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Year : 1998  |  Volume : 46  |  Issue : 1  |  Page : 15-19

Treatment of threshold retinopathy of prematurity

Medical and Vision Research Foundations, Chennai, India

Correspondence Address:
D A Deshpande
Medical and Vision Research Foundations, Chennai
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Source of Support: None, Conflict of Interest: None

PMID: 9707842

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This report deals with our experience in the management of threshold retinopathy of prematurity (ROP). A total of 45 eyes of 23 infants were subjected to treatment of threshold ROP. 26.1% of these infants had a birth weight of >l,500 gm. The preferred modality of treatment was laser indirect photocoagulation, which was facilitated by scleral depression. Cryopexy was done in cases with nondilating pupils or medial haze and was always under general anaesthesia. Retreatment with either modality was needed in 42.2% eyes; in this the skip areas were covered. Total regression of diseases was achieved in 91.1% eyes with no sequelae. All the 4 eyes that progressed to stage 5 despite treatment had zone 1 disease. Major treatment-induced complications did not occur in this series. This study underscores the importance of routine screening of infants upto 2,000 gm birth weight for ROP and the excellent response that is achieved with laser photocoagulation in inducing regression of threshold ROP. Laser is the preferred method of treatment in view of the absence of treatment-related morbidity to the premature infants.

Keywords: Retinopathy of prematurity, laser photocoagulation, cryopexy, outcome

How to cite this article:
Deshpande D A, Chaturvedi M, Gopal L, Ramachandran S, Shanmugasundaram R. Treatment of threshold retinopathy of prematurity. Indian J Ophthalmol 1998;46:15-9

How to cite this URL:
Deshpande D A, Chaturvedi M, Gopal L, Ramachandran S, Shanmugasundaram R. Treatment of threshold retinopathy of prematurity. Indian J Ophthalmol [serial online] 1998 [cited 2023 Feb 2];46:15-9. Available from: https://www.ijo.in/text.asp?1998/46/1/15/14983

Retinopathy of prematurity (ROP), an abnormal vascular proliferative retinopathy seen in premature infants with low birth weight, is fast becoming a major concern. In the recent past, there has been a rise in the incidence of ROP concurrent with the rise in the survival rate of babies with low birth weight. Indian studies have reported the incidence of ROP in premature infants as 38-47%.[1],[2] Prematurity, low birth weight, and oxygen administration have been identified as some of the major risk factors associated with ROP. The International classification for retinopathy of prematurity (ICROP)[3] and the Cryotherapy for retinopathy of prematurity (CRYO-ROP) trial[4] have paved the way for a better understanding of the natural history of ROP and to define better what constitutes threshold ROP. ROP may regress completely and spontaneously or may progress to total retinal detachment. It can also regress leaving behind sequelae such as ectopic macula, dragged disc, and straightening of blood vessels. The treatment of threshold disease can be performed by cryotherapy[5] or with laser photocoagulation.[6][7][8] In this paper, we report our experience in treating 45 eyes of 23 patients with threshold ROP.

  Materials and Methods Top

Between October 1992 and May 1996, on routine screening of premature infants with birth weight <2000 gm, threshold ROP was identified in 45 eyes of 23 patients. All the infants except one were referred for ROP screening from a single neonatal unit.

Detailed history was recorded including the gestational age, the birth weight, significant post natal problems such as apnoeic spells, septicemia, need for blood transfusions, and intraventicular hemorrhages. The age at first presentation was noted. The ocular examination was mostly conducted in the ophthalmology outpatient department. In cases where the infant was still in the neonatal unit at 4 weeks after birth, screening was done in the neonatal unit. All ocular examinations were conducted by the same observer.

Ocular examination was done without anaesthesia. Anterior segment was examined for corneal opacities, non-dilating pupil, persistent tunica vasculosa lentis, and plus disease of the iris. The pupils were dilated using 2.5% phenylephrine and 1% tropicamide, instilled twice at an interval of 15 minutes. The infant was wrapped warmly. An Alfonso speculum was used to separate the lids, and the fundus was examined with a binocular indirect ophthalmoscope and a +30 diopter (D) lens. Fundus findings were classified according to ICROP.[3]

A strict protocol was adopted for follow-up of these infants. Infants with peripheral avascular retina without ROP, and patients with ROP of any prethreshold stage, were followed-up till they regressed and developed normal peripheral vascularisation, or till they progressed to the threshold stage. All eyes presenting with threshold disease at first examination or developing the same on review examination were treated within 48 hours. Threshold disease was identified as per the CRYO-ROP recommendations as stage 3 plus disease involving atleast 5 continuous clock hours or 8 discontinuous clock hours. Stage 3 disease was identified by the presence of extraretinal neovascularisation.

