Outcomes of double frequency 532 nm neodymium-doped: Yttrium aluminum garnet laser treatment in retinopathy of prematurity spectrum

Ritesh Verma; Jitender Phogat; Satvir Singh; Manisha Nada; Jagjit Singh Dalal; Sakshi Lochab

doi:10.4103/erj.erj_5_20

ORIGINAL ARTICLE

Year : 2020 | Volume : 7 | Issue : 1 | Page : 7-12

Outcomes of double frequency 532 nm neodymium-doped: Yttrium aluminum garnet laser treatment in retinopathy of prematurity spectrum

Ritesh Verma¹, Jitender Phogat¹, Satvir Singh¹, Manisha Nada¹, Jagjit Singh Dalal², Sakshi Lochab¹
¹ Department of Ophthalmology, Regional institute of ophthalmology, Postgraduate Institute of Medical Sciences, Rohtak, Haryana, India
² Department of Pediatrics, Postgraduate Institute of Medical Sciences, Rohtak, Haryana, India

Date of Submission	04-Jun-2020
Date of Acceptance	25-Jul-2020
Date of Web Publication	11-Dec-2020

Correspondence Address:
Dr. Ritesh Verma
3875 Sector 32-A, Chandigarh Road, Ludhiana, Punjab
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/erj.erj_5_20

Abstract

Context: In recent years, the use of double-frequency 532 nm neodymium-doped:yttrium aluminum garnet (Nd:YAG) laser has increased in retinopathy of prematurity (ROP) spectrum with excellent structural outcomes, but there are very few studies in this context. Aims: The aim of the study was to study the safety and efficacy of 532 nm Nd:YAG laser in the ROP spectrum. Materials and Methods: This retrospective, noncomparative, and interventional study was conducted on patients who underwent laser treatment for ROP between January 2019 and March 2020. A complete analysis of clinical records including type and zone of ROP, the laser parameter used during the procedure, and complications related to laser photocoagulation was done. Statistical Analysis Used: Quantitative variables were compared using Paired t-test/Wilcoxon rank-sum test across follow-up. Univariate/multivariate logistic regression analysis was used to assess the association of a risk factor in ROP. A P < 0.05 was considered statistically significant. Results: Of total 42 eyes in our study irrespective of the type of ROP, 85.7% of the eyes showed complete regression after initial photocoagulation. Six eyes (14.2%) required supplemental laser photocoagulation. Progressing to Stage 4 ROP was seen in one eye even after supplemental laser therapy. The mean number of laser spots required at initial treatment was 3897 ± 1171 (range: 1961–5110) in aggressive posterior ROP eyes as compared to 1391 ± 562 (range: 897–3042) in Type 1 ROP eyes. Tunica vasculosa lentis was present in bilateral eyes of four infants at the time of laser treatment, but it did not alter the treatment completion or outcome. None of our patients developed cataract or anterior segment ischemia. Conclusions: Double-frequency 532 nm Nd: YAG laser is a safe and effective alternative to diode laser photocoagulation in ROP cases.

Keywords: Aggressive posterior retinopathy of prematurity, neodymium-doped yttrium aluminum garnet green laser, retinopathy of prematurity, tunica vasculosa lentis

How to cite this article:
Verma R, Phogat J, Singh S, Nada M, Dalal JS, Lochab S. Outcomes of double frequency 532 nm neodymium-doped: Yttrium aluminum garnet laser treatment in retinopathy of prematurity spectrum. Egypt Retina J 2020;7:7-12

How to cite this URL:
Verma R, Phogat J, Singh S, Nada M, Dalal JS, Lochab S. Outcomes of double frequency 532 nm neodymium-doped: Yttrium aluminum garnet laser treatment in retinopathy of prematurity spectrum. Egypt Retina J [serial online] 2020 [cited 2023 Jun 2];7:7-12. Available from: https://www.egyptretinaj.com/text.asp?2020/7/1/7/302995

