Retinopathy of prematurity treatment in the UK: trends in neonatal anaesthetic support and location of treatment from a national surveillance study.

The aim of this study is to evaluate current anaesthetic practice for retinopathy of prematurity (ROP) interventions in the UK. We collected the data from the 12-month prospective British Ophthalmic Surveillance Unit study carried out in 2013/2014 that were analysed with regard to type of anaesthesia used for primary ROP procedures and the hospital department in which treatment took place. A total of 327 cases of treated ROP from 55 different UK units were reported in the study. Type of anaesthesia used during treatment was available for 324 (99.1%) cases and the treatment location in 316 (96.6%). Overall, 266 (89.3%) laser treatments and 13 (50.0%) of primary intravitreal injections were performed with the neonate intubated, using intravenous sedation (IVS) in 158 (59.4%) and the remainder, under general anaesthesia (GA). Two hundred thirteen (67.4%) of all ROP procedures took place in the neonatal unit. GA was used in 98 (95.1%) of theatre cases compared with 19 (8.9%) of cases treated in the neonatal unit. Three (0.9%) neonates suffered significant respiratory distress during or immediately after laser treatment.Conclusion: This survey suggests that the preference in UK units is to undertake ROP laser treatment in the neonatal unit with the neonate intubated and sedated intravenously. Those babies treated in the operating theatre are more likely to receive GA. In the surveyed year, half of the neonates receiving intravitreal injections as sole primary therapy was intubated; the reason for this could not be elucidated from the responses. Adverse respiratory reactions during or after laser treatment affected fewer than 1% of the neonates in this study. What is Known: • Prior to the introduction of intravitreal anti-VEGF, almost all ROP treatments in the UK were performed under general anaesthetic (GA). • The technique of intravitreal injection is described using topical anaesthesia and was thought to be changing anaesthesia preferences for ROP treatment. What is New: • Half of the neonates receiving primary anti-VEGF injection in the UK were treated under intravenous sedation or GA. • The increasing use of primary anti-VEGF treatment has not influenced trends in anaesthetic practice in the UK since the last review 10 years ago.

Enteral Docosahexaenoic Acid and Retinopathy of Prematurity: A Randomized Clinical Trial.

BACKGROUND: Retinopathy of prematurity (ROP) is a disorder of the retina of low-birth-weight preterm infants that potentially leads to blindness. Docosahexaenoic acid (DHA), is protective in experimental models, but its administration as part of parenteral nutrition has shown inconsistent results. We test the effect of enteral DHA to prevent ROP and/or severity and to reduce hospital stay. METHODS: This was a double-blind parallel clinical trial. Preterm infants (n = 110; 55 per group) with birth weight <1500 g but ≥1000 g were recruited in a neonatal intensive care unit. Infants were randomized to receive 75 mg of DHA/kg/d (DHA group) or high oleic sunflower oil (control group) for 14 days by enteral feeding. The effect of DHA was evaluated on any stage of ROP, severe ROP (stage ≥3) incidence, and hospital stay. Groups were compared with relative risk (RR) and 95% confidence interval (CI), Fisher's exact test, Student's t-test, or Mann-Whitney U-test, as appropriate. Logistic regression was applied to adjust for confounders. RESULTS: There was no difference between the DHA and control groups in ROP risk (RR for DHA = 0.79; 95% CI, 0.49-1.27; P = 0.33). However, patients who received DHA showed lower risk for stage 3 ROP (RR for DHA = 0.66; 95% CI, 0.44-0.99; P = 0.03). After adjusting for confounders, this decreased risk remained significant (adjusted odds ratio = 0.10; 95% CI, 0.011-0.886; P = 0.04). Hospital stay was similar between groups. CONCLUSION: Enteral DHA may reduce the incidence of stage 3 ROP.

A systematic study on the prevention and treatment of retinopathy of prematurity in China.

