Swept-source optical coherence tomography findings in premature children with a history of retinopathy of prematurity at 5 years of age / Achados de tomografia de coerência óptica swept-source em crianças de 5 anos de idade com história de retinopatia da prematuridade

ABSTRACT Purpose: To compare central foveal thickness, retinal nerve fiber layer thickness, and subfoveal choroidal thickness using swept-source optical coherence tomography in premature children with a history of treated retinopathy of prematurity (either with intravitreal bevacizumab or laser photocoagulation) or spontaneously regressed retinopathy of prematurity versus age-matched healthy children at the age of 5 years. Methods: A total of 79 children were divided into four groups: group 1, children who received intravitreal bevacizumab treatment; group 2, children who received laser photocoagulation treatment; group 3, children who had spontaneously regressed retinopathy of prematurity; and group 4, age matched, full-term healthy children. At the age of 5 years, visual functions and refractive status were assessed. The optical coherence tomography analysis was performed using swept-source optical coherence tomography (DRI-OCT Triton; Topcon, USA). Results: There were 12 (15.2%), 23 (29.1%), 30 (38%), and 14 (17.7%) children in groups 1, 2, 3, and 4, respectively. Sex distribution was similar between the groups (p=0.420). Best corrected visual acuity was significantly better in group 4 compared with groups 1, 2, and 3 (p=0.035, p=0.001, and p=0.001, respectively). Refractive error results were similar between the groups (p=0.119). Central foveal thickness was significantly higher in group 2 than in group 1 (p=0.023). There were no significant differences observed between the groups in retinal nerve fiber layer thickness and subfoveal choroidal thickness (p>0.05). Conclusions: Visual functional outcomes were better in term-born healthy children compared with those noted in children with a history of treated retinopathy of prematurity and spontaneously regressed retinopathy of prematurity. Laser treatment exerted a signifi­cant effect on central foveal thickness in premature children at the age of 5 years, as revealed by swept-source optical coherence tomography.

RESUMO Objetivo: Comparar a espessura central foveal, a da camada de fibras nervosas da retina e a da coróide subfoveal através da tomografia de coerência óptica swept-source em crianças de 5 anos de idade com história de retinopatia da prematuridade (RP) tratada com bevacizumabe intravítreo, ou com fo­tocoagulação a laser, com crianças em regressão espontânea da retinopatia da prematuridade, e com crianças saudáveis da mes­ma idade. Métodos: Um total de 79 crianças foi dividido em quatro grupos. Grupo 1: crianças que receberam tratamento com bevacizumabe intravítreo. Grupo 2: crianças que foram tratadas com fotocoagulação a laser. Grupo 3: crianças que ti­veram regressão espontânea da retinopatia da prematuridade . Grupo 4: crianças da mesma idade saudáveis e nascidas a termo. As funções visuais e o status refrativo foram avaliados aos 5 anos de idade. A análise de tomografia de coerência óptica foi feita por um dispositivo do tipo swept-source (DRI-OCT Triton; Topcon, EUA). Resultados: Haviam 12 crianças (15,2%) no grupo 1, 23 crianças (29,1%) no grupo 2, 30 crianças (38%) no grupo 3 e 14 crianças (17,7%) no grupo 4. A distribuição por sexo foi semelhante em todos os grupos (p=0,420). A acuidade visual com a melhor correção mostrou-se significativamente maior no grupo 4 em comparação com os grupos 1, 2 e 3 (respectivamente, p=0,035, p=0,001 e p=0,001). Os resultados dos erros de refração foram semelhantes em todos os grupos (p=0,119). A espessura foveal central mostrou-se significativamente maior no grupo 2 do que no grupo 1 (p=0,023). Não foram observadas diferenças significativas entre os grupos quanto à espessura da camada de fibras nervosas da retina e à espessura da coroide subfoveal (p>0,05). Conclusões: Os desfechos visuais funcionais foram melhores nas crianças saudáveis nascidas a termo, em comparação com aqueles observados nas crianças com história de retinopatia da prematuridade tratada ou com regressão espontânea. O tratamento com laser teve um efeito significativo na espessura foveal central em crianças de 5 anos de idade, nascidas prematuras, como revelado pela tomografia de coerência óptica swept-source.