Introduction

Retinopathy of prematurity (ROP) is a multifactorial vasoproliferative disorder that occurs exclusively in premature infants.^[1] ROP is one of the leading causes of preventable childhood blindness. There is an ongoing epidemic of ROP in low- and middle-income countries with severe forms of ROP occurring in bigger premature infants.^[2],[3] ROP is a rapidly progressive disease with a narrow window of opportunity for treatment and progresses to retinal detachment if left untreated.^[4] Cryotherapy was the initial treatment of choice for ROP, but it was associated with complication such as scleral damage and was cumbersome to perform.^[5] It was eventually replaced by laser treatment as it had better structural and functional outcomes, and it was easier to perform.^{[6],[7],[8],[9]} The safety and efficacy of diode laser (810 nm) in Type 1 prethreshold ROP was established by the early treatment ROP trial.^[10] Recently, the use of frequency-doubled 532 nm neodymium-doped: yttrium aluminum garnet (Nd: YAG) laser in ROP has been reported in various studies.^{[11],[12],[13]} The major concern with the use of green laser in ROP has been the risk of cataract formation in cases with coexisting tunica vasculosa lentis (TVL). It was postulated that hemoglobin preferentially absorbs green wavelengths and generates thermal energy during treatment leading to cataract.^[14] Anterior segment ischemia after heavy laser photocoagulation in severe forms of ROP has also been postulated to be the cause of cataract development by Fallaha et al.^[15] The incidence of cataract after diode laser photocoagulation is significantly lower as compared to argon laser.^[10] Although the risk of cataract after 532 nm Nd: YAG is theoretically high, various studies have reported the safety profile comparable to diode laser photocoagulation.^[12],[13] The purpose of this study is to evaluate the safety and efficacy of frequency-doubled 532 nm Nd:YAG laser in ROP cases.

Materials and Methods

This retrospective, noncomparative, and interventional study was conducted, with approval from the institutional ethics committee, among the premature neonates born and referred to our institute, who underwent laser treatment for ROP between January 2019 and March 2020.

Patients with ROP treated with double-frequency Nd:YAG laser in either eye were enrolled in the study. There were no exclusion criteria.

ROP was classified according to revised International Classification ROP Guidelines. Type 1 ROP was defined as (1) zone I any stage with plus; (2) Zone I Stage 3 with or without plus; (3) Zone II Stage 3 with plus. Aggressive posterior ROP (APROP) was defined as extreme vessel dilation and tortuosity in four quadrants, direct arteriovenous shunting, flat neovascularization, and rapid evolution, without following Stage 1–3 progression.^[16] Infants were treated in accordance with the early treatment of ROP guidelines by laser photocoagulation.^[10]

The pupils were dilated with a mixture of tropicamide 0.5% and phenylephrine 0.5% administered three times with punctual occlusion. Topical proparacaine hydrochloride 0.5% was administered once to achieve anesthesia 2 min before the procedure. Infants with treatable forms of ROP as Early Treatment for Retinopathy of Prematurity (ETROP) guidelines underwent laser photocoagulation with a portable 532 nm frequency-doubled Nd:YAG green laser (IRIS Medical Oculight GLX, IRIDEX, CA, USA) under topical anesthesia. Continuous monitoring of the pulse and oxygen saturation was done if the procedure was performed in the ophthalmology outpatient department. Power settings varied between 100 and 200 mW with an exposure duration of 100 ms–200 ms. The number of shots varied according to the zone of retina subjected to laser therapy as near confluent burns were applied to the avascular retina. Posttreatment, all eyes received prednisolone 0.1% and tobramycin 0.3% eye drops, four times a day for 2 weeks. Patients were followed up weekly after treatment for the initial 4 weeks and the biweekly for at least 10 weeks postlaser therapy. Skip areas (if found) were lasered at 1-week follow-up. The status of plus disease, vitreous adjacent to ridge, and stage of ROP was documented at each follow-up.

