The authors report the formation of hard exudates and macular scarring after laser photocoagulation therapy in patients with retinopathy of prematurity (ROP). Two premature neonates, the first born at 24 weeks and the second at 25 weeks gestational age, were diagnosed as having ROP that necessitated laser photocoagulation treatment at 32 and 36 weeks, respectively. Subretinal fluid and macular hard exudation developed in both patients that eventually caused bilateral macular scarring. Subretinal macular fluid with hard exudation could lead to macular scar formation in neonates with ROP after laser photocoagulation that could significantly affect the visual prognosis in preterm infants. [J Pediatr Ophthalmol Strabismus 2013;50:e30–e32.]
From the Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.
The authors have no financial or proprietary interest in the materials presented herein.
Correspondence: Hassan A. Aziz, MD, Bascom Palmer Eye Institute, 900 N.W. 17th Street, Miami, FL 33136. E-mail:
Received: April 25, 2013
Accepted: May 08, 2013
Posted Online: July 02, 2013
Retinopathy of prematurity (ROP) is a proliferative vascular retinopathy stemming from incomplete retinal vascularization in preterm infants. The Early Treatment for Retinopathy of Prematurity Cooperative Group showed a 5% reduction in poor visual outcomes and a 6.5% reduction in poor structural outcomes when laser photocoagulation was given earlier compared to at threshold disease.1
Progressive disease after laser treatment poses a particular challenge to the clinician. We report macular hard exudate formation in patients with progressive ROP after laser treatment, which resulted in significant scarring and poor visual outcomes.
A former 24-week premature, 760 g neonate was transferred at 34 weeks postmenstrual age to the Bascom Palmer Eye Institute, Jackson Memorial Hospital for management of persistent plus disease. The patient received laser treatment at 32 weeks postmenstrual age at an outside facility for zone 1, stage 2 ROP with plus disease.
Funduscopic evaluation demonstrated stage 3+ in both eyes, that was worse in the right eye. Supplemental laser treatment was given to both eyes, and an intravitreal injection of bevacizumab 0.625 g/0.05 mL was given in the right eye. Evaluation 2 days following treatment demonstrated retinal vasculature engorgement and subretinal fluid in the right eye. At 36 weeks postmenstrual age, the right eye demonstrated resolution of plus disease and decreased subretinal fluid; however, foveal hard exudates were now present. Serial outpatient retinal examinations demonstrated resolution of subretinal fluid with improving exudate in the right eye by 40 weeks post-menstrual age. Over the following month, a macular retinal pigment epithelium scar formed in the right eye. Visual acuity with correction at the current age of 5 years is 8/400 in the right eye and 20/150 in the left eye (Figure 1
Figure 1. (A) Fundus color photograph of case 1 at 36 weeks of gestation with subretinal fluid with hard exudates in the macular area. (B) Fundus color photograph at 4 years of age demonstrating macular scarring with retinal pigment epithelium clumping.
A former 25-week premature, 780 g neonate was transferred at 39 weeks postmenstrual age to the Bascom Palmer Eye Institute, Jackson Memorial Hospital for management of bilateral tractional retinal detachments. The patient received laser treatment at 36 weeks postmenstrual age at an outside facility for zone 2, stage 3+ ROP.
Funduscopic evaluation demonstrated stage 4A disease in the right eye, stage 4B disease in the left eye, and minimal plus disease in both eyes. Supplemental laser treatment was given in the right eye, and scleral buckles were implanted in both eyes. At 1 week postoperatively, the right retina appeared flat and the left retina demonstrated anterior elevation with temporal dragging of vessels. At 2 weeks postoperatively, hard exudates were noted in the left retina. The hard exudates appeared to decrease after 4 weeks, and both retinas were attached with persistent macular dragging. Funduscopic evaluation at the time of scleral buckle release, 6 months after their placement, demonstrated retinal pigment epithelium hypopigmentation in both eyes, including the right fovea (Figure 2
). Visual acuity with correction at the current age of 8 years is 20/400 in the right eye and 20/800 in the left eye.
Figure 2. Fundus color photograph of case 2 at 3 years of age demonstrating macular scarring with retinal pigment epithelium clumping.
These cases represent the first report of macular retinal pigment epithelium scars developing in ROP after treatment. The infants in both cases received initial laser treatments at outside facilities in accordance with Early Treatment for Retinopathy of Prematurity Cooperative Group guidelines, but required supplemental interventions for progressive disease. The subsequent formation of retinal pigment epithelium scarring, especially in the macula and fovea, was unexpected and led to the poor visual outcomes in these patients.
The macular damage was likely due to the deposition of hard exudates observed in the cases rather than direct laser burns. Hard exudation is not typically associated with ROP, but certain scenarios have provided exceptions. Exudative retinopathy was reported as a late sequelae of ROP in adults in a series by Brown et al.2
Additionally, we have previously encountered hard exudation in cases of progressive ROP after laser treatment. The average postmenstrual age at birth in the previous series was 25 weeks with laser treatments given at 42 weeks postmenstrual age. The exudative retinal detachments that formed thereafter resolved by 50 weeks postmenstrual age with intravenous steroid treatment, leaving hard exudate deposits and macular retinal pigment epithelium mottling.3
We hypothesize that if laser photocoagulation does not sufficiently subdue the vascular proliferation underlying ROP and there is progression of disease, it is possible that the inflammatory effects of the laser to surrounding areas may be more pronounced. Increased vascular permeability in the central retina would lead to extravasation of a more exudative fluid. The hard exudate residue depositing in the immature retina would then lead to long-term structural damage. On the other hand, if the reactive subretinal fluid after laser treatment resolves without the formation of hard exudates, we would not expect retinal pigment epithelium damage to occur. To this effect, Noonan and Clark reported subretinal fluid causing a serious macular detachment after a single treatment of laser photocoagulation for ROP. The fluid fully regressed after 2 weeks without any hard exudation, and there was no long-term structural damage.4
From our experience with the aforementioned cases, the progression of ROP after laser treatment should raise an alarm in the clinician. Supplemental and salvage treatment should not be delayed because of the potential for the deposition of hard exudates in the developing retina and the poor structural and visual outcomes that they may cause, especially if located in the macula.
- Early Treatment for Retinopathy of Prematurity Cooperative Group. Revised indications for the treatment of retinopathy of prematurity: results of the early treatment of retinopathy of prematurity randomized trial. Arch Ophthalmol. 2003;121:1684–1694.
- Brown MM, Brown GC, Duker JS, Tasman WS, Augsburger JJ. Exudative retinopathy of adults: a late sequela of retinopathy of prematurity. Int Ophthalmol. 1995;18:281–285 doi:10.1007/BF00917831 [CrossRef] .
- Moshfeghi DM, Silva AR, Berrocal AM. Exudative Retinal Detachment following photocoagulation in older premature infants for retinopathy of prematurity: description and management. In press.
- Noonan CP, Clark DI. Acute serous detachment with argon laser photocoagulation in retinopathy of prematurity. J AAPOS. 1997;1:183–184 doi:10.1016/S1091-8531(97)90064-1 [CrossRef] .