BACKGROUND: To identify the prevention situation, the main factors influencing prevention effects and to develop control measures over retinopathy of prematurity in China. METHODS: Using stratified random sampling method, we randomly selected 23 provincial and ministerial hospitals (8 in Guangdong province, 5 in Hunan province and 10 in Shaanxi province), 81 municipal hospitals (38 in Guangdong province, 19 in Hunan province and 24 in Shaanxi province), 180 district and county hospitals (76 in Guangdong province, 57 in Hunan province and 47 in Shaanxi province) in China. A total of 284 hospitals were enrolled in the study, with questionnaires distributed investigating the status and constrain factors of ROP presentation. Significant outcomes were analyzed thereafter by SPSS 19.0. RESULTS: The screening rate of ROP in medical institutions from eastern, central and western China were 84.6%, 35.0% and 56.7%, respectively. The screening rate of tertiary and secondary medical institutions were 84.6% and 25.7% in the eastern, 35.0% and 4.9% in the central, 56.7% and 5.9% in the western region. Screening was carried out better in the tertiary than that in the secondary and primary institutions. Treatment for ROP was available in 15.7% of all the tertiary hospitals surveyed. Lack of professionals, equipments and technologies were considered to be major restrain factors for screening. CONCLUSIONS: The ROP screening and treatment status have demonstrated significant regional diversity due to uneven distribution of medical resources in China. Developed areas had established intraregional cooperation models, whereas less-developed areas should consider set up a large-scale, three-level ROP prevention network. It is of paramount importance that education and training towards ophthalmologists should be vigorously strengthened. It is strongly recommended that implement ROP telemedicine and integrated ROP prevention and management platforms through the Internet should be established.

Ranibizumab after laser photocoagulation failure in retinopathy of prematurity (ROP) treatment.

The purpose of this study was to investigate the anatomical and functional outcomes of the two-stage treatment of severe retinopathy of prematurity (ROP) using laser photocoagulation and intravitreal ranibizumab injection. The medical records of 53 eyes of 28 infants treated by conventional laser photocoagulation with deferred intravitreal 0.25 mg/0.025 mL ranibizumab injection were analysed. All patients had at least 11 months of follow-up. In the analysed group, the mean gestational age at birth was 25 weeks and mean birthweight was 790 g. The mean time of laser photocoagulation was 34 weeks of postmenstrual age (PMA). Ranibizumab injection was performed on average at 37 weeks of PMA. The mean time between interventions was 19 days. Retinal detachment occurred in 12 eyes (22.6%), in three children bilaterally. Visual responses were obtained in 23 of 28 treated children. Our results indicate that ranibizumab injection can be taken into consideration in the selected cases of laser photocoagulation failure. The unsatisfactory results of this study elicited a change in the ROP treatment protocol in our medical centre. The study gives an insight into anatomical and functional outcomes of ROP treatment in the Central and Eastern European population.

Parenteral Fish-Oil Lipid Emulsions in the Prevention of Severe Retinopathy of Prematurity: A Systematic Review and Meta-Analysis.

Objective Omega-3 fatty acids are vital for brain and retinal maturation. It is not clear if early use of ω-3 fatty acids in the form of fish-oil lipid emulsions (FLEs) prevents retinopathy of prematurity (ROP) in preterm infants. The aim of this meta-analysis is to evaluate whether early administration of parenteral FLEs reduces ROP requiring laser therapy or severe ROP ≥stage 3 in preterm infants. Methods A literature search was performed to identify studies comparing parenteral FLEs with soybean-based lipid emulsions (SLEs) in preventing ROP. The main outcome was incidence of severe ROP or ROP requiring laser therapy. Results Studies met the inclusion criteria (four RCTs and two observational studies). The pooled relative risk of ROP requiring laser therapy or severe ROP ≥ stage 3 in FLEs group was 0.47 [95% CI: 0.24-0.90] and 0.40 [95% CI: 0.22-0.76] in RCTs and observational studies, respectively. FLEs also reduced cholestasis; however, other secondary outcomes of bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), sepsis, intraventricular hemorrhage (IVH), and mortality were similar. Conclusion The use of FLEs may reduce the incidence of severe ROP or need for laser therapy in preterm infants. A large multicenter RCT is required to confirm this.

