Prevalence and course of strabismus in the first year of life for infants with prethreshold retinopathy of prematurity: findings from the Early Treatment for Retinopathy of Prematurity study.

OBJECTIVE: To present strabismus data for premature infants with prethreshold retinopathy of prematurity (ROP) enrolled in the Early Treatment for Retinopathy of Prematurity study. DESIGN: The prevalence of strabismus was tabulated for all of the infants with high-risk prethreshold disease who participated in the randomized trial of the Early Treatment for Retinopathy of Prematurity study and were examined at 6 and/or 9 months' corrected age as well as for all of the infants with low-risk prethreshold disease who were examined at 6 months' corrected age. MAIN OUTCOME MEASURES: Presence or absence of strabismus at 6 and 9 months' corrected age. RESULTS: The prevalence of strabismus at 6 months was higher for infants with high-risk prethreshold ROP than for those with low-risk prethreshold ROP (20.3% vs 9.6%, respectively; P<.001). Risk factors associated with the development of strabismus at 9 months include abnormal fixation behavior, presence of amblyopia, and outborn birth status (ie, born outside of a study-affiliated hospital). At 9 months, 30% of infants with high-risk prethreshold ROP had strabismus, although only 42% showed strabismus at 6 months. Thirty percent of infants with strabismus at 6 months showed normal alignment at 9 months. CONCLUSIONS: Infants with high-risk prethreshold ROP show significant variability in the presence vs absence of strabismus in the first year of life; thus, conservative management is recommended. APPLICATION TO CLINICAL PRACTICE: Ophthalmologists managing strabismus in infants who have high-risk prethreshold ROP should be aware of the significant variability in ocular alignment during the first year of life.

Gelatin-based biomimetic tissue adhesive. Potential for retinal reattachment.

An adhesive that cures under moist/wet conditions could facilitate surgical procedures for retinal reattachment. We are investigating an adhesive that mimics the factor XIIIa-mediated crosslinking of fibrin that occurs in the late stages of the blood coagulation cascade. Specifically, we use gelatin as the structural protein (in place of fibrin), and crosslink gelatin using a calcium-independent microbial transglutaminase (in place of the calcium-dependent transglutaminase factor XIIIa). Injection of gelatin and microbial transglutaminase (mTG) into the vitreous cavity of Sprague Dawley white rats did not elicit structural or cellular damage to the retina as evidenced from histological evaluation 2 weeks post-injection. Qualitative in vitro studies indicate that the gelatin-mTG adhesive binds to bovine retinal tissue under wet conditions. Quantitative lap-shear tests were performed with more robust bovine tissue from the choroid and sclera. The lap-shear strength of the biomimetic gelatin-mTG adhesive was independent of tissue-type and ranged from 15 to 45 kPa, which is comparable to the values reported for other soft-tissue adhesives. These studies suggest that the mTG-crosslinked gelatin may provide a simple, safe, and effective adhesive for ophthalmic applications.

Retinopathy in monkeys with spontaneous type 2 diabetes.

PURPOSE: Type 2 diabetes occurs spontaneously in rhesus monkeys and shows an extraordinary similarity to human diabetes in clinical features and relative time course. The purpose of this study was to investigate clinically and histopathologically the ocular changes in these monkeys. METHODS: Ophthalmoscopic examinations were performed on aged normal and diabetic monkeys. Retinas from 16 diabetic monkeys and 6 nondiabetic monkeys were incubated postmortem for adenosine diphosphatase (ADPase) activity (labels viable retinal blood vessels) and flat-embedded in JB-4. Tissue sections were cut through areas of interest. RESULTS: Cotton-wool spots, intraretinal hemorrhages, and hard exudates in the macula were observed by ophthalmoscopy in some diabetic monkeys. Dot/blot hemorrhages, cotton-wool spots, and small nonperfused areas were the earliest histologically documented changes in the retinas. Large nonperfused areas extending from optic disc to midfovea were observed in four diabetic monkeys. Formation of small intraretinal microvascular abnormalities (IRMAs) and microaneurysms were associated with the areas of nonperfusion. There were apparent fluid-filled spaces in the outer plexiform layer in three of these maculas, suggesting macular edema. There was a significant correlation between the occurrence of retinopathy and hypertension (P = 0.037 for systolic pressure; P = 0.019 for diastolic pressure). In elastase-digested retinas, the ratio of pericytes to endothelial cells was 0.66:1 in diabetic and 0.64:1 in nondiabetic (P = 0.75) retinas. CONCLUSIONS: This is the first detailed analysis of retinopathy in a colony of spontaneous type 2 diabetic monkeys. Monkeys with type 2 diabetes have many of the angiopathic changes associated with human diabetic retinopathy. Hypertension correlates with the severity of the diabetic retinopathy.

