Combination of Ranibizumab and Dexamethasone intravitreal implant for macular edema secondary to retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the differences in the efficacy and safety of combination of intravitreal dexamethasone(Ozurdex)and ranibizumab or monotherapy of ranibizumab in eyes with macular edema secondary to retinal vein occlusion(RVO-ME).METHODS: Patients diagnosed with non-ischemic RVO-ME by fluorescein fundus angiography in our hospital from June 2020 to December 2022 were selected. All patients were initially treated with intravitreal injection of ranibizumab(0.5 mg), and 42 patients(42 eyes)who had central retinal thickness(CRT)≥300 μm after 2 wk were included. They were randomly divided into combined treatment group and monotherapy group. The combined treatment group(21 eyes)received Ozurdex intravitreal injection immediately, while the monotherapy group(21 eyes)was treated with ranibizumab intravitreal injection by 3+pro re nata(PRN). The changes of best corrected visual acuity(BCVA), CRT, and intraocular pressure before and at 2 wk, 1, 2, 3, 4, 5, and 6 mo after treatment were recorded, and the ocular or systemic complications were observed.RESULTS:The BCVA and CRT of all patients at 2 wk, 1, 2, 3, 4, 5, and 6 mo after treatment were significantly better than those before treatment(all P<0.01). There were statistical significance in the BCVA and CRT between two groups at 2 and 3 mo after treatment(all P<0.05). The most significant increase of BCVA in the combined treatment group occurred at 2 mo after treatment. The mean recurrence time of macular edema in the monotherapy group was 1.45±0.53 mo, with 4.21±0.78 injection times of ranibizumab. None of the patients showed serious complications after treatment. The most common complications in the combined treatment group were subconjunctival hemorrhage and elevated intraocular pressure, which were manageable with topical ocular hypotensive agents, and no patient required antiglaucoma or cataract surgery.CONCLUSION: Compared with monotherapy of ranibizumab, intravitreal injection of dexamethasone combined with ranibizumab can significantly improve the visual acuity and effectively reduce the macular edema in the treatment of RVO-ME, with a long duration of efficacy and less intravitreal injection of drugs.

Efficacy of a biosimilar ranibizumab monotherapy for the treatment of retinopathy of prematurity

Purpose: To evaluate the efficacy of a biosimilar ranibizumab (Razumab) on outcomes of retinopathy of prematurity (ROP) for the first time. Methods: This retrospective study included infants presenting with stage 3+ ROP either in zone 1 or zone 2 posterior or aggressive posterior ROP (APROP). All eligible infants received intravitreal razumab (0.25 mg/0.025 ml) monotherapy. Follow?up was continued monthly till complete retinal vascularization was achieved while retreatment with razumab was given when recurrent neovascularization was noted. In case of no recurrence but incomplete vascularization, laser photocoagulation was done to the residual avascular retina. Results: We included 118 eyes of 59 infants with a median gestational age of 30 weeks and median birth weight of 1250 grams. At presentation, APROP was found in 28 eyes (24%) of 14 babies while stage 3 disease was seen in zone 1 in another 28 eyes (24%) and the remaining 62 eyes (52%) had stage 3 ROP in zone 2 posterior region. Complete resolution of ROP along with complete vascularization was seen in 22 eyes (19%) at a median of 55 days (IQR = 31–56 days) and 42 eyes (35%) showed a recurrent neovascularization at a median of 51 days post razumab (IQR = 42– 55 days). The cumulative incidence of recurrence of neovascularization (21%, 95% CI = 14%–29%) peaked at seven weeks and was significantly higher in eyes with APROP (43%, 95% CI = 27%–63%) compared to eyes without APROP (13.4%, 95%CI, 8%?22%) (P < 0.001). Conclusion: Razumab appears to be safe and effective in treating ROP, with about a third requiring reinjection at seven weeks after the first dose.

Retinopatía de la prematuridad agresiva posterior / Aggressive Posterior Retinopathy of Prematurity

Introducción: La retinopatía del prematuro es una enfermedad ocular provocada por una alteración en la vasculogénesis de la retina, que lleva a la pérdida parcial o total de la visión. Objetivo: Presentar el primer caso, en la provincia de Santa Clara, de retinopatía de la prematuridad agresiva posterior y el tratamiento realizado. Presentación del caso: Niña prematura con más de 5 factores de riesgo al nacer que presentó retinopatía de la prematuridad agresiva posterior y se le realizó tratamiento con bevacizumab intravítreo. Conclusiones: La evolución de la niña en un período de un 1 año resultó satisfactoria con regresión total de la enfermedad. El tratamiento establecido constituye un método alternativo con buenos resultados en algunas condiciones específicas como la retinopatía del prematuro agresiva posterior(AU)

Introduction: Retinopathy of prematurity is an ocular disease caused by an alteration in retinal vasculogenesis, leading to partial or total loss of sight. Objective: To present the first case, in the province of Santa Clara, of aggressive posterior retinopathy of prematurity and the treatment performed. Case presentation: Premature girl with more than 5 risk factors at birth who presented aggressive posterior retinopathy of prematurity and was treated with intravitreal bevacizumab. Conclusions: The evolution of the girl in a period of 1 year was satisfactory with total regression of the disease. The established treatment constitutes an alternative method with good results in some specific conditions such as aggressive posterior retinopathy of prematurity(AU)

