Ophthalmic Surgery, Lasers and Imaging Retina

Clinical Science 

Large Spot Laser for Treatment of Retinopathy of Prematurity

Parijat Chandra, MD, DNB; Priti Bhoutekar, MD; Rajvardhan Azad, MD; Ramesh Agarwal, MD

Abstract

BACKGROUND AND OBJECTIVE:

To compare large spot versus standard spot laser for treatment of retinopathy of prematurity (ROP).

PATIENTS AND METHODS:

Eighty eyes of 40 infants with bilateral type 1 ROP were randomized for laser photocoagulation using laser indirect ophthalmoscope with either standard spot or large spot size laser. During the procedure, total time taken and Premature Infant Pain Profile (PIPP) scores were noted. Regression of disease and refractive error were noted on follow-up.

RESULTS:

The infants were randomized into two groups. All infants in both groups had regression of ROP. Large spot laser significantly reduced total treatment duration in zone I by 32% (P = .005) and zone II by 63.4% (P = .0006). Moderate-to-severe pain occurred in PIPP scores in both groups throughout the procedure (under topical anesthesia) and was comparable between the groups. Mean change in refractive error (myopia) from pre-laser (2.090 diopters [D] ± 1.345 D) to 3 months' post-laser (2.465 D ± 1.399 D) was not statistically significant between the groups.

CONCLUSIONS:

Large spot laser significantly reduced total duration of laser treatment in zone I/II ROP. Large spot laser is a useful alternative for treatment of ROP in terms of faster procedure, lesser total duration of pain, and similar regression profile. It does not cause additional myopia and can be performed without additional training.

[Ophthalmic Surg Lasers Imaging Retina. 2018;49:e233–e239.]

Abstract

BACKGROUND AND OBJECTIVE:

To compare large spot versus standard spot laser for treatment of retinopathy of prematurity (ROP).

PATIENTS AND METHODS:

Eighty eyes of 40 infants with bilateral type 1 ROP were randomized for laser photocoagulation using laser indirect ophthalmoscope with either standard spot or large spot size laser. During the procedure, total time taken and Premature Infant Pain Profile (PIPP) scores were noted. Regression of disease and refractive error were noted on follow-up.

RESULTS:

The infants were randomized into two groups. All infants in both groups had regression of ROP. Large spot laser significantly reduced total treatment duration in zone I by 32% (P = .005) and zone II by 63.4% (P = .0006). Moderate-to-severe pain occurred in PIPP scores in both groups throughout the procedure (under topical anesthesia) and was comparable between the groups. Mean change in refractive error (myopia) from pre-laser (2.090 diopters [D] ± 1.345 D) to 3 months' post-laser (2.465 D ± 1.399 D) was not statistically significant between the groups.

CONCLUSIONS:

Large spot laser significantly reduced total duration of laser treatment in zone I/II ROP. Large spot laser is a useful alternative for treatment of ROP in terms of faster procedure, lesser total duration of pain, and similar regression profile. It does not cause additional myopia and can be performed without additional training.

[Ophthalmic Surg Lasers Imaging Retina. 2018;49:e233–e239.]

Introduction

Laser photocoagulation is the gold standard for treatment of retinopathy of prematurity (ROP), but it is a stressful and time-consuming procedure for premature infants as well as the treating surgeon when performed under topical anesthesia in developing countries.

Large spot laser is a novel technique used in transpupillary thermotherapy for lesions such as retinoblastoma, choroidal melanoma, and choroidal neovascularization. The study tests the usage of large spot laser (OcuLight SLx Tri-Mode; Iridex, Mountain View, CA) with four-times-larger spot size to treat type 1 ROP, based on the premise that it would help to laser a larger area in less time and can be a faster treatment alternative to current standard spot laser technique, thereby helping to reduce duration of pain for preterm infants undergoing laser treatment under topical anesthesia. The paper discusses benefits, caution steps, and a detailed comparison with standard spot laser.