Vitreous hemorrhage in patients with high-risk retinopathy of prematurity.

PURPOSE: To investigate outcomes in premature infants with high-risk retinopathy of prematurity and secondary vitreous hemorrhage. DESIGN: Retrospective chart review. METHODS: Patients were selected from a database of infants undergoing retinopathy of prematurity screening from September 1997 to November 1999. Infants with high-risk retinopathy of prematurity (zone I or posterior zone II threshold disease) with and without vitreous hemorrhage were compared. MAIN OUTCOME MEASURES: Final stage of retinopathy of prematurity and short-term structural outcome were assessed. Visual acuity and refraction were measured when possible. RESULTS: Twenty-two eyes of 11 patients (group 1) had high-risk (posterior zone II or zone I threshold) retinopathy of prematurity without vitreous hemorrhage. Group 1 patients had a 91% favorable short-term structural outcome. Eight eyes of five infants developed vitreous hemorrhage with high-risk retinopathy of prematurity (group 2). Group 2 patients had only a 12.5% favorable short-term structural outcome. Seven of eight (87.5%) progressed to stage IVa or IVb retinopathy of prematurity. Six eyes underwent vitreoretinal surgery after a median duration of hemorrhage of 36 +/- 29 days (4-70 days). Three eyes developed stage V detachments and three progressed to phthisical degeneration. Final visual acuity was no light perception in three eyes. CONCLUSION: Vitreous hemorrhage, in association with advanced retinopathy of prematurity, is a poor prognostic sign.

2,4-Dinitrophenol pharmacologically promotes retinal detachment in rabbits.

PURPOSE: The most difficult and unpredictable step of macular translocation surgery is creating the retinal detachment. The authors evaluated the efficacy of 2,4-dinitrophenol (2,4-DNP) to promote retinal detachment in the rabbit. METHODS: A vitrectomy was performed in each eye of a Dutch-belted rabbit. One eye was injected with 0.1 cc of a 5 mmol/L 2,4-DNP, the other eye with 0.1 cc of BSS+. After 30 minutes, the minimum aspiration pressure required to visibly elevate the retina was recorded. Four nonvitrectomized eyes received an intravitreal injection of either 0.1 cc of BSS+ or 5 mmol/L 2,4-DNP, and were enucleated and fixated for histopathologic examination. RESULTS: In the 12 masked eyes, the mean aspiration pressure decreased from 217 +/- 20 mmHg in the six BSS+ eyes to 117 +/- 20 mmHg in the six 2,4-DNP treated eyes (P = 0.0022). A retinal detachment was present in three of six masked and two of two unmasked 2,4-DNP treated eyes and none of eight BSS+ treated eyes. There was no short-term toxicity to the retina at the light microscope level. CONCLUSION: Intravitreal injection of 2,4-DNP reduced the retinal adhesive force by over 50% when compared to the BSS+ treated control eyes, without any short-term retinal toxicity.

Subretinal organization in stage 5 retinopathy of prematurity.

BACKGROUND: The subretinal organization (SRO) seen in patients who undergo vitrectomy for stage 5 retinopathy of prematurity has not previously been characterized. We report our observations of SRO and correlate its development with previous laser and cryotreatment for neovascular disease. METHODS: We surveyed data from 426 eyes in a retrospective chart review of 263 patients that underwent open-sky vitrectomy for stage 5 retinopathy of prematurity. RESULTS: Of 426 eyes evaluated, 130 eyes received laser, cryo, or a combination of both treatments. In 44 eyes (10.3%), SRO was observed and considered the cause of incomplete retinal attachment. Three forms of SRO were identified: subretinal bands (63.6%), subretinal plaques (15.9%), and diffuse SRO (18.2%). One patient had both a band and a plaque. SRO developed in 24 eyes after cryotreatment, 3 after laser, and 2 after combination cryo and laser treatment. Fewer untreated eyes than cryotreatment eyes developed SRO (15 of 296 eyes, 5.1%; ( P=0.0001). Eyes without laser or cryotreatment had a 5.1% frequency of developing SRO. CONCLUSION: Subretinal organization, a previously uncharacterized entity in retinopathy of prematurity, was most frequently identified in the form of subretinal band formation. SRO was identified in 10.3% of all stage 5 eyes evaluated, and was associated with incomplete retinal reattachment in all cases.