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 Table of Contents    
ORIGINAL ARTICLE
Year : 2022  |  Volume : 15  |  Issue : 3  |  Page : 331-336  

Refractive outcomes following yttrium aluminum garnet laser (532 nm green laser) in severe retinopathy of prematurity


1 Department of Ophthalmology, Jawaharlal Postgraduate Medical Education and Research, Puducherry, India
2 Department of Preventive and Social Medicine, Jawaharlal Postgraduate Medical Education and Research, Puducherry, India

Date of Submission30-Oct-2021
Date of Decision15-Jul-2022
Date of Acceptance23-Jul-2022
Date of Web Publication02-Nov-2022

Correspondence Address:
Nirupama Kasturi
Department of Ophthalmology, Jawaharlal Postgraduate Medical Education and Research, Puducherry - 605 006
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ojo.ojo_315_21

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   Abstract 


PURPOSE: To assess the refractive outcomes in eyes with severe Retinopathy of prematurity (ROP) after treatment with the frequency-doubled neodymium-doped yttrium aluminum garnet (Nd-YAG) laser 532 nm (green laser) at 1–2 years of age and compare with eyes that underwent spontaneous regression of ROP and to identify the risk factors associated with the refractive outcomes in laser-treated eyes with severe ROP.
METHODOLOGY: Infants who underwent laser treatment with green laser were enrolled in Group 1 and those who had spontaneous regression of ROP were enrolled in Group 2. All these children underwent a visual assessment, refraction using 1% cyclopentolate eye drops and indirect ophthalmoscopy at 1–2 years of age. Data regarding the gestational age, sex, birth weight, inborn (born in our institution) or outborn (born outside and referred to us), stage and zone of ROP and laser spots given were obtained from the treatment records. Data were analyzed using SSPS 19.0 software for Windows (SSPS Inc., Chicago, Illinois, USA).
RESULTS: A total of 102 infants were enrolled, 51 in each group. Visual acuity ranged from 0.25–1 cycles per cm in both groups. Spherical equivalent (SE) ranged from − 8.25 D to + 5.50 D in Group 1 and −1.00D to +4.00D in Group 2. Group 1 had an incidence of 23.5% Myopia and 33.4% Astigmatism which was significantly more than Group 2. The linear regression model predicted a decrease in the SE by 0.658D if the number of laser spots increased by 1000 (P < 0.001). No other risk factors (gestational age/birth weight) were found to have a significant association with refractive errors in the lasered ROP group.
CONCLUSIONS: Eyes with laser-treated severe ROP are frequently associated with myopia and astigmatism when compared to spontaneously regressed ROP. The number of laser spots delivered has a direct association with the amount of refractive error.

Keywords: Laser photocoagulation, refractive outcomes, retinopathy of prematurity


How to cite this article:
Jossy A, Kasturi N, Madhukar SP, Babu K R, Elias S. Refractive outcomes following yttrium aluminum garnet laser (532 nm green laser) in severe retinopathy of prematurity. Oman J Ophthalmol 2022;15:331-6

How to cite this URL:
Jossy A, Kasturi N, Madhukar SP, Babu K R, Elias S. Refractive outcomes following yttrium aluminum garnet laser (532 nm green laser) in severe retinopathy of prematurity. Oman J Ophthalmol [serial online] 2022 [cited 2022 Dec 2];15:331-6. Available from: https://www.ojoonline.org/text.asp?2022/15/3/331/360413




   Introduction Top


Retinopathy of prematurity (ROP) is a retinal vasoproliferative disorder occurring in premature infants. It is a potentially blinding disorder prevalent in developed countries and is now emerging as an important cause of blindness in developing countries. This is mainly due to the advancements made in the field of medicine and neonatal care.[1] The incidence of ROP ranges from 0% to 34.8% in high-income countries and 3.4% to 44.8% in middle- and low-income countries among premature infants.[2] ROP has a small window period for treatment and if missed can lead to permanent blindness. Over the years, the treatment protocol for ROP has changed from cryotherapy to laser photocoagulation.[3] However, significant refractive errors are developing following laser photocoagulation and high rates of myopia have been reported for threshold ROP treated with the diode laser. Early treatment for ROP (ETROP) study reported myopia in nearly 80% of threshold eyes treated with laser photocoagulation.[4]

Most of the literature mentions the structural and functional outcome of diode laser in the treatment of severe ROP. Two studies in the literature have mentioned favorable outcomes in ROP treated with frequency-doubled neodymium-doped yttrium aluminum garnet (Nd-YAG) 532 nm green laser which is now considered a safe and efficient alternative to diode laser.[5],[6] However, very few studies in the literature mention the refractive outcome following this laser treatment. Hence, this study was undertaken to evaluate the incidence and severity of myopia, astigmatism, and anisometropia in babies who are treated with frequency-doubled Nd-YAG laser 532 nm (green laser) for severe ROP by comparing it with eyes that had spontaneously regressed ROP and analyze various factors associated with the refractive outcomes in these eyes which will help us to plan optimal visual rehabilitation for these children.


