Retinopathy of prematurity: two distinct mechanisms that underlie zone 1 and zone 2 disease

PURPOSE: In its most severe form, retinopathy of prematurity (ROP) is located in posterior retina and affects the smallest, most premature infants. We hypothesize that, depending on whether vasculogenesis (de novo formation of new vessels by transformation of vascular precursor cells (VPCs)) or angiogenesis (budding from existing vessels) is perturbed, it results in significant differences in clinical presentation and therapeutic outcome observed in zone 1 vs zone 2 ROP. DESIGN: The study is a retrospective analysis of the difference in outcome between zones 1 and 2 ROP after cryotherapy and laser therapy. METHODS: A review of the clinical presentation of zones 1 and 2 ROP that correlate this with the topography of formation of human retinal vasculature through vasculogenesis and angiogenesis. RESULTS: Population data on susceptible infants, and outcome statistics of clinical trials are given. Digital images show a correlation between ROP in zone 1 with the region of the retina vascularized through vasculogenesis. CONCLUSION: Zone 1 ROP is correlated with vessel development by vasculogenesis, relative insensitivity to laser/cryotherapy and poorer anatomic and visual outcomes. This suggests that, if the vasculogenic process is perturbed, it results in a distinct clinical presentation, poorer response to therapy, and poorer visual outcome. When the current international classification was developed, knowledge of the processes of human retinal vascular development was incomplete. The work presented here provides a framework for the development of a modification to incorporate these ideas without sacrifice of the essential elements of the international classification of ROP.     

Treatment of retinopathy of prematurity in extremely premature infants over an 18‐year period

Background: To report the efficacy of laser diode therapy in the treatment of retinopathy of prematurity (ROP) in extremely premature (EP) infants over an 18‐year period. Design: Retrospective study. Participants: One hundred twenty‐eight eyes in 66 infants treated between 23 and 25.6 weeks. Methods: Five hundred fifty‐four infants between 23 and 25.6 weeks gestational age (GA) were admitted to The Royal Brisbane and Women's Hospital Neonatal Intensive Care Unit (NICU) between 1992 and 2009. Three hundred seventy‐three patients survived to undergo screening, 304 were diagnosed with ROP, and 66 infants required diode laser therapy. Main Outcome Measures: Success of treatment, visual and refractive outcomes. Results: One hundred twenty‐eight eyes from 66 infants (18.8% of those screened) underwent laser treatment with a mean GA of 24.3 weeks and mean birth weight of 711.4g. Fifty‐six eyes were treated at pre‐threshold disease, and 72 eyes at threshold disease. Over the study period, the number of laser spots and regression rate of ROP increased, while the frequency of re‐treatment decreased. At 40 weeks, 119 eyes had regressed ROP (93%), two advanced to stage 4a, three to stage 4b and four to stage 5. Aggressive posterior ROP (AP‐ROP) occurred in 15 eyes (11.7% of those treated). Forty‐three patients (65%) were followed up for a mean of 56.5 months. The number of laser spots correlated well with subsequent refractive error but poorly with corrected visual acuity. Conclusions: In EP infants, laser diode therapy is an effective technique to halt the progression of ROP in most cases. AP‐ROP is uncommon, even in this subgroup of extremely premature infants.     

早产儿视网膜病变治疗新进展

早产儿视网膜病变(retinopathy of prematurity,ROP)是早产儿和低体质量儿发生的一种视网膜血管增生性病变。近年来随着医疗护理水平不断提高,早产儿的存活率不断提高,ROP的发生率也明显增加。传统治疗方式包括冷冻治疗和激光治疗,这些治疗对操作医生的技术有较高的要求。因此,寻找一种在病变早期应用,且操作简单、安全、有效的治疗方法,已成为研究者的共识。我们就目前治疗ROP的新进展进行综述。     

