Cryotherapy has been shown to be an effective treatment for retinopathy of prematurity (ROP) stage 3+. However, the outcome of cryotherapy is less favorable in zone 1 ROP than in zone 2 ROP. We suspected whether there may be differences in the outcomes of cryotherapy if the zone of ROP is further divided. So we reviewed the records of 85 premature infants (145 eyes) who had undergone cryotherapy for ROP. The frequencies of favorable outcome were 42.9% of 14 eyes (zone 1), 78.9% of 38 eyes (posterior zone 2), 92.9% of 70 eyes (mid zone 2), and 100.0% of 23 eyes (anterior zone 2), respectively (p < 0.001). These results suggest that the more posteriorly the ROP is located, the less favorable the outcome of cryotherapy.
Cryotherapy/*methods ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Postoperative Complications ; Retinopathy of Prematurity/pathology/*therapy ; Retrospective Studies ; Treatment Outcome

PURPOSE: To report the clinical features, clinical course, and treatment outcomes after laser photocoagulation in infants with aggressive posterior retinopathy of prematurity (APROP) and capillary-free zones in vascularized retina. METHODS: Six patients (12 eyes) with APROP and capillary-free zones in vascularized retina were retrospectively reviewed. Twelve eyes of six infants were included and were treated with laser photocoagulation for avascular retina and for capillary-free zones in vascularized retina, except for the posterior pole, and fundus findings were photographically-documented in sequence. In addition, anatomic and visual outcomes were evaluated with complications of APROP. RESULTS: Among all of the consecutive infants with APROP, capillary-free zones in vascularized retina were demonstrated in 24% of the infants. All of the infants were >27 weeks of gestation age and had birth weights >1,000 g. After laser treatment, 7 eyes (58.3%) had favorable outcomes, and late capillary filling in capillary-free zones of vascularized retina were noted, however 4 eyes (33.3%) progressed to retinal detachment and 1 eye (8.3%) was complicated by a retinal fold-distorting posterior pole. The visual outcomes were associated with anatomic outcomes. CONCLUSIONS: The anatomic outcomes in infants with APROP who had capillary-free zones were comparable to previously reported infants with APROP. The late capillary filling of capillary-free zones in vascularized retina was noted, and angiogenesis was considered to be involved. This process toward normal capillary formation or neovascularization in APROP, might determine its outcome.
Capillaries/*pathology ; Female ; Humans ; Infant ; Laser Coagulation/*methods ; Male ; Retina/*pathology/surgery ; Retinal Vessels/*pathology/surgery ; Retinopathy of Prematurity/*pathology/*surgery ; Retrospective Studies ; Treatment Outcome

PURPOSE: To report the clinical features, clinical course, and treatment outcomes after laser photocoagulation in infants with aggressive posterior retinopathy of prematurity (APROP) and capillary-free zones in vascularized retina. METHODS: Six patients (12 eyes) with APROP and capillary-free zones in vascularized retina were retrospectively reviewed. Twelve eyes of six infants were included and were treated with laser photocoagulation for avascular retina and for capillary-free zones in vascularized retina, except for the posterior pole, and fundus findings were photographically-documented in sequence. In addition, anatomic and visual outcomes were evaluated with complications of APROP. RESULTS: Among all of the consecutive infants with APROP, capillary-free zones in vascularized retina were demonstrated in 24% of the infants. All of the infants were >27 weeks of gestation age and had birth weights >1,000 g. After laser treatment, 7 eyes (58.3%) had favorable outcomes, and late capillary filling in capillary-free zones of vascularized retina were noted, however 4 eyes (33.3%) progressed to retinal detachment and 1 eye (8.3%) was complicated by a retinal fold-distorting posterior pole. The visual outcomes were associated with anatomic outcomes. CONCLUSIONS: The anatomic outcomes in infants with APROP who had capillary-free zones were comparable to previously reported infants with APROP. The late capillary filling of capillary-free zones in vascularized retina was noted, and angiogenesis was considered to be involved. This process toward normal capillary formation or neovascularization in APROP, might determine its outcome.
Capillaries/*pathology ; Female ; Humans ; Infant ; Laser Coagulation/*methods ; Male ; Retina/*pathology/surgery ; Retinal Vessels/*pathology/surgery ; Retinopathy of Prematurity/*pathology/*surgery ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo investigate the role of oxidative stress in the pathogenesis of retinal injury induced by hyperoxia.

METHODSSixty immature Sprague-Dawley (SD) rats born at a gestational age of 21 days, were randomly exposed to room air (air group, n=30) or 95% oxygen (hyperoxia group, n=30) immediately after birth. Plasma 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) levels were determined by ELISA. The ultrastructures of the retina were observed under a transmission electron microscope.