Postlaser regression was defined as the absence of plus or preplus, no fresh preretinal hemorrhage, and regression of stage if any. The regression of TVL, decrease/complete regression of plus disease, and neovascularization were considered as early signs of regression of APROP. Reactivation was defined as the recurrence of plus disease, progression of retinal neovascularization, and new preretinal hemorrhage. Laser supplementation was done in cases with progression despite treatment or if there was a reactivation of ROP. Treatment failure was defined as progression to retinal detachment or severe macular drag postlaser.

A complete analysis of clinical records including the demographic profile (birth weight, gestational age [GA], and postmenstrual age [PMA]), maternal risk factors (gestational diabetes, preeclampsia, and multiple pregnancies), neonatal risk factors (respiratory distress syndrome, surfactant, blood transfusion, sepsis, necrotizing enterocolitis, neonatal jaundice, intracranial hemorrhage, and a number of oxygen dependent days), type and zone of ROP, the laser parameter used during the procedure, and complications related to laser photocoagulation was done.

Statistical analysis

The data were entered in Microsoft Excel Spreadsheet, and analysis was done using IBM® SPSS® (Statistical Package for the Social Sciences) version 21.0.

Categorical variables were presented in number and percentage (%), and continuous variables were presented as mean ± standard deviation (SD) and range. The normality of data was tested by Kolmogorov–Smirnov test. If the normality was rejected, then nonparametric test was used.

Quantitative variables were compared using paired t-test/Wilcoxon rank-sum test (when the data sets were not normally distributed) across follow-up. Univariate/multivariate logistic regression analysis was used to assess the association of a risk factor in ROP development and regression postlaser. A P < 0.05 was considered statistically significant.

Results

Forty-two eyes of 23 infants were treated with 532 nm Nd: YAG laser photocoagulation treatment for ROP during our study period. The mean GA of infants in our study was 30.39 ± 2.4 weeks (range: 27–36 weeks). The mean birth weight of infants was 1256.17 ± 254.75 g (range: 890–1810). The mean PMA at the time of initial treatment was 35.17 ± 2.88 weeks (range: 30–40). TVL was present in bilateral eyes of four infants at the time of laser treatment, of which two infants had APROP and the rest of them had Type 1 ROP. Anterior segment was normal in rest of the patients with clear media. All the infants included in the study received oxygen during neonatal intensive care unit (NICU) stay. The mean number of days, for which oxygen was administered, was 13.3 ± 7.8 days (range: 3–35 days). The demographic profile and the associated neonatal comorbidities have been tabulated in [Table 1].

Table 1: Demographic and clinical profile of the patients in our study

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APROP was present in eight eyes of four infants and the rest of the 34 patients had Type 1 ROP. Only two eyes with Type 1 ROP had Zone I ROP and Zone II disease was present in the rest 32 eyes. The mean GA of infants with APROP was 30.5 ± 3.8 weeks as compared to 30.3 ± 2.1 weeks in patients with Type 1 ROP, but this difference was not statistically significant. The mean birth weight of patients in APROP group was 1405.0 ± 299.07 g and 1224.8 ± 241.7 g in patients with Type 1 ROP. The PMA at the time of treatment was 34.2 ± 3.7 weeks in APROP group and 35.3 ± 2.7 weeks in Type 1 ROP group. The mean APGAR score at 1 min and 5 min was also compared between APROP and Type 1 ROP group, but the difference was not statistically significant.

Laser photocoagulation was successfully completed in all but one infant who had fall in oxygen saturation due to hypothermia; the procedure was subsequently completed the following day in NICU. There were no anterior segment complications during the procedure. The presence of TVL did not hamper the completion of the procedure. Vitreous hemorrhage was present in two eyes postlaser, which resolved completely on subsequent follow-ups. The mean number of laser spots required at initial treatment was 3897 ± 1171 (range: 1961–5110) in APROP eyes as compared to 1391 ± 562 (range: 897–3042) in Type 1 ROP eyes, which is highly significant statistically (P = 0.003) [Figure 1]. The supplemental laser was performed in six eyes (three eyes in APROP group and three eyes in Type 1 ROP group). The mean number of spots used in supplemental laser was 542 ± 57 in APROP eyes and 304 ± 78 in Type 1 ROP eyes. Progression to Stage 4A was seen in only one eye in Type 1 ROP group even after supplemental laser treatment which was classified as treatment failure. This infant eventually underwent lens-sparing vitrectomy. A favorable structural outcome was present in remaining 41 eyes [Figure 2]. None of our patients developed cataract or anterior segment ischemia which is common after heavy laser treatment. The comparison between the APROP and Type 1 ROP group has been tabulated in [Table 2], and the clinical profile of the patient with treatment failure is shown in [Table 3].

