Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity: A Randomized Clinical Trial.

Importance: Anti-vascular endothelial growth factor (VEGF) therapies are a novel treatment option in retinopathy of prematurity (ROP). Data on dosing, efficacy, and safety are insufficient. Objective: To investigate lower doses of anti-VEGF therapy with ranibizumab, a substance with a significantly shorter systemic half-life than the standard treatment, bevacizumab. Design, Setting, and Participants: This randomized, multicenter, double-blind, investigator-initiated trial at 9 academic medical centers in Germany compared ranibizumab doses of 0.12 mg vs 0.20 mg in infants with bilateral aggressive posterior ROP; ROP stage 1 with plus disease, 2 with plus disease, or 3 with or without plus disease in zone I; or ROP stage 3 with plus disease in posterior zone II. Patients were recruited between September 2014 and August 2016. Twenty infants were screened and 19 were randomized. Interventions: All infants received 1 baseline ranibizumab injection per eye. Reinjections were allowed in case of ROP recurrence after at least 28 days. Main Outcomes and Measures: The primary end point was the number of infants who did not require rescue therapy at 24 weeks. Key secondary end points included time-to-event analyses, progression of physiologic vascularization, and plasma VEGF levels. Stages of ROP were photodocumented and reviewed by an expert committee. Results: Nineteen infants with ROP were enrolled (9 [47.4%] female; median [range] postmenstrual age at first treatment, 36.4 [34.7-39.7] weeks), 3 of whom died during the study (1 in the 0.12-mg group and 2 in the 0.20-mg group). Of the surviving infants, 8 (88.9%) (17 eyes [94.4%]) in the 0.12-mg group and 6 (85.7%) (13 eyes [92.9%]) in the 0.20-mg group did not require rescue therapy. Both ranibizumab doses were equally successful in controlling acute ROP (Cochran-Mantel-Haenszel analysis; odds ratio, 1.88; 95% CI, 0.26-13.49; P = .53). Physiologic intraretinal vascularization was superior in the 0.12-mg group. The VEGF plasma levels were not systematically altered in either group. Conclusions and Relevance: This pilot study demonstrates that ranibizumab is effective in controlling acute ROP and that 24% of the standard adult dose (0.12 mg) appears equally effective as 40% (0.20 mg). Superior vascularization of the peripheral retina with 0.12 mg of ranibizumab indicates that the lower dose may be favorable. Unchanged plasma VEGF levels point toward a limited systemic drug exposure after ranibizumab. Trial Registration: clinicaltrials.gov Identifier: NCT02134457 and clinicaltrialsregister.eu Identifier: 2013-002539-13.

Primary vitrectomy for rhegmatogenous retinal detachment: an analysis of 512 cases.

BACKGROUND: Primary pars plana vitrectomy (PPPV) has gained widespread popularity in the treatment of rhegmatogenous retinal detachments (RRD). However, the surgical procedure is still flawed by a significant rate of anatomical and functional failures. The study was conducted to analyse the risk factors for a dissatisfying postoperative outcome. METHODS: We carried out a retrospective study of 512 cases of PPPV with a minimum follow-up of 3 months from one institution over a 9-year period. Preoperatively, 24.8% of patients (127 out of 512) were pseudophakic, 16.4% (84 out of 512) highly myopic, 19.9% (102 out of 512) had preoperative proliferative vitreoretinopathy (PVR) and 14.6% (75 out of 512) had vitreous haemorrhage. RESULTS: The follow-up period ranged from 3 to 108 months (median 14.8). Retinal reattachment was achieved with one operation in 70.7% (362 out of 512) and after one or more operations in 97.5% of cases (499 out of 512). The major reasons for redetachments were new retinal breaks, followed by a combination of new breaks and PVR, and PVR without apparent breaks. Postoperative visual acuities of > or =0.1 and > or =0.4 were achieved in 82.8% (424 out of 512) and 48.2% (247 out of 512) respectively. Out of 376 phakic patients at study entry, 66.4% (250 out of 376) underwent cataract surgery either in combination with PPPV or during the postoperative course. Factors that were significantly associated with either anatomical or functional failure included duration of symptoms, low preoperative visual acuity, myopia, amblyopia, hypotony, macular detachment, preoperative PVR, extent of detachment, involvement of inferior quadrants, no detectable breaks, large breaks, breaks posterior to the equator, surgeon, level of surgical training, endocryotherapy, and combined scleral buckling surgery. CONCLUSION: Primary pars plana vitrectomy is still flawed by a relatively high primary redetachment rate following the initial procedure. The advantages of the technique are a high final reattachment rate and relatively good functional results in a subset of patients with more complicated types of RRD. The risk factors for postoperative failures following PPPV for RRD match to a large extent those following scleral buckling surgery (SBS). Future improvements of the technique will have to focus on modifiable risk factors, such as details of the surgical procedures, surgical training and case selection, to distinguish it from SBS.

[Late Retinal Complications in Former Preterm Infants with Regressed ROP]. / Späte retinale Komplikationen bei Frühgeborenen mit regressiven Veränderungen.

BACKGROUND: The purpose of this study is to evaluate late retinal complications in former preterm infants with regressed stages of acute retinopathy of prematurity (ROP). PATIENTS AND METHODS: Between 1995 and 2002 a consecutive series of 15 patients (16 eyes) with loss in visual acuity were examined. Gestational age was < 32 weeks, birth weight < 1500 g. The reason for visual disturbances was: RD (n = 14), vitreous haemorrhage (n = 3) and posterior vitreous detachment (n = 1). RESULTS: Two eyes recovered spontaneously. Surgery was performed in 14/16 eyes, with a pars plana vitrectomy (n = 14), or buckling procedure (n = 2). Four eyes with a severe form of regressed ROP needed multiple procedures for reattachment At last follow-up in 13/14 (93.0 %) eyes the retina was completely attached. Visual acuity ranged from light projection to 20/25. CONCLUSIONS: Former premature patients with vitreoretinal changes due to regressed ROP may develop vitreous traction and subsequent late-onset retinal detachment. Surgery with primary vitrectomy technique in eyes with retinal detachment can remove the vitreoretinal adhesions and is an effective treatment technique. In eyes without retinal detachment the natural course can be awaited.

Long-term results following pars plana vitrectomy with platelet concentrate in pediatric patients with traumatic macular hole.

PURPOSE: To describe the long-term clinical course in children with a traumatic macular hole after vitrectomy with platelet concentrate. DESIGN: Interventional case series. METHODS: Four pediatric patients with a mean age of 13.2 years (range, 10-15 years) underwent pars plana vitrectomy with platelet concentrate, internal limiting membrane peeling, and SF6 gas tamponade for stage 3 traumatic macular hole repair. RESULTS: Primary closure was achieved by a single intervention in all patients with a marked visual improvement of three to seven lines after surgery. The surgically achieved visual improvement remained stable and no vision-threatening complications occurred during the mean follow up of 35.2 months (range, 27-51 months). CONCLUSION: We regard pars plana vitrectomy with platelet concentrate and SF6 gas instillation as safe and effective and, therefore, as the therapy of choice for traumatic macular holes particularly in children after a period of observation no longer than 3 to 4 months.