   Methodology Top


This study was a cross-sectional comparative study conducted in the Department of Ophthalmology, from January 2017 to December 2018. The study was approved by the institute ethics committee (human studies) and informed consent from the parents of the babies was obtained before enrolment. The sample size was estimated using the statistical test for comparing two independent proportions. The minimum expected difference in refractive error between the groups in a similar study was 18% and the sample size was estimated at a 5% level of significance and 80% power to be 102 eyes in each group. ROP screening was done at 3–4 weeks of postnatal age or a postmenstrual age of 31 weeks, and follow-up examinations until the disease regressed. Laser Photocoagulation was done by a qualified retina specialist (A) within 24 h of diagnosis of treatable ROP using Nd-YAG 532nm Ophthalmic Laser (ZEISS, VISULAS green ®) at 100–300 mW with spots at half-burn width apart expanding to a near confluent pattern. All these babies underwent visual assessment, anterior segment evaluation, cycloplegic refraction, and posterior segment examination at 1–2 years of age on follow-up.

Group 1 (lasered group) included eyes that underwent laser treatment with green laser for severe ROP (defined as treatable ROP according to the ETROP study) excluding eyes progressing to Stage IV or V despite laser treatment. Group 2 (spontaneously regressed) included eyes with spontaneously regressed ROP. Eyes with congenital corneal opacity or cataracts were excluded from both groups.

Vision assessment

Qualitative assessment was made using the central steady and maintained fixation (CSM) method and quantitative assessment using LEA grating test paddles.

Anterior segment examination

Any signs of squinting or nystagmus were looked for in the babies. Detailed examination of the cornea for opacity, the lens for cataract, and neovascularization of iris was checked using a handheld slit-lamp.

Posterior segment examination

Fundus examination was performed by a single examiner (A) using an indirect ophthalmoscope and a +20 D lens and all the detailed fundus findings were documented. The posterior pole, followed by the whole of the retina was thoroughly examined to rule out any recurrence or sequelae.

Retinoscopy/cycloplegic refraction

Retinoscopy was performed to measure refractive outcomes by a single masked examiner (B) using a self-illuminated streak retinoscope (HEINE BETA 200 Retinoscope with HEINE PARASTOP 3.5V®) after cyclopleging the patient with 1% cyclopentolate eye drops. Refractive errors were defined based on the Baltimore Pediatric Eye Disease Study[7] Emmetropia was defined as spherical equivalent (SE) refractive error of >−1.00 D and <+1.00 D. Myopia was defined as SE refractive error less than or equal to −1.00 D and hyperopia was defined as SE refractive error greater than or equal to +1.00 D. Astigmatism was defined as cylinder power of 1.5 D or greater and anisometropia was defined as an interocular difference of 1.0D or more in SE.

Statistical analysis

Data were analyzed using SSPS 19.0 software for Windows (SSPS Inc., Chicago, Illinois, USA). The distributions of categorical variables such as gender, clinical characteristics, and treatment characteristics were expressed in terms of frequency/percentage. The distributions of continuous variables such as SE, age, birth weight, and gestational age were expressed in terms of mean with standard deviation or median with range based on the distribution of data. The associations of refractive outcomes with other categorical variables mentioned above were carried out by using the Chi-square test or Fisher's exact test. The comparison of continuous variables between the groups was carried out using the independent Student's-t-test/Mann–Whitney test. The independent factors associated with different refractive outcomes were expressed using binary logistic regression analysis or multiple logistic regression analysis. All statistical analysis was carried out at a 5% level of statistical significance and P < 0.05 was considered statistically significant.


   Results Top


Patient characteristics

It was found that Group 1 or lasered group had 45 (88.2%) outborn and 6 (11.7%) inborn babies and that of a lower gestational (P < 0.05), whereas the control group had all inborn babies only. It was found that both Group 1 and Group 2 had a higher percentage of females in the study population. The mean birth weight of Group 1 babies was 1153.14 g (740 g–1954 g). The mean birth weight of Group 2 babies was 1250.94 g (700 g–1942 g) [Table 1]. Group 1 had more cases of advanced stages of ROP in Zone I and II, whereas Group 2 mainly comprised stage 1 ROP in Zone II and III, which underwent spontaneous regression (P < 0.05) [Figure 1] and [Figure 2] In Group 1, most of the eyes received around 1500–4500 number of laser spots. The mean number of spots was 2831 (range 709–7635).
Figure 1: Bar graph showing the comparison of stage of ROP between Group 1 and Group 2. ROP: Retinopathy of prematurity

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Figure 2: Bar graph showing the comparison of Zone of ROP between Group 1 and Group 2. ROP: Retinopathy of prematurity

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Table 1: Patient characteristics in Group 1 (lasered group) and Group 2 (spontaneously regressed)

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Around 11 eyes had more severe ROP and received more than 4500 laser spots.