Eyes with threshold disease were treated preferentially with laser photocoagulation using the indirect delivery system (LIP). Transconjunctival cryopexy (TCC) was done only in case of a nondilating pupil, inability to treat up to the ora with laser, or media haze.

  Procedure for laser photocoagulation Top

LIP was done using either the argon green laser (Coherent Inc, USA) or diode laser (IRIS Medical Inc, USA). Treatment was performed without general anaesthesia. Due to its portability, diode laser was used when the treatment had to be conducted in the neonatal unit. Diode laser was also chosen if significant tunica vasculosa lentis was present. In other cases, either argon or diode was used without preference. Cardiac monitoring was done throughout the procedure. Topical anaesthesia with 4% lignocaine eye drops was used to facilitate transconjunctival scleral depression. The child was restrained by an assistant. Alfonso speculum was used to retract the eye lids. Intermittent corneal wetting was done with ringer lactate solution taking care to mop up the excess fluid with cotton-tipped applicators as excess fluid, if allowed to collect in the fornices, interferes with the clear visualisation of the fundus. The surgeon stabilized the head of the infant with one hand while holding the condensing lens with the other. A +20 D lens was used for treatment. The usual settings used for argon laser were: power 150 mW and duration 150 msec, and that for diode laser were: power 200 mW and duration 300 msec. The avascular retina was treated starting just anterior to the ridge. Treatment of the more anterior retina was aided by scleral depression using an infant scleral depressor.[9]While using the infant scleral depressor, the infants head was stabilized by an assistant so as to permit the surgeon to use both hands. The burns were placed at roughly half a burn width apart. Treatment of both eyes was done in one sitting.

  Procedure for transconjunctival cryopexy Top

TCC was always done under general anaesthesia with endotracheal intubation. Adult retina cryoprobe was utilized, and using contiguous applications, the avascular retina was treated. Both eyes were treated simultaneously. None of the eyes in this series had conjunctival incision. A 24 hour monitoring of the infants for apnoeic spells, was done after extubation. Steroid ointment was instilled at conclusion of treatment and steroid drops (betamethasone 0.1%) were instilled twice a day for 3 days subsequently.

  Follow-up after treatment Top

Weekly examinations were carried out to monitor the progress of the disease. If adequate regression was not noted by 1-2 weeks, additional treatment was done. Regression was identified by disappearance or reduction of plus disease, as well as by reduction in the prominence of the ridge. By third week normal vascularisation started to proceed into the previously avascular area, between the burns caused by laser or cryo. If cryo was done in the first sitting, laser was usually performed in the second sitting. If laser was done in the first sitting, retreatment was either with laser or with cryo. Where the initial laser treatment could not reach upto the ora serrata, retreatment was done with cryo, while if only skip areas had to be filled up, retreatment was done with laser.

  Results Top

Of 220 premature infants with birth weight <2,000 gm screened between October 1992 and May 1996, a total of 45 eyes of 23 infants which developed threshold ROP were included in this study. The incidence of threshold ROP in this series was 10.5%. Of these infants, 12 were males and 11 females. The gestational age ranged from 26 to 35 (mean 31.6) weeks. The birth weight ranged from 900 to 1,950 (mean 1,406, median 1,500) gm. Six infants had birth weight >l,500 gm; one infant weighed 1,950 gm at birth and yet developed threshold ROP. 19 of the 23 infants had received oxygen postnatally for variable durations. 16 infants received phototherapy for neonatal jaundice and 14 had septicemia. All the infants with birth weight of >l,500 gm who developed threshold ROP, had a stormy postnatal course in the form of septicemia, attacks of hypoglycemia and spells of apnoea. The age at first examination ranged from 30 to 66 (median 33) days. Only 6 children had their first examination later than 45 days after birth.

Of the total 45 eyes, 26 eyes (57.8%) of 14 infants had threshold disease at first examination. The rest presented with either only non-vascularised periphery or pre-threshold ROP that progressed to threshold ROP subsequently. Sixteen infants (69.6%) had bilateral symmetrical disease. Age at diagnosis of threshold disease ranged from 30 to 78 (mean 40) days. An eye of one patient did not develop threshold disease and regressed spontaneously, thus accounting for 45 eyes of 23 infants that needed treatment. Zone I disease was seen only in 4 eyes of 2 patients. The circumferential extent of the disease was variable, with most cases having about 8 clock hours involvement. The disease was mostly continuous. Nasal retina around the horizontal meridian was involved in 8 eyes (17.8%). In this series, temporal retina was found to harbour more advanced disease compared to nasasl retina in all except the 4 eyes with zone I disease, wherein the disease was more or less uniform all round.

