DISCUSSION

    ROP was first reported in 1942 by Terry, who published a description of the histological findings of what would now be considered end-stage cicatricial disease[11,12]. In its advanced forms, it can result in severe visual impairment or blindness, affecting the normal motor, language, conceptual, and social development of the child and having a high financial cost for the community[13].

    Programs for the prevention of blindness from ROP were initiated in many countries beginning in the 80's when the Cryotherapy for Retinopathy of Prematurity Cooperative Group(Cryo-ROP) demonstrated the first positive results from the treatment of this disease with cryotherapy[7,14-18]. This large study set the incidence of ROP in some degree at 65.8% considering all patients and in 81.6% considering all children born with less than 1 000g[19].

    Larsson et al [20]. published the development of ROP in 25.5% of the 392 children prospectively studied in Stockholm, Sweden between 1998 and 2000 and also the appearance of stage 3 of ROP in 11.7%. Also in Europe, a retrospective study was published in 2002 about 194 children born prematurely with less than 1 500g or with less than 32 weeks of GA from 1992 to 2000. In this population, stages 1 and 2 occurred in 26.3% and only 2.5% of those examined needed cryotherapy[21].

    At John Dempsey Hospital from the University of Connecticut School of Medicine, USA, between 1989 and 1997, the data of 950 newborns were evaluated retrospectively. The authors obtained 21.3% of ROP considering all stages and only 4.6% of the children examined reached stage 3 of ROP or more. This study also determined that none of the children born with more than 1 000g or with more than 28 weeks of GA developed stages of ROP that would need intervention by laser or by surgery[22].

    In Brazil, the study by Graziano et al.[23] published in 1997, analyzed retrospectively the data from 102 premature infants born with less than 1 500g from January 1992 to December 1993 and detected a percentage of 29.1% of ROP including all stages. This work stands out due to the very high prevalence of ROP (78.5%) in the group of patients with BW less than 1 000g and 72.7% in infants born with GA of less than 30 weeks. The authors concluded that the children of lower BW or GA (below 1 000 g or below 28 weeks) have a greater risk of developing ROP in stage 3 or more.

    Our findings confirmed the high incidence of ROP(42.5%) and threshold disease in the extremely premature group. In HCPA, the survival rate among ELBW infants was estimated over 33.7% and 70.1% in the VLBW. In the present study, ROP at any stage affected 42.5% of the ELBW and only 16.2% of the VLBW infants and threshold disease, needing laser treatment, occurred in 17 patients and, among of them, 14 were included in the ELBW group.

    Chen et al. [24] in China (2006) reported that the mean GA of all the children reaching higher stages of ROP was 29.8 weeks (SD 1.9 weeks, range 26-34 weeks) and the mean BW was 1 432g (SD 319 g, range 760-2 500g) and that 31 babies of all 114 treated babies had BW more than 1 500g and the authors call attention to the fact of in China many bigger and more mature babies are developing severe and treatable ROP stages. These results differ in many aspects form the number related in our cohort of patients from Brazil.

    In the management of ROP, several studies have demonstrated laser photocoagulation to be as effective as cryotherapy in reducing the incidence of unfavourable structural outcome and nowadays most of the specialized centers in the treatment of ROP use the transpupillary photocoagulation by argon or diode laser applied by binocular indirect ophthalmoscopy as the best of the alternatives for treatment[25-27].

    In our study, the 17 patients with threshold disease were considered for treatment with approximately 800 confluent laser spots at the peripheral avascular retina in each eye. The treatment regressed the disease in all treated patients despite of 17.6% laser re-treatment required. Some reasons for this high re-treatment level in patients with posterior Zone II threshold disease could be explained by the low number of laser spots applied to each eye.

    Bannach in 2000 and Rezai in 2005, published that the near confluent pattern of laser photocoagulation may reduce the rate of progression of threshold ROP in Zone II. The near confluent pattern with approximately 1200 laser spots may also reduce the re-treatment rate of the disease, but larger studies are needed to confirm these findings[28-29].

    McNamara et al.[30] analyzed in 1993, the complications of the laser photocoagulation treatment in ROP and showed mainly complications restricted to the anterior segment, as corneal edema, iris damage, lens damage and cataract formation. Most of the related complications at the anterior segment were observed after argon laser therapy and none with diode laser therapy. Retinal and choroidal hemorrhages, choroidal neovascularization, epi-retinal membrane formation and later retinal detachment were the main complications associated with the diode laser treatment for ROP. None of the 16 patients treated in the HCPA showed any of these complications.

    The objective of the systemic care of the newborns in the risk group for the development of ROP is to determine the adequate moment for treatment. In our study all neonates were treated in threshold disease once, classically, the threshold disease is considered the right moment to treat, but recently, the results of a new multi centric and prospective clinical trial(The Early Treatment for ROP Cooperative Group) showed that treatments at the prethreshold disease significantly reduced unfavorable outcomes in both primary and secondary (structural) measures. These new results can induce the clinicians all over the world to treat the disease at the prethreshold moment[31].

    Our study also suggests a higher risk for myopia (especially on ROP group that was submitted to retinal photocoagulation) and retinal changes among patients treated after developed ROP. The association between myopia and ROP has been recognized for many years occurring mainly after cryotherapy but also after the laser photocoagulation in spite of the laser produces less myopic shift[25].

    Theng et al.[32]reported in 2000 that in Caucasian populations, premature infants with ROP have higher risks of developing refractive errors and strabismus. The risk of ROP was higher with lower BW and earlier GA. At 1-year follow-up, the rate of myopia was 33.3% in babies with ROP compared to 3.7% in babies with no ROP (P <0.001). The higher rates of myopia in babies with ROP remained with longer follow-up (33.3% and 25.0% in ROP group versus 3.4% and 3.8% in no ROP group, at 2 and 3 years respectively). These results look very similar with our observations in our follow-up cohort of 91 patients at HCPA, where at six-month of corrected age, patients who developed ROP were significantly more myopic (31.0%) than those who didn't (3.3%).

    The results here presented in threshold disease are in agreement with other studies published in the literature in spite of the paper from Davitt et al.[33] from the Early Treatment for ROP Cooperative Group that demonstrated that the early treatment at a high-risk prethreshold did not raise the risk of developing myopia compared with conventional management. Previous results from the multicenter study of Cryotherapy for ROP(Cryo-ROP) demonstrated that anisometropia, astigmatism, and presence of posterior pole residua from ROP are associated with high incidence of myopia (≥5.0 Diopters). However, when results from treated versus control eyes were compared, there was little change in the distribution of the refractive error in treated or control eyes between 1 year and 10 years of age[33-34].

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