Possible Role of Sildenafil Citrate in the Recurrence of Neovascularization in Laser-regressed Aggressive Posterior ROP.

BACKGROUND: Systemic diseases and their treatment influence aggressive posterior retinopathy of prematurity. CASE CHARACTERISTICS: A premature infant with aggressive posterior retinopathy of prematurity underwent laser treatment with a favourable outcome. She was started on oral sidenafil citrate for pulmonary hypertension. Ten days later she developed neovascularization within the lasered retina. INTERVENTION/OUTCOME: Considering the possible role of sildenafil in this unusual development, the drug was withdrawn resulting in regression of the neovascularization. MESSAGE: The clinician should be aware of this retinal adverse effect of sildanefil in neonates with aggressive posterior retinopathy of prematurity.

Recent advances in the management of infants born <1000†g.

In this review, we survey some significant advances in the medical care of babies <1000 g and we highlight the development of care pathways that ensure optimal antenatal care, which is a prerequisite for good neonatal outcomes. We also suggest that the long overdue development of family integrated care will in the end prove at least as important as the recent medical advances.

A safety and feasibility study of the use of 670 nm red light in premature neonates.

OBJECTIVE: Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the retina affecting extremely preterm or low birth weight infants The aim of this study was to assess the feasibility and safety of 670 nm red light use in a neonatal intensive care unit. STUDY DESIGN: Neonates <30 weeks gestation and <1150 g were enrolled within 48 h of birth. Data collected included cause of preterm delivery, Apgar scores and birthweight. 670 nm red light was administered for 15 min per day from a distance of 25 cm, delivering 9 J cm(-)(2), from the time of inclusion in the study until 34 weeks postmenstrual age. Infants were assessed daily for the presence of any skin burns or other adverse signs. RESULT: Twenty-eight neonates were enrolled, seven 24 to 26 weeks and twenty-one 27 to 29 weeks gestation. The most common cause for preterm delivery was preterm labor (14/28) with five of these having evidence of chorioamnionitis. There were no skin burns or other documented adverse events. Entry into the study was readily achieved and treatment was well accepted by parents and nursing staff. CONCLUSION: 670 nm red light appears to be a safe and feasible treatment for further research in respect to ROP.

"Oxygen with love" and diode laser treatment decreases comorbidity and avoidable blindness due to retinopathy of prematurity: results achieved in the past 12 years.

AIM: To determine whether the "Oxygen with Love" (OWL) and diode laser treatment provided in a neonatal intensive care unit has reduced the risk of avoidable blindness caused by retinopathy of prematurity (ROP) over the past decade. MATERIALS AND METHODS: A prospective observational cohort study was performed, in which 351 infants were examined for ROP. The inclusion conditions were as follows: preterm infants, birthweight <1500 g or <32 weeks' gestational age, and birth between 1 Jan 2000 to 31 August 2012. From mid-2009, the OWL program was implemented and the ventilation protocols for such infants were amended. We tested whether the incidence of unfavorable structural outcomes of ROP had decreased following these changes. RESULTS: From 2004 to 2012, the survival rates of younger children increased (p < 0.003). From 2005 to 2012, laser treatment rather than cryotherapy was applied, and the incidence of unfavorable structural outcomes of ROP fell from 13% to 5.6% (not significant). From 2009 to 2012, the incidence of ROP decreased from 55% to 29% (p < 0.002). From 1 August 2009 to 31 August 2012, there was less need for ablative treatment for premature infants, with the rate falling from 11.81% to 3.9% (p < 0.03). This improvement was significantly associated with a reduction in the number of days of intubation (p < 0.0017), lower rates of sepsis (p < 0.003), and improvements in postnatal weight gain (p < 0.0002). CONCLUSION: The introduction of the OWL program, together with lower rates of sepsis, improvements in postnatal weight gain, and the use of diode laser treatment, has reduced the incidence of unfavorable structural outcomes of ROP.

Retinopathy of prematurity: a study of prevalence and risk factors.