Micropulse laser combined with intravitreal injection of Ranibizumab in the treatment of macular edema secondary to non-ischemic branch retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the efficacy of micropulse laser combined with intravitreal injection of ranibizumab in the treatment of macular edema(ME)secondary to non-ischemic branch retinal vein occlusion(BRVO).METHODS: A total of 200 cases(200 eyes)of non-ischemic BRVO secondary to ME who were treated in our hospital from January 2020 to March 2022 were selected and divided into the control group(100 cases, 100 eyes)and the observation group(100 cases, 100 eyes)by random number table. The control group was given intravitreal injection of ranibizumab, and the observation group was given micropulse laser combined with intravitreal injection of ranibizumab. The best corrected visual acuity(BCVA), central macular thickness(CMT), subfoveal choroidal thickness(SFCT), total number of injections, macular leakage and complications were compared between two groups.RESULTS: After treatment, the BCVA of the two groups were improved, and the BCVA of the observation group was better than those in the control group at 1, 3, 6 and 12mo after treatment(all P&#x0026;#x003C;0.05). After treatment, the CMT and SFCT of the two groups decreased, and the CMT and SFCT of the observation group was lower than those in the control group at 1, 3, 6 and 12mo after treatment(all P&#x0026;#x003C;0.05). The total number of injections in the observation group during the treatment period was less than that in the control group [(4.06±1.12)times vs.(5.32±1.15)times](t=5.852, P&#x0026;#x003C;0.001). The leakage rates of the control group and the observation group after 12mo of treatment were 69.0% and 27.0% respectively, with statistical significance between the two groups(χ2=35.337, P&#x0026;#x003C;0.001). The incidence of complications in the control group and observation group were 11.0% and 5.0% respectively, with no statistical significance between the two groups(χ2=2.446, P=0.118).CONCLUSION: Micropulse laser combined with intravitreal injection of ranibizumab has a significant clinical efficacy in the treatment of ME secondary to non-ischemic BRVO, which is safe and can improve patients' vision and ME, reduce the total doses of ranibizumab without increasing the incidence of complications.

Clinical analysis and curative effect of reactivation of retinopathy of prematurity after intravitreous injection of ranibizumab / 中华眼底病杂志

Objective:To observe the clinical characteristics and therapeutic effect of reactivation of retinopathy of prematurity (ROP) patients after intravitreal injection of ranibizumab (IVR).Methods:A retrospective case series study. Eleven children with ROP (21 eyes) who were reactivated after IVR in Shenzhen Eye Hospital from January 2019 to October 2021 were included in the study. Among them, there were 6 males (11 eyes) and 5 females (10 eyes), with the gestational age of (27.6±2.2) weeks and birth weight of (1 034.6±306.5) g. At the first IVR treatment, 14 eyes (63.7%, 14/22) had acute ROP (AROP), 8 eyes (36.3%, 8/22) had threshold lesions. Post-reactivation treatments include IVR, retinal laser photocoagulation (LP), or minimally invasive vitrectomy (MIVS). The follow-up time after treatment was 12 to 18 months. Birth gestational age, birth weight, treatment method, corrected gestational age at treatment, lesion stage before and after treatment, lesion reactivation and regression time were recorded. The clinical characteristics and efficacy were observed and analyzed.Results:The time from initial IVR treatment to reactivation was (8.2±3.5) weeks. The corrected gestational age of the child was (43.62±4.08) weeks. In 21 eyes, AROP, threshold lesion, prethreshold lesion, and stage 4 lesion were in 2, 4, 12, and 3 eyes, respectively. The patients were treated with IVR, LP, IVR+LP, IVR+MIVS in 2, 13, 4 and 2 eyes, respectively. After the first reactivation treatment, the time of regression and stability was (8.4±4.9) weeks after treatment. There were 5 eyes with secondary reactivation of the lesion, and the lesion stages were stage 3, stage 4a and stage 5 in 2, 1 and 2 eyes, respectively. The mean reactivation time was (19.3±6.0) weeks after the last treatment. The patients in stage 3, stage 4a and stage 5 were treated with LP, LP+MIVS and IVR, respecitively, and the lesions subsided steadily during follow-up. At the last follow-up, 19 out of 21 eyes showed complete regression of the lesions, stable photocoagulation, regression of crista-like lesions, no additional lesions, and retinal leveling. All retinal detachment was "funnel-shaped" in 2 eyes.Conclusions:The lesion reactivation of AROP after IVR treatment is more common. The early reactivation rate is higher after treatment. There is a possibility of reactivation twice after re-treatment.

Establishment and validation of nomogram model for visual prognosis of macular edema secondary to retinal branch vein occlusion treated with ranibizumab / 中华眼底病杂志

Objective:To explore the influencing factors of visual prognosis of macular edema secondary to branch retinal vein occlusion (BRVO-ME) after treatment with ranibizumab, and construct and verify the nomogram model.Methods:A retrospective study. A total of 130 patients with BRVO-ME diagnosed by ophthalmology examination in the Department of Ophthalmology, Liuzhou Red Cross Hospital from January 2019 to December 2021 were selected in this study. All patients received intravitreal injection of ranibizumab. According to the random number table method, the patients were divided into the training set and the test set with a ratio of 3:1, which were 98 patients (98 eyes) and 32 patients (32 eyes), respectively. According to the difference of logarithm of the minimum angle of resolution (logMAR) best corrected visual acuity (BCVA) at 6 months after treatment and logMAR BCVA before treatment, 98 patients (98 eyes) in the training set were divided into good prognosis group (difference ≤-0.3) and poor prognosis group (difference >-0.3), which were 58 patients (58 eyes) and 40 patients (40 eyes), respectively. The clinical data of patients in the two groups were analyzed, univariate and multivariate logistic regression analysis were carried out for the different indicators, and the visualization regression analysis results were obtained by using R software. The consistency index (C-index), convolutional neural network (CNN), calibration curve and receiver operating characteristic (ROC) curve were used to verify the accuracy of the nomogram model.Results:Univariate analysis showed that age, disease course, outer membrane (ELM) integrity, elliptical zone (EZ) integrity, BCVA, center macular thickness (CMT), outer hyperreflective retinal foci (HRF), inner retina HRF, and the blood flow density of retinal deep capillary plexus (DCP) were risk factors affecting the visual prognosis after treatment with ranibizumab in BRVO-ME patients ( P<0.05). Multivariate logistic regression analysis showed that course of disease, ELM integrity, BCVA and outer HRF were independent risk factors for visual prognosis after ranibizumab treatment for BRVO-ME patients ( P<0.05). The ROC area under the curve of the training set and the test set were 0.846[95% confidence interval ( CI) 0.789-0.887) and 0.852 (95% CI 0.794 -0.873)], respectively; C-index were 0.836 (95% CI 0.793-0.865) and 0.845 (95% CI 0.780-0.872), respectively. CNN showed that the error rate gradually stabilized after 300 cycles, with good model accuracy and strong prediction ability. Conclusions:Course of disease, ELM integrity, BCVA and outer HRF were independent risk factors of visual prognosis after ranibizumab treatment in BRVO-ME patients. The nomogram model based on risk factors has good differentiation and accuracy.