Patients and Methods

All consecutive infants screened in our ROP clinic with bilateral type 1 ROP, as per Early Treatment for Retinopathy of Prematurity (ETROP) guidelines,1 were enrolled and, based on zone, were randomized using a computer-generated random number table into either standard spot laser treatment group 1 (40 eyes) or large spot laser treatment group 2 (40 eyes). Infants with advanced ROP beyond ETROP treatment guidelines, eyes with media haze, and systemically unstable infants were excluded from the study. Institutional ethics clearance was obtained for this study, and it adhered to the tenets of the Declaration of Helsinki.

Informed consent was taken from parents prior to laser treatment. During the procedure, laser parameters and total time taken for laser in both eyes were recorded. All laser procedures were performed by a single experienced surgeon under topical anesthesia using 0.5% proparacaine eye drops, two drops 5 minutes before the start of the procedure and repeated whenever needed during the procedure. All infants received non-nutritive sucking with sterile cotton dipped in 10% dextrose.

We also measured Premature Infant Pain Profile (PIPP),2 a validated scoring system for evaluating procedural pain response by summation of seven indicators (gestational age, behavioral state, heart rate, oxygen saturation, brow bulge, eye squeeze, and nasolabial furrows). PIPP scores from 0 to 6 points reflect mild pain, 7 to 12 moderate pain, and 13 to 21 severe pain. The PIPP scores were recorded at 0, 5, and 30 minutes from the end of the procedure in the first eye followed by 0, 5, and 30 minutes from the end of the procedure in the second eye. On follow-up, regression pattern of disease and cycloplegic refraction were noted at 1, 3, and 6 weeks and at 3 months.

The two groups were analyzed for differences in total duration of treatment, procedural pain, regression of disease, and refractive changes until 3 months' follow-up. Statistical analysis was done using Stata 11.2 (StataCorp, College Station, TX) using two sample Student's t-tests and two sample Wilcoxon rank sum (Mann-Whitney) tests as appropriate.

Results

Forty infants were successfully enrolled and followed up. Mean gestational age at birth in group 1 was 29.55 weeks ± 1.35 weeks and group 2 was 29.60 weeks ± 1.93 weeks. Mean post-menstrual age at treatment in group 1 was 36.35 weeks ± 2.7 weeks and group 2 was 36.60 weeks ± 3.39 weeks.

Enrolled infants were randomized into a standard spot laser group or a large spot laser group based on zone. Out of 40 infants, 20 infants (six infants in zone I; 11 infants in zone II; three infants in zone III) received standard spot laser and 20 infants (seven infants in zone I; 11 infants in zone II; two infants in zone III) underwent large spot laser. All the baseline characteristics were comparable between the groups except history of sepsis, which was higher in the standard spot laser group.

We used the large spot size in repeat mode and did not use the long pulse mode. All settings were similar between both laser techniques, except sometimes higher power was needed for the large spot laser. Non-confluent gray burns were given in both eyes.

All infants (100%) had complete regression of ROP in both eyes within 4 weeks of laser treatment. None of the patients had progression, which was defined as stage 4 or 5 ROP. One patient in the standard spot laser group and one patient in the large spot laser group achieved regression within the next 2 weeks after additional laser augmentation with the same laser type as per their allotted group. Both laser procedures had an excellent safety profile, and no laser procedure-related complications were noted.

The total duration of treatment (both eyes) in the standard spot laser group was a median of 65 minutes and the large spot laser group was a median of 28 minutes. It was significantly reduced in the large spot group (P = .0002). On analysis of zones, large spot laser significantly reduced total treatment duration in zone I by 32% (P = .005) and zone II by 63.4% (P = .0006) (Table 1, Figure 1). In zone III, there was a reduction in treatment duration that did not reach statistical significance. We also noted significantly fewer number of spots were needed in zone I (P = .0027), zone II (P = .0003), and zone III (P = .5) (Table 2).