BACKGROUND: Retinopathy of prematurity (ROP) is a serious complication of prematurity treatment and can lead to blindness unless recognized and treated early. OBJECTIVE: The objective was to estimate the prevalence of ROP in preterm infants in the Neonatal Intensive Care Unit (NICU), to identify the risk factors which predispose to ROP, and to assess the outcome of these cases. MATERIALS AND METHODS: A ROP prospective screening survey was performed enrolling all prematures admitted to the NICU from January 2009 to December 2010, with a gestational age of 32 weeks or less at birth and a birth weight of 1500 g or less. Infants whose gestational age was >32 weeks or birth weight was >1500 g were included if they were exposed to oxygen therapy for more than 7 days. A total of 172 infants (84 males and 88 females) had retinal evaluation by indirect ophthalmoscopy from the fourth postnatal week and followed up periodically. Perinatal risk factors for ROP were assessed using univariate and multivariate analysis. Infants who progressed to stage 3 ROP were given laser therapy. RESULTS: Out of the studied 172 infants, 33 infants (19.2%) developed ROP in one or both eyes; 18 (54.5%) cases stage 1, 9 (27.3%) cases stage 2, and 6 (18.2%) cases stage 3. None of the studied neonates presented ROP at stages 4 or 5. The six cases diagnosed as ROP stage 3 underwent laser ablative therapy. Univariate analysis showed that there was a significant relationship between the occurrence of ROP and gestational age (P = 0.000), sepsis (P = 0.004), oxygen therapy (P = 0.018), and frequency of blood transfusions (P = 0.030). However, an insignificant relationship was found between the occurrence of ROP and sex, mode of delivery, birth weight, respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage, hypotension, phototherapy, duration of oxygen therapy, mechanical ventilation, and CPAP (all P > 0.05). Gestational age, sepsis, oxygen therapy, and frequency of blood transfusions remained significant variables after logistic regression analysis. CONCLUSION: The prevalence of ROP in this study was 19.2%; low gestational age, sepsis, oxygen therapy, and frequent blood transfusions were significant risk factors for ROP. Laser was effective in treatment and decreasing the progression of ROP. As this is a unit-based study, a comprehensive countrywide survey on ROP in Egypt is recommended to determine any regional differences in disease prevalence.

Understanding retinopathy of prematurity: update on pathogenesis.

Retinopathy of prematurity (ROP), an ocular disease characterized by the onset of vascular abnormalities in the developing retina, is the major cause of visual impairment and blindness in premature neonates. ROP is a complex condition in which various factors participate at different stages of the disease leading to microvascular degeneration followed by neovascularization, which in turn predisposes to retinal detachment. Current ablative therapies (cryotherapy and laser photocoagulation) used in the clinic for the treatment of ROP have limitations and patients can still have long-term effects even after successful treatment. New treatment modalities are still emerging. The most promising are the therapies directed against VEGF; more recently the use of preventive dietary supplementation with ω-3 polyunsaturated fatty acid may also be promising. Other than pharmacologic and nutritional approaches, cell-based strategies for vascular repair are likely to arise from advances in regenerative medicine using stem cells. In addition to all of these, a greater understanding of other factors involved in regulating pathologic retinal angiogenesis continues to emerge, suggesting potential targets for therapeutic approaches. This review summarizes an update on the current state of knowledge on ROP from our and other laboratories, with particular focus on the role of nitro-oxidative stress and notably trans-arachidonic acids in microvascular degeneration, semaphorin 3 operating as vasorepulsive molecules in the avascular hypoxic retina and in turn impairing revascularization, succinate and its receptor GPR91 in neuron-mediated retinal neovascularization, and ω-3 lipids as modulators of preretinal neovascularization.

Large spot transpupillary thermotherapy: a quicker laser for treatment of high risk prethreshold retinopathy of prematurity - a randomized study.

