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Original Article Long term refractive and structural outcome following laser treatment for zone 1 aggressive posterior retinopathy of prematurity

Parag K. Shah, Minu Ramakrishnan1, Bani Sadat, Sandeep Bachu, V. Narendran, N. Kalpana

Department of Pediatric and Ocular Oncology, Aravind Eye Hospital and Postgraduate Institute of , Coimbatore, Tamil Nadu, 1Department of Ophthalmology, K J Somaiya Medical College and Research Centre, Mumbai, Maharashtra, India

Aim: To report the long term refractive, visual and Results: Forty-eight eyes of 25 infants were included structural outcome post-laser for zone 1 aggressive in the study. Average follow-up was 6.91 years posterior retinopathy of prematurity (AP-ROP). (range, 3.8-9.5years) after laser treatment. was noted in 43 out of 48 eyes (89.6%). Two eyes Materials and Methods: A retrospective analysis had simple whereas three eyes had no was performed of refractive status of premature . infants with zone 1 AP-ROP who underwent laser photocoagulation from 2002 to 2007 and followed up Conclusion:After successful laser treatment for zone 1 retinopathy of prematurity (ROP), 94% of our cases till 2013. Once the disease regressed, children were developed refractive error. Although most had a favorable followed up six monthly with detailed examination anatomical and visual outcome, long-term follow-up even regarding fixation pattern, ocular motility, , after a successful laser treatment in ROP was necessary. detailed anterior segment and posterior segment examination, and refractive status including best Keywords: Retinopathy of prematurity, refractive corrected . outcome, zone 1

Introduction Evolution of laser treatment for ROP was associated with better structural and functional outcome compared to that for eyes [3] Retinopathy of prematurity (ROP) is a potentially blinding treated with cryotherapy. There are multiple reports of use vasoproliferative retinopathy seen in premature infants with low of various lasers for threshold ROP with good structural and [4-7] birth weight. Blindness from ROP is a very significant problem, long-term refractive outcome. However, there are no reports with an incidence of 8% in developed countries[1] and 40% in the on long-term refractive outcome of zone 1 disease. Our data developing countries.[2] represents long term refractive and structural outcome for zone 1 ROP.

Access this article online Quick Response Code: Materials and Methods Website: www.ojoonline.org It is an interventional retrospective case series of premature infants with zone 1 aggressive posterior ROP (AP-ROP) who underwent DOI: laser photocoagulation, during the study period from 2002 to 10.4103/0974-620X.142592 2007. Data was analyzed in 2013. The study was approved by the ethics committee of our institute. All infants weighing 1800 g or

Copyright: © 2014 Shah PK et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Correspondence: Dr. Parag K. Shah, Department of Pediatric Retina and Ocular Oncology, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Avinashi Road, Coimbatore - 641 014, Tamil Nadu, India. E-mail: [email protected]

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Shah, et al.: Refractive outcome of zone 1 ROP