The progress of prophylactic treatment in retinopathy of prematurity

Retinopathy of prematurity (ROP) is a retinal vascular disorder frequently found in premature infants. Different therapeutic strategies have been developed to treat ROP. However, there are still many children with ROP suffering by severe limitations in vision or even blindness. Recently, ROP has been suggested to be caused by abnormal development of the retinal vasculature, but not simply resulted by retinal neovascularization which takes about 4 to 6wk after birth in premature infants. Thus, instead of focusing on how to reduce retinal neovascularization, understanding the pathological changes and mechanisms that occur prior to retinal neovascularization is meaningful, which may lead to identify novel target(s) for the development of novel strategy to promote the healthy growth of retinal blood vessels rather than passively waiting for the appearance of retinal neovascularization and removing it by force. In this review, we discussed recent studies about, 1) the pathogenesis prior to retinal neovascularization in oxygen-induced retinopathy (OIR; a ROP in animal model) and in premature infants with ROP; 2) the preclinical and clinical research on preventive treatment of early OIR and ROP. We will not only highlight the importance of the mechanisms and signalling pathways in regulating early stage of ROP but also will provide guidance for actively exploring novel mechanisms and discovering novel treatments for early phase OIR and ROP prior to retinal neovascularization in the future.     

【In Press】 The progress of prophylactic treatment in retinopathy of prematurity

Retinopathy of prematurity (ROP) is a retinal vascular disorder frequently found in premature infants. Different therapeutic strategies have been developed to treat ROP. However, there are still many children with ROP suffering by severe limitations in vision or even blindness. Recently, ROP has been suggested to be caused by abnormal development of the retinal vasculature, but not simply resulted by retinal neovascularization which takes about 4-6wk after birth in premature infants. Thus, instead of focusing on how to reduce retinal neovascularization, understanding the pathological changes and mechanisms that occur prior to retinal neovascularization is meaningful, which may lead to identify novel target(s) for the development of novel strategy to promote the healthy growth of retinal blood vessels rather than passively waiting for the appearance of retinal neovascularization and removing it by force. In this review, we discussed recent studies about: 1) the pathogenesis prior to retinal neovascularization in oxygen-induced retinopathy (OIR, a ROP in animal model) and in premature infants with ROP; 2) the preclinical and clinical research on preventive treatment of early OIR and ROP. We will not only highlight the importance of the mechanisms and signalling pathways in regulating early stage of ROP but also will provide guidance for actively exploring novel mechanisms and discovering novel treatments for early phase OIR and ROP prior to retinal neovascularization in the future.     

玻璃体内注射雷珠单抗联合激光光凝治疗早产儿视网膜病变疗效观察

目的　观察激光光凝联合玻璃体内注射雷珠单抗治疗早产儿视网膜病变（retinopathy of prematurity,ROP）的安全性及有效性。方法　对32例（64眼）ROP患儿行玻璃体内注射雷珠单抗治疗,观察附加病变、嵴、嵴上新生血管的消退情况以及周边视网膜,其中12例（24眼）附加病变、嵴及嵴上新生血管不完全消退者进行激光光凝治疗。结果　32例64眼ROP患儿中,经玻璃体内注射雷珠单抗治疗病变完全消退者20例40眼,占62.5%;12例24眼病变复发,经联合激光光凝治疗病情稳定,占37.5%。病变复发的24眼中,包括急进型后极部ROP 14眼,阈值期ROP 6眼,阈值前期ROP 4眼。所有患儿视网膜病变不同程度消退。给予玻璃体内注射雷珠单抗治疗后新生血管及出血吸收,血管继续发育至锯齿缘或病变瘢痕化。12例（24眼）病变复发者联合视网膜光凝治疗后病变完全消退。32例ROP患儿眼部及全身未见不良反应。结论　玻璃体内注射雷珠单抗治疗ROP效果好,不但可以使嵴、嵴上新生血管及附加病变完全消退,而且还可使视网膜血管继续生长,对于病变不能完全消退的患儿联合视网膜激光光凝治疗后也可获得较好疗效。     

Combination of Intravitreal Ranibizumab and Laser Photocoagulation for Aggressive Posterior Retinopathy of Prematurity

Purpose

To report on 2 cases of aggressive posterior retinopathy of prematurity (ROP) treated with intravitreal ranibizumab (Lucentis^®) and laser photocoagulation.