Comparison of Total Time Taken (Minutes) for Laser Treatment and Between Subgroups (Based on Zones) in Both Treatment Groups

Table 1:

Comparison of Total Time Taken (Minutes) for Laser Treatment and Between Subgroups (Based on Zones) in Both Treatment Groups

Mean total time taken for laser treatment in both groups in different zones. Large spot laser significantly reduced total treatment duration in zone I by 32% (P = .005) and zone II by 63.4% (P = .0006).

Figure 1.

Mean total time taken for laser treatment in both groups in different zones. Large spot laser significantly reduced total treatment duration in zone I by 32% (P = .005) and zone II by 63.4% (P = .0006).

Total Number of Spots Required Per Eye in Subgroups (Based on Zone)

Table 2:

Total Number of Spots Required Per Eye in Subgroups (Based on Zone)

The mean values of PIPP scores at 0, 5, and 30 minutes, and end of the procedure in the first eye followed by 0, 5, and 30 minutes, and end of the procedure in the second eye were analyzed. PIPP scores during the laser procedure were between 9 and 12, which indicates moderate-to-severe pain during laser treatment. Pain scores were high but comparable in both treatment groups (Table 3).

Mean PIPP Scores During Laser Procedure Between the Groups

Table 3:

Mean PIPP Scores During Laser Procedure Between the Groups

Spherical equivalent pre-laser treatment and 3 months after laser in the standard spot laser group was +1.375 diopters (D) (−3.25 D to +7 D) and 0 D (−4.5 D to +3 D), respectively, and in the large spot laser group was +2 D (−1 D to +5 D) and −0.25 D (−4 D to +3 D), respectively. Due to highly variable refractive error pre-laser, it was useful to calculate mean change in refractive error (myopia) from pre-laser (2.090 D ± 1.345 D) to 3 months' post-laser (2.465 D ± 1.399 D), but it was not statistically significant between the groups (Figure 2).

Pattern of spherical equivalent in both groups from pre-laser to 3 months' post-laser, which demonstrates a trend toward myopia in both the standard spot laser group (right boxes) and the large spot laser group (left boxes).

Figure 2.

Pattern of spherical equivalent in both groups from pre-laser to 3 months' post-laser, which demonstrates a trend toward myopia in both the standard spot laser group (right boxes) and the large spot laser group (left boxes).

Discussion

We studied 80 eyes of 40 premature infants with zone I (32.5%; 13 infants), zone II (55%; 22 infants), and zone III (12.5%; five infants) ROP. One hundred percent regression of disease occurred in all eyes in both treatment groups, reaffirming excellent results of laser photocoagulation when infants are screened / referred in time. It is observed that some cases in zone III also needed laser, as in our experience rarely stage III does occur in this area, and although it mostly regresses spontaneously, it many times leads to persistent fibrotic ridge and minimal macular dragging, which can be avoided as complete regression easily occurs with laser treatment.

There have been reports of use of large spot laser in treatment of ROP, but in very few patients. Shah et al.,3 in a series of 10 eyes, reported the mean time taken for conventional diode laser was 20.07 minutes, while that for large spot continuous mode was 12.3 minutes per eye and found it to be more time-efficient than the conventional laser. In their study, Balasubramaniam et al.4 had one patient with bilateral ROP with standard spot size burns placed adjacent to large spot size burns, which showed that large spot laser halves the number of spots required for treatment and reduces fluence by almost one-quarter, producing uniform spots.

We agree with concerns raised by Gupta et al.5 in reply to an above report that longer-duration continuous mode laser burns are more painful due to prolonged thermal effect and cause more retinal damage, with a high risk for overtreatment, and suggested a validated pain score be used. Therefore, unlike previous studies, we preferred to use interrupted (non-continuous) laser mode without the long pulse option, as we believe it had a more controlled and better safety profile.