RESULTSThe plasma 8-iso-PGF2alpha contents of the air group were 19.09 +/-5.57, 18.24+/-5.91 and 17.00 +/- 5.58 pg/mL on the 3rd, 7th and 14th days after birth, respectively (F=1.024, P> 0.05). The plasma 8-iso-PGF2 contents in the hyperoxia group on the 3rd (28.33 +/- 5.59 pg/mL), the 7th day (51.20 +/- 15.01 pg/mL) and 14th day (84.54 +/- 14.85 pg/mL) after birth were significantly higher than those of the air group (t=2.863, P< 0.05; t=5.073, P< 0.01; t=11.006, P< 0.01). Moreover, the plasma 8-iso-PGF2 contents in the hyperoxia group increased with the prolonged hyperoxia exposure (F=150.7, P < 0.01). The ultrastructures of retina in the air group were normal. Hyperoxia exposure resulted in abnormalities of the ultrastructures of retina, manifesting as the membrane discs rarefied, twisted and disrupted and mitochondrial swelling.

CONCLUSIONSOxidative stress can results in retinal injury in immature rats. An increased plasma level of 8-iso-PGF2alpha is related to the injury degree of retina.

Animals ; Dinoprost ; analogs & derivatives ; blood ; Humans ; Hyperoxia ; complications ; metabolism ; pathology ; Infant, Newborn ; Lipid Peroxidation ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Retina ; metabolism ; pathology ; ultrastructure ; Retinopathy of Prematurity ; etiology

A 6-year-old boy was referred to our hospital with symblepharon and lateral canthal deformity in both eyes, which developed 6 years ago. The patient was born at 27 weeks gestation. He had received cryotherapy for retinopathy of prematurity. One month after cryotherapy, he developed a conjunctival scar with symblepharon in both eyes and underwent symblepharon lysis at another hospital 5 years prior. Ocular examination revealed an extensive conjunctival hypertrophic scar with symblepharon and limitation of extraocular movements. An excisional biopsy, lateral canthoplasty, and symblepharon lysis with conjunctival autograft from the contralateral eye were performed in the left eye. Histopathologic examination revealed diffuse proliferation and infiltration of collagenous tissue.
Biopsy ; Child ; Cicatrix, Hypertrophic/diagnosis/*etiology ; Conjunctiva/pathology ; Conjunctival Diseases/diagnosis/*etiology ; Cryotherapy/*adverse effects ; Diagnosis, Differential ; Follow-Up Studies ; Humans ; Male ; Retinopathy of Prematurity/*therapy

To find out whether the cryotherapy for the treatment of the retinopathy of prematurity (ROP) causes structural changes of the extraocular muscle (EOM), and also whether the changes are related with the occurrence of strabismus. To examine the acute stage change, we conducted a transconjunctival cryotherapy around the superior rectus muscle of a rabbit and resected it 0, 3, 7, 14, and 28 days after the cryotherapy. In observing chronic changes, we first categorized patients who had an esotropia surgery into groups, one of which combined prematurity and cryotherapy and one group affected by prematurity but without having had cryotherapy. Then we compared the change of EOM with that of a fullterm infant group. In a rabbit, edema, acute inflammatory cells and a large amount of degenerated muscle fibers were observed immediately after the cryotherapy and on the 3rd day. On the 7th day, regenerated muscle fibers were observed and on the 14th day, the inflammatory cells decreased and the amount of regenerated muscle fiber increased. On the 28th day, abnormal findings were not observed any more and the muscle was found to be normal. When chronic changes of EOM in human on 1 1/2 to 8 1/2 years after cryotherapy, there were no abnormal findings observed in three groups. From the study, we can infer that cryotherapy can cause acute inflammation and necrosis of muscle fiber but such an acute change will improve and does not result in structural change in the long term. Therefore, the occurrence of strabismus in patients with ROP is considered to be attributable to reasons other than injury of EOM.
Animal ; Child ; Child, Preschool ; Cryotherapy/*adverse effects ; Human ; Infant ; Infant, Newborn ; Oculomotor Muscles/*surgery ; Rabbits ; Retinopathy of Prematurity/*pathology/*surgery ; Strabismus/*etiology

