Retinopathy of prematurity (ROP) has an annual incidence of 0.12% to 0.17% and is the leading cause of preventable blindness in children in the United States.1,2 ROP occurs most commonly in premature infants younger than 32 weeks gestation or those with birthweights less than 1,500 grams.1,3 Early detection and treatment are essential in preventing severe vision loss that may be induced by this vasoproliferative disorder. Screening in select infants in the United States is performed via indirect ophthalmoscopy with scleral depression or telemedicine using widefield retinal imaging.4 The gold standard of care for ROP eyes warranting treatment is indirect laser photocoagulation.5 However, a rare clinical sequelae of laser photocoagulation in the treatment of ROP is exudative retinal detachment (ERD). In this paper, we report the occurrence of severe ERD following laser photocoagulation for type I ROP and present the imaging features of this rare complication.
A 610-gram premature male infant was born at 24 and three-sevenths weeks gestational age. Examination at 36 weeks postmenstrual age (PMA) demonstrated posterior zone II, stage 3 ROP with plus disease in both eyes (OU). Red diode laser was used to treat both eyes at the time of type I ROP diagnosis with the settings of 200 mW to 300 mW power and 0.1 second to 0.2 second duration. The right eye (OD) received 2,776 spots and the left eye (OS) received 1,991 spots in near contiguous fashion. There were no complications. Platelet count was not available on the day of treatment but measured 176,000 per microliter (μL) 48 hours post-treatment. One week following laser treatment, ERD was noted in OS only with persistent plus disease (Figure 1). After extensive discussion with the family, the patient was started on intravenous dexamethasone every 12 hours tapered during a 10-day period and topical prednisolone acetate (1%) every 2 hours OS. Platelet count increased to 317,000/μL 48 hours after diagnosis of ERD.
Fundus photographs of the right (A) and left eyes (B) at 37 weeks postmenstrual age (1 week after laser photocoagulation). The right eye demonstrated the resolution of plus disease with residual ridge and laser scars in the avascular retina. Severe exudative retinal detachment (ERD) with persistent vascular dilation noted in the left eye.
Follow-up examination at 39 weeks PMA revealed near-complete resolution of ERD with mild dilation and tortuosity of posterior pole vessels (Figure 2). Four weeks later, topical prednisolone drops were tapered and ultimately discontinued. Examination at 46-week PMA (10 weeks post laser treatment) demonstrated complete regression of ROP and extensive accumulation of subretinal lipid in the posterior pole (Figure 2). An examination under anesthesia (EUA) and fluorescein angiography was performed at 62 weeks PMA. OS fundus findings included multifocal subretinal lipid deposits, increased choroidal fluorescence in the macula including the fovea, and late hyperfluorescence of the optic disc (Figure 3). At most recent follow-up at 2 years of age, visual acuity was central, unsteady, and maintained (CUSM) in the right eye and central, steady, and unmaintained (CSUM) in the OS with intermittent esotropia bilaterally. Cycloplegic refraction demonstrated −14.00 diopters (D) and −10.00 D of spherical error in the right and left eyes, respectively.
Serial fundus photographs of the left eye at various follow-up intervals. Improving exudative retinal detachment (ERD) at 38 weeks postmenstrual age (PMA), 2 weeks after receiving laser photocoagulation (A). Near completely resolved ERD at 39 weeks PMA (B). Resolved ERD, and improving vascular dilation and tortuosity observed progressively at 40 weeks (C), 42 weeks (D), and 45 weeks PMA (E). Complete regression of retinopathy of prematurity at 46 weeks PMA (F) with posterior pole subretinal lipid accumulation 10 weeks following laser photocoagulation treatment. Multifocal subretinal lipid deposits and pigmentary abnormalities of the central macula at 62 weeks PMA (G).
Composite fundus photograph and fluorescein angiograph of the right and left eyes at 62 weeks postmenstrual age. Complete regression of retinopathy of prematurity (ROP) observed in right eye with laser scars in the avascular retina (A). Fluorescein angiography revealed peripheral vascular abnormalities and normal development of foveal avascular zone in the right eye (C). Left eye fundus photograph (B) showed regressed ROP with laser scars in the avascular retina and multifocal lipid deposition posteriorly and in the inferior midperiphery. Fluorescein angiograph of the left eye (D) demonstrated optic disc hyperfluorescence, increased macular hyperfluorescence involving the inferior fovea, and more pronounced peripheral vascular abnormalities.