Efficacy and related factors of intravitreal injection with conbercept for retinopathy of premature / 中华眼底病杂志

Objective To observe the effect ofintravitreal injection ofconbercept in the treatment of retinopathy of premature (ROP) and to analyze the factors related to the therapy.Methods A retrospective study.A total of 57 patients (57 eyes) with pre-threshold type 1 (30 patients,30 eyes),threshold ROP (21 patients,21 eyes) and acute aggressive posterior ROP (APROP,6 patients,6 eyes)) from premature infants by retinal screening in Henan Provincial People's Hospital during October 2017 and June 2018 were enrolled in this study.All children were received routinely intravitreal injected 10 mg/ml conbercept 0.025 ml (0.25 mg) within 24 hours after diagnosis.Fundus examination was performed 7 days after injection.The interval of examination was 1-3 weeks according to fundus conditions.The mean follow-up was 30.1 ± 4.6 weeks.For patients with relapse or no response to treatment,repeated intravitreal injection of conbercept or laser photocoagulation therapy was given.The retinal blood vessels of the affected eyes were observed.Logistic stepwise regression analysis was used for the correlation test of multiple factors.Results Among 57 eyes,49eyes and 8 eyes were treated with 1 or 2 times of intravitreal injection of conbercept.After 24 weeks of treatment,in 57 eyes,26 eyes were cured (45.6％),22 eyes improved (38.6％),8 eyes relapsed (14.0％),and 1 eye aggravated (1.8％).The recurrence time was 12.9± 4.5 weeks after the first injection,and the corrected gestational age was 49.0±6.7 weeks.There were significant differences in initial injection time,lesion range among the cure,improved and recurrence eyes (F=5.124,7.122;P＜0.01,＜ 0.01).Parameters of ROP condition,including ROP diagnosis (pre-threshold type 1,threshold and APROP),zone (zone 1 and 2),stage (stage 2 and 3) and plus lesions,were significant different among the cure,improved and recurrence eyes (x2=l 1.784,14.100,6.896,9.935;P＜0.01,＜0.01,＜0.05,＜0.01).Logistic stepwise regression analysis showed that the recurrence rate was correlated with ROP zone,more likely recurrence at zone 1 than zone 2 (Wald=9.879,OR=27.333,P=0.002).No injection-related complications such as endophthalmitis,cataract and glaucoma were found during treatment and follow-up period.Conclusions Intravitreal injection ofconbercept is effective in the treatment of ROP without obvious adverse reactions.Lesion zoning is associated with recurrence after treatment.

Pay attention to the outcome and the end point of anti-vascular endothelial growth factor therapy for retinopathy of prematurity / 中华眼底病杂志

In the expert consensus published by the Pediatrics in 2013,it was first proposed that anti-VEGF drugs can be considered for retinopathy ofprematurity (ROP) with stage 3,zone Ⅰ with plus disease.However,there are many problems worth the attention of ophthalmologists,including the advantages and disadvantages of anti-VEGF therapy compared with traditional laser therapy,systemic and ocular complications after anti-VEGF therapy,and what indicators are the end points of anti-VEGF therapy.Combined with this consensus and numerous research findings,we recommend that the first treatment for anti-VEGF or laser therapy should be considered from disease control effects.For the threshold and pre-threshold lesions,the effect of anti-VEGF therapy for zone Ⅱ lesions is better than that for zone Ⅰ lesions and the single-time effective rate is high.So,it is suggested that anti-VEGF therapy should be preferred for the first treatment.The choice of repeat treatment should be considered from the final retinal structure and functional prognosis.Laser therapy is advisable for the abnormal vascular regression slower and abnormalities in the posterior pole.It can reduce the number of reexaminations and prolong the interval between re-examinations.However,the premature use of laser has an inevitable effect on peripheral vision field.Excluding the above problems,supplemental therapy can still choose anti-VEGF therapy again.Most of the children with twice anti-VEGF therapy are sufficient to control the disease.Anti-VEGF therapy should be terminated when there are signs such as plus regression,threshold or pre-threshold lesions controlled without recurrence,peripheral vascularization,etc.