Vision assessment

The vision was CSM fixation, and 0.25–0.5 cycles/cm using Lea Paddles in all the babies enrolled in the two groups in our study.

Anterior segment evaluation

In Group 1, four babies had esotropia, four babies had significant corneal opacity following laser involving the visual axis, and two had corneal opacities not involving the visual axis. There was no squinting and no corneal or lenticular opacities in Group 2.

Posterior segment evaluation

In Group 1, 86% had regressed ROP, while six eyes (12%) had preretinal fibrosis at the end of 1–2 years of age. There were no cases with tractional retinal detachment. Group 2 all babies had regressed ROP in the posterior segment. Patients treated with laser showed scarring in the peripheral retina at the end of 1 year [Figure 3].
Figure 3: Fundus photograph of the left eye showing fresh ROP laser marks (a) and laser scars at 1 year of age (b). ROP: Retinopathy of prematurity

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Refractive error of patients in the lasered group and spontaneously regressed group

In Group 1, mean SE was + 0.14 ± 2.50 D (range from − 8.25 D to + 5.50 D), whereas it was + 2.50 ± 1.25 D (range from −1.00 to +4.00 D) in Group 2 (P < 0.05). In Group 1, the mean cylinder power was 0.25 ± 0.86 D (range from −2.5 D to 1.5 D). In Group 2, the mean cylinder power of 0.14 ± 0.31 D had a (range from 0 to 1.5 D). Group 1 had around 33 eyes with astigmatism, whereas Group 2 only had around 5 eyes with astigmatism (P < 0.05). There were four babies with anisometropia in Group 1. Group 2 did not have any cases of anisometropia. However, this difference was not statistically significant (P > 0.05) [Table 2].
Table 2: Refractive error of patients in the Group 1 (lasered group) and Group 2 (spontaneously regressed) group

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Association between risk factors and spherical equivalent

Statistical analysis did not show any significant association between the birth weight, gestational age, gender, stage, and zone of ROP with refractive error. Regression analysis was done between the number of laser spots given and the SE. The regression model predicts the decrease in SE was 0.6581/1000 increase in the laser spots. With P < 0.001, this was significant. Hence, it was found that there was a significant association between the laser spots given and a decrease in the SE.


   Discussion Top


ROP is now considered one of the important potentially avoidable causes of childhood blindness both in developed and developing countries. The incidence of ROP in developed countries is decreasing due to astute care and proper guidelines of oxygen supplementation maintained in the intensive care units. On the other hand, in developing or middle-income countries like India the incidence of ROP is still on the rise due to an increase in birth rate, increase in premature birth rate, and increase in preterm survival rate.[8] Laser has now replaced cryotherapy for the treatment of ROP and is still considered above anti-VEGF treatments due to the unknown systemic and local side effects of anti-VEGFs.[9]

Goktas et al., in their study, found that children born prematurely had more incidences of refractive error and strabismus. It was also found in their study that the more premature the child is the higher myopia can be.[10] Moreover if premature babies developed ROP needing laser photocoagulation as treatment, the incidence rate of myopia and other refractive errors were higher.[11],[12],[13]

Developing countries like India are in the third epidemic of ROP, where there is a rise in children with severe ROP. Thus, cases of ROP requiring laser treatment are also increasing.[2] Even though we are protecting the child from blindness due to ROP with timely intervention with laser treatment, the child is left with refractive errors such as myopia, astigmatism, and strabismus. which cause visual impairment in the child. Since the children requiring laser therapy is increasing, the refractive errors are also increasing in the population of children following laser treatment for ROP. The lifestyle and productivity of the child will be burdened by these refractive errors. Early screening and visual rehabilitation are thus necessary for the protection of these children from developing refractive amblyopia.

Most of the studies regarding refractive outcome following laser therapy for ROP in literature has used a diode laser for photocoagulation.[11],[12],[13],[14],[15],[16],[17],[18]

Many hospitals in India do not have access to the diode laser. Instead, they have access to green laser or frequency-doubled Nd-YAG laser which is now established as a safe and efficacious alternative to diode laser for treatment of ROP.[19],[20] 532 nm green laser also results in less pain, brighter and whiter spots which become more confluent with time.[6]