Methods

Two premature females, born at 25 and 26 weeks’ gestation with a birth weight of 530 and 550 g, respectively, with aggressive posterior ROP received combined treatment with laser photocoagulation and intravitreal ranibizumab (0.3 mg [30 µl]) to each eye. Structural outcomes were evaluated by indirect ophthalmoscopy and documented by retinography.

Results

An intravitreal injection was made at 34 weeks of postmenstrual age in the first case, followed by laser photocoagulation 1 week later. There was a partial regression of ROP with treatment. Five weeks later, neovascularization regrowth with bleeding in both eyes (intraretinal and subhyaloid) occurred and retreatment with combined therapy was performed. In the second case, single therapy with laser photocoagulation was made at 34 weeks of postmenstrual age. In spite of the confluent photocoagulation in the avascular area, progression to 4A ROP stage occurred 1 week later. Both eyes were retreated 1 week later with intravitreal ranibizumab and laser photocoagulation. Treatment resulted in ROP regression in both cases. There were no signs of systemic or ocular adverse side effects.

Conclusion

The cases presented show that combination therapy of indirect laser photocoagulation and intravitreal ranibizumab can be effective in the management of aggressive posterior ROP. Further investigation on anti-VEGF safety in premature infants is necessary. Additional studies are needed to define the role of anti-VEGF in ROP treatment.Key Words: Retinopathy of prematurity, Laser photocoagulation, Ranibizumab, Anti-VEGF therapy     

Comparison of structural outcome between intravitreal bevacizumab and laser treatment for type 1 retinopathy of prematurity after long-term follow-up

Background:To compare the structural outcome of intravitreal bevacizumab (IVB) and laser treatment for type 1 retinopathy of prematurity (ROP). Methods: This is a retrospective comparative study. From December 2002 to April 2009, patients with type 1 ROP according to criteria of Early Treatment of Retinopathy of Prematurity (ETROP) study were treated by peripheral retinal diode laser photocoagulation in nearly confluent pattern. From May 2009 to January 2015, we performed IVB for patients with type 1 ROP. The patients were closely followed until disappearance of retinal neovascularization in the laser group and regression of avascular zone in the bevacizumab group. The demographical data, postmenstrual age (PMA) for treatment, and fundus ifndings were recorded by chart review. The difference between laser and bevacizumab groups was compared by Studentt-test and Fisher exact test. Results: We collected 43 patients (86 eyes) with type 1 ROP, including 30 male and 13 female infants. Their mean gestation age and birth body weight (BBW) were 27.5 weeks and 1,034 gm. Zone I and zone II disease were found in 8 and 35 patients. The mean PMA for treatment was 37.3 weeks. The mean follow-up period was 54.4 months. Laser treatment was administered in 26 patients, and bevacizumab injection for 17 infants. Single session of laser was performed in all patients of laser group without recurrence of retinal neovascularization. Complete regression of ROP was found in 15 infants of bevacizumab group following the ifrst IVB. Four eyes in two patients (2/17, 11.7%) had recurrence of ROP and received additional injections and adjuvant laser treatment. There was no unfavorable anatomical results such as retinal detachment or macular ectopia or complications such as cataract or endophthalmitis in either bevacizumab or laser management. Conclusions: Laser therapy and IVB were both effective treatments for type 1 ROP to cause favorable anatomical outcomes. Single session of laser ablation in nearly conlfuent pattern was sufifcient for complete regression of ROP in laser group. Single IVB was appropriate for managing most of cases with ROP in bevacizumab group, but a small proportion (nearly one tenth) of them had recurrent episodes requiring adjuvant therapies.     

Time to consider a new treatment protocol for aggressive posterior retinopathy of prematurity?