Clinical characteristics and effect of anti-vascular endothelial growth factor therapy in retinopathy of prematurity in Sichuan province / 中华眼底病杂志

Objective:To analyze the clinical characteristics and evaluate the effect and safety of anti-vascular endothelial growth factor (VEGF) therapy in retinopathy of prematurity (ROP) in Sichuan province.Methods:A retrospective study. From January 2013 to January 2022, 156 patients (306 eyes) with ROP who received intravitreal anti-VEGF therapy for the first time in the Department of Ophthalmology, West China Hospital of Sichuan University were selected. According to the type of anti-VEGF drugs, the children were divided into intravitreal injection of ranibizumab (IVR) group and intravitreal injection of conbercept (IVC) group; IVC group was divided into hospital group and referral group according to the different paths of patients. After treatment, the patients were followed up until the disease degenerated (vascular degeneration or complete retinal vascularization) or were hospitalized again for at least 6 months. If the disease recurred or progressed, the patients were re-admitted to the hospital and received anti-VEGF drug treatment, laser treatment or surgical treatment according to the severity of the disease. Clinical data of these children was collected, including general clinical characteristics: gender, gestational age at birth (GA), birth weight (BW), history of oxygen inhalation; pathological condition: ROP stage, zone, whether there were plus lesions; treatment: treatment time, postmenstrual gestational age at the time of the first anti-VEGF drug treatment; prognosis: re-treat or not, time of re-treatment, mode of re-treatment; adverse events: corneal edema, lens opacity, endophthalmitis, retinal injury, and treatment-related systemic adverse reactions. The measurement data between groups were compared by t test, and the count data were compared by χ2 test or rank sum test. Results:Of the 306 eyes of 156 children with ROP, 74 were male (47.44%, 74/156) and 82 were female (52.56%, 82/156). Each included child had a history of oxygen inhalation at birth. The GA was (28.43±2.19) (23.86-36.57) weeks, BW was (1 129±335) (510-2 600) g, and the postmenstrual gestational age was (39.80±3.04) (31.71-49.71) weeks at the time of the first anti-VEGF drug treatment. All patients were diagnosed as type 1 ROP, including 26 eyes (8.50%, 26/306) of aggressive ROP (A-ROP), 39 eyes (12.74%, 39/306) of zone Ⅰ lesions, and 241 eyes (78.76%, 241/306) of zone Ⅱ lesions. The children were treated with intravitreal injection of anti-VEGF drugs within 72 hours after diagnosis. Among them, 134 eyes (43.79%, 134/306) of 68 patients were treated with IVR, and 172 eyes (56.21%, 172/306) of 88 patients were treated with IVC. In IVC group, 67 eyes of 34 patients (38.95%, 67/172) were in the hospital group and 105 eyes of 54 patients (61.05%, 105/172) were in the referral group. 279 eyes (91.18%, 279/306) were improved after one treatment, 15 eyes (4.90%, 15/306) were improved after two treatments, and 12 eyes (3.92%, 12/306) were improved after three treatments. The one-time cure rate of IVR group was lower than that of IVC group, but the difference was not statistically significant ( χ2=1.665, P=0.197). In different ROP categories, IVC showed better therapeutic effect in A-ROP, and its one-time cure rate was higher than that in IVR group, with statistically significant difference ( χ2=7.797, P<0.05). In the hospital group of IVC group, the GA, BW and the postmenstrual gestational age at first time of anti-VEGF drug treatment were lower than those in the referral group, and the difference was statistically significant ( t=-2.485, -2.940, -3.796; P<0.05). The one-time cure rate of the hospital group and the referral group were 94.94%, 92.38%, respectively. The one-time cure rate of the hospital group was slightly higher than that of the referral group, but the difference was not statistically significant ( χ2=0.171, P=0.679). In this study, there were no ocular and systemic adverse reactions related to drug or intravitreal injection in children after treatment. Conclusions:Compared with the characteristics of ROP in developed countries, the GA, BW and postmenstrual gestational age of the children in Sichuan province are higher. Both IVR and IVC can treat ROP safely and effectively. There is no significant difference between the two drugs in the overall one-time cure effect of ROP, but IVC performed better in the treatment of A-ROP in this study.

