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ORIGINAL ARTICLE
Year : 2001  |  Volume : 49  |  Issue : 2  |  Page : 97-101

Threshold retinopathy of prematurity: ocular changes and sequelae following cryotherapy


Department of Ophthalmology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Correspondence Address:
Mangat R Dogra
Department of Ophthalmology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

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Source of Support: None, Conflict of Interest: None


PMID: 15884513

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  Abstract 

Purpose: To determine ocular changes and sequelae following cryotherapy for threshold retinopathy of prematurity (ROP).
Methods: This is a retrospective study of 49 eyes of 26 premature babies with threshold ROP treated with cryotherapy between 1995 and 1998. All eyes included in the study had favourable structural outcome after cryotherapy. Follow-up examination of all babies was done 12 - 62 months (average 28 months) after cryotherapy. Visual axis, fixation pattern, anterior segment examination, cycloplegic refraction and dilated fundus examination with indirect ophthalmoscopy were undertaken in all eyes during follow-up.
Results: Posterior pole retinal residuae observed following cryotherapy were tortousity of blood vessels in 32 (65.3%), narrow temporal arcade in 22 (44.89%), temporal crescent in 17 (34.69%), disc drag in 13 (26.53%) and macular heterotopia in 7 (14.28%) eyes. Myopia was observed in 20 (40.82%) eyes and strabismus in 5 (19.23%) babies. The significant risk factor for ocular changes was ROP with more clock hours of involvement (p < 0.05). Higher period of gestation was associated with posterior pole changes (p< 0.05).
Conclusions: All premature babies with threshold ROP treated with cryotherapy require frequent and long-term follow up to look for retinal residuae, refractive status, and ocular motility disorders.

Keywords: Retinopathy of prematurity, cryotherapy, CRYO-ROP study


How to cite this article:
Dogra MR, Narang S, Biswas C, Gupta A, Narang A. Threshold retinopathy of prematurity: ocular changes and sequelae following cryotherapy. Indian J Ophthalmol 2001;49:97-101

How to cite this URL:
Dogra MR, Narang S, Biswas C, Gupta A, Narang A. Threshold retinopathy of prematurity: ocular changes and sequelae following cryotherapy. Indian J Ophthalmol [serial online] 2001 [cited 2020 Apr 4];49:97-101. Available from: http://www.ijo.in/text.asp?2001/49/2/97/22656

POG-PERIOD OF GESTATION; BIRTH WT-BIRTH WEIGHT; C.H.INVOLVEMENT-CLOCK HOUR INVOLVEMENT; POST CON. AGE-POST CONCEPTION AGE; R.E-RIGHT EYE; L.E-LEFT EYE.

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POG-PERIOD OF GESTATION; BIRTH WT-BIRTH WEIGHT; C.H.INVOLVEMENT-CLOCK HOUR INVOLVEMENT; POST CON. AGE-POST CONCEPTION AGE; R.E-RIGHT EYE; L.E-LEFT EYE.

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Retinopathy of prematurity (ROP), first described by Terry in 1942, is a potentially blinding vasoproliferative disease of retina occurring in premature infants.[1] The incidence of ROP has increased in recent years due to the higher survival rate of extremely low birth weight babies. [2,3] The incidence of ROP in India varies from 38% to 47.27%.[4-6] Early detection and prompt intervention is needed to prevent the potentially blinding complications of the threshold disease. CRYO-ROP study, the multicentric randomized control clinical trial, established cryotherapy as a standard treatment for threshold ROP.[7-10] In the CRYO- ROP study, 5 year follow-up after cryotherapy showed a reduction in unfavourable structural and visual outcomes in treated versus control eyes from 61.7% to 47.1% and 45.4% to 26.9% respectively.[10] Various changes described after spontaneously regressed ROP and following cryotherapy include macular heterotopia, disc drag, retinal fold involving the posterior pole, preretinal membrane, foveal pigmentation, exudative detachment, vitreous haemorrhage, vitreous membranes, abnormal angle of insertion of major vessels at disc and tortousity of posterior pole vessels.[7-16] There is also increased frequency of myopia, strabismus and nystagmus in children with regressed disease.[7-16] All babies following cryotherapy required long-term follow-up and monitoring for these changes and their management.

To the best of our knowledge there are no reports from India regarding sequelae following cryotherapy. In the present study we have evaluated the retinal residuae and sequelae in threshold ROP after at least one year of cryotherapy treatment. The changes are correlated with the severity of the disease. We have also studied the possible correlation between the development of myopia and strabismus with the structural residuae of the regressed disease.


  Materials and Methods Top


This was a retrospective study of 49 eyes of 26 premature babies with threshold ROP treated with cryotherapy at our institute between 1995 and 1998. All the eyes included in the study had favourable structural outcome and were available for a complete examination after a minimum of one year after cryotherapy. We included only those babies in whom complete pretreatment and treatment information could be retrieved from the hospital records regarding period of gestation, birth weight, duration of oxygen exposure, associated systemic illness, stage, zone, extent and severity of the disease. The disease was documented as per the international ROP classification.[17-18] Mild, moderate and severe disease was defined as involvement of 5-7 clock hours, 8- 10 clock hours and 11-12 clock hours respectively, as per CRYO- ROP study.[19] Prethreshold, stage IV, stage V and the eyes with unfavourable structural outcome following cryotherapy were excluded from the study.