Initial treatment was with LIP (argon laser) in 30 eyes, LIP (diode) in 10 eyes, and TCC in 5 eyes. The average number of laser burns per eye was 336 and the average number of cryo applications was 20. 19 eyes did not show adequate regression by 2 weeks. Although the plus disease had regressed, the ridge remaned prominent. Hence retreatment was done. In 14 eyes laser and in 5 cryo was used for the retreatment.

There were been no occurences of corneal or lenticular burns in this series. Transient bradycardia occured in all infants that had general anaesthesia for TCC. Laser under topical anaesthesia produced only very mild bradycardia in a few infants during scleraldepression. This was not significant enough to halt the process of treatment. Lid edema of severe degree was noted on the first post-treatment day in all eyes that underwent cryo but regressed rapidly by 3-4 days. There were no instances of vitreous or retinal haemorrhages.

Follow-up ranged from 23 days to 32 months (mean 8.8 months). The infants with the least follow-up also had either total regression or progression to stage 5 and thus could be included in the analysis without affecting the validity of inferences. Regression was noticed in 41 (91.1%) eyes. None of these eyes showed any vision affecting sequelae such as ectopic macula. In 2 cases there was minimal gliosis in the temporal periphery which did not exert any traction on the retina. The Figure shows fundus photograph of one eye of a 4 year old child treated with LIP at the age of 1 month. Four (8.9%) eyes of 2 patients progressed to-stage 5 ROP despite initial reduction in vascularity. Both these infants had zone I disease involving 360. One infant received TCC followed by LIP on a second sitting while the other received only laser photocoagulation. One of the infants was seen for the first time by us at 66 days after birth and had significant vitreous haze. Of these 2 infants that progressed to stage 5, one underwent lensectomy and vitrectomy by closed route in both eyes with successfully attached retina, while the other refused treatment.

  Discussion Top

Retinopathy of prematurity is a disease that is fast assuming epidemic proportions because of the improved neonatal care offered to infants with low birth weight. That retinopathy of prematurity may be a significant problem in India as well, has been suggested by two recent studies.[1],[2] The ICROP has made it convenient to classify ROP and has enabled setting up of guidelines to decide on treatment of ROP. Threshold stage by definition involves 5 continuous or 8 discontinuous clock hours of stage 3 plus disease. CRYO-ROP study has shown a 50% reduction in the unfavourable outcome of treated versus untreated groups of threshold ROP.[5] In view of the results of this study, cryo had been the mainstay of treatment of threshold disease. Laser was used for this treatment as early as 1968 by Nagata et al.[6] However, it did not become popular till the advent of the indirect delivery system. The advent of diode laser has made the treatment of such infants possible in the neonatal unit itself as the machine is portable. McNamara et al[7] have shown argon laser photocoagulation to be as effective as cryo in the management of threshold ROP. In a subsequent study the same authors reported equally effective results with diode laser as well.[10]

Several advantages have been cited for laser photocoagulation vis-a-vis cryo. Cryo usually is performed under general anaesthesia with the attendant risk involved in view of the prematurity and the postnatal problems that the child usually develops. Cryo treatment under local anaesthesia has been done by some authors.[7] Local anaesthesia does not necessarily eliminate the morbidity associated with cryopexy in view of the pain component that cannot be eliminated totally with subconjunctival anaesthesia alone. Cryopexy of posterior areas as in zone I disease entails a surgical procedure involving conjunctival incision. Postoperatively cryotherapy is associated with severe orbital and lid edema. Very often, one is not able to see the fundus on the first postoperative day. In contrast, indirect delivery laser photocoagulation has a lot of advantages. There is practically no need for anaesthesia. Topical anaesthesia alone is needed for scleral depression when indicated. In most cases one is able to satisfactorily treat right up to the periphery with the help of scleral depression. The morbidity to the child is almost nil, barring the occasional oculo-cardiac reflex caused by scleral depression. Postoperatively, the eyes remain quiet and do not need any medication.

Laser photocoagulation needs more patience and effort from the surgeon's point of view compared to cryotherapy. Since there is no control on the movement of the infants eye, one has to wait for the opportune moment to press the foot switch while focusing on the retina. Scleral depression not only helps in treating the periphery, but helps stabilize the eye even for posterior treatment. Reaching the periphery is also facilitated by the surgeon bending and bringing his eye level down rather than trying to turn the infant's head away. In view of the clear media, usually very low power settings are enough to produce good retinal burns. Where obvious tunica vasculosa lentis is present, it is preferable to use diode laser to reduce the risk of iatrogenic lens opacities. Regression was usually noted by 1 week after treatment; but total regression has sometimes taken up to 3 weeks.