Pediatric Coats disease of stage 2 and greater managed with 532 nm wavelength laser using indirect ophthalmoscope combined with ranibizumab / 中华眼底病杂志

Objective:To investigate the efficacy of 532 nm wavelength laser using indirect ophthalmoscope combined with ranibizumab (IVR) in treating stage 2 and greater pediatric Coats disease.Methods:A retrospective, non-controlled clinical study. From February 2018 to August 2020, 21 eyes of 21 patients with Coats disease stage 2 and greater diagnosed by examination in the Eye Center of Beijing Tongren Hospital were included in the study. Among them, 20 patients were males; 1 patient was female. Mean age was 5.00±1.92 years old. Stage 2A, 2B, 3A, 3B, and 4 were 2, 8, 7, 2, and 2 eyes, respectively. All eyes underwent wide-field fundus color photography and fluorescein fundus angiography (FFA). Best corrected visual acuity (BCVA) was performed in 17 eyes. Abnormal dilated retinal blood vessels, interretinal and subretinal exudates were found in all eyes. Abnormally dilated capillaries and aneurysms in the retina was shown in FFA examination. All eyes underwent 532 nm laser photocoagulation using indirect ophthalmoscope combined with IVR. Patients with severe retinal detachment of stage 3B or greater were treated by external drainage of subretinal fluid (SRF). The subsequent treatment was the same as before. The follow-up time was 35.67±6.13 months. Relevant examinations were performed using the same equipment and methods before. The frequency of treatment, visual acuity changes, anatomic prognosis, and complications were observed.Results:The frequency of eye photocoagulation was 2.43±0.98. The number of IVR treatments was 2.00±0.89. Three eyes were treated with SRF drainage in the first time. At the last follow-up, visual acuity improved, no change, and decreased in 5, 11, and 1 eyes after BCVA examination, respectively. In 21 eyes, the retina was in situ in 17 eyes; 5 eyes with retinal cysts. During the follow-up, cataract and vitreous hyperplasia occurred in 1 eye, which was treated by vitrectomy, and mild vitreous hyperplasia occurred in 1 eye.Conclusion:Indirect ophthalmoscope 532 nm wavelength laser combined with IVR is an effective treatment for pediatric Coats disease.

Anti-vascular endothelial growth factor treatment in X-linked retinoschisis with vitreous hemorrhage / 中华眼底病杂志

Objective:To review the outcome of intravitreous anti-vascular endothelial growth factor (VEGF) treatment in patients with X-linked retinoschisis (XLRS) complicated with vitreous hemorrhage (VH).Methods:A retrospective clinical study. From March 1, 2016 to April 1, 2022, 18 patients (19 eyes) diagnosed with XLRS complicated with vitreous hemorrhage in Beijing Tongren Hospital, Capital Medical University of Eye Center were included. All the patients were male, with a median age of 7.05±3.8 years. Best corrected visual acuity (BCVA) and wide-angle fundus photography were performed in all the patients. BCVA was carried out using international standard visual acuity chart, and converted into logarithm of minimum resolution angle (logMAR) in statistics analysis. According to whether the patients received intravitreal injection of ranibizumab (IVR), the patients were divided into injection group and observation group, with 11 eyes in 10 cases and 8 eyes in 8 cases, respectively. In the injection group, 0.025 ml of 10 mg/ml ranibizumab (including 0.25 mg of ranibizumab) was injected into the vitreous cavity of the affected eye. Follow-up time after treatment was 24.82±20.77 months. The VH absorption time, visual acuity changes and complications were observed in the injection group after treatment. Paired sample t test was used to compare BCVA before and after VH and IVR treatment. Independent sample t test was used to compare the VH absorption time between the injection group and the observation group. Results:LogMAR BCVA before and after VH were 0.73±0.32 and 1.80±0.77, respectively. BCVA decreased significantly after VH ( t=-3.620, P=0.006). LogMAR BCVA after VH and IVR were 1.87±0.55 and 0.62±0.29, respectively. BCVA was significantly improved after IVR treatment ( t=6.684, P<0.001). BCVA records were available in 5 eyes before and after IVR, and the BCVA values after VH and IVR were 0.58±0.31 and 0.48±0.20, respectively, with no statistically significant difference ( t=1.000, P=0.374). BCVA increased in 1 eye and remained unchanged in 4 eyes after treatment. BCVA records were available in 5 eyes before VH and after VH absorption in the 8 eyes of the observation group. LogMAR BCVA before VH and after VH absorption were 0.88±0.28 and 0.90±0.26, respectively, with no significant difference ( t=-1.000, P=0.374). After VH absorption, BCVA remained unchanged in 4 eyes and decreased in 1 eye. The absorption time of VH in the injection group and the observation group were 1.80±1.06 and 7.25±5.04 months, respectively. The absorption time of VH was significantly shorter in the injection group than in the observation group, the difference was statistically significant ( t=-3.005, P=0.018). Multivariate linear regression analysis showed that IVR treatment was significantly correlated with VH absorption time ( B=-6.66, 95% confidence interval -10.93--2.39, t=-3.40, P=0.005). In the injection group, VH recurrence occurred in 1 eye after IVR treatment. Vitrectomy (PPV) was performed in one eye. In the 8 eyes of the observation group, VH recurrence occurred in 2 eyes, subsequent PPV in 1 eye. The rate of VH recurrence and PPV was lower in the injection group, however, the difference was not statistically significant( P=0.576, 1.000). In terms of complications, minor subconjunctival hemorrhage occurred in 2 eyes and minor corneal epithelial injury occurred in 1 eye in the injection group, and all recovered spontaneously within a short time. In the injection group, 9 eyes had wide-angle fundus photography before and after IVR treatment. There was no significant change in the range of peripheral retinoschisis after treatment. No obvious proliferative vitreoretinopathy, infectious endophthalmitis, retinal detachment, macular hole, complicated cataract, secondary glaucoma or other serious complications were found in all the treated eyes, and there were no systemic complications. Conclusion:Intravitreous anti-VEGF treatment may accelerate the absorption of vitreous hemorrhage in patients with XLRS. No impact is found regarding to the peripheral retinoschisis.