To compare structural and functional outcome and time efficiency between standard spot sized conventional pulsed mode diode laser and continuous mode large spot transpupillary thermotherapy (LS TTT) for treatment of high risk prethreshold retinopathy of prematurity (ROP). Ten eyes of five preterm babies having bilateral symmetrical high risk prethreshold ROP were included in this study. One eye of each baby was randomized to get either standard spot sized conventional pulsed mode diode laser or continuous mode LS TTT. There was no significant difference between structural or functional outcome in either group. The mean time taken for conventional diode laser was 20.07 minutes, while that for LS TTT was 12.3 minutes. LS TTT was 40% more time efficient than the conventional laser. It may be better suited for the very small fragile premature infants as it is quicker than the conventional laser.

Fish-oil fat emulsion supplementation may reduce the risk of severe retinopathy in VLBW infants.

OBJECTIVE: The retina contains rods and cones that have membranes highly enriched with docosahexaenoic acid (DHA). Infants born prematurely are at risk of DHA insufficiency, because they may not have benefited from a full third trimester of the mother's lipid stores. Moreover, within the first 2 to 3 weeks of life, the main sources of lipids for premature infants are fat emulsions, which do not contain DHA. PATIENTS AND METHODS: This observational study was designed to compare the safety and efficacy outcomes of an intravenous fat emulsion that consists of fish-oil emulsion (contains DHA) with soybean and olive oil, administered from the first day of life to 40 infants who weighed <1250 g; results were obtained from a historical cohort of 44 preterm neonates who were given an emulsion of soybean and olive oil. The primary study outcomes were the occurrence of retinopathy and need for laser therapy and cholestasis. Infants in the 2 groups were comparable with regard to demographic and clinical characteristics and were subjected to the same conventional therapy. RESULTS: There was a significantly lower risk of laser therapy for infants who received an emulsion of soybean, olive oil, and fish oil (P = .023). No significant differences were found in acuity and latency of visual evoked potentials between infants in the 2 groups. There was no infant with cholestasis among those who received fish-oil emulsion, and there were 5 subjects with cholestasis in the historical group (P = .056). CONCLUSION: Fish-oil-based fat emulsion administered from the first day of life may be effective in the prophylaxis of severe retinopathy.

[Risk factors of 3rd stage retinopathy of prematurity progression]. / Czynniki ryzyka rozwoju 3 stadium retinopatii wczesniaków.

Retinopathy of prematurity is a vasoproliferative, multifactorial disease of retina affecting the preterm neonates. Purpose of the study was to assess the association between a range of clinical features and the development of the stage 3 ROP. The studies comprised 79 preterm infants with diagnosed 3rd stage of ROP and 1117 preterm neonates without ROP as a control group. The analysis included the clinical data of patients--gestational age, birth weight, presence of hypotrophy, Apgar score, duration of oxygen therapy, ventilation and phototherapy. Among the potential risk factors, hypotrophy and duration of phototherapy had no significant influence on the development of 3rd stage ROP. High risk of development of 3rd stage ROP was observed in neonates born before 28th week of gestation, weighing at birth less than 1000 g. The significant risk factors were also the asphyxia, duration of ventillation exceeding 30 days and oxygen therapy longer than 40 days.

Outcomes of extremely premature infants related to their peak serum bilirubin concentrations and exposure to phototherapy.

OBJECTIVES: To analyze, in extremely low birth weight infants, associations between peak bilirubin concentration and evidence of brain damage, and between peak bilirubin concentration and blindness attributable to retinopathy of prematurity. METHODS: Retrospective study of 128 infants of /=9.4 mg/dL (odds ratio [OR] confidence interval [CI] 4.48 [1.15-17.43])), low gestational age (OR [CI] per week 1.95 [1.05-3.63]), and longer duration of phototherapy (OR [CI] per 10 hours 1.17 [1.02-1.33]). The association of neurodevelopmental impairment with grades 3 and 4 intraventricular hemorrhage was statistically significant (OR 5.39 [1.83-15.84]), but with high-peak serum bilirubin concentration >/=11.7 mg/dL (>/=200 micromol/L), was not significant (OR 2.89 [0. 87-9.53]). CONCLUSIONS: In these infants, prolonged phototherapy and low-peak serum bilirubin concentrations were associated with severe visual loss attributable to retinopathy of prematurity. The findings should be interpreted with caution until the evidence is reinforced in other patient populations.

