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Arch Ophthalmol. 2001;119:615-617.

The Cryo-ROP study established exocryotherapy as a beneficial treatment for threshold retinopathy of prematurity (ROP).¹ More recently, the diode and argon indirect lasers have been used to treat threshold ROP because they are technically easier to use and more easily tolerated by the patient compared with cryotherapy.^2-5 In addition, it has been demonstrated that a more confluent laser pattern has a higher success rate than a less confluent laser pattern.⁶ Previously reported complications of cryotherapy include conjunctival and subconjunctival hemorrhage, conjunctival laceration, elevated intraocular pressure (IOP), and vision-threatening preretinal, retinal, or vitreous hemorrhage.^7-8 Reported complications of laser therapy include cataract development and hyphemas, and very rarely corneal, iris, and lens burns and choroidal rupture with hemorrhages and subsequent neovascularization.^9-11

We report on cataracts, iris atrophy, and hypotony in 8 eyes of 5 patients following confluent treatment for threshold ROP. None of the eyes demonstrated a retinal detachment at the time the anterior segment changes were identified. We feel that this represents an anterior segment ischemia.

Patients and Methods
Five patients were referred to William Beaumont Hospital in Royal Oak, Mich, from January 1997 to July 1999 for evaluation of complications from treatment of threshold ROP at various medical centers in the United States. All 10 eyes of the 5 patients had been treated for threshold ROP. Seven of the eyes that developed additional complications had been treated with diode laser and 1 eye had been treated with cryotherapy. All 7 eyes underwent lensectomy and vitrectomy. Two of the 7 eyes received silicone oil.

Report of Cases
Case 1

A 570-g baby was born after 23 weeks' gestation. At 13 weeks of age (36 weeks' postconceptual age [PCA]), the child was diagnosed as having threshold ROP in both eyes and was treated with exocryotherapy in both eyes. Four days after treatment the right eye was diagnosed as having a hyphema and corneal haze. The ROP regressed without complication in the left eye.

The patient was referred to William Beaumont Hospital for evaluation. Examination under anesthesia revealed regressed ROP in the left eye. Examination of the right eye showed a cataract, iris atrophy, and hypotony. A lensectomy, vitrectomy, and a fluid-air exchange were performed successfully. It was noted during surgery that the retina was in good position except for a small radial fold temporally. There was no evidence of active ROP. Follow-up examinations showed the right eye to be phthisical.

Case 2

A 592-g baby was born after a gestational period of 24 weeks 6 days. At 8 weeks of age (33 weeks' PCA) the patient was diagnosed as having stage 3 threshold ROP. The patient received confluent laser treatment for both eyes and developed bilateral hyphemas and cataracts. Partial lensectomies were performed when the baby was 12 weeks old.

The patient was referred to William Beaumont Hospital for evaluation. The right eye was soft with evidence of iris atrophy and had large lens pearls, which reduced the view of the posterior pole. The left eye had a normal IOP and anterior segment. Fundus examination demonstrated attached retina and suggested regression of ROP. The patient underwent a vitrectomy, membrane peeling, and removal of retained lens materials in both eyes. Subsequent follow-up examinations showed both eyes to be phthisical.

Case 3

A 705-g baby was born after 24 weeks 3 days' gestation. The patient developed threshold ROP in both eyes at 8 weeks of age (33 weeks' PCA) and was treated with confluent laser treatment to both eyes. The left eye responded to the laser therapy and the retinopathy regressed. The right eye subsequently developed large pupillary cysts and a cataract and became hypotonous.

The patient was referred to William Beaumont Hospital for evaluation and had the cysts and lens surgically removed from the right eye. The retina was attached and demonstrated evidence of regressed ROP; however, the eye went on to develop phthisis.

Case 4

A 790-g baby was born at 25 weeks' gestation. The patient went on to develop threshold ROP in both eyes and was treated with laser photocoagulation in both eyes at 38 weeks' PCA. Following laser treatment, the baby developed severe posttreatment anterior segment inflammation in both eyes and bilateral cataracts. One month after laser treatment, the patient underwent bilateral lensectomies and vitrectomies. Two months after surgery the child was referred to William Beaumont Hospital and the right eye was found, despite regressed ROP, to have developed early phthisis. The left eye went on to develop a retinal detachment secondary to advancing ROP and was treated with a second vitrectomy and membrane peeling. This eye also went on to develop phthisis.

Case 5

A 632-g baby was born at 24 weeks' gestation. The patient developed threshold ROP in both eyes and at 14 weeks of age (38 weeks' PCA) was treated with confluent laser treatment to both eyes. After treatment, both eyes developed cataracts, iris atrophy, and hypotony (Figure 1).

View larger version (34K): [in this window] [in a new window] Anterior segment photograph of the right eye demonstrating a cataract in a patient with iris atrophy and hypotony following confluent laser treatment for retinopathy of prematurity.

The patient was referred for evaluation and underwent lensectomy, vitrectomy, sector inferior iridotomy, and placement of silicone oil in both eyes. A follow-up examination with the patient under anesthesia 1 week later revealed the IOP to be 10 to 12 mm Hg. Fundus examination of both eyes demonstrated complete laser treatment, retinal attachment, and regressed ROP. Postoperative examination, 6 months after placement of silicone oil, revealed a well-formed anterior chamber, and ocular pressure,and globe contour were both normal.

Results
Eight eyes were evaluated for complications following treatment for threshold ROP and found to have signs of anterior segment ischemia including cataracts, iris atrophy, hypotony, and corneal haze. Four of the 5 patients were male and 5 of the eyes were right eyes. The birth weights ranged from 570 to 790 g, with a mean of 657 g. The PCA at the time of initial treatment for threshold ROP ranged from 33 to 38 weeks with a mean of 35 weeks.