Electron microscopic examination of proliferative membranes in retinopathy of prematurity (ROP) was performed in order to evaluate the components of the membranes. The proliferative membranes were obtained from nine patients with ROP stage 5 during pars plicata lensectomy, vitrectomy, and delamination of membrane. Fibrous astrocytes, myofibroblasts, lymphocytes, macrophages, and calcification were found respectively in two cases, and fibroblast-like cells were found in one case. Varying amounts of collagen tissues were found in eight cases and vascular tissues in four cases. Most of membranes were hypocellular and composed mainly of collagen matrix. It is considered that fibrous astrocytes, myofibroblasts, fibroblasts, and vascular structures are involved in the formation of proliferative membranes of ROP, and that later these cells degenerate and disappear, and that finally only collagen matrix remains in the membranes.
Cataract Extraction ; Child, Preschool ; Gestational Age ; Humans ; Infant ; Infant, Low Birth Weight ; Infant, Newborn ; Microscopy, Electron ; Retina/*ultrastructure ; Retinopathy of Prematurity/*pathology

OBJECTIVETo evaluate the role of different oxygen concentration (FiO2) and different period of oxygen exposure on oxygen-induced retinopathy (OIR) in neonatal mice and to provide evidences for proper clinical oxygen therapy.

METHODSTwo hundred and four 7-day-old (P7) C57BL/6J mice were exposed to different FiO2 30%, 50% and 75% for 5, 7 and 9 days. The mice were divided into eight groups: groups 1 - 3 (n = 24 in each) were exposed to 30% oxygen for 5, 7 and 9 days, respectively; groups 4 - 6 (n = 24 in each) were exposed to 50% oxygen for 5, 7 and 9 days, respectively; group 7 (n = 30) was exposed to 75% hyperoxia for 5 days; group 8 (n = 30) was exposed to room air. Proliferative neovascular responses were estimated by observing vascular patterns in adenosine diphosphate-ase (ADPase) stained retina flat-mounts and quantitated by counting the number of new vascular cell nuclei extending into the internal limiting membrane in cross-sections.

RESULTS(1) Vascular patterns in retina flat-mounts: a) When FiO2 was 30%, the entire vascular pattern was completely normal after 5 and 7 days exposure; although the deep vascular system seemed slightly constricted after 9 days exposure, it recovered 2 days later and matured at P21. b) When FiO2 was 50%, after 5 days exposure (group 4), the larger vessels constricted and central perfusion decreased moderately; after exposing to room air for 2 days, neovascularization was seen; however, the entire vascular pattern was almost normal at P17. After 7 days of exposure to 50% O2 (group 5), the vascular pattern recovered a bit, seemed to be better than that of group 4; after 9 days of exposure to 50% O2 (group 6), only slight constriction could be seen and it disappeared 2 days later and all vessels matured later. c) When FiO2 was 75%, after 5 days exposure to hyperoxia, the larger vessels became tortuous and constricted, central perfusion became decreased obviously; after exposing to room air for 2 days, neovascularization was seen; and this response was maximal at P17 - P21. However, the mortality of nurser mice and pups increased dramatically when the duration of hyperoxia was prolonged. (2) Quantitative results in cross-sections: neovascular nuclei extending into the vitreous reached (41.9 +/- 2.8) per section in 75% oxygen group, while less than 1 in every other groups, which was statistically different (P < 0.0001).

CONCLUSIONSFiO2 and the duration of hyperoxia could affect retinal vascular development. Low and moderate FiO2 could induce reversible vessel changes, while high FiO2 induced irreversible changes which should be avoided in clinic.

Animals ; Disease Models, Animal ; Humans ; Hyperoxia ; pathology ; Infant, Newborn ; Mice ; Mice, Inbred C57BL ; Oxygen ; adverse effects ; Oxygen Inhalation Therapy ; adverse effects ; Retinal Neovascularization ; pathology ; Retinal Vessels ; pathology ; Retinopathy of Prematurity ; pathology

OBJECTIVEFluctuations in arterial oxygen are associated with development of severe retinopathy of prematurity (ROP) in humans. However, the causal relationship between oxygen variability and ROP remains unknown. The authors developed a rat model of retinal neovascularization by repeated fluctuations of inhaled oxygen between hypoxia and hyperoxia to investigate the mechanism of the development of retinal neovascularization, the regulation of vascular endothelial growth factor (VEGF) and KDR/Flk-1 (VEGFR-2) expression.