Therapeutic effect of liposomal superoxide dismutase in an animal model of retinopathy of prematurity.

A newborn rat model of retinopathy of prematurity was used to test the hypothesis that a lack of superoxide dismutase contributes to the retinal vaso-attenuation seen during exposure of the animals to hyperoxic conditions. To determine the endogenous superoxide dismutase activity of the retina under hyperoxic conditions, litters of albino rats were placed in either constant 80% ambient oxygen (constant hyperoxia), or placed in 21% oxygen (room air) immediately after birth. Every other day, for 14 days, several rat pups were sacrificed and their retinas removed for the determination of total superoxide dismutase (SOD) activity and manganese-associated SOD activity. An attempt was made to increase retinal SOD activity by intraperitoneal administration of exogenous SOD encapsulated in polyethylene glycol-modified liposomes. Additional litters were exposed to the same oxygen treatments and supplemented twice daily with either liposome-encapsulated superoxide dismutase in saline or liposomes containing saline without SOD. Animals were sacrificed at various time points for the determination of total superoxide dismutase activity and computer-assisted analysis of vessel density and avascular area. Animals raised in an atmosphere of constant 80% oxygen had significantly reduced levels of retinal superoxide dismutase activity through 6 days of life when compared to their room air-raised littermates. At 6 days of age, daily supplementation with liposome-encapsulated SOD had significantly increased retinal superoxide dismutase activity and reduced oxygen-induced vaso-attenuation as evidenced by increased vessel density and decreased avascular area, when compared to littermates exposed to constant hyperoxia that received control liposomes. Superoxide dismutase had no adverse effects on any of the animals regardless of treatment. Tracing experiments demonstrated that liposomes entered the retina and were found in cells morphologically resembling microglia. Delivery of SOD to the retina via long-circulating liposomes proved beneficial, suggesting that restoration and/or supplementation of endogenous antioxidants in oxygen-damaged retinal tissue is a potentially valuable therapeutic strategy.

[Prospective biochemical study of the antioxidant defense capacity in retinopathy of prematurity]. / Az antioxidáns védekezóképesség prospektív, biokémiai vizsgálata retinopathia preamaturorumban.

The study was carried out on 60 oxygen-treated premature infants weighed less than 2000 g (1529 +/- 302 g, x mean +/- S. D.) and on their mothers. Both the Retinopathy of Prematurity screening and the biochemical tests were started at the age of 6 weeks. According to our results, the signs of an acute oxidative stress could be seen in all 60 oxygen-treated prematures erythrocyte's glutathione redox system, independently of the presence of the retinopathy compared to prematures (n = 20) with the same gestational age but without oxygen therapy (1720 +/- 305 g, mean +/- S.D.). The concentrations of free sulfhydril groups in the plasma, and the blood selenium levels were significantly lower in the prematures suffering from moderate retinopathy (n = 5) than in the other oxygen-treated premature without retinopathy (n = 27) and with "any retinopathy" (n = 28) patients groups. The same tendency was seen in the mothers. Vitamin E treatment of "any retinopathy" infants seemed to have a positive effect against the development of Retinopathy of Prematurity. The close correlation found between the antioxidant capacity of the mothers and babies suggest that the supplementation of feeding with sulfur-containing amino acids (methionine, cysteine) during pregnancy would improve the antioxidant capacity of prematures. An antioxidant cocktail (selenium + vitamin E) given to the high-risk mothers (advanced age, smoking, pregnancy-induced hypertension) before delivery as suggested in literature might be useful in prevention of Retinopathy of Prematurity.

Severe retinopathy of prematurity in infants with birth weights less than 1250 grams: incidence and outcome of treatment with pharmacologic serum levels of vitamin E in addition to cryotherapy from 1985 to 1991.