Efficacy of Aflibercept and Ranibizumab in the treatment of diabetic macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the efficacy of aflibercept and ranibizumab in the treatment of diabetic macular edema(DME).METHODS: Prospective randomized controlled trial. A total of 35 patients(60 eyes)with non-proliferative diabetic retinopathy complicated with DME confirmed in our hospital from June 2020 to September 2021 were included. Intravitreal injection was performed using the 3+PRN protocol in all cases, of which 17 cases(30 eyes)received aflibercept treatment(aflibercept group)and 18 cases(30 eyes)received ranibizumab(ranibizumab group). The two groups were followed up for 12mo, observing the central macular thickness(CMT)and the best corrected visual acuity(BCVA)of the two groups, and recording the number of intravitreal injections and the occurrence of complications.RESULTS: After treatment, CMT and BCVA in the aflibercept group were significantly better than that in the ranibizumab group at 1, 3, 6 and 12 mo(all P&#x003C;0.001). During the follow-up period, the number of intravitreal injections in the aflibercept group was lower than that in the ranibizumab group(4.23±0.86 vs. 6.40±0.97, P&#x003C;0.05), there were no serious complications such as drug-related adverse reactions, intraocular infection, and vascular embolism in either group.CONCLUSION: Both aflibercept and ranibizumab have clear efficacy and safety in the treatment of DME, and aflibercept may be a more effective and convenient treatment option than ranibizumab for DME patients.

Effect of repeated intravitreal Ranibizumab and Aflibercept injections on the corneal nerves in patients with macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of repeated intravitreal injection of ranibizumab and aflibercept on corneal nerve of patients with macular edema.METHODS: A total of 64 patients(64 eyes)enrolled in our hospital from June 2021 to June 2022 were treated with intravitreal injection of anti-vascular endothelial growth factor(VEGF). There were 20 cases(20 eyes)of diabetic macular edema, 19 cases(19 eyes)of wet age-related macular degeneration and 25 cases(25 eyes)of retinal vein occlusion. Corneal confocal microscope was used to collect images of corneal subbasal nerve plexus before injections and at 1mo after each intravitreal injection based on 3+pro re nata(PRN)treatment regimen. Furthermore, the length and density of corneal nerve were measured.RESULTS: There was no significant difference in corneal nerve density of patients injected with aflibercept between pre-injection and post-injection(P&#x003E;0.05), while the corneal nerve length after 2nd and 3rd injections was lower than that of pre-injection(all P&#x003C;0.01). There were no significant changes in corneal nerve density and length in patients with intravitreal injections of ranibizumab(all P&#x003E;0.05), and there was no significant differences in corneal nerve density and length after 3 injections of the two drugs(all P&#x003E;0.05).CONCLUSION: Repeated intravitreal anti-VEGF drug may affect corneal nerve to some extent. For patients who need repeated intravitreal injections of anti-VEGF, attention should be paid to the changes of corneal nerves.

Effects of Ranibizumab on ocular biological parameters in the treatment of retinopathy of prematurity / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of intravitreal ranibizumab injection on ocular parameters in the treatment of retinopathy of prematurity(ROP), and analyze its relationship with birth weight(BW)and postmenstrual age(PMA).METHODS: A total of 98 premature infants who received routine ROP screening at Northwest Women's and Children's Hospital from January 1, 2016 to January 31, 2022 were selected, and they were divided into ROP group(49 cases)and non-ROP group(49 cases)according to the results of Retcam3 fundus screening. All children in ROP group were treated with intravitreal ranibizumab injection, with an average PMA of 38.02±3.03 weeks. The ocular parameters were measured at the PMA of 0 month(40 weeks±14d), 3 months(52 weeks±28d)and 6 months(64 weeks±28d), respectively.RESULTS: There was no difference in axial length(AL), anterior chamber depth(ACD), lens thickness(LT), vitreous length(VL)and central corneal thickness(CCT)between ROP group and non-ROP group at the PMA of 0 month(P&#x003E;0.05); At the PMA of 3 and 6 months, ACD in ROP group was higher than that in non-ROP group, and LT was lower than that in non-ROP group(P&#x003C;0.05); at the PMA of 6 months, AL and VL in ROP group were lower than those in non-ROP group(P&#x003C;0.05). AL, ACD and VL were positively correlated with PMA in ROP group and non-ROP group, while CCT was negatively correlated with PMA; there was a positive correlation between LT and PMA in children without ROP. There was no correlation among LT, BW and PMA in ROP group.CONCLUSION: The ocular development of children with early ROP(PMA 0～6 months)treated by intravitreal ranibizumab injection is slower than that of premature infants without ROP, and BW and PMA are the main influencing factors of ocular parameters of premature infants.

Inhibitory effect of ranibizumab on retinal oxidative stress in a rat model of choroidal neovascularization and its mechanism / 中华实验眼科杂志