Fresh follow-up examination included evaluation of the visual axis, ocular movements, presence of any nystagmus or strabismus with flashlight and prisms. Anterior segment abnormalities like iris atrophy, anterior chamber depth and cataract were evaluated with the help of magnification offered by + 20 D lens and indirect ophthalmoscope or slitlamp examination wherever possible. Dilated posterior segment examination was done by direct and indirect ophthalmoscopy for any posterior pole abnormalities or peripheral fundus changes. Cycloplegic refraction was carried out in all eyes after instillation of atropine (1%) eye ointment twice a day for 3 days. Spherical equivalent of retinoscopy findings was used for statistical analysis in all cases. All the recorded changes at follow-up were correlated with period of gestation, birth weight, oxygen exposure, severity and extent of ROP, myopia and strabismus.

Statistical analysis was done in two phases. In phase 1 of the analysis, proportion of risk factors for ROP sequelae, myopia and squint were taken, and T-test or 'chi' square test was applied to test hypothesis of equality of proportions at 5% level of significance. In phase II of the analysis, the compound effect of various variables significant in phase I was analysed using multivariate logistic regression (SPSS software).


  Results Top


Of the 26 babies, 16 were males and 10 females. The birth weight of babies ranged from 780 to 1750 grams (mean 1227.7633.25 grams) and the gestational age at birth from 26 to 34 weeks (mean 29.860.29 weeks). Post-conceptional age (gestational age + postnatal age) at the time of treatment varied from 33 to 46 weeks (mean 39.690.37 weeks). Twenty-one babies (80.76%) had oxygen exposure ranging from 1 to 30 days (mean 7.67 days). The predominant associated diseases in most of the babies were respiratory distress, apnoea, neonatal jaundice and septicaemia.

Threshold ROP involved zone II in all the eyes. Number of clock hours involved varied from 5 to 12 (mean 7.780.27) clock hours. Mild, moderate and severe disease was present in 24(48.97%), 20(40.8%) and 5(10.7%) eyes respectively. Three of 49 eyes had preretinal bleed and 4 had disc drag at the time of treatment. The clinical details are shown in the Table.

Follow-up after cryotherapy ranged from 12 to 62 months (mean 28 months). Posterior pole ocular changes following cryotherapy at the last follow-up included sequelae due to peripheral scarring, such as narrow temporal vascular arcade in 22 (44.89%) eyes, retinal drag over the disc in 13 (26.53%) eyes, and macular heterotopia in 7 (14.28%) eyes. Other changes observed were vessel tortousity in 32 (65.3%) eyes, temporal crescent in 17 (34.69%) eyes, elliptical disc in 4 (8.16%), opaque nerve fibre in 2 (4.08%) eyes and macular pigmentation in one (2.04%) eye.

Peripheral ocular changes included diffuse cryo scars with pigmentation in all the eyes. In addition, vitreous membranes were observed in 13 (26.53%) and localised peripheral fractional retinal detachment in 6 (12.24%) eyes. Myopia ≥ 1 D (range 1 to 14 Dioptre) was observed in 20 eyes of 12 babies (40.82%). Of the 4 babies with unilateral myopia, 2 babies had unilateral threshold disease, 2 had bilateral threshold disease. In all these affected eyes cryotherapy was done. The fellow eye of the latter 2 patients had hyperopia < 3 D. Anisometropia of > 1 D was seen in 7 babies. Strabismus was recorded in 5 babies (19.23%), 3 had exotropia and 2 esotropia [Table - 1].

The severity of ROP in terms of clock-hour involvement was significantly correlated with presence of vascular tortousity (p=0.0368), narrow temporal arcade (p=0.0002), disc drag (p=0.0030), temporal crescent (p=0.0037), macular heterotopia (0.003), myopia (0.0009) and strabismus (p=0.0086) in phase I and II of statistical analysis. Higher period of gestation was significantly correlated with the risk of developing narrow temporal vascular arcade (p=0.0057), retinal drag over disc (p=0.0185), and myopia (p=0.0018) in phase I and II of statistical analysis. Macular heterotopia was significantly associated with longer gestation period in phase I of the statistical analysis only while phase II multivariate analysis did not reveal any significant association between the two.

Disc drag, macular heterotopia and temporal crescent was also found to have statistically significant association with birth weight (p<0.05) in phase I of the statistical analysis. However, in phase II multivariate analysis, after controlling for other variables, birth weight was found to be significantly associated with temporal crescent (p=0.0285) only. Oxygen exposure was significantly associated with macular heterotopia, temporal crescent and narrow temporal vascular arcade (p<0.05) in phase I only and no significant association was found in phase II of the analysis.