We describe the evolution and imaging characteristics of ERD 1 week after laser photocoagulation for Type I ROP in a 36 weeks PMA infant. The present case differs from previous reports in that ERD occurred in the eye receiving less laser photocoagulation in an infant receiving treatment at less than 40 weeks PMA.6–13 This finding suggests the amount and intensity of laser photocoagulation administered in ROP may not be directly correlated with the onset of ERD. Although the best management strategy for ERD following laser photocoagulation for ROP is unclear, systemic and topical corticosteroids may facilitate rapid resolution, therefore minimizing structural and functional risk to the developing retina.
Although intravitreal bevacizumab (IVB) (Avastin; Genentech, South San Francisco, CA) has shown promising results, laser photocoagulation remains the gold standard for type I ROP.14,15 Despite the effectiveness of treatment, laser photocoagulation is not without risk. Rare complications including primary anterior segment ischemia, corneal edema, iris atrophy, and the formation of posterior segment synechiae have been observed in to 2% to 3% of treated eyes.16 Cataract formation remains the most frequently reported adverse event, reported in between 0.003% up to 6% of eyes treated with laser photocoagulation.17–20 It is postulated that lens opacification likely results from a combination of the focal thermal effects of the laser beam and anterior segment ischemia.21,22
ERD after laser photocoagulation for ROP is comparatively rarer and more complex. Based on experimental findings in cat eyes, Marmor and Yao proposed that laser damage to the retinal pigment epithelium and choriocapillaris introduces a defect in the blood-retinal barrier and impairs fluid transport.23 Moshfeghi et al. suggested a similar process in infant ROP eyes that permits shunting of fluid from the periphery.6 Low birth-weight, multiple gestations, and pulmonary hypertension may be contributing factors to developing ERD after laser photocoagulation.8,13 In addition, neonatal events such as sildenafil use may further facilitate ERD by augmenting choroidal circulation and inducing uveal venous stasis.13
Given the rare occurrence of ERD after laser photocoagulation in ROP, there is no evidence-based consensus on management. Both Mulvihill et al. and Noonan and Clark reported spontaneous resolution without sequelae 2 weeks to 3 weeks after laser photocoagulation in a subtype of ERD involving the macula only and diagnosed immediately following treatment.7,8 Muni et al. observed self-resolution at 10 weeks, with extended time to resolution attributed to second laser treatment 2 weeks after initial laser photocoagulation.9 Treatment with corticosteroids has resulted in relative success. Kabatas et al. reported resorption of bilateral ERD with intravenous dexamethasone (0.6 mg/kg/day) after 17 days.10 Moshfeghi et al. described the courses of three infants undergoing laser photocoagulation at less than 40 weeks PMA, and reported near-complete resolution in ERD eyes with intravenous dexamethasone and daily topical prednisolone acetate (1%) by 50 weeks PMA.6
IVB as a monotherapy or as part of a combination regimen has also been reported for the treatment of ERD.11,12 Lalwani et al. reported bilateral ERD in which the left eye was treated with two IVB injections 14 days apart remained stable, whereas the right eye received only one injection and progressed to tractional retinal detachment.11 Ehmann and Greve described two patients, one treated with IVB and intravenous dexamethasone with resolution of ERD after 7 days and the other treated with IVB alone improving in 11 days, suggesting combination IVB and systemic dexamethasone may result in a synergistic therapeutic effect.12 However, we and others have noted rapid resolution of ERD with corticosteroid treatment alone, indicating that the addition of IVB may potentially provide only marginal improvement in outcomes. Surgical intervention with external subretinal drainage and scleral buckle placement has been reported for a refractory case of ERD.13
ERD after laser photocoagulation remains a rare but serious complication of ROP treatment. We recommend providers maintain high degree of suspicion for ERD irrespective of the amount, duration, or intensity of laser administered. Limited evidence suggests treatment with systemic and local steroids decreases inflammation and minimizes threat to the structural integrity of the retina in a developmentally critical period. Future studies would benefit from evaluating the impact of prenatal events, neonatal course, and the use of anti-VEGF alongside corticosteroids in management.