Objective:To study the effect of ranibizumab on retinal oxidative stress in a rat model of choroidal neovascularization (CNV) and its mechanism.Methods:Sixty SPF male SD rats aged 10 weeks were randomly divided into normal control group, model control group, ranibizumab group, nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor (ML385) group, ranibizumab+ ML385 group, with 12 rats in each group according to a random number table.Except for the normal control group, the CNV model was established in the other four groups via krypton laser induction.According to grouping, the ranibizumab group, ML385 group and ranibizumab+ ML385 group were intravitreally injected with 1 μl of ranibizumab, ML385 and ranibizumab+ ML385, respectively.Model control group and normal control group received an intravitreal injection of normal saline of equal volume.The CNV area was measured through choroidal wholemounts.Pathological change of the retina was observed by hematoxylin and eosin staining.Expressions of Nrf2, superoxide dismutase (SOD) and quinone oxidoreductase 1 (NQO1) were detected using Western blot and real-time PCR.The use and care of animals complied with laboratory animal welfare guidelines.The study protocol was approved by the Laboratory Animal Welfare and Ethics Committee of Tengzhou Central People's Hospital (No.JN.No20210214S1200430[121]).Results:CNV areas of the model control group, ML385 group and ranibizumab+ ML385 group were (23.01±1.52)×10 3, (30.23±2.01)×10 3 and (18.56±1.85)×10 3 μm 2, respectively, which were significantly higher than (12.35±1.22)×10 3 μm 2 of ranibizumab group (all at P<0.001). The CNV area of ranibizumab+ ML385 group was smaller than that of model control group and ML385 group, and the CNV area of ML385 group was larger than that of model control group, showing statistically significant differences (all at P<0.001). Hematoxylin and eosin staining showed that the structural damage of the retinal pigment epithelium-choroid-sclera complex was slighter in ranibizumab group than model control group, severer in ranibizumab+ ML385 group than ranibizumab group but slighter than model control group, severer in ML385 group than model control group.The mRNA and protein expressions of Nrf2, SOD and NQO1 of ranibizumab group were lower than those of normal control group but higher than those of model control group, ML385 group and ranibizumab+ ML385 group, and the differences were statistically significant (all at P<0.05). The mRNA and protein expressions of Nrf2, SOD and NQO1 were higher in ranibizumab+ ML385 group than model control group and ML385 group, showing statistically significant differences (all at P<0.05). Conclusions:Ranibizumab can inhibit the growth of CNV induced by krypton laser and reduce RPE damage caused by retinal oxidative stress.The mechanism is related to the activation of Nrf2/ARE pathway.

Meta-analysis of the efficacy of intravitreal Ranibizumab combined with compound trabeculectomy and panretinal photocoagulation in the treatment of neovascular glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To systematically evaluate the efficacy and safety of intravitreal ranibizumab combined with compound trabeculectomy and panretinal photocoagulation(PRP)compared with compound trabeculectomy combined with PRP in the treatment of neovascular glaucoma(NVG).METHODS: Databases including Wanfang database, China National Knowledge Infrastructure(CNKI), PubMed, EMbase, China Biomedical Document Service System(CBM), Clinicalkey, and Cochrane Library were retrieved. Literatures about intravitreal ranibizumab combined with compound trabeculectomy and PRP in the treatment of NVG in the experimental group and compound trabeculectomy and PRP in the treatment of NVG in the control group from creation of database to July 20, 2022 were searched. At the same time, relevant reference were consulted. The best corrected visual acuity, intraocular pressure, occurrence of complications and the success rate of the surgery were systematically evaluated.RESULTS: A total of 8 clinical studies were included, with 864 patients(864 eyes)with NVG. Meta-analysis showed that the intraocular pressure of patients in the experimental group was lower than that in the control group at 1wk, 1 and 3mo after surgery(1wk: MD=-4.00, 95%CI: -4.62～-3.38, P&#x0026;#x003C;0.05; 1mo: MD=-4.11, 95%CI: -4.66～-3.56, P&#x0026;#x003C;0.05; 3mo: MD=-4.58, 95%CI: -5.61～-3.55, P&#x0026;#x003C;0.05). The best corrected visual acuity of the experimental group was better than that of the control group at 1mo after surgery(MD=0.17, 95%CI: 0.11～0.23, P&#x0026;#x003C;0.05), but there was no significant difference at 1wk after surgery(MD=0.08, 95%CI: -0.13～0.29, P=0.47). The patients in the experimental group had fewer complications(OR=0.30, 95%CI: 0.18～0.52, P&#x0026;#x003C;0.05)and higher surgical success rate(OR=5.15, 95%CI: 2.78～9.53, P&#x0026;#x003C;0.05).CONCLUSION:With decreased intraocular pressure, improved visual acuity and surgical success rate, intravitreal ranibizumab combined with compound trabeculectomy and PRP was better than the compound trabeculectomy and PRP in the treatment of NVG.

A prospective, randomized, parallel group, double blind, multicenter study to compare the efficacy, safety and immunogenicity of Lupin’s Ranibizumab with Lucentis® in patients with neovascular age-related macular degeneration

Purpose: The present study compares the efficacy, safety, and immunogenicity of Lupin’s biosimilar ranibizumab with that of Lucentis® in patients with neovascular age-related macular degeneration. Methods: This prospective, double-blind, multi-centric phase-III study was conducted across 19 centers in India. A total of 202 patients with neovascular age-related macular degeneration were randomized (1:1) to receive either Lupin’s biosimilar ranibizumab or Lucentis®, 0.5 mg, as an intravitreous injection once every month for 3 months. The primary efficacy endpoint was the proportion of patients who lost fewer than 15 letters from baseline in best-corrected visual acuity. The safety profile included assessment of adverse events, ophthalmic examination, physical and systemic examination, and vital parameters. The immunogenicity assessment was based on evaluation of anti-drug antibodies. Results: Overall, 174 patients (87 [86.14%] in each group) completed the study. The demographics and baseline characteristics were comparable between the treatment groups. The proportion of patients losing fewer than 15 letters from baseline best corrected visual acuity score in the study eye was comparable between two groups. The difference between Lupin’s ranibizumab and Lucentis® for the proportion of patients who lost fewer than 15 letters was within the predefined equivalence margin (intention-to-treat population: 1.0%; 95% confidence interval [CI], ?3.3% to 5.4% and per protocol population: 1.2%; 95% CI, ?3.2% to 6.4%). The incidence of treatment-emergent adverse events was comparable, and 11 (10.89%) patients in Lupin’s ranibizumab and 19 (18.81%) patients in Lucentis® group had at least one treatment-emergent adverse event. The immunogenicity incidence as assessed by proportion of patients with positive anti-drug antibodies was numerically lower in Lupin’s ranibizumab (4.95%) than Lucentis® (12.87%). Conclusion: Lupin’s biosimilar ranibizumab demonstrated therapeutic equivalence, desirable safety, and favorable immunogenicity profile compared to Lucentis

