ATYPICAL FORM OF RETINOPATHY OF PREMATURITY WITH SEVERE FIBROVASCULAR PROLIFERATION IN THE OPTIC DISK REGION.

PURPOSE: To describe severe fibrovascular proliferation that developed in the optic disk region in an atypical form of retinopathy of prematurity (ROP). METHODS: Retrospective observational case reports. RESULTS: Four patients (8 eyes) with ROP were included. Three patients were born very prematurely (24-25 weeks of gestational age; weight, 500-1,000 grams); 1 patient was born at 33 weeks of gestational age. Among all eight eyes of four patients who received prompt ROP screening and underwent laser photocoagulation, six eyes had atypical and severe fibrovascular proliferation mainly in the optic disk region; the other two eyes, including one eye with classic ROP and one eye with aggressive posterior ROP, did not have the atypical form. All eight eyes had a total to partial retinal detachment. Among the six eyes with the atypical form, early vitreous surgery with lensectomy was possible in three eyes; only late vitreous surgery with lensectomy was possible in two eyes; one eye was inoperable. Three eyes had a partial or complete reattachment, whereas three eyes had a total retinal detachment. Among the six eyes with atypical fibrovascular proliferation, only two eyes obtained light perception vision. CONCLUSION: An atypical and severe form of ROP, in which fibrovascular proliferation grew mainly from the optic disk region, needs further investigation for treatment in addition to laser photocoagulation and vitreous surgery.

Genetic screening of Wnt signaling factors in advanced retinopathy of prematurity.

PURPOSE: To evaluate the possibility of genetic involvement in retinopathy of prematurity (ROP). Although ROP is most often associated with low birthweight and low gestational age, these factors do not necessarily predict the severity of ROP. The possible involvement of other factors, including genetic variants, has been considered. Familial exudative vitreoretinopathy (FEVR) is a hereditary vitreoretinal disorder with clinical manifestations similar to those of ROP. Three genes involving the wingless/int1 (Wnt) receptor signaling pathway-FZD4 for frizzled 4, LRP5 for low-density lipoprotein receptor-related protein 5, and ND for Norrie disease protein-are associated with the development of FEVR. METHODS: In the present study, 17 Japanese patients with advanced ROP were screened for these three candidate genes of FEVR. Genomic DNA from each patient was subjected to PCR and direct sequencing of the ND, FZD4, and LRP5 genes. RESULTS: One patient had a heterozygous mutation in the 5' untranslated region of the ND gene. Another had a leucine insertion in the signal peptide of LRP5. None showed any mutation in FZD4. CONCLUSIONS: These findings suggest that genetic changes in the Wnt receptor signaling pathway associate to the development of advanced ROP.

[Optimum timing of initial examination for retinopathy of prematurity].

OBJECTIVE: To determine when to begin examination for retinopathy of prematurity (ROP). METHODS: We retrospectively reviewed the medical records of 663 infants with birth weights of less than 1,500 g in Tokyo Metropolitan Bokutoh Hospital between June 1999 and March 2009, and investigated the timing of onset and initial treatment. In addition, we investigated visibility of fundus for infants of less than 27 weeks gestational age (GA). RESULTS: The mean GA was 28.7 weeks and the mean birth weight was 1,032.6 g. For infants of less than 27 weeks GA, the earliest onset was 29 weeks postmenstrual age (PMA) and the earliest initial treatment was performed at 30 weeks 0 days PMA. Regarding the visibility of the fundus, zone I could be seen for 50.8% of those infants receiving examination during the latter half of 29 weeks PMA and 71.7% of those infants receiving examination during the former half of 30 weeks. For the infants of a GA of 27 weeks or more, the earliest onset was 2 weeks chronologic age (CA) and the earliest initial treatment was performed at 3 weeks 3 days CA. CONCLUSIONS: The optimum timing of initial examination for ROP proved to be between the latter half of 29 weeks and 30 weeks 0 days PMA for infants of a GA of less than 27 weeks; and 3 weeks CA for the infants of a GA of 27 weeks or more.