- Lad EM, Nguyen TC, Morton JM, Moshfeghi DM. Retinopathy of prematurity in the United States. Br J Ophthalmol. 2008;92(3):320–325. doi:10.1136/bjo.2007.126201 [CrossRef]
- Lad EM, Hernandez-Boussard T, Morton JM, Moshfeghi DM. Incidence of retinopathy of prematurity in the United States: 1997 through 2005. Am J Ophthalmol. 2009;148(3):451–458. doi:10.1016/j.ajo.2009.04.018 [CrossRef]
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- Richter GM, Williams SL, Starren J, Flynn JT, Chiang MF. Telemedicine for retinopathy of prematurity diagnosis: Evaluation and challenges. Surv Ophthalmol. 2009;54(6):671–685. doi:10.1016/j.survophthal.2009.02.020 [CrossRef]
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- Moshfeghi DM, Silva RA, Berrocal AM. Exudative retinal detachment following photocoagulation in older premature infants for retinopathy of prematurity: Description and management. Retina. 2014;34(1):83–86. doi:10.1097/IAE.0b013e3182993d5f [CrossRef]
- Noonan CP, Clark DI. Acute serous detachment with argon laser photocoagulation in retinopathy of prematurity. J AAPOS. 1997;1(3):183–184. doi:10.1016/S1091-8531(97)90064-1 [CrossRef]
- Mulvihill A, Lanigan B, O'Keefe M. Bilateral serous retinal detachments following diode laser treatment for retinopathy of prematurity. Arch Ophthalmol. 2003;121(1):129–130. doi:10.1001/archopht.121.1.129 [CrossRef]
- Muni RH, Kohly RP, Charonis AC, Lee TC. Retinoschisis detected with handheld spectral-domain optical coherence tomography in neonates with advanced retinopathy of prematurity. Arch Ophthalmol. 2010;128(1):57–62. doi:10.1001/archophthalmol.2009.361 [CrossRef]
- Kabatas EH, Ozer PA, Kurtul BE, et al. Systemic steroid for exudative retinal detachment following laser photocoagulation for retinopathy of prematurity. American Journal of Medical Sciences and Medicine. 2015;3(5):67–69.
- Lalwani GA, Berrocal AM, Murray TG, et al. Off-label use of intravitreal bevacizumab (Avastin) for salvage treatment in progressive threshold retinopathy of prematurity. Retina1. 2008;28(3 Suppl):S13–S18. doi:10.1097/IAE.0b013e3181644ad2 [CrossRef]
- Ehmann D, Greve M. Intravitreal bevacizumab for exudative retinal detachment post laser therapy for retinopathy of prematurity. Can J Ophthalmol. 2014;49(2):228–231. doi:10.1016/j.jcjo.2013.12.014 [CrossRef]
- Armada-Maresca F, Peralta-Calvo J, Pastora-Salvador N, Grabowska A, Vallejo-Garcia J. External subretinal drainage, bevacizumab, and scleral buckling for complete exudative retinal detachment after photocoagulation in retinopathy of prematurity. Retin Cases Brief Rep. 2014;8(1):33–36. doi:10.1097/ICB.0b013e3182a48bf1 [CrossRef]
- Mintz-Hittner HA, Kennedy KA, Chuang AZBEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011;364(7):603–615. doi:10.1056/NEJMoa1007374 [CrossRef]
- Fielder AR. Revised indications for the treatment of retinopathy of prematurity: Results of the Early Treatment for Retinopathy of Prematurity randomized trial. Arch Ophthal. 2003;121(12):1769–1771. doi:10.1001/archopht.121.12.1769 [CrossRef]
- Fallaha N, Lynn MJ, Aaberg TM Jr, Lambert SR. Clinical outcome of confluent laser photoablation for retinopathy of prematurity. J AAPOS. 2002;6(2):81–85. doi:10.1067/mpa.2002.121452 [CrossRef]
- O'Neil JW, Hutchinson AK, Saunders RA, Wilson ME. Acquired cataracts after argon laser photocoagulation for retinopathy of prematurity. J AAPOS. 1998;2(1):48–51. doi:10.1016/S1091-8531(98)90110-0 [CrossRef]
- Christiansen SP, Bradford JD. Cataract in infants treated with argon laser photocoagulation for threshold retinopathy of prematurity. Am J Ophthalmol. 1995;119(2):175–180. doi:10.1016/S0002-9394(14)73870-X [CrossRef]
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