Figure 1: Fundus image of the left eye of an infant born at 35-week gestation as a result of twin pregnancy, with birth weight of 1000 g and was kept on hood oxygen for 35 days. Laser treatment was done at postmenstrual age of 40 weeks. This image was taken at 1 week postlaser showing persistence of plus disease. Supplemental laser was done and 360 additional spots were delivered. The disease regressed 2 weeks postsupplemental laser

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Figure 2: Fundus picture of the right of an infant taken 4 weeks postlaser showing complete regression of retinopathy of prematurity with typical 532 nm neodymium-doped:yttrium aluminum garnet laser scar temporally

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Table 2: Univariate logistic regression analysis between aggressive posterior retinopathy of prematurity and Type 1 retinopathy of prematurity group

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Table 3: Description of patient with treatment failure after laser

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Discussion

The management of ROP has evolved drastically after the landmark ETROP trial with diode laser replacing the conventional cryotherapy and argon laser in ROP treatment.^[10] Diode laser therapy has less systemic and local complications as compared to cryotherapy and can be performed in topical anesthesia. The benefits of argon laser outweighed the cryotherapy to an extent that the need of multicentric trial to establish its safety and efficacy was questioned in some publications at that time.^[17] Argon blue–green laser was used before diode laser for ROP treatment. Diffuse corneal haze leading to multiple sessions of laser, iris photocoagulation, pupillary constriction, and absorption of laser energy by TVL were the main drawbacks of argon laser treatment.^[18] In the present study, we compared the outcomes of 532 nm double-frequency Nd:YAG laser between APROP and Type 1 ROP cases, and we also compared our results with the previous studies on the subject.

Of total 42 eyes in our study irrespective of the type of ROP, 85.7% of the eyes showed complete regression after initial photocoagulation with 532 nm double-frequency Nd:YAG laser. These results are comparable to some of the large studies with diode laser photocoagulation having regression rates ranging from 71% to 97% after initial treatment.^{[13],[19],[20],[21]} Six eyes (14.2%) required supplemental laser photocoagulation with only one eye (2.3%) progressing to Stage 4 ROP even after supplemental laser therapy. Progression of ROP to retinal detachment has been reported in previous studies.^[11],[13] Singh et al.^[13] reported treatment failure in 24 eyes (7.45%) after treatment with Nd: YAG laser. The higher percentage of treatment failure was attributed to a higher number of APROP eyes in their study. The higher use of supplemental laser therapy in our study can be attributed to a higher number of APROP eyes requiring retreatment as three out of eight eyes in APROP group required supplemental laser photocoagulation. The overall success rate in our study is 97.6% which is comparable to previous studies with Nd:YAG laser.^[13],[22]

The mean number of laser spots applied at primary treatment in our study was 3897 ± 1171 in the APROP eyes and 1391 ± 562 in the eyes with Type 1 ROP. This difference is highly significant statistically with P = 0.003. A study by Chhabra et al.^[23] reported the mean of 2710.24 ± 747.97 laser spots (range: 720–4437 spots), but they did not differentiate between the APROP and Type 1 ROP group which leads to a higher number of mean spots in their study. In contrast to our study, Lira et al.^[11] reported a mean of 320 laser spots per eye with a success rate of 97%, but they did not include APROP eyes in their study. The mean number of supplemental laser spots was 542 ± 57 in APROP eyes and 304 ± 78 in Type 1 ROP eyes, and this difference was statistically significant with a greater number of spots required in APROP eyes (P = 0.01). None of the previous studies mentioned the spots required in supplemental laser.