Purpose: To discuss treatment modalities for aggressive posterior retinopathy of prematurity (AP‐ROP). Methods: The medical charts of all infants with AP‐ROP at Uppsala University Hospital, Sweden, during a 2‐year period (2009 and 2010) were reviewed. Eight infants (16 eyes) with a mean gestational age of 23.8 weeks and a mean birth weight of 592 g were treated with laser and/or intravitreal injections of bevacizumab (0.4 and 0.625 mg). RetCam photography was used to document the retinal appearance before and after treatment. Results: All infants (16 eyes) had AP‐ROP in zone I. Mean time at initial treatment was 34 weeks postmenstrual age. Two eyes (one infant) were only treated with laser, and six eyes (three infants) were treated with laser therapy or cryopexy and, because of lack of regression, with bevacizumab as salvage therapy. Eight eyes (four infants) were treated with a first‐line bevacizumab injection and four of these eyes (two infants) with additional laser ablation for continued disease progression in zone II. Macular dragging occurred in one eye of one infant primarily treated with laser. Conclusions: Given the high complication rate of the extensive laser treatment for zone I ROP, it is worth considering anti‐vascular endothelial growth factor treatment as an alternative therapy. Further knowledge concerning side effects and long‐term ocular and systemic outcome is warranted before this drug becomes general clinical practice.     

早产儿视网膜病变筛查和阈值期治疗的研究

目的研究早产儿视网膜病变(ROP)的发生率,评估ROP阈值期治疗效果。方法使用双目间接检眼镜对108例早产儿进行ROP筛查,将筛查结果进行统计学分析,达到阈值病变的患儿及时进行视网膜激光光凝或经巩膜、视网膜冷凝术。结果筛查108例早产儿,发现ROP23例,发生率为21.3%。在所有ROP患儿中,ROP1期13例,占56.5%;ROP2期3例,占13.0%;ROP3期7例,占30.4%。其中ROP3期患儿均伴有附加病变,达到阈值病变标准。ROP患儿出生体重为(1.43±0.25)kg(t=4.059,P<0.001);孕周为(31.0±2.3)周(t=2.637,P=0.013);吸氧时间为1~49d,平均17d(n=23,Z=-3.630,P<0.001);需要机械辅助呼吸患儿18例(χ2=12.009,P=0.001);上述指标与非ROP患儿比较,差异均有统计学意义;而与是否多胎的差异无统计学意义(χ2=1.013,P=0.314)。Logistic回归分析:出生体重低(β=-2.542,OR=0.079,P=0.032)和使用机械辅助呼吸(β=1.341,OR=3.823,P=0.025)的患儿是发生ROP的相关高危因素。7例阈值期病变患儿中,6例进行激光光凝或冷凝治疗。术后随访2个月至2年,手术眼的结构和视功能未见异常。1例阈值期病变患儿未予治疗,于1个月后出现视网膜脱离。结论出生体重轻、孕周少、吸氧时间长、需要机械辅助呼吸的早产儿发生ROP的风险较高。对阈值期病变患儿应及时进行激光光凝或冷凝治疗。     

Analysis of the clinical characteristics and refraction state in premature infants: a 10-year retrospective analysis

AIM: To report the visual outcomes and refractive status in premature infants with and without retinopathy of prematurity (ROP) who were or not treated. METHODS: The clinical records of all premature infants with or without ROP and with or without treatment between 2007 and 2017 were retrospectively reviewed. Basic demographic data, serial changes in ROP incidence, treatment and outcomes, and the refractive states were analyzed. Correlations among myopia and astigmatism progression, birth weight, gestational age, and treatment methods were also analyzed. RESULTS: A total of 562 screened premature infants (all Chinese, 1124 eyes), were recruited with a 378:184 male-to-female ratio. Birth weight did not directly influence ROP incidence. The overall ROP incidence was 16.55% (93/562 cases). The incidences in boys and girls were 16.14% (33/378 cases) and 17.39% (32/184 cases), respectively, and this difference was not significant. However, all infants with serious ROP (stage IV and V) were male. Myopia combined with astigmatism was common in premature infants with and without ROP (30.99%, 172/555 cases), and myopic refraction (including myopia and myopia combined with astigmatism) was more common in premature infants with ROP (48.84%, 42/86 cases). In the >8.00 diopter group, there were significantly more ROP infants than without ROP. Myopic refraction (including myopia and myopia combined with astigmatism) was most common in infants with ROP after treatment (63.63%, 7/11 cases). CONCLUSION: The refractive state is different between premature infants and mature infants. Those treated for ROP had a higher chance of developing myopia, astigmatism, and higher diopter.     