Evaluation of contrast sensitivity in non-high-risk proliferative diabetic retinopathy treated with panretinal photocoagulation with and without intravitreal injections of ranibizumab / Avaliação da sensibilidade ao contraste em retinopatia diabética proliferativa de não alto risco tratada com panfotocoagulação retiniana com ou sem injeções intravítrea de ranibizumabe

ABSTRACT Purpose: To evaluate contrast sensitivity in non-high-risk, treatment-naïve proliferative diabetic retinopathy patients treated with panretinal photocoagulation and intravitreal injections of ranibizumab) versus panretinal photocoagulation alone. Methods: Sixty eyes of 30 patients with bilateral proliferative diabetic retinopathy were randomized into two groups: one received panretinal photocoagulation and ranibizumab injections (study group), while the other received panretinal photocoagulation alone (control group). All eyes were treated with panretinal photocoagulation in three sessions according to the Early Treatment Diabetic Retinopathy Study guidelines. Contrast sensitivity measurements were performed under photopic conditions (85 cd/m2) with the Visual Contrast Test Sensitivity 6500 chart, allowing for the evaluation of five spatial frequencies with sine wave grating charts: 1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree (cpd). Outcomes were measured in contrast sensitivity threshold scores among and within groups, from baseline to 1, 3, and 6 months. Results: Fifty-eight eyes (28 in the study group and 30 in the control group) reached the study endpoint. A comparative analysis of changes in contrast sensitivity between the groups showed significant differences mainly in low frequencies as follows: at month 1 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.04); at month 3 in 1.5 cpd (p=0.016), and at month 6 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.026) in favor of the study group. Conclusions: In eyes of patients with non-high-risk proliferative diabetic retinopathy, panretinal photocoagulation treatment with ranibizumab appears to cause less damage to contrast sensitivity compared with panretinal photocoagulation treatment alone. Thus, our evaluation of contrast sensitivity may support the use of ranabizumab as an adjuvant to panretinal photocoagulation for the treatment of proliferative diabetic retinopathy.

RESUMO Objetivos: Avaliar a sensibilidade ao contraste em pacientes virgens de tratamento com retinopatia diabética proliferativa de não alto risco, submetidos a panfotocoagulação retiniana com injeções intravítreas de ranibizumabe versus pan­fotocoagulação isolada. Métodos: Sessenta olhos de 30 pa­cientes foram randomizados em dois grupos: um submetido a panfotocoagulação com injeções de ranibizumabe (grupo estudo), e o outro submetimedo a panfotocoagulação isolada (grupo controle). Todos olhos foram tratados em 3 sessões de laser, seguindo recomendação do Early Treatment Diabetic Retinopathy Study (ETDRS). Avaliação da sensibilidade ao contraste foi realizada sob condições fotópicas (85 cd/m2) com tabela Visual Contrast Test Sensitivity 6500, permitindo avaliação de cinco frequências espaciais medidas com redes senoidais: 1.5, 3.0, 6.0, 12.0 e 18.0 ciclos por grau de ângulo visual (cpd). Foram realizadas medidas dos limiares de sensibilidade ao contraste intra e entre grupos na visita inicial, no 1º, 3º, e 6º mês de seguimento. Resultados: Cinquenta e oito olhos, 28 do grupo estudo e 30 do grupo controle, atingiram o término do estudo. Análise comparativa da SC entre os grupos mostrou diferença estatisticamente significante, nas baixas frequências espaciais, no 1º mês em 1.5 cpd (p=0,001) e 3.0 cpd (p=0,04), no 3º mês em 1.5 cpd (p=0,016) e no 6º mês em 3.0 cpd (p=0,026) a favor do grupo estudo. Conclusão: O tratamento com panfotocoagulação associada a injeção de ranibizumabe parece causar menos danos a sensibilidade ao contraste quando comparada com panfotocoagulação isolada em olhos com retinopatia diabética proliferativa de não alto risco. Dessa forma, os resultados apresentados podem justificar a associação do ranibizumabe à panfotocoagulação nestes pacientes.

Intravitreal Conbercept or Ranibizumab for myopic choroidal neovascularization / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To compare the efficacy of intravitreal conbercept or ranibizumab for myopic choroidal neovascularization(CNV).<p>METHODS: A retrospective cohort study. This study included 46 patients(46 eyes)with myopic CNV who were treated with conbercept(conbercept group, 20 cases, 20 eyes)or ranibizumab(ranibizumab group, 26 cases, 26 eyes)from March 2015 to August 2019. Central macular thickness(CMT), the number of injections and complications measured by best-corrected visual acuity(BCVA)and optical coherence tomography(OCT)were compared between the two groups before treatment and 1, 3, 6mo after treatment.<p>RESULTS: Before treatment, the BCVA(LogMAR)of conbercept and ranibizumab groups were 0.81±0.51, 0.83±0.66(<i>P</i>=0.900). After treatment, the BCVA(LogMAR)in the conbercept group at 1, 3 and 6mo were 0.59±0.33, 0.49±0.34, 0.44±0.32, in the ranibizumab group were 0.53±0.54, 0.47±0.47, 0.40±0.43. The BCVA was significantly improved in both groups after treatment(all <i>P</i><0.001). Before treatment, the CMT of conbercept and ranibizumab groups were 242.30±73.27, 233.38±66.63μm(<i>P</i>=0.669). After treatment, the CMT in the conbercept group at 1, 3, and 6mo were 217.00±54.78, 208.65±55.38, 206.00±45.34μm, in the ranibizumab group were 197.42±50.47, 198.38±55.19, 192.15±51.97μm. The CMT was significantly decreased in both groups after treatment(all <i>P</i><0.05). There were no significant differences in the number of injections, BCVA and CMT at each follow-up time points between conbercept and ranibizumab groups(all <i>P</i>>0.05). Systemic adverse reactions and serious ocular complications were not found during the treatment period.<p>CONCLUSION: Intravitreal conbercept or ranibizumab provide similar efficacy to improve the BCVA and reduce the CMT in the patients with myopic CNV. Both conbercept and ranibizumab could be a choice of treatment for myopic CNV.