Effect of early vitreous surgery for aggressive posterior retinopathy of prematurity detected by fundus fluorescein angiography.

OBJECTIVE: To assess the effect of early vitrectomy for aggressive posterior retinopathy of prematurity (APROP) using fundus fluorescein angiography. DESIGN: Retrospective, observational case series. PARTICIPANTS: Eleven eyes of 7 patients with APROP that underwent early vitreous surgery. METHODS: All eyes underwent vitrectomy with lensectomy that removed the vitreous gel around the fibrovascular proliferative tissue, but not the proliferative tissue when fibrovascular proliferation and retinal detachment occurred despite retinal photocoagulation. Fundus fluorescein angiography was performed before and after the early vitreous surgery. MAIN OUTCOME MEASURES: Dye leakage from the fibrovascular tissue, dilation and tortuosity of the retinal vasculature, and shunt vessels were evaluated by fundus fluorescein angiography. The status of the retinal reattachment was assessed postoperatively. RESULTS: Nine eyes had severe dye leakage from the fibrovascular tissue and 2 eyes had moderate leakage seen by preoperative fluorescein angiography. Severe dilation and tortuosity of the retinal vessels were detected in 10 eyes and shunt vessels in 7 eyes. Six to 12 days after successful surgery, the retina reattached and dilation and tortuosity of the retinal vessels decreased substantially. Dye leakage diminished markedly in all eyes, resolved completely in 7 eyes, and was still apparent slightly in 4. At the final examination, fibrovascular proliferation and retinal detachment did not progress in any eyes; however, 2 eyes had a dragged or folded retina. Follow-up ranged from 6 to 19 months (mean, 9.2). CONCLUSIONS: Early vitrectomy that removes vitreous gel from around the proliferative tissue promptly reduces vascular activity and may limit progression of retinal detachment in APROP.

Congenital rotated macula with good vision and binocular function.

BACKGROUND: Two patients presented with congenital rotated macula with good vision and binocular function. CASES: Two patients had retinal folds with an extremely rotated macula OD as the result of peripheral fibrous proliferation on the retina. Each macula was substantially rotated to the nasal border of the disc. OBSERVATIONS: A 3-year-old girl (case 1) with best-corrected visual acuity (VA) of 0.5 OD and 1.0 OS was treated for amblyopia, after which she successfully achieved 1.0 bilaterally as well as good stereopsis of 120 seconds of arc measured with the TNO test. A 6-year-old girl (case 2) obtained a VA of 0.7 OD and 1.0 OS, and her stereopsis was of 240 seconds of arc. CONCLUSIONS: Good VA and stereopsis may be achieved by adaptation in the brain and an extremely large fusional potential at an early infantile age or a gradual shift of the macula. Appropriate treatment of amblyopia should be performed in patients with rotated macula if the macula appears normal.

Evaluation of scleral buckling for stage 4A retinopathy of prematurity by fluorescein angiography.

PURPOSE: To determine the early efficacy of scleral buckling for active neovascularization by fundus fluorescein angiography (FA) in eyes with stage 4A retinopathy of prematurity. DESIGN: A retrospective, nonrandomized, observational case series. METHODS: Patients who underwent scleral buckling for stage 4A ROP at the National Center for Child Health and Development, Tokyo, Japan, from October 2007 through November 2008 were included. Preoperative and postoperative FA and fundus photographs obtained with a wide-field digital pediatric imaging system were reviewed. Three patients (5 eyes; gestational ages at birth, 23 to 25 weeks; birth weights, 574 to 811 g) with zone II stage 4A ROP who underwent postoperative FA, 2 weeks or less after scleral buckling (range, 7 to 12 days; postmenstrual ages at postoperative FA, 41 to 45 weeks) were evaluated. Patients who underwent postoperative FA 2 weeks or more after scleral buckling were excluded. RESULTS: Despite fluorescein leakage from fibrovascular tissue in all eyes before surgery, markedly decreased leakage occurred only between 7 to 12 days after surgery. The retinas were reattached completely in all eyes after surgery. CONCLUSIONS: Scleral buckling may prevent progression of retinal detachment in stage 4A ROP by reducing the tractional force and stabilizing the neovascular activity of the fibrovascular tissue.