Retinopathy of prematurity. Results of fundus examination performed in 94 preterm infants

PURPOSE: The purpose of this study was to evaluate the incidence and severity of retinopathy of prematurity (ROP) in infants of birth weight less than 1.500 g and/or under 32 weeks'gestation. METHODS: Ninety-four preterm infants were examined following the Royal College of Ophthalmologists guidelines and retinopathy was graded using the International Classification of ROP. Screening limits were 1 500 g birth weight or 32 weeks'gestational age. Fundus examinations for ROP were performed at 5 weeks'chronological age from birth. Pupil dilation was obtained with instillation of 1% tropicamide three times at 15-minute intervals. RESULTS: The 94 infants examined for ROP had a median gestational age of 292.3 weeks and a median birth weight of 1 110340 g. ROP was diagnosed in 21 of 94 subjects (22.3%) by fundus examination. ROP stage 3 developed in one preterm infant, ROP stage 2 developed in five preterm infants, and ROP stage 1 developed in 15 preterm infants. No premature babies developed stage 4 or stage 5 ROP. The disease regressed spontaneously in all cases and none of the infants required cryo/laser therapy. In the most premature infants, 23-26 weeks'gestation, 57% developed ROP and one developed severe ROP (stage 3). No disease more posterior to peripheral zone 2 was observed. The incidence of ROP was higher in infants exposed to greater than 21% oxygen (24.2%) than in infants who did not receive oxygen (17.8%). Oxygen, blood transfusion, and cardiopathy appear to be associated with an increased incidence of retinopathy of prematurity. CONCLUSIONS: ROP continues to be a common problem associated with prematurity in France. This study found a similar incidence of prethreshold ROP when compared to recent studies. The data showed that blood transfusion and cardiopathy may play a role in the development of ROP in premature infants.     

湖北地区早产儿视网膜病变筛查结果及相关因素分析

目的 了解湖北地区早产儿视网膜病变（ROP）的发病情况以及相关影响因素。方法 2009年7月至2011年5月对出生胎龄＜37周的313例早产儿的626只眼采用双目间接检眼镜和二代广角数码视网膜成像系统（RetcamⅡ）进行了ROP筛查。其中,男性200例, 女性113例。出生体重890～3500 g,平均出生体重（1977.37±497.03） g。出生胎龄26～37周,平均出生胎龄（33.13±2.44）周。根据筛查结果分为ROP组和无ROP组。所有ROP患儿均随访至视网膜完全血管化;如视网膜未能完全血管化则随访至视网膜情况稳定或进行激光光凝治疗。同时对两组间性别、出生胎龄、出生体重、妊娠年龄、分娩方式、试管婴儿、多胎妊娠、孕期吸氧、宫内缺氧、子痫、先兆流产、婴儿吸氧史、呼吸窘迫综合征、缺血缺氧性脑病、黄疸、蓝光照射治疗等相关因素进行统计学分析。结果313例626只眼中,ROP组52例87只眼,分别占早产儿人数及眼数的16.61%和13.90%。其中,急进性后部型ROP 2只眼;1期38只眼;2期36只眼;3期11只眼。无ROP组261人539只眼,分别占受检早产儿人数及眼数的83.39%和86.10%。接受激光光凝治疗20只眼。统计学分析结果显示,ROP组和无ROP组在出生胎龄（t=-4.348）、出生体重（t=-3.966）、婴儿吸氧史(χ2=9.05;比值比=3.403,95%可信区间1.475~7.854)间比较,差异有统计学意义（P＜0.05）。性别、妊娠年龄、分娩方式、试管婴儿、多胎妊娠、孕期吸氧、宫内缺氧、子痫、先兆流产、呼吸窘迫综合征、缺血缺氧性脑病、黄疸、蓝光照射治疗两组比较,差异无统计学意义（P＞0.05）。结论湖北地区ROP发生率为16.61％;出生胎龄、出生体重、婴儿吸氧史是影响ROP发病率的重要影响因素。     