Clinical therapeutic effects of Aflibercept or Ranibizumab combined with Ahmed glaucoma valve implantation on neovascular glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To observe the clinical therapeutic efficacy of Ahmed glaucoma valve(AGV)implantation with intravitreal injection of aflibercept or ranibizumab in patients with neovascular glaucoma(NVG). <p>METHODS: A retrospective study. The clinical data of 33 cases(33 eyes)with NVG angle-closure glaucoma who were received intravitreal injection of aflibercept or ranibizumab with AGV implantation from January 2018 to August 2020 in our hospital were involved in this study. There were 18 eyes in the aflibercept group and 15 eyes in the ranibizumab group. All patients were followed-up for 6mo. The best-corrected visual acuity(BCVA), intraocular pressure, neovascularization, and postoperative complications were recorded and evaluated.<p>RESULTS: Before the first intravitreal injection and 1wk after intravitreal injection, the differences of intraocular pressure and BCVA in two groups were not statistically significant(<i>P</i>>0.05); The changes of intraocular pressure and BCVA before the first intravitreal injection and after AGV implant 1wk, 1, 3, 6mo were statistically significant in two groups(<i>P</i><0.01), but there were no statistically significant differences intraocular pressure and BCVA between the two groups at each follow-up time point(<i>P</i>>0.05). There were no significant differences in average number of injections between aflibercept group(1.61±0.98)and ranibizumab group(1.80±0.86)(<i>P</i>>0.05). The differences of neovascular recurrence rate, incidence of early and late complications and surgical success rates were not statistically significant(<i>P</i>>0.05).<p>CONCLUSION: Intravitreal aflibercept or ranibizumab injection combined with AGV implantation is an effective treatment for NVG. The clinical efficacy of aflibercept and ranibizumab were similar.

Comparison of Ranibizumab and Conbercept combined with photodynamic therapy in the treatment of polypoid choroidal vascular disease / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To explore the effects of ranibizumab and conbercept combined with photodynamic therapy(PDT)on vision and hemorheology of polypoid choroidal vascular(PCV)lesions. <p>METHODS: Prospective research. A total of 120(120 eyes)PCV patients who were admitted to our hospital from 2017-02/2020-06 were enrolled and divided into 61 cases(61 eyes)in the ranibizumab combined with PDT treatment group according to the random number table. Conbercept combined with PDT treatment group of 59 patients(59 eyes), compared the intraocular pressure, best corrected visual acuity(BCVA), central retinal thickness(CRT), blood flow, and the incidence of complications within 3mo of follow-up between the two groups before and after treatment.<p>RESULTS: There was no difference in intraocular pressure, CRT, and BCVA at 1 and 3mo after treatment between the two groups(all <i>P</i>>0.05). The whole blood high shear viscosity and whole blood of the ranibizumab combined with PDT treatment group were 1 and 3mo after treatment. The low-shear viscosity was lower than the conbercept combined with PDT treatment group(all <i>P</i><0.05). At the same time, the complication rate in the ranibizumab combined with PDT treatment group during the follow-up period of 3mo was lower than that in the conbercept combined with PDT treatment group(3.3% <i>vs</i> 16.9%, <i>P</i><0.05). <p>CONCLUSION: The treatment of ranibizumab combined with PDT for patients with PCV disease is more conducive to hemorheological stability and reduces the incidence of complications.

Effect of intravitreal anti-VEGF injection on choroidal thickness in patients with diabetic macula edema / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate for any detectable change in sub-foveal choroidal thickness following intravitreal injections of Ranibizumab or Aflibercept in patients with central involving diabetic macula edema(DME), evidenced by optical coherence tomography(OCT).<p>METHODS: Totally 17 patients with central involving DME who required and agreed to intravitreal anti-VEGF injection were invited to be the subject of this study. These injection-naive subjects were undergone three loading doses of monthly intravitreal anti-VEGF(Ranibizumab 0.5 mg/0.05 mL for 9 patients or Aflibercept 2 mg/0.05 mL for 8 patients)injection, and a clinic review appointment 1mo after the third injection. The changes of foveal choroidal thickness, visual acuity and central retinal thickness at 1mo were observed before and after treatment in 2 groups by enhanced depth image-optical coherence tomography(EDI-OCT). <p>RESULTS: We recorded a significant sub-foveal choroidal thinning and vision improvement after three loading doses of anti-VEGF(all <i>P</i><0.05). The thinning effect between Ranibizumab and Aflibercept group was insignificant(all <i>P</i>>0.05). There was no significant correlation between pre-treatment sub-foveal choroidal thickness and vision improvement(<i>r_s</i>=-0.269, <i>P</i>=0.296). There was also no significant correlation between choroidal thickness changes with vision improvement, central retinal thickness change and age of subjects(all <i>P</i> >0.05).<p>CONCLUSION: Intravitreal Ranibizumab and Aflibercept injections both leads to significant sub-foveal choroidal thinning in DME subjects. It was accompanied with significant vision improvement with no evidence of immediate detrimental effect of choroidal thinning. Future research with a longer study duration would help in establishing the duration and long term effect of choroidal thinning.