However, care has to be taken to recognize the burn and shift focus more quickly as the spots are larger in size, and we need to avoid re-treatment over the same spot. Even then, large spot laser spots will be more confluent than standard spot laser spots (Figures 3 and 4), but then near confluent laser is reported to be better.6 Also, the spot that initially appeared faint would appear grayer / whiter during the next few minutes, so temptation to raise the laser power should be avoided. We suggest only experienced users well versed in use of standard spot laser should try this alternative as excessive uncontrolled burns may lead to overtreatment, leading to hemorrhages, retinal breaks, and other related complications. We found the large spot laser easy to use with no additional training required.

RetCam (Natus Medical Incorporated, Pleasanton, CA) fundus picture showing standard spot laser treatment in left eye at 3 months' follow-up.

Figure 3.

RetCam (Natus Medical Incorporated, Pleasanton, CA) fundus picture showing standard spot laser treatment in left eye at 3 months' follow-up.

RetCam (Natus Medical Incorporated, Pleasanton, CA) fundus picture showing large spot laser treatment in left eye at 3 months' follow-up. A more confluent laser pattern is seen.

Figure 4.

RetCam (Natus Medical Incorporated, Pleasanton, CA) fundus picture showing large spot laser treatment in left eye at 3 months' follow-up. A more confluent laser pattern is seen.

There are possibly concerns of disease regression, procedure time, experience needed, extent of pain, induced refractive errors, and complications using large spot laser, which this paper attempts to address, by studying all these parameters to assess safety while comparing with standard spot laser.

We found large spot laser significantly reduced total laser duration time in zone I by 32% and zone II by 63.4%. Many factors contribute to total duration required for laser treatment such as zone of ROP, expertise of treating surgeon, difficulty in pupillary dilation in advanced plus disease, media clarity, corneal haze, and limited cooperation under topical anesthesia by often systemically unstable infants. However, the large spot size being four times larger than standard spot size requires a fewer number of spots to laser the same area of avascular retina, and the procedure is completed faster. The faster procedure reduces total duration of pain and stress for the infant.

Ideally laser should be done under general anesthesia, yet in most developing countries, it is usually not done due to unavailability of expert neonatal anesthesiologists, difficulty in administering anesthesia frequently, and anesthesia-related morbidity and mortality in these sick, unstable infants. Thus, undoubtedly laser is a stressful and painful procedure for the child under topical anesthesia. Multiple factors contribute to pain during the laser procedure. It starts with forceful eyelid opening with an eyelid speculum, repeated scleral indentation, traction on rectus muscles, bright light of indirect ophthalmoscope, painful laser spots, and physical restraining of the infant during laser. Repeated application of topical anesthetic drugs and non-nutritive sucking pacifiers are insufficient to relieve pain, and our study demonstrates moderate-to-severe pain throughout the procedure. Incessant crying is of no help to end the procedure, which may last for hours in smaller ROP zones.

The study of pain in infants, including evaluation and intervention, is a growing concern as it is associated with impaired long-term neurodevelopmental, social, and emotional functions in later life.7 We find PIPP is a useful tool for evaluation of procedural pain in premature infants. By virtue of completing laser treatment faster, large spot reduced the total duration of pain experienced by the child.

Another concern is that premature infants with lasered ROP often develop induced myopia as compared with full-term infants.8 We also noted the trend toward myopia on follow-up, but the mean change in refractive error (myopia) was comparable between the two laser groups and was not statistically significant.

In conclusion, although laser treatment of ROP is a time-consuming and stressful procedure for preterm infants under topical anesthesia, large spot laser can significantly reduce total duration of pain and stress for the infant with better systemic stability and also be less tiring for the treating surgeon. With similar efficacy and no need for extra training, it can be suggested as an alternative to standard spot laser for treatment of ROP wherever the equipment is available. ROP planners may consider this technique in developing countries as they look for easier and faster ways to train specialists in laser treatment.