Current status and progress of recurrence of retinopathy in prematurity after intravitreal injection with anti-vascular endothelial growth factor drugs / 中华眼底病杂志

Intravitreal injection of anti-VEGF drugs for the treatment of retinopathy of prematurity (ROP) is a hot topic of research,and it can be used to treat the ROP (Ⅰ zone).The current anti-VEGF drugs include bevacizumab,ranibizumab,aflibercept and conbercept,etc.However,in recent years,several studies have confirmed that anti-VEGF drugs have an increased recurrence rate and a longer recurrence time than conventional laser photocoagulation therapy.The follow-up period should be extended and repeated injections may be required.Due to the lack of large-scale prospective clinical studies,the recurrence rate,time window of recurrence,risk factors and treatment methods of various anti-VEGF drugs for ROP are still unclear.Anti-VEGF drugs in the treatment of ROP needs to accumulate more evidence-based medical evidence.

Current status and progress of recurrence of retinopathy in prematurity after intravitreal injection with anti-vascular endothelial growth factor drugs / 中华眼底病杂志

Intravitreal injection of anti-VEGF drugs for the treatment of retinopathy of prematurity(ROP) is a hot topic of research, and it can be used to treat the ROP (Ⅰzone). The current anti-VEGF drugs include bevacizumab, ranibizumab, aflibercept and conbercept, etc. However, in recent years, several studies have confirmed that anti-VEGF drugs have an increased recurrence rate and a longer recurrence time than conventional laser photocoagulation therapy. The follow-up period should be extended and repeated injections may be required. Due to the lack of large-scale prospective clinical studies, the recurrence rate, time window of recurrence, risk factors and treatment methods of various anti-VEGF drugs for ROP are still unclear. Anti-VEGF drugs in the treatment of ROP needs to accumulate more evidence-based medical evidence.

The vascularization process after intravitreal ranibizumab injections for aggressive posterior retinopathy of prematurity / Processo de vascularização após injeções intravítreas de ranibizumab para retinopatia da prematuridade posterior agressiva

ABSTRACT Purpose: To evaluate the retinal vascularization process after intravitreal ranibizumab was administered to infants with aggressive posterior retinopathy of prematurity (AP-ROP). Methods: Twenty-six eyes of 13 infants with AP-ROP who received 0.25 mg intravitreal ranibizumab were retrospectively investigated. The patients were evaluated at weekly follow-up visits, and the findings were analyzed after retinal vascularization was complete. Results: The results showed regression in the AP-ROP of all the patients within the first 48-72 h. Average time for complete vascularization of the nasal quadrant (zone II) was postmenstrual week 45 (range 41-56), and vascularization of the temporal quadrant (zone III) was completed in the postmenstrual week 56 (range 50-65). Reactivation was observed in seven patients, on average at postmenstrual week 42; two of these patients underwent additional treatment. Two patients presented with avascular areas in the peripheral retina despite being 1 year old. Conclusion: These results showed that retinal vascularization following intravitreal ranibizumab was completed after a delay in patients with AP-ROP. Further studies are necessary to evaluate when and how vascularization occurs after intravitreal anti-vascular endothelial growth factor treatments.