Intravitreal bevacizumab for exudative retinal detachment post laser therapy for retinopathy of prematurity

Retinopathy of prematurity (ROP), a leading cause of pediatric blindness, predominantly affects premature and low-birth-weight infants. Although many cases are self-limiting, a minority progress to retinal detachment despite treatment. Exudative retinal detachments, although uncommon, have been reported after conventional laser therapy.^{1, 2 and 3} We report 2 cases of exudative retinal detachment after laser therapy for prethreshold and threshold ROP that responded favourably to a series of intravitreal bevacizumab injections.     

早产儿视网膜病变七年筛查治疗结果临床分析

目的 观察遵循我国早产儿视网膜病变(ROP)防治指南进行ROP筛查和及时治疗对ROP预后的影响。方法 2003~2010年7年间筛查确诊的1379例ROP患儿纳入研究。所有患儿均由经验丰富的小儿视网膜专科医生用双目间接检眼镜或二代广角数码视网膜成像系统（RetCamⅡ）检查确诊,并密切随访记录病变发展过程。对于1期病变,2周复查1次,直至病变完全退化、视网膜血管长到锯齿缘。对于2期病变或阈值前病变,1周复查1次,若病变程度下降,改为2周复查一次,直至病变完全退化。对于3期病变或怀疑急进性后部型ROP,1周复查2~3次,如达到阈值病变或阈值前病变1型,在72 h内进行激光光凝治疗。激光光凝治疗后每1~2周复查ROP变化,病变退化者随访处理,病变进展者行视网膜激光光凝或视网膜冷冻治疗,出现视网膜脱离的4、5期患者接受巩膜环扎手术、闭合式玻璃体切割手术治疗。本组患儿随访6个月~2年,平均随访时间为152.3 d。结果 7年间筛查确诊ROP 1379例2758只眼。患儿出生孕周26~35周,平均孕周30.6周。出生体重800~2200 g,平均体重1424.6 g。其中,206例400只眼达阈值病变或阈值前病变1型需进行激光光凝治疗,占患眼数的14.5%。激光光凝治疗后,345只眼病变完全退化,占治疗眼数的86.2%;55只眼进展到视网膜结构不良,占治疗眼数的13.8%。其中,10只眼仅有视盘黄斑牵引,32只眼进展至4期,13只眼进展至5期。未达到需要治疗程度的2358只患眼病变均退化。病变自然退化或干预后退化者共2703只,占98.0%;视网膜结构不良55只眼,占2.0%。其中,4期占1.2%,5期占0.5%。进展至4、5期的45只眼中,6只眼行巩膜外环扎或垫压手术治疗,视网膜均复位,但残留视盘黄斑牵引;39只眼行保留或不保留晶状体的闭合式玻璃体切割手术治疗。17只4a期患眼视网膜均复位,15只4b期患眼中10只眼视网膜复位,5只眼未复位,13只5期患眼中仅4只眼视网膜复位,1只眼视网膜大部复位。结论 及时有效的筛查和早期治疗能够减少导致视网膜结构不良的严重ROP的发生。     

早产儿视网膜病变治疗研究新进展

早产儿视网膜病变(retinopathy of prematurity,ROP)是早产儿和低体重儿发生的一种视网膜血管增生性病变,近年来随着早产儿的存活率不断提高,ROP的发生率也明显增加。以往ROP的治疗主要是在阈值期或阈值后期,给予视网膜激光及手术治疗为主,同时给予机体全身应用激素药物,因治疗时机晚,且手术风险大、并发症多,治疗效果很不理想。寻找一种在病变发生早期应用,且操作简单的安全、有效的治疗方法,已成为研究者的共识。我们就目前治疗ROP的新进展进行综述。     