Six of the 8 eyes underwent lensectomy and vitrectomy with a fluid-air exchange and yet still went on to develop phthisis. Two of the 8 eyes underwent lensectomy and vitrectomy and received silicone oil instead of a fluid-air exchange. These eyes had a beneficial anatomic result from this therapy.

Comment
Treatment for ROP, whether with cryotherapy or laser, has clearly proven to be beneficial but is not without complication. This article sites vision and ocular threatening complications from confluent laser or cryotherapy of threshold ROP. Clinical examination of all eyes during examination with the patient under anesthesia or at the time of lensectomy or vitrectomy revealed confluent anterior retinal treatment, regression of threshold ROP, and the absence of a retinal detachment in all the eyes. In addition, it should be noted that the ciliary body was not accidentally treated in any of the cases reported.

A possible mechanism for developing anterior segment ischemia following treatment of ROP can be made by comparing laser treatment in proliferative diabetic retinopathy with laser treatment in ROP. The major difference in treating these diseases is the location and confluence of the laser burns. Laser burn placement for the treatment of proliferative diabetic retinopathy tends to spare the far peripheral portions of the retina. Treatment of ROP includes the entire anterior avascular retina from the edge of the pars plicata back to the anterior edge of the ridge of proliferative retinopathy covering the entire circumference of the far peripheral retina. The long posterior ciliary arteries travel along the horizontal meridians in the suprachoroidal space and anastomose with the anterior ciliary arteries to form the anterior vascular arcade and supply the anterior segment of the eye with blood. In addition, during treatment of ROP there is significant scleral depression, which could impair the circulation in the long posterior ciliary arteries. Furthermore, treatment in the horizontal meridians tends to be more confluent than in other areas because these sectors of retina are more accessible with relation to the medial and lateral canthi. Impairment of blood flow and simultaneous confluent tissue ablation could increase the risk of inducing anterior segment ischemia that includes cataract, iris atrophy, and hypotony.

A potential treatment to preserve the physical structure of the eye after this reported complication is with the use of silicone oil. The 2 eyes in which silicone oil was placed maintained normal anatomic structure compared with the eyes that only had a fluid-air exchange and went on to become hypotonous. The adult and pediatric literature has reported on the safety of silicone oil used for extended periods.^12-13 It should be noted that follow-up for the eyes with silicone oil was for 6 months; therefore, it is possible that the anatomic success is only temporary. There are reported side effects of using silicone oil, but at this time we feel this treatment provides the best possible outcome for a difficult complication of ROP treatment.

It has been the impression of many clinicians that confluent is a more effective treatment than nonconfluent laser. We have identified a complication of confluent treatment, but it may be avoided. Perhaps one should treat with more space between laser burns or cryospots for the clock hours position of the retina in the horizontal meridians to decrease the risk of ablating the long ciliary arteries. This report should not discourage physicians from being aggressive with the treatment of ROP but instead should prompt investigation to further advance our methods of treatment and our understanding of its complications.

AUTHOR INFORMATION
The authors have no conflicting commercial interests.

Presented at the Association for Research in Vision and Ophthalmology annual meeting, Fort Lauderdale, Fla, May 2000.

Reprints not available from the authors.

Richard S. Kaiser, MD; Michael T. Trese, MD
Royal Oak, Mich

REFERENCES
1. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Snellen visual acuity and structural outcome at 5 years after randomization. Arch Ophthalmol. 1996;114:417-424. FREE FULL TEXT 2. The Laser ROP Study Group. Laser therapy for retinopathy of prematurity. Arch Ophthalmol. 1994;112:154-156. 3. Preslan MW. Laser therapy for retinopathy of prematurity. J Pediatr Ophthalmol Strabismus. 1993;30:80-83. ISI | PUBMED 4. McNamara JA, Tasman W, Brown GC, Federman JL. Laser photocoagulation for stage 3+ retinopathy of prematurity. Ophthalmology. 1991;98:576-580. ISI | PUBMED 5. Ling CS, Fleck BW, Wright E, et al. Diode laser treatment for retinopathy of prematurity: structural and functional outcome. Br J Ophthalmol. 1995;79:637-641. FREE FULL TEXT 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;107:324-328. FULL TEXT | ISI | PUBMED 7. Greven CM, Tasman W. Rhegmatogenous retinal detachment following cryotherapy in retinopathy of prematurity. Arch Ophthalmol. 1989;107:1017-1018. FREE FULL TEXT 8. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity: three-month outcome. Arch Ophthalmol. 1990;108:195-209. FREE FULL TEXT 9. Christiansen SP, Bradford JD. Cataract in infants treated with argon laser photocoagulation for threshold retinopathy of prematurity. Am J Ophthalmol. 1995;119:175-180. ISI | PUBMED 10. Hunt L. Complications of indirect laser photocoagulation. Insight. 1994;19(4):24-25. 11. Simons BD, Wilson MC, Hertle RW, Schaefer DB. Bilateral hyphemas and cataracts after diode laser retinal photoablation for retinopathy of prematurity. J Pediatr Ophthalmol Strabismus. 1998;35:185-187. ISI | PUBMED 12. Abrams GW, Azen SP, Barr CC, et al. The incidence of corneal abnormalities in the Silicone Study: Silicone Study report 7. Arch Ophthalmol. 1995;113:764-769. FREE FULL TEXT 13. Scott IU, Flynn HW, Azen SP, et al. Silicone oil in the repair of pediatric complex retinal detachments. Ophthalmology. 1999;106:1399-1408. FULL TEXT | ISI | PUBMED

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