Vascular abnormalities in aggressive posterior retinopathy of prematurity detected by fluorescein angiography.

PURPOSE: To evaluate fluorescein angiography (FA) in eyes with aggressive posterior retinopathy of prematurity (AP-ROP). DESIGN: Retrospective, nonrandomized case series. PARTICIPANTS: Three patients (6 eyes) with AP-ROP. METHODS: Three patients (6 eyes) diagnosed with AP-ROP during ROP screening between July 2007 and July 2008 were included in this study. Fundus photographs and FA were obtained before and after laser and surgical treatment using a wide-field digital pediatric imaging system. MAIN OUTCOME MEASURES: Fluorescein angiography and fundus photographs. RESULTS: At the initial stage of AP-ROP, FA showed vascular abnormalities, including capillary nonperfusion throughout the vascularized retina, shunting in the vascularized retina, a circumferential demarcation line, and limited vessel development, which was difficult to identify only by ophthalmoscopy. After treatment, FA showed poorly developed retinal vessels, including 4 small major vessels without an arcade pattern, small macular vessels, an inhomogeneous capillary bed, and absence of a capillary-free zone in the fovea. CONCLUSIONS: Capillary bed loss throughout the vascularized posterior retina is characteristic of AP-ROP and may exacerbate retinopathy.

Early vitreous surgery for aggressive posterior retinopathy of prematurity.

PURPOSE: To assess the efficacy of early vitrectomy for aggressive posterior retinopathy of prematurity (ROP) to stop progression of retinal detachment. DESIGN: Retrospective, noncomparative, consecutive case series. METHODS: Twenty-two eyes (15 patients) with aggressive posterior ROP underwent vitrectomy with or without lens sparing, because retinal photocoagulation failed to stop progression of fibrovascular proliferation, despite being performed early, densely, and with early retreatment. We assessed the status of retinal attachment and foveal formation ophthalmoscopically and the presence or absence of fixation of visual behavior. RESULTS: Follow-up ranged from six to 12 months (mean, 9 months). Six eyes (100%) in which a lens-sparing vitrectomy was performed developed a large tractional retinal detachment. In contrast, the retinas were completely reattached in 16 eyes (100%) in which vitrectomy with lensectomy was performed, nine eyes (56%) had foveal configuration, and 14 eyes (88%) had steady fixation. CONCLUSIONS: These results suggest that early vitrectomy is effective for preventing retinal detachment in aggressive posterior ROP.

[Retinopathy of prematurity in extremely low birth weight infants: a Tokyo multicenter study].

OBJECTIVE: To investigate how the increase in survival rate in extremely low birth weight (a birth weight of 1,000 g or less) infants had affected the incidence of retinopathy of prematurity (ROP) and the frequency of laser treatment. METHODS: We retrospectively reviewed the medical records of 122 surviving premature infants with birthweights less than 1,000 g to determine the severity of ROP observed at 16 neonatal intensive care units in Tokyo between April and October 2002. RESULTS: The survival rate was 85.6%. The mean gestational age was 26.74 weeks and the mean birth weight was 782.25 g. One-hundred-and-five infants (86.1%) developed ROP, fifty (41.0%) received laser treatment, and six (4.9%) had retinal detachment. The median postmenstrual age (gestational age at birth plus chronological age in weeks, PMA) at the onset of ROP was 32.5 weeks, and the first laser treatment was performed at the median PMA of 35.7 weeks. CONCLUSIONS: In these extremely low birth weight infants, there was an increase in the survival rate and in the incidence of severe ROP that progressed to the stage that required treatment.