The mean SE was leaning toward the myopic side in Group 1, whereas in Group 2 SE mean was more in the normal range for the age group. The occurrence of myopia in our study in Group 1 or lasered ROP group was 23.5%, occurrence of astigmatism was 33.4%, anisometropia was there in 4% of the babies and strabismus was present in 8% of the babies. Myopia and astigmatism were the dominant refractive errors in our study. We found similar studies in the literature analyzing the refractive error following laser photocoagulation where diode laser was used which showed the comparable incidence of myopia and some with a higher incidence of myopia [Table 3]. However, the above studies had an older age at refraction and longer follow up which would have contributed to the higher myopia in their study population.
Table 3: Comparison of refractive outcome using diode and green laser for severe retinopathy of prematurity

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In our study, we have calculated the SE and defined myopia based on the Baltimore pediatric eye disease study as SE less than or equal to − 1 D.[7]

Moreover, the mean age at which the babies in our study underwent refraction was 13.94 months. The above two factors may have contributed to the lower incidence of myopia in our study. Our study population had a relatively younger age at refraction and if followed up other babies who had borderline SE can develop myopia and thereby increasing the incidence of myopia in our study population. Hence, a close follow-up is needed even in the children who were not included as myopia in our study.

Ruan et al. studied the refractive outcome in ROP treated with green laser in the Chinese population. They found an incidence of around 30.2% myopia and astigmatism of 46% in a study population of 102 eyes. The age at refraction was taken nearer to 24 months in their study.[13] Kaur et al., in a long-term study, in which they analyzed refractive outcomes in children aged 6–12 years of age who had undergone laser treatment for ROP in a tertiary center in North India found that there is an incidence of 78% astigmatism in their study population.[24] The residual ROP sequelae may be the reason for the progression of astigmatism in the children who underwent laser therapy for ROP.

Davitt et al., in their study, analyzed the progression of astigmatism in laser-treated children. Their study population was the group who had undergone laser therapy for ROP and participated in the ETROP study. Their design was an observational cohort study. They found that 42% of the study population developed astigmatism by 4 years of age and by 6 years over 50% had developed astigmatism.[25] They also concluded that there was a pattern of astigmatism progression in children who had ROP residua. These findings reinforce the need for follow-up examinations in all the children who underwent laser treatment to prevent the development of amblyopia of any form in them by early detection and treatment.

Anisometropia in our study was 4% in Group 1 and Group 2 did not have any incidence of anisometropia. Ruan et al., in their study, had an incidence of 18% anisometropia; they also had a control group like our Group 2 which showed no incidence of anisometropia.[13]

In contrast to the findings in our study, the study done by Bonotto et al. found no significant difference in the visual function between the ROP treated with laser group and the group that underwent ROP regression in their study. They had a large age group comprising from 4 years to 18 years and they excluded severe premature children who had severe impairment, this may have led to the result they obtained in their study.[26]

Strabismus in our study was 8% in Group 1, whereas Group 2 did not show any incidence of strabismus. However, in similar studies where they analyzed the anterior segment of children who underwent laser photocoagulation for ROP they found a higher incidence of strabismus. Nguyen et al. had a 10% incidence of strabismus in their study[18] and Yang et al. had an incidence of 30% strabismus in their study.[27] This may be attributed to the fact the above two studies had an older mean age at the time of study 5 years and 7 years, respectively, whereas our mean age of the population was relatively young with 13.94 months. Moreover, in addition, our study had 12 eyes that developed corneal opacities due to laser treatment; they are at more risk of developing strabismus in the future. The younger age group of our study and the presence of anterior segment abnormalities in our study reinforce the need for further follow-up for identifying the squinting at an early stage so that early visual rehabilitation can be done.

Statistical analysis showed no significant association between birth weight and gestational age with the refractive error in Group 1. We obtained a significant association between the laser spots given and shifting of SE to the myopic side.

The large study population and the presence of a control group or Group 2 with regressed ROP added to the strengths of our study. Furthermore, the examiner who viewed the fundus was masked to refractive error determination; the examiner who performed retinoscopy was masked to the treatment group. This eliminated the chances of bias.

The limitations of the study included the use of 1% cyclopentolate instead of 1% atropine for refraction which was deferred due to the need for an additional visit of the subject for refraction and fundus examination after the prescription of atropine. Subjects in our study were followed up for a short period. This may have led to underestimating the incidence of refractive errors/strabismus in the lasered or spontaneously regressed group. Future studies should have longer follow-up for timely identification of refractive errors or strabismus in laser-treated babies for ROP.


   Conclusions Top


Patients with severe ROP after treatment with frequency-doubled Nd-YAG laser at the end of 1–2 years of age had a significant incidence of myopia (23.5%) and astigmatism (33.4%) (P < 0.05) when compared to the spontaneously regressed group.

The multivariate regression model predicted a statistically significant decrease in SE by 0.6581 if the laser dose increases by 1000 spots. No other risk factors (gestational age/birth weight) were found to have a significant association with refractive errors in the lasered ROP group.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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