with gestational age 34 weeks and those infants weighing >1800 g 1 D was seen in 12 eyes (27.9%) whereas eight with an unstable course were screened for ROP. All infants with eyes (18.6%) had anisometropia 2 D. The visual outcome was zone 1 AP-ROP, which regressed after laser treatment, were good with BCVA of 6/6 in five eyes and 6/12 in 39 eyes (81%) included in the study. Laser used was diode 810 nm (Oculight on Snellen’s chart. SLx, Iridex Co, LA, USA). Power settings were titrated to achieve a gray-white burn of moderate intensity, and spots were applied Two cases had poor visual outcome. One infant had disc pallor in in a confluent manner to cover the entire avascular retina from both eyes with nystagmus and another infant with birth weight the ridge to ora serrata. All lasers were performed under topical of 1690 g and gestational age of 31 weeks developed very high anesthesia with an anesthetist on standby. Treated eyes were myopia (SE both eyes: −18.5 D) with poor visual outcome. One followed up closely, often weekly or more frequently, for signs of child required additional cryotherapy with laser to control the regression or need for further laser. Once ROP regressed, children vascular process and ended up having nystagmus with pale disc. were followed up six monthly with detailed examination regarding This child had a birth weight of 1230 g and gestational age of fixation pattern, ocular motility, nystagmus, detailed anterior 29 weeks. Coming to structural outcome, one eye developed segment and posterior segment examination, and refractive fibrous proliferation with disc dragging while two eyes developed status including best corrected visual acuity (BCVA). Spherical lamellar . equivalent (SE) was calculated for all eyes with compound myopic astigmatism using the formula SE = Sphere + ½ Cylinder. Discussion High myopia was defined as spherical correction −6 diopter (D). Astigmatism was calculated in plus cylinder form and classified Our study presented the visual outcome and refractive status over a as with-the-rule (WTR) 75°-105°, against-the-rule (ATR) period of 6.91 years in infants treated with laser photocoagulation 0°-15° and 165°-180° and oblique (OBL) 16°-74° and 106°-164°. for zone 1 ROP. Majority of our patients had favorable anatomical Astigmatism was defined as cylindrical correction 1 D whereas and visual outcomes. high astigmatism was defined as cylindrical correction 2 D. We defined good visual outcome as 6/12 on Snellen’s chart.[4] This study showed that most of the children had a myopic Spherical equivalent of the refractive error and the degree and axis refraction, with mean spherical equivalent in right eye was of astigmatism were evaluated. −6.14 D (range, −18.5-1.25 D) and in left eye was − 5.11 D (range, −18.75-0.5 D). The visual outcome was good, with Results BCVA 6/12 on Snellen’s chart seen in 81% children. In a study using diode laser for threshold ROP by Yang et al.,[4] 65.5% eyes achieved 6/12 vision. Of all eyes, 77% were myopic with mean Forty-eight eyes of 25 infants with zone 1 AP-ROP were included SE of −3.87 D and 16.7% of them had myopia 6 D over a mean in the study, of which 15 were males and 10 females. Mean birth follow-up of 7.8 years. McLoone et al.[5] reported similar results weight was 1509.6 g (range, 850-2080 g) and mean gestational age with 50% of their laser-treated eyes being myopic and 35% having was 32 weeks (range, 28-35 weeks). Average post-conceptional myopia >4 D with diode laser in children with threshold ROP with age at laser was 35.6 weeks. The average laser spots were a mean follow up of 11 years. 3261 spots (range, 800-6416). One patient needed additional cryotherapy to control the progression. Mean follow-up period In a study using argon laser photocoagulation for threshold ROP was 6.91 years (range, 3.8-9.5 years). Three eyes had no refractive by Ospina et al.,[8] at a follow-up of 5 years, 30 eyes (71.4%) had error. Two eyes had simple myopia. The average spherical a BCVA of 20/40 or better. In all, 26 (62%) eyes were myopic and equivalent in right eye was − 6.14 D (range, −18.5-1.25 D) and in the overall mean spherical equivalent was −4.95 D. In a study with left eye was − 5.11 D (range, −18.75-0.5 D). Overall astigmatism 1 year follow-up of patients with laser-treated threshold ROP by was seen in 43 out of 48 eyes (89.6%). All 43 children had a Dhawan et al. in 2008,[6] mean refractive error with SE −4.71 D myopic astigmatism; 36 had with-the-rule (WTR) astigmatism, was seen, with myopia occurring in 80.43% of eyes. five eyes had against-the-rule (ATR) astigmatism, and two eyes had oblique astigmatism (16°-74° and 106°–164°) [Table 1]. It is known that most babies with ROP subsequently become myopic.[9] This myopic tendency is augmented by both cryotherapy Thirty-nine out of 43 eyes (90.7%) had astigmatism 1 D, of and laser treatment, but its mechanism is controversial. Knight which 21 (48.8%) had astigmatism 2 D. The average astigmatism Nonan and O’Keefe in a three-year nonrandomized retrospective in right eye was − 2.08 D (range, −4.0-−0.5 D) and in left eye study demonstrated lower myopia following laser treatment.[10] was − 1.78 D (range, −4–−0.5 D). This was confirmed by other studies, the most important being the 10-year prospective nonrandomized trial by Ng et al.[3] and Table 1: Type of astigmatism Kent et al.,[11] which compared both the treatments and found Astigmatism type Total eyes (n=43) Percentage less myopia in the laser-treated eyes. Cryotherapy-treated With-the-rule 36 83.7 eyes had shallower anterior chamber depth and thicker lenses Against-the-rule 5 11.6 with increased axial length compared to laser-treated eyes. Oblique 2 4.6 Cryotherapy causes larger areas of chorioretinal adhesion and

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Shah, et al.: Refractive outcome of zone 1 ROP