OBJECTIVE: To determine the effect of vitamin E prophylaxis and treatment on the sequelae of severe (threshold) retinopathy of prematurity (ROP) in infants treated with cryotherapy at Pennsylvania Hospital from 1985 to 1991. STUDY DESIGN: Beginning on day 0, all infants with birth weights < or = 1250 gm received supplements of vitamin E using standard preparations. Serum E levels of 23 to 58 mumol/L (1 to 2.5 mg/dl) were targeted for infants with immature retinal vasculature or ROP of stage 2 or less in severity, and levels of 58 to 81 mumol/L (2.5 to 3.5 mg/dl) for infants with prethreshold ROP. At diagnosis of threshold ROP, treatment with a parenteral investigational new drug preparation of alpha-tocopherol was begun to raise serum levels to the pharmacologic range (93 to 116 mumol/L or 4 to 5 mg/dl). Within 3 days of diagnosis, and at the discretion of the retinal specialist, one or both eyes were treated with cryotherapy. Visual outcome at 4 years was compared with the 42-month outcome reported for eyes in the infants randomly assigned to treatment in the 1986-1987 Multicenter Trial of Cryotherapy for ROP (CRYO-ROP). RESULTS: Threshold ROP developed in 22 of 450 surviving infants (age 3 months). All were treated with pharmacologic serum levels of vitamin E; 17 infants were also treated with cryotherapy (10 in one eye and 7 in both eyes). These 17 infants, in comparison with infants in the CRYO-ROP trial (n = 187), were at least at equal risk for poor visual outcome on the basis of birth weight, gestational age, the percentage of zone 1 ROP, and mean interval from appearance of ROP to diagnosis of prethreshold ROP, which was shorter at Pennsylvania Hospital (4.1 days for the Pennsylvania Hospital group, 10.3 days for the CRYO-ROP group). However, on the basis of the mean number of days from diagnosis of prethreshold to threshold ROP (12.5 days for Pennsylvania Hospital, 10.5 days for CRYO-ROP) and the extent of extraretinal neovascularization at threshold (mean 7.9 sectors for Pennsylvania Hospital, 9.7 for CRYO-ROP), progression of retinopathy beyond the prethreshold stage had slowed and visual outcome in the eyes of infants at Pennsylvania Hospital treated with both cryotherapy and vitamin E (worse eye used for those treated with bilateral cryotherapy) was better than that reported for the treated eye of infants in the CRYO-ROP group (percentage of favorable visual acuity, 76% vs 48%, p = 0.04; percentage of normal structure posterior retinal pole, 71% vs 38%, p < or = 0.02). CONCLUSIONS: In this small case series, the combination of cryotherapy with anti-oxidant prophylaxis and treatment appeared to decrease the severity and sequelae of threshold ROP. This hypothesis deserves testing in a large, randomized clinical trial.

Oxygen-induced retinopathy in the newborn rat: effects of hyperbarism and topical administration of timolol maleate.

BACKGROUND: Lesions resembling those of human retinopathy of prematurity can be provoked in newborn Wistar rats by exposure to an FiO2 of 80% for the first 5 days of life followed by 5 days recovery under room-air conditions. METHODS: We evaluated the effects of moderate hyperbarism (+60.75 kPa, i.e. 455 mmHg or 0.6 atm) and topical administration of 0.25% timolol maleate on oxygen-induced retinopathy (OIR) in this experimental model. RESULTS: OIR (including neovascularization in most cases) was observed in 100% of the retinas of normobaric oxygen-reared ratlings that did not receive timolol. OIR was less frequent in oxygen-reared ratlings treated with hyperbarism (60%) or timolol (65%). Hyperbaric oxygen supplementation combined with timolol treatment during both the hyperoxic and room-air phases reduced the incidence of OIR to 30%. There was no sign of vasoproliferation in any of the retinas from the latter three groups. CONCLUSIONS: The highly significant protective effects of hyperbarism and timolol observed in this study are not fully understood. We speculate that vasoconstriction induced by the hyperbarism reduces the amount of oxygen that reaches the retina from the choroid during O2 supplementation, while an increased ocular perfusion pressure caused by timolol-induced reduction of the intraocular pressure might decrease the stimulus to vasoproliferation that normally occurs with room-air recovery.