Vitreous hemorrhage occurred in two eyes in our study which resolved spontaneously at 6 weeks. Chhabra et al.^[23] also reported self-resolving vitreous hemorrhage in two of their infants. TVL was present in 19% of the eyes included in our study as compared to 44% in the study by Singh et al.^[13] Despite the presence of TVL, none of our patients developed cataract postlaser neither the presence of TVL hampered completion of laser in a primary sitting. None of our patients had anterior segment ischemia which was reported by Singh et al.^[13] in one patient postlaser. A study by Lira et al.^[11] did not mention any anterior segment complications postlaser.

The mean GA (± SD) in our study was 30.39 ± 2.4, and the mean birth weight was 1256.17 ± 254.75 (range: 890–1810). Severe ROP in bigger babies has been reported in studies from India and middle-income countries.^[3],[24] Lira et al.^[11] reported the mean GA of 30 ± 3 weeks in their study. The mean PMA at the time of treatment was 34.2 ± 3.7 in APROP group and 35.3 ± 2.7 in Type 1 ROP group, and there was no statistically significant difference in two groups (P = 0.16). Singh et al.^[13] mentioned mean PMA at the time of treatment to be 35.37 ± 3.16 weeks, but difference in the two groups was not mentioned.

A comparison was done on the mean number of days the infants received oxygen in two groups mentioned in [Table 2], but there was no significant difference in two groups. As the low Apgar score has been demonstrated to be a risk factor for the development and progression of ROP either alone or in combination with other perinatal comorbidities,^[25],[26] we compared it between the two mentioned groups. The mean APGAR 1 min/5 min was 5.25/8.0 in APROP infants and 5.7/8.52 in Type 1 ROP infants. The difference in two groups was not significant (P = 0.1).

The main limitation of our study is the retrospective nature of the study and lack of control group. Another limitation is the small sample size and limited follow-up duration of a mean of 30 weeks. The refractive status of the patients has not been mentioned in this study. As compared to previous studies, less APROP cases were included in our study because we prefer intravitreal bevacizumab injection in APROP cases which led to a higher success rate in our study as compared to some of the previous studies which had a higher number of APROP eyes in their study group.