destruction of normal choroidal architecture, which changes fibrous proliferation in one case which was more due to progression the scleral structure, making it susceptible to stretching, leading of disease and lamellar cataract in both eyes of one child. to high myopia with cryotherapy than with laser. The greater incidence of myopia in ROP is mostly associated with lens The main limitation of our study is that it is retrospective and thickness and lens power with lesser contribution from corneal we have not assessed progression of refractive error over the steepness and axial length and a more forward position of the lens follow-up period; only the final follow-up refraction was used for center. Evidence of altered anterior segment development in ROP, analysis. Since all eyes were treated, there was no comparative as shown by the increased lens thickness with shallow anterior group to assess refractive and visual outcome with untreated eyes. chamber depth and maintenance of anterior segment depth, leads Thus pre-existing myopia and laser-induced myopia could not be to high myopia in these infants.[12] Also, it has been shown that classified separately. spontaneously regressed ROP has lesser myopia compared to treatment groups.[13] Only one study by Kieselbach et al.[7] showed In conclusion, majority of our patients treated with laser predominant hypermetropia seen post laser photocoagulation for photocoagulation for zone 1 AP-ROP had favorable anatomical and ROP. Wani et al.[14] had unfavorable structural outcome in 7.4% visual outcome at an average follow-up of 6.91 years. Anisometropia eyes and poor visual outcome (visual acuity <20/40) in 47% and advanced refractive error are common causes of impaired visual eyes. They found zone I disease as the significant risk factor for function in these patients and emphasize the need for a long-term unfavorable structural outcome (P < 0.0001). Katoch D[15] et al. follow-up even after a successful laser treatment in ROP. in a retrospective review of 36 infants (69 eyes) with Type 1 pre-threshold ROP treated with laser, reported myopia in nearly References one-fourth of the eyes. Harder et al.[16] compared refractive outcome between intravitreal and conventional retinal laser 1. Jacobson L, Fernell E, Broberger U, Ek U, Gillberg C. Children with group and found that at a one-year follow-up, bevacizumab group blindness due to retinopathy of prematurity- a population based study. led to less myopization and less astigmatism. Perinatal data, neurological and ophthalmological outcome. Dev Med Child Neurol 1998;40:155-9. 2. Gilbert C, Rahi J, Eckstein M, O’Sullivan J, Foster A. Retinopathy of In our study, overall high astigmatism of 2.0 D was seen in 48.8% prematurity in middle income countries. Lancet 1997;350:12-4. eyes. WTR astigmatism was seen in 36 eyes (83.7%) and ATR in 3. Ng EY, Cannolly BP, McNamara JA, Regillo CD, Vander JF, Tasman W. five eyes (11.6%) and two eyes (4.6%) had oblique astigmatism. A comparison of laser photocoagulation with cryotherapy for threshold A study by Davitt et al.[17] in patients under Early Treatment for ROP at 10 years: Part 1. Visual function and structural outcome. Ophthalmology 2002;109:928-34. ROP (ETROP) study revealed that astigmatism was not influenced 4. Yang CS, Wang AG, Sung CS, Hsu WM, Lee FL, Lee SM. Long-term by zone of acute phase ROP, presence of plus disease, or retinal visual outcomes of laser-treated threshold retinopathy of prematurity: residua. Most often the eyes had WTR astigmatism, similar to our A study of refractive status at 7 years. Eye 2010;24:14-20. study. In our study, 43% developed astigmatism of 1 D and 20% 5. McLoone E, O’Keefe M, McLoone S, Lanigan B. Long term functional and had 2 D. It has been reported that most preterm infants have structural outcomes of laser therapy for retinopathy of prematurity. Br J Ophthalmol 2006;90:754-9. WTR astigmatism.[18,19] Several studies have shown that there is no 6. Dhawan A, Dogra M, Vinekar A, Gupta A, Dutta S. Structural sequelae and difference in the prevalence of astigmatism between cryotherapy refractive outcome after successful laser treatment for threshold retinopathy and laser photocoagulation groups.[10,20] The only difference is of prematurity. J Pediatr Ophthalmol 2008;45:356-61. that patients receiving cryotherapy are more likely to have ATR 7. Kieselbach GF, Ramharter, Baldissera I, Kralinger MT. Laser astigmatism than those receiving laser photocoagulation.[20] The photocoagulation for retinopathy of prematurity: Structural and functional outcome. 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The infl uence of retinopathy Various types of lasers with various delivery systems have been of prematurity on ocular growth. Eye 2000;14:23-9. tried for ROP treatment with good success.[4,6-8,21-23] Complications 12. Garcia-Valenzuela E, Kaufman LM. High myopia associated with observed with laser treatment include corneal edema, anterior retinopathy of prematurity is primarily lenticular. J AAPOS 2005;9:121-8. segment , , posterior synechiae, 13. Sahni J, Subhedar NV, Clark D. Treated threshold stage 3 versus spontaneously regressed subthreshold stage 3 ROP: A study of motility, cataract, and macular ectopia. Others include abnormal refractive and anatomical outcomes at 6 months and 36 months. Br J [24] liquefied vitreous with fibrillar condensation, fibrovascular Ophthalmol 2005;89:154-9. [25] [26] organization, and subretinal haemorrhages. Also, changes in 14. Wani VB, Sabti KA, Kumar N, Raizada S, Kandari JA, Harbi MA, et al. [27] retinal vessel diameter, slight constriction of the peripheral visual Structural and functional results of indirect diode laser treatment for fields,[28] and angle closure [29] have been documented. retinopathy of prematurity from 1999 to 2003 in Kuwait. Clin Ophthalmol Our case series showed none of the major complications, except 2013;7:271-8.

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