Myopia was found to be significantly associated with higher gestation age, vascular tortousity at posterior pole, straightening of temporal arcade, retinal drag over disc, temporal crescent, macular heterotopia and tractional retinal detachment (p<0.05) in phase I of analysis. However, none of the factors was found to be the independent risk factor for myopia in phase II of the statistical analysis. Strabismus was correlated with retinal drag over disc (p<0.05) and more clock hour involvement in phase I of the analysis. However, none of the factors was found to be the independent risk factors for myopia in phase II of the statistical analysis. No statistical correlation was found between strabismus and myopia or macular heterotopia.


  Discussion Top


Retinopathy of prematurity (ROP) may regress completely or leave sequelae ranging from mild myopia to bilateral total blindness.[7-16,19] The multicentric randomized control trial established the efficacy of cryotherapy in reducing unfavourable outcome in threshold ROP.[7-10] The major structural residuae following cryotherapy as reported by CRYO-ROP study included narrow temporal vascular arcade, tortousity of posterior pole vessels, pigment disturbances at macula, preretinal membrane and macular heterotopia. Other changes reported by CRYO-ROP study were shallow anterior chamber, pupillary reaction abnormality, vitreous membranes and tractional retinal detachment.[7-10,20] The incidence of these changes was determined in the present study and correlated to the severity of disease.

The tortousity of posterior pole vessels in 32 (65.3%) eyes was the most common sequelae of cryotherapy in eyes with threshold ROP. This was in contrast to the findings of the CRYO-ROP study, in which vessel tortousity was observed in 1.3% cases only at 5 years' follow-up.[10] While it is possible that mild tortousity of vessel may not have been considered in the CRYO-ROP study, Hindle reports vascular tortousity in 40% of his treated eyes.[21] The incidence of sequelae like narrowing of temporal arcade, vitreous membranes and tractional retinal detachment was comparable to the CRYO-ROP study and various other series.[7-10,22] However, we observed lower incidence of macular heterotopia (14.28%) and macular depigmentation (2%) as compared to CRYO-ROP study which reported these sequelae in 23.3% and 16.3% respectively at 5 year follow-up.[8]

We observed disc drag (26.53%) and temporal crescent (34.51%) in our cases. The CRYO-ROP study does not mention these two changes. Other studies report disc drag in 15.62% to 20.83%. [23,24]

No cases of nystagmus or anterior segment abnormalities were observed. This could be explained by the lower severity of threshold ROP in our series as compared to the CRYO-ROP group. The incidence of mild, moderate and severe disease in our study was 48.97%, 40.8%, 10.2% cases respectively, compared to 17.5%, 55.4% and 27% in symmetric and 11.5%, 65.4% and 23.01% in asymmetric group in CRYO-ROP study.[7]

In the present study, residual changes were found to be associated with more severe disease (p<0.05). similar association was reported in the CRYO-ROP study and various other studies. Period of gestation and birth weight were also found to have bearing on sequelae of ROP. Higher period of gestation and birth weight was associated with higher incidence of posterior pole changes which was contrary to most of the Western reports.[7-10, 12, 14]

We observed myopia in 20 (40.82 %) eyes. Others have reported higher incidence of myopia ranging from 50% to 94%. [8, 9, 21, 25-29] CRYO-ROP study reported myopia ≥ 2 D in 52.7% of the cases of which myopia ≥ 6 D was present in 33% cases. The lower incidence of myopia in this study could be explained by the less severe threshold ROP in our series. Mild to moderate disease involving zone 2 was present in 90% of the eyes in our series. High incidence of myopia in the CRYO-ROP study had positive correlation with lower birth weight and increased severity of ROP.[29-30] In this study we found statistically significant association of myopia with more severe disease (p < 0.0009). None of the sequelae was found to be the independent risk factor for the development of myopia. Higher incidence as well as severity of myopia is reported after cryotherapy as compared to laser treatment. [31, 32, 33] We report lower incidence of myopia which is comparable to a series reported following laser treatment.[33] However, we encountered high myopia (≥ - 5 D) in 4 (8.16%) of our cryo-treated eyes while Knight-Nanan and O' Kneefe report no high myopes in the laser treated group.[33]

Strabismus has been reported in 11.5% to 58% of ROP eyes. We observed strabismus in 5 (19.2%) of the eyes. Esotropia is reported in majority of the eyes contrary to our report of exotropia in 3 (6.12%) of the eyes.[7-10, 15, 24, 34, [35] The strabismus has statistically significant correlation with more clock-hour involvement and disc drag. There was no correlation between myopia and strabismus in the present study.

It is difficult to compare ocular changes among various studies undertaken before international classification of ROP and CRYO-ROP study because different parameters have been used in patient enrolment. Our experience shows that retinal residuae and sequelae were not comparable to the Western reports. The possible explanation could be less severe threshold ROP and higher birth weight babies in our series. Ophthalmologists must identify these changes early for further and timely management. All premature babies with threshold ROP treated with cryotherapy require frequent and long-term follow up to monitor for retinal residuae, refractive status, ocular motility disorders and development of vision. We need larger and longer follow-up studies from our country to establish guidelines and management plan for babies follolwing the cryotherapy for threshold ROP.



 
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    Tables

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