METHODSTwo hundred and eight newborn Sprague Dawley rats were randomly divided into oxygen and air groups. The oxygen concentration in the oxygen group was alternated between 50% and 10% every 24 hours for 14 days. The control group were kept in room air environment. VEGF and Flk-1 expression was observed at 14, 18 and 25 days after birth in both exposed group and control group by immunohistochemical staining and semiquantitative RT-PCR. The status of retinal vasculature on day 4 after oxygen exposure was also observed. The retinas were dissected and stained by using a histochemical method for detecting adenosine diphosphatase (ADPase) activity, digital images of the retinas were captured and the peripheral avascular retina were measured. HE staining on methacrylate sections of eyes was used for counting the number of nuclei extending from retinal area into vitreous to identify extraretinal neovascularization. Numeric data were expressed as the mean +/- standard deviation (SD). Statistical calculations were performed using the SAS 8.1 statistical package. Differences in measured variables between experimental and control groups were determined using comparison of the means using two-way analysis of variance (ANOVA) statistical calculations and T-test. AP value less than 0.05 was regarded as significant.

RESULTS(1) The animal model was successfully established: the avascular areas of retina of 18-day-old rats were larger than those of the control group and the numbers of nuclei extending from retinal area into vitreous in exposed group were significantly higher compared to the control (P < 0.05). (2) The expression of VEGF and Flk-1 on the 14(th) day in the oxygen group was significantly stronger than that of the control group (P < 0.05). In the oxygen group, VEGF and Flk-1 expression was the strongest in the retina on the 18(th) day, the result had significant difference as compared with the 14(th) and 25(th) day (P < 0.05), and they were also stronger than that of the control group (P < 0.05). The expression of VEGF and Flk-1 decreased on the 25(th) day and had no significant difference as compared with the control group (P > 0.05). (3) Both VEGF-mRNA and Flk-1-mRNA significantly increased on the 14(th) day and the 18th day (P < 0.05). On the 25(th) day, the amounts of VEGF-mRNA and Flk-1-mRNA were similar between the control and oxygen group (P > 0.05).

CONCLUSIONFluctuation in oxygen is associated with the development of retinal neovascularization in the retinopathy. Increased expressions of VEGF and Flk-1 in the oxgen fluctuations-induced neovascularized retina suggested that VEGF and Flk-1 might play a critical role in the pathogenesis of ROP. The results also indicated the positive feedback in the pathogenesis of ROP that the synergistic interaction of VEGF and Flk-1 in the retinal vascular proliferation. These findings provide insight into the effect of repeated oxygen fluctuation on the development of severe ROP in preterm infants.

Animals ; Disease Models, Animal ; Humans ; Hyperoxia ; pathology ; Hypoxia ; pathology ; Infant, Newborn ; Oxygen ; adverse effects ; Rats ; Rats, Sprague-Dawley ; Retinal Neovascularization ; pathology ; Retinopathy of Prematurity ; pathology ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

PURPOSE: To describe the results of lens-sparing vitrectomy for the correction of retinal detachment associated with retinopathy of prematurity (ROP) and its associated complications. METHODS: Seventeen patients who underwent a lens-sparing vitrectomy for stage 4 and stage 5 ROP with plus disease at Seoul National University Children's Hospital between 1999 and 2003 were enrolled in this study. The patients who had bilateral retinal detachment of ROP underwent a lens-sparing vitrectomy in one eye and a scleral buckling surgery or lensectomy-vitrectomy in the other eye. The patients who had a retinal detachment in one eye and a regressed ROP in the other eye underwent unilateral lens-sparing vitrectomies. A review of their preoperative clinical findings (including the status of retinal detachment and plus disease), post-operative results, and any complications encountered was performed. RESULTS: In 17 patients, the postoperative success rate of lens-sparing vitrectomy was 58.8%. However, lens-sparing vitrectomy as a treatment for stage 5 ROP (25.0%) produced more negative post-operative results than it did when used to treat either those for stage 4a (75,0%) or 4b (66.7%) ROP. Among the 10 eyes in which the retina was attached, form vision was shown in six eyes, light could be followed by three eyes, and no light perception was present in one eye. Intra- and post-operative complications included retinal break formation, cataracts, vitreous hemorrhages, and glaucoma in patients with stages 4b and stage 5 ROP. CONCLUSIONS: Lens-sparing vitrectomy resulted in encouraging surgical outcomes in the correction of retinal detachment of ROP, especially in stage 4 patients. Therefore, a lens-sparing vitrectomy for stage 4 ROP patient may be beneficial, although it is still associated with some intra- and post-operative complications.
Vitrectomy/*methods ; Treatment Outcome ; Severity of Illness Index ; Scleral Buckling/methods ; Retrospective Studies ; Retinopathy of Prematurity/complications/pathology/*surgery ; Retinal Detachment/etiology/pathology/surgery ; Retina/*pathology ; Male ; Lens, Crystalline/*surgery ; Infant, Newborn ; Infant ; Humans ; Follow-Up Studies ; Female ; Child, Preschool