RESUMO Objetivo: Avaliar o processo de vascularização da retina após injeção intravítrea de ranibizumab aplicada em crianças com retinopatia da prematuridade posterior agressiva (AP-ROP). Métodos: Vinte e seis olhos de 13 crianças com AP-ROP que receberam 0,25 mg de ranibizumab intravítreo foram investigados retrospectivamente. Os resultados foram avaliados após a completa vascularização da retina, observada em acompanhamentos semanais. Resultados: Verificou-se que houve regressão na AP-ROP de todos os pacientes durante as primeiras 48 a 72 horas. Na média, a vascularização do quadrante nasal (zona II) foi concluída na semana 45 pós-menstrual (variação 41-56), enquanto a vascularização do quadrante temporal (zona III) foi concluída na semana 56 pós-menstrual (variação 50-65). Sete pacientes (7/13) apresentaram reativação, que aconteceram em média a 42,14 semanas pós-menstruais, dois pacientes receberam tratamento adicional. Dois pacientes apresentaram áreas avasculares na retina periférica apesar de terem um ano de idade. Conclusões: O presente estudo mostrou que a vascularização da retina após a injeção intravítrea de ranibizumab foi concluída com atraso na AP-ROP. Ensaios clínicos randomizados são necessários para avaliar quando e como a vascularização acontece após tratamentos com injeções intravítreas de anti-VEGF.

Screening and treatment of retinopathy of prematurity: current status, problems and prospects in China / 中华眼底病杂志

Early detection and timely treatment hold the key to cure retinopathy of prematurity (ROP).ROP screening is carried out unevenly in China.Examination equipments and personnel experiences are the major factors to constraint ROP screening.In addition to strengthening personnel training,it is necessary to establish a standard guideline and pipeline for ROP consultation and referral. Laser photocoagulation and cryotherapy are the first options for the threshold ROP and Type 1 pre-threshold ROP.Scleral buckling or vitrectomy is needed for advanced ROP when retinal detachment occurs. The clinical efficacy of intravitreal injection of bevacizumab (an anti-vascular endothelial growth factor monoclonal antibody) for severe ROP is encouraging,but needs further verification.Genetic interference and stem cell therapy will be the prosperous futures in the treatment of ROP.The screening and treatment of ROP in China is becoming more common and improved,but it is still a long way to go considering the huge population of China.

The inhibitory effect of Bevacizumab on retinal neovascularization in oxygen-induced retinopathy in the mouse / 中华眼底病杂志

Objective To observe the inhibitory effect of Bevacizumab on retinal neovascularization in oxygen-induced retinopathy in the mouse. Methods 90 one-week-old C57BL/6J mice were divided into four groups at random.15 mice in the 1st group as normal control group,15 mice in the 2nd group as oxygen control group,30 mice in the 3rd group as high-dose Bevacizumab treatment group,30 mice in the 4th group as low-dose Bevacizumab treatment group.The 2nd,3rd and 4th groups were exposed to 75%oxygen for 5 days and then to room air.At the 12th day,One eye of each mouse of two control groups were received an intravitreal injection with Bevacizumab at 2μl、1μl respectively,and the same volume of BSS was injected into the other eye of the mice.The adenosine diphosphatase(ADPase)histochemical technique was used for retinal flat mount to assess the oxygen-induced changes of retinal vessels.The number of the endothelium cell nuclei of proliferative neovascularization was quantified by retinal microtome chromoscopy.Real-time PCR analysis was performed to examine the expression of VEGF mRNA. Results Comparing with oxygen control group,regular distributions,reduced density of retinal vascular and reduced endothelium cell nuclei which extending retinal membrane were observed in the treatment groups(P＜0.001).But the differences between two treatment groups are not statistically significant(P＞0.05).The expression of VEGF mRNA was not significantly different in oxygen control group whatever it whether accepted Bevacizumab treatment or high or low dose(P＞0.05). Conclusion Intravitreal injection with Bevacizumab can effectively inhibits the retinal neovascularization in oxygeninduced retinopathy in the mouse.Intravitreal injection with Bevacizumab might become to the new method to treat retinopathy of premature.