References

  1. Good WVEarly Treatment for Retinopathy of Prematurity Cooperative Group. Final results of the Early Treatment for Retinopathy of Prematurity (ETROP) randomized trial. Trans Am Ophthalmol Soc. 2004;102:233–248; discussion 248–250.
  2. Stevens B, Johnston C, Petryshen P, Taddio A. Premature Infant Pain Profile: development and initial validation. Clin J Pain. 1996;12(1):13–22. doi:10.1097/00002508-199603000-00004 [CrossRef]
  3. Shah PK, Narendran V, Kalpana N. Large spot transpupillary thermotherapy: a quicker laser for treatment of high risk prethreshold retinopathy of prematurity - a randomized study. Indian J Ophthalmol. 2011;59(2):155–158. doi:10.4103/0301-4738.77046 [CrossRef]
  4. Balasubramaniam SC, Mohney BG, Bang GM, Link TP, Pulido JS. Utility of large spot binocular indirect laser delivery for peripheral photocoagulation therapy in children. Arch Ophthalmol. 2012;130(9):1213–1217. doi:10.1001/archophthalmol.2012.1978 [CrossRef]
  5. Gupta A, Khetan V. Continuous mode large spot transpupillary thermotherapy for retinopathy of prematurity. Indian J Ophthalmol. 2012;60(6):577; author reply 577–578. doi:10.4103/0301-4738.103805 [CrossRef]
  6. Banach MJ, Ferrone PJ, Trese MT. A comparison of dense versus less dense diode laser photocoagulation patterns for threshold retinopathy of prematurity. Ophthalmology. 2000;107(2):324–327; discussion 328. doi:10.1016/S0161-6420(99)00042-1 [CrossRef]
  7. Grunau R. Early pain in preterm infants. A model of long-term effects. Clin Perinatol. 2002;29(3):373–394, vii–viii. doi:10.1016/S0095-5108(02)00012-X [CrossRef]
  8. Quinn GE, Dobson V, Davitt BV, et al. Early Treatment for Retinopathy of Prematurity Cooperative Group. Progression of myopia and high myopia in the early treatment for retinopathy of prematurity study: findings to 3 years of age. Ophthalmology. 2008;115(6):1058–1064.e1. doi:10.1016/j.ophtha.2007.07.028 [CrossRef]

Comparison of Total Time Taken (Minutes) for Laser Treatment and Between Subgroups (Based on Zones) in Both Treatment Groups

Standard Spot Laser Group (n = 20)Large Spot Laser Group (n = 20)P Value
All Zones65 (25–115)28 (10–75).0002
Zone I83 (65–88)57 (26–75).005
Zone II65 (25–115)22 (10–40).0006
Zone III30 (27–35)17 (10–24).083

Total Number of Spots Required Per Eye in Subgroups (Based on Zone)

Standard Spot Laser Group (n = 20)Large Spot Laser Group (n = 20)P Value
Zone I3,498 ± 7141,387 ± 342.0027
Zone II2,503 ± 1,335640 ± 285.0003
Zone III1,070 ± 702605 ± 712.5

Mean PIPP Scores During Laser Procedure Between the Groups

Standard Spot Laser Group (n = 20)Large Spot Laser Group (n = 20)P Value

First Eye
  0 min9.7 ± 1.89.6 ± 0.9.74
  5 min11.3 ± 1.910.3 ± 2.0.12
  30 min11.9 ± 1.310.0 ± 1.7.18
  End11.3 ± 1.410.9 ± 1.2.36

Second Eye
  0 min9.8 ± 1.210.1 ± 1.0.48
  5 min11.0 ± 1.59.5 ± 1.0.03
  30 min11.6 ± 1.412.0 ± 1.8.75
  End11.1 ± 1.310.6 ± 1.2.22
Authors

From Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India (PC, PB, RA); and the Department of Neonatology, All India Institute of Medical Sciences, New Delhi, India (R Agarwal).

The authors report no relevant financial disclosures.

Address correspondence to Parijat Chandra, MD, DNB, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India; email: parijatchandra@gmail.com.

Received: September 05, 2017
Accepted: April 25, 2018

10.3928/23258160-20181203-13

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