involved in the care of these infantsmust grapple with better methods to detect vision outcome.One such method will undoubtedly be proteomics-based.Identification of molecular substrates of vision will providenew insights into management of this compelling disease.

William V Good MD

1

and Robert L Gendron PhD

2

1

Smith-Kettlewell Eye Research Institute, San Francisco, California,USA; and

2

Memorial University, St. John’s, Newfoundland, Canada

R

EFERENCES

1. Gilbert C, Fielder A, Gordillo L

et al.

Characteristics of infantswith severe retinopathy of prematurity in countries with low,moderate, and high levels of development: implications forscreening programs.

Pediatrics

2005;

115

: e518–25. Epub: 1April 2005.

2. Steinkuller PG, Du L, Gilbert C, Foster A, Collins ML, CoatsDA. Childhood blindness.

J AAPOS

1999;

3

: 26–32.3. Essex RW, Carden SM, Elder JE. Two-year results of laser

treatment for retinopathy of prematurity at a single neonatalintensive care unit.

Clin Experiment Ophthalmol

2005;

33

: 390–94.4. Early Treatment For Retinopathy of Prematurity Cooperative

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

Arch Ophthalmol

2003;

121

:1684–94.

5. Palmer EA, Hardy RJ, Dobson V

et al.

15-year outcomes fol-lowing threshold retinopathy of prematurity: final results fromthe multicenter trial of cryotherapy for retinopathy of prema-turity.

Arch Ophthalmol

2005;

123

: 311–18.6. Zhang Z, Bast RC Jr, Yu Y

et al.

Three biomarkers identifiedfrom serum proteomic analysis for the detection of early stageovarian cancer.

Cancer Res

2004;

64

: 5882–90.