Conclusions

Double-frequency 532 nm Nd:YAG laser is a safe and effective alternative to the conventional diode laser. TVL does not seem to alter the treatment outcome in our study. Long-term studies are still required on the subject as there is no study in literature with long-term functional and refractive outcomes.^[13]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Hartnett ME, Penn JS. Mechanisms and management of retinopathy of prematurity. N Engl J Med 2012;367:2515-26.
2.	Gilbert C, Rahi J, Eckstein M, O'Sullivan J, Foster A. Retinopathy of prematurity in middle-income countries. Lancet 1997;350:12-4.
3.	Shah PK, Narendran V, Kalpana N, Gilbert C. Severe retinopathy of prematurity in big babies in India: History repeating itself? Indian J Pediatr 2009;76:801-4.
4.	Charan R, Dogra MR, Gupta A, Narang A. The incidence of retinopathy of prematurity in a neonatal care unit. Indian J Ophthalmol 1995;43:123-6. [PUBMED] [Full text]
5.	Cryotherapy for Retinopathy of Prematurity Cooperative Group (1990). Multicenter trial of cryotherapy for retinopathy of prematurity: Three month outcome. Arch Ophthalmol 1990;108:195-204.
6.	McNamara JA, Tasman W, Brown GC, Federman JL. Laser photocoagulation for stage 3+ retinopathy of prematurity. Ophthalmology 1991;98:576-80.
7.	Iverson DA, Trese MT, Orgel IK, Williams GA. Laser photocoagulation for threshold retinopathy of prematurity. Arch Ophthalmol 1991;109:1342-3.
8.	Shalev B, Farr AK, Repka MX. Randomized comparison of diode laser photocoagulation versus cryotherapy for threshold retinopathy of prematurity: Seven-year outcome. Am J Ophthalmol 2001;132:76-80.
9.	Axer-Siegel R, Maharshak I, Snir M, Friling R, Ehrlich R, Sherf I, et al. Diode laser treatment of retinopathy of prematurity: anatomical and refractive outcomes. Retina 2008;28:839-46.
10.	Early Treatment for Retinopathy Of Prematurity Cooperative Group. Revised indications for the treatment of retinopathy of prematurity: Results of the early treatment for retinopathy of prematurity randomized trial. Arch Ophthalmol 2003;121:1684-94.
11.	Lira RP, Calheiros AB, Barbosa MM, Oliveira CV, Viana SL, Lima DC. Efficacy and safety of green laser photocoagulation for threshold retinopathy of prematurity. Arq Bras Oftalmol 2008;71:49-51.
12.	Sanghi G, Dogra MR, Vinekar A, Gupta A. Frequency-doubled Nd: YAG (532 nm green) versus diode laser (810 nm) in treatment of retinopathy of prematurity. Br J Ophthalmol 2010;94:1264-5.
13.	Singh SR, Katoch D, Handa S, Kaur S, Moharana B, Dogra M, et al. Safety and efficacy of 532 nm frequency-doubled Nd-YAG green laser photocoagulation for treatment of retinopathy of prematurity. Indian J Ophthalmol 2019;67:860-5. [PUBMED] [Full text]
14.	Paysse EA, Miller A, Brady McCreery KM, Coats DK. Acquired cataracts after diode laser photocoagulation for threshold retinopathy of prematurity. Ophthalmology 2002;109:1662-5.
15.	Fallaha N, Lynn MJ, Aaberg TM Jr., Lambert SR. Clinical outcome of confluent laser photoablation for retinopathy of prematurity. J AAPOS 2002;6:81-5.
16.	International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol 2005;123:991-9.
17.	Tasman W. Threshold retinopathy of prematurity revisited. Arch Ophthalmol 1992;110:623-4.
18.	Landers MB 3^rd, Toth CA, Semple HC, Morse LS. Treatment of retinopathy of prematurity with argon laser photocoagulation. Arch Ophthalmol 1992;110:44-7.
19.	Drenser KA, Trese MT, Capone A Jr. Aggressive posterior retinopathy of prematurity. Retina 2010;30:S37-40.
20.	Jalali S, Kesarwani S, Hussain A. Outcomes of a protocol-based management for zone 1 retinopathy of prematurity: The Indian Twin Cities ROP Screening Program report number 2. Am J Ophthalmol 2011;151:719-2400.
21.	Kieselbach GF, Ramharter A, Baldissera I, Kralinger MT. Laser photocoagulation for retinopathy of prematurity: Structural and functional outcome. Acta Ophthalmol Scand 2006;84:21-6.
22.	Shi C, Jin J, Lu B, Zhu H, Xie H, Ren Y, et al. Clinical effects of laser photocoagulation in 160 cases of retinopathy of prematurity. Int J Clin Exp Med 2016;9:2813-21.
23.	Chhabra K, Kaur P, Singh K, Aggarwal A, Chalia D. Outcome of solid-state 532 nm green laser in high-risk retinopathy of prematurity at a tertiary care centre in India. Int Ophthalmol 2018;38:287-91.
24.	Jalali S, Matalia J, Hussain A, Anand R. Modification of screening criteria for retinopathy of prematurity in India and other middle-income countries. Am J Ophthalmol 2006;141:966-8.
25.	Ke XY, Ju RH, Zhang JQ, Chen H, Wei EX, Chen XH. Risk factors for severe retinopathy of prematurity in premature infants: A single-center study. Nan Fang Yi Ke Da Xue Xue Bao 2011;31:1963-7.
26.	Fortes Filho JB, Dill JC, Ishizaki A, Aguiar WW, Silveira RC, Procianoy RS. Score for Neonatal Acute Physiology and Perinatal Extension II as a predictor of retinopathy of prematurity: Study in 304 very-low-birth-weight preterm infants. Ophthalmologica 2009;223:177-82.