Risikofaktoren und Prävention der Retinopathia praematurorum

The history of retinopathy of prematurity (ROP) gives a prime example of how dangerous the uncontrolled introduction of a new medical treatment – particularly in the field of neonatology – may be. The most important risk factors for the development of ROP are the immaturity of premature infants as well as uncontrolled and/or inadequate treatment with oxygen. In comparison to the fetus, the premature infant is exposed to a nonphysiologically high oxygen concentration. This hyperoxia leads to formation of aggressive oxygen radicals on the one hand and, on the other hand, to temporarily reduced production of growth factors such as vascular endothelial growth factor and erythropoietin, which both play an important role in the pathogenesis of ROP. The most important measure to prevent ROP is restrictive and carefully monitored oxygen treatment. Medical treatment to prevent ROP includes injection of D-penicillamine and retinol, but the available data are still limited, particularly with regard to the long-term effects of this treatment. A higher oxygenation in prethreshold ROP does not lead to recovery of ocular findings, but it increases the incidence of pulmonary complications. A reduction of light intensity in neonatal intensive care units proved not to be efficient for preventing ROP. To avoid blindness, standardized screening of the risk group is needed.     

Prospective randomized evaluation of diode-laser and cryotherapy in prethreshold retinopathy of prematurity

PURPOSE: To study the efficacy of indirect diode laser photocoagulation and cryotherapy in prethreshold retinopathy of prematurity (ROP). METHODS: Thirty-six eyes of 18 premature infants less than 34 weeks gestational age and/or less than 1600 g birth weight with prethreshold ROP were prospectively randomized to treatment with either indirect laser photocoagulation or cryotherapy. Prethreshold ROP was defined as any stage of ROP in zone I with plus disease; or stage 3 with three or more contiguous clock hours or five or more total clock hours of involvement of retina in zone II with plus disease but less than threshold disease. Regression of the ROP was assessed for a minimum period of 6 months. RESULTS: Regression of ROP occurred in all 36 eyes (100%) in both groups. CONCLUSIONS: Excellent results are achieved if ROP is treated at the prethreshold stage with both indirect laser photocoagulation and cryotherapy. Although laser has definite advantages, cryotherapy can be considered as an alternative modality of treatment in developing countries due to economic reasons.     

Retinopathy of prematurity in infants with birth weights greater than 1250 grams.

PURPOSE: To determine whether severe retinopathy of prematurity (ROP) occurs in infants whose birth weights exceed 1250 g. METHODS: We retrospectively reviewed the medical records of 1118 premature infants with birth weights > 1250 g, who were referred for screening examinations for ROP, to determine the severity of ROP observed. We then cross-tabulated these data with each infant's estimated gestational age and birth weight. Finally, we applied currently recommended screening guidelines retrospectively to determine whether they would have identified infants who had developed severe disease and who were subsequently treated. RESULTS: Stage 3 ROP was detected in infants with estimated gestational ages up to and including 32 weeks and birth weights up to and including 1874 g. A total of 26 of the participants received laser treatment for threshold ROP. Seven of these infants would not have been referred for screening according to current guidelines. CONCLUSIONS: Current screenings guidelines may fail to detect severe ROP in larger, more mature infants.     

Results of screening low-birth-weight infants for retinopathy of prematurity.

Retinopathy of prematurity (ROP) continues to be an important cause of potentially preventable blindness worldwide. The pattern of visual impairment from ROP in some middle-income countries--high rates affecting larger and more mature infants--resembles that seen in more developed countries two decades ago and has been called a "third epidemic" of the disease. Expert bodies in the United Kingdom and the United States have recently issued new guidelines for screening for ROP that utilize both birth weight and gestational age criteria. Studies in both countries suggest these criteria might be further revised to decrease time spent on screening without missing any significant disease. Population-based follow-up studies of extremely preterm infants suggest that although more preterm infants are surviving, with adequate screening and treatment, rates of blindness from ROP may be declining. Further information on the longer-term impact of ROP comes from a number of studies and particularly the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) study. The risk of both myopia and strabismus is increased with any and each higher stage of ROP. Evidence is emerging that laser therapy for threshold disease may be associated with better visual outcome than cryotherapy, although complications following the former remain a concern. The fight against ROP may be enhanced by new information on the pathogenesis, including possible genetic predisposition and the role of vascular endothelial growth factor.