Fleming et al[11] recommend early treatment for zone I disease. They treated these eyes as soon as plus disease was noted and did not wait for stage 3 to develop. They reported good success in all the 9 infants treated. Capone et a18 also reported good regression with diode laser for zone I disease in 25 of the 30 eyes treated by them. In our series 2 infants had zone I disease. One was referred to us only at 66 days after birth and had severe stage 3 plus disease. After initial cryo to the accessible periphery, LIP was done to the posterior retina in a second sitting. After the initial cryo, the media cleared and the pupils dilated better, enabling laser photocoagulation to the untreated posterior retina. The second case was treated fairly early with diode laser when only plus disease was identified even before stage 3 developed. Despite initial signs of regression, there was delayed fibrosis leading to stage 5 ROP. The number of eyes with zone I disease was too small in this series for comment on the efficacy of the treatment in these eyes. The CRYO-ROP study[5] showed reduction in unfavourable outcome from 91.7% to only 75% with treatment in eyes with zone I disease, while the studies by Capone et al[8]and Fleming et al[11] show much better results using diode laser. Laser also leads to less tissue destruction than cryo and theoretically, the retina between burns may function as in panretinal photocoagulation for diabetic retinopathy. This may not be a significant factor in case of anterior zone II disease but in zone I and posterior zone II disease it may assume significance. Our study does not claim to answer the question as to whether cryo or laser is superior, since it is only a retrospective analysis and not a randomised controlled clinical trial. Our choice of cryotherapy was in eyes that presented with significant vitreous haze and wherein the pupils did not dilate well. In the rest wherein both modalities could be used, we preferred laser for the reasons already explained. Most studies have quoted threshold ROP as occurring in infants with birth weight <l,250 gm.[4],[7],[10] Hunter and Repka[12] in their series of 19 infants, report threshold ROP only in infants with birth weight <863 gm, although infants with birth weight up to 1,500 gms were screened. Hence it is surprising to note that 26.1% of infants with threshold ROP in this series had birth weight >l,500 gm, and that there was one infant with 1,950 gm birth weight that developed threshold disease. Whether the lack of a routine use of surfactant therapy in premature infants has anything to do with this behavior is a point to be considered. Hunter and Repka[12]believe that larger infants possibly escape ROP with surfactant therapy. In conclusion, we would like to stress the need for routine screening of premature infants with a birth weight of up to 2,000 gm and would recommend laser as the preferred modality of treatment of threshold ROP.

  References Top

Gopal L, Sharma T, Ramachandran S, Shanmugasundaram R, Asha V. Retinopathy of prematurity:a study. Indian J Ophthalmol 1995;43:59-61.  Back to cited text no. 1
Charan R, Dogra MR, Gupta A, Narang A. The incidence of retinopathy of prematurity in a neonatal care unit. Indian J Ophthalmol 1995;43:123-26.  Back to cited text no. 2
Committee for the Classification of Retinopathy of Prematurity. An International Classification of Retinopathy of Prematurity. Arch Ophthalmol 1984;102:1130-34.  Back to cited text no. 3
Cryotherapy for Retinopathy of Prematurity Co-operative Group. Multicenter trial of cryotherapy for retinopathy of prematurit:preliminary results. Arch Ophthalmol 1988;106:471-79.  Back to cited text no. 4
Cryotherapy for Retinopathy of Prematurity Co-operative Group. Multicenter trial of cryotherapy for retinopathy of prematurity:one year outcome-structure and function. Arch Ophthalmol 1990;108:1408-16.  Back to cited text no. 5
Nagata M, Kobayashi Y, Fukuda H, Suekane K. Photocoagulation for the treatment of retinopathy of prematurity. Jap J Clin Ophthalmol 1968;22:419-27.  Back to cited text no. 6
McNamara JA, Tasman W, Brown GC, Federman JL. Laser photocoagulation for stage 3+retinopathy of prematurity. Ophthalmology 1991;98:576-80.  Back to cited text no. 7
Capone A, Diaz-Rohena R, Sternberg P, Mandell B, Lambert HM, Lopez PF. Diode laser photocoagulation for zone I threshold retinopathy of prematurity. Am J Ophthalmol 1993;116:444-50.  Back to cited text no. 8
Kumar KS, Gopal L, Badrinath SS. Infant scleral depressor. Retina 1992;12:376.  Back to cited text no. 9
Mc Namara JA, Tasman W, Vander JF, Brown GC. Diode laser photocoagulation for retinopathy of prematurity:preliminary results. Arch Ophthalmol 1992;110:1714-16.  Back to cited text no. 10
Fleming TN, Runge PE, Charles ST. Diode laser photocoagulation for prethreshold posterior retinopathy of prematurity. Am] Ophthalmol 1992;114:589-92.  Back to cited text no. 11
Hunter DG, Repka MX. Diode laser photocoagulation for threshold retinopathy of prematurity:a randomized study. Ophthalmology 1993;100:238